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c980175e43c450c51f8c194b0ccf8876445c6000	wikidoc	LOXL3	LOXL3 Lysyl oxidase homolog 3 is an enzyme that in humans is encoded by the LOXL3 gene. This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Alternatively spliced transcript variants of this gene have been reported but their full-length nature has not been determined. # Clinical significance An autosomal recessive mutation (missense variant) in the LOXL3 gene is one of the causes of Stickler syndrome, a disease where collagen is not crosslinked properly. Common features are high myopia and cleft palate due to arthropathy (joint pathology) and vitreoretinopathy (pathology of the eye).	LOXL3 Lysyl oxidase homolog 3 is an enzyme that in humans is encoded by the LOXL3 gene.[1][2] This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Alternatively spliced transcript variants of this gene have been reported but their full-length nature has not been determined.[2] # Clinical significance An autosomal recessive mutation (missense variant) in the LOXL3 gene is one of the causes of Stickler syndrome, a disease where collagen is not crosslinked properly. Common features are high myopia and cleft palate due to arthropathy (joint pathology) and vitreoretinopathy (pathology of the eye).[3]	https://www.wikidoc.org/index.php/LOXL3
62a20fb84ae7ad76cb60696a5a98d0fb05d3d4fb	wikidoc	LPAR6	LPAR6 Lysophosphatidic acid receptor 6 also known as LPA6, P2RY5, and GPR87, is a protein that in humans is encoded by the LPAR6 gene. LPA6 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA). The protein encoded by this gene belongs to the family of G-protein coupled receptors, that are preferentially activated by adenosine and uridine nucleotides. This gene aligns with an internal intron of the retinoblastoma susceptibility gene in the reverse orientation. # Role in hair growth/loss In February 2008 researchers at the University of Bonn announced they have found the genetic basis of two distinct forms of inherited hair loss, opening a broad path to treatments for baldness. They found that mutations in the gene P2RY5 causes a rare, inherited form of hair loss called Hypotrichosis simplex. It is the first receptor in humans known to play a role in hair growth. The fact that any receptor plays a specific role in hair growth was previously unknown to scientists and with this new knowledge a focus on finding more of these genes may be able to lead to therapies for many different types of hair loss.	LPAR6 Lysophosphatidic acid receptor 6 also known as LPA6, P2RY5, and GPR87, is a protein that in humans is encoded by the LPAR6 gene.[1][2][3][4] LPA6 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA).[5][6] The protein encoded by this gene belongs to the family of G-protein coupled receptors, that are preferentially activated by adenosine and uridine nucleotides. This gene aligns with an internal intron of the retinoblastoma susceptibility gene in the reverse orientation.[4] # Role in hair growth/loss In February 2008 researchers at the University of Bonn announced they have found the genetic basis of two distinct forms of inherited hair loss, opening a broad path to treatments for baldness. They found that mutations in the gene P2RY5 causes a rare, inherited form of hair loss called Hypotrichosis simplex. It is the first receptor in humans known to play a role in hair growth. The fact that any receptor plays a specific role in hair growth was previously unknown to scientists and with this new knowledge a focus on finding more of these genes may be able to lead to therapies for many different types of hair loss.[5]	https://www.wikidoc.org/index.php/LPAR6
048f7fb26ff132494f865ec9576857b3e0dff4ef	wikidoc	LPIN1	LPIN1 Lipin-1 is a protein that in humans is encoded by the LPIN1 gene. # Function Lipin-1 has phosphatidate phosphatase activity. The nuclear localization of Lipin 1 is regulated by the mammalian Target Of Rapamycin protein kinase and links mTORC1 activity to the regulation of Sterol regulatory element-binding proteins (SREBP)-dependent gene transcription. # Clinical significance This gene represents a candidate gene for human lipodystrophy, characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance. Mouse studies suggest that this gene functions during normal adipose tissue development and may also play a role in human triglyceride metabolism.	LPIN1 Lipin-1 is a protein that in humans is encoded by the LPIN1 gene.[1][2][3][4] # Function Lipin-1 has phosphatidate phosphatase activity.[5][6][7] The nuclear localization of Lipin 1 is regulated by the mammalian Target Of Rapamycin protein kinase and links mTORC1 activity to the regulation of Sterol regulatory element-binding proteins (SREBP)-dependent gene transcription.[8][9][10] # Clinical significance This gene represents a candidate gene for human lipodystrophy, characterized by loss of body fat, fatty liver, hypertriglyceridemia, and insulin resistance. Mouse studies suggest that this gene functions during normal adipose tissue development and may also play a role in human triglyceride metabolism.[4][8]	https://www.wikidoc.org/index.php/LPIN1
059d5ee8a2667878322b46b3ae16a8490cf48465	wikidoc	LQT10	LQT10 # Overview Only one mutation in one patient of this Long QT syndrome subtype has been found. # LQT10 This novel susceptibility gene for LQT is SCN4B encoding the protein NaVβ4, an auxiliary subunit to the pore-forming NaV1.5 (gene: SCN5A) subunit of the voltage-gated sodium channel of the heart. The mutation leads to a positive shift in inactivation of the sodium current, thus increasing sodium current. Only one mutation in one patient has so far been found. ## History and Symptoms - Seizures - due to oxygen deprivation that occurs during arrhythmia. - Fainting - fainting or syncope is the most common symptom LQTS. - A prodrome may occur before losing consciousness, which may consist of lightheadedness, heart palpitations, blurred vision or weakness. - Sudden death - a fatal arrhythmia that is not quickly intervened on, may cause sudden death. ## Therapy - Beta-blockers are the first line treatment in LQTS, even in asymptomatic carriers, as they reduce the incidence of syncope and sudden cardiac death. - Other medications to control non-malignant arrhythmias. - Electrolytes should be repleted as neccesary. - Avoidance of triggers (drugs, supplements, loud noises, exercise). - LQTs is one of the few diseases where genetic testing can provide important guidance, such as in whom to place an AICD (defibrillator) for the primary prevention of cardiac events. - Placement of a pacemaker may be indicated. - Left stellectomy is not a cure, but is a second line therapy to reduce the risk of sudden cardiac death and is indicated if the patient does not tolerate beta blockers, as well as in young patients under the age of 12 where beta blockers are not deemed protective enough and AICD is not appropriate. - Patients with long QT syndrome should undergo secondary prevention with AICD implantation if they sustain an aborted cardiac arrest or sudden cardiac death.	LQT10 Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] # Overview Only one mutation in one patient of this Long QT syndrome subtype has been found. # LQT10 This novel susceptibility gene for LQT is SCN4B encoding the protein NaVβ4, an auxiliary subunit to the pore-forming NaV1.5 (gene: SCN5A) subunit of the voltage-gated sodium channel of the heart. The mutation leads to a positive shift in inactivation of the sodium current, thus increasing sodium current. Only one mutation in one patient has so far been found. ## History and Symptoms - Seizures - due to oxygen deprivation that occurs during arrhythmia. - Fainting - fainting or syncope is the most common symptom LQTS. - A prodrome may occur before losing consciousness, which may consist of lightheadedness, heart palpitations, blurred vision or weakness. - Sudden death - a fatal arrhythmia that is not quickly intervened on, may cause sudden death. ## Therapy - Beta-blockers are the first line treatment in LQTS, even in asymptomatic carriers, as they reduce the incidence of syncope and sudden cardiac death. - Other medications to control non-malignant arrhythmias. - Electrolytes should be repleted as neccesary. - Avoidance of triggers (drugs, supplements, loud noises, exercise). - LQTs is one of the few diseases where genetic testing can provide important guidance, such as in whom to place an AICD (defibrillator) for the primary prevention of cardiac events. [1] - Placement of a pacemaker may be indicated. - Left stellectomy is not a cure, but is a second line therapy to reduce the risk of sudden cardiac death and is indicated if the patient does not tolerate beta blockers, as well as in young patients under the age of 12 where beta blockers are not deemed protective enough and AICD is not appropriate. - Patients with long QT syndrome should undergo secondary prevention with AICD implantation if they sustain an aborted cardiac arrest or sudden cardiac death.	https://www.wikidoc.org/index.php/LQT10
d43e33399e1d7cbeea10e75da035f75e987c00f3	wikidoc	LRIG1	LRIG1 Leucine-rich repeats and immunoglobulin-like domains protein 1 is a protein that in humans is encoded by the LRIG1 gene. It encodes a transmembrane protein that has been shown to interact with receptor tyrosine kinases of the EGFR-family , MET and RET. # Model organisms Model organisms have been used in the study of LRIG1 function. A conditional knockout mouse line, called Lrig1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on homozygous mutant mice and ten significant abnormalities were observed, including decreased body weight and total body fat, scaly skin, abnormal hair shedding, a moderate degree of hearing impairment, vertebral fusion, abnormal plasma chemistry and an increased susceptibility to bacterial infection (with both Salmonella and Citrobacter).	LRIG1 Leucine-rich repeats and immunoglobulin-like domains protein 1 is a protein that in humans is encoded by the LRIG1 gene.[1][2][3] It encodes a transmembrane protein that has been shown to interact with receptor tyrosine kinases of the EGFR-family[4] , MET[5] and RET.[6] # Model organisms Model organisms have been used in the study of LRIG1 function. A conditional knockout mouse line, called Lrig1tm1a(EUCOMM)Wtsi[16][17] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[18][19][20] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[14][21] Twenty five tests were carried out on homozygous mutant mice and ten significant abnormalities were observed, including decreased body weight and total body fat, scaly skin, abnormal hair shedding, a moderate degree of hearing impairment, vertebral fusion, abnormal plasma chemistry and an increased susceptibility to bacterial infection (with both Salmonella and Citrobacter).[14]	https://www.wikidoc.org/index.php/LRIG1
887ad5e1981168851237098ce712aad68b5d6b7b	wikidoc	LRRC7	LRRC7 Leucine rich repeat containing 7 also known as LRRC7, Densin-180, or LAP1 is a protein which in humans is encoded by the LRRC7 gene. # Structure Found to be densely associated to the postsynaptic density (PSD), it has been characterised as a 188 kDa (originally thought to be 180 kDa, hence nomenclature), 1495 residues long, brain-specific protein containing 16 leucine-rich repeats (LRRs) within the 500 N-terminal residues, and one Psd95/Discs large/Zona occludens (PDZ) domain within the 200 C-terminal residues. Originally postulated to have an apparent transmembrane domain, it has now been shown that the protein has numerous phosphorylation sites both N- and C-term of this domain, and that protein is therefore cytoplasmic; palmitoylation is thought to occur near the N-terminus of the protein which would account for localisation of the protein at the PSD. # Interactions LRRC7 has been shown to interact with CDH2. The currently exposed interactions of Densin-180 portray the protein as a promiscuous player amongst key synaptic players, fitting with the original observation of the protein’s dense presence among core PSD proteins by Mary B. Kennedy's Laboratory. Identified interaction partners include: CaMKII-alpha, alpha-Actinin and NR2B (via CaMKII-alpha), Cav1.3 (L-type Ca2+) channels, MAGUIN-1, Shank, PSD-95 (via Shank and MAGUIN-1), beta-Catenin, delta-Catenins and NCadherin (via the Catenins). The nature and function of these interactions, detailed in tables 1-1 and 1-2, portray Densin-180 as a key interactor in the midst of receptor proteins, scaffolding proteins and structural proteins. It is also quite possible that Densin-180 dimerises or multimerises through interactions between its PDZ domain and its own terminal amino acid residues. [Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells Ranatunga, J.M. (2011) Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells. Masters thesis, UCL (University College London). /]	LRRC7 Leucine rich repeat containing 7 also known as LRRC7, Densin-180, or LAP1 is a protein which in humans is encoded by the LRRC7 gene.[1] # Structure Found to be densely associated to the postsynaptic density (PSD), it has been characterised as a 188 kDa (originally thought to be 180 kDa, hence nomenclature), 1495 residues long, brain-specific protein containing 16 leucine-rich repeats (LRRs) within the 500 N-terminal residues, and one Psd95/Discs large/Zona occludens (PDZ) domain within the 200 C-terminal residues. Originally postulated to have an apparent transmembrane domain, it has now been shown that the protein has numerous phosphorylation sites both N- and C-term of this domain, and that protein is therefore cytoplasmic; palmitoylation is thought to occur near the N-terminus of the protein which would account for localisation of the protein at the PSD.[2] # Interactions LRRC7 has been shown to interact with CDH2.[3] The currently exposed interactions of Densin-180 portray the protein as a promiscuous player amongst key synaptic players, fitting with the original observation of the protein’s dense presence among core PSD proteins by Mary B. Kennedy's Laboratory. Identified interaction partners include: CaMKII-alpha, alpha-Actinin and NR2B (via CaMKII-alpha), Cav1.3 (L-type Ca2+) channels, MAGUIN-1, Shank, PSD-95 (via Shank and MAGUIN-1), beta-Catenin, delta-Catenins and NCadherin (via the Catenins). The nature and function of these interactions, detailed in tables 1-1 and 1-2, portray Densin-180 as a key interactor in the midst of receptor proteins, scaffolding proteins and structural proteins. [number of sources - referenced in - Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells Ranatunga, J.M. (2011) Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells. Masters thesis, UCL (University College London). http://discovery.ucl.ac.uk/1322972/] It is also quite possible that Densin-180 dimerises or multimerises through interactions between its PDZ domain and its own terminal amino acid residues. [Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells Ranatunga, J.M. (2011) Subcellular localisation of recombinant Densin-180 clones expressed in HEK293 TSA cells. Masters thesis, UCL (University College London). http://discovery.ucl.ac.uk/1322972/]	https://www.wikidoc.org/index.php/LRRC7
dcf4dda4614fece577b3c00b58e0f31529967704	wikidoc	LRRN3	LRRN3 Leucine-rich repeat neuronal protein 3, also known as neuronal leucine-rich repeat protein 3 (NLRR-3), is a protein that in humans is encoded by the LRRN3 gene. # Gene The LRRN3 is located on human chromosome 7, at 7q31.1. It contains 6 distinct gt-ag introns, and transcription produces five different mRNAs that appear to differ by truncation of the 3' end. There are only three main transcript variants that actually encode for the LRRN3 protein, with the longest transcript variant being 3744 base pairs in length. All three of these transcript variants have differing lengths and number of exons, but they all have the exon that includes the entire coding sequence for the LRRN3 protein. There are also two paralogs to the LRRN3 gene. These include the LRRN1 and LRRN2 genes, both of which have the same leucine-rich repeats that are characteristic to this family of genes. # Protein The LRRN3 protein is 708 amino acids in length. The molecular weight of this protein is 79,424 Daltons, with an isoelectric point of 8.02. It is known to be a single-pass type I membrane protein because it spans the membrane once, with its N-terminus on the extracellular side of the membrane, and its signal sequence is removed. The LRRN3 protein contains 12 leucine-rich repeats, along with an LRRNT and an LRR_RI domain. Leucine-rich repeats are unusually rich in the hydrophobic amino acid leucine. They are common in protein-protein interaction motifs and are typically 20-29 amino acids in length. All major classes of LRRs are known to have a curved horseshoe structure with a parallel beta sheet on the concave side and mostly helical elements on the convex side. The LRRN3 protein also has an immunoglobulin domain, a fibronectin type III domain, and a transmembrane region toward the end of the protein. The composition of this protein is shown below. # Gene Conservation The LRRN3 gene has been shown to be extremely highly conserved. There are 21 orthologs and homologs for this gene going back to zebra fish. This gene has not been found in any invertebrates or plant species. A multiple sequence alignment has shown this very high conservation of the LRRN3 gene among many different species. All 12 of the leucine-rich repeats, along with the LRRNT and the LRR_RI regions, are highly conserved in all vertebrates for which orthologs of this protein have been obtained. The Ig and FN3 domains also show high conservation in all of the orthologous sequences for mammals and birds, but are not as highly conserved for the rest of the homologous sequences. The high conservation of the leucine-rich repeats, the Ig domain, and the FN3 domain show that these regions must be of importance to the functionality of the LRRN3 gene. # Gene Expression Gene Expression data has shown that the LRRN3 gene is expressed at very high levels in humans, about 2.3 times the average gene. It is most highly expressed in brain, heart, and testes tissues. It is also slightly expressed in kidney, muscle, pharynx, placental, and thymus tissue. The highest expression of the LRRN3 gene for the developmental stages is the fetal stage, but it is also expressed in the infant, juvenile, and adult stages, as can be seen in the EST profile. The expression data for the LRRN3 gene shows that it has its highest expression in the brain. Overall, the LRRN3 gene seems to have high to moderate expression throughout the majority of brain tissue. The highest expression being found in the cerebral cortex, the hippocampal formation, the cerebellar cortex, and the paraflocculus. All of these regions play a role in some key cognitive function, involving the processing of language and sensory stimuli, memory, and oculomotor behavior. The high expression of the LRRN3 gene in these regions of the brain could show that the LRRN3 gene has some importance in these cognitive function. # Structure The characteristic shape of leucine-rich repeat proteins is an arc or horseshoe shape. This horseshoe shape of the protein is created by a parallel beta sheet on the concave side and mostly helical elements on the convex side. Eleven residue segments of the LRRs, corresponding to the beta-strand and adjacent loop regions are conserved in LRR proteins, whereas the remaining parts of the repeats may be different. The concave face and the adjacent loops are the most common protein interaction surfaces on LRR proteins. 3D structures of some LRR protein-ligand complexes show that the concave surfact of the LRR domain is ideal for interaction with alpha-helix, thus supporting the conclusions that the elongated and curved LRR structure provides a framework for achieving diverse protein-protein interactions. Comparison of the LRRN3 protein with the chain A of the crystal structure of the LINGO1 ectodomain shows that the LRRN3 protein takes on the characteristic horseshoe shape of most leucine-rich repeat proteins. The LINGO1 ectodomain also has a very long stretch of leucine-rich repeats which is the region that has the best alignment with the LRRN3 protein. This similar region shows that the LRRN3 protein has a structure that includes mostly beta-strands that are connected by loops, with a few alpha helices throughout.	LRRN3 Leucine-rich repeat neuronal protein 3, also known as neuronal leucine-rich repeat protein 3 (NLRR-3), is a protein that in humans is encoded by the LRRN3 gene.[1][2] # Gene The LRRN3 is located on human chromosome 7, at 7q31.1.[3] It contains 6 distinct gt-ag introns, and transcription produces five different mRNAs that appear to differ by truncation of the 3' end. There are only three main transcript variants that actually encode for the LRRN3 protein, with the longest transcript variant being 3744 base pairs in length. All three of these transcript variants have differing lengths and number of exons, but they all have the exon that includes the entire coding sequence for the LRRN3 protein.[4] There are also two paralogs to the LRRN3 gene. These include the LRRN1 and LRRN2 genes, both of which have the same leucine-rich repeats that are characteristic to this family of genes.[1] # Protein The LRRN3 protein is 708 amino acids in length. The molecular weight of this protein is 79,424 Daltons, with an isoelectric point of 8.02.[5] It is known to be a single-pass type I membrane protein because it spans the membrane once, with its N-terminus on the extracellular side of the membrane, and its signal sequence is removed.[3] The LRRN3 protein contains 12 leucine-rich repeats, along with an LRRNT and an LRR_RI domain. Leucine-rich repeats are unusually rich in the hydrophobic amino acid leucine. They are common in protein-protein interaction motifs and are typically 20-29 amino acids in length. All major classes of LRRs are known to have a curved horseshoe structure with a parallel beta sheet on the concave side and mostly helical elements on the convex side. The LRRN3 protein also has an immunoglobulin domain, a fibronectin type III domain, and a transmembrane region toward the end of the protein.[6] The composition of this protein is shown below. # Gene Conservation The LRRN3 gene has been shown to be extremely highly conserved. There are 21 orthologs and homologs for this gene going back to zebra fish. This gene has not been found in any invertebrates or plant species. A multiple sequence alignment has shown this very high conservation of the LRRN3 gene among many different species. All 12 of the leucine-rich repeats, along with the LRRNT and the LRR_RI regions, are highly conserved in all vertebrates for which orthologs of this protein have been obtained. The Ig and FN3 domains also show high conservation in all of the orthologous sequences for mammals and birds, but are not as highly conserved for the rest of the homologous sequences. The high conservation of the leucine-rich repeats, the Ig domain, and the FN3 domain show that these regions must be of importance to the functionality of the LRRN3 gene.[7] # Gene Expression Gene Expression data has shown that the LRRN3 gene is expressed at very high levels in humans, about 2.3 times the average gene.[4] It is most highly expressed in brain, heart, and testes tissues. It is also slightly expressed in kidney, muscle, pharynx, placental, and thymus tissue. The highest expression of the LRRN3 gene for the developmental stages is the fetal stage, but it is also expressed in the infant, juvenile, and adult stages, as can be seen in the EST profile.[8] The expression data for the LRRN3 gene shows that it has its highest expression in the brain. Overall, the LRRN3 gene seems to have high to moderate expression throughout the majority of brain tissue. The highest expression being found in the cerebral cortex, the hippocampal formation, the cerebellar cortex, and the paraflocculus. All of these regions play a role in some key cognitive function, involving the processing of language and sensory stimuli, memory, and oculomotor behavior.[9] The high expression of the LRRN3 gene in these regions of the brain could show that the LRRN3 gene has some importance in these cognitive function. # Structure The characteristic shape of leucine-rich repeat proteins is an arc or horseshoe shape. This horseshoe shape of the protein is created by a parallel beta sheet on the concave side and mostly helical elements on the convex side. Eleven residue segments of the LRRs, corresponding to the beta-strand and adjacent loop regions are conserved in LRR proteins, whereas the remaining parts of the repeats may be different. The concave face and the adjacent loops are the most common protein interaction surfaces on LRR proteins. 3D structures of some LRR protein-ligand complexes show that the concave surfact of the LRR domain is ideal for interaction with alpha-helix, thus supporting the conclusions that the elongated and curved LRR structure provides a framework for achieving diverse protein-protein interactions.[6] Comparison of the LRRN3 protein with the chain A of the crystal structure of the LINGO1 ectodomain shows that the LRRN3 protein takes on the characteristic horseshoe shape of most leucine-rich repeat proteins. The LINGO1 ectodomain also has a very long stretch of leucine-rich repeats which is the region that has the best alignment with the LRRN3 protein. This similar region shows that the LRRN3 protein has a structure that includes mostly beta-strands that are connected by loops, with a few alpha helices throughout.[10]	https://www.wikidoc.org/index.php/LRRN3
6c1529c99fea95e5eed86e066f0e859aeeda4ab8	wikidoc	LYNX1	LYNX1 Ly6/neurotoxin 1 is a protein in humans that is encoded by the LYNX1 gene. Alternatively spliced variants encoding different isoforms have been identified. # Function This gene encodes a member of the Ly-6/neurotoxin gene family, a group of lymphocyte antigens that attach to the cell surface by a glycosylphosphatidylinositol anchor and have a unique structure showing conserved 8-10 cysteine residues with a characteristic spacing pattern. Functional analysis indicates that this protein is not a ligand or neurotransmitter but has the capacity to enhance nicotinic acetylcholine receptor function in the presence of acetylcholine. This gene may also play a role in the pathogenesis of psoriasis vulgaris. The LYNX1 gene codes for a protein (Lynx1) that binds to acetylcholine receptors in the brain. Lynx1 a member of the Ly6 superfamily of proteins that are capable of modulating neurotransmitter receptors. ## Lynx1 and Visual Plasticity Transgenic mice without Lynx1 expression do not have a normal critical period of neuroplasticity in the visual cortex for development of ocular dominance columns. These mice show unusually rapid recovery from amblyopia in adulthood indicating a role in reduction of synaptic plasticity during the normal expression of Lynx1 in adult brain. Lynx1 reduces adult visual cortex plasticity by binding to nicotinic acetylcholine receptors (NAchR) and diminishing acetylcholine signaling. After the developmental critical period and into adulthood, both Lynx1 mRNA and protein levels increase in the adult V1 and the lateral geniculate nucleus (LGN). Lynx1 and nAChR mRNAs are co-expressed in the LGN, as well as in parvalbumin-positive GABAergic interneurons. After monocular deprivation during the critical period to induce amblyopia, Lynx1 knock-out rat models spontaneously recovered normal visual acuity by reopening the closed eye. Similarly, an infusion of physostigmine to increase acetylcholine signaling prompted recovery from amblyopia in wild type mice Inhibition of Lynx1 may be a possible therapeutic mechanism to prolong synaptic plasticity of the visual cortex and improve binocular function of some amblyopes.	LYNX1 Ly6/neurotoxin 1 is a protein in humans that is encoded by the LYNX1 gene.[1] Alternatively spliced variants encoding different isoforms have been identified. # Function This gene encodes a member of the Ly-6/neurotoxin gene family, a group of lymphocyte antigens that attach to the cell surface by a glycosylphosphatidylinositol anchor and have a unique structure showing conserved 8-10 cysteine residues with a characteristic spacing pattern. Functional analysis indicates that this protein is not a ligand or neurotransmitter but has the capacity to enhance nicotinic acetylcholine receptor function in the presence of acetylcholine. This gene may also play a role in the pathogenesis of psoriasis vulgaris.[1] The LYNX1 gene codes for a protein (Lynx1) that binds to acetylcholine receptors in the brain.[2] Lynx1 a member of the Ly6 superfamily of proteins that are capable of modulating neurotransmitter receptors.[3] ## Lynx1 and Visual Plasticity Transgenic mice without Lynx1 expression do not have a normal critical period of neuroplasticity in the visual cortex for development of ocular dominance columns.[4] These mice show unusually rapid recovery from amblyopia in adulthood indicating a role in reduction of synaptic plasticity during the normal expression of Lynx1 in adult brain.[2] Lynx1 reduces adult visual cortex plasticity by binding to nicotinic acetylcholine receptors (NAchR) and diminishing acetylcholine signaling.[5] After the developmental critical period and into adulthood, both Lynx1 mRNA and protein levels increase in the adult V1 and the lateral geniculate nucleus (LGN).[5] Lynx1 and nAChR mRNAs are co-expressed in the LGN, as well as in parvalbumin-positive GABAergic interneurons.[5] After monocular deprivation during the critical period to induce amblyopia, Lynx1 knock-out rat models spontaneously recovered normal visual acuity by reopening the closed eye.[5] Similarly, an infusion of physostigmine to increase acetylcholine signaling prompted recovery from amblyopia in wild type mice[5] Inhibition of Lynx1 may be a possible therapeutic mechanism to prolong synaptic plasticity of the visual cortex and improve binocular function of some amblyopes.	https://www.wikidoc.org/index.php/LYNX1
8723e7068963541f96e3336d0a9048a053379f2e	wikidoc	LYRM7	LYRM7 LYR motif containing 7, also known as Complex III assembly factor LYRM7 or LYR motif-containing protein 7 is a protein that in humans is encoded by the LYRM7 gene. The protein encoded by this gene is a nuclear-encoded mitochondrial matrix protein that stabilizes UQCRFS1 and chaperones it to the CIII complex. Defects in this gene are a cause of mitochondrial complex III deficiency, nuclear type 8. Three transcript variants encoding two different isoforms have been found for this gene. # Structure The LYRM7 gene is located on the q arm of chromosome 5 at position 23.3 to 31.1, spans 34,512 base pairs, and has 5 exons. The LYRM7 gene produces a 6.2 kDa protein composed of 53 amino acids, which is a soluble matrix protein with an N-terminal LYR motif. LYRM7 is an assembly factor of the enzyme Ubiquinol Cytochrome c Reductase (UQCR, Complex III or Cytochrome bc1 complex) of the mitochondrial respiratory chain. # Function The LYRM7 gene encodes for an assembly factor necessary for the incorporation of the iron-sulfur cluster in the Rieske (Fe-S) protein (UQCRFS1), which is an essential subunit of the Ubiquinol Cytochrome c Reductase (complex III) of the mitochondrial respiratory chain. LYRM7 acts by binding to the co-chaperone HSC20 of the Fe-S biogenesis machinery, which brings a cluster assembled on the main scaffold protein ISCU. Direct binding of HSC20 to the LYR motif of LYRM7 in a pre-assembled UQCRFS1-LYRM7 intermediate in the mitochondrial matrix facilitates transfer of the Fe-S cluster from holo-ISCU to UQCRFS1. UQCRFS1, or Rieske (Fe-S) protein (UQCRFS1) is the last catalytic subunit added to the complex. Complex III is required for the catalysis of electron transfer from coenzyme Q to cytochrome c as well as the pumping of protons into the inner membrane from the matrix for the generation of an ATP-coupled electrochemical potential. # Clinical significance Variants of LYRM7 have been associated with mitochondrial complex III deficiency, nuclear 8 (MC3DN8). Mitochondrial complex III deficiency, nuclear 8 is a form of mitochondrial complex III deficiency, a disorder of Complex III of the mitochondrial respiratory chain. The deficiency is known to be highly variable in phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance. Pathogenic Mutations of the LYRM7 gene have included (c.73G>A), (c.214C>T), (c.37delA), and others.	LYRM7 LYR motif containing 7, also known as Complex III assembly factor LYRM7 or LYR motif-containing protein 7 is a protein that in humans is encoded by the LYRM7 gene.[1] The protein encoded by this gene is a nuclear-encoded mitochondrial matrix protein that stabilizes UQCRFS1 and chaperones it to the CIII complex. Defects in this gene are a cause of mitochondrial complex III deficiency, nuclear type 8. Three transcript variants encoding two different isoforms have been found for this gene.[1] # Structure The LYRM7 gene is located on the q arm of chromosome 5 at position 23.3 to 31.1, spans 34,512 base pairs, and has 5 exons.[1] The LYRM7 gene produces a 6.2 kDa protein composed of 53 amino acids, which is a soluble matrix protein with an N-terminal LYR motif.[2][3][4] LYRM7 is an assembly factor of the enzyme Ubiquinol Cytochrome c Reductase (UQCR, Complex III or Cytochrome bc1 complex) of the mitochondrial respiratory chain.[1][5] # Function The LYRM7 gene encodes for an assembly factor necessary for the incorporation of the iron-sulfur cluster in the Rieske (Fe-S) protein (UQCRFS1),[5] which is an essential subunit of the Ubiquinol Cytochrome c Reductase (complex III) of the mitochondrial respiratory chain. LYRM7 acts by binding to the co-chaperone HSC20 of the Fe-S biogenesis machinery, which brings a cluster assembled on the main scaffold protein ISCU.[5] Direct binding of HSC20 to the LYR motif of LYRM7 in a pre-assembled UQCRFS1-LYRM7 intermediate in the mitochondrial matrix facilitates transfer of the Fe-S cluster from holo-ISCU to UQCRFS1.[5] UQCRFS1, or Rieske (Fe-S) protein (UQCRFS1) is the last catalytic subunit added to the complex. Complex III is required for the catalysis of electron transfer from coenzyme Q to cytochrome c as well as the pumping of protons into the inner membrane from the matrix for the generation of an ATP-coupled electrochemical potential.[6][7] # Clinical significance Variants of LYRM7 have been associated with mitochondrial complex III deficiency, nuclear 8 (MC3DN8). Mitochondrial complex III deficiency, nuclear 8 is a form of mitochondrial complex III deficiency, a disorder of Complex III of the mitochondrial respiratory chain. The deficiency is known to be highly variable in phenotype depending on which tissues are affected. Clinical features include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness and exercise intolerance.[6][7] Pathogenic Mutations of the LYRM7 gene have included (c.73G>A), (c.214C>T), (c.37delA), and others.[8][9]	https://www.wikidoc.org/index.php/LYRM7
e3e620b82f4ed83683bb0295893ce93ed13373c6	wikidoc	LZTR1	LZTR1 Leucine-zipper-like transcriptional regulator 1 is a protein that in humans is encoded by the LZTR1 gene. This gene encodes a member of the BTB-kelch superfamily. Initially described as a putative transcriptional regulator based on weak homology to members of the basic leucine zipper-like family, the encoded protein subsequently has been shown to localize exclusively to the Golgi network where it may help stabilize the Golgi complex. # Clinical significance Deletion of this gene may be associated with DiGeorge syndrome. This gene has also been implicated in an autosomal dominant form of schwannomatosis.	LZTR1 Leucine-zipper-like transcriptional regulator 1 is a protein that in humans is encoded by the LZTR1 gene.[1][2][3] This gene encodes a member of the BTB-kelch superfamily. Initially described as a putative transcriptional regulator based on weak homology to members of the basic leucine zipper-like family, the encoded protein subsequently has been shown to localize exclusively to the Golgi network where it may help stabilize the Golgi complex.[3] # Clinical significance Deletion of this gene may be associated with DiGeorge syndrome.[3] This gene has also been implicated in an autosomal dominant form of schwannomatosis.[4]	https://www.wikidoc.org/index.php/LZTR1
0f52c9147001046df53e959246d7e7e6c1036b9c	wikidoc	Laser	Laser # Overview A laser is an electronic-optical device that produces coherent radiation. The term "laser" is an acronym for "Light Amplification by Stimulated Emission of Radiation". A typical laser emits light in a narrow, low-divergence beam and with a well-defined wavelength (i.e., monochromatic, corresponding to a particular colour if the laser is operating in the visible spectrum). This is in contrast to a light source such as the incandescent light bulb, which emits into a large solid angle and over a wide spectrum of wavelength. A laser consists of a gain medium inside an optical cavity, with a means to supply energy to the gain medium. The gain medium is a material (gas, liquid, solid or free electrons) with appropriate optical properties. In its simplest form, a cavity consists of two mirrors arranged such that light bounces back and forth, each time passing through the gain medium. Typically, one of the two mirrors, the output coupler, is partially transparent. The output laser beam is emitted through this mirror. Light of a specific wavelength that passes through the gain medium is amplified (increases in power); the surrounding mirrors ensure that most of the light makes many passes through the gain medium. Part of the light that is between the mirrors (i.e., is in the cavity) passes through the partially transparent mirror and appears as a beam of light. The process of supplying the energy required for the amplification is called pumping and the energy is typically supplied as an electrical current or as light at a different wavelength. In the latter case, the light source can be a flash lamp or another laser. Most practical lasers contain additional elements that affect properties such as the wavelength of the emitted light and the shape of the beam. The first working laser was demonstrated in May 1960 by Theodore Maiman at Hughes Research Laboratories. Recently, lasers have become a multi-billion dollar industry. The most widespread use of lasers is in optical storage devices such as compact disc and DVD players, in which the laser (a few millimeters in size) scans the surface of the disc. Other common applications of lasers are bar code readers and laser pointers. In industry, lasers are used for cutting steel and other metals and for inscribing patterns (such as the letters on computer keyboards). Lasers are also commonly used in various fields in science, especially spectroscopy, typically because of their well-defined wavelength or short pulse duration in the case of pulsed lasers. Lasers are also used for military and medical applications. # Physics A laser is composed of an active laser medium, or gain medium, and a resonant optical cavity. The gain medium transfers external energy into the laser beam. It is a material of controlled purity, size, concentration, and shape, which amplifies the beam by the process of stimulated emission. The gain medium is energized, or pumped, by an external energy source. Examples of pump sources include electricity and light, for example from a flash lamp or from another laser. The pump energy is absorbed by the laser medium, placing some of its particles into high-energy ("excited") quantum states. Particles can interact with light both by absorbing photons or by emitting photons. Emission can be spontaneous or stimulated. In the latter case, the photon is emitted in the same direction as the light that is passing by. When the number of particles in one excited state exceeds the number of particles in some lower-energy state, population inversion is achieved and the amount of stimulated emission due to light that passes through is larger than the amount of absorption. Hence, the light is amplified. Strictly speaking, these are the essential ingredients of a laser. However, usually the term laser is used for devices where the light that is amplified is produced as spontaneous emission from the same gain medium as where the amplification takes place. Devices where light from an external source is amplified are normally called optical amplifiers. The light generated by stimulated emission is very similar to the input signal in terms of wavelength, phase, and polarization. This gives laser light its characteristic coherence, and allows it to maintain the uniform polarization and often monochromaticity established by the optical cavity design. The optical cavity, a type of cavity resonator, contains a coherent beam of light between reflective surfaces so that the light passes through the gain medium more than once before it is emitted from the output aperture or lost to diffraction or absorption. As light circulates through the cavity, passing through the gain medium, if the gain (amplification) in the medium is stronger than the resonator losses, the power of the circulating light can rise exponentially. But each stimulated emission event returns a particle from its excited state to the ground state, reducing the capacity of the gain medium for further amplification. When this effect becomes strong, the gain is said to be saturated. The balance of pump power against gain saturation and cavity losses produces an equilibrium value of the laser power inside the cavity; this equilibrium determines the operating point of the laser. If the chosen pump power is too small, the gain is not sufficient to overcome the resonator losses, and the laser will emit only very small light powers. The minimum pump power needed to begin laser action is called the lasing threshold. The gain medium will amplify any photons passing through it, regardless of direction; but only the photons aligned with the cavity manage to pass more than once through the medium and so have significant amplification. The beam in the cavity and the output beam of the laser, if they occur in free space rather than waveguides (as in an optical fiber laser), are, at best, low order Gaussian beams. However this is rarely the case with powerful lasers. If the beam is not a low-order Gaussian shape, the transverse modes of the beam can be described as a superposition of Hermite-Gaussian or Laguerre-Gaussian beams (for stable-cavity lasers). Unstable laser resonators on the other hand, have been shown to produce fractal shaped beams. The beam may be highly collimated, that is being parallel without diverging. However, a perfectly collimated beam cannot be created, due to diffraction. The beam remains collimated over a distance which varies with the square of the beam diameter, and eventually diverges at an angle which varies inversely with the beam diameter. Thus, a beam generated by a small laboratory laser such as a helium-neon laser spreads to about 1.6 kilometers (1 mile) diameter if shone from the Earth to the Moon. By comparison, the output of a typical semiconductor laser, due to its small diameter, diverges almost as soon as it leaves the aperture, at an angle of anything up to 50°. However, such a divergent beam can be transformed into a collimated beam by means of a lens. In contrast, the light from non-laser light sources cannot be collimated by optics as well or much. The output of a laser may be a continuous constant-amplitude output (known as CW or continuous wave); or pulsed, by using the techniques of Q-switching, modelocking, or gain-switching. In pulsed operation, much higher peak powers can be achieved. Some types of lasers, such as dye lasers and vibronic solid-state lasers can produce light over a broad range of wavelengths; this property makes them suitable for generating extremely short pulses of light, on the order of a few femtoseconds (10-15 s). Although the laser phenomenon was discovered with the help of quantum physics, it is not essentially more quantum mechanical than other light sources. The operation of a free electron laser can be explained without reference to quantum mechanics. It is understood that the word light in the acronym Light Amplification by Stimulated Emission of Radiation is typically used in the expansive sense, as photons of any energy; it is not limited to photons in the visible spectrum. Hence there are infrared lasers, ultraviolet lasers, X-ray lasers, etc. For example, a source of atoms in a coherent state can be called an atom laser. Because the microwave equivalent of the laser, the maser, was developed first, devices that emit microwave and radio frequencies are usually called masers. In early literature, particularly from researchers at Bell Telephone Laboratories, the laser was often called the optical maser. This usage has since become uncommon, and as of 1998 even Bell Labs uses the term laser. # History ## Foundations In 1917, Albert Einstein in his paper Zur Quantentheorie der Strahlung (On the Quantum Theory of Radiation), laid the foundation for the invention of the laser and its predecessor, the maser, in a ground-breaking rederivation of Max Planck's law of radiation based on the concepts of probability coefficients (later to be termed 'Einstein coefficients') for the absorption, spontaneous, and stimulated emission. In 1928, Rudolph W. Landenburg confirmed the existence of stimulated emission and negative absorption. In 1939, Valentin A. Fabrikant (USSR) predicted the use of stimulated emission to amplify "short" waves. In 1947, Willis E. Lamb and R. C. Retherford found apparent stimulated emission in hydrogen spectra and made the first demonstration of stimulated emission. In 1950, Alfred Kastler (Nobel Prize for Physics 1966) proposed the method of optical pumping, which was experimentally confirmed by Brossel, Kastler and Winter two years later. ## Maser In 1953, Charles H. Townes and graduate students James P. Gordon and Herbert J. Zeiger produced the first microwave amplifier, a device operating on similar principles to the laser, but amplifying microwave rather than infrared or visible radiation. Townes's maser was incapable of continuous output. Nikolay Basov and Aleksandr Prokhorov of the Soviet Union worked independently on the quantum oscillator and solved the problem of continuous output systems by using more than two energy levels and produced the first maser. These systems could release stimulated emission without falling to the ground state, thus maintaining a population inversion. In 1955 Prokhorov and Basov suggested an optical pumping of multilevel system as a method for obtaining the population inversion, which later became one of the main methods of laser pumping. Townes reports that he encountered opposition from a number of eminent colleagues who thought the maser was theoretically impossible -- including Niels Bohr, John von Neumann, Isidor Rabi, Polykarp Kusch, and Llewellyn H. Thomas. Townes, Basov, and Prokhorov shared the Nobel Prize in Physics in 1964 "For fundamental work in the field of quantum electronics, which has led to the construction of oscillators and amplifiers based on the maser-laser principle". ## Laser In 1957, Charles Hard Townes and Arthur Leonard Schawlow, then at Bell Labs, began a serious study of the infrared laser. As ideas were developed, infrared frequencies were abandoned with focus on visible light instead. The concept was originally known as an "optical maser". Bell Labs filed a patent application for their proposed optical maser a year later. Schawlow and Townes sent a manuscript of their theoretical calculations to Physical Review, which published their paper that year (Volume 112, Issue 6). At the same time Gordon Gould, a graduate student at Columbia University, was working on a doctoral thesis on the energy levels of excited thallium. Gould and Townes met and had conversations on the general subject of radiation emission. Afterwards Gould made notes about his ideas for a "laser" in November 1957, including suggesting using an open resonator, which became an important ingredient of future lasers. In 1958, Prokhorov independently proposed using an open resonator, the first published appearance of this idea. Schawlow and Townes also settled on an open resonator design, apparently unaware of both the published work of Prokhorov and the unpublished work of Gould. The term "laser" was first introduced to the public in Gould's 1959 conference paper "The LASER, Light Amplification by Stimulated Emission of Radiation". Gould intended "-aser" to be a suffix, to be used with an appropriate prefix for the spectra of light emitted by the device (x-ray laser = xaser, ultraviolet laser = uvaser, etc.). None of the other terms became popular, although "raser" was used for a short time to describe radio-frequency emitting devices. Gould's notes included possible applications for a laser, such as spectrometry, interferometry, radar, and nuclear fusion. He continued working on his idea and filed a patent application in April 1959. The U.S. Patent Office denied his application and awarded a patent to Bell Labs in 1960. This sparked a legal battle that ran 28 years, with scientific prestige and much money at stake. Gould won his first minor patent in 1977, but it was not until 1987 that he could claim his first significant patent victory when a federal judge ordered the government to issue patents to him for the optically pumped laser and the gas discharge laser. The first working laser was made by Theodore H. Maiman in 1960 at Hughes Research Laboratories in Malibu, California, beating several research teams including those of Townes at Columbia University, Arthur L. Schawlow at Bell Labs, and Gould at a company called TRG (Technical Research Group). Maiman used a solid-state flashlamp-pumped synthetic ruby crystal to produce red laser light at 694 nanometres wavelength. Maiman's laser, however, was only capable of pulsed operation due to its three energy level pumping scheme. Later in 1960 the Iranian physicist Ali Javan, working with William R. Bennett and Donald Herriot, made the first gas laser using helium and neon. Javan later received the Albert Einstein Award in 1993. The concept of the semiconductor laser diode was proposed by Basov and Javan. The first laser diode was demonstrated by Robert N. Hall in 1962. Hall's device was made of gallium arsenide and emitted at 850 nm in the near-infrared region of the spectrum. The first semiconductor laser with visible emission was demonstrated later the same year by Nick Holonyak, Jr. As with the first gas lasers, these early semiconductor lasers could be used only in pulsed operation, and indeed only when cooled to liquid nitrogen temperatures (77 K). In 1970, Zhores Alferov in the Soviet Union and Izuo Hayashi and Morton Panish of Bell Telephone Laboratories independently developed laser diodes continuously operating at room temperature, using the heterojunction structure. ## Recent innovations Since the early period of laser history, laser research has produced a variety of improved and specialized laser types, optimized for different performance goals, including: - new wavelength bands - maximum average output power - maximum peak output power - minimum output pulse duration - maximum power efficiency - maximum charging - maximum firing and this research continues to this day. Lasing without maintaining the medium excited into a population inversion, was discovered in 1992 in sodium gas and again in 1995 in rubidium gas by various international teams. This was accomplished by using an external maser to induce "optical transparency" in the medium by introducing and destructively interfering the ground electron transitions between two paths, so that the likelihood for the ground electrons to absorb any energy has been cancelled. In 1985 at the University of Rochester's Laboratory for Laser Energetics a breakthrough in creating ultrashort-pulse, very high-intensity (terawatts) laser pulses became available using a technique called chirped pulse amplification, or CPA, discovered by Gérard Mourou. These high intensity pulses can produce filament propagation in the atmosphere. # Continuous wave and pulsed lasing A laser may either be built to emit a continuous beam or a train of short pulses. This makes fundamental differences in construction, usable laser media, and applications. ## Continuous wave operation In the continuous wave (CW) mode of operation, the output of a laser is relatively consistent with respect to time. The population inversion required for lasing is continually maintained by a steady pump source. ## Pulsed operation In the pulsed mode of operation, the output of a laser varies with respect to time, typically taking the form of alternating 'on' and 'off' periods. In many applications one aims to deposit as much energy as possible at a given place in as short time as possible. In laser ablation for example, a small volume of material at the surface of a work piece might evaporate if it gets the energy required to heat it up far enough in very short time. If, however, the same energy is spread over a longer time, the heat may have time to disperse into the bulk of the piece, and less material evaporates. There are a number of methods to achieve this. ### Q-switching In a Q-switched laser, the population inversion (usually produced in the same way as CW operation) is allowed to build up by making the cavity conditions (the 'Q') unfavorable for lasing. Then, when the pump energy stored in the laser medium is at the desired level, the 'Q' is adjusted (electro- or acousto-optically) to favorable conditions, releasing the pulse. This results in high peak powers as the average power of the laser (were it running in CW mode) is packed into a shorter time frame. ### Modelocking A modelocked laser emits extremely short pulses on the order of tens of picoseconds down to less than 10 femtoseconds. These pulses are typically separated by the time that a pulse takes to complete one round trip in the resonator cavity. Due to the Fourier limit (also known as energy-time uncertainty), a pulse of such short temporal length has a spectrum which contains a wide range of wavelengths. Because of this, the laser medium must have a broad enough gain profile to amplify them all. An example of a suitable material is titanium-doped, artificially grown sapphire (Ti:sapphire). The modelocked laser is a most versatile tool for researching processes happening at extremely fast time scales (femtosecond physics and femtosecond chemistry, also called ultrafast science), for maximizing the effect of nonlinearity in optical materials (e.g. in second-harmonic generation, parametric down-conversion, optical parametric oscillators and the like), and in ablation applications. Again, because of the short timescales involved, these lasers can achieve extremely high powers. ### Pulsed pumping Another method of achieving pulsed laser operation is to pump the laser material with a source that is itself pulsed, either through electronic charging in the case of flashlamps, or another laser which is already pulsed. Pulsed pumping was historically used with dye lasers where the inverted population lifetime of a dye molecule was so short that a high energy, fast pump was needed. The way to overcome this problem was to charge up large capacitors which are then switched to discharge through flashlamps, producing a broad spectrum pump flash. Pulsed pumping is also required for lasers which disrupt the gain medium so much during the laser process that lasing has to cease for a short period. These lasers, such as the excimer laser and the copper vapour laser, can never be operated in CW mode. # Types and operating principles ## Gas lasers Gas lasers using many gases have been built and used for many purposes. They are one of the oldest types of laser. The helium-neon laser (HeNe) emits at a variety of wavelengths and units operating at 633 nm are very common in education because of its low cost. Carbon dioxide lasers can emit hundreds of kilowatts at 9.6 µm and 10.6 µm, and are often used in industry for cutting and welding. The efficiency of a CO2 laser is over 10%. Argon-ion lasers emit light in the range 351-528.7 nm. Depending on the optics and the laser tube a different number of lines is usable but the most commonly used lines are 458 nm, 488 nm and 514.5 nm. A nitrogen transverse electrical discharge in gas at atmospheric pressure (TEA) laser is an inexpensive gas laser producing UV Light at 337.1 nm. Metal ion lasers are gas lasers that generate deep ultraviolet wavelengths. Helium-silver (HeAg) 224 nm and neon-copper (NeCu) 248 nm are two examples. These lasers have particularly narrow oscillation linewidths of less than 3 GHz (0.5 picometers), making them candidates for use in fluorescence suppressed Raman spectroscopy. ## Chemical lasers Chemical lasers are powered by a chemical reaction, and can achieve high powers in continuous operation. For example, in the Hydrogen fluoride laser (2700-2900 nm) and the Deuterium fluoride laser (3800 nm) the reaction is the combination of hydrogen or deuterium gas with combustion products of ethylene in nitrogen trifluoride. They were invented by George C. Pimentel. ### Excimer lasers Excimer lasers are powered by a chemical reaction involving an excited dimer, or excimer, which is a short-lived dimeric or heterodimeric molecule formed from two species (atoms), at least one of which is in an excited electronic state. They typically produce ultraviolet light, and are used in semiconductor photolithography and in LASIK eye surgery. Commonly used excimer molecules include F2 (fluorine, emitting at 157 nm), and noble gas compounds (ArF , KrCl , KrF , XeCl , and XeF ). ## Solid-state lasers Starfire Optical Range Solid state laser materials are commonly made by doping a crystalline solid host with ions that provide the required energy states. For example, the first working laser was a ruby laser, made from ruby (chromium-doped corundum). Formally, the class of solid-state lasers includes also fiber laser, as the active medium (fiber) is in the solid state. Practically, in the scientific literature, solid-state laser usually means a laser with bulk active medium; while wave-guide lasers are caller fiber lasers. Neodymium is a common dopant in various solid state laser crystals, including yttrium orthovanadate (Nd:YVO4), yttrium lithium fluoride (Nd:YLF) and yttrium aluminium garnet (Nd:YAG). All these lasers can produce high powers in the infrared spectrum at 1064 nm. They are used for cutting, welding and marking of metals and other materials, and also in spectroscopy and for pumping dye lasers. These lasers are also commonly frequency doubled, tripled or quadrupled to produce 532 nm (green, visible), 355 nm (UV) and 266 nm (UV) light when those wavelengths are needed. Ytterbium, holmium, thulium, and erbium are other common dopants in solid state lasers. Ytterbium is used in crystals such as Yb:YAG, Yb:KGW, Yb:KYW, Yb:SYS, Yb:BOYS, Yb:CaF2, typically operating around 1020-1050 nm. They are potentially very efficient and high powered due to a small quantum defect. Extremely high powers in ultrashort pulses can be achieved with Yb:YAG. Holmium-doped YAG crystals emit at 2097 nm and form an efficient laser operating at infrared wavelengths strongly absorbed by water-bearing tissues. The Ho-YAG is usually operated in a pulsed mode, and passed through optical fiber surgical devices to resurface joints, remove rot from teeth, vaporize cancers, and pulverize kidney and gall stones. Titanium-doped sapphire (Ti:sapphire) produces a highly tunable infrared laser, commonly used for spectroscopy as well as the most common ultrashort pulse laser. Thermal limitations in solid-state lasers arise from unconverted pump power that manifests itself as heat and phonon energy. This heat, when coupled with a high thermo-optic coefficient (dn/dT) can give rise to thermal lensing as well as reduced quantum efficiency. These types of issues can be overcome by another novel diode-pumped solid state laser, the diode-pumped thin disk laser. The thermal limitations in this laser type are mitigated by utilizing a laser medium geometry in which the thickness is much smaller than the diameter of the pump beam. This allows for a more even thermal gradient in the material. Thin disk lasers have been shown to produce up to kilowatt levels of power. ## Fiber-hosted lasers Solid-state lasers where the light is guided due to the total internal reflection in a wavequide are called fiber lasers because of huge ratio of the length to the transversal size; this ratio may vary from 106 to 109; visually, the active element of such a laser looks as a fiber. Guiding of light allows extremely long gain regions providing good cooling conditions; fibers have high surface area to volume ratio allows efficient cooling. In addition, the fiber's waveguiding properties tend to reduce thermal distortion of the beam. double-clad fibers. Quite often, the fiber laser is designed as a double-clad fiber. This type of fiber consists of a fiber core, an inner cladding and an outer cladding. The index of the three concentric layers is chosen so that the fiber core acts as a single-mode fiber for the laser emission while the outer cladding acts as a highly multimode core for the pump laser. This lets the pump propagate a large amount of power into and through the active inner core region, while still having a high numerical aperture (NA) to have easy launching conditions. Fiber disk lasers. The efficient use of pump in fiber laser can be achieved at the transversal delivery of pump; however, several lasers should be formed into a stack. Such stack may have shape of a disk, which is an alternative to the double-clad fiber. Maximal length of a fiber laser. Fiber lasers have a fundamental limit in that the intensity of the light in the fiber cannot be so high that optical nonlinearities induced by the local electric field strength can become dominant and prevent laser operation and/or lead to the material destruction of the fiber. This effect is called photodarkening. In bulk laser materials, the cooling is not so efficient, and it is difficult to separate the effects of photodarkening from the thermal effects, but the experiments in fibers the photodarkening can be attributed to the forming og long-living color centers. ### Semiconductor lasers Commercial laser diodes emit at wavelengths from 375 nm to 1800 nm, and wavelengths of over 3 µm have been demonstrated. Low power laser diodes are used in laser printers and CD/DVD players. More powerful laser diodes are frequently used to optically pump other lasers with high efficiency. The highest power industrial laser diodes, with power up to 10 kW, are used in industry for cutting and welding. External-cavity semiconductor lasers have a semiconductor active medium in a larger cavity. These devices can generate high power outputs with good beam quality, wavelength-tunable narrow-linewidth radiation, or ultrashort laser pulses. Vertical cavity surface-emitting lasers (VCSELs) are semiconductor lasers whose emission direction is perpendicular to the surface of the wafer. VCSEL devices typically have a more circular output beam than conventional laser diodes, and potentially could be much cheaper to manufacture. As of 2005, only 850 nm VCSELs are widely available, with 1300 nm VCSELs beginning to be commercialized, and 1550 nm devices an area of research. VECSELs are external-cavity VCSELs. Quantum cascade lasers are semiconductor lasers that have an active transition between energy sub-bands of an electron in a structure containing several quantum wells. The development of a silicon laser is important in the field of optical computing, since it means that if silicon, the chief ingredient of computer chips, were able to produce lasers, it would allow the light to be manipulated like electrons are in normal integrated circuits. Thus, photons would replace electrons in the circuits, which dramatically increases the speed of the computer. Unfortunately, silicon is a difficult lasing material to deal with, since it has certain properties which block lasing. However, recently teams have produced silicon lasers through methods such as fabricating the lasing material from silicon and other semiconductor materials, such as indium(III) phosphide or gallium(III) arsenide, materials which allow coherent light to be produced from silicon. These are called hybrid silicon laser. Another type is a Raman laser, which takes advantage of Raman scattering to produce a laser from materials such as silicon. ## Dye lasers Dye lasers use an organic dye as the gain medium. The wide gain spectrum of available dyes allows these lasers to be highly tunable, or to produce very short-duration pulses (on the order of a few femtoseconds) ## Free electron lasers Free electron lasers, or FELs, generate coherent, high power radiation, that is widely tunable, currently ranging in wavelength from microwaves, through terahertz radiation and infrared, to the visible spectrum, to soft X-rays. They have the widest frequency range of any laser type. While FEL beams share the same optical traits as other lasers, such as coherent radiation, FEL operation is quite different. Unlike gas, liquid, or solid-state lasers, which rely on bound atomic or molecular states, FELs use a relativistic electron beam as the lasing medium, hence the term free electron. ## Nuclear reaction lasers In September 2007, the BBC News reported that there was speculation about the possibility of using positronium annihilation to drive a very powerful gamma ray laser. This laser is believed to be powerful enough to jump-start a nuclear reaction, with a single gamma ray laser, rather than the hundreds of conventional lasers involved in current experiments. # Uses When lasers were invented in 1960, they were called "a solution looking for a problem". Since then, they have become ubiquitous, finding utility in thousands of highly varied applications in every section of modern society, including consumer electronics, information technology, science, medicine, industry, law enforcement, entertainment, and the military. The first application of lasers visible in the daily lives of the general population was the supermarket barcode scanner, introduced in 1974. The laserdisc player, introduced in 1978, was the first successful consumer product to include a laser, but the compact disc player was the first laser-equipped device to become truly common in consumers' homes, beginning in 1982, followed shortly by laser printers. Some of the other applications include: - Medicine: Bleedless surgery, laser healing, survical treatment, kidney stone treatment, eye treatment, dentistry - Industry: Cutting, welding, material heat treatment, marking parts - Defense: Marking targets, guiding munitions, missile defence, electro-optical countermeasures (EOCM), RADAR alternative - Research: Spectroscopy, laser ablation, Laser annealing, laser scattering, laser interferometry, LIDAR - Product development/Commercial: Laser Printers, CDs, Barcode scanners, laser pointers, Holograms) In 2004, excluding diode lasers, approximately 131,000 lasers were sold world-wide, with a value of US$2.19 billion. In the same year, approximately 733 million diode lasers, valued at $3.20 billion, were sold. ## Example uses by typical output power Different uses need lasers with different output powers. Many lasers are designed for a higher peak output with an extremely short pulse, and this requires different technology from a continuous wave (constant output) lasers, as are used in communication, or cutting. Output power is always less than the input power needed to generate the beam. The peak power required for some uses: - 5 mW - CD-ROM drive - 5-10 mW - DVD player - 100 mW - CD-R drive - 250 mW - output power of Sony SLD253VL red laser diode, used in consumer 48-52 speed CD-R burner. - 500 mW - output power of Sony SLD1332V red laser diode, used in consumer DVD-R burner. - 1 W - green laser in current Holographic Versatile Disc prototype development. - 100 to 3000 W (peak output 1.5 kW) - typical sealed CO2 lasers used in industrial laser cutting. - 1 kW - Output power expected to be achieved by "a single 1 cm diode laser bar" - 700 terawatts (TW) - The National Ignition Facility is working on a system that, when complete, will contain a 192-beam, 1.8-megajoule laser system adjoining a 10-meter-diameter target chamber. The system is expected to be completed in April of 2009. - 1.25 petawatts (PW) - world's most powerful laser (claimed on 23 May 1996 by Lawrence Livermore Laboratory). ## Hobby uses In recent years, some hobbyists have taken interests in lasers. Lasers used by hobbyists are generally of class IIIa or IIIb, although some have made their own class IV types. However, compared to other hobbyists, laser hobbyists are far less common, due to the cost and potential dangers involved. Due to the cost of lasers, some hobbyists use inexpensive means to obtain lasers, such as extracting diodes from DVD burners. # Laser safety Even the first laser was recognized as being potentially dangerous. Theodore Maiman characterized the first laser as having a power of one "Gillette"; as it could burn through one Gillette razor blade. Today, it is accepted that even low-power lasers with only a few milliwatts of output power can be hazardous to human eyesight. At wavelengths which the cornea and the lens can focus well, the coherence and low divergence of laser light means that it can be focused by the eye into an extremely small spot on the retina, resulting in localized burning and permanent damage in seconds or even less time. Lasers are classified into safety classes numbered I (inherently safe) to IV (even scattered light can cause eye and/or skin damage). Laser products available for consumers, such as CD players and laser pointers are usually in class I, II, or III. Certain infrared lasers with wavelengths beyond about 1.4 micrometres are often referred to as being "eye-safe". This is because the intrinsic molecular vibrations of water molecules very strongly absorb light in this part of the spectrum, and thus a laser beam at these wavelengths is attenuated so completely as it passes through the eye's cornea that no light remains to be focused by the lens onto the retina. The label "eye-safe" can be misleading, however, as it only applies to relatively low power continuous wave beams and any high power or q-switched laser at these wavelengths can burn the cornea, causing severe eye damage. # Related terminology In analogy with optical lasers, a device which produces any particles or electromagnetic radiation in a coherent state is also called a "laser", usually with indication of type of particle as prefix (for example, atom laser.) In most cases, "laser" refers to a source of coherent light or other electromagnetic radiation. The back-formed verb lase means "to produce laser light" or "to apply laser light to". # Fictional predictions Before stimulated emission was discovered, novelists used to describe machines that we can identify as "lasers". - The first fictional device similar to a military CO2 laser (see Heat-Ray) appears in the sci-fi novel The War of the Worlds by H. G. Wells in 1898. - A laser-like device was described in Alexey Tolstoy's sci-fi novel The Hyperboloid of Engineer Garin in 1927: see Raygun#In specific scenarios (scroll down to alphabetical order 'H' in the left column). - Mikhail Bulgakov exaggerated the biological effect (laser biostimulation) of intensive red light in his sci-fi novel Fatal Eggs (1925), without any reasonable description of the source of this red light. (In that novel, the red light first appears occasionally from the illuminating system of an advanced microscope; then the protagonist Prof. Persikov arranges the special set-up for generation of the red light.) # Popular misconceptions The representation of lasers in popular culture, especially in science fiction and action movies, is often misleading. Contrary to their portrayal in many science fiction movies, a laser beam would not be visible (at least to the naked eye) in the near vacuum of space as there would be insufficient matter to cause scattering, except if there were a significant amount of fine shrapnel and other organic particles in that region. In air, however, moderate intensity (tens of mW/cm²) laser beams of shorter green and blue wavelengths and high intensity beams of longer orange and red wavelengths can be visible due to Rayleigh scattering. With even higher intensity pulsed beams, the air can be heated to the point where it becomes a plasma, which is also visible. This causes rapid heating and explosive expansion of the surrounding air, which makes a popping noise analogous to the thunder which accompanies lightning. The term "thermal blooming" is used to describe these self-induced thermal distortions. This phenomenon can cause retro-reflection of the laser beam back into the laser source, possibly damaging its optics. When this phenomenon occurs in certain scientific experiments it is referred to as a "plasma mirror" or "plasma shutter". One approach for overcoming thermal distortion is to use a short-duration laser pulse. Some action movies depict security systems using lasers of visible light (and their foiling by the hero, typically using mirrors); the hero may see the path of the beam by sprinkling some dust in the air. It is far easier and cheaper to build infrared laser diodes rather than visible light laser diodes, and such systems almost never use visible light lasers. Additionally, putting enough dust in the air to make the beam visible is likely to be enough to "break" the beam and trigger the alarm (as demonstrated on an episode of MythBusters on the Discovery Channel). Science fiction films special effects often depict laser beams propagating at only a few metres per second—slowly enough to see their progress, in a manner reminiscent of conventional tracer ammunition—whereas in reality a laser beam travels at the speed of light and would seem to appear instantly to the naked eye from start to end. Several of these misconceptions can be found in the 1964 James Bond film Goldfinger. In one of the most famous scenes in the Bond films, Bond, played by Sean Connery, faces a laser beam approaching his groin while melting the solid gold table to which he is strapped. The director Guy Hamilton found that a real laser beam would not show up on camera so it was added as an optical effect. The table was precut up the middle and coated with gold paint, while the melting effect was achieved by a man below the table with an oxyacetylene torch. Goldfinger's laser makes a whirring electronic sound, while a real laser would have produced a fairly heat-free and silent cut. In addition to movies and popular culture, laser misconceptions are present in some popular science publications or simple introductory explanations. For example, laser light is not perfectly parallel as is sometimes claimed; all laser beams spread out to some degree as they propagate due to diffraction. In addition, no laser is perfectly monochromatic (i.e. coherent); most operate at several closely spaced frequencies (colors) and even those that nominally operate a single frequency still exhibit some variation in frequency. Furthermore, mode locked lasers are designed to operate with thousands or millions of frequencies locked together to form a short pulse.	Laser # Overview A laser is an electronic-optical device that produces coherent radiation. The term "laser" is an acronym for "Light Amplification by Stimulated Emission of Radiation".[1][2] A typical laser emits light in a narrow, low-divergence beam and with a well-defined wavelength (i.e., monochromatic, corresponding to a particular colour if the laser is operating in the visible spectrum). This is in contrast to a light source such as the incandescent light bulb, which emits into a large solid angle and over a wide spectrum of wavelength. A laser consists of a gain medium inside an optical cavity, with a means to supply energy to the gain medium. The gain medium is a material (gas, liquid, solid or free electrons) with appropriate optical properties. In its simplest form, a cavity consists of two mirrors arranged such that light bounces back and forth, each time passing through the gain medium. Typically, one of the two mirrors, the output coupler, is partially transparent. The output laser beam is emitted through this mirror. Light of a specific wavelength that passes through the gain medium is amplified (increases in power); the surrounding mirrors ensure that most of the light makes many passes through the gain medium. Part of the light that is between the mirrors (i.e., is in the cavity) passes through the partially transparent mirror and appears as a beam of light. The process of supplying the energy required for the amplification is called pumping and the energy is typically supplied as an electrical current or as light at a different wavelength. In the latter case, the light source can be a flash lamp or another laser. Most practical lasers contain additional elements that affect properties such as the wavelength of the emitted light and the shape of the beam. The first working laser was demonstrated in May 1960 by Theodore Maiman at Hughes Research Laboratories. Recently, lasers have become a multi-billion dollar industry. The most widespread use of lasers is in optical storage devices such as compact disc and DVD players, in which the laser (a few millimeters in size) scans the surface of the disc. Other common applications of lasers are bar code readers and laser pointers. In industry, lasers are used for cutting steel and other metals and for inscribing patterns (such as the letters on computer keyboards). Lasers are also commonly used in various fields in science, especially spectroscopy, typically because of their well-defined wavelength or short pulse duration in the case of pulsed lasers. Lasers are also used for military and medical applications. Template:TOClimit # Physics A laser is composed of an active laser medium, or gain medium, and a resonant optical cavity. The gain medium transfers external energy into the laser beam. It is a material of controlled purity, size, concentration, and shape, which amplifies the beam by the process of stimulated emission. The gain medium is energized, or pumped, by an external energy source. Examples of pump sources include electricity and light, for example from a flash lamp or from another laser. The pump energy is absorbed by the laser medium, placing some of its particles into high-energy ("excited") quantum states. Particles can interact with light both by absorbing photons or by emitting photons. Emission can be spontaneous or stimulated. In the latter case, the photon is emitted in the same direction as the light that is passing by. When the number of particles in one excited state exceeds the number of particles in some lower-energy state, population inversion is achieved and the amount of stimulated emission due to light that passes through is larger than the amount of absorption. Hence, the light is amplified. Strictly speaking, these are the essential ingredients of a laser. However, usually the term laser is used for devices where the light that is amplified is produced as spontaneous emission from the same gain medium as where the amplification takes place. Devices where light from an external source is amplified are normally called optical amplifiers. The light generated by stimulated emission is very similar to the input signal in terms of wavelength, phase, and polarization. This gives laser light its characteristic coherence, and allows it to maintain the uniform polarization and often monochromaticity established by the optical cavity design. The optical cavity, a type of cavity resonator, contains a coherent beam of light between reflective surfaces so that the light passes through the gain medium more than once before it is emitted from the output aperture or lost to diffraction or absorption. As light circulates through the cavity, passing through the gain medium, if the gain (amplification) in the medium is stronger than the resonator losses, the power of the circulating light can rise exponentially. But each stimulated emission event returns a particle from its excited state to the ground state, reducing the capacity of the gain medium for further amplification. When this effect becomes strong, the gain is said to be saturated. The balance of pump power against gain saturation and cavity losses produces an equilibrium value of the laser power inside the cavity; this equilibrium determines the operating point of the laser. If the chosen pump power is too small, the gain is not sufficient to overcome the resonator losses, and the laser will emit only very small light powers. The minimum pump power needed to begin laser action is called the lasing threshold. The gain medium will amplify any photons passing through it, regardless of direction; but only the photons aligned with the cavity manage to pass more than once through the medium and so have significant amplification. The beam in the cavity and the output beam of the laser, if they occur in free space rather than waveguides (as in an optical fiber laser), are, at best, low order Gaussian beams. However this is rarely the case with powerful lasers. If the beam is not a low-order Gaussian shape, the transverse modes of the beam can be described as a superposition of Hermite-Gaussian or Laguerre-Gaussian beams (for stable-cavity lasers). Unstable laser resonators on the other hand, have been shown to produce fractal shaped beams.[3] The beam may be highly collimated, that is being parallel without diverging. However, a perfectly collimated beam cannot be created, due to diffraction. The beam remains collimated over a distance which varies with the square of the beam diameter, and eventually diverges at an angle which varies inversely with the beam diameter. Thus, a beam generated by a small laboratory laser such as a helium-neon laser spreads to about 1.6 kilometers (1 mile) diameter if shone from the Earth to the Moon. By comparison, the output of a typical semiconductor laser, due to its small diameter, diverges almost as soon as it leaves the aperture, at an angle of anything up to 50°. However, such a divergent beam can be transformed into a collimated beam by means of a lens. In contrast, the light from non-laser light sources cannot be collimated by optics as well or much. The output of a laser may be a continuous constant-amplitude output (known as CW or continuous wave); or pulsed, by using the techniques of Q-switching, modelocking, or gain-switching. In pulsed operation, much higher peak powers can be achieved. Some types of lasers, such as dye lasers and vibronic solid-state lasers can produce light over a broad range of wavelengths; this property makes them suitable for generating extremely short pulses of light, on the order of a few femtoseconds (10-15 s). Although the laser phenomenon was discovered with the help of quantum physics, it is not essentially more quantum mechanical than other light sources. The operation of a free electron laser can be explained without reference to quantum mechanics. It is understood that the word light in the acronym Light Amplification by Stimulated Emission of Radiation is typically used in the expansive sense, as photons of any energy; it is not limited to photons in the visible spectrum. Hence there are infrared lasers, ultraviolet lasers, X-ray lasers, etc. For example, a source of atoms in a coherent state can be called an atom laser. Because the microwave equivalent of the laser, the maser, was developed first, devices that emit microwave and radio frequencies are usually called masers. In early literature, particularly from researchers at Bell Telephone Laboratories, the laser was often called the optical maser. This usage has since become uncommon, and as of 1998 even Bell Labs uses the term laser.[4] # History ## Foundations In 1917, Albert Einstein in his paper Zur Quantentheorie der Strahlung (On the Quantum Theory of Radiation), laid the foundation for the invention of the laser and its predecessor, the maser, in a ground-breaking rederivation of Max Planck's law of radiation based on the concepts of probability coefficients (later to be termed 'Einstein coefficients') for the absorption, spontaneous, and stimulated emission. In 1928, Rudolph W. Landenburg confirmed the existence of stimulated emission and negative absorption.[5] In 1939, Valentin A. Fabrikant (USSR) predicted the use of stimulated emission to amplify "short" waves.[6] In 1947, Willis E. Lamb and R. C. Retherford found apparent stimulated emission in hydrogen spectra and made the first demonstration of stimulated emission.[7] In 1950, Alfred Kastler (Nobel Prize for Physics 1966) proposed the method of optical pumping, which was experimentally confirmed by Brossel, Kastler and Winter two years later.[8] ## Maser In 1953, Charles H. Townes and graduate students James P. Gordon and Herbert J. Zeiger produced the first microwave amplifier, a device operating on similar principles to the laser, but amplifying microwave rather than infrared or visible radiation. Townes's maser was incapable of continuous output. Nikolay Basov and Aleksandr Prokhorov of the Soviet Union worked independently on the quantum oscillator and solved the problem of continuous output systems by using more than two energy levels and produced the first maser. These systems could release stimulated emission without falling to the ground state, thus maintaining a population inversion. In 1955 Prokhorov and Basov suggested an optical pumping of multilevel system as a method for obtaining the population inversion, which later became one of the main methods of laser pumping. Townes reports that he encountered opposition from a number of eminent colleagues who thought the maser was theoretically impossible -- including Niels Bohr, John von Neumann, Isidor Rabi, Polykarp Kusch, and Llewellyn H. Thomas[2]. Townes, Basov, and Prokhorov shared the Nobel Prize in Physics in 1964 "For fundamental work in the field of quantum electronics, which has led to the construction of oscillators and amplifiers based on the maser-laser principle". ## Laser In 1957, Charles Hard Townes and Arthur Leonard Schawlow, then at Bell Labs, began a serious study of the infrared laser. As ideas were developed, infrared frequencies were abandoned with focus on visible light instead. The concept was originally known as an "optical maser". Bell Labs filed a patent application for their proposed optical maser a year later. Schawlow and Townes sent a manuscript of their theoretical calculations to Physical Review, which published their paper that year (Volume 112, Issue 6). At the same time Gordon Gould, a graduate student at Columbia University, was working on a doctoral thesis on the energy levels of excited thallium. Gould and Townes met and had conversations on the general subject of radiation emission. Afterwards Gould made notes about his ideas for a "laser" in November 1957, including suggesting using an open resonator, which became an important ingredient of future lasers. In 1958, Prokhorov independently proposed using an open resonator, the first published appearance of this idea. Schawlow and Townes also settled on an open resonator design, apparently unaware of both the published work of Prokhorov and the unpublished work of Gould. The term "laser" was first introduced to the public in Gould's 1959 conference paper "The LASER, Light Amplification by Stimulated Emission of Radiation".[9] [10] Gould intended "-aser" to be a suffix, to be used with an appropriate prefix for the spectra of light emitted by the device (x-ray laser = xaser, ultraviolet laser = uvaser, etc.). None of the other terms became popular, although "raser" was used for a short time to describe radio-frequency emitting devices. Gould's notes included possible applications for a laser, such as spectrometry, interferometry, radar, and nuclear fusion. He continued working on his idea and filed a patent application in April 1959. The U.S. Patent Office denied his application and awarded a patent to Bell Labs in 1960. This sparked a legal battle that ran 28 years, with scientific prestige and much money at stake. Gould won his first minor patent in 1977, but it was not until 1987 that he could claim his first significant patent victory when a federal judge ordered the government to issue patents to him for the optically pumped laser and the gas discharge laser. The first working laser was made by Theodore H. Maiman in 1960[11] at Hughes Research Laboratories in Malibu, California, beating several research teams including those of Townes at Columbia University, Arthur L. Schawlow at Bell Labs,[12] and Gould at a company called TRG (Technical Research Group). Maiman used a solid-state flashlamp-pumped synthetic ruby crystal to produce red laser light at 694 nanometres wavelength. Maiman's laser, however, was only capable of pulsed operation due to its three energy level pumping scheme. Later in 1960 the Iranian physicist Ali Javan, working with William R. Bennett and Donald Herriot, made the first gas laser using helium and neon. Javan later received the Albert Einstein Award in 1993. The concept of the semiconductor laser diode was proposed by Basov and Javan. The first laser diode was demonstrated by Robert N. Hall in 1962. Hall's device was made of gallium arsenide and emitted at 850 nm in the near-infrared region of the spectrum. The first semiconductor laser with visible emission was demonstrated later the same year by Nick Holonyak, Jr. As with the first gas lasers, these early semiconductor lasers could be used only in pulsed operation, and indeed only when cooled to liquid nitrogen temperatures (77 K). In 1970, Zhores Alferov in the Soviet Union and Izuo Hayashi and Morton Panish of Bell Telephone Laboratories independently developed laser diodes continuously operating at room temperature, using the heterojunction structure. ## Recent innovations Since the early period of laser history, laser research has produced a variety of improved and specialized laser types, optimized for different performance goals, including: - new wavelength bands - maximum average output power - maximum peak output power - minimum output pulse duration - maximum power efficiency - maximum charging - maximum firing and this research continues to this day. Lasing without maintaining the medium excited into a population inversion, was discovered in 1992 in sodium gas and again in 1995 in rubidium gas by various international teams. This was accomplished by using an external maser to induce "optical transparency" in the medium by introducing and destructively interfering the ground electron transitions between two paths, so that the likelihood for the ground electrons to absorb any energy has been cancelled. In 1985 at the University of Rochester's Laboratory for Laser Energetics a breakthrough in creating ultrashort-pulse, very high-intensity (terawatts) laser pulses became available using a technique called chirped pulse amplification, or CPA, discovered by Gérard Mourou. These high intensity pulses can produce filament propagation in the atmosphere. # Continuous wave and pulsed lasing A laser may either be built to emit a continuous beam or a train of short pulses. This makes fundamental differences in construction, usable laser media, and applications. ## Continuous wave operation In the continuous wave (CW) mode of operation, the output of a laser is relatively consistent with respect to time. The population inversion required for lasing is continually maintained by a steady pump source. ## Pulsed operation In the pulsed mode of operation, the output of a laser varies with respect to time, typically taking the form of alternating 'on' and 'off' periods. In many applications one aims to deposit as much energy as possible at a given place in as short time as possible. In laser ablation for example, a small volume of material at the surface of a work piece might evaporate if it gets the energy required to heat it up far enough in very short time. If, however, the same energy is spread over a longer time, the heat may have time to disperse into the bulk of the piece, and less material evaporates. There are a number of methods to achieve this. ### Q-switching In a Q-switched laser, the population inversion (usually produced in the same way as CW operation) is allowed to build up by making the cavity conditions (the 'Q') unfavorable for lasing. Then, when the pump energy stored in the laser medium is at the desired level, the 'Q' is adjusted (electro- or acousto-optically) to favorable conditions, releasing the pulse. This results in high peak powers as the average power of the laser (were it running in CW mode) is packed into a shorter time frame. ### Modelocking A modelocked laser emits extremely short pulses on the order of tens of picoseconds down to less than 10 femtoseconds. These pulses are typically separated by the time that a pulse takes to complete one round trip in the resonator cavity. Due to the Fourier limit (also known as energy-time uncertainty), a pulse of such short temporal length has a spectrum which contains a wide range of wavelengths. Because of this, the laser medium must have a broad enough gain profile to amplify them all. An example of a suitable material is titanium-doped, artificially grown sapphire (Ti:sapphire). The modelocked laser is a most versatile tool for researching processes happening at extremely fast time scales (femtosecond physics and femtosecond chemistry, also called ultrafast science), for maximizing the effect of nonlinearity in optical materials (e.g. in second-harmonic generation, parametric down-conversion, optical parametric oscillators and the like), and in ablation applications. Again, because of the short timescales involved, these lasers can achieve extremely high powers. ### Pulsed pumping Another method of achieving pulsed laser operation is to pump the laser material with a source that is itself pulsed, either through electronic charging in the case of flashlamps, or another laser which is already pulsed. Pulsed pumping was historically used with dye lasers where the inverted population lifetime of a dye molecule was so short that a high energy, fast pump was needed. The way to overcome this problem was to charge up large capacitors which are then switched to discharge through flashlamps, producing a broad spectrum pump flash. Pulsed pumping is also required for lasers which disrupt the gain medium so much during the laser process that lasing has to cease for a short period. These lasers, such as the excimer laser and the copper vapour laser, can never be operated in CW mode. # Types and operating principles ## Gas lasers Gas lasers using many gases have been built and used for many purposes. They are one of the oldest types of laser. The helium-neon laser (HeNe) emits at a variety of wavelengths and units operating at 633 nm are very common in education because of its low cost. Carbon dioxide lasers can emit hundreds of kilowatts[13] at 9.6 µm and 10.6 µm, and are often used in industry for cutting and welding. The efficiency of a CO2 laser is over 10%. Argon-ion lasers emit light in the range 351-528.7 nm. Depending on the optics and the laser tube a different number of lines is usable but the most commonly used lines are 458 nm, 488 nm and 514.5 nm. A nitrogen transverse electrical discharge in gas at atmospheric pressure (TEA) laser is an inexpensive gas laser producing UV Light at 337.1 nm.[14] Metal ion lasers are gas lasers that generate deep ultraviolet wavelengths. Helium-silver (HeAg) 224 nm and neon-copper (NeCu) 248 nm are two examples. These lasers have particularly narrow oscillation linewidths of less than 3 GHz (0.5 picometers),[15] making them candidates for use in fluorescence suppressed Raman spectroscopy. ## Chemical lasers Chemical lasers are powered by a chemical reaction, and can achieve high powers in continuous operation. For example, in the Hydrogen fluoride laser (2700-2900 nm) and the Deuterium fluoride laser (3800 nm) the reaction is the combination of hydrogen or deuterium gas with combustion products of ethylene in nitrogen trifluoride. They were invented by George C. Pimentel. ### Excimer lasers Excimer lasers are powered by a chemical reaction involving an excited dimer, or excimer, which is a short-lived dimeric or heterodimeric molecule formed from two species (atoms), at least one of which is in an excited electronic state. They typically produce ultraviolet light, and are used in semiconductor photolithography and in LASIK eye surgery. Commonly used excimer molecules include F2 (fluorine, emitting at 157 nm), and noble gas compounds (ArF [193 nm], KrCl [222 nm], KrF [248 nm], XeCl [308 nm], and XeF [351 nm]).[16] ## Solid-state lasers Starfire Optical Range Solid state laser materials are commonly made by doping a crystalline solid host with ions that provide the required energy states. For example, the first working laser was a ruby laser, made from ruby (chromium-doped corundum). Formally, the class of solid-state lasers includes also fiber laser, as the active medium (fiber) is in the solid state. Practically, in the scientific literature, solid-state laser usually means a laser with bulk active medium; while wave-guide lasers are caller fiber lasers. Neodymium is a common dopant in various solid state laser crystals, including yttrium orthovanadate (Nd:YVO4), yttrium lithium fluoride (Nd:YLF) and yttrium aluminium garnet (Nd:YAG). All these lasers can produce high powers in the infrared spectrum at 1064 nm. They are used for cutting, welding and marking of metals and other materials, and also in spectroscopy and for pumping dye lasers. These lasers are also commonly frequency doubled, tripled or quadrupled to produce 532 nm (green, visible), 355 nm (UV) and 266 nm (UV) light when those wavelengths are needed. Ytterbium, holmium, thulium, and erbium are other common dopants in solid state lasers. Ytterbium is used in crystals such as Yb:YAG, Yb:KGW, Yb:KYW, Yb:SYS, Yb:BOYS, Yb:CaF2, typically operating around 1020-1050 nm. They are potentially very efficient and high powered due to a small quantum defect. Extremely high powers in ultrashort pulses can be achieved with Yb:YAG. Holmium-doped YAG crystals emit at 2097 nm and form an efficient laser operating at infrared wavelengths strongly absorbed by water-bearing tissues. The Ho-YAG is usually operated in a pulsed mode, and passed through optical fiber surgical devices to resurface joints, remove rot from teeth, vaporize cancers, and pulverize kidney and gall stones. Titanium-doped sapphire (Ti:sapphire) produces a highly tunable infrared laser, commonly used for spectroscopy as well as the most common ultrashort pulse laser. Thermal limitations in solid-state lasers arise from unconverted pump power that manifests itself as heat and phonon energy. This heat, when coupled with a high thermo-optic coefficient (dn/dT) can give rise to thermal lensing as well as reduced quantum efficiency. These types of issues can be overcome by another novel diode-pumped solid state laser, the diode-pumped thin disk laser. The thermal limitations in this laser type are mitigated by utilizing a laser medium geometry in which the thickness is much smaller than the diameter of the pump beam. This allows for a more even thermal gradient in the material. Thin disk lasers have been shown to produce up to kilowatt levels of power.[17] ## Fiber-hosted lasers Solid-state lasers where the light is guided due to the total internal reflection in a wavequide are called fiber lasers because of huge ratio of the length to the transversal size; this ratio may vary from 106 to 109; visually, the active element of such a laser looks as a fiber. Guiding of light allows extremely long gain regions providing good cooling conditions; fibers have high surface area to volume ratio allows efficient cooling. In addition, the fiber's waveguiding properties tend to reduce thermal distortion of the beam. double-clad fibers. Quite often, the fiber laser is designed as a double-clad fiber. This type of fiber consists of a fiber core, an inner cladding and an outer cladding. The index of the three concentric layers is chosen so that the fiber core acts as a single-mode fiber for the laser emission while the outer cladding acts as a highly multimode core for the pump laser. This lets the pump propagate a large amount of power into and through the active inner core region, while still having a high numerical aperture (NA) to have easy launching conditions. Fiber disk lasers. The efficient use of pump in fiber laser can be achieved at the transversal delivery of pump; however, several lasers should be formed into a stack. Such stack may have shape of a disk, which is an alternative to the double-clad fiber. Maximal length of a fiber laser. Fiber lasers have a fundamental limit in that the intensity of the light in the fiber cannot be so high that optical nonlinearities induced by the local electric field strength can become dominant and prevent laser operation and/or lead to the material destruction of the fiber. This effect is called photodarkening. In bulk laser materials, the cooling is not so efficient, and it is difficult to separate the effects of photodarkening from the thermal effects, but the experiments in fibers the photodarkening can be attributed to the forming og long-living color centers. ### Semiconductor lasers Commercial laser diodes emit at wavelengths from 375 nm to 1800 nm, and wavelengths of over 3 µm have been demonstrated. Low power laser diodes are used in laser printers and CD/DVD players. More powerful laser diodes are frequently used to optically pump other lasers with high efficiency. The highest power industrial laser diodes, with power up to 10 kW, are used in industry for cutting and welding. External-cavity semiconductor lasers have a semiconductor active medium in a larger cavity. These devices can generate high power outputs with good beam quality, wavelength-tunable narrow-linewidth radiation, or ultrashort laser pulses. Vertical cavity surface-emitting lasers (VCSELs) are semiconductor lasers whose emission direction is perpendicular to the surface of the wafer. VCSEL devices typically have a more circular output beam than conventional laser diodes, and potentially could be much cheaper to manufacture. As of 2005, only 850 nm VCSELs are widely available, with 1300 nm VCSELs beginning to be commercialized,[18] and 1550 nm devices an area of research. VECSELs are external-cavity VCSELs. Quantum cascade lasers are semiconductor lasers that have an active transition between energy sub-bands of an electron in a structure containing several quantum wells. The development of a silicon laser is important in the field of optical computing, since it means that if silicon, the chief ingredient of computer chips, were able to produce lasers, it would allow the light to be manipulated like electrons are in normal integrated circuits. Thus, photons would replace electrons in the circuits, which dramatically increases the speed of the computer. Unfortunately, silicon is a difficult lasing material to deal with, since it has certain properties which block lasing. However, recently teams have produced silicon lasers through methods such as fabricating the lasing material from silicon and other semiconductor materials, such as indium(III) phosphide or gallium(III) arsenide, materials which allow coherent light to be produced from silicon. These are called hybrid silicon laser. Another type is a Raman laser, which takes advantage of Raman scattering to produce a laser from materials such as silicon. ## Dye lasers Dye lasers use an organic dye as the gain medium. The wide gain spectrum of available dyes allows these lasers to be highly tunable, or to produce very short-duration pulses (on the order of a few femtoseconds) ## Free electron lasers Free electron lasers, or FELs, generate coherent, high power radiation, that is widely tunable, currently ranging in wavelength from microwaves, through terahertz radiation and infrared, to the visible spectrum, to soft X-rays. They have the widest frequency range of any laser type. While FEL beams share the same optical traits as other lasers, such as coherent radiation, FEL operation is quite different. Unlike gas, liquid, or solid-state lasers, which rely on bound atomic or molecular states, FELs use a relativistic electron beam as the lasing medium, hence the term free electron. ## Nuclear reaction lasers In September 2007, the BBC News reported that there was speculation about the possibility of using positronium annihilation to drive a very powerful gamma ray laser. [19] This laser is believed to be powerful enough to jump-start a nuclear reaction, with a single gamma ray laser, rather than the hundreds of conventional lasers involved in current experiments. # Uses When lasers were invented in 1960, they were called "a solution looking for a problem". Since then, they have become ubiquitous, finding utility in thousands of highly varied applications in every section of modern society, including consumer electronics, information technology, science, medicine, industry, law enforcement, entertainment, and the military. The first application of lasers visible in the daily lives of the general population was the supermarket barcode scanner, introduced in 1974. The laserdisc player, introduced in 1978, was the first successful consumer product to include a laser, but the compact disc player was the first laser-equipped device to become truly common in consumers' homes, beginning in 1982, followed shortly by laser printers. Some of the other applications include: - Medicine: Bleedless surgery, laser healing, survical treatment, kidney stone treatment, eye treatment, dentistry - Industry: Cutting, welding, material heat treatment, marking parts - Defense: Marking targets, guiding munitions, missile defence, electro-optical countermeasures (EOCM), RADAR alternative - Research: Spectroscopy, laser ablation, Laser annealing, laser scattering, laser interferometry, LIDAR - Product development/Commercial: Laser Printers, CDs, Barcode scanners, laser pointers, Holograms) In 2004, excluding diode lasers, approximately 131,000 lasers were sold world-wide, with a value of US$2.19 billion.[20] In the same year, approximately 733 million diode lasers, valued at $3.20 billion, were sold.[21] ## Example uses by typical output power Different uses need lasers with different output powers. Many lasers are designed for a higher peak output with an extremely short pulse, and this requires different technology from a continuous wave (constant output) lasers, as are used in communication, or cutting. Output power is always less than the input power needed to generate the beam. The peak power required for some uses: - 5 mW - CD-ROM drive - 5-10 mW - DVD player - 100 mW - CD-R drive - 250 mW - output power of Sony SLD253VL red laser diode, used in consumer 48-52 speed CD-R burner.[22] - 500 mW - output power of Sony SLD1332V red laser diode, used in consumer DVD-R burner.[23] - 1 W - green laser in current Holographic Versatile Disc prototype development. - 100 to 3000 W (peak output 1.5 kW) - typical sealed CO2 lasers used in industrial laser cutting. - 1 kW - Output power expected to be achieved by "a single 1 cm diode laser bar"[24] - 700 terawatts (TW) - The National Ignition Facility is working on a system that, when complete, will contain a 192-beam, 1.8-megajoule laser system adjoining a 10-meter-diameter target chamber.[25] The system is expected to be completed in April of 2009. - 1.25 petawatts (PW) - world's most powerful laser (claimed on 23 May 1996 by Lawrence Livermore Laboratory). ## Hobby uses In recent years, some hobbyists have taken interests in lasers. Lasers used by hobbyists are generally of class IIIa or IIIb, although some have made their own class IV types.[26] However, compared to other hobbyists, laser hobbyists are far less common, due to the cost and potential dangers involved. Due to the cost of lasers, some hobbyists use inexpensive means to obtain lasers, such as extracting diodes from DVD burners.[27] # Laser safety Even the first laser was recognized as being potentially dangerous. Theodore Maiman characterized the first laser as having a power of one "Gillette"; as it could burn through one Gillette razor blade. Today, it is accepted that even low-power lasers with only a few milliwatts of output power can be hazardous to human eyesight. At wavelengths which the cornea and the lens can focus well, the coherence and low divergence of laser light means that it can be focused by the eye into an extremely small spot on the retina, resulting in localized burning and permanent damage in seconds or even less time. Lasers are classified into safety classes numbered I (inherently safe) to IV (even scattered light can cause eye and/or skin damage). Laser products available for consumers, such as CD players and laser pointers are usually in class I, II, or III. Certain infrared lasers with wavelengths beyond about 1.4 micrometres are often referred to as being "eye-safe". This is because the intrinsic molecular vibrations of water molecules very strongly absorb light in this part of the spectrum, and thus a laser beam at these wavelengths is attenuated so completely as it passes through the eye's cornea that no light remains to be focused by the lens onto the retina. The label "eye-safe" can be misleading, however, as it only applies to relatively low power continuous wave beams and any high power or q-switched laser at these wavelengths can burn the cornea, causing severe eye damage. # Related terminology In analogy with optical lasers, a device which produces any particles or electromagnetic radiation in a coherent state is also called a "laser", usually with indication of type of particle as prefix (for example, atom laser.) In most cases, "laser" refers to a source of coherent light or other electromagnetic radiation. The back-formed verb lase means "to produce laser light" or "to apply laser light to".[28] # Fictional predictions Before stimulated emission was discovered, novelists used to describe machines that we can identify as "lasers". - The first fictional device similar to a military CO2 laser (see Heat-Ray) appears in the sci-fi novel The War of the Worlds by H. G. Wells in 1898. - A laser-like device was described in Alexey Tolstoy's sci-fi novel The Hyperboloid of Engineer Garin in 1927: see Raygun#In specific scenarios (scroll down to alphabetical order 'H' in the left column). - Mikhail Bulgakov exaggerated the biological effect (laser biostimulation) of intensive red light in his sci-fi novel Fatal Eggs (1925), without any reasonable description of the source of this red light. (In that novel, the red light first appears occasionally from the illuminating system of an advanced microscope; then the protagonist Prof. Persikov arranges the special set-up for generation of the red light.) # Popular misconceptions The representation of lasers in popular culture, especially in science fiction and action movies, is often misleading. Contrary to their portrayal in many science fiction movies, a laser beam would not be visible (at least to the naked eye) in the near vacuum of space as there would be insufficient matter to cause scattering, except if there were a significant amount of fine shrapnel and other organic particles in that region. In air, however, moderate intensity (tens of mW/cm²) laser beams of shorter green and blue wavelengths and high intensity beams of longer orange and red wavelengths can be visible due to Rayleigh scattering. With even higher intensity pulsed beams, the air can be heated to the point where it becomes a plasma, which is also visible. This causes rapid heating and explosive expansion of the surrounding air, which makes a popping noise analogous to the thunder which accompanies lightning. The term "thermal blooming" is used to describe these self-induced thermal distortions. This phenomenon can cause retro-reflection of the laser beam back into the laser source, possibly damaging its optics. When this phenomenon occurs in certain scientific experiments it is referred to as a "plasma mirror" or "plasma shutter". One approach for overcoming thermal distortion is to use a short-duration laser pulse. Some action movies depict security systems using lasers of visible light (and their foiling by the hero, typically using mirrors); the hero may see the path of the beam by sprinkling some dust in the air. It is far easier and cheaper to build infrared laser diodes rather than visible light laser diodes, and such systems almost never use visible light lasers. Additionally, putting enough dust in the air to make the beam visible is likely to be enough to "break" the beam and trigger the alarm (as demonstrated on an episode of MythBusters on the Discovery Channel). Science fiction films special effects often depict laser beams propagating at only a few metres per second—slowly enough to see their progress, in a manner reminiscent of conventional tracer ammunition—whereas in reality a laser beam travels at the speed of light and would seem to appear instantly to the naked eye from start to end. Several of these misconceptions can be found in the 1964 James Bond film Goldfinger. In one of the most famous scenes in the Bond films, Bond, played by Sean Connery, faces a laser beam approaching his groin while melting the solid gold table to which he is strapped. The director Guy Hamilton found that a real laser beam would not show up on camera so it was added as an optical effect. The table was precut up the middle and coated with gold paint, while the melting effect was achieved by a man below the table with an oxyacetylene torch. Goldfinger's laser makes a whirring electronic sound, while a real laser would have produced a fairly heat-free and silent cut.[29] In addition to movies and popular culture, laser misconceptions are present in some popular science publications or simple introductory explanations. For example, laser light is not perfectly parallel as is sometimes claimed; all laser beams spread out to some degree as they propagate due to diffraction. In addition, no laser is perfectly monochromatic (i.e. coherent); most operate at several closely spaced frequencies (colors) and even those that nominally operate a single frequency still exhibit some variation in frequency. Furthermore, mode locked lasers are designed to operate with thousands or millions of frequencies locked together to form a short pulse.	https://www.wikidoc.org/index.php/Laser
21db7462cd6fe17bf5e3e4a215a5a793ce5d2c1d	wikidoc	Latin	Latin Latin (Latīna, pronounced Template:IPA) is an ancient Indo-European language that was spoken in the Roman Republic and the Roman Empire. The conquests of Rome spread the language all around the Mediterranean and a large part of Europe. It existed in two forms: Classical Latin, used in poetry and formal prose, and Vulgar Latin, spoken by the people. After the fall of the Roman Empire and the rise of the Roman Catholic Church, Latin became the universal ecclesiastical language and the lingua franca of educated Europeans. Having lasted 2,200 years, Latin began a slow decline around the 1600s. Vulgar Latin, however, was preserved: it split into several regional dialects, which by the 800s had become the ancestors of today's Romance languages. English, though a Germanic language, derives 35% of its words from Latin: largely by way of French, but partly through direct borrowings made especially during the 1600s in England. Latin also lives on in the form of Ecclesiastical Latin spoken in the Roman Catholic Church. Latin is borrowed from, as a source of vocabulary, in science, academia, and law. Classical Latin, the literary language of the late Republic and early Empire, is still taught in many primary, grammar, and secondary schools, often combined with Greek in the study of Classics, though its role has diminished since the early 20th century. The Latin alphabet is the most widely used alphabet. # History Latin is a member of the Italic languages and its alphabet is based on the Old Italic alphabet, derived from the Greek alphabet. In the 9th or 8th century BC Latin was brought to the Italian peninsula by the migrating Latins who settled in Latium, around the River Tiber, where Roman civilization would develop. During those early years Latin came under the influence of the non-Indo-European Etruscan language of northern Italy. Although surviving Roman literature consists almost entirely of Classical Latin, the actual spoken language of the Western Roman Empire was Vulgar Latin, which differed from Classical Latin in grammar, vocabulary, and (eventually) pronunciation. Although Latin long remained the legal and governmental language of the Roman Empire, Greek became the dominant language of the well-educated elite, as much of the literature and philosophy studied by upper-class Romans had been produced by Greek (usually Athenian) authors. In the eastern half of the Roman Empire, which would become the Byzantine Empire after the final split of the Eastern and Western Roman Empires in 395, Greek eventually supplanted Latin as the legal and governmental language; and it had long been the spoken language of most Eastern citizens (of all classes). ## Orthography To write Latin, the Romans invented the Latin alphabet, basing it on the Etruscan Alphabet, which was based on the Greek alphabet. The Latin alphabet lives today in modified form as the writing system for Romance, Celtic, Slavic, and Germanic languages. English is a Germanic language and is written with a form of the Latin alphabet. However, the Ancient Romans used their alphabet differently than it is used today: they didn't use punctuation, letter spacing, or lowercase letters. So the ancient Roman wrote PHILOSOPHIAESTARSVITAE; the modern editor prints this sentence as Philosophia est ars vitae; and the student translates this sentence as Philosophy is the art of life (or, the art of living). ## Legacy The expansion of the Roman Empire spread Latin throughout Europe, and, eventually, Vulgar Latin began to dialectize, based on the location of its various speakers. Vulgar Latin gradually evolved into a number of distinct Romance languages, a process well underway by the 9th century. These were for many centuries only oral languages, Latin still being used for writing. For example, Latin was still the official language of Portugal in 1296, after which it was replaced by Portuguese. Many of these "daughter" languages, including Italian, French, Spanish, Portuguese, Romanian, Catalan, and Romansh, flourished, the differences between them growing greater and more formal over time. Out of the Romance languages, Italian is the purest descendant of Latin in terms of vocabulary, though Sardinian is the most conservative in terms of phonology. Some of the differences between Classical Latin and the Romance languages have been used in attempts to reconstruct Vulgar Latin. For example, the Romance languages have distinctive stress on certain syllables, whereas Latin had this feature in addition to distinctive length of vowels. In Italian and Sardo logudorese, there is distinctive length of consonants as well as stress; in Spanish and Portuguese, only distinctive stress; while in French length and stress are no longer distinctive. Another major distinction between Romance and Latin is that all Romance languages, excluding Romanian, have lost their case endings in most words, except for some pronouns. Romanian exhibits a direct case (nominative/accusative), an indirect case (dative/genitive), and a vocative, but linguists have said that the case endings are a Balkan innovation. There has also been a major Latin influence in English. English is Germanic in grammar, largely Romance in vocabulary, with Greek influence. Sixty percent of the English vocabulary has its roots in Latin (although a large amount of this is indirect, mostly via French). In the medieval period, much of this borrowing occurred through ecclesiastical usage established by Saint Augustine of Canterbury in the 6th Century, or indirectly after the Norman Conquest—through the Anglo-Norman language. From the 16th to the 18th centuries, English writers cobbled together huge numbers of new words from Latin and Greek roots. These words were dubbed "inkhorn" or "inkpot" words, as if they had spilled from a pot of ink. Many of these words were used once by the author and then forgotten, but some were so useful that they survived. Imbibe, extrapolate, dormant and employer are all inkhorn terms created from Latin words. Many of the most common polysyllabic "English" words are simply adapted Latin forms, in a large number of cases adapted by way of Old French. Latin mottos are used as guidelines by many organizations. # Grammar Latin is a synthetic, fusional language: affixes (often suffixes, which usually encode more than one grammatical category) are attached to fixed stems to express gender, number, and case in adjectives, nouns, and pronouns—a process called declension. Affixes are attached to fixed stems of verbs, as well, to denote person, number, tense, voice, mood, and aspect—a process called conjugation. ## Nouns There are five Latin noun declensions. Almost every one is used when the noun is the direct object of the verb or object of certain prepositions, or to denote movement towards. Due to these declensions, word order is not as important in Latin as it is in other languages. With the declensions, words can be moved around in a sentence and the meaning will stay exactly the same, but of course the emphasis will have altered. - Nominative: used when the noun is the subject of the sentence or phrase. - Genitive: used when the noun is the possessor of an object (example: "the horse of the man", or "the man's horse"—in both of these cases, the word man would be in the genitive case when translated into Latin). Also indicates material of which something greater is made of (example: "a group of people"; "a number of gifts"—people and gifts would be in the genetive case). Some nouns are genitive with special verbs too. - Dative: used when the noun is the indirect object of the sentence, with special verbs, with certain prepositions, and if used as agent, or reference. - Accusative: used when the noun is the direct object of the sentence/phrase, with certain prepositions, or as the subject of indirect statement. - Ablative: used when the noun demonstrates separation or movement from a source, cause, agent, or instrument, or when the noun is used as the object of certain prepositions; adverbial. - Vocative: used when the noun is used in a direct address (usually of a person, but not always). ## Verbs Verbs in Latin are usually identified by the four main conjugations—the groups of verbs with similar inflected forms. The first conjugation is typified by infinitive forms ending in -āre, the second by infinitives ending in -ēre, the third by infinitives ending in -ere, and the fourth by infinitives ending in -īre. However, there are a few key exceptions to these rules. There are six general tenses in Latin (present, imperfect, future, perfect, pluperfect, and future perfect), four grammatical moods (indicative, infinitive, imperative and subjunctive), six persons (first, second, and third, each in singular and plural), two voices (active and passive), and a few aspects. Verbs are described by four principal parts: - The first principal part is the first person, singular, present tense, and it is the indicative mood form of the verb. - The second principal part is the infinitive form of the verb. - The third principal part is the first person, singular, perfect tense, active indicative mood form of the verb. - The fourth principal part is the supine form, or alternatively, the participial form, nominative case, singular, perfect tense, passive voice participle form of the verb. The fourth principal part can show either one gender of the participle, or all three genders (-us for masculine, -a for feminine, and -um for neuter). It can also be the future participle when that verb cannot be made passive. # Instruction in Latin The linguistic element of Latin courses offered in secondary schools and in universities is primarily geared toward an ability to translate Latin texts into modern languages, rather than using it for the purpose of oral communication. As such, the skills of reading and writing are heavily emphasized, and speaking and listening skills are left inchoate. However, there is a growing movement, sometimes known as the Living Latin movement, whose supporters believe that Latin can be taught in the same way that modern "living" languages are taught, i.e., as a means of both spoken and written communication. This approach to learning the language assists speculative insight into how ancient authors spoke and incorporated sounds of the language stylistically; patterns in Latin poetry and literature can be difficult to identify without an understanding of the sounds of words. Institutions that offer Living Latin instruction include the Vatican and the University of Kentucky. In Great Britain, the Classical Association encourages this approach, and Latin language books describing the adventures of a mouse called Minimus have been published. In the United States, the National Junior Classical League (with more than 50,000 members) encourages high school students to pursue the study of Latin, and the National Senior Classical League encourages college students to continue their studies of the language. Many international auxiliary languages have been heavily influenced by Latin. Interlingua, which lays claim to a sizeable following, is sometimes considered a simplified, modern version of the language. Latino sine Flexione, popular in the early 20th century, is a language created from Latin with its inflections dropped. Latin translations of modern literature such as Paddington Bear, Winnie the Pooh, Tintin, Asterix, Harry Potter, The Lord of the Rings, Le Petit Prince, Max und Moritz, and The Cat in the Hat are intended to bolster interest in the language. # Modern use of Latin Today, Latin terminology is widely used, inter alia, in philosophy, medicine and law, in terms and abbreviations such as subpoena duces tecum and q.i.d. (quater in die: "four times a day"). The Latin terms are used in isolation, as technical terms. Some films set in the Roman empire have been made with dialogue in Latin, such as Sebastiane and The Passion of the Christ. The Pope delivers his written messages in Latin.	Latin Template:Infobox Language Latin (Latīna, pronounced Template:IPA) is an ancient Indo-European language that was spoken in the Roman Republic and the Roman Empire. The conquests of Rome spread the language all around the Mediterranean and a large part of Europe. It existed in two forms: Classical Latin, used in poetry and formal prose, and Vulgar Latin, spoken by the people. After the fall of the Roman Empire and the rise of the Roman Catholic Church, Latin became the universal ecclesiastical language and the lingua franca of educated Europeans. Having lasted 2,200 years, Latin began a slow decline around the 1600s. Vulgar Latin, however, was preserved: it split into several regional dialects, which by the 800s had become the ancestors of today's Romance languages. English, though a Germanic language, derives 35% of its words from Latin:[1] largely by way of French, but partly through direct borrowings made especially during the 1600s in England. Latin also lives on in the form of Ecclesiastical Latin spoken in the Roman Catholic Church. Latin is borrowed from, as a source of vocabulary, in science, academia, and law. Classical Latin, the literary language of the late Republic and early Empire, is still taught in many primary, grammar, and secondary schools, often combined with Greek in the study of Classics, though its role has diminished since the early 20th century. The Latin alphabet is the most widely used alphabet. # History Latin is a member of the Italic languages and its alphabet is based on the Old Italic alphabet, derived from the Greek alphabet. In the 9th or 8th century BC Latin was brought to the Italian peninsula by the migrating Latins who settled in Latium, around the River Tiber, where Roman civilization would develop. During those early years Latin came under the influence of the non-Indo-European Etruscan language of northern Italy. Although surviving Roman literature consists almost entirely of Classical Latin, the actual spoken language of the Western Roman Empire was Vulgar Latin, which differed from Classical Latin in grammar, vocabulary, and (eventually) pronunciation. Although Latin long remained the legal and governmental language of the Roman Empire, Greek became the dominant language of the well-educated elite, as much of the literature and philosophy studied by upper-class Romans had been produced by Greek (usually Athenian) authors. In the eastern half of the Roman Empire, which would become the Byzantine Empire after the final split of the Eastern and Western Roman Empires in 395, Greek eventually supplanted Latin as the legal and governmental language; and it had long been the spoken language of most Eastern citizens (of all classes). ## Orthography To write Latin, the Romans invented the Latin alphabet, basing it on the Etruscan Alphabet, which was based on the Greek alphabet. The Latin alphabet lives today in modified form as the writing system for Romance, Celtic, Slavic, and Germanic languages. English is a Germanic language and is written with a form of the Latin alphabet. However, the Ancient Romans used their alphabet differently than it is used today: they didn't use punctuation, letter spacing, or lowercase letters. So the ancient Roman wrote PHILOSOPHIAESTARSVITAE; the modern editor prints this sentence as Philosophia est ars vitae; and the student translates this sentence as Philosophy is the art of life (or, the art of living). ## Legacy The expansion of the Roman Empire spread Latin throughout Europe, and, eventually, Vulgar Latin began to dialectize, based on the location of its various speakers. Vulgar Latin gradually evolved into a number of distinct Romance languages, a process well underway by the 9th century. These were for many centuries only oral languages, Latin still being used for writing. For example, Latin was still the official language of Portugal in 1296, after which it was replaced by Portuguese. Many of these "daughter" languages, including Italian, French, Spanish, Portuguese, Romanian, Catalan, and Romansh, flourished, the differences between them growing greater and more formal over time. Out of the Romance languages, Italian is the purest descendant of Latin in terms of vocabulary, though Sardinian is the most conservative in terms of phonology.[citation needed] Some of the differences between Classical Latin and the Romance languages have been used in attempts to reconstruct Vulgar Latin. For example, the Romance languages have distinctive stress on certain syllables, whereas Latin had this feature in addition to distinctive length of vowels. In Italian and Sardo logudorese, there is distinctive length of consonants as well as stress; in Spanish and Portuguese, only distinctive stress; while in French length and stress are no longer distinctive. Another major distinction between Romance and Latin is that all Romance languages, excluding Romanian, have lost their case endings in most words, except for some pronouns. Romanian exhibits a direct case (nominative/accusative), an indirect case (dative/genitive), and a vocative, but linguists have said that the case endings are a Balkan innovation. There has also been a major Latin influence in English. English is Germanic in grammar, largely Romance in vocabulary, with Greek influence. Sixty percent of the English vocabulary has its roots in Latin[1] (although a large amount of this is indirect, mostly via French). In the medieval period, much of this borrowing occurred through ecclesiastical usage established by Saint Augustine of Canterbury in the 6th Century, or indirectly after the Norman Conquest—through the Anglo-Norman language. From the 16th to the 18th centuries, English writers cobbled together huge numbers of new words from Latin and Greek roots. These words were dubbed "inkhorn" or "inkpot" words, as if they had spilled from a pot of ink. Many of these words were used once by the author and then forgotten, but some were so useful that they survived. Imbibe, extrapolate, dormant and employer are all inkhorn terms created from Latin words. Many of the most common polysyllabic "English" words are simply adapted Latin forms, in a large number of cases adapted by way of Old French. Latin mottos are used as guidelines by many organizations. # Grammar Latin is a synthetic, fusional language: affixes (often suffixes, which usually encode more than one grammatical category) are attached to fixed stems to express gender, number, and case in adjectives, nouns, and pronouns—a process called declension. Affixes are attached to fixed stems of verbs, as well, to denote person, number, tense, voice, mood, and aspect—a process called conjugation. ## Nouns There are five Latin noun declensions. Almost every one is used when the noun is the direct object of the verb or object of certain prepositions, or to denote movement towards. Due to these declensions, word order is not as important in Latin as it is in other languages. With the declensions, words can be moved around in a sentence and the meaning will stay exactly the same, but of course the emphasis will have altered. - Nominative: used when the noun is the subject of the sentence or phrase. - Genitive: used when the noun is the possessor of an object (example: "the horse of the man", or "the man's horse"—in both of these cases, the word man would be in the genitive case when translated into Latin). Also indicates material of which something greater is made of (example: "a group of people"; "a number of gifts"—people and gifts would be in the genetive case). Some nouns are genitive with special verbs too. - Dative: used when the noun is the indirect object of the sentence, with special verbs, with certain prepositions, and if used as agent, or reference. - Accusative: used when the noun is the direct object of the sentence/phrase, with certain prepositions, or as the subject of indirect statement. - Ablative: used when the noun demonstrates separation or movement from a source, cause, agent, or instrument, or when the noun is used as the object of certain prepositions; adverbial. - Vocative: used when the noun is used in a direct address (usually of a person, but not always). ## Verbs Verbs in Latin are usually identified by the four main conjugations—the groups of verbs with similar inflected forms. The first conjugation is typified by infinitive forms ending in -āre, the second by infinitives ending in -ēre, the third by infinitives ending in -ere, and the fourth by infinitives ending in -īre. However, there are a few key exceptions to these rules. There are six general tenses in Latin (present, imperfect, future, perfect, pluperfect, and future perfect), four grammatical moods (indicative, infinitive, imperative and subjunctive), six persons (first, second, and third, each in singular and plural), two voices (active and passive), and a few aspects. Verbs are described by four principal parts: - The first principal part is the first person, singular, present tense, and it is the indicative mood form of the verb. - The second principal part is the infinitive form of the verb. - The third principal part is the first person, singular, perfect tense, active indicative mood form of the verb. - The fourth principal part is the supine form, or alternatively, the participial form, nominative case, singular, perfect tense, passive voice participle form of the verb. The fourth principal part can show either one gender of the participle, or all three genders (-us for masculine, -a for feminine, and -um for neuter). It can also be the future participle when that verb cannot be made passive. # Instruction in Latin The linguistic element of Latin courses offered in secondary schools and in universities is primarily geared toward an ability to translate Latin texts into modern languages, rather than using it for the purpose of oral communication. As such, the skills of reading and writing are heavily emphasized, and speaking and listening skills are left inchoate. However, there is a growing movement, sometimes known as the Living Latin movement, whose supporters believe that Latin can be taught in the same way that modern "living" languages are taught, i.e., as a means of both spoken and written communication. This approach to learning the language assists speculative insight into how ancient authors spoke and incorporated sounds of the language stylistically; patterns in Latin poetry and literature can be difficult to identify without an understanding of the sounds of words. Institutions that offer Living Latin instruction include the Vatican and the University of Kentucky. In Great Britain, the Classical Association encourages this approach, and Latin language books describing the adventures of a mouse called Minimus have been published. In the United States, the National Junior Classical League (with more than 50,000 members) encourages high school students to pursue the study of Latin, and the National Senior Classical League encourages college students to continue their studies of the language. Many international auxiliary languages have been heavily influenced by Latin. Interlingua, which lays claim to a sizeable following, is sometimes considered a simplified, modern version of the language. Latino sine Flexione, popular in the early 20th century, is a language created from Latin with its inflections dropped. Latin translations of modern literature such as Paddington Bear, Winnie the Pooh, Tintin, Asterix, Harry Potter, The Lord of the Rings, Le Petit Prince, Max und Moritz, and The Cat in the Hat are intended to bolster interest in the language. # Modern use of Latin Today, Latin terminology is widely used, inter alia, in philosophy, medicine and law, in terms and abbreviations such as subpoena duces tecum and q.i.d. (quater in die: "four times a day"). The Latin terms are used in isolation, as technical terms. Some films set in the Roman empire have been made with dialogue in Latin, such as Sebastiane and The Passion of the Christ. The Pope delivers his written messages in Latin.	https://www.wikidoc.org/index.php/Latin
7584cf13a4fd622a8aa2aaf5fe00b415c32e9702	wikidoc	Lexan	Lexan LEXAN is a registered trademark for General Electric's brand of highly durable polycarbonate resin thermoplastic intended to replace glass where the need for strength justifies its higher cost. It is a polycarbonate polymer produced by reacting Bisphenol A with carbonyl chloride, also known as phosgene. Lexan is the brand name for polycarbonate sheet in thicknesses from 0.75 mm (0.03 in) to 12 mm (0.48 in). Applications are mainly in three domains — building (glazing and domes), industry (machine protection and fabricated parts) and communication and signage. Lexan was discovered in 1953 by GE chemist Dr. Daniel Fox, while working on a wire coating. Dr. Hermann Schnell of Bayer in Germany applied for a U.S. patent on a virtually identical molecule the same year that GE filed for a patent, 1955. Lexan is manufactured by GE Plastics, a unit of General Electric. It is manufactured at several GE plants, the largest being in Mt. Vernon, Indiana; Cartagena, Spain; and Bergen op Zoom, The Netherlands. GE Plastics is headquartered in Pittsfield, MA. Jack Welch, former CEO of GE, started as a chemical engineer in this division in Pittsfield. Lexan is similar to polymethyl methacrylate (Plexiglas/Lucite/Perspex)—commonly described as acrylic—in appearance, but is far more durable, often to the point of being described as "bulletproof" (depending on the thickness of the sample and the type of weapon used). Lexan is used in the aerospace industry for aircraft canopies, windscreens and other windows, but can be found in household items, such as bottles, compact discs, and DVDs. Perhaps the most visible Lexan consumer product is the Apple Computer iBook and the iPod; the gleaming white plastic is Lexan. It also is used by Nalgene for their 1-liter wide mouth water bottle, popular with hikers and mountaineers. Lexan is also used by other water bottle manufacturers. However, Lexan leaches bisphenol A, a chemical that some studies linked to cancer. These studies indicate exposure to low levels of BPA causes a range of serious health effects in laboratory animals. An expert panel of 12 scientists has found that there is "some concern that exposure to the chemical bisphenol A in utero causes neural and behavioral effects," according to the draft report prepared by The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction. For the general adult population, the expert panel found a "negligible concern for adverse reproductive effects following exposures." For similar products offered by other companies, see polycarbonates. Lexan is also used in: - racing cars to replace heavier (and breakable) glass windshields and windows. - greenhouses for covering. - the Flexdex skateboards "Clear" models - for radio-controlled car bodies - for motorcycle goggles - Radio-controlled helicopter fins and gyro mounts by RDLohr - Rubik's cube colored tiles - Air hockey pucks - Some guitar picks - An alternative for brass mouthpieces in brass musical instruments. - All New York City Subway cars, from R110A to newer cars such as R160B feature Lexan as a defense against vandalism. # Lexan in popular culture - The molecule of Lexan was featured on Star Trek IV: The Voyage Home visually depicted on the Apple Macintosh computer screen, described in the film as "transparent aluminum". - Lexan is often used in Mythbusters to protect the show's hosts and crew from any explosions.	Lexan LEXAN is a registered trademark for General Electric's brand of highly durable polycarbonate resin thermoplastic intended to replace glass where the need for strength justifies its higher cost. It is a polycarbonate polymer produced by reacting Bisphenol A with carbonyl chloride, also known as phosgene. Lexan is the brand name for polycarbonate sheet in thicknesses from 0.75 mm (0.03 in) to 12 mm (0.48 in). Applications are mainly in three domains — building (glazing and domes), industry (machine protection and fabricated parts) and communication and signage. Lexan was discovered in 1953 by GE chemist Dr. Daniel Fox, while working on a wire coating. Dr. Hermann Schnell of Bayer in Germany applied for a U.S. patent on a virtually identical molecule the same year that GE filed for a patent, 1955. Lexan is manufactured by GE Plastics, a unit of General Electric. It is manufactured at several GE plants, the largest being in Mt. Vernon, Indiana; Cartagena, Spain; and Bergen op Zoom, The Netherlands. GE Plastics is headquartered in Pittsfield, MA. Jack Welch, former CEO of GE, started as a chemical engineer in this division in Pittsfield. Lexan is similar to polymethyl methacrylate (Plexiglas/Lucite/Perspex)—commonly described as acrylic—in appearance, but is far more durable, often to the point of being described as "bulletproof" (depending on the thickness of the sample and the type of weapon used). Lexan is used in the aerospace industry for aircraft canopies, windscreens and other windows, but can be found in household items, such as bottles, compact discs, and DVDs. Perhaps the most visible Lexan consumer product is the Apple Computer iBook and the iPod; the gleaming white plastic is Lexan. It also is used by Nalgene for their 1-liter wide mouth water bottle, popular with hikers and mountaineers. Lexan is also used by other water bottle manufacturers. However, Lexan leaches bisphenol A, a chemical that some studies linked to cancer. These studies indicate exposure to low levels of BPA causes a range of serious health effects in laboratory animals.[1] An expert panel of 12 scientists has found that there is "some concern that exposure to the chemical bisphenol A in utero causes neural and behavioral effects," according to the draft report prepared by The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction. For the general adult population, the expert panel found a "negligible concern for adverse reproductive effects following exposures." [2] For similar products offered by other companies, see polycarbonates. Lexan is also used in: - racing cars to replace heavier (and breakable) glass windshields and windows. - greenhouses for covering. - the Flexdex skateboards "Clear" models - for radio-controlled car bodies - for motorcycle goggles - Radio-controlled helicopter fins and gyro mounts by RDLohr - Rubik's cube colored tiles - Air hockey pucks - Some guitar picks - An alternative for brass mouthpieces in brass musical instruments. - All New York City Subway cars, from R110A to newer cars such as R160B feature Lexan as a defense against vandalism.[3] # Lexan in popular culture - The molecule of Lexan was featured on Star Trek IV: The Voyage Home visually depicted on the Apple Macintosh computer screen, described in the film as "transparent aluminum".[citation needed] - Lexan is often used in Mythbusters to protect the show's hosts and crew from any explosions. # External links - GE LEXAN®	https://www.wikidoc.org/index.php/Lexan
7c120b8279380260a345ca57403591dd6376a27d	wikidoc	Light	Light Light, or visible light, is electromagnetic radiation of a wavelength that is visible to the human eye (about 400–700 nm). In a scientific context, the word light is sometimes used to refer to the entire electromagnetic spectrum. Light is composed of elementary particles called photons. Three primary properties of light are: - Intensity; - Frequency or wavelength and; - Polarization. Light can exhibit properties of both waves and particles. This property is referred to as wave-particle duality. The study of light, known as optics, is an important research area in modern physics. # Speed of light The speed of light in a vacuum is exactly 299,792,458 m/s (about 186,282.397 miles per second). The speed of light depends upon the medium in which it is traveling, and the speed will be lower in a transparent medium. Although commonly called the "velocity of light", technically the word velocity is a vector quantity, having both magnitude and direction. Speed refers only to the magnitude of the velocity vector. This fixed definition of the speed of light is a result of the modern attempt, in physics, to define the basic unit of length in terms of the speed of light, rather than defining the speed of light in terms of a length. Different physicists have attempted to measure the speed of light throughout history. Galileo attempted to measure the speed of light in the seventeenth century. A good early experiment to measure the speed of light was conducted by Ole Rømer, a Danish physicist, in 1676. Using a telescope, Ole observed the motions of Jupiter and one of its moons, Io. Noting discrepancies in the apparent period of Io's orbit, Rømer calculated that light takes about 18 minutes to traverse the diameter of Earth's orbit. Unfortunately, this was not a value that was known at that time. If Ole had known the diameter of the earth's orbit, he would have calculated a speed of 227,000,000 m/s. Another, more accurate, measurement of the speed of light was performed in Europe by Hippolyte Fizeau in 1849. Fizeau directed a beam of light at a mirror several kilometers away. A rotating cog wheel was placed in the path of the light beam as it traveled from the source, to the mirror and then returned to its origin. Fizeau found that at a certain rate of rotation, the beam would pass through one gap in the wheel on the way out and the next gap on the way back. Knowing the distance to the mirror, the number of teeth on the wheel, and the rate of rotation, Fizeau was able to calculate the speed of light as 313,000,000 m/s. Léon Foucault used an experiment which used rotating mirrors to obtain a value of 298,000,000 m/s in 1862. Albert A. Michelson conducted experiments on the speed of light from 1877 until his death in 1931. He refined Foucault's methods in 1926 using improved rotating mirrors to measure the time it took light to make a round trip from Mt. Wilson to Mt. San Antonio in California. The precise measurements yielded a speed of 299,796,000 m/s. Some scientists were able to bring light to a complete standstill by passing it through a Bose-Einstein Condensate of the element rubidium. # Refraction Light in a vacuum propagates at a maximum finite speed, defined above, and denoted by the symbol c. While passing through any other transparent medium, the speed of light slows to some fraction of c. The reduction of the speed of light traveling in a transparent medium is indicated by the refractive index, n, which is defined as: where v denotes the speed that light travels in the transparent medium. Note, n = 1 in a vacuum and n > 1 in a transparent medium. When a beam of light crosses the boundary between a vacuum and another medium, or between two different mediums, the wavelength of the light changes, but the frequency remains constant. If the beam of light is not orthogonal to the boundary, the change in wavelength results in a change in the direction of the beam. This change of direction is known as refraction. The refraction quality of lenses is frequently used to manipulate light in order to change the apparent size of images. Magnifying glasses, spectacles, contact lenses, microscopes and refracting telescopes are all examples of this manipulation. # Optics The study of light and the interaction of light and matter is termed optics. The observation and study of optical phenomena such as rainbows and the aurora borealis offer many clues as to the nature of light as well as much enjoyment. # Light sources There are many sources of light. The most common light sources are thermal: a body at a given temperature emits a characteristic spectrum of black-body radiation. Examples include sunlight (the radiation emitted by the chromosphere of the Sun at around 6,000 K peaks in the visible region of the electromagnetic spectrum), incandescent light bulbs (which emit only around 10% of their energy as visible light and the remainder as infrared), and glowing solid particles in flames. The peak of the blackbody spectrum is in the infrared for relatively cool objects like human beings. As the temperature increases, the peak shifts to shorter wavelengths, producing first a red glow, then a white one, and finally a blue color as the peak moves out of the visible part of the spectrum and into the ultraviolet. These colors can be seen when metal is heated to "red hot" or "white hot". The blue color is most commonly seen in a gas flame or a welder's torch. Atoms emit and absorb light at characteristic energies. This produces "emission lines" in the spectrum of each atom. Emission can be spontaneous, as in light-emitting diodes, gas discharge lamps (such as neon lamps and neon signs, mercury-vapor lamps, etc.), and flames (light from the hot gas itself—so, for example, sodium in a gas flame emits characteristic yellow light). Emission can also be stimulated, as in a laser or a microwave maser. Acceleration of a free charged particle, such as an electron, can produce visible radiation: cyclotron radiation, synchrotron radiation, and bremsstrahlung radiation are all examples of this. Particles moving through a medium faster than the speed of light in that medium can produce visible Cherenkov radiation. Certain chemicals produce visible radiation by chemoluminescence. In living things, this process is called bioluminescence. For example, fireflies produce light by this means, and boats moving through water can disturb plankton which produce a glowing wake. Certain substances produce light when they are illuminated by more energetic radiation, a process known as fluorescence. This is used in fluorescent lights. Some substances emit light slowly after excitation by more energetic radiation. This is known as phosphorescence. Phosphorescent materials can also be excited by bombarding them with subatomic particles. Cathodoluminescence is one example of this. This mechanism is used in cathode ray tube televisions. Certain other mechanisms can produce light: - scintillation - electroluminescence - sonoluminescence - triboluminescence - Cherenkov radiation When the concept of light is intended to include very-high-energy photons (gamma rays), additional generation mechanisms include: - radioactive decay - particle–antiparticle annihilation # Theories about light ## Indian theories In ancient India, the philosophical schools of Samkhya and Vaisheshika, from around the 6th–5th century BC, developed theories on light. According to the Samkhya school, light is one of the five fundamental "subtle" elements (tanmatra) out of which emerge the gross elements. The atomicity of these elements is not specifically mentioned and it appears that they were actually taken to be continuous. On the other hand, the Vaisheshika school gives an atomic theory of the physical world on the non-atomic ground of ether, space and time. (See Indian atomism.) The basic atoms are those of earth (prthivı), water (apas), fire (tejas), and air (vayu), that should not be confused with the ordinary meaning of these terms. These atoms are taken to form binary molecules that combine further to form larger molecules. Motion is defined in terms of the movement of the physical atoms and it appears that it is taken to be non-instantaneous. Light rays are taken to be a stream of high velocity of tejas (fire) atoms. The particles of light can exhibit different characteristics depending on the speed and the arrangements of the tejas atoms. Around the first century BC, the Vishnu Purana correctly refers to sunlight as the "the seven rays of the sun". Later in 499, Aryabhata, who proposed a heliocentric solar system of gravitation in his Aryabhatiya, wrote that the planets and the Moon do not have their own light but reflect the light of the Sun. The Indian Buddhists, such as Dignāga in the 5th century and Dharmakirti in the 7th century, developed a type of atomism that is a philosophy about reality being composed of atomic entities that are momentary flashes of light or energy. They viewed light as being an atomic entity equivalent to energy, similar to the modern concept of photons, though they also viewed all matter as being composed of these light/energy particles. ## Greek and Hellenistic theories In the fifth century BC, Empedocles postulated that everything was composed of four elements; fire, air, earth and water. He believed that Aphrodite made the human eye out of the four elements and that she lit the fire in the eye which shone out from the eye making sight possible. If this were true, then one could see during the night just as well as during the day, so Empedocles postulated an interaction between rays from the eyes and rays from a source such as the sun. In about 300 BC, Euclid wrote Optica, in which he studied the properties of light. Euclid postulated that light travelled in straight lines and he described the laws of reflection and studied them mathematically. He questioned that sight is the result of a beam from the eye, for he asks how one sees the stars immediately, if one closes one's eyes, then opens them at night. Of course if the beam from the eye travels infinitely fast this is not a problem. In 55 BC, Lucretius, a Roman who carried on the ideas of earlier Greek atomists, wrote: "The light and heat of the sun; these are composed of minute atoms which, when they are shoved off, lose no time in shooting right across the interspace of air in the direction imparted by the shove." - On the nature of the Universe Despite being similar to later particle theories, Lucretius's views were not generally accepted and light was still theorized as emanating from the eye. Ptolemy (c. 2nd century) wrote about the refraction of light, and developed a theory of vision that objects are seen by rays of light emanating from the eyes. ## Optical theory The Muslim scientist Ibn al-Haytham (c. 965-1040), known as Alhacen in the West, in his Book of Optics, developed a broad theory that explained vision, using geometry and anatomy, which stated that each point on an illuminated area or object radiates light rays in every direction, but that only one ray from each point, which strikes the eye perpendicularly, can be seen. The other rays strike at different angles and are not seen. He described the pinhole camera and invented the camera obscura, which produces an inverted image, and used it as an example to support his argument. This contradicted Ptolemy's theory of vision that objects are seen by rays of light emanating from the eyes. Alhacen held light rays to be streams of minute particles that travelled at a finite speed. He improved Ptolemy's theory of the refraction of light, and went on to discover the laws of refraction. He also carried out the first experiments on the dispersion of light into its constituent colors. His major work Kitab al-Manazir was translated into Latin in the Middle Ages, as well his book dealing with the colors of sunset. He dealt at length with the theory of various physical phenomena like shadows, eclipses, the rainbow. He also attempted to explain binocular vision, and gave a correct explanation of the apparent increase in size of the sun and the moon when near the horizon. Because of his extensive research on optics, Al-Haytham is considered the father of modern optics. Al-Haytham also correctly argued that we see objects because the sun's rays of light, which he believed to be streams of tiny particles travelling in straight lines, are reflected from objects into our eyes. He understood that light must travel at a large but finite velocity, and that refraction is caused by the velocity being different in different substances. He also studied spherical and parabolic mirrors, and understood how refraction by a lens will allow images to be focused and magnification to take place. He understood mathematically why a spherical mirror produces aberration. ## The 'plenum' René Descartes (1596-1650) held that light was a disturbance of the plenum, the continuous substance of which the universe was composed. In 1637 he published a theory of the refraction of light that assumed, incorrectly, that light travelled faster in a denser medium than in a less dense medium. Descartes arrived at this conclusion by analogy with the behaviour of sound waves. Although Descartes was incorrect about the relative speeds, he was correct in assuming that light behaved like a wave and in concluding that refraction could be explained by the speed of light in different media. As a result, Descartes' theory is often regarded as the forerunner of the wave theory of light. ## Particle theory Pierre Gassendi (1592-1655), an atomist, proposed a particle theory of light which was published posthumously in the 1660s. Isaac Newton studied Gassendi's work at an early age, and preferred his view to Descartes' theory of the plenum. He stated in his Hypothesis of Light of 1675 that light was composed of corpuscles (particles of matter) which were emitted in all directions from a source. One of Newton's arguments against the wave nature of light was that waves were known to bend around obstacles, while light travelled only in straight lines. He did, however, explain the phenomenon of the diffraction of light (which had been observed by Francesco Grimaldi) by allowing that a light particle could create a localised wave in the aether. Newton's theory could be used to predict the reflection of light, but could only explain refraction by incorrectly assuming that light accelerated upon entering a denser medium because the gravitational pull was greater. Newton published the final version of his theory in his Opticks of 1704. His reputation helped the particle theory of light to hold sway during the 18th century. The particle theory of light led Laplace to argue that a body could be so massive that light could not escape from it. In other words it would become what is now called a black hole. Laplace withdrew his suggestion when the wave theory of light was firmly established. A translation of his essay appears in The large scale structure of space-time, by Stephen Hawking and George F. R. Ellis. ## Wave theory In the 1660s, Robert Hooke published a wave theory of light. Christiaan Huygens worked out his own wave theory of light in 1678, and published it in his Treatise on light in 1690. He proposed that light was emitted in all directions as a series of waves in a medium called the Luminiferous ether. As waves are not affected by gravity, it was assumed that they slowed down upon entering a denser medium. The wave theory predicted that light waves could interfere with each other like sound waves (as noted around 1800 by Thomas Young), and that light could be polarized. Young showed by means of a diffraction experiment that light behaved as waves. He also proposed that different colors were caused by different wavelengths of light, and explained color vision in terms of three-colored receptors in the eye. Another supporter of the wave theory was Leonhard Euler. He argued in Nova theoria lucis et colorum (1746) that diffraction could more easily be explained by a wave theory. Later, Augustin-Jean Fresnel independently worked out his own wave theory of light, and presented it to the Académie des Sciences in 1817. Simeon Denis Poisson added to Fresnel's mathematical work to produce a convincing argument in favour of the wave theory, helping to overturn Newton's corpuscular theory. The weakness of the wave theory was that light waves, like sound waves, would need a medium for transmission. A hypothetical substance called the luminiferous aether was proposed, but its existence was cast into strong doubt in the late nineteenth century by the Michelson-Morley experiment. Newton's corpuscular theory implied that light would travel faster in a denser medium, while the wave theory of Huygens and others implied the opposite. At that time, the speed of light could not be measured accurately enough to decide which theory was correct. The first to make a sufficiently accurate measurement was Léon Foucault, in 1850. His result supported the wave theory, and the classical particle theory was finally abandoned. ## Electromagnetic theory In 1845, Michael Faraday discovered that the angle of polarization of a beam of light as it passed through a polarizing material could be altered by a magnetic field, an effect now known as Faraday rotation. This was the first evidence that light was related to electromagnetism. Faraday proposed in 1847 that light was a high-frequency electromagnetic vibration, which could propagate even in the absence of a medium such as the ether. Faraday's work inspired James Clerk Maxwell to study electromagnetic radiation and light. Maxwell discovered that self-propagating electromagnetic waves would travel through space at a constant speed, which happened to be equal to the previously measured speed of light. From this, Maxwell concluded that light was a form of electromagnetic radiation: he first stated this result in 1862 in On Physical Lines of Force. In 1873, he published A Treatise on Electricity and Magnetism, which contained a full mathematical description of the behaviour of electric and magnetic fields, still known as Maxwell's equations. Soon after, Heinrich Hertz confirmed Maxwell's theory experimentally by generating and detecting radio waves in the laboratory, and demonstrating that these waves behaved exactly like visible light, exhibiting properties such as reflection, refraction, diffraction, and interference. Maxwell's theory and Hertz's experiments led directly to the development of modern radio, radar, television, electromagnetic imaging, and wireless communications. ## The special theory of relativity The wave theory was wildly successful in explaining nearly all optical and electromagnetic phenomena, and was a great triumph of nineteenth century physics. By the late nineteenth century, however, a handful of experimental anomalies remained that could not be explained by or were in direct conflict with the wave theory. One of these anomalies involved a controversy over the speed of light. The constant speed of light predicted by Maxwell's equations and confirmed by the Michelson-Morley experiment contradicted the mechanical laws of motion that had been unchallenged since the time of Galileo, which stated that all speeds were relative to the speed of the observer. In 1905, Albert Einstein resolved this paradox by revising the Galilean model of space and time to account for the constancy of the speed of light. Einstein formulated his ideas in his special theory of relativity, which radically altered humankind's understanding of space and time. Einstein also demonstrated a previously unknown fundamental equivalence between energy and mass with his famous equation where E is energy, m is rest mass, and c is the speed of light. ## Particle theory revisited Another experimental anomaly was the photoelectric effect, by which light striking a metal surface ejected electrons from the surface, causing an electric current to flow across an applied voltage. Experimental measurements demonstrated that the energy of individual ejected electrons was proportional to the frequency, rather than the intensity, of the light. Furthermore, below a certain minimum frequency, which depended on the particular metal, no current would flow regardless of the intensity. These observations clearly contradicted the wave theory, and for years physicists tried in vain to find an explanation. In 1905, Einstein solved this puzzle as well, this time by resurrecting the particle theory of light to explain the observed effect. Because of the preponderance of evidence in favor of the wave theory, however, Einstein's ideas were met initially by great skepticism among established physicists. But eventually Einstein's explanation of the photoelectric effect would triumph, and it ultimately formed the basis for wave–particle duality and much of quantum mechanics. ## Quantum theory A third anomaly that arose in the late 19th century involved a contradiction between the wave theory of light and measurements of the electromagnetic spectrum emitted by thermal radiators, or so-called black bodies. Physicists struggled with this problem, which later became known as the ultraviolet catastrophe, unsuccessfully for many years. In 1900, Max Planck developed a new theory of black-body radiation that explained the observed spectrum correctly. Planck's theory was based on the idea that black bodies emit light (and other electromagnetic radiation) only as discrete bundles or packets of energy. These packets were called quanta, and the particle of light was given the name photon, to correspond with other particles being described around this time, such as the electron and proton. A photon has an energy, E, proportional to its frequency, f, by where h is Planck's constant, \lambda is the wavelength and c is the speed of light. Likewise, the momentum p of a photon is also proportional to its frequency and inversely proportional to its wavelength: As it originally stood, this theory did not explain the simultaneous wave- and particle-like natures of light, though Planck would later work on theories that did. In 1918, Planck received the Nobel Prize in Physics for his part in the founding of quantum theory. ## Wave–particle duality The modern theory that explains the nature of light includes the notion of wave–particle duality, described by Albert Einstein in the early 1900s, based on his study of the photoelectric effect and Planck's results. Einstein asserted that the energy of a photon is proportional to its frequency. More generally, the theory states that everything has both a particle nature and a wave nature, and various experiments can be done to bring out one or the other. The particle nature is more easily discerned if an object has a large mass, so it took until a bold proposition by Louis de Broglie in 1924 to realise that electrons also exhibited wave–particle duality. The wave nature of electrons was experimentally demonstrated by Davission and Germer in 1927. Einstein received the Nobel Prize in 1921 for his work with the wave–particle duality on photons (especially explaining the photoelectric effect thereby), and de Broglie followed in 1929 for his extension to other particles. ## Quantum electrodynamics The quantum mechanical theory of light and electromagnetic radiation continued to evolve through the 1920's and 1930's, and culminated with the development during the 1940's of the theory of quantum electrodynamics, or QED. This so-called quantum field theory is among the most comprehensive and experimentally successful theories ever formulated to explain a set of natural phenomena. QED was developed primarily by physicists Richard Feynman, Freeman Dyson, Julian Schwinger, and Shin-Ichiro Tomonaga. Feynman, Schwinger, and Tomonaga shared the 1965 Nobel Prize in Physics for their contributions. # Light pressure Light pushes on objects in its way, just as the wind would do. This pressure is most easily explainable in particle theory: photons hit and transfer their momentum. Light pressure can cause asteroids to spin faster, acting on their irregular shapes as on the vanes of a windmill. The possibility to make solar sails that would accelerate spaceships in space is also under investigation. Although the motion of the Crookes radiometer was originally attributed to light pressure, this interpretation is incorrect; the characteristic Crookes rotation is the result of a partial vacuum. This should not be confused with the Nichols radiometer, in which the motion is directly caused by light pressure. # Spirituality The sensory perception of light plays a central role in spirituality (vision, enlightenment, darshan, Tabor Light), and the presence of light as opposed to its absence (darkness) is a common Western metaphor of good and evil, knowledge and ignorance, and similar concepts.	Light Template:Other Light, or visible light, is electromagnetic radiation of a wavelength that is visible to the human eye (about 400–700 nm). In a scientific context, the word light is sometimes used to refer to the entire electromagnetic spectrum.[1] Light is composed of elementary particles called photons. Three primary properties of light are: - Intensity; - Frequency or wavelength and; - Polarization. Light can exhibit properties of both waves and particles. This property is referred to as wave-particle duality. The study of light, known as optics, is an important research area in modern physics. # Speed of light The speed of light in a vacuum is exactly 299,792,458 m/s (about 186,282.397 miles per second). The speed of light depends upon the medium in which it is traveling, and the speed will be lower in a transparent medium. Although commonly called the "velocity of light", technically the word velocity is a vector quantity, having both magnitude and direction. Speed refers only to the magnitude of the velocity vector. This fixed definition of the speed of light is a result of the modern attempt, in physics, to define the basic unit of length in terms of the speed of light, rather than defining the speed of light in terms of a length. Different physicists have attempted to measure the speed of light throughout history. Galileo attempted to measure the speed of light in the seventeenth century. A good early experiment to measure the speed of light was conducted by Ole Rømer, a Danish physicist, in 1676. Using a telescope, Ole observed the motions of Jupiter and one of its moons, Io. Noting discrepancies in the apparent period of Io's orbit, Rømer calculated that light takes about 18 minutes to traverse the diameter of Earth's orbit. Unfortunately, this was not a value that was known at that time. If Ole had known the diameter of the earth's orbit, he would have calculated a speed of 227,000,000 m/s. Another, more accurate, measurement of the speed of light was performed in Europe by Hippolyte Fizeau in 1849. Fizeau directed a beam of light at a mirror several kilometers away. A rotating cog wheel was placed in the path of the light beam as it traveled from the source, to the mirror and then returned to its origin. Fizeau found that at a certain rate of rotation, the beam would pass through one gap in the wheel on the way out and the next gap on the way back. Knowing the distance to the mirror, the number of teeth on the wheel, and the rate of rotation, Fizeau was able to calculate the speed of light as 313,000,000 m/s. Léon Foucault used an experiment which used rotating mirrors to obtain a value of 298,000,000 m/s in 1862. Albert A. Michelson conducted experiments on the speed of light from 1877 until his death in 1931. He refined Foucault's methods in 1926 using improved rotating mirrors to measure the time it took light to make a round trip from Mt. Wilson to Mt. San Antonio in California. The precise measurements yielded a speed of 299,796,000 m/s. Some scientists were able to bring light to a complete standstill by passing it through a Bose-Einstein Condensate of the element rubidium. # Refraction Light in a vacuum propagates at a maximum finite speed, defined above, and denoted by the symbol c. While passing through any other transparent medium, the speed of light slows to some fraction of c. The reduction of the speed of light traveling in a transparent medium is indicated by the refractive index, n, which is defined as: where v denotes the speed that light travels in the transparent medium. Note, n = 1 in a vacuum and n > 1 in a transparent medium. When a beam of light crosses the boundary between a vacuum and another medium, or between two different mediums, the wavelength of the light changes, but the frequency remains constant. If the beam of light is not orthogonal to the boundary, the change in wavelength results in a change in the direction of the beam. This change of direction is known as refraction. The refraction quality of lenses is frequently used to manipulate light in order to change the apparent size of images. Magnifying glasses, spectacles, contact lenses, microscopes and refracting telescopes are all examples of this manipulation. # Optics The study of light and the interaction of light and matter is termed optics. The observation and study of optical phenomena such as rainbows and the aurora borealis offer many clues as to the nature of light as well as much enjoyment. # Light sources Template:Seealso There are many sources of light. The most common light sources are thermal: a body at a given temperature emits a characteristic spectrum of black-body radiation. Examples include sunlight (the radiation emitted by the chromosphere of the Sun at around 6,000 K peaks in the visible region of the electromagnetic spectrum), incandescent light bulbs (which emit only around 10% of their energy as visible light and the remainder as infrared), and glowing solid particles in flames. The peak of the blackbody spectrum is in the infrared for relatively cool objects like human beings. As the temperature increases, the peak shifts to shorter wavelengths, producing first a red glow, then a white one, and finally a blue color as the peak moves out of the visible part of the spectrum and into the ultraviolet. These colors can be seen when metal is heated to "red hot" or "white hot". The blue color is most commonly seen in a gas flame or a welder's torch. Atoms emit and absorb light at characteristic energies. This produces "emission lines" in the spectrum of each atom. Emission can be spontaneous, as in light-emitting diodes, gas discharge lamps (such as neon lamps and neon signs, mercury-vapor lamps, etc.), and flames (light from the hot gas itself—so, for example, sodium in a gas flame emits characteristic yellow light). Emission can also be stimulated, as in a laser or a microwave maser. Acceleration of a free charged particle, such as an electron, can produce visible radiation: cyclotron radiation, synchrotron radiation, and bremsstrahlung radiation are all examples of this. Particles moving through a medium faster than the speed of light in that medium can produce visible Cherenkov radiation. Certain chemicals produce visible radiation by chemoluminescence. In living things, this process is called bioluminescence. For example, fireflies produce light by this means, and boats moving through water can disturb plankton which produce a glowing wake. Certain substances produce light when they are illuminated by more energetic radiation, a process known as fluorescence. This is used in fluorescent lights. Some substances emit light slowly after excitation by more energetic radiation. This is known as phosphorescence. Phosphorescent materials can also be excited by bombarding them with subatomic particles. Cathodoluminescence is one example of this. This mechanism is used in cathode ray tube televisions. Certain other mechanisms can produce light: - scintillation - electroluminescence - sonoluminescence - triboluminescence - Cherenkov radiation When the concept of light is intended to include very-high-energy photons (gamma rays), additional generation mechanisms include: - radioactive decay - particle–antiparticle annihilation # Theories about light ## Indian theories In ancient India, the philosophical schools of Samkhya and Vaisheshika, from around the 6th–5th century BC, developed theories on light. According to the Samkhya school, light is one of the five fundamental "subtle" elements (tanmatra) out of which emerge the gross elements. The atomicity of these elements is not specifically mentioned and it appears that they were actually taken to be continuous. On the other hand, the Vaisheshika school gives an atomic theory of the physical world on the non-atomic ground of ether, space and time. (See Indian atomism.) The basic atoms are those of earth (prthivı), water (apas), fire (tejas), and air (vayu), that should not be confused with the ordinary meaning of these terms. These atoms are taken to form binary molecules that combine further to form larger molecules. Motion is defined in terms of the movement of the physical atoms and it appears that it is taken to be non-instantaneous. Light rays are taken to be a stream of high velocity of tejas (fire) atoms. The particles of light can exhibit different characteristics depending on the speed and the arrangements of the tejas atoms. Around the first century BC, the Vishnu Purana correctly refers to sunlight as the "the seven rays of the sun". Later in 499, Aryabhata, who proposed a heliocentric solar system of gravitation in his Aryabhatiya, wrote that the planets and the Moon do not have their own light but reflect the light of the Sun. The Indian Buddhists, such as Dignāga in the 5th century and Dharmakirti in the 7th century, developed a type of atomism that is a philosophy about reality being composed of atomic entities that are momentary flashes of light or energy. They viewed light as being an atomic entity equivalent to energy, similar to the modern concept of photons, though they also viewed all matter as being composed of these light/energy particles. ## Greek and Hellenistic theories In the fifth century BC, Empedocles postulated that everything was composed of four elements; fire, air, earth and water. He believed that Aphrodite made the human eye out of the four elements and that she lit the fire in the eye which shone out from the eye making sight possible. If this were true, then one could see during the night just as well as during the day, so Empedocles postulated an interaction between rays from the eyes and rays from a source such as the sun. In about 300 BC, Euclid wrote Optica, in which he studied the properties of light. Euclid postulated that light travelled in straight lines and he described the laws of reflection and studied them mathematically. He questioned that sight is the result of a beam from the eye, for he asks how one sees the stars immediately, if one closes one's eyes, then opens them at night. Of course if the beam from the eye travels infinitely fast this is not a problem. In 55 BC, Lucretius, a Roman who carried on the ideas of earlier Greek atomists, wrote: "The light and heat of the sun; these are composed of minute atoms which, when they are shoved off, lose no time in shooting right across the interspace of air in the direction imparted by the shove." - On the nature of the Universe Despite being similar to later particle theories, Lucretius's views were not generally accepted and light was still theorized as emanating from the eye. Ptolemy (c. 2nd century) wrote about the refraction of light, and developed a theory of vision that objects are seen by rays of light emanating from the eyes. ## Optical theory The Muslim scientist Ibn al-Haytham (c. 965-1040), known as Alhacen in the West, in his Book of Optics, developed a broad theory that explained vision, using geometry and anatomy, which stated that each point on an illuminated area or object radiates light rays in every direction, but that only one ray from each point, which strikes the eye perpendicularly, can be seen. The other rays strike at different angles and are not seen. He described the pinhole camera and invented the camera obscura, which produces an inverted image, and used it as an example to support his argument.[1] This contradicted Ptolemy's theory of vision that objects are seen by rays of light emanating from the eyes. Alhacen held light rays to be streams of minute particles that travelled at a finite speed. He improved Ptolemy's theory of the refraction of light, and went on to discover the laws of refraction. He also carried out the first experiments on the dispersion of light into its constituent colors. His major work Kitab al-Manazir was translated into Latin in the Middle Ages, as well his book dealing with the colors of sunset. He dealt at length with the theory of various physical phenomena like shadows, eclipses, the rainbow. He also attempted to explain binocular vision, and gave a correct explanation of the apparent increase in size of the sun and the moon when near the horizon. Because of his extensive research on optics, Al-Haytham is considered the father of modern optics. Al-Haytham also correctly argued that we see objects because the sun's rays of light, which he believed to be streams of tiny particles travelling in straight lines, are reflected from objects into our eyes. He understood that light must travel at a large but finite velocity, and that refraction is caused by the velocity being different in different substances. He also studied spherical and parabolic mirrors, and understood how refraction by a lens will allow images to be focused and magnification to take place. He understood mathematically why a spherical mirror produces aberration. ## The 'plenum' René Descartes (1596-1650) held that light was a disturbance of the plenum, the continuous substance of which the universe was composed. In 1637 he published a theory of the refraction of light that assumed, incorrectly, that light travelled faster in a denser medium than in a less dense medium. Descartes arrived at this conclusion by analogy with the behaviour of sound waves. Although Descartes was incorrect about the relative speeds, he was correct in assuming that light behaved like a wave and in concluding that refraction could be explained by the speed of light in different media. As a result, Descartes' theory is often regarded as the forerunner of the wave theory of light. ## Particle theory Pierre Gassendi (1592-1655), an atomist, proposed a particle theory of light which was published posthumously in the 1660s. Isaac Newton studied Gassendi's work at an early age, and preferred his view to Descartes' theory of the plenum. He stated in his Hypothesis of Light of 1675 that light was composed of corpuscles (particles of matter) which were emitted in all directions from a source. One of Newton's arguments against the wave nature of light was that waves were known to bend around obstacles, while light travelled only in straight lines. He did, however, explain the phenomenon of the diffraction of light (which had been observed by Francesco Grimaldi) by allowing that a light particle could create a localised wave in the aether. Newton's theory could be used to predict the reflection of light, but could only explain refraction by incorrectly assuming that light accelerated upon entering a denser medium because the gravitational pull was greater. Newton published the final version of his theory in his Opticks of 1704. His reputation helped the particle theory of light to hold sway during the 18th century. The particle theory of light led Laplace to argue that a body could be so massive that light could not escape from it. In other words it would become what is now called a black hole. Laplace withdrew his suggestion when the wave theory of light was firmly established. A translation of his essay appears in The large scale structure of space-time, by Stephen Hawking and George F. R. Ellis. ## Wave theory In the 1660s, Robert Hooke published a wave theory of light. Christiaan Huygens worked out his own wave theory of light in 1678, and published it in his Treatise on light in 1690. He proposed that light was emitted in all directions as a series of waves in a medium called the Luminiferous ether. As waves are not affected by gravity, it was assumed that they slowed down upon entering a denser medium. The wave theory predicted that light waves could interfere with each other like sound waves (as noted around 1800 by Thomas Young), and that light could be polarized. Young showed by means of a diffraction experiment that light behaved as waves. He also proposed that different colors were caused by different wavelengths of light, and explained color vision in terms of three-colored receptors in the eye. Another supporter of the wave theory was Leonhard Euler. He argued in Nova theoria lucis et colorum (1746) that diffraction could more easily be explained by a wave theory. Later, Augustin-Jean Fresnel independently worked out his own wave theory of light, and presented it to the Académie des Sciences in 1817. Simeon Denis Poisson added to Fresnel's mathematical work to produce a convincing argument in favour of the wave theory, helping to overturn Newton's corpuscular theory. The weakness of the wave theory was that light waves, like sound waves, would need a medium for transmission. A hypothetical substance called the luminiferous aether was proposed, but its existence was cast into strong doubt in the late nineteenth century by the Michelson-Morley experiment. Newton's corpuscular theory implied that light would travel faster in a denser medium, while the wave theory of Huygens and others implied the opposite. At that time, the speed of light could not be measured accurately enough to decide which theory was correct. The first to make a sufficiently accurate measurement was Léon Foucault, in 1850. His result supported the wave theory, and the classical particle theory was finally abandoned. ## Electromagnetic theory In 1845, Michael Faraday discovered that the angle of polarization of a beam of light as it passed through a polarizing material could be altered by a magnetic field, an effect now known as Faraday rotation. This was the first evidence that light was related to electromagnetism. Faraday proposed in 1847 that light was a high-frequency electromagnetic vibration, which could propagate even in the absence of a medium such as the ether. Faraday's work inspired James Clerk Maxwell to study electromagnetic radiation and light. Maxwell discovered that self-propagating electromagnetic waves would travel through space at a constant speed, which happened to be equal to the previously measured speed of light. From this, Maxwell concluded that light was a form of electromagnetic radiation: he first stated this result in 1862 in On Physical Lines of Force. In 1873, he published A Treatise on Electricity and Magnetism, which contained a full mathematical description of the behaviour of electric and magnetic fields, still known as Maxwell's equations. Soon after, Heinrich Hertz confirmed Maxwell's theory experimentally by generating and detecting radio waves in the laboratory, and demonstrating that these waves behaved exactly like visible light, exhibiting properties such as reflection, refraction, diffraction, and interference. Maxwell's theory and Hertz's experiments led directly to the development of modern radio, radar, television, electromagnetic imaging, and wireless communications. ## The special theory of relativity The wave theory was wildly successful in explaining nearly all optical and electromagnetic phenomena, and was a great triumph of nineteenth century physics. By the late nineteenth century, however, a handful of experimental anomalies remained that could not be explained by or were in direct conflict with the wave theory. One of these anomalies involved a controversy over the speed of light. The constant speed of light predicted by Maxwell's equations and confirmed by the Michelson-Morley experiment contradicted the mechanical laws of motion that had been unchallenged since the time of Galileo, which stated that all speeds were relative to the speed of the observer. In 1905, Albert Einstein resolved this paradox by revising the Galilean model of space and time to account for the constancy of the speed of light. Einstein formulated his ideas in his special theory of relativity, which radically altered humankind's understanding of space and time. Einstein also demonstrated a previously unknown fundamental equivalence between energy and mass with his famous equation where E is energy, m is rest mass, and c is the speed of light. ## Particle theory revisited Another experimental anomaly was the photoelectric effect, by which light striking a metal surface ejected electrons from the surface, causing an electric current to flow across an applied voltage. Experimental measurements demonstrated that the energy of individual ejected electrons was proportional to the frequency, rather than the intensity, of the light. Furthermore, below a certain minimum frequency, which depended on the particular metal, no current would flow regardless of the intensity. These observations clearly contradicted the wave theory, and for years physicists tried in vain to find an explanation. In 1905, Einstein solved this puzzle as well, this time by resurrecting the particle theory of light to explain the observed effect. Because of the preponderance of evidence in favor of the wave theory, however, Einstein's ideas were met initially by great skepticism among established physicists. But eventually Einstein's explanation of the photoelectric effect would triumph, and it ultimately formed the basis for wave–particle duality and much of quantum mechanics. ## Quantum theory A third anomaly that arose in the late 19th century involved a contradiction between the wave theory of light and measurements of the electromagnetic spectrum emitted by thermal radiators, or so-called black bodies. Physicists struggled with this problem, which later became known as the ultraviolet catastrophe, unsuccessfully for many years. In 1900, Max Planck developed a new theory of black-body radiation that explained the observed spectrum correctly. Planck's theory was based on the idea that black bodies emit light (and other electromagnetic radiation) only as discrete bundles or packets of energy. These packets were called quanta, and the particle of light was given the name photon, to correspond with other particles being described around this time, such as the electron and proton. A photon has an energy, E, proportional to its frequency, f, by where h is Planck's constant, <math>\lambda</math> is the wavelength and c is the speed of light. Likewise, the momentum p of a photon is also proportional to its frequency and inversely proportional to its wavelength: As it originally stood, this theory did not explain the simultaneous wave- and particle-like natures of light, though Planck would later work on theories that did. In 1918, Planck received the Nobel Prize in Physics for his part in the founding of quantum theory. ## Wave–particle duality The modern theory that explains the nature of light includes the notion of wave–particle duality, described by Albert Einstein in the early 1900s, based on his study of the photoelectric effect and Planck's results. Einstein asserted that the energy of a photon is proportional to its frequency. More generally, the theory states that everything has both a particle nature and a wave nature, and various experiments can be done to bring out one or the other. The particle nature is more easily discerned if an object has a large mass, so it took until a bold proposition by Louis de Broglie in 1924 to realise that electrons also exhibited wave–particle duality. The wave nature of electrons was experimentally demonstrated by Davission and Germer in 1927. Einstein received the Nobel Prize in 1921 for his work with the wave–particle duality on photons (especially explaining the photoelectric effect thereby), and de Broglie followed in 1929 for his extension to other particles. ## Quantum electrodynamics The quantum mechanical theory of light and electromagnetic radiation continued to evolve through the 1920's and 1930's, and culminated with the development during the 1940's of the theory of quantum electrodynamics, or QED. This so-called quantum field theory is among the most comprehensive and experimentally successful theories ever formulated to explain a set of natural phenomena. QED was developed primarily by physicists Richard Feynman, Freeman Dyson, Julian Schwinger, and Shin-Ichiro Tomonaga. Feynman, Schwinger, and Tomonaga shared the 1965 Nobel Prize in Physics for their contributions. # Light pressure Light pushes on objects in its way, just as the wind would do. This pressure is most easily explainable in particle theory: photons hit and transfer their momentum. Light pressure can cause asteroids to spin faster,[2] acting on their irregular shapes as on the vanes of a windmill. The possibility to make solar sails that would accelerate spaceships in space is also under investigation.[citation needed] Although the motion of the Crookes radiometer was originally attributed to light pressure, this interpretation is incorrect; the characteristic Crookes rotation is the result of a partial vacuum.[3] This should not be confused with the Nichols radiometer, in which the motion is directly caused by light pressure.[4] # Spirituality The sensory perception of light plays a central role in spirituality (vision, enlightenment, darshan, Tabor Light), and the presence of light as opposed to its absence (darkness) is a common Western metaphor of good and evil, knowledge and ignorance, and similar concepts.	https://www.wikidoc.org/index.php/Light
e21102b68c3bf18a504f73137ba192ee5c7414d3	wikidoc	Lists	Lists # Overview You can create two types of lists: - Bullet Lists: which are unordered and not numbered and have a blue square before the text, or - Numbered Lists: which order or number each item # How to Make a Bullet List: To create a bulletted list, start the line with a star sign "". Typing this: Yields this: - This is a list - This is part of the same list - As is this! # How to Make a Numbered List: Numbered lists are just as easy. Instead of starting the line with a "", instead start each line with a "#". Typing this: Yields this: - I'm number one! - I'm number two! - I'm number three! Be Careful! A list ends when there is a line that has no # sign at the beginning. Numbering starts over with the number 1 again when the # sign is encountered again. So for instance: Typing this: Yields this: - List 1 - List 1 No List - List 2 # Multi-leveled Lists Adding more levels to a list is simple - just add another list character to the front. So: becomes: - List Level 1 List Level 2 List Level 3 List Level 2 - List Level 2 List Level 3 - List Level 3 - List Level 2 - List Level 1 This works with both styles of list: becomes: - List Level 1 List Level 2 List Level 3 List Level 2 - List Level 2 List Level 3 - List Level 3 - List Level 2 - List Level 1 # Mixing Bullett Lists and Ordered Lists: You can even create mixed lists Typing this: Yields this: - and nest them like this can I mix definition list as well? yes how? it's easy as a b c - and nest them like this can I mix definition list as well? yes how? it's easy as a b c - like this can I mix definition list as well? yes how? it's easy as a b c - a - b - c # Structure inside List elements Due to the issue of lists ending on the first non-list character line, special efforts must be taken in order to build multi-paragraph and multi-element list items. Breaking up a paragraph should be done with . This will create a new line without breaking the list. will do this as well, but is a little trickier to get right. Sometimes an element in a list needs to consist of both a sub-list, and further text that isn't a part of the sub-list. This too is achievable, placing a colon at the correct level will allow you to continue the list element without mess. This is not a perfect solution, as the indent is not always well-aligned with the list indents. - List Element 1 Sub-list element 1 Sub-list element 2 Continuing List Element 1 - Sub-list element 1 - Sub-list element 2 - This is an example of a list element across several lines.By inserting , we can spread the list element across several lines without having to go into multiple list elements.Pretty spiffy, no? - In this example, we use paragraph markers to make multiple lines.This works just as well, but does require a little foresight, as paragraph markers need to surround the text.This, to many is not a hindrance - A ordinary ol' List element # Numbered lists across multiple columns In some cases, it's necessary or useful to spread a numbered list across several columns (such as in a table). Wiki mark-up cannot handle this. Instead, HTML code needs to be used: becomes: This system, of course, does not need to be used for bullet-point lists, as number preservation isn't an issue.	Lists Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview You can create two types of lists: - Bullet Lists: which are unordered and not numbered and have a blue square before the text, or - Numbered Lists: which order or number each item # How to Make a Bullet List: To create a bulletted list, start the line with a star sign "". Typing this: Yields this: - This is a list - This is part of the same list - As is this! # How to Make a Numbered List: Numbered lists are just as easy. Instead of starting the line with a "", instead start each line with a "#". Typing this: Yields this: - I'm number one! - I'm number two! - I'm number three! Be Careful! A list ends when there is a line that has no # sign at the beginning. Numbering starts over with the number 1 again when the # sign is encountered again. So for instance: Typing this: Yields this: - List 1 - List 1 No List - List 2 # Multi-leveled Lists Adding more levels to a list is simple - just add another list character to the front. So: becomes: - List Level 1 List Level 2 List Level 3 List Level 2 - List Level 2 List Level 3 - List Level 3 - List Level 2 - List Level 1 This works with both styles of list: becomes: - List Level 1 List Level 2 List Level 3 List Level 2 - List Level 2 List Level 3 - List Level 3 - List Level 2 - List Level 1 # Mixing Bullett Lists and Ordered Lists: You can even create mixed lists Typing this: Yields this: - and nest them like this can I mix definition list as well? yes how? it's easy as a b c - and nest them like this can I mix definition list as well? yes how? it's easy as a b c - like this can I mix definition list as well? yes how? it's easy as a b c - a - b - c # Structure inside List elements Due to the issue of lists ending on the first non-list character line, special efforts must be taken in order to build multi-paragraph and multi-element list items. Breaking up a paragraph should be done with <br>. This will create a new line without breaking the list. <p></p> will do this as well, but is a little trickier to get right. Sometimes an element in a list needs to consist of both a sub-list, and further text that isn't a part of the sub-list. This too is achievable, placing a colon at the correct level will allow you to continue the list element without mess. This is not a perfect solution, as the indent is not always well-aligned with the list indents. - List Element 1 Sub-list element 1 Sub-list element 2 Continuing List Element 1 - Sub-list element 1 - Sub-list element 2 - This is an example of a list element across several lines.By inserting <br>, we can spread the list element across several lines without having to go into multiple list elements.Pretty spiffy, no? - In this example, we use paragraph markers to make multiple lines.This works just as well, but does require a little foresight, as paragraph markers need to surround the text.This, to many is not a hindrance - A ordinary ol' List element # Numbered lists across multiple columns In some cases, it's necessary or useful to spread a numbered list across several columns (such as in a table). Wiki mark-up cannot handle this. Instead, HTML code needs to be used: becomes: This system, of course, does not need to be used for bullet-point lists, as number preservation isn't an issue. Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Lists
1a0bb34832282bf210854a7887b4ed569490b184	wikidoc	Login	Login # Log In to WikiDoc to Get Credit for Your Contributions! - In the upper right corner there is a link to log in - Enter the required information including your full name (your full name is preferred so that you can be appropriately credited) - Select ‘create new account’ - Your account has been created! - You will receive an email verifying that you have joined WikiDoc Ensure that you are logged in every time you are making a contribution to get credit for your contribution on the history page. In the event that you fail to log in, your IP address will appear in place of your name and you will not receive the credit due for your contribution.	Login # Log In to WikiDoc to Get Credit for Your Contributions! - In the upper right corner there is a link to log in - Enter the required information including your full name (your full name is preferred so that you can be appropriately credited) - Select ‘create new account’ - Your account has been created! - You will receive an email verifying that you have joined WikiDoc Ensure that you are logged in every time you are making a contribution to get credit for your contribution on the history page. In the event that you fail to log in, your IP address will appear in place of your name and you will not receive the credit due for your contribution. Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Log_in
a97dab923a07a4985963f7196a0c77630d8690a4	wikidoc	Loupe	Loupe A loupe (pronounced loop), is a type of magnification device used to see things one is looking at more closely. In this respect, they are simply a form of a modified microscope, allowing the user to be able to better apply the phenomenon of microscopy to his or her trade. # Commercial uses of loupes Loupes are used in a number of different of industries, notably the jewelry trade, photography, printing, ophthalmology and dentistry. ## Jewelers Jewelers typically use a monocular, handheld loupe in order to magnify gemstones and other jewelry that they wish to inspect. A 10x magnification is good to use for inspecting jewelry. A 10x loupe is the standard instrument used to determine a diamond's clarity grade in the gemological industry. While higher-power magnification devices may be used to examine the stone, inclusions (internal flaws) and blemishes (surface irregularities) are not factored into the stone's final clarity grade if they are small enough to be undetectable when the stone is examined under 10x magnification. ## Electronics For many soldering applications engineers and technicians will use a loupe to inspect a printed circuit board with small surface components on it. ## Printing Offset printing sees frequent use of loupes in order to carefully analyze how ink lays on paper. Strippers use loupes in order to register film separations to one another. Pressmen use them to check registration of colors, estimate dot-gain, and diagnose issues with roller pressure and chemistry based on the shape of individual dots and rosettes. ## Photography Photographers use loupes to review, edit or analyze negatives and slides on a light table.Photographers using large format cameras also use loupes for viewing the ground glass image to aid focussing ## Dentistry Many dentists will use loupes to better scrutinize the entities within their patients' mouths in order to make a better diagnosis, for example, to determine how far a crack proceeds along the surface of a tooth. Loupes are also used in order to perform on a more precise level; while dentists drill teeth on a millimeter scale, magnification can enlarge the dentists' view of the teeth, perhaps making it easier to inspect teeth for decay and/or see things that ordinarily would not be seen without magnification. Specialties of dentistry, such oral surgery and periodontics, may benefit from the use of loupes as well. Even though they may be performing surgical procedures on the gingiva or bony structures of the oral cavity, the oral cavity is notorious for being a place containing small entities with limited access. Magnification can be very helpful when suturing a flap. Because dentists use both of their hands while performing dental procedures, dental loupes are binocular and usually take on the form of a pair of glasses. Some dental loupes are flip-types, which take the form of two small cylinders, one in front of each lense of the glasses. Other types are inset within the lense of the glasses. A typical magnification for use in dentistry is 2.5x, but dental loupes can be anywhere in the range from 2x to 5x. Together with proper access to the oral cavity, light is an important part of performing precision dentistry. Because a dentist's head often eclipses the overhead dental lamp, loupes may be fitted with a light source. This light source, emanating from in front of the loupes, cannot be blocked by the position of the dentists' head, and so provides for a continuous source of light during the extent of dental procedures. Loupe-mounted lights used to be fed by fiber optic cables that connected to either a wall-mounted or table-top light source, and often introduces a limiting range for the dentist, as he or she would be required to remain close to the wall or table, respectively. Additionally, the fiber optic cord can be damaged by excess flexing or crushing, such as would occur should the cord be rolled over by a chair. Newer models feature an LED lamp within the loupe-mounted light and an electric cord coming from either the conventional wall-mounted/table-top light source or a belt clip rechargeable battery pack. Options for loupe-mounted cameras and video recorders are also available.	Loupe A loupe (pronounced loop), is a type of magnification device used to see things one is looking at more closely. In this respect, they are simply a form of a modified microscope, allowing the user to be able to better apply the phenomenon of microscopy to his or her trade. # Commercial uses of loupes Loupes are used in a number of different of industries, notably the jewelry trade, photography, printing, ophthalmology and dentistry. ## Jewelers Jewelers typically use a monocular, handheld loupe in order to magnify gemstones and other jewelry that they wish to inspect. [1] A 10x magnification is good to use for inspecting jewelry.[1] A 10x loupe is the standard instrument used to determine a diamond's clarity grade in the gemological industry. While higher-power magnification devices may be used to examine the stone, inclusions (internal flaws) and blemishes (surface irregularities) are not factored into the stone's final clarity grade if they are small enough to be undetectable when the stone is examined under 10x magnification.[2] ## Electronics For many soldering applications engineers and technicians will use a loupe to inspect a printed circuit board with small surface components on it. ## Printing Offset printing sees frequent use of loupes in order to carefully analyze how ink lays on paper. Strippers use loupes in order to register film separations to one another. Pressmen use them to check registration of colors, estimate dot-gain, and diagnose issues with roller pressure and chemistry based on the shape of individual dots and rosettes. ## Photography Photographers use loupes to review, edit or analyze negatives and slides on a light table.Photographers using large format cameras also use loupes for viewing the ground glass image to aid focussing ## Dentistry Many dentists will use loupes to better scrutinize the entities within their patients' mouths in order to make a better diagnosis, for example, to determine how far a crack proceeds along the surface of a tooth. Loupes are also used in order to perform on a more precise level; while dentists drill teeth on a millimeter scale, magnification can enlarge the dentists' view of the teeth, perhaps making it easier to inspect teeth for decay and/or see things that ordinarily would not be seen without magnification. Specialties of dentistry, such oral surgery and periodontics, may benefit from the use of loupes as well. Even though they may be performing surgical procedures on the gingiva or bony structures of the oral cavity, the oral cavity is notorious for being a place containing small entities with limited access. Magnification can be very helpful when suturing a flap. Because dentists use both of their hands while performing dental procedures, dental loupes are binocular and usually take on the form of a pair of glasses. Some dental loupes are flip-types, which take the form of two small cylinders, one in front of each lense of the glasses. Other types are inset within the lense of the glasses. A typical magnification for use in dentistry is 2.5x, but dental loupes can be anywhere in the range from 2x to 5x. Together with proper access to the oral cavity, light is an important part of performing precision dentistry. Because a dentist's head often eclipses the overhead dental lamp, loupes may be fitted with a light source. This light source, emanating from in front of the loupes, cannot be blocked by the position of the dentists' head, and so provides for a continuous source of light during the extent of dental procedures. Loupe-mounted lights used to be fed by fiber optic cables that connected to either a wall-mounted or table-top light source, and often introduces a limiting range for the dentist, as he or she would be required to remain close to the wall or table, respectively. Additionally, the fiber optic cord can be damaged by excess flexing or crushing, such as would occur should the cord be rolled over by a chair. Newer models feature an LED lamp within the loupe-mounted light and an electric cord coming from either the conventional wall-mounted/table-top light source or a belt clip rechargeable battery pack. Options for loupe-mounted cameras and video recorders are also available.	https://www.wikidoc.org/index.php/Loupe
638116472aa8f6328656bf5d38c462a0ab20aa13	wikidoc	Lupin	Lupin Lupin, often spelled lupine in North America, is the common name for members of the genus Lupinus in the legume family (Fabaceae). The genus comprises between 200-600 species, with major centers of diversity in South America and western North America - subgen.Platycarpos) and subgen. Lupinus - in the Mediterranean region and Africa. The species are mostly herbaceous perennial plants 0.3-1.5 m (1-5 ft) tall, but some are annual plants and a few are shrubs up to 3 m (10 ft) tall - see also bush lupin -, with one species (Lupinus jaimehintoniana, from the Mexican state of Oaxaca) a tree up to 8 m high with a trunk 20 cm (8 in) in diameter. They have a characteristic and easily recognised leaf shape, with soft green to grey-green leaves which in many species bear silvery hairs, often densely so. The leaf blades are usually palmately divided into 5–28 leaflets or reduced to a single leaflet in a few species of the southeastern United States. The flowers are produced in dense or open whorls on an erect spike, each flower 1-2 cm long, with a typical peaflower shape with an upper 'standard', two lateral 'wings' and two lower petals fused as a 'keel'. Due to the flower shape, several species are known as bluebonnets or quaker bonnets. The fruit is a pod containing several seeds. Like most members of their family, lupins can fix nitrogen from the atmosphere into ammonia, fertilizing the soil for other plants. The genus Lupinus is nodulated by Bradyrhizobium soil bacteria. Some species have a long central tap roots or proteoid roots. Lupins contain significant amounts of certain secondary compounds like isoflavones and toxic alkaloids, e.g. lupinine. # Cultivation and uses The yellow legume seeds of lupins, commonly called lupin beans, were quite popular with the Romans and they spread the cultivation of them throughout the Roman Empire; hence common names like lupini in Romance languages. Lupin beans are commonly sold in a salty solution in jars (like olives and pickles) and can be eaten with or without the skin. Lupins are also cultivated as forage and grain legumes. Today, lupini dishes are most commonly found in Mediterranean countries, especially in Portugal, Egypt, and Italy, and also in Brazil and in Spanish Harlem, where they are popularly consumed with beer. The Andean variety of this bean is from the Andean Lupin (tarwi, L. mutabilis) and was a widespread food in the Incan Empire. The Andean Lupin and the Mediterranean L. albus (White Lupin), L. angustifolius (Blue Lupin) and Lupinus hirsutus are also edible after soaking the seeds for some days in salted water. They are known as altramuz in Spain and Argentina. In Portuguese the lupin beans are known as tremoços, and in Antalya (Turkey) as tirmis. Lupins were also used by Native Americans in North America, e.g. the Yavapai people. These lupins are referred to as sweet lupins because they contain smaller amounts of toxic alkaloids than the bitter lupin varieties. Newly bred variants of sweet lupins are grown extensively in Germany; they lack any bitter taste and require no soaking in salt solution. The seeds are used for different foods from vegan sausages to lupin-tofu or baking-enhancing lupin flour. Given that lupin seeds have the full range of essential amino acids and that they, contrary to soy, can be grown in more temperate to cool climates, lupins are becoming increasingly recognized as a cash crop alternative to soy. Lupin milk is a milk substitute made from lupin protein. Three Mediterranean species of lupin, Blue Lupin, White Lupin and Yellow Lupin (L. luteus) are widely cultivated for livestock and poultry feed. Both sweet and bitter lupins in feed can cause livestock poisoning. Lupin poisoning is a nervous syndrome caused by alkaloids in bitter lupins, similar to neurolathyrism. Mycotoxic lupinosis is a disease caused by lupin material that is infected with the fungus Diaporthe toxica; the fungus produces mycotoxins called phomopsins, which cause liver damage. On 22 December 2006, the European Commission submitted directive 2006/142/EC, which amends the EU foodstuff allergen list to include "lupin and products thereof". ## Horticulture and ecology Lupins are popular ornamental plants in gardens. There are numerous hybrids and cultivars. Some species, such as Garden Lupin (Lupinus polyphyllus) and hybrids like the Rainbow Lupin (L. × regalis) are common garden flowers. Others, such as the Yellow Bush Lupin (L. arboreus) are considered invasive weeds when they appear outside their native range. In New Zealand lupins have escaped into the wild and grow in large numbers along main roads and streams on the South Island. The seeds are carried by car tires and water flow, and unfortunately, some tourist shops in the major tourist areas have been reported to have sold packets of lupin seeds, with the instructions to plant, water and watch them grow into a giant beanstalk. They are usually Garden Lupins, principally blue, pink and violet, with some yellow, and are very attractive, providing colourful vistas with a backdrop of mountains and lakes; however, they smother the original vegetation. The New Zealand environment authorities have a campaign to reduce their numbers, although this seems a hopeless task, especially when faced with such ignorance as mentioned above. In fields they seem to be eradicated by sheep, and hence remain largely restricted to ungrazed roadside verges and stream banks. For several Lepidoptera (butterflies and moths), lupins are an important larval food. These include: - Callophrys irus (Frosted Elfin) - Chesias legatella (The Streak) - Chionodes braunella - Glaucopsyche xerces (Xerces Blue) - extinct - Icaricia icarioides missionensis (Mission Blue) - Lycaeides melissa samuelis (Karner Blue) - Melanchra persicariae (Dot Moth) - Phymatopus behrensii - Schinia suetus The endangered Lange's Metalmark (Apodemia mormo langei) mates on Silver Bush Lupin (L. albifrons). The most significant diseases of lupins are anthracnose as well as wilting and root rot diseases caused by Fusarium and other pathogens, and some bacterial and viral diseases. # Selected species - Lupinus albicaulis – Sickle-keel Lupin - Lupinus albifrons – Silver Bush Lupin - Lupinus albus – White Lupin - Lupinus × alpestris - Lupinus angustifolius – Blue Lupin or Narrowleaf Lupin - Lupinus arboreus – Yellow Bush Lupin or Tree Lupin - Lupinus arbustus – Longspur Lupin - Lupinus arcticus – Arctic Lupin - Lupinus argenteus – Silvery Lupin Lupinus argenteus var. palmeri - Lupinus argenteus var. palmeri - Lupinus aridorum – Scrub Lupin - Lupinus arizonicus – Arizona Lupin - Lupinus benthamii - Lupinus bicolor – Miniature Lupin, Bicolor Lupin or Lindley's (Annual) Lupin - Lupinus bingenensis – Bingen Lupin - Lupinus burkei – Burke's Lupin - Lupinus caespitosus – Stemless Dwarf Lupin - Lupinus caudatus – Kellogg's Spurred Lupin - Lupinus chamissonis – Chamisso Bush Lupin - Lupinus concinnus - Lupinus cosentinii - Lupinus diffusus – Spreading Lupin, Oak Ridge Lupin or Sky-blue Lupin - Lupinus excubitus – Grape Soda Lupin - Lupinus foliolosus - Lupinus formosus – Summer Lupin - Lupinus havardii - Lupinus hirsutus - Lupinus hirsutissimus - Lupinus jaimehintoniana - Lupinus kuntii - Lupinus kuschei – Yukon Lupin - Lupinus latifolius – Broadleaf Lupin Lupinus latifolius var. barbatus – Klamath Lupin or Bearded Lupin - Lupinus latifolius var. barbatus – Klamath Lupin or Bearded Lupin - Lupinus lepidus – Prairie Lupin - Lupinus leucophyllus – Woolly-leaf Lupin - Lupinus littoralis – Seashore Lupin - Lupinus longifolius – Longleaf Bush Lupin - Lupinus luteus – Yellow Lupin - Lupinus lyallii – Lyall's Lupin - Lupinus macbrideanus - Lupinus michelianus - Lupinus micranthus - Lupinus microcarpus – Wide-bannered Lupin or Chick Lupin Lupinus microcarpus var. densiflorus – Dense-flowered Lupin - Lupinus microcarpus var. densiflorus – Dense-flowered Lupin - Lupinus minimus – Kettle Falls Lupin - Lupinus mutabilis – Andean Lupin, Pearl Lupin, South American Lupin, tarwi/tarhui or chocho - Lupinus nanus – Dwarf Lupin, Field Lupin, Sky Lupin or Douglas' Annual Lupin - Lupinus niveus - Lupinus nootkatensis – Nootka Lupin - Lupinus nubigenus - Lupinus odoratus – Royal Mojave Lupin - Lupinus oreganus – Oregon Lupin - Lupinus parviflorus – Lodgepole Lupin - Lupinus peirsonii – Peirson's Lupin - Lupinus perennis – Wild Perennial Lupin, Sundial Lupin, Indian beet or Old maid's bonnets - Lupinus plattensis - Lupinus polycarpus – Smallflower Lupin - Lupinus polyphyllus – Largeleaf Lupin, Bigleaf Lupin, Garden Lupin or Russell Lupin - Lupinus prunophilus – Hairy Bigleaf Lupin - Lupinus pusillus – Small Lupin - Lupinus × regalis – Rainbow Lupin - Lupinus rivularis – Riverbank Lupin - Lupinus rupestris - Lupinus sericeus – Pursh's Silky Lupin - Lupinus smithianus - Lupinus sparsiflorus – Desert Lupin, Coulter's Lupin or Mojave Lupin - Lupinus stiversii - Lupinus subcarnosus – "Buffalo clover" - Lupinus succulentus – Succulent Lupin, Arroyo Lupin or Hollowleaf Annual Lupin - Lupinus sulphureus – Sulphur Lupin or Sulphur-flower Lupin Lupinus sulphureus ssp. kincaidii – Kincaid's Lupin; formerly in L. oreganus - Lupinus sulphureus ssp. kincaidii – Kincaid's Lupin; formerly in L. oreganus - Lupinus texensis – Texas Bluebonnet - Lupinus tidestromii – Tidestrom's Lupin - Lupinus vallicola – Open Lupin - Lupinus variicolor – Varied Lupin - Lupinus villosus - Lupinus wyethii – Wyeth's Lupin # Lupins in popular culture - Bluebonnet lupins, notably the Texas Bluebonnet (Lupinus texensis) are the state flower of Texas, USA. - A Monty Python sketch featured a would-be Robin Hood named Dennis Moore, who stole lupins from the rich and gave them to the poor. Although he was very successful, the poor argued that money or food would be more practical. - The lupin has also lent its name to Arsène Lupin, the main character in a series of stories by Maurice Leblanc (the name is a parody of Edgar Allan Poe's C. Auguste Dupin). He was a gentleman thief who first appeared in 1905. The popular Japanese comic book/Anime character Lupin III is an unofficial spin-off of this series. - In the British adventure series The Avengers, in the episode Who's Who it is revealed the British Secret Service gives their agents code name based on flowers worn on the lapel (e.g. "Tulip", "Daffodil", "Rose"). Though he is only seen dead, one agent is clearly wearing a lupin. - In the children's book Miss Rumphius by Barbara Cooney, the protagonist plants lupins to make the world a more beautiful place. - In the Colin Hopper novel The Eye of the Wall the main characters are served lupin stew. - In the Japanese magical girl anime Ojamajo Doremi, the character Onpu Segawa frequently sings a lullaby titled Lupinus no Komoriuta ("Lullaby of the Lupins") to baby Hana Makihatayama during season 2. - As a first name, "Lupin" is used in two famous works of fiction. In George Grossmith's comic novel The Diary of a Nobody, the protagonists' son is named Lupin, and in J.K. Rowling's Harry Potter series, Harry has a friend and teacher named Remus Lupin, who is a werewolf.	Lupin Lupin, often spelled lupine in North America, is the common name for members of the genus Lupinus in the legume family (Fabaceae). The genus comprises between 200-600 species, with major centers of diversity in South America and western North America - subgen.Platycarpos) and subgen. Lupinus - in the Mediterranean region and Africa.[1] The species are mostly herbaceous perennial plants 0.3-1.5 m (1-5 ft) tall, but some are annual plants and a few are shrubs up to 3 m (10 ft) tall - see also bush lupin -, with one species (Lupinus jaimehintoniana, from the Mexican state of Oaxaca) a tree up to 8 m high with a trunk 20 cm (8 in) in diameter. They have a characteristic and easily recognised leaf shape, with soft green to grey-green leaves which in many species bear silvery hairs, often densely so. The leaf blades are usually palmately divided into 5–28 leaflets or reduced to a single leaflet in a few species of the southeastern United States. The flowers are produced in dense or open whorls on an erect spike, each flower 1-2 cm long, with a typical peaflower shape with an upper 'standard', two lateral 'wings' and two lower petals fused as a 'keel'. Due to the flower shape, several species are known as bluebonnets or quaker bonnets. The fruit is a pod containing several seeds. Like most members of their family, lupins can fix nitrogen from the atmosphere into ammonia, fertilizing the soil for other plants. The genus Lupinus is nodulated by Bradyrhizobium soil bacteria[2]. Some species have a long central tap roots or proteoid roots. Lupins contain significant amounts of certain secondary compounds like isoflavones and toxic alkaloids, e.g. lupinine. # Cultivation and uses The yellow legume seeds of lupins, commonly called lupin beans, were quite popular with the Romans and they spread the cultivation of them throughout the Roman Empire; hence common names like lupini in Romance languages. Lupin beans are commonly sold in a salty solution in jars (like olives and pickles) and can be eaten with or without the skin. Lupins are also cultivated as forage and grain legumes. Today, lupini dishes are most commonly found in Mediterranean countries, especially in Portugal, Egypt, and Italy, and also in Brazil and in Spanish Harlem, where they are popularly consumed with beer. The Andean variety of this bean is from the Andean Lupin (tarwi, L. mutabilis) and was a widespread food in the Incan Empire. The Andean Lupin and the Mediterranean L. albus (White Lupin), L. angustifolius (Blue Lupin)[3] and Lupinus hirsutus[4] are also edible after soaking the seeds for some days in salted water[5]. They are known as altramuz in Spain and Argentina. In Portuguese the lupin beans are known as tremoços, and in Antalya (Turkey) as tirmis[verification needed]. Lupins were also used by Native Americans in North America, e.g. the Yavapai people. These lupins are referred to as sweet lupins because they contain smaller amounts of toxic alkaloids than the bitter lupin varieties. Newly bred variants of sweet lupins are grown extensively in Germany; they lack any bitter taste and require no soaking in salt solution. The seeds are used for different foods from vegan sausages to lupin-tofu or baking-enhancing lupin flour. Given that lupin seeds have the full range of essential amino acids and that they, contrary to soy, can be grown in more temperate to cool climates, lupins are becoming increasingly recognized as a cash crop alternative to soy. Lupin milk is a milk substitute made from lupin protein[citation needed]. Three Mediterranean species of lupin, Blue Lupin, White Lupin and Yellow Lupin (L. luteus) are widely cultivated for livestock and poultry feed. Both sweet and bitter lupins in feed can cause livestock poisoning. Lupin poisoning is a nervous syndrome caused by alkaloids in bitter lupins, similar to neurolathyrism. Mycotoxic lupinosis is a disease caused by lupin material that is infected with the fungus Diaporthe toxica[6]; the fungus produces mycotoxins called phomopsins, which cause liver damage. On 22 December 2006, the European Commission submitted directive 2006/142/EC, which amends the EU foodstuff allergen list to include "lupin and products thereof". ## Horticulture and ecology Lupins are popular ornamental plants in gardens. There are numerous hybrids and cultivars. Some species, such as Garden Lupin (Lupinus polyphyllus) and hybrids like the Rainbow Lupin (L. × regalis) are common garden flowers. Others, such as the Yellow Bush Lupin (L. arboreus) are considered invasive weeds when they appear outside their native range. In New Zealand lupins have escaped into the wild and grow in large numbers along main roads and streams on the South Island. The seeds are carried by car tires and water flow, and unfortunately, some tourist shops in the major tourist areas have been reported to have sold packets of lupin seeds, with the instructions to plant, water and watch them grow into a giant beanstalk[citation needed]. They are usually Garden Lupins, principally blue, pink and violet, with some yellow, and are very attractive, providing colourful vistas with a backdrop of mountains and lakes; however, they smother the original vegetation. The New Zealand environment authorities have a campaign to reduce their numbers, although this seems a hopeless task, especially when faced with such ignorance as mentioned above. In fields they seem to be eradicated by sheep, and hence remain largely restricted to ungrazed roadside verges and stream banks. For several Lepidoptera (butterflies and moths), lupins are an important larval food. These include: - Callophrys irus (Frosted Elfin)[7][8] - Chesias legatella (The Streak)[9] - Chionodes braunella - Glaucopsyche xerces (Xerces Blue) - extinct - Icaricia icarioides missionensis (Mission Blue)[10][8] - Lycaeides melissa samuelis (Karner Blue)[7][8] - Melanchra persicariae (Dot Moth) - Phymatopus behrensii - Schinia suetus[11] The endangered Lange's Metalmark (Apodemia mormo langei) mates on Silver Bush Lupin (L. albifrons). The most significant diseases of lupins are anthracnose as well as wilting and root rot diseases caused by Fusarium and other pathogens, and some bacterial and viral diseases.[12] # Selected species - Lupinus albicaulis – Sickle-keel Lupin - Lupinus albifrons – Silver Bush Lupin - Lupinus albus – White Lupin - Lupinus × alpestris - Lupinus angustifolius – Blue Lupin or Narrowleaf Lupin - Lupinus arboreus – Yellow Bush Lupin or Tree Lupin - Lupinus arbustus – Longspur Lupin - Lupinus arcticus – Arctic Lupin - Lupinus argenteus – Silvery Lupin Lupinus argenteus var. palmeri - Lupinus argenteus var. palmeri - Lupinus aridorum – Scrub Lupin - Lupinus arizonicus – Arizona Lupin - Lupinus benthamii - Lupinus bicolor – Miniature Lupin, Bicolor Lupin or Lindley's (Annual) Lupin - Lupinus bingenensis – Bingen Lupin - Lupinus burkei – Burke's Lupin - Lupinus caespitosus – Stemless Dwarf Lupin - Lupinus caudatus – Kellogg's Spurred Lupin - Lupinus chamissonis – Chamisso Bush Lupin - Lupinus concinnus - Lupinus cosentinii - Lupinus diffusus – Spreading Lupin, Oak Ridge Lupin or Sky-blue Lupin - Lupinus excubitus – Grape Soda Lupin - Lupinus foliolosus - Lupinus formosus – Summer Lupin - Lupinus havardii - Lupinus hirsutus - Lupinus hirsutissimus - Lupinus jaimehintoniana - Lupinus kuntii - Lupinus kuschei – Yukon Lupin - Lupinus latifolius – Broadleaf Lupin Lupinus latifolius var. barbatus – Klamath Lupin or Bearded Lupin - Lupinus latifolius var. barbatus – Klamath Lupin or Bearded Lupin - Lupinus lepidus – Prairie Lupin - Lupinus leucophyllus – Woolly-leaf Lupin - Lupinus littoralis – Seashore Lupin - Lupinus longifolius – Longleaf Bush Lupin - Lupinus luteus – Yellow Lupin - Lupinus lyallii – Lyall's Lupin - Lupinus macbrideanus - Lupinus michelianus - Lupinus micranthus - Lupinus microcarpus – Wide-bannered Lupin or Chick Lupin Lupinus microcarpus var. densiflorus – Dense-flowered Lupin - Lupinus microcarpus var. densiflorus – Dense-flowered Lupin - Lupinus minimus – Kettle Falls Lupin - Lupinus mutabilis – Andean Lupin, Pearl Lupin, South American Lupin, tarwi/tarhui or chocho - Lupinus nanus – Dwarf Lupin, Field Lupin, Sky Lupin or Douglas' Annual Lupin - Lupinus niveus - Lupinus nootkatensis – Nootka Lupin - Lupinus nubigenus - Lupinus odoratus – Royal Mojave Lupin - Lupinus oreganus – Oregon Lupin - Lupinus parviflorus – Lodgepole Lupin - Lupinus peirsonii – Peirson's Lupin - Lupinus perennis – Wild Perennial Lupin, Sundial Lupin, Indian beet or Old maid's bonnets - Lupinus plattensis - Lupinus polycarpus – Smallflower Lupin - Lupinus polyphyllus – Largeleaf Lupin, Bigleaf Lupin, Garden Lupin or Russell Lupin - Lupinus prunophilus – Hairy Bigleaf Lupin - Lupinus pusillus – Small Lupin - Lupinus × regalis – Rainbow Lupin - Lupinus rivularis – Riverbank Lupin - Lupinus rupestris - Lupinus sericeus – Pursh's Silky Lupin - Lupinus smithianus - Lupinus sparsiflorus – Desert Lupin, Coulter's Lupin or Mojave Lupin - Lupinus stiversii - Lupinus subcarnosus – "Buffalo clover" - Lupinus succulentus – Succulent Lupin, Arroyo Lupin or Hollowleaf Annual Lupin - Lupinus sulphureus – Sulphur Lupin or Sulphur-flower Lupin Lupinus sulphureus ssp. kincaidii – Kincaid's Lupin; formerly in L. oreganus - Lupinus sulphureus ssp. kincaidii – Kincaid's Lupin; formerly in L. oreganus - Lupinus texensis – Texas Bluebonnet - Lupinus tidestromii – Tidestrom's Lupin - Lupinus vallicola – Open Lupin - Lupinus variicolor – Varied Lupin - Lupinus villosus - Lupinus wyethii – Wyeth's Lupin # Lupins in popular culture - Bluebonnet lupins, notably the Texas Bluebonnet (Lupinus texensis) are the state flower of Texas, USA. - A Monty Python sketch featured a would-be Robin Hood named Dennis Moore, who stole lupins from the rich and gave them to the poor. Although he was very successful, the poor argued that money or food would be more practical. - The lupin has also lent its name to Arsène Lupin, the main character in a series of stories by Maurice Leblanc (the name is a parody of Edgar Allan Poe's C. Auguste Dupin). He was a gentleman thief who first appeared in 1905. The popular Japanese comic book/Anime character Lupin III is an unofficial spin-off of this series. - In the British adventure series The Avengers, in the episode Who's Who it is revealed the British Secret Service gives their agents code name based on flowers worn on the lapel (e.g. "Tulip", "Daffodil", "Rose"). Though he is only seen dead, one agent is clearly wearing a lupin. - In the children's book Miss Rumphius by Barbara Cooney, the protagonist plants lupins to make the world a more beautiful place. - In the Colin Hopper novel The Eye of the Wall the main characters are served lupin stew. - In the Japanese magical girl anime Ojamajo Doremi, the character Onpu Segawa frequently sings a lullaby titled Lupinus no Komoriuta ("Lullaby of the Lupins") to baby Hana Makihatayama during season 2. - As a first name, "Lupin" is used in two famous works of fiction. In George Grossmith's comic novel The Diary of a Nobody, the protagonists' son is named Lupin, and in J.K. Rowling's Harry Potter series, Harry has a friend and teacher named Remus Lupin, who is a werewolf.	https://www.wikidoc.org/index.php/Lupin
deb1b644a76df18155fada6ec441f3ba424eb18f	wikidoc	MACF1	MACF1 Microtubule-actin cross-linking factor 1, isoforms 1/2/3/5 is a protein that in humans is encoded by the MACF1 gene. MACF1 encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. MACF1 is a member of a family of proteins that form bridges between different cytoskeletal elements. This protein facilitates actin-microtubule interactions at the cell periphery and couples the microtubule network to cellular junctions. MACF1 belongs to a subset of +TIPs or proteins which bind to growing microtubule ends called spectraplakins. Spectraplakins characteristically have distinctive microtubule and actin binding domains, which allow MACF1 to bind to both cytoskeletal elements. MACF1 goes by many names and is also called ACF7 or actin cross-linking factor 7, MACF, macrophin, trabeculin α, and ABP620. Alternatively spliced transcript variants encoding distinct isoforms of MACF1 have been described. MACF1 is also an important protein for cell migration in processes such as wound healing. # Structure MACF1 is an enormous protein of 5380 amino acid residues. The N-terminal segment has an actin binding domain and the C-terminal segment has a +TIP binding site as well as microtubule interacting domains. This allows MACF1 to crosslink both actin and microtubules. The C-terminal region contains both a Gas2-related domain and a GSR-repeat domain, which both are involved with interacting with microtubules. The C-terminus of MACF1 is thought to associate to the microtubule lattice through the acidic C-terminal tails of tubulin subunits. However, MACF1 does not always associate with the microtubule directly, and also binds through many proteins which localize at the microtubule plus end. Such proteins include EB1, CLASP1, and CLASP2, whose interactions with MACF1 were determined through coimmunoprecipitation assay. Not only does MACF1's C-terminal tail bind to microtubules, but it also has key phosphorylation sites. When these sites are phosphorylated by its regulator GSK3β, the ability of MACF1 to bind to microtubules is disrupted. MACF1 also has an actin-regulated ATPase domain, which is approximately 3000 amino acid residues long in the C-terminal region, and is responsible for cytoskeletal dynamics. # Function ## Embryonic development MACF1 is important for embryonic development. For mice, by embryonic day 7.5 (E7.5), MACF1 is expressed in the headfold and primitive streak, and by E8.5 the protein is expressed in neuronal tissues and the foregut. MACF1 was shown to be present in the Wnt signaling pathway. When Wnt signalling is not present, MACF1 associates with a complex containing axin, β-catenin, GSK3β, and APC. However, upon Wnt signaling, MACF1 is involved in a translation and binding of the axin complex to LTP6 at the cell membrane. Also, MACF1 is required for sufficient β-catenin to travel to the nucleus, where subsequently TCF/β-catenin-dependent transcriptional activation of a gene T encoding the protein brachyury occurs. Brachyury is an essential transcription factor required for mesoderm formation. Without MACF1, insufficient brachyury is transcribed, and hence, the mesoderm does not form. In fact, MACF1 knock-out mice, which lack the protein, show clear developmental retardation by E7.5, and eventually die at gastrulation due to defects in the formation of the primitive streak, node, and mesoderm. ## Cell migration Mice with conditional knock-outs in MACF1 in hair follicle stem cells have defects in cell migration. The focal adhesions in cells lacking MACF1 associate with cables of F-actin, causing cell migration to stall. Wild-type cells with MACF1 present have coordinated cytoskeletal dynamics, which allow for proper cell migration. MACF1 plays an important role in microtubule organization, and without MACF1, microtubules in migrating cells are bending and curly, instead of straight and radial. When wounded, conditional knock-outs for MACF1 have around a 40% delay in migration over 4 to 6 days after injury compared to the wild-type controls, showing that MACF1 plays an important role in cell migration. There are suggestions that imply that MACF1 may play a role in golgi polarization. The major known regulator of MACF1 is GSK3β, which when uninhibited phosphorylates MACF1 among its many other substrates and uncouples MACF1 from microtubules. The phosphorylation of MACF1 occurs in the GSR domain, which is involved in microtubule binding, and has 32% of the amino acid residues are serines or threonines. MACF1 has 6 serines, which are possible GSK3β phosphorylation sites. GSK3β activity is high in non-stimulated cells, but during cell migration its activity is dampened along the cell leading edge. In vivo, GSK3β activity is inhibited by Wnt signalling, but in vitro it is typically inhibited by cdc42. Extracellular Wnt signalling acts on the Frizzled receptor on the cellular membrane, which then, through a signalling cascade inhibits GSK3β. The inhibition of GSK3β creates a gradient at the leading edge, allowing MACF1 to remain active and unphosphorylated, so that it can form necessary connections between microtubules and actin so migration can occur. It was found in hair follicle stem cells that phosphorylation-refractile MACF1 rescues microtubule architecture from a MACF1 knock-out, whereas phosphorylation-constitutive MACF1 is unable to rescue the phenotype. However, neither phosphorylation-refractile MACF1 nor phosphorylation-constitutive MACF1 are able to rescue polarized cell movement. This implies that the phospho-regulation dynamics permitted in the wild type MACF1 are necessary for polarized cell movement to take place. # Clinical significance In breast carcinoma cells, addition of heregulin β activates ErbB2, a receptor tyrosine, which causes microtubules to form many cell protrusions to cause cell motility. ErbB2 controls microtubule outgrowth and stabilization at the cell cortex through a specific pathway. When GSK3β is active, APC and CLASP2 are sequentially inactivated by the kinase, which gives a condition where microtubule formation is not favoured at the front of the cell. For cell migration to occur, a mechanism is needed to decrease the activity of GSK3β to promote growth of microtubules. First, ErbB2 recruits Memo (mediator of ErbB2-driven motility) to the plasma membrane, which then promotes the phosphorylation of GSK3β on serine 9. This decreases the amount of GSK3β activity, and permits the localization of APC and CLASP2 to the cell membrane, which are both microtubule +TIPs. Although CLASP2 is present at the cell membrane, it appears to have a separate, independent mechanism for microtubule growth than APC. When ErbB2 inactivates GSK3β, APC localizes to the membrane and is then able to recruit MACF1 to the membrane as well. The APC-mediated recruitment of MACF1 to the membrane is required and sufficient for microtubule capture and stabilization at the cell cortex during breast carcinoma cell motility.	MACF1 Microtubule-actin cross-linking factor 1, isoforms 1/2/3/5 is a protein that in humans is encoded by the MACF1 gene.[1][2] MACF1 encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. MACF1 is a member of a family of proteins that form bridges between different cytoskeletal elements. This protein facilitates actin-microtubule interactions at the cell periphery and couples the microtubule network to cellular junctions.[3] MACF1 belongs to a subset of +TIPs or proteins which bind to growing microtubule ends called spectraplakins.[4] Spectraplakins characteristically have distinctive microtubule and actin binding domains, which allow MACF1 to bind to both cytoskeletal elements.[5] MACF1 goes by many names and is also called ACF7 or actin cross-linking factor 7, MACF, macrophin, trabeculin α, and ABP620.[6] Alternatively spliced transcript variants encoding distinct isoforms of MACF1 have been described.[3] MACF1 is also an important protein for cell migration in processes such as wound healing.[7] # Structure MACF1 is an enormous protein of 5380 amino acid residues. The N-terminal segment has an actin binding domain and the C-terminal segment has a +TIP binding site as well as microtubule interacting domains. This allows MACF1 to crosslink both actin and microtubules.[5] The C-terminal region contains both a Gas2-related domain and a GSR-repeat domain, which both are involved with interacting with microtubules. The C-terminus of MACF1 is thought to associate to the microtubule lattice through the acidic C-terminal tails of tubulin subunits.[8] However, MACF1 does not always associate with the microtubule directly, and also binds through many proteins which localize at the microtubule plus end. Such proteins include EB1, CLASP1, and CLASP2, whose interactions with MACF1 were determined through coimmunoprecipitation assay.[9] Not only does MACF1's C-terminal tail bind to microtubules, but it also has key phosphorylation sites. When these sites are phosphorylated by its regulator GSK3β, the ability of MACF1 to bind to microtubules is disrupted.[8] MACF1 also has an actin-regulated ATPase domain, which is approximately 3000 amino acid residues long in the C-terminal region, and is responsible for cytoskeletal dynamics.[9] # Function ## Embryonic development MACF1 is important for embryonic development. For mice, by embryonic day 7.5 (E7.5), MACF1 is expressed in the headfold and primitive streak, and by E8.5 the protein is expressed in neuronal tissues and the foregut. MACF1 was shown to be present in the Wnt signaling pathway. When Wnt signalling is not present, MACF1 associates with a complex containing axin, β-catenin, GSK3β, and APC. However, upon Wnt signaling, MACF1 is involved in a translation and binding of the axin complex to LTP6 at the cell membrane. Also, MACF1 is required for sufficient β-catenin to travel to the nucleus, where subsequently TCF/β-catenin-dependent transcriptional activation of a gene T encoding the protein brachyury occurs. Brachyury is an essential transcription factor required for mesoderm formation. Without MACF1, insufficient brachyury is transcribed, and hence, the mesoderm does not form. In fact, MACF1 knock-out mice, which lack the protein, show clear developmental retardation by E7.5, and eventually die at gastrulation due to defects in the formation of the primitive streak, node, and mesoderm.[10] ## Cell migration Mice with conditional knock-outs in MACF1 in hair follicle stem cells have defects in cell migration. The focal adhesions in cells lacking MACF1 associate with cables of F-actin, causing cell migration to stall. Wild-type cells with MACF1 present have coordinated cytoskeletal dynamics, which allow for proper cell migration.[9] MACF1 plays an important role in microtubule organization, and without MACF1, microtubules in migrating cells are bending and curly, instead of straight and radial.[5] When wounded, conditional knock-outs for MACF1 have around a 40% delay in migration over 4 to 6 days after injury compared to the wild-type controls, showing that MACF1 plays an important role in cell migration. There are suggestions that imply that MACF1 may play a role in golgi polarization.[8] The major known regulator of MACF1 is GSK3β, which when uninhibited phosphorylates MACF1 among its many other substrates and uncouples MACF1 from microtubules. The phosphorylation of MACF1 occurs in the GSR domain, which is involved in microtubule binding, and has 32% of the amino acid residues are serines or threonines. MACF1 has 6 serines, which are possible GSK3β phosphorylation sites. GSK3β activity is high in non-stimulated cells, but during cell migration its activity is dampened along the cell leading edge.[8] In vivo, GSK3β activity is inhibited by Wnt signalling, but in vitro it is typically inhibited by cdc42. Extracellular Wnt signalling acts on the Frizzled receptor on the cellular membrane, which then, through a signalling cascade inhibits GSK3β. The inhibition of GSK3β creates a gradient at the leading edge, allowing MACF1 to remain active and unphosphorylated, so that it can form necessary connections between microtubules and actin so migration can occur. It was found in hair follicle stem cells that phosphorylation-refractile MACF1 rescues microtubule architecture from a MACF1 knock-out, whereas phosphorylation-constitutive MACF1 is unable to rescue the phenotype. However, neither phosphorylation-refractile MACF1 nor phosphorylation-constitutive MACF1 are able to rescue polarized cell movement. This implies that the phospho-regulation dynamics permitted in the wild type MACF1 are necessary for polarized cell movement to take place.[8] # Clinical significance In breast carcinoma cells, addition of heregulin β activates ErbB2, a receptor tyrosine, which causes microtubules to form many cell protrusions to cause cell motility. ErbB2 controls microtubule outgrowth and stabilization at the cell cortex through a specific pathway. When GSK3β is active, APC and CLASP2 are sequentially inactivated by the kinase, which gives a condition where microtubule formation is not favoured at the front of the cell. For cell migration to occur, a mechanism is needed to decrease the activity of GSK3β to promote growth of microtubules. First, ErbB2 recruits Memo (mediator of ErbB2-driven motility) to the plasma membrane, which then promotes the phosphorylation of GSK3β on serine 9. This decreases the amount of GSK3β activity, and permits the localization of APC and CLASP2 to the cell membrane, which are both microtubule +TIPs. Although CLASP2 is present at the cell membrane, it appears to have a separate, independent mechanism for microtubule growth than APC. When ErbB2 inactivates GSK3β, APC localizes to the membrane and is then able to recruit MACF1 to the membrane as well. The APC-mediated recruitment of MACF1 to the membrane is required and sufficient for microtubule capture and stabilization at the cell cortex during breast carcinoma cell motility.[11]	https://www.wikidoc.org/index.php/MACF1
69661e72236f0e347b67152cb4f22f71fde38d2b	wikidoc	MAGI2	MAGI2 Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 also known as membrane-associated guanylate kinase inverted 2 (MAGI-2) and atrophin-1-interacting protein 1 (AIP-1) is an enzyme that in humans is encoded by the MAGI2 gene. # Function The protein encoded by this gene interacts with atrophin-1. Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral-pallidoluysian atrophy. This encoded protein is characterized by two WW domains, a guanylate kinase-like domain, and multiple PDZ domains. It has structural similarity to the membrane-associated guanylate kinase homologue (MAGUK) family. # Interactions MAGI2 has been shown to interact with ATN1 and PTEN (gene).	MAGI2 Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 also known as membrane-associated guanylate kinase inverted 2 (MAGI-2) and atrophin-1-interacting protein 1 (AIP-1) is an enzyme that in humans is encoded by the MAGI2 gene.[1][2][3] # Function The protein encoded by this gene interacts with atrophin-1. Atrophin-1 contains a polyglutamine repeat, expansion of which is responsible for dentatorubral-pallidoluysian atrophy. This encoded protein is characterized by two WW domains, a guanylate kinase-like domain, and multiple PDZ domains. It has structural similarity to the membrane-associated guanylate kinase homologue (MAGUK) family.[3] # Interactions MAGI2 has been shown to interact with ATN1[4] and PTEN (gene).	https://www.wikidoc.org/index.php/MAGI2
3f0f6e7296154ef47a3901a5755b3f88bce1970d	wikidoc	MAGOH	MAGOH Protein mago nashi homolog is a protein that in humans is encoded by the MAGOH gene. Drosophila that have mutations in their mago nashi (grandchildless) gene produce progeny with defects in germplasm assembly and germline development. This gene encodes the mammalian mago nashi homolog. In mammals, mRNA expression is not limited to the germ plasm, but is expressed ubiquitously in adult tissues and can be induced by serum stimulation of quiescent fibroblasts. # Interactions MAGOH has been shown to interact with RBM8A and NXF1. In Drosophila melanogaster, Mago Nashi and Tsunagi/Y14 (core components of the exon junction complex) form a complex with a novel zinc finger protein, Ranshi, that has a role in oocyte differentiation.	MAGOH Protein mago nashi homolog is a protein that in humans is encoded by the MAGOH gene.[1][2] Drosophila that have mutations in their mago nashi (grandchildless) gene produce progeny with defects in germplasm assembly and germline development. This gene encodes the mammalian mago nashi homolog. In mammals, mRNA expression is not limited to the germ plasm, but is expressed ubiquitously in adult tissues and can be induced by serum stimulation of quiescent fibroblasts.[2] # Interactions MAGOH has been shown to interact with RBM8A[3][4] and NXF1.[4] In Drosophila melanogaster, Mago Nashi and Tsunagi/Y14 (core components of the exon junction complex) form a complex with a novel zinc finger protein, Ranshi, that has a role in oocyte differentiation.[5]	https://www.wikidoc.org/index.php/MAGOH
a8da06648db24130878b7c6cc89f03118a01cfd8	wikidoc	MALT1	MALT1 Mucosa-associated lymphoid tissue lymphoma translocation protein 1 is a protein that in humans is encoded by the MALT1 gene. It's the human paracaspase. # Function Genetic ablation of the paracaspase gene in mice and biochemical studies have shown that paracaspase is a crucial protein for T and B lymphocytes activation. It has an important role in the activation of the transcription factor NF-κB, in the production of interleukin-2 (IL-2) and in T and B lymphocytes proliferation Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. In addition, a role for paracaspase has been shown in the innate immune response mediated by the zymosan receptor Dectin-1 in macrophages and dendritic cells, and in response to the stimulation of certain G protein-coupled receptors. Sequence analysis proposes that paracaspase has an N-terminal death domain, two central immunoglobulin-like domains involved in the binding to the B-cell lymphoma 10 (Bcl10) protein and a caspase-like domain. Paracaspase has been shown to have proteolytic activity through its caspase-like domain in T lymphocytes. Cysteine 464 and histidine 414 are crucial for this activity. Like metacaspases, the paracaspase cleaves substrates after an arginine residue. To date, several paracaspase substrates have been described (see below). Bcl10 is cut after arginine 228. This removes the last five amino acids at the C-terminus and is crucial for T cell adhesion to fibronectin, but not for NF-κB activation and IL-2 production. However, using a peptide-based inhibitor (z-VRPR-fmk) of the paracaspase proteolytic activity, it has been shown that this activity is required for a sustain NF-κB activation and IL-2 production, suggesting that paracaspase may have others substrates involved in T cell-mediated NF-κB activation. A20, a deubiquitinase, has been shown to be cut by paracaspase in Human and in mouse. Cells expressing an uncleavable A20 mutant is however still capable to activate NF-κB, but cells expressing the C-terminal or the N-terminal A20 cleavage products activates more NF-κB than cells expressing wild-type A20, indicating that cleavage of A20 leads to its inactivation. Since A20 has been described has an inhibitor of NF-κB, this suggests that paracaspase-mediated A20 cleavage in T lymphocytes is necessary for a proper NF-κB activation. By targeting paracaspase proteolytic activity, it might be possible to develop new drugs that might be useful for the treatment of certain lymphomas or autoimmune disorders. # Interactions MALT1 has been shown to interact with BCL10, TRAF6 and SQSTM1/p62. # Protease substrates MALT1 (PCASP1) is part of the paracaspase family and shows proteolytic activity. Since many of the substrates are involved in regulation of inflammatory responses, the protease activity of MALT1 has emerged as an interesting therapeutic target. Currently known protease substrates are: - TNFAIP3 (A20) - BCL10 - CYLD - RELB - regnase-1 (MCPIP1) - Roquin-1 and -2 - MALT1 auto-proteolysis - HOIL1 Specifically by the oncogenic IAP2-MALT1 fusion: - NIK - LIMA1	MALT1 Mucosa-associated lymphoid tissue lymphoma translocation protein 1 is a protein that in humans is encoded by the MALT1 gene.[1][2][3] It's the human paracaspase. # Function Genetic ablation of the paracaspase gene in mice and biochemical studies have shown that paracaspase is a crucial protein for T and B lymphocytes activation. It has an important role in the activation of the transcription factor NF-κB, in the production of interleukin-2 (IL-2) and in T and B lymphocytes proliferation[4][5] Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.[6] In addition, a role for paracaspase has been shown in the innate immune response mediated by the zymosan receptor Dectin-1 in macrophages and dendritic cells, and in response to the stimulation of certain G protein-coupled receptors.[7] Sequence analysis proposes that paracaspase has an N-terminal death domain, two central immunoglobulin-like domains involved in the binding to the B-cell lymphoma 10 (Bcl10) protein and a caspase-like domain. Paracaspase has been shown to have proteolytic activity through its caspase-like domain in T lymphocytes. Cysteine 464 and histidine 414 are crucial for this activity. Like metacaspases, the paracaspase cleaves substrates after an arginine residue. To date, several paracaspase substrates have been described (see below). Bcl10 is cut after arginine 228. This removes the last five amino acids at the C-terminus and is crucial for T cell adhesion to fibronectin, but not for NF-κB activation and IL-2 production. However, using a peptide-based inhibitor (z-VRPR-fmk) of the paracaspase proteolytic activity, it has been shown that this activity is required for a sustain NF-κB activation and IL-2 production, suggesting that paracaspase may have others substrates involved in T cell-mediated NF-κB activation.[8] A20, a deubiquitinase, has been shown to be cut by paracaspase in Human and in mouse. Cells expressing an uncleavable A20 mutant is however still capable to activate NF-κB, but cells expressing the C-terminal or the N-terminal A20 cleavage products activates more NF-κB than cells expressing wild-type A20, indicating that cleavage of A20 leads to its inactivation. Since A20 has been described has an inhibitor of NF-κB, this suggests that paracaspase-mediated A20 cleavage in T lymphocytes is necessary for a proper NF-κB activation.[9] By targeting paracaspase proteolytic activity, it might be possible to develop new drugs that might be useful for the treatment of certain lymphomas or autoimmune disorders. # Interactions MALT1 has been shown to interact with BCL10,[10] TRAF6 and SQSTM1/p62. # Protease substrates MALT1 (PCASP1) is part of the paracaspase family and shows proteolytic activity. Since many of the substrates are involved in regulation of inflammatory responses, the protease activity of MALT1 has emerged as an interesting therapeutic target. Currently known protease substrates are: - TNFAIP3 (A20) [9] - BCL10 [8] - CYLD [11] - RELB [12] - regnase-1 (MCPIP1) [13] - Roquin-1 and -2 [14] - MALT1 auto-proteolysis [15] - HOIL1 [16][17] Specifically by the oncogenic IAP2-MALT1 fusion: - NIK [18] - LIMA1 [19]	https://www.wikidoc.org/index.php/MALT1
5db0701e091865c5962c0047f83f60929f8aeda7	wikidoc	MAML1	MAML1 Mastermind-like protein 1 is a protein that in humans is encoded by the MAML1 gene. # Function This protein is the human homolog of mastermind, a Drosophila protein that plays a role in the Notch signaling pathway involved in cell-fate determination. There is in vitro evidence that the human homolog forms a complex with the intracellular portion of human Notch receptors and can increase expression of a Notch-induced gene. This evidence supports its proposed function as a transcriptional co-activator in the Notch signaling pathway. Details on the activity of the N-terminal domain of Mastermind-like protein 1 may be found under MamL-1. # Interactions MAML1 has been shown to interact with EP300 and NOTCH1.	MAML1 Mastermind-like protein 1 is a protein that in humans is encoded by the MAML1 gene.[1][2][3] # Function This protein is the human homolog of mastermind, a Drosophila protein that plays a role in the Notch signaling pathway involved in cell-fate determination. There is in vitro evidence that the human homolog forms a complex with the intracellular portion of human Notch receptors and can increase expression of a Notch-induced gene. This evidence supports its proposed function as a transcriptional co-activator in the Notch signaling pathway.[3] Details on the activity of the N-terminal domain of Mastermind-like protein 1 may be found under MamL-1. # Interactions MAML1 has been shown to interact with EP300[4][5] and NOTCH1.[1][6]	https://www.wikidoc.org/index.php/MAML1
2c2b604f824f70b525d836d98307c762314a8436	wikidoc	MAP1B	MAP1B Microtubule-associated protein 1B is a protein that in humans is encoded by the MAP1B gene. # Function This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The product of this gene is a precursor polypeptide that presumably undergoes proteolytic processing to generate the final MAP1B heavy chain and LC1 light chain. Gene knockout studies of the mouse microtubule-associated protein 1B gene suggested an important role in development and function of the nervous system. Two alternatively spliced transcript variants have been described. # Interactions MAP1B has been shown to interact with Acidic leucine-rich nuclear phosphoprotein 32 family member A and RASSF1.	MAP1B Microtubule-associated protein 1B is a protein that in humans is encoded by the MAP1B gene.[1][2] # Function This gene encodes a protein that belongs to the microtubule-associated protein family. The proteins of this family are thought to be involved in microtubule assembly, which is an essential step in neurogenesis. The product of this gene is a precursor polypeptide that presumably undergoes proteolytic processing to generate the final MAP1B heavy chain and LC1 light chain. Gene knockout studies of the mouse microtubule-associated protein 1B gene suggested an important role in development and function of the nervous system. Two alternatively spliced transcript variants have been described.[2] # Interactions MAP1B has been shown to interact with Acidic leucine-rich nuclear phosphoprotein 32 family member A[3] and RASSF1.[4]	https://www.wikidoc.org/index.php/MAP1B
c221672a9cc588eafba350fc6f81f2296fa2eee7	wikidoc	MAPK1	MAPK1 Mitogen-activated protein kinase 1, also known as MAPK1, p42MAPK, and ERK2, is an enzyme that in humans is encoded by the MAPK1 gene. # Function The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene. # Model organisms Model organisms have been used in the study of MAPK1 function. A conditional knockout mouse line, called Mapk1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty seven tests were carried out on mutant mice and three significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and males had decreased circulating amylase levels. # Interactions MAPK1 has been shown to interact with: - ADAM17, - CIITA, - DUSP1, - DUSP22, - DUSP3, - ELK1, - FHL2, - HDAC4, - MAP2K1, - MAP3K1 - MAPK14, - MKNK1, - MKNK2, - Myc, - NEK2, - PEA15, - PTPN7, - Phosphatidylethanolamine binding protein 1, - RPS6KA1, - RPS6KA2, - RPS6KA3, - SORBS3, - STAT5A, - TNIP1, - TOB1, - TSC2, - UBR5, and - VAV1. # Clinical significance Mutations in MAPK1 are implicated in many types of cancer.	MAPK1 Mitogen-activated protein kinase 1, also known as MAPK1, p42MAPK, and ERK2, is an enzyme that in humans is encoded by the MAPK1 gene.[1] # Function The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene.[2] # Model organisms Model organisms have been used in the study of MAPK1 function. A conditional knockout mouse line, called Mapk1tm1a(EUCOMM)Wtsi[9][10] was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[11][12][13] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][14] Twenty seven tests were carried out on mutant mice and three significant abnormalities were observed.[7] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and males had decreased circulating amylase levels.[7] # Interactions MAPK1 has been shown to interact with: - ADAM17,[15] - CIITA,[16] - DUSP1,[17][18] - DUSP22,[19] - DUSP3,[20] - ELK1,[21][22] - FHL2,[23] - HDAC4,[24] - MAP2K1,[25][26][27][28][29][30] - MAP3K1[31] - MAPK14,[25][32] - MKNK1,[33] - MKNK2,[33][34] - Myc,[35][36][37] - NEK2,[38] - PEA15,[39] - PTPN7,[40][41] - Phosphatidylethanolamine binding protein 1,[27] - RPS6KA1,[21][42][43] - RPS6KA2,[43][44] - RPS6KA3,[42][44] - SORBS3,[45] - STAT5A,[46][47] - TNIP1,[48] - TOB1,[49] - TSC2,[50] - UBR5,[21] and - VAV1.[51][52] # Clinical significance Mutations in MAPK1 are implicated in many types of cancer.[53]	https://www.wikidoc.org/index.php/MAPK1
4e3fcc44e56658056cfa071368ed10b129f0f3c8	wikidoc	MAPK3	MAPK3 Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the MAPK3 gene. # Function The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described. # Clinical significance It has been suggested that MAPK3, along with the gene IRAK1, is turned off by two microRNAs that were activated after the influenza A virus had been made to infect human lung cells. # Signaling pathways Pharmacological inhibition of ERK1/2 restores GSK3β activity and protein synthesis levels in a model of tuberous sclerosis. # Interactions MAPK3 has been shown to interact with: - DUSP3, - DUSP6 - GTF2I, - HDAC4, - MAP2K1, - MAP2K2, - PTPN7, - RPS6KA2, and - SPIB.	MAPK3 Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1,[1] is an enzyme that in humans is encoded by the MAPK3 gene.[2] # Function The protein encoded by this gene is a member of the mitogen-activated protein kinase (MAP kinase) family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described.[3] # Clinical significance It has been suggested that MAPK3, along with the gene IRAK1, is turned off by two microRNAs that were activated after the influenza A virus had been made to infect human lung cells.[4] # Signaling pathways Pharmacological inhibition of ERK1/2 restores GSK3β activity and protein synthesis levels in a model of tuberous sclerosis.[5] # Interactions MAPK3 has been shown to interact with: - DUSP3,[6] - DUSP6[7] - GTF2I,[8] - HDAC4,[9] - MAP2K1,[10][11][12][13][14] - MAP2K2,[10][11][14] - PTPN7,[15][16][17] - RPS6KA2,[18][19] and - SPIB.[20]	https://www.wikidoc.org/index.php/MAPK3
9cebb8dc9515d407e6a6e4596d19c63f4d5af010	wikidoc	MAPK6	MAPK6 Mitogen-activated protein kinase 6 is an enzyme that in humans is encoded by the MAPK6 gene. The protein encoded by this gene is a member of the Ser/Thr protein kinase family, and is most closely related to mitogen-activated protein kinases (MAP kinases). MAP kinases, also known as extracellular signal-regulated kinases (ERKs), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. This kinase is localized in the nucleus, and has been reported to be activated in fibroblasts upon treatment with serum or phorbol esters. # Discovery ERK3/MAPK6 was initially cloned from the rat brain cDNA library by homology screening with probes ERK1 derived probe. # Gene location In humans, MAPK 6 gene is located on the distal arm of chromosome 15 (15q21.2). It is 47.01kb long and is transcribed in the centromere to telomere orientation. It consist of 6 exons with the translation initiation codon which is located in exon2. # Structure It is an atypical member of the mitogen activated kinases family. The molecular mass of the translated protein is approximately 100kDa, and is made up of 721 amino acid residues. It contains a typical kinase domain at the N- terminal and an extended C- terminal. The first 150 residues at c- terminal are 50% similar to ERK4 protein. At the kinase domain it exhibits about 70% similarity with the ERK4 protein. The activation loop of the phosphorylation motif contains only one phospho acceptor site (Ser-Glu-Gly). The structure is predicted by homology modelling using the crystal structure of phoshphorylated ERK2. According to the model, the structure of ERK3/MAPK6 kinase domain resembles other MAP kinases. The modelled ERK3/MAPK6 kinase domain is predicted to fold with a topology similar to other MAP kinases. # Expression ERK3/MAPK6 is widely expressed protein however it is expressed in significantly higher amounts in skeletal muscles and brain. It is localized in cytoplasm and the nucleus of cells. ERK3/MAPK6 is a highly unstable protein and has a very little half life of less than an hour. It is degraded by ubiquitin mediated proteasomal pathway. # Function It is very important for neonatal growth and survival. ERK3/MAPK6 forms a complex with microtubule associated protein2 (MAP2) and MAPKAPK5 which mediates the phosphorylation of MAPKAPK5 which in turn phosphorylates ERK3/MAPK6 at serine 189 residue mediating the entry into cell cycle. It also acts as a regulator for T- cell development. The catalytic activity of ERK3/MAPK6 plays an important for the proper differentiation of T-cells in the thymus. The long c- terminal is responsible for thymic differentiation. # Role in cancer ERK3/MAPK6 interacts with and phosphorylated steroid receptor coactivator 3 (SRC-3) This coreceptor is an oncogenic protein which when overexpressed at serine 857 leads to cancer. After the phosphorylation of SRC-3 results in the upregulation of MMP activity ERK3-mediated phosphorylation at S857 was essential for interaction of SRC-3 with the ETS transcription factor PEA3, which promotes upregulation of MMP gene expression and proinvasive activity.	MAPK6 Mitogen-activated protein kinase 6 is an enzyme that in humans is encoded by the MAPK6 gene.[1][2] The protein encoded by this gene is a member of the Ser/Thr protein kinase family, and is most closely related to mitogen-activated protein kinases (MAP kinases). MAP kinases, also known as extracellular signal-regulated kinases (ERKs), are activated through protein phosphorylation cascades and act as integration points for multiple biochemical signals. This kinase is localized in the nucleus, and has been reported to be activated in fibroblasts upon treatment with serum or phorbol esters.[2] # Discovery ERK3/MAPK6 was initially cloned from the rat brain cDNA library by homology screening with probes ERK1 derived probe.[3] # Gene location In humans, MAPK 6 gene is located on the distal arm of chromosome 15 (15q21.2). It is 47.01kb long and is transcribed in the centromere to telomere orientation. It consist of 6 exons with the translation initiation codon which is located in exon2.[4] # Structure It is an atypical member of the mitogen activated kinases family. The molecular mass of the translated protein is approximately 100kDa, and is made up of 721 amino acid residues.[4][3] It contains a typical kinase domain at the N- terminal and an extended C- terminal. The first 150 residues at c- terminal are 50% similar to ERK4 protein. At the kinase domain it exhibits about 70% similarity with the ERK4 protein.[4][3] The activation loop of the phosphorylation motif contains only one phospho acceptor site (Ser-Glu-Gly).[3] The structure is predicted by homology modelling using the crystal structure of phoshphorylated ERK2. According to the model, the structure of ERK3/MAPK6 kinase domain resembles other MAP kinases. The modelled ERK3/MAPK6 kinase domain is predicted to fold with a topology similar to other MAP kinases.[3] # Expression ERK3/MAPK6 is widely expressed protein however it is expressed in significantly higher amounts in skeletal muscles and brain. It is localized in cytoplasm and the nucleus of cells. ERK3/MAPK6 is a highly unstable protein and has a very little half life of less than an hour. It is degraded by ubiquitin mediated proteasomal pathway.[4] # Function It is very important for neonatal growth and survival. ERK3/MAPK6 forms a complex with microtubule associated protein2 (MAP2) and MAPKAPK5 which mediates the phosphorylation of MAPKAPK5 which in turn phosphorylates ERK3/MAPK6 at serine 189 residue mediating the entry into cell cycle.[5] It also acts as a regulator for T- cell development. The catalytic activity of ERK3/MAPK6 plays an important for the proper differentiation of T-cells in the thymus. The long c- terminal is responsible for thymic differentiation.[6] # Role in cancer ERK3/MAPK6 interacts with and phosphorylated steroid receptor coactivator 3 (SRC-3) This coreceptor is an oncogenic protein which when overexpressed at serine 857 leads to cancer. After the phosphorylation of SRC-3 results in the upregulation of MMP activity ERK3-mediated phosphorylation at S857 was essential for interaction of SRC-3 with the ETS transcription factor PEA3, which promotes upregulation of MMP gene expression and proinvasive activity.[7]	https://www.wikidoc.org/index.php/MAPK6
1b920c8325ab171cc415c4b708c3f443920a13e8	wikidoc	MAPK7	MAPK7 Mitogen-activated protein kinase 7 also known as MAP kinase 7 is an enzyme that in humans is encoded by the MAPK7 gene. # Function MAPK7 is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor tyrosine kinases, and G protein-coupled receptors. In response to extracellular signals, this kinase translocates to the cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported. MAPK7 is also critical for cardiovascular development and is essential for endothelial cell function. # Interactions MAPK7 has been shown to interact with: - C-Raf, - Gap junction protein, alpha 1 - MAP2K5, - MEF2C, - MEF2D, - PTPRR, - SGK, and - YWHAB.	MAPK7 Mitogen-activated protein kinase 7 also known as MAP kinase 7 is an enzyme that in humans is encoded by the MAPK7 gene.[1][2] # Function MAPK7 is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is specifically activated by mitogen-activated protein kinase kinase 5 (MAP2K5/MEK5). It is involved in the downstream signaling processes of various receptor molecules including receptor tyrosine kinases, and G protein-coupled receptors. In response to extracellular signals, this kinase translocates to the cell nucleus, where it regulates gene expression by phosphorylating, and activating different transcription factors. Four alternatively spliced transcript variants of this gene encoding two distinct isoforms have been reported.[3] MAPK7 is also critical for cardiovascular development [4] and is essential for endothelial cell function.[5][6] # Interactions MAPK7 has been shown to interact with: - C-Raf,[7] - Gap junction protein, alpha 1[8] - MAP2K5,[2] - MEF2C,[9] - MEF2D,[9] - PTPRR,[10] - SGK,[11] and - YWHAB.[12]	https://www.wikidoc.org/index.php/MAPK7
256818b718a00c6638182e5cd63b6b3e85ea25b3	wikidoc	MARCO	MARCO Macrophage receptor MARCO also known as macrophage receptor with collagenous structure (MARCO) is a protein that in humans is encoded by the MARCO gene. MARCO is a class A scavenger receptor that is found on particular subsets of macrophages. Scavenger receptors are pattern recognition receptors (PRRs) and are most commonly found on immune cells. Their defining feature is that they bind to polyanions and modified forms of a type of cholesterol called low-density lipoprotein (LDL). MARCO is able to bind and phagocytose these ligands and pathogen-associated molecular patterns (PAMPs), leading to the clearance of pathogens as well as causing downstream effects in the cell that lead to inflammation. As part of the innate immune system, MARCO clears, or scavenges, pathogens and leads to inflammatory responses. The scavenger receptor cysteine-rich (SRCR) domain at the end of the extracellular side of MARCO is responsible for ligand binding and the subsequent immune responses. MARCO expression on macrophages is also associated with diseases since Alzheimer's disease is associated with decreased response within the cell when a ligand binds to MARCO. # Cell expression Certain subtypes of macrophages are likely to express MARCO, but the receptor is also present on circulating monocytes, dendritic cells, and B cells. MARCO is typically present on the macrophages in the marginal zone of the spleen and the medullary lymph nodes, but it is also found in the liver. Dendritic cells increase expression of MARCO when exposed to certain pathogens, which leads to an increase in phagocytosis by the dendritic cell. When ligand binds to MARCO on dendritic cells, the cytoskeleton of the cell is altered, allowing for the formation of the long arms that also increase the phagocytic ability of dendritic cells. Macrophages that constitutively express MARCO are within the spleen marginal zone and medullary lymph nodes. Certain interactions between the macrophage and bacteria up-regulate its expression, as well as stimulating the expression of MARCO on tissue macrophages. # Function ## Phagocytosis The primary function of scavenger receptors is to phagocytose pathogens, but they are also able to participate in cell–cell recognition and are important in initiating inflammatory responses. MARCO, being a PRR, is able to bind to a wide variety of bacteria, making it an important receptor for immunity against bacteria. Both soluble LPS and entire bacteria are able to bind to MARCO. MARCO is also able to bind to both acetylated LDL (AcLDL) and oxidized LDL (OxLDL), as well as to B cells in the marginal zone of the spleen and apoptotic cells. Since MARCO is able to recognize and phagocytose pathogens and apoptotic cells, expression of MARCO increases the phagocytic ability of the cell. MARCO operates independently of opsonization. ## Inflammation MARCO does not directly cause an inflammatory response, but it helps other receptors interact with PAMPs, so they may initiate inflammation. One way MARCO does this is by tethering a pathogen to other proteins on the cell that do cause an inflammatory response. These proteins could be other PRRs such as TLR2. These receptors may then lead to the activation of NF-κB which allows for the production and release of pro-inflammatory cytokines. Through phagocytosis, MARCO also brings pathogens into the cell so that there are more pathogens available to intracellular compartments containing receptors such as TLR3, NOD2, and NALP3 that are capable of initiating an inflammatory response. # Structure MARCO is a transmembrane protein that has five domains. The first domain is within the cell, called the cytoplasmic domain. Moving into the cell membrane is the transmembrane domain, which is followed by the spacer domain located outside of the cell, then the collagenous domain, and finally the SRCR domain. The SRCR domain is necessary for MARCO to bind to ligands. Other members of the class A scavenger receptors tend to have alpha helical coiled coil domains, but MARCO does not. The C-terminal SRCR domain of MARCO plays a key role in the ability of the receptor to bind and take up ligand, enhance downstream inflammatory responses, and adhere to surfaces. The SRCR domain is where the ligand binds to MARCO. There are two highly conserved arginine amino acids, called the RxR motif, that are crucial for the binding of the ligand. # Associated diseases The activity of MARCO on microglia, the macrophages of the brain, is associated with Alzheimer's disease. One primary characteristic of Alzheimer's disease is the presence of numerous senile plaques in the brain that contain amyloid beta peptides (Aβ). Initially, the microglia clear the Aβ which binds to receptors such as MARCO. As the disease progresses, however, their ability to clear Aβ decreases, resulting in Aβ accumulation. This accumulation of Aβ occurs early on in Alzheimer's disease, harming the brain as Aβ is neurotoxic. MARCO also interacts with formyl peptide receptor (FPR2) to form a complex that causes the microglia to release pro-inflammatory cytokines which leads to inflammation that results in damage to neurons.	MARCO Macrophage receptor MARCO also known as macrophage receptor with collagenous structure (MARCO) is a protein that in humans is encoded by the MARCO gene.[1][2][3][4] MARCO is a class A scavenger receptor that is found on particular subsets of macrophages.[5][6][7] Scavenger receptors are pattern recognition receptors (PRRs) and are most commonly found on immune cells.[6] Their defining feature is that they bind to polyanions and modified forms of a type of cholesterol called low-density lipoprotein (LDL).[5][6] MARCO is able to bind and phagocytose these ligands and pathogen-associated molecular patterns (PAMPs), leading to the clearance of pathogens as well as causing downstream effects in the cell that lead to inflammation.[7][8] As part of the innate immune system, MARCO clears, or scavenges, pathogens and leads to inflammatory responses.[8] The scavenger receptor cysteine-rich (SRCR) domain at the end of the extracellular side of MARCO is responsible for ligand binding and the subsequent immune responses.[8] MARCO expression on macrophages is also associated with diseases since Alzheimer's disease is associated with decreased response within the cell when a ligand binds to MARCO.[9][10] # Cell expression Certain subtypes of macrophages are likely to express MARCO, but the receptor is also present on circulating monocytes, dendritic cells, and B cells.[6][11] MARCO is typically present on the macrophages in the marginal zone of the spleen and the medullary lymph nodes, but it is also found in the liver.[9] Dendritic cells increase expression of MARCO when exposed to certain pathogens, which leads to an increase in phagocytosis by the dendritic cell.[5] When ligand binds to MARCO on dendritic cells, the cytoskeleton of the cell is altered, allowing for the formation of the long arms that also increase the phagocytic ability of dendritic cells.[5][12] Macrophages that constitutively express MARCO are within the spleen marginal zone and medullary lymph nodes.[5] Certain interactions between the macrophage and bacteria up-regulate its expression, as well as stimulating the expression of MARCO on tissue macrophages.[5][6] # Function ## Phagocytosis The primary function of scavenger receptors is to phagocytose pathogens, but they are also able to participate in cell–cell recognition and are important in initiating inflammatory responses.[7][6] MARCO, being a PRR, is able to bind to a wide variety of bacteria, making it an important receptor for immunity against bacteria.[8] Both soluble LPS and entire bacteria are able to bind to MARCO.[13] MARCO is also able to bind to both acetylated LDL (AcLDL) and oxidized LDL (OxLDL), as well as to B cells in the marginal zone of the spleen and apoptotic cells.[5][6] Since MARCO is able to recognize and phagocytose pathogens and apoptotic cells, expression of MARCO increases the phagocytic ability of the cell. MARCO operates independently of opsonization.[8] ## Inflammation MARCO does not directly cause an inflammatory response, but it helps other receptors interact with PAMPs, so they may initiate inflammation.[7][8] One way MARCO does this is by tethering a pathogen to other proteins on the cell that do cause an inflammatory response.[8] These proteins could be other PRRs such as TLR2.[8] These receptors may then lead to the activation of NF-κB which allows for the production and release of pro-inflammatory cytokines.[8] Through phagocytosis, MARCO also brings pathogens into the cell so that there are more pathogens available to intracellular compartments containing receptors such as TLR3, NOD2, and NALP3 that are capable of initiating an inflammatory response.[7] # Structure MARCO is a transmembrane protein that has five domains.[6] The first domain is within the cell, called the cytoplasmic domain.[6] Moving into the cell membrane is the transmembrane domain, which is followed by the spacer domain located outside of the cell, then the collagenous domain, and finally the SRCR domain.[6] The SRCR domain is necessary for MARCO to bind to ligands.[6] Other members of the class A scavenger receptors tend to have alpha helical coiled coil domains, but MARCO does not.[5] The C-terminal SRCR domain of MARCO plays a key role in the ability of the receptor to bind and take up ligand, enhance downstream inflammatory responses, and adhere to surfaces.[8] The SRCR domain is where the ligand binds to MARCO.[8] There are two highly conserved arginine amino acids, called the RxR motif, that are crucial for the binding of the ligand.[8] # Associated diseases The activity of MARCO on microglia, the macrophages of the brain, is associated with Alzheimer's disease.[7][10] One primary characteristic of Alzheimer's disease is the presence of numerous senile plaques in the brain that contain amyloid beta peptides (Aβ).[10] Initially, the microglia clear the Aβ which binds to receptors such as MARCO.[10] As the disease progresses, however, their ability to clear Aβ decreases, resulting in Aβ accumulation.[10] This accumulation of Aβ occurs early on in Alzheimer's disease, harming the brain as Aβ is neurotoxic.[10] MARCO also interacts with formyl peptide receptor (FPR2) to form a complex that causes the microglia to release pro-inflammatory cytokines which leads to inflammation that results in damage to neurons.[10]	https://www.wikidoc.org/index.php/MARCO
28e22aabbedb9a3421877089174e447cc8dbee82	wikidoc	MARK4	MARK4 MAP/microtubule affinity-regulating kinase 4 is an enzyme that in humans is encoded by the MARK4 gene. MARK4 belongs to the family of serine/threonine kinases that phosphorylate microtubule-associated proteins (MAP) causing their detachment from microtubules. Detachment thereby increases microtubule dynamics and facilitates a number of cell activities including cell division, cell cycle control, cell polarity determination, and cell shape alterations. There are four members of the MARK protein family, MARK1-4, which are highly conserved. MARK4 kinase has been shown to be involved in microtubule organization in neuronal cells. Levels of MARK4 are elevated in Alzheimer's disease and may contribute to the pathological phosphorylation of tau in this disease. # Interactions MARK4 has been shown to interact with USP9X and Ubiquitin C.	MARK4 MAP/microtubule affinity-regulating kinase 4 is an enzyme that in humans is encoded by the MARK4 gene.[1][2][3] MARK4 belongs to the family of serine/threonine kinases that phosphorylate microtubule-associated proteins (MAP) causing their detachment from microtubules.[4] Detachment thereby increases microtubule dynamics and facilitates a number of cell activities including cell division, cell cycle control, cell polarity determination, and cell shape alterations.[5] There are four members of the MARK protein family, MARK1-4, which are highly conserved. MARK4 kinase has been shown to be involved in microtubule organization in neuronal cells. Levels of MARK4 are elevated in Alzheimer's disease and may contribute to the pathological phosphorylation of tau in this disease. # Interactions MARK4 has been shown to interact with USP9X[6] and Ubiquitin C.[6]	https://www.wikidoc.org/index.php/MARK4
1795578625736688f68927b4f253feb89312eb2a	wikidoc	MASTL	MASTL MASTL is an official symbol provided by HGNC for human gene whose official name is micro tubule associated serine/threonine kinase like. This gene is 32,1 kbps long. This gene is also known as GW, GWL, THC2, MAST-L, GREATWALL. This is present in mainly mammalian cells like human, house mouse, cattle, monkey, etc. It is in the 10th chromosome of the mammalian nucleus. Recent studies have been carried on zebrafish and frogs. This gene encodes for the protein micro tubule associated serine/threonine kinase and its sub-classes. Micro-tubule-associated serine/threonine protein kinase is a mammalian enzyme which was first discovered in Drosophila as an essential kinase (great wall) for correct chromosome condensation and mitotic progression. The EC number for this enzyme is 2.7.11.12. This enzyme is active during mitotic division and is mainly localized in the nucleus during interphase. They get dispersed into the cytoplasm upon the degradation of nuclear envelope during mitosis. The MASTL depleted cells are delayed by RNAi in G2 phase and show a decreased condensation of the chromosomes. RNAi cells which pass through the mitosis, might not get separated into their sister chromatids in anaphase. This causes the chromatin to be trapped in the cleavage furrow and form 4N G1 cells due to cytokinesis failure. This enzyme enhances the cyclin B1-Cdk1-dependent mitotic phosphorylation events during mitosis. This enzyme is also essential for metaphase entry by suppressing protein phosphatase 2A which will in turn leads to high level of Cdk1 substrate phosphorylation. It also provides the timely activation of APC/C during Meiosis I and Cdk1 reactivation in meiosis II. Mutation in the gene A missense mutation in the MASTL gene can lead to an autosomal dominant inherited thrombocytopenia. The mutation is due to the change in amino acid glutamic acid at 167 to aspartic acid. Common phenotype of a mild thrombocytopenia patient is the decrease average plate counts of 60,000 platelets per ml of blood. Uses in the therapeutic field MASTL enzyme is also used for therapeutic applications such as cancer progression and tumor recurrence after free cancer therapy and this enzyme can be of higher value in the therapeutic market.	MASTL MASTL is an official symbol provided by HGNC for human gene whose official name is micro tubule associated serine/threonine kinase like. This gene is 32,1 kbps long. This gene is also known as GW, GWL, THC2, MAST-L, GREATWALL. This is present in mainly mammalian cells like human, house mouse, cattle, monkey, etc. It is in the 10th chromosome of the mammalian nucleus. Recent studies have been carried on zebrafish and frogs. This gene encodes for the protein micro tubule associated serine/threonine kinase and its sub-classes. Micro-tubule-associated serine/threonine protein kinase is a mammalian enzyme which was first discovered in Drosophila as an essential kinase (great wall) for correct chromosome condensation and mitotic progression. The EC number for this enzyme is 2.7.11.12. This enzyme is active during mitotic division and is mainly localized in the nucleus during interphase. They get dispersed into the cytoplasm upon the degradation of nuclear envelope during mitosis. The MASTL depleted cells are delayed by RNAi in G2 phase and show a decreased condensation of the chromosomes. RNAi cells which pass through the mitosis, might not get separated into their sister chromatids in anaphase. This causes the chromatin to be trapped in the cleavage furrow and form 4N G1 cells due to cytokinesis failure. This enzyme enhances the cyclin B1-Cdk1-dependent mitotic phosphorylation events during mitosis.[1] This enzyme is also essential for metaphase entry by suppressing protein phosphatase 2A which will in turn leads to high level of Cdk1 substrate phosphorylation. It also provides the timely activation of APC/C during Meiosis I and Cdk1 reactivation in meiosis II.[2] Mutation in the gene A missense mutation in the MASTL gene can lead to an autosomal dominant inherited thrombocytopenia. The mutation is due to the change in amino acid glutamic acid at 167 to aspartic acid. Common phenotype of a mild thrombocytopenia patient is the decrease average plate counts of 60,000 platelets per ml of blood. Uses in the therapeutic field MASTL enzyme is also used for therapeutic applications such as cancer progression and tumor recurrence after free cancer therapy and this enzyme can be of higher value in the therapeutic market.[3]	https://www.wikidoc.org/index.php/MASTL
c227c3caa07e61f781f761d46248a6d10410db74	wikidoc	MATR3	MATR3 Matrin-3 is a protein that in humans is encoded by the MATR3 gene. # Function The protein encoded by this gene is localized in the nuclear matrix. It may play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. Two transcript variants encoding the same protein have been identified for this gene. # Pathology Mutations in the Matrin 3 gene are associated with familial amyotrophic lateral sclerosis.	MATR3 Matrin-3 is a protein that in humans is encoded by the MATR3 gene.[1][2] # Function The protein encoded by this gene is localized in the nuclear matrix. It may play a role in transcription or may interact with other nuclear matrix proteins to form the internal fibrogranular network. Two transcript variants encoding the same protein have been identified for this gene.[2] # Pathology Mutations in the Matrin 3 gene are associated with familial amyotrophic lateral sclerosis.[3]	https://www.wikidoc.org/index.php/MATR3
514b412fbf601bd2500dfc16774b5e88bef7d99c	wikidoc	Wrist	Wrist In human anatomy, the wrist is the flexible and narrower connection between the forearm and the palm. The wrist is essentially a double row of small short bones, called carpals, intertwined to form a malleable hinge. The wrist-joint (articulatio radiocarpea) is a condyloid articulation allowing three degrees of freedom. # Structure of joint The parts forming it are the lower end of the radius and under surface of the articular disk above; and the scaphoid, lunate, and triquetral bones below. The articular surface of the radius and the under surface of the articular disk form together a transversely elliptical concave surface, the receiving cavity. The superior articular surfaces of the scaphoid, lunate, and triquetrum form a smooth convex surface, the condyle, which is received into the concavity. The bones of the wrist can be easily remembered by the mnemonic SLTPTTCH - Some Lovers Try Positions That They Can't Handle. These represent the bones in order of proximal row radial to ulnar and then distal row radial to ulnar: Scaphoid, Lunate, Triquetral, Pisiform; Trapezium, Trapezoid, Capitate, Hamate. # Ligaments The joint is surrounded by a capsule, strengthened by the following ligaments: - Palmar radiocarpal ligament - Dorsal radiocarpal ligament - Ulnar collateral ligament (wrist) - Radial collateral ligament (wrist) The synovial membrane lines the deep surfaces of the ligaments above described, extending from the margin of the lower end of the radius and articular disk above to the margins of the articular surfaces of the carpal bones below. It is loose and lax, and presents numerous folds, especially behind. # Movements The movements permitted in this joint are flexion, extension, abduction, adduction, and circumduction. They are studied with those of the carpus, with which they are combined.	Wrist Template:Infobox Anatomy Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] In human anatomy, the wrist is the flexible and narrower connection between the forearm and the palm. The wrist is essentially a double row of small short bones, called carpals, intertwined to form a malleable hinge. The wrist-joint (articulatio radiocarpea) is a condyloid articulation allowing three degrees of freedom. # Structure of joint The parts forming it are the lower end of the radius and under surface of the articular disk above; and the scaphoid, lunate, and triquetral bones below. The articular surface of the radius and the under surface of the articular disk form together a transversely elliptical concave surface, the receiving cavity. The superior articular surfaces of the scaphoid, lunate, and triquetrum form a smooth convex surface, the condyle, which is received into the concavity. The bones of the wrist can be easily remembered by the mnemonic SLTPTTCH - Some Lovers Try Positions That They Can't Handle. These represent the bones in order of proximal row radial to ulnar and then distal row radial to ulnar: Scaphoid, Lunate, Triquetral, Pisiform; Trapezium, Trapezoid, Capitate, Hamate. # Ligaments The joint is surrounded by a capsule, strengthened by the following ligaments: - Palmar radiocarpal ligament - Dorsal radiocarpal ligament - Ulnar collateral ligament (wrist) - Radial collateral ligament (wrist) The synovial membrane lines the deep surfaces of the ligaments above described, extending from the margin of the lower end of the radius and articular disk above to the margins of the articular surfaces of the carpal bones below. It is loose and lax, and presents numerous folds, especially behind. # Movements The movements permitted in this joint are flexion, extension, abduction, adduction, and circumduction. They are studied with those of the carpus, with which they are combined.	https://www.wikidoc.org/index.php/MCP_joint
c0a972ad21ca1bb88bbdd8ee46c17548953bd63b	wikidoc	MDGA2	MDGA2 MDGA2 (MAM domain containing glycosylphosphatidylinositol anchor 2) is a human gene. It has previously been called MAMDC1. MDGA2 is located on chromosome 14. The gene has a homologue in rat and mouse, Mdga2, and investigations in rats have found that the gene is expressed in the central and peripheral nervous system in a subpopulation of neurons, e.g., in the basilar pons and cerebral cortex. There are several variants in the human gene, and a genome-wide association study has pointed to that single-nucleotide polymorphisms in MDGA2 is associated with neuroticism. However, a more recent study has failed to replicate that finding.	MDGA2 MDGA2 (MAM domain containing glycosylphosphatidylinositol anchor 2) is a human gene. It has previously been called MAMDC1.[1] MDGA2 is located on chromosome 14. The gene has a homologue in rat and mouse, Mdga2,[2] and investigations in rats have found that the gene is expressed in the central and peripheral nervous system in a subpopulation of neurons, e.g., in the basilar pons and cerebral cortex.[3] There are several variants in the human gene,[4] and a genome-wide association study has pointed to that single-nucleotide polymorphisms in MDGA2 is associated with neuroticism.[5] However, a more recent study has failed to replicate that finding.[6]	https://www.wikidoc.org/index.php/MDGA2
98988990ceefa29a570ff28d57775e8ddd700c24	wikidoc	MECOM	MECOM MDS1 and EVI1 complex locus protein EVI1 (MECOM) also known as ecotropic virus integration site 1 protein homolog (EVI-1) or positive regulatory domain zinc finger protein 3 (PRDM3) is a protein that in humans is encoded by the MECOM gene. EVI1 was first identified as a common retroviral integration site in AKXD murine myeloid tumors. It has since been identified in a plethora of other organisms, and seems to play a relatively conserved developmental role in embryogenesis. EVI1 is a nuclear transcription factor involved in many signaling pathways for both coexpression and coactivation of cell cycle genes. # Gene structure The EVI1 gene is located in the human genome on chromosome 3 (3q26.2). The gene spans 60 kilobases and encodes 16 exons, 10 of which are protein-coding. The first in-frame ATG start codon is in exon 3. ## mRNA A large number of transcript variations exist, encoding different isoforms or chimeric proteins. Some of the most common ones are: - EVI_1a, EVI_1b, EVI_1c, EVI_1d, and EVI_3L are all variants in the 5' untranslated region, and all except EVI_1a are specific to human cells. - −Rp9 variant is quite common in human and mouse cells, lacks 9 amino acids in the repression domain. - Δ324 found at low levels in human and mouse cells - an alternative splice variant encoding an 88kDa protein lacking zinc fingers 6 and 7 - Δ105 variant is unique to mice, and results in a protein truncated by 105 amino acids at the acidic C-terminus. - Fusion transcripts with upstream genes such as MDS1/EVI1 (ME), AML1/MDS1/EVI1 (AME), ETV6/MDS1/EVI1 have all been identified ## Protein The MECOM is primarily found in the nucleus, either soluble or bound to DNA. The 145kDa isoform is the most-studied, encoding 1051 amino acids, although there are many EVI1 fusion products detectable in cells expressing EVI1. The MECOM protein contains 2 domains characterized by 7 zinc finger motifs followed by a proline-rich transcription repression domain, 3 more zinc finger motifs and an acidic C-terminus. # Biological role EVI1 is a proto-oncogene conserved across humans, mice, and rats, sharing 91% homology in nucleotide sequence and 94% homology in amino acid sequence between humans and mice. It is a transcription factor localized to the nucleus and binds DNA through specific conserved sequences of GACAAGATA with the potential to interact with both corepressors and coactivators. # Association with cancer EVI1 has been described as a proto-oncogene since its first discovery in 1988. Overexpression and aberrant expression of EVI1 has been associated with human acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS) and chronic myelogenous leukemia (CML), and more recently has been shown as a poor prognostic indicator. Its function in these cells may be regulated by phosphorylation of serine196, in its N-terminal DNA binding domain. All of these involve erratic cellular development and differentiation in the bone marrow leading to dramatic alterations in the normal population of blood cells. EVI1 has also been found to play a role in solid ovarian and colon tumors, although it is not yet well characterized in this context. It has been hypothesized that it acts as a survival factor in tumor cell lines, preventing therapeutic-induced apoptosis and rendering the tumor cells more resistant to current treatments. ## Role in tumor suppressor signaling and prevention of apoptosis ### TGF-β and cell cycle progression EVI1 has been shown to be involved in the downstream signaling pathway of transforming growth factor beta (TGF-β). TGF-β, along with other TGF-β family ligands such as bone morphogenic protein (BMP) and activin are involved in regulating important cellular functions such as proliferation, differentiation, apoptosis, and matrix production. These biological roles are not only important for cellular development, but also in understanding oncogenesis. TGF-β signaling induces transcription of the cyclin-dependent kinase (CDK) inhibitors p15Ink4B or p21Cip1, which, as a consequence, act to halt the cell cycle and stop proliferation. This inhibition can lead to cellular differentiation or apoptosis, and therefore any resistance to TGF-β is thought to contribute in some way to human leukemogenesis. As shown in the figure below, the downstream effectors of TGF-β are the Smad receptors (also known as receptor-activated Smads). Smad2 and Smad3 are phosphorylated in response to TGF-β ligand binding, and translocate into the nucleus of the cell, where they can then bind to DNA and other transcription factors. Stable binding to promoters occurs through a conserved MH1 domain, and transcription activation occurs through an MH2 domain, and involves accompanying coactivators such as CBP/p300 and Sp1. The majority of literature discusses the interaction between EVI1 and Smad3, however there have been some experiments done showing that EVI1 interacts with all of the Smad proteins at varying levels, indicating a potential involvement in all of the pathways that include Smads as downstream effectors. The translocation of phosphorylated Smad3 into the nucleus allows for direct interaction with EVI1, mediated by the first zinc finger domain on EVI1 and the MH2 domain on Smad3. As the Smad3 MH2 domain is required for transcription activation, EVI1 binding effectively prevents transcription of the TGF-β induced anti-growth genes through structural blocking, and also leads to recruitment of other transcriptional repressors (see Epigenetics). By inhibiting an important checkpoint pathway for tumor suppression and growth control, overexpression or aberrant expression of EVI1 has characteristic oncogenic activity. As an additional confirmation of the role of EVI1 expression on cell cycle progression, it has been shown that high EVI1 expression is correlated with the well-known tumor suppressor and cell cycle mediator Retinoblastoma, remaining in a hyperphosphorylated state, even in the presence of TGF-β. ### JNK and inhibition of apoptosis c-Jun N-terminal kinase (JNK) is a MAP kinase activated by extracellular stress signals such as gamma-radiation, ultraviolet light, Fas ligand, tumor necrosis factor α (TNF-α), and interleukin-1. Phosphorylation on two separate residues, Thr183 and Tyr185, cause JNK to become activated and translocate to the nucleus to phosphorylate and activate key transcription factors for the apoptotic response. Experiments co-expressing EVI1 and JNK have shown that levels of JNK-phosphorylated transcription factors (such as c-Jun) are drastically decreased in the presence of EVI1. Binding of EVI1 and JNK has been shown to occur through the first zinc finger motif on EVI1, and that this interaction does not block JNK phosphorylation and activation, but blocks JNK binding to substrate in the nucleus. Subsequent in vitro assays showed that stress-induced cell death from a variety of stimuli is significantly inhibited by EVI1 and JNK binding. EVI1 does not bind other MAP kinases such as p38 or ERK. ## Oncogenesis and induced proliferation of HSCs Among the many other observed defects, EVI1−/− mouse embryos have been shown to have defects in both the development and proliferation of hematopoietic stem cells (HSCs). It is presumed that this is due to direct interaction with the transcription factor GATA-2, which is crucial for HSC development. It has subsequently been shown many times in vitro that EVI1 upregulation can induce proliferation and differentiation of HSCs and some other cell types such as rat fibroblasts. However, existing data is inconclusive regarding the absolute role of EVI1 in cell cycle progression. It appears to depend on the specific cell type, cell line and growth conditions being used as to whether EVI1 expression induces growth arrest or cell differentiation/proliferation, or whether it has any effect at all. The data showing direct interaction of EVI1 with the promoters for a diverse array of genes supports the theory that this is a complex transcription factor associated with many different signalling pathways involved in development and growth. ### Angiogenesis Although the literature is limited on the subject, the well-documented effects on HSCs imply that there is a potential indirect effect of aberrant EVI1 expression on tumoral angiogenesis. HSCs secrete angiopoietin, and its receptor molecule Tie2 has been implicated in angiogenesis of tumors in both humans and mice. Upregulation of Tie2 has been shown to occur under hypoxic conditions, and to increase angiogenesis when coinjected with tumor cells in mice. Observations that EVI1−/− mutants have substantially downregulated Tie2 and Ang-I expression, therefore, hints at an interesting role of high EVI1 expression in tumor progression. This is likely, at least in part, a reason for the widespread hemorrhaging and minimal vascular development in EVI1 deleted embryos, and has potential to indicate yet another reason for poor prognosis of EVI1 positive cancers. ## Epigenetics EVI1 has also been shown to directly interact with C-terminal-binding protein (CtBP, a known transcriptional repressor) through in vitro techniques such as yeast 2-hybrid screens and immunoprecipitation. This interaction has been specifically shown to rely on amino acids 544-607 on the EVI1 protein, a stretch that contains two CtBP-binding consensus motifs. This binding leads to recruitment of histone deacetylases (HDACs) as well as many other corepressor molecules leading to transcription repression via chromatin remodelling. EVI1 interaction with Smad3 followed by recruitment of corepressors can inhibit transcription and de-sensitize a cell to TGF-β signaling without ever displacing Smad3 from a gene's promoter. The epigenetic modification is clearly enough to make the DNA inaccessible to the transcription machinery. Although EVI1 has mainly been implicated as a transcription repressor, there is some data that has shown a possible dual role for this protein. Studies show that EVI1 also binds to known coactivators cAMP responsive element binding protein (CBP) and p300/CBP-associated factor (P/CAF). These both have histone acetyltransferase activity, and lead to subsequent transcription activation. In addition, structural changes have been visualized within the nucleus of a cell, depending on the presence of corepressors or coactivators, leading researchers to believe that EVI1 has a unique response to each kind of molecule. In approximately 90% of cells, EVI1 is diffuse within the nucleus; however, when CBP and P/CAF are added, extensive nuclear speckle formation occurs. The complete physiological repercussions of this complex role of EVI1 have yet to be elucidated, however, could provide insight into the wide variety of results that have been reported regarding the effect of EVI1 on in vitro cell proliferation. Interaction with corepressors and coactivators appears to occur in distinct domains, and there are theories that EVI1 exists in a periodical, reversible acetylated state within the cell. Contrasting theories indicate that the interplay between different EVI1 binding proteins acts to stabilize interactions with different transcription factors and DNA, leading to a response of EVI1 to a diverse set of stimuli. ## Chromosome instability Since it was first identified in murine myeloid leukemia as a common site of retroviral integration into the chromosome, EVI1 and its surrounding DNA have been a site of many identified chromosomal translocations and abnormalities. This can lead to aberrant expression of EVI1, and, as shown in the figure below, commonly involved chromosomal breakpoints have been mapped extensively. One major cause of EVI1 activation and consequent overexpression is a clinical condition called 3q21q26 syndrome from inv(3)(q21q26) or t(3;3)(q21;q26). The result is the placement of a strong enhancing region for the housekeeping gene Ribophorin 1 (RPN1) next to the EVI1 coding sequence, resulting in a dramatic increase of EVI1 levels in the cell. A summary of common chromosomal abnormalities involving EVI1 and its fusion genes can be found in a review by Nucifora et al.. The most common circumstance involves chromosomal translocations in human AML or MDS, leading to constitutive expression of EVI1 and eventually to cancer. Not only are these abnormalities in the 3q26 region associated with very poor patient prognosis they are also commonly accompanied by additional karyotypic changes such as chromosome 7 monosomy, deletion of the short arm of chromosome 7, or partial deletions of chromosome 5. In addition, it has been shown that development of acute myelogenous leukemia is likely due to several sequential genetic changes, and that expression of EVI1 or its chimeric counterparts ME and AME alone is not enough to completely block myeloid differentiation. BCR-Abl, a fusion gene caused by t(9;22)(q34;q11)is thought to have a cooperative effect with EVI1 during the progression of AML and CML. Together, these two systems disrupt tyrosine kinase signaling and hematopoietic gene transcription. Despite the extensively studied chromosomal abnormalities at the EVI1 locus, it should be noted that, in anywhere from 10-50% of identified cases, EVI1 overexpression is detectable without any chromosomal abnormalities, indicating that there are other not-yet-understood systems, likely epigenetic, leading to EVI1 promoter activation. In many of these cases, it is noted that a variety of 5' transcript variants are detectable at relatively high levels. Clinical studies have shown that these variants (EVI1_1a, EVI1_1b, EVI1_1d, EVI1_3L) as well as the MDS1-EVI1 fusion transcript are all associated with poor prognosis and increased likelihood of rapid remission in cases of de novo AML. ## Pharmacogenomics and cancer treatment Very little research has been done in an attempt to therapeutically target EVI1 or any of its chimeric counterparts. However, since it has become an established fact that overexpression of EVI1 derivatives is a bad prognostic indicator, it is likely that the literature will begin to examine specific targeting within the next few years. One very promising therapeutic agent for myelogenous leukemia and potentially other forms of cancer is arsenic trioxide (ATO). One study has been done showing that ATO treatment leads to specific degradation of the AML1/MDS1/EVI1 oncoprotein and induces both apoptosis and differentiation. As an atypical use of traditional pharmacogenomics, this knowledge may lead to an increased ability to treat EVI1 positive leukemias that would normally have poor prognoses. If it is established that a clinical cancer case is EVI1 positive, altering the chemotherapeutic cocktail to include a specific EVI1 antagonist may aid to increase lifespan and prevent potential relapse. Arsenic is a fairly ancient human therapeutic agent, however it has only recently returned to the forefront of cancer treatment. It has been observed that it not only induces apoptosis but can also inhibit the cell cycle, and has marked anti-angiogenesis effects. As of 2006, Phase I and II clinical trials were being conducted to test this compound on a wide variety of cancer types, and currently (2008) a number of publications are showing positive outcomes in individual case studies, both pediatric and adult. ## Hormones The important and essential role of EVI1 in embryogenesis clearly indicates a close association with hormonal fluctuations in developing cells. However, to date, the presence of EVI1 in cancer has not been linked to aberrant production of any hormones or hormone receptors. It is likely that EVI1 is far enough downstream of hormonal signaling that once overproduced, it can function independently. # Future and current research ## Affect on gene therapy Areas where retroviral integration into the human genome is favored such as EVI1 have very important implications for the development of gene therapy. It was initially thought that delivery of genetic material through a non-replicating virus vector would pose no significant risk, as the likelihood of a random incorporation near a proto-oncogene was minimal. By 2008 it was realised that sites such as EVI1 are "highly over-represented" when it comes to vector insertions. # Interactions EVI1 has been shown to interact with: - CREB binding protein, - CTBP1, - HDAC1, - Mothers against decapentaplegic homolog 3, and - PCAF and	MECOM MDS1 and EVI1 complex locus protein EVI1 (MECOM) also known as ecotropic virus integration site 1 protein homolog (EVI-1) or positive regulatory domain zinc finger protein 3 (PRDM3) is a protein that in humans is encoded by the MECOM gene. EVI1 was first identified as a common retroviral integration site in AKXD murine myeloid tumors. It has since been identified in a plethora of other organisms, and seems to play a relatively conserved developmental role in embryogenesis. EVI1 is a nuclear transcription factor involved in many signaling pathways for both coexpression and coactivation of cell cycle genes. # Gene structure The EVI1 gene is located in the human genome on chromosome 3 (3q26.2). The gene spans 60 kilobases and encodes 16 exons, 10 of which are protein-coding. The first in-frame ATG start codon is in exon 3.[1] ## mRNA A large number of transcript variations exist, encoding different isoforms or chimeric proteins. Some of the most common ones are: - EVI_1a, EVI_1b, EVI_1c, EVI_1d, and EVI_3L are all variants in the 5' untranslated region, and all except EVI_1a are specific to human cells.[2] - −Rp9 variant is quite common in human and mouse cells, lacks 9 amino acids in the repression domain.[2] - Δ324 found at low levels in human and mouse cells - an alternative splice variant encoding an 88kDa protein lacking zinc fingers 6 and 7 [2][3] - Δ105 variant is unique to mice, and results in a protein truncated by 105 amino acids at the acidic C-terminus.[2] - Fusion transcripts with upstream genes such as MDS1/EVI1 (ME), AML1/MDS1/EVI1 (AME), ETV6/MDS1/EVI1 have all been identified [2] ## Protein The MECOM is primarily found in the nucleus, either soluble or bound to DNA. The 145kDa isoform is the most-studied, encoding 1051 amino acids,[3] although there are many EVI1 fusion products detectable in cells expressing EVI1. The MECOM protein contains 2 domains characterized by 7 zinc finger motifs followed by a proline-rich transcription repression domain, 3 more zinc finger motifs and an acidic C-terminus.[2] # Biological role EVI1 is a proto-oncogene conserved across humans, mice, and rats, sharing 91% homology in nucleotide sequence and 94% homology in amino acid sequence between humans and mice.[3] It is a transcription factor localized to the nucleus and binds DNA through specific conserved sequences of GACAAGATA [4] with the potential to interact with both corepressors and coactivators. # Association with cancer EVI1 has been described as a proto-oncogene since its first discovery in 1988.[5] Overexpression and aberrant expression of EVI1 has been associated with human acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS) and chronic myelogenous leukemia (CML), and more recently has been shown as a poor prognostic indicator. Its function in these cells may be regulated by phosphorylation of serine196, in its N-terminal DNA binding domain.[6] All of these involve erratic cellular development and differentiation in the bone marrow leading to dramatic alterations in the normal population of blood cells. EVI1 has also been found to play a role in solid ovarian and colon tumors,[7] although it is not yet well characterized in this context. It has been hypothesized that it acts as a survival factor in tumor cell lines, preventing therapeutic-induced apoptosis and rendering the tumor cells more resistant to current treatments.[8] ## Role in tumor suppressor signaling and prevention of apoptosis ### TGF-β and cell cycle progression EVI1 has been shown to be involved in the downstream signaling pathway of transforming growth factor beta (TGF-β). TGF-β, along with other TGF-β family ligands such as bone morphogenic protein (BMP) and activin are involved in regulating important cellular functions such as proliferation, differentiation, apoptosis, and matrix production.[9] These biological roles are not only important for cellular development, but also in understanding oncogenesis. TGF-β signaling induces transcription of the cyclin-dependent kinase (CDK) inhibitors p15Ink4B or p21Cip1, which, as a consequence, act to halt the cell cycle and stop proliferation. This inhibition can lead to cellular differentiation or apoptosis, and therefore any resistance to TGF-β is thought to contribute in some way to human leukemogenesis.[10] As shown in the figure below, the downstream effectors of TGF-β are the Smad receptors (also known as receptor-activated Smads). Smad2 and Smad3 are phosphorylated in response to TGF-β ligand binding, and translocate into the nucleus of the cell, where they can then bind to DNA and other transcription factors.[9] Stable binding to promoters occurs through a conserved MH1 domain, and transcription activation occurs through an MH2 domain, and involves accompanying coactivators such as CBP/p300 and Sp1.[9] The majority of literature discusses the interaction between EVI1 and Smad3, however there have been some experiments done showing that EVI1 interacts with all of the Smad proteins at varying levels, indicating a potential involvement in all of the pathways that include Smads as downstream effectors.[9] The translocation of phosphorylated Smad3 into the nucleus allows for direct interaction with EVI1, mediated by the first zinc finger domain on EVI1 and the MH2 domain on Smad3.[9][10] As the Smad3 MH2 domain is required for transcription activation, EVI1 binding effectively prevents transcription of the TGF-β induced anti-growth genes through structural blocking, and also leads to recruitment of other transcriptional repressors (see Epigenetics). By inhibiting an important checkpoint pathway for tumor suppression and growth control, overexpression or aberrant expression of EVI1 has characteristic oncogenic activity. As an additional confirmation of the role of EVI1 expression on cell cycle progression, it has been shown that high EVI1 expression is correlated with the well-known tumor suppressor and cell cycle mediator Retinoblastoma, remaining in a hyperphosphorylated state, even in the presence of TGF-β.[11] ### JNK and inhibition of apoptosis c-Jun N-terminal kinase (JNK) is a MAP kinase activated by extracellular stress signals such as gamma-radiation, ultraviolet light, Fas ligand, tumor necrosis factor α (TNF-α), and interleukin-1.[12] Phosphorylation on two separate residues, Thr183 and Tyr185, cause JNK to become activated and translocate to the nucleus to phosphorylate and activate key transcription factors for the apoptotic response.[12] Experiments co-expressing EVI1 and JNK have shown that levels of JNK-phosphorylated transcription factors (such as c-Jun) are drastically decreased in the presence of EVI1. Binding of EVI1 and JNK has been shown to occur through the first zinc finger motif on EVI1, and that this interaction does not block JNK phosphorylation and activation, but blocks JNK binding to substrate in the nucleus.[12] Subsequent in vitro assays showed that stress-induced cell death from a variety of stimuli is significantly inhibited by EVI1 and JNK binding.[12] EVI1 does not bind other MAP kinases such as p38 or ERK.[12] ## Oncogenesis and induced proliferation of HSCs Among the many other observed defects, EVI1−/− mouse embryos have been shown to have defects in both the development and proliferation of hematopoietic stem cells (HSCs). It is presumed that this is due to direct interaction with the transcription factor GATA-2, which is crucial for HSC development.[13] It has subsequently been shown many times in vitro that EVI1 upregulation can induce proliferation and differentiation of HSCs and some other cell types such as rat fibroblasts.[2] However, existing data is inconclusive regarding the absolute role of EVI1 in cell cycle progression. It appears to depend on the specific cell type, cell line and growth conditions being used as to whether EVI1 expression induces growth arrest or cell differentiation/proliferation, or whether it has any effect at all.[2] The data showing direct interaction of EVI1 with the promoters for a diverse array of genes supports the theory that this is a complex transcription factor associated with many different signalling pathways involved in development and growth. ### Angiogenesis Although the literature is limited on the subject, the well-documented effects on HSCs imply that there is a potential indirect effect of aberrant EVI1 expression on tumoral angiogenesis. HSCs secrete angiopoietin, and its receptor molecule Tie2 has been implicated in angiogenesis of tumors in both humans and mice.[14] Upregulation of Tie2 has been shown to occur under hypoxic conditions, and to increase angiogenesis when coinjected with tumor cells in mice.[14] Observations that EVI1−/− mutants have substantially downregulated Tie2 and Ang-I expression, therefore, hints at an interesting role of high EVI1 expression in tumor progression. This is likely, at least in part, a reason for the widespread hemorrhaging and minimal vascular development in EVI1 deleted embryos,[13] and has potential to indicate yet another reason for poor prognosis of EVI1 positive cancers. ## Epigenetics EVI1 has also been shown to directly interact with C-terminal-binding protein (CtBP, a known transcriptional repressor) through in vitro techniques such as yeast 2-hybrid screens and immunoprecipitation.[10] This interaction has been specifically shown to rely on amino acids 544-607 on the EVI1 protein, a stretch that contains two CtBP-binding consensus motifs.[11] This binding leads to recruitment of histone deacetylases (HDACs) as well as many other corepressor molecules leading to transcription repression via chromatin remodelling.[10] EVI1 interaction with Smad3 followed by recruitment of corepressors can inhibit transcription and de-sensitize a cell to TGF-β signaling without ever displacing Smad3 from a gene's promoter.[9] The epigenetic modification is clearly enough to make the DNA inaccessible to the transcription machinery. Although EVI1 has mainly been implicated as a transcription repressor, there is some data that has shown a possible dual role for this protein. Studies show that EVI1 also binds to known coactivators cAMP responsive element binding protein (CBP) and p300/CBP-associated factor (P/CAF).[9] These both have histone acetyltransferase activity, and lead to subsequent transcription activation. In addition, structural changes have been visualized within the nucleus of a cell, depending on the presence of corepressors or coactivators, leading researchers to believe that EVI1 has a unique response to each kind of molecule. In approximately 90% of cells, EVI1 is diffuse within the nucleus; however, when CBP and P/CAF are added, extensive nuclear speckle formation occurs.[15] The complete physiological repercussions of this complex role of EVI1 have yet to be elucidated, however, could provide insight into the wide variety of results that have been reported regarding the effect of EVI1 on in vitro cell proliferation.[2] Interaction with corepressors and coactivators appears to occur in distinct domains,[15] and there are theories that EVI1 exists in a periodical, reversible acetylated state [3] within the cell. Contrasting theories indicate that the interplay between different EVI1 binding proteins acts to stabilize interactions with different transcription factors and DNA, leading to a response of EVI1 to a diverse set of stimuli.[9] ## Chromosome instability Since it was first identified in murine myeloid leukemia as a common site of retroviral integration into the chromosome, EVI1 and its surrounding DNA have been a site of many identified chromosomal translocations and abnormalities.[16] This can lead to aberrant expression of EVI1, and, as shown in the figure below, commonly involved chromosomal breakpoints have been mapped extensively. One major cause of EVI1 activation and consequent overexpression is a clinical condition called 3q21q26 syndrome from inv(3)(q21q26) or t(3;3)(q21;q26).[3] The result is the placement of a strong enhancing region for the housekeeping gene Ribophorin 1 (RPN1)[17] next to the EVI1 coding sequence, resulting in a dramatic increase of EVI1 levels in the cell.[3] A summary of common chromosomal abnormalities involving EVI1 and its fusion genes can be found in a review by Nucifora et al..[18] The most common circumstance involves chromosomal translocations in human AML or MDS, leading to constitutive expression of EVI1 and eventually to cancer.[18] Not only are these abnormalities in the 3q26 region associated with very poor patient prognosis they are also commonly accompanied by additional karyotypic changes such as chromosome 7 monosomy, deletion of the short arm of chromosome 7, or partial deletions of chromosome 5.[19] In addition, it has been shown that development of acute myelogenous leukemia is likely due to several sequential genetic changes, and that expression of EVI1 or its chimeric counterparts ME and AME alone is not enough to completely block myeloid differentiation.[20] BCR-Abl, a fusion gene caused by t(9;22)(q34;q11)is thought to have a cooperative effect with EVI1 during the progression of AML and CML.[20] Together, these two systems disrupt tyrosine kinase signaling and hematopoietic gene transcription. Despite the extensively studied chromosomal abnormalities at the EVI1 locus, it should be noted that, in anywhere from 10-50% of identified cases, EVI1 overexpression is detectable without any chromosomal abnormalities, indicating that there are other not-yet-understood systems, likely epigenetic, leading to EVI1 promoter activation.[2] In many of these cases, it is noted that a variety of 5' transcript variants are detectable at relatively high levels. Clinical studies have shown that these variants (EVI1_1a, EVI1_1b, EVI1_1d, EVI1_3L) as well as the MDS1-EVI1 fusion transcript are all associated with poor prognosis and increased likelihood of rapid remission in cases of de novo AML.[21] ## Pharmacogenomics and cancer treatment Very little research has been done in an attempt to therapeutically target EVI1 or any of its chimeric counterparts. However, since it has become an established fact that overexpression of EVI1 derivatives is a bad prognostic indicator, it is likely that the literature will begin to examine specific targeting within the next few years. One very promising therapeutic agent for myelogenous leukemia and potentially other forms of cancer is arsenic trioxide (ATO). One study has been done showing that ATO treatment leads to specific degradation of the AML1/MDS1/EVI1 oncoprotein and induces both apoptosis and differentiation.[7] As an atypical use of traditional pharmacogenomics, this knowledge may lead to an increased ability to treat EVI1 positive leukemias that would normally have poor prognoses. If it is established that a clinical cancer case is EVI1 positive, altering the chemotherapeutic cocktail to include a specific EVI1 antagonist may aid to increase lifespan and prevent potential relapse. Arsenic is a fairly ancient human therapeutic agent,[7] however it has only recently returned to the forefront of cancer treatment. It has been observed that it not only induces apoptosis but can also inhibit the cell cycle, and has marked anti-angiogenesis effects.[22] As of 2006, Phase I and II clinical trials were being conducted to test this compound on a wide variety of cancer types, and currently (2008) a number of publications are showing positive outcomes in individual case studies, both pediatric and adult.[citation needed] ## Hormones The important and essential role of EVI1 in embryogenesis clearly indicates a close association with hormonal fluctuations in developing cells. However, to date, the presence of EVI1 in cancer has not been linked to aberrant production of any hormones or hormone receptors. It is likely that EVI1 is far enough downstream of hormonal signaling that once overproduced, it can function independently. # Future and current research ## Affect on gene therapy Areas where retroviral integration into the human genome is favored such as EVI1 have very important implications for the development of gene therapy. It was initially thought that delivery of genetic material through a non-replicating virus vector would pose no significant risk, as the likelihood of a random incorporation near a proto-oncogene was minimal. By 2008 it was realised that sites such as EVI1 are "highly over-represented" when it comes to vector insertions.[1] # Interactions EVI1 has been shown to interact with: - CREB binding protein,[23] - CTBP1,[23][24] - HDAC1,[23][25] - Mothers against decapentaplegic homolog 3,[26] and - PCAF[23] and	https://www.wikidoc.org/index.php/MECOM
14d390c2beccf50201d7f9e1027d35691b3bc2fc	wikidoc	MECP2	MECP2 MECP2 (methyl CpG binding protein 2) is a gene that encodes the protein MECP2. MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in high levels. The MECP2 protein is likely to be involved in turning off ("repressing" or "silencing") several other genes. This prevents the genes from making proteins when they are not needed. Recent work has shown that MECP2 can also activate other genes. The MECP2 gene is located on the long (q) arm of the X chromosome in band 28 ("Xq28"), from base pair 152,808,110 to base pair 152,878,611. DNA methylation is a major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2 (this protein), MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensable in stem cells. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of mental retardation in females. # Function MECP2 protein is found in all cells in the body, including the brain, acting as a transcriptional repressor and activator, depending on the context. However, the idea that MECP2 functions as an activator is relatively new and remains controversial. In the brain, it is found in high concentrations in neurons and is associated with maturation of the central nervous system (CNS) and in forming synaptic contacts. # Mechanism of action The MeCP2 protein binds to forms of DNA that have been methylated. The MeCP2 protein then interacts with other proteins to form a complex that turns off the gene. MeCP2 prefers to bind to sites on the genome with a chemical alteration made to a cytosine (C) when it occurs in a particular DNA sequence, "CpG". This is a form of DNA methylation. Many genes have CpG islands, which frequently occur near the beginning of the gene. MECP2 does not bind to these islands in most cases, as they are not methylated. The expression of a few genes may be regulated through methylation of their CpG island, and MECP2 may play a role in a subset of these. Researchers have not yet determined which genes are targeted by the MeCP2 protein, but such genes are probably important for the normal function of the central nervous system. However, the first large-scale mapping of MECP2 binding sites in neurons found that only 6% of the binding sites are in CpG islands, and that 63% of MECP2-bound promoters are actively expressed and only 6% are highly methylated, indicating that MECP2's main function is something other than silencing methylated promoters. Once bound, MeCP2 will condense the chromatin structure, form a complex with histone deacetylases (HDAC), or block transcription factors directly. More recent studies have demonstrated that MeCP2 may also function as a transcriptional activator, through recruiting the transcription factor CREB1. This was an unexpected finding which suggests that MeCP2 is a key transcriptional regulator with potentially dual roles in gene expression. In fact, the majority of genes that are regulated by MeCP2 appear to be activated rather than repressed. However, it remains controversial whether MeCP2 regulates these genes directly or whether these changes are secondary in nature. Further studies have shown MeCP2 may be able to bind directly to un-methylated DNA in some instances. MeCP2 has been implicated in regulation of imprinted genes and loci that include UBE3A and DLX5. Reduced expression of MECP2 in Mecp2+/- neural stem cells causes an increase in senescence, impairment of proliferative capacity and accumulation of unrepaired DNA damages. After treatment of Mecp2+/- cells with either of three different DNA damaging agents, the cells accumulated more DNA damages and were more prone to cell death than control cells. # Structure MECP2 is part of a family of methyl-CpG-binding domain proteins (MBD), but possesses its own unique differences which help set it apart from the group. It has two functional domains: - a methyl-cytosine-binding domain (MBD) composed of 85 amino acids; and - a transcriptional repression domain (TRD) composed of 104 amino acids The MBD domain forms a wedge and attaches to the methylated CpG sites on the DNA strands. The TRD region then reacts with SIN3A to recruit histone deacetylases (HDAC). There are also unusual, repetitive sequences found at the carboxyl terminus. This region is closely related to the fork head family, at the amino acid level. # Role in disease The role of MECP2 in disease is primarily associated with either a loss of function (under expression) of the MECP2 gene as in Rett syndrome or in a gain of function (over expression) as in MECP2 Duplication Syndrome. Many mutations have been associated with loss of expression of the MECP2 gene and have been identified in Rett syndrome patients. These mutations include changes in single DNA base pairs (SNP), insertions or deletions of DNA in the MECP2 gene, and changes that affect how the gene information is processed into a protein (RNA splicing). Mutations in the gene alter the structure of the MeCP2 protein or lead to reduced amounts of the protein. As a result, the protein is unable to bind to DNA or turn other genes on or off. Genes that are normally repressed by MeCP2 remain active when their products are not needed. Other genes that are normally activated by MeCP2 remain inactive leading to a lack of gene product. This defect probably disrupts the normal functioning of nerve cells, leading to the signs and symptoms of Rett syndrome. Rett syndrome is mainly found in girls with a prevalence of around 1 in every 10,000. Patients are born with very hard to find signs of a disorder, but after about six months to a year and half, speech and motor function capabilities start to decrease. This is followed by seizures, growth retardation and cognitive and motor impairment. The MECP2 locus is X-linked and the disease-causing alleles are dominant. Due to its prevalence in females, it has been linked to male lethality, or to a predominant transmission with the paternal X chromosome; nevertheless, in rare cases some males can also be affected by Rett Syndrome. Males with gene duplications of MECP-2 at the Xq28 locus are also at risk for recurrent infections & meningitis in infancy. Mutations in the MECP2 gene have also been identified in people with several other disorders affecting the central nervous system. For example, MECP2 mutations are associated with some cases of moderate to severe X-linked mental retardation. Mutations in the gene have also been found in males with severe brain dysfunction (neonatal encephalopathy) who live only into early childhood. In addition, several people with features of both Rett syndrome and Angelman syndrome (a condition characterized by mental retardation, problems with movement, and inappropriate laughter and excitability) have mutations in the MECP2 gene. Lastly, MECP2 mutations or changes in the gene's activity have been reported in some cases of autism (a developmental disorder that affects communication and social interaction). More recent studies reported genetic polymorphisms in the MeCP2 genes in patients with systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disease that can affect multiple organs. MeCP2 polymorphisms have been reported so far in European-derived and Asian lupus patients. The genetic loss of MECP2 has been identified as changing the properties of cells in the locus ceruleus the exclusive source of noradrenergic innervation to the cerebral cortex and hippocampus. Researchers have concluded that "Because these neurons are a pivotal source of norepinephrine throughout the brainstem and forebrain and are involved in the regulation of diverse functions disrupted in Rett syndrome, such as respiration and cognition, we hypothesize that the locus ceruleus is a critical site at which loss of MECP2 results in CNS dysfunction." # Interactive pathway map Click on genes, proteins and metabolites below to visit related articles. - ↑ The interactive pathway map can be edited at WikiPathways: "WP3584"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} # Interactions MECP2 has been shown to interact with SKI protein and Nuclear receptor co-repressor 1. In neuronal cells the MECP2 mRNA is thought to interact with miR-132, which silences the expression of the protein. This forms part of a homeostatic mechanism that could regulate MECP2 levels in the brain. # MeCP2 and Hormones MeCP2 in the developing rat brain regulates important social development in a sexually dimorphic manner. MeCP2 levels are different between males and females in the developing rat brain 24 hours after birth within the amygdala and hypothalamus, but this difference is no longer observed 10 days after birth. Specifically, males express less MeCP2 than females, and this aligns with the steroid-sensitive time period of the neonatal rat brain. Reductions in MeCP2 with Small interfering RNA (siRNA) during the first few days of life reduce male levels of juvenile social play behavior to female typical levels, but do not affect female juvenile play behavior. MeCP2 is important in organizing hormone-related behaviors and sex differences in the developing rat amygdala. MeCP2 appears to regulate arginine vasopressin (AVP) and androgen receptor (AR) production in male rats but not in females. Vasopressin is known to regulate many social behaviors including pair bonding and social recognition. While male rats typically have higher levels of vasopressin in the amygdala, MeCP2 reduction during the first 3 days of life causes a lasting reduction of vasopressin to female typical levels in this brain region that lasted through adulthood. Male rats with reduced MeCP2 levels also show a significant reduction of AR at two weeks following infusion, but this effect is gone by adulthood. # Early life stress MeCP2 monitors the response to early life stress. Early life stress is correlated with hyper-phosphorylation of the MeCP2 protein in the paraventricular nucleus of the hypothalamus. This thus causes a reduced occupancy of MeCP2 at the AVP gene's promotor region, and therefore elevated levels of AVP. Vasopressin is a primary hormone involved in the Hypothalmic-Pituitary-Adrenal Axis, the connectivity in the brain that regulates processing of and reaction to stress. Decreased functioning of the MeCP2 protein thus upregulates the neuronal stress response.	MECP2 MECP2 (methyl CpG binding protein 2) is a gene[1] that encodes the protein MECP2.[2] MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in high levels. The MECP2 protein is likely to be involved in turning off ("repressing" or "silencing") several other genes. This prevents the genes from making proteins when they are not needed. Recent work has shown that MECP2 can also activate other genes.[3] The MECP2 gene is located on the long (q) arm of the X chromosome in band 28 ("Xq28"), from base pair 152,808,110 to base pair 152,878,611. DNA methylation is a major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2 (this protein), MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensable in stem cells. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of mental retardation in females.[4] # Function MECP2 protein is found in all cells in the body, including the brain, acting as a transcriptional repressor and activator, depending on the context. However, the idea that MECP2 functions as an activator is relatively new and remains controversial.[5] In the brain, it is found in high concentrations in neurons and is associated with maturation of the central nervous system (CNS) and in forming synaptic contacts.[6] # Mechanism of action The MeCP2 protein binds to forms of DNA that have been methylated. The MeCP2 protein then interacts with other proteins to form a complex that turns off the gene. MeCP2 prefers to bind to sites on the genome with a chemical alteration made to a cytosine (C) when it occurs in a particular DNA sequence, "CpG". This is a form of DNA methylation. Many genes have CpG islands, which frequently occur near the beginning of the gene. MECP2 does not bind to these islands in most cases, as they are not methylated. The expression of a few genes may be regulated through methylation of their CpG island, and MECP2 may play a role in a subset of these. Researchers have not yet determined which genes are targeted by the MeCP2 protein, but such genes are probably important for the normal function of the central nervous system. However, the first large-scale mapping of MECP2 binding sites in neurons found that only 6% of the binding sites are in CpG islands, and that 63% of MECP2-bound promoters are actively expressed and only 6% are highly methylated, indicating that MECP2's main function is something other than silencing methylated promoters.[7] Once bound, MeCP2 will condense the chromatin structure, form a complex with histone deacetylases (HDAC), or block transcription factors directly. More recent studies have demonstrated that MeCP2 may also function as a transcriptional activator, through recruiting the transcription factor CREB1. This was an unexpected finding which suggests that MeCP2 is a key transcriptional regulator with potentially dual roles in gene expression. In fact, the majority of genes that are regulated by MeCP2 appear to be activated rather than repressed.[8] However, it remains controversial whether MeCP2 regulates these genes directly or whether these changes are secondary in nature.[5] Further studies have shown MeCP2 may be able to bind directly to un-methylated DNA in some instances.[9] MeCP2 has been implicated in regulation of imprinted genes and loci that include UBE3A and DLX5.[10] Reduced expression of MECP2 in Mecp2+/- neural stem cells causes an increase in senescence, impairment of proliferative capacity and accumulation of unrepaired DNA damages.[11] After treatment of Mecp2+/- cells with either of three different DNA damaging agents, the cells accumulated more DNA damages and were more prone to cell death than control cells.[11] # Structure MECP2 is part of a family of methyl-CpG-binding domain proteins (MBD), but possesses its own unique differences which help set it apart from the group. It has two functional domains: - a methyl-cytosine-binding domain (MBD) composed of 85 amino acids; and - a transcriptional repression domain (TRD) composed of 104 amino acids The MBD domain forms a wedge and attaches to the methylated CpG sites on the DNA strands. The TRD region then reacts with SIN3A to recruit histone deacetylases (HDAC).[12] There are also unusual, repetitive sequences found at the carboxyl terminus. This region is closely related to the fork head family, at the amino acid level.[13] # Role in disease The role of MECP2 in disease is primarily associated with either a loss of function (under expression) of the MECP2 gene as in Rett syndrome or in a gain of function (over expression) as in MECP2 Duplication Syndrome. Many mutations have been associated with loss of expression of the MECP2 gene and have been identified in Rett syndrome patients. These mutations include changes in single DNA base pairs (SNP), insertions or deletions of DNA in the MECP2 gene, and changes that affect how the gene information is processed into a protein (RNA splicing). Mutations in the gene alter the structure of the MeCP2 protein or lead to reduced amounts of the protein. As a result, the protein is unable to bind to DNA or turn other genes on or off. Genes that are normally repressed by MeCP2 remain active when their products are not needed. Other genes that are normally activated by MeCP2 remain inactive leading to a lack of gene product. This defect probably disrupts the normal functioning of nerve cells, leading to the signs and symptoms of Rett syndrome. Rett syndrome is mainly found in girls with a prevalence of around 1 in every 10,000. Patients are born with very hard to find signs of a disorder, but after about six months to a year and half, speech and motor function capabilities start to decrease. This is followed by seizures, growth retardation and cognitive and motor impairment.[14] The MECP2 locus is X-linked and the disease-causing alleles are dominant. Due to its prevalence in females, it has been linked to male lethality, or to a predominant transmission with the paternal X chromosome; nevertheless, in rare cases some males can also be affected by Rett Syndrome.[15] Males with gene duplications of MECP-2 at the Xq28 locus are also at risk for recurrent infections & meningitis in infancy. Mutations in the MECP2 gene have also been identified in people with several other disorders affecting the central nervous system. For example, MECP2 mutations are associated with some cases of moderate to severe X-linked mental retardation. Mutations in the gene have also been found in males with severe brain dysfunction (neonatal encephalopathy) who live only into early childhood. In addition, several people with features of both Rett syndrome and Angelman syndrome (a condition characterized by mental retardation, problems with movement, and inappropriate laughter and excitability) have mutations in the MECP2 gene. Lastly, MECP2 mutations or changes in the gene's activity have been reported in some cases of autism (a developmental disorder that affects communication and social interaction).[16] More recent studies reported genetic polymorphisms in the MeCP2 genes in patients with systemic lupus erythematosus (SLE).[17] SLE is a systemic autoimmune disease that can affect multiple organs. MeCP2 polymorphisms have been reported so far in European-derived and Asian lupus patients. The genetic loss of MECP2 has been identified as changing the properties of cells in the locus ceruleus the exclusive source of noradrenergic innervation to the cerebral cortex and hippocampus.[18] Researchers have concluded that "Because these neurons are a pivotal source of norepinephrine throughout the brainstem and forebrain and are involved in the regulation of diverse functions disrupted in Rett syndrome, such as respiration and cognition, we hypothesize that the locus ceruleus is a critical site at which loss of MECP2 results in CNS dysfunction."[18] # Interactive pathway map Click on genes, proteins and metabolites below to visit related articles. [§ 1] - ↑ The interactive pathway map can be edited at WikiPathways: "WP3584"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} # Interactions MECP2 has been shown to interact with SKI protein[19] and Nuclear receptor co-repressor 1.[19] In neuronal cells the MECP2 mRNA is thought to interact with miR-132, which silences the expression of the protein. This forms part of a homeostatic mechanism that could regulate MECP2 levels in the brain.[20] # MeCP2 and Hormones MeCP2 in the developing rat brain regulates important social development in a sexually dimorphic manner. MeCP2 levels are different between males and females in the developing rat brain 24 hours after birth within the amygdala and hypothalamus, but this difference is no longer observed 10 days after birth. Specifically, males express less MeCP2 than females,[21] and this aligns with the steroid-sensitive time period of the neonatal rat brain. Reductions in MeCP2 with Small interfering RNA (siRNA) during the first few days of life reduce male levels of juvenile social play behavior to female typical levels, but do not affect female juvenile play behavior.[22] MeCP2 is important in organizing hormone-related behaviors and sex differences in the developing rat amygdala. MeCP2 appears to regulate arginine vasopressin (AVP) and androgen receptor (AR) production in male rats but not in females. Vasopressin is known to regulate many social behaviors including pair bonding[23] and social recognition.[24] While male rats typically have higher levels of vasopressin in the amygdala,[25] MeCP2 reduction during the first 3 days of life causes a lasting reduction of vasopressin to female typical levels in this brain region that lasted through adulthood. Male rats with reduced MeCP2 levels also show a significant reduction of AR at two weeks following infusion, but this effect is gone by adulthood.[26] # Early life stress MeCP2 monitors the response to early life stress. Early life stress is correlated with hyper-phosphorylation of the MeCP2 protein in the paraventricular nucleus of the hypothalamus.[27] This thus causes a reduced occupancy of MeCP2 at the AVP gene's promotor region, and therefore elevated levels of AVP. Vasopressin is a primary hormone involved in the Hypothalmic-Pituitary-Adrenal Axis, the connectivity in the brain that regulates processing of and reaction to stress. Decreased functioning of the MeCP2 protein thus upregulates the neuronal stress response.	https://www.wikidoc.org/index.php/MECP2
4d217aec0a6aeb875e391071e61f28612449ba0f	wikidoc	MED12	MED12 Mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae), also known as MED12, is a human gene found on the X chromosome. # Clinical significance Mutations in MED12 are responsible for at least two different forms of X-linked dominant mental retardation, Lujan-Fryns syndrome and FG syndrome, as well as instances of prostate cancer. Mutations in MED12 are associated with uterine leiomyomas and breast fibroepithelial tumors (e.g. fibroadenoma and phyllodes tumors). # Interactions MED12 has been shown to interact with: - Calcitriol receptor, - Cyclin-dependent kinase 8 - Estrogen receptor alpha, - Gli3, G9a, PPARGC1A, - MED26, - SOX9, and - Thyroid hormone receptor alpha.	MED12 Mediator of RNA polymerase II transcription, subunit 12 homolog (S. cerevisiae), also known as MED12, is a human gene found on the X chromosome.[1] # Clinical significance Mutations in MED12 are responsible for at least two different forms of X-linked dominant mental retardation, Lujan-Fryns syndrome and FG syndrome, as well as instances of prostate cancer.[2] Mutations in MED12 are associated with uterine leiomyomas [3] and breast fibroepithelial tumors (e.g. fibroadenoma and phyllodes tumors).[4] # Interactions MED12 has been shown to interact with: - Calcitriol receptor,[5][6] - Cyclin-dependent kinase 8[5][7] - Estrogen receptor alpha,[7] - Gli3, G9a, PPARGC1A,[8] - MED26,[9] - SOX9,[10] and - Thyroid hormone receptor alpha.[5]	https://www.wikidoc.org/index.php/MED12
c64951e06efa4fac040a64cd086477921d868bdc	wikidoc	MED14	MED14 Mediator of RNA polymerase II transcription subunit 14 is an enzyme that in humans is encoded by the MED14 gene. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. This protein contains a bipartite nuclear localization signal. This gene is known to escape chromosome X-inactivation. # Interactions MED14 has been shown to interact with PPARGC1A, Estrogen receptor alpha, STAT2, Cyclin-dependent kinase 8, Glucocorticoid receptor and Hepatocyte nuclear factor 4 alpha.	MED14 Mediator of RNA polymerase II transcription subunit 14 is an enzyme that in humans is encoded by the MED14 gene.[1][2][3] The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. This protein contains a bipartite nuclear localization signal. This gene is known to escape chromosome X-inactivation.[3] # Interactions MED14 has been shown to interact with PPARGC1A,[4] Estrogen receptor alpha,[5] STAT2,[6] Cyclin-dependent kinase 8,[7][8] Glucocorticoid receptor[9] and Hepatocyte nuclear factor 4 alpha.[10][11]	https://www.wikidoc.org/index.php/MED14
b6ac7ae886e34cdd83e9fafe10271b7296ac82f7	wikidoc	MED15	MED15 Mediator of RNA polymerase II transcription subunit 15, also known as Gal11,Spt13 in yeast and PCQAP, ARC105, or TIG-1 in humans is a protein encoded by the MED15 gene. # Function MED15 is a general transcriptional cofactor of the mediator complex involved in RNA polymerase II dependent transcription, originally called Gal11 and Spt13 and found in yeast as an essential factor for Gal4 dependent transactivation by T.Fukasawa and F.Winston labs. Transcription factors Gcn4, Pho4, Msn2, Ino2, members of the Gal4 family - Gal4, Oaf1, Pdr1, and viral VP16 have been reported to interact with yeast MED15. Most of these transcription factors share the same transactivation domain, 9aaTAD, which directly interacts with KIX domain of the MED15. Furthermore, human MED15 cooperates in mediator complex (previously known as PC2, ARC, or DRIP) with transcription factors like VP16 and SREBP. Human SREBP regulates sterol responsive gene expression, and this regulatory action is conserved in the genetic model organism C. elegans, a roundworm (homologues MDT-15 and SBP-1). Also in C. elegans, MDT-15 is essential for the response to several stresses (fasting, heavy metal, toxin, and oxidative stress); at least in part the fasting response is conferred by interactions of MDT-15 with nuclear receptors, including NHR-49. # Gene The MED15 gene contains stretches of trinucleotide repeats and is located in the chromosome 22 region which is deleted in DiGeorge's syndrome. Two transcript variants encoding different isoforms have been found for this gene.	MED15 Mediator of RNA polymerase II transcription subunit 15, also known as Gal11,Spt13 in yeast and PCQAP, ARC105, or TIG-1 in humans is a protein encoded by the MED15 gene.[1] # Function MED15 is a general transcriptional cofactor of the mediator complex involved in RNA polymerase II dependent transcription, originally called Gal11 and Spt13 and found in yeast as an essential factor for Gal4 dependent transactivation by T.Fukasawa and F.Winston labs. Transcription factors Gcn4, Pho4, Msn2, Ino2, members of the Gal4 family - Gal4, Oaf1, Pdr1, and viral VP16 have been reported to interact with yeast MED15.[2] Most of these transcription factors share the same transactivation domain, 9aaTAD, which directly interacts with KIX domain of the MED15.[3] Furthermore, human MED15 cooperates in mediator complex (previously known as PC2, ARC, or DRIP) with transcription factors like VP16 and SREBP. Human SREBP regulates sterol responsive gene expression, and this regulatory action is conserved in the genetic model organism C. elegans, a roundworm (homologues MDT-15 and SBP-1). Also in C. elegans, MDT-15 is essential for the response to several stresses (fasting, heavy metal, toxin, and oxidative stress); at least in part the fasting response is conferred by interactions of MDT-15 with nuclear receptors, including NHR-49.[1] # Gene The MED15 gene contains stretches of trinucleotide repeats and is located in the chromosome 22 region which is deleted in DiGeorge's syndrome. Two transcript variants encoding different isoforms have been found for this gene.[1]	https://www.wikidoc.org/index.php/MED15
f424e554f8e254c07bf7f7332319585a7f0fcf6e	wikidoc	MED17	MED17 Mediator of RNA polymerase II transcription subunit 17 is an enzyme that in humans is encoded by the MED17 gene. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. # Interactions MED17 has been shown to interact with PPARGC1A, Cyclin-dependent kinase 8 and BRCA1.	MED17 Mediator of RNA polymerase II transcription subunit 17 is an enzyme that in humans is encoded by the MED17 gene.[1][2][3] The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors.[3] # Interactions MED17 has been shown to interact with PPARGC1A,[4] Cyclin-dependent kinase 8[2][5] and BRCA1.[6][7][8]	https://www.wikidoc.org/index.php/MED17
22198244d401e7edbc8c787022cf88afba17100a	wikidoc	MED22	MED22 Mediator of RNA polymerase II transcription subunit 22 is an enzyme that in humans is encoded by the MED22 gene. # Function This gene is located in the surfeit gene cluster, a group of very tightly linked housekeeping genes that do not share sequence similarity. The gene is oriented in a head-to-head fashion with RPL7A (SURF3) and the two genes share a bidirectional promoter. The encoded proteins are localized to the cytoplasm. Two alternative transcript variants encoding different isoforms have been identified for this gene. # Interactions MED22 has been shown to interact with MED30. # Model organisms Model organisms have been used in the study of MED22 function. A conditional knockout mouse line called Med22tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping	MED22 Mediator of RNA polymerase II transcription subunit 22 is an enzyme that in humans is encoded by the MED22 gene.[1][2][3] # Function This gene is located in the surfeit gene cluster, a group of very tightly linked housekeeping genes that do not share sequence similarity. The gene is oriented in a head-to-head fashion with RPL7A (SURF3) and the two genes share a bidirectional promoter. The encoded proteins are localized to the cytoplasm. Two alternative transcript variants encoding different isoforms have been identified for this gene.[3] # Interactions MED22 has been shown to interact with MED30.[4] # Model organisms Model organisms have been used in the study of MED22 function. A conditional knockout mouse line called Med22tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[5] Male and female animals underwent a standardized phenotypic screen[6] to determine the effects of deletion.[7][8][9][10] Additional screens performed: - In-depth immunological phenotyping[11]	https://www.wikidoc.org/index.php/MED22
61428d968493ec50494a0ce506d21364704d618f	wikidoc	MED24	MED24 Mediator of RNA polymerase II transcription subunit 24 is an enzyme that in humans is encoded by the MED24 gene. # Function This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. Multiple transcript variants encoding different isoforms have been found for this gene. # Interactions MED24 has been shown to interact with Estrogen receptor alpha, Cyclin-dependent kinase 8, Calcitriol receptor and BRCA1.	MED24 Mediator of RNA polymerase II transcription subunit 24 is an enzyme that in humans is encoded by the MED24 gene.[1] # Function This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. Multiple transcript variants encoding different isoforms have been found for this gene.[1] # Interactions MED24 has been shown to interact with Estrogen receptor alpha,[2][3] Cyclin-dependent kinase 8,[3][4] Calcitriol receptor[2][4] and BRCA1.[5]	https://www.wikidoc.org/index.php/MED24
1134d0159a4f52a2c5fc6810a8279d1be3aa187e	wikidoc	MED26	MED26 Mediator of RNA polymerase II transcription subunit 26 is an enzyme that in humans is encoded by the MED26 gene. It forms part of the Mediator complex. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. # Activity MED26 is a transcription elongation factor that increases the overall transcription rate of RNA polymerase II by reactivating transcription elongation complexes that have arrested transcription. It does this through recruiting ELL/EAF- and P-TEFb- containing complexes to promoters via a direct interaction with the N-terminal domain (NTD). The MED26 NTD also binds TFIID, and TFIID and elongation complexes interact with MED26 through overlapping binding sites. MED26 NTD may function as a molecular switch contributing to the transition of Pol II into productive elongation. The three structural domains of TFIIS are conserved from yeast to human. The 80 or so N-terminal residues form a protein interaction domain containing a conserved motif, which has been called the LW motif because of the invariant leucine and tryptophan residues it contains. Although the N-terminal domain is not needed for transcriptional activity, a similar sequence has been identified in other transcription factors and proteins that are predominantly nuclear localized,: - MED26 (also known as CRSP70 and ARC70), a subunit of the Mediator complex, which is required for the activity of the enhancer-binding protein Sp1. - Elongin A, a subunit of a transcription elongation factor previously known as SIII. It increases the rate of transcription by suppressing transient pausing of the elongation complex. - PPP1R10, a nuclear regulatory subunit of protein phosphatase 1 that was previously known as p99, FB19 or PNUTS. - PIBP, a small hypothetical protein that could be a phosphoinositide binding protein. - IWS1, which is thought to function in both transcription initiation and elongation. The TFIIS N-terminal domain is a compact four-helix bundle. The hydrophobic core residues of helices 2, 3, and 4 are well conserved among TFIIS domains, although helix 1 is less conserved. # Interactions MED26 has been shown to interact with MED8, Cyclin-dependent kinase 8, POLR2A, MED12 and MED28. It also acts synergistically to mediate the interaction between REST (a Kruppel-type zinc finger transcription factor that binds to a 21-bp RE1 silencing element present in over 900 human genes) and Mediator.	MED26 Mediator of RNA polymerase II transcription subunit 26 is an enzyme that in humans is encoded by the MED26 gene.[1][2] It forms part of the Mediator complex. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors.[2] # Activity MED26 is a transcription elongation factor that increases the overall transcription rate of RNA polymerase II by reactivating transcription elongation complexes that have arrested transcription. It does this through recruiting ELL/EAF- and P-TEFb- containing complexes to promoters via a direct interaction with the N-terminal domain (NTD). The MED26 NTD also binds TFIID, and TFIID and elongation complexes interact with MED26 through overlapping binding sites. [3] MED26 NTD may function as a molecular switch contributing to the transition of Pol II into productive elongation. The three structural domains of TFIIS are conserved from yeast to human. The 80 or so N-terminal residues form a protein interaction domain containing a conserved motif, which has been called the LW motif because of the invariant leucine and tryptophan residues it contains. Although the N-terminal domain is not needed for transcriptional activity, a similar sequence has been identified in other transcription factors and proteins that are predominantly nuclear localized,:[4][5] - MED26 (also known as CRSP70 and ARC70), a subunit of the Mediator complex, which is required for the activity of the enhancer-binding protein Sp1. - Elongin A, a subunit of a transcription elongation factor previously known as SIII. It increases the rate of transcription by suppressing transient pausing of the elongation complex. - PPP1R10, a nuclear regulatory subunit of protein phosphatase 1 that was previously known as p99, FB19 or PNUTS. - PIBP, a small hypothetical protein that could be a phosphoinositide binding protein. - IWS1, which is thought to function in both transcription initiation and elongation. The TFIIS N-terminal domain is a compact four-helix bundle. The hydrophobic core residues of helices 2, 3, and 4 are well conserved among TFIIS domains, although helix 1 is less conserved.[5] # Interactions MED26 has been shown to interact with MED8,[6] Cyclin-dependent kinase 8,[6] POLR2A,[6] MED12[6] and MED28.[6] It also acts synergistically to mediate the interaction between REST (a Kruppel-type zinc finger transcription factor that binds to a 21-bp RE1 silencing element present in over 900 human genes) and Mediator.[7]	https://www.wikidoc.org/index.php/MED26
41939584158077ac32e40159bb41d0661e1564c2	wikidoc	MED27	MED27 Mediator of RNA polymerase II transcription subunit 27 is an enzyme that in humans is encoded by the MED27 gene. It forms part of the Mediator complex. The ubiquitous expression of Med27 mRNA suggests a universal requirement for Med27 in transcriptional initiation. Loss of Crsp34/Med27 decreases amacrine cell number, but increases the number of rod photoreceptor cells. The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors.	MED27 Mediator of RNA polymerase II transcription subunit 27 is an enzyme that in humans is encoded by the MED27 gene.[1][2] It forms part of the Mediator complex. The ubiquitous expression of Med27 mRNA suggests a universal requirement for Med27 in transcriptional initiation. Loss of Crsp34/Med27 decreases amacrine cell number, but increases the number of rod photoreceptor cells.[3] The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors.[2]	https://www.wikidoc.org/index.php/MED27
c1a3a4d33b66079bb311419876bd18fb14bfecbf	wikidoc	MED28	MED28 Mediator of RNA polymerase II transcription subunit 28 is an enzyme that in humans is encoded by the MED28 gene. It forms part of the Mediator complex. # Function Subunit Med28 of the Mediator may function as a scaffolding protein within Mediator by maintaining the stability of a submodule within the head module, and components of this submodule act together in a gene-regulatory programme to suppress smooth muscle cell differentiation. Thus, mammalian Mediator subunit Med28 functions as a repressor of smooth muscle-cell differentiation, which could have implications for disorders associated with abnormalities in smooth muscle cell growth and differentiation, including atherosclerosis, asthma, hypertension, and smooth muscle tumours. # Interactions MED28 has been shown to interact with Merlin, Grb2 and MED26.	MED28 Mediator of RNA polymerase II transcription subunit 28 is an enzyme that in humans is encoded by the MED28 gene.[1][2][3] It forms part of the Mediator complex. # Function Subunit Med28 of the Mediator may function as a scaffolding protein within Mediator by maintaining the stability of a submodule within the head module, and components of this submodule act together in a gene-regulatory programme to suppress smooth muscle cell differentiation. Thus, mammalian Mediator subunit Med28 functions as a repressor of smooth muscle-cell differentiation, which could have implications for disorders associated with abnormalities in smooth muscle cell growth and differentiation, including atherosclerosis, asthma, hypertension, and smooth muscle tumours.[4] # Interactions MED28 has been shown to interact with Merlin,[2] Grb2[2] and MED26.[5]	https://www.wikidoc.org/index.php/MED28
7a0c1b17761c5063744a35d96206d8dfa92f1857	wikidoc	MEF2B	MEF2B Myocyte enhancer binding factor 2B (MEF2B) is a transcription factor part of the MEF2 gene family including MEF2A, MEF2C, and MEF2D. However, MEF2B is distant from the other three branches of MEF2 genes as it lacks the protein-coding Holliday junction recognition protein C-terminal (HJURP_C) region in vertebrates. # Functions The MEF2 gene family is expressed in muscle-specific gene activation and maintenance during development. MEF2B mRNA is present in skeletal, smooth, brain and heart muscles. MEF2B is directly involved in smooth muscle myosin heavy chain (SMHC) gene regulation. Overexpression of MEF2B will activate the SMHC promoter in smooth muscle when it is bound to the A/T-rich element of the promoter. # Interactions MEF2B has been shown to interact with CABIN1. # Clinical relevance Recurrent mutations in this gene have been associated with cases of diffuse large B-cell lymphoma. In its mutated form, MEF2B can lead to deregulation of the proto-oncogene BCL6 expression in diffuse large B-cell lymphomas (DLBCL). Mutations of MEF2B enhance its transcriptional activity due to either a disruption with its corepressor CABIN1 or causing the gene to become insensitive to inhibitory signaling events.	MEF2B Myocyte enhancer binding factor 2B (MEF2B) is a transcription factor part of the MEF2 gene family including MEF2A, MEF2C, and MEF2D.[1][2] However, MEF2B is distant from the other three branches of MEF2 genes as it lacks the protein-coding Holliday junction recognition protein C-terminal (HJURP_C) region in vertebrates.[3] # Functions The MEF2 gene family is expressed in muscle-specific gene activation and maintenance during development.[3][4] MEF2B mRNA is present in skeletal, smooth, brain and heart muscles.[5] MEF2B is directly involved in smooth muscle myosin heavy chain (SMHC) gene regulation. Overexpression of MEF2B will activate the SMHC promoter in smooth muscle when it is bound to the A/T-rich element of the promoter.[5] # Interactions MEF2B has been shown to interact with CABIN1.[6][7] # Clinical relevance Recurrent mutations in this gene have been associated with cases of diffuse large B-cell lymphoma.[8] In its mutated form, MEF2B can lead to deregulation of the proto-oncogene BCL6 expression in diffuse large B-cell lymphomas (DLBCL).[9] Mutations of MEF2B enhance its transcriptional activity due to either a disruption with its corepressor CABIN1 or causing the gene to become insensitive to inhibitory signaling events.[9]	https://www.wikidoc.org/index.php/MEF2B
507dde35e66c9989f0594a2434ddaf3767aa8899	wikidoc	MEF2C	MEF2C Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the MEF2C gene. MEF2C is a transcription factor in the Mef2 family. # Genomics The gene is located at 5q14.3 on the minus (Crick) strand and is 200,723 bases in length. The encoded protein has 473 amino acids with a predicted molecular weight of 51.221 kiloDaltons. Three isoforms have been identified. Several post translational modifications have been identified including phosphorylation on serine-59 and serine-396, sumoylation on lysine-391, acetylation on lysine-4 and proteolytic cleavage. # Interactions MEF2C has been shown to interact with: - EP300, - HDAC4, HDAC7, HDAC9, - MAPK7, - SOX18 - SP1, and - TEAD1. # Biological significance This gene is involved in cardiac morphogenesis and myogenesis and vascular development. It may also be involved in neurogenesis and in the development of cortical architecture. Mice without a functional copy of the Mef2c gene die before birth and have abnormalities in the heart and vascular system. It is one of the targets of an oncomiR, MIRN21. In humans mutations of this gene result in autosomal dominant mental retardation 20 (MRD20), characterised by severe psychomotor impairment, periodic tremor and an abnormal motor pattern with mirror movement of the upper limbs observed during infancy, hypotonia, abnormal EEG, epilepsy, absence of speech, autistic behavior, bruxism, and mild dysmorphic features, mild thinning of the corpus callosum and delay of white matter myelination in the occipital lobes MEF2C-binding site is associated with minor allele of SNP rs630923, associated with the risk of multiple sclerosis, and responsible for reduced CXCR5 gene promoter activity in B-cells during activation, that could lead to decreased autoimmune response	MEF2C Myocyte-specific enhancer factor 2C also known as MADS box transcription enhancer factor 2, polypeptide C is a protein that in humans is encoded by the MEF2C gene.[1][2] MEF2C is a transcription factor in the Mef2 family.[3][4] # Genomics The gene is located at 5q14.3 on the minus (Crick) strand and is 200,723 bases in length. The encoded protein has 473 amino acids with a predicted molecular weight of 51.221 kiloDaltons. Three isoforms have been identified. Several post translational modifications have been identified including phosphorylation on serine-59 and serine-396, sumoylation on lysine-391, acetylation on lysine-4 and proteolytic cleavage. # Interactions MEF2C has been shown to interact with: - EP300,[5] - HDAC4, HDAC7, HDAC9,[6][7] - MAPK7,[8] - SOX18[9] - SP1,[10] and - TEAD1.[11] # Biological significance This gene is involved in cardiac morphogenesis and myogenesis and vascular development. It may also be involved in neurogenesis and in the development of cortical architecture. Mice without a functional copy of the Mef2c gene die before birth and have abnormalities in the heart and vascular system.[12] It is one of the targets of an oncomiR, MIRN21. In humans mutations of this gene result in autosomal dominant mental retardation 20 (MRD20),[13] characterised by severe psychomotor impairment, periodic tremor and an abnormal motor pattern with mirror movement of the upper limbs observed during infancy, hypotonia, abnormal EEG, epilepsy, absence of speech, autistic behavior, bruxism, and mild dysmorphic features, mild thinning of the corpus callosum and delay of white matter myelination in the occipital lobes[14] MEF2C-binding site is associated with minor allele of SNP rs630923, associated with the risk of multiple sclerosis, and responsible for reduced CXCR5 gene promoter activity in B-cells during activation, that could lead to decreased autoimmune response [15]	https://www.wikidoc.org/index.php/MEF2C
e6d6bb0d6ea0e9dab8c2655bda53a2463b3e620d	wikidoc	MESP2	MESP2 Mesoderm posterior protein 2 (MESP2), also known as class C basic helix-loop-helix protein 6 (bHLHc6), is a protein that in humans is encoded by the MESP2 gene. # Function This gene encodes a member of the bHLH family of transcription factors and plays a key role in defining the rostrocaudal patterning of somites via interactions with multiple Notch signaling pathways. This gene is expressed in the anterior presomitic mesoderm and is downregulated immediately after the formation of segmented somites. This gene also plays a role in the formation of epithelial somitic mesoderm and cardiac mesoderm. In zebrafish, the homolog mesp-b is critical for dermomyotome development. # Clinical significance Mutations in the MESP2 gene cause autosomal recessive Spondylocostal dysostosis type 2.	MESP2 Mesoderm posterior protein 2 (MESP2), also known as class C basic helix-loop-helix protein 6 (bHLHc6), is a protein that in humans is encoded by the MESP2 gene.[1] # Function This gene encodes a member of the bHLH family of transcription factors and plays a key role in defining the rostrocaudal patterning of somites via interactions with multiple Notch signaling pathways. This gene is expressed in the anterior presomitic mesoderm and is downregulated immediately after the formation of segmented somites. This gene also plays a role in the formation of epithelial somitic mesoderm and cardiac mesoderm.[1] In zebrafish, the homolog mesp-b is critical for dermomyotome development.[2] # Clinical significance Mutations in the MESP2 gene cause autosomal recessive Spondylocostal dysostosis type 2.[3]	https://www.wikidoc.org/index.php/MESP2
f4a92c7b149d7c7fb6816a06664cbabaaf73cbc0	wikidoc	MEX3D	MEX3D Mex-3 homolog D (C. elegans), also known as MEX3D, is a protein that in humans is encoded by the MEX3D gene. # Function MEX3D is an RNA binding protein that interacts with AU-rich elements of Bcl-2. Upon binding, MEX3D has a negative regulatory action on Bcl-2 expression at the posttranscriptional level. # Structure MEX3 proteins contain two N-terminal heterogeneous nuclear ribonucleoprotein K homology motifs ( KH domain ) and a RING domain at the C-terminus.	MEX3D Mex-3 homolog D (C. elegans), also known as MEX3D, is a protein that in humans is encoded by the MEX3D gene.[1][2] # Function MEX3D is an RNA binding protein that interacts with AU-rich elements of Bcl-2. Upon binding, MEX3D has a negative regulatory action on Bcl-2 expression at the posttranscriptional level.[2] # Structure MEX3 proteins contain two N-terminal heterogeneous nuclear ribonucleoprotein K homology motifs ( KH domain ) and a RING domain at the C-terminus.[2]	https://www.wikidoc.org/index.php/MEX3D
c23b4202118e249ffebcb7b5f6d36cf1234ec745	wikidoc	MFGE8	MFGE8 Milk fat globule-EGF factor 8 protein (Mfge8), also known as lactadherin, is a protein which in humans is encoded by the MFGE8 gene. # Species distribution Mfge8 is secreted protein found in vertebrates, including mammals as well as birds. # Function MFGE8 may function as a cell adhesion protein to connect smooth muscle to elastic fiber in arteries. An amyloid fragment of MFGE8 known as medin accumulates in the aorta with aging. MFGE8 in the vasculature of adults can induce recovery from ischemia by facilitating angiogenesis. It has been suggested that antagonizing MFGE8-induced angiogenesis could be a way of fighting cancer. MFGE8 contains a phosphatidylserine (PS) binding domain, as well as an Arginine-Glycine-Aspartic acid motif, which enables the binding to integrins. MFGE8 binds PS, which is exposed on the surface of apoptotic cells. Opsonization of the apoptotic cells and binding to integrins on the surface of phagocytic cells, mediates the engulfment of the dead cell.	MFGE8 Milk fat globule-EGF factor 8 protein (Mfge8), also known as lactadherin, is a protein which in humans is encoded by the MFGE8 gene.[1][2] # Species distribution Mfge8 is secreted protein found in vertebrates, including mammals as well as birds. # Function MFGE8 may function as a cell adhesion protein to connect smooth muscle to elastic fiber in arteries.[3] An amyloid fragment of MFGE8 known as medin accumulates in the aorta with aging.[4] MFGE8 in the vasculature of adults can induce recovery from ischemia by facilitating angiogenesis.[5] It has been suggested that antagonizing MFGE8-induced angiogenesis could be a way of fighting cancer.[6] MFGE8 contains a phosphatidylserine (PS) binding domain, as well as an Arginine-Glycine-Aspartic acid motif, which enables the binding to integrins. MFGE8 binds PS, which is exposed on the surface of apoptotic cells. Opsonization of the apoptotic cells and binding to integrins on the surface of phagocytic cells, mediates the engulfment of the dead cell.	https://www.wikidoc.org/index.php/MFGE8
2d1cfecccb305421e268d29553f24d6024242a02	wikidoc	MFSD2	MFSD2 Major facilitator superfamily domain-containing protein 2 (MFSD2 or MFSD2A) -- also known as sodium-dependent lysophosphatidylcholine symporter 1 -- is a protein that in humans is encoded by the MFSD2A gene. MFSD2A is a membrane transport protein that is expressed in the endothelium of the blood–brain barrier (BBB) and has an essential role in BBB formation and function. Genetic ablation of MFSD2A results in leaky BBB and increases central nervous system endothelial cell vesicular transcytosis without otherwise affecting tight junctions. MFSD2A is an atypical SLC, thus a predicted SLC transporter. It clusters phylogenetically to AMTF8. In addition to transport of other lysophosphatidylcholines across the BBB, MSFD2A is the primary mechanism for docosahexaenoic acid (DHA, an omega-3 fatty acid) uptake and transport into the brain. It may also be responsible for uptake and transport of tunicamycin. Complete loss of MFSD2A in human leads to a recessive lethal microcephaly syndrome consisting of enlarged lateral ventricles and underdevelopment of the cerebellum and brainstem. This is presumably due to loss of uptake of essential polyunsaturated fatty acids by the brain endothelial cells, which utilize MFSD2A as a transporter for these fats. Serum from patients showed elevated levels of essential polyunsaturated fatty acids, presumably due to the inability of vascular cells to uptake these lipids in the absence of protein function. Without the ability to uptake these fats into endothelial cells, there is breakdown of the blood-brain-barrier and loss of brain volume. This was demonstrated in a zebrafish model by intracardiac injection of dye, which was found to extravasate into the brain parenchyma following inactivating one of the paralogues of MSFD2A known as mfsd2aa.	MFSD2 Major facilitator superfamily domain-containing protein 2 (MFSD2 or MFSD2A) -- also known as sodium-dependent lysophosphatidylcholine symporter 1 -- is a protein that in humans is encoded by the MFSD2A gene.[1] MFSD2A is a membrane transport protein that is expressed in the endothelium of the blood–brain barrier (BBB) and has an essential role in BBB formation and function.[1] Genetic ablation of MFSD2A results in leaky BBB and increases central nervous system endothelial cell vesicular transcytosis without otherwise affecting tight junctions.[2] MFSD2A is an atypical SLC,[3] thus a predicted SLC transporter.[4] It clusters phylogenetically to AMTF8.[4] In addition to transport of other lysophosphatidylcholines across the BBB, MSFD2A is the primary mechanism for docosahexaenoic acid (DHA, an omega-3 fatty acid) uptake and transport into the brain.[1] It may also be responsible for uptake and transport of tunicamycin.[5][6][7] Complete loss of MFSD2A in human leads to a recessive lethal microcephaly syndrome consisting of enlarged lateral ventricles and underdevelopment of the cerebellum and brainstem. This is presumably due to loss of uptake of essential polyunsaturated fatty acids by the brain endothelial cells, which utilize MFSD2A as a transporter for these fats. Serum from patients showed elevated levels of essential polyunsaturated fatty acids, presumably due to the inability of vascular cells to uptake these lipids in the absence of protein function. Without the ability to uptake these fats into endothelial cells, there is breakdown of the blood-brain-barrier and loss of brain volume. This was demonstrated in a zebrafish model by intracardiac injection of dye, which was found to extravasate into the brain parenchyma following inactivating one of the paralogues of MSFD2A known as mfsd2aa.[8]	https://www.wikidoc.org/index.php/MFSD2
c38205cb259bcbbc9710d3a0de64f458eae31706	wikidoc	MFSD8	MFSD8 Major facilitator superfamily domain containing 8 also known as MFSD8 is a protein that in humans is encoded by the MFSD8 gene. MFSD8 is an atypical SLC, thus a predicted SLC transporter. It clusters phylogenetically to the Atypical MFS Transporter family 2 (AMTF2). # Function MFSD8 is a ubiquitous integral membrane protein that contains a transporter domain and a major facilitator superfamily (MFS) domain. Other members of the major facilitator superfamily transport small solutes through chemiosmotic ion gradients. The substrate transported by this protein is unknown. The protein likely localizes to lysosomal membranes. # Clinical significance Mutations in the MFSD8 gene have been associated with neuronal ceroid lipofuscinosis.	MFSD8 Major facilitator superfamily domain containing 8 also known as MFSD8 is a protein that in humans is encoded by the MFSD8 gene.[1] MFSD8 is an atypical SLC,[2][3] thus a predicted SLC transporter. It clusters phylogenetically to the Atypical MFS Transporter family 2 (AMTF2).[3] # Function MFSD8 is a ubiquitous integral membrane protein that contains a transporter domain and a major facilitator superfamily (MFS) domain. Other members of the major facilitator superfamily transport small solutes through chemiosmotic ion gradients. The substrate transported by this protein is unknown. The protein likely localizes to lysosomal membranes.[4] # Clinical significance Mutations in the MFSD8 gene have been associated with neuronal ceroid lipofuscinosis.[5]	https://www.wikidoc.org/index.php/MFSD8
4dcb6c431c7cf02ad6cde38d4029ffefc734c618	wikidoc	MGST3	MGST3 Microsomal glutathione S-transferase 3 is an enzyme that in humans is encoded by the MGST3 gene. The MAPEG (Membrane-Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, several of which are involved the production of leukotrienes and prostaglandin E, important mediators of inflammation. This gene encodes an enzyme that catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4. This enzyme also demonstrates glutathione-dependent peroxidase activity towards lipid hydroperoxides. # Model organisms Model organisms have been used in the study of MGST3 function. A conditional knockout mouse line, called Mgst3tm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice but no significant abnormalities were observed.	MGST3 Microsomal glutathione S-transferase 3 is an enzyme that in humans is encoded by the MGST3 gene.[1][2] The MAPEG (Membrane-Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, several of which are involved the production of leukotrienes and prostaglandin E, important mediators of inflammation. This gene encodes an enzyme that catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4. This enzyme also demonstrates glutathione-dependent peroxidase activity towards lipid hydroperoxides.[2] # Model organisms Model organisms have been used in the study of MGST3 function. A conditional knockout mouse line, called Mgst3tm1a(KOMP)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[9][10][11] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty five tests were carried out on mutant mice but no significant abnormalities were observed.[5]	https://www.wikidoc.org/index.php/MGST3
bed60acf26f9b916e6ace12dcefe36eff9b0deca	wikidoc	MIPEP	MIPEP Mitochondrial intermediate peptidase is an enzyme that in humans is encoded by the MIPEP gene. This protein is a critical component of human mitochondrial protein import machinery involved in the maturing process of nuclear coded mitochondrial proteins that with a mitochondrial translocation peptide, especially those OXPHOS-related proteins. # Structure ## Gene The gene MIPEP encodes one metalloprotease that hydrolyzes peptide fragment of eight amino acids in lengths to process mitochondria-targeted proteins. a. The human gene MIPEP has 21 Exons and locates at chromosome band13q12. Evidences showed that the human gene MIPEP is highly expressed in the heart, skeletal muscle, and pancreas, three organ systems that are frequently reported with OXPHOS disorders. ## Protein The human protein Mitochondrial intermediate peptidase is 80.6 kDa in size and composed of 713 amino acids. It contains a mitonchondria targeting peptide (Amino acid 1-35 of the peptide sequence). The mature protein has a theoretical pI of 6.03. # Function Working in concert with general mitochondrial processing peptidase (MPP), MIPEP plays critical role in the maturation of a specific class of nuclear-encoded precursor proteins characterized by the motif, XRX(f)(F/L/I)XX(T/S/G)XXXX(f). Initially, peptidase MPP cleaves the precursors at positions two peptide bonds from the R residue, leaving a typical octapeptide at the protein N- terminus; subsequently, MIP cleaves the octapeptide, completing the final maturation of processed protein. A recent study showed that mitochondrial intermediate peptidase can degrade the transmembrane receptor Notch at its S5 site and assist Notch protein maturation. # Clinical significance Since MIPEP plays critical roles in mitochondrial protein maturation, it has been linked to many diseases associated with mitochondrial dysfunctions. In a GWAS study of Chinese population, a significant association between high myopia and a variant at chromosome band region 13q12.12. Gene MIPEP locates in the same locus and appears to expressed in the retina and retinal pigment epithelium (RPE) and are more likely associated with high myopia. Biallelic pathogenic variants in MIPEP cause the autosomal recessive disorder Eldomery-Sutton syndrome. This typically presents in infancy or early childhood with hypotonia (low muscle tone) and a rare type of cardiomyopathy, called left ventricular non-compaction. Cataracts may also be seen. In the limited number of cases reported to date, the cardiomyopathy is progressive and results in death in the first few years of life. # Eldomery-Sutton syndrome Description of the human clinical phenotype of an autosomal recessive neuromuscular disorder caused by deficiency of the mitochondrial intermediate presequence protease (MIP), encoded by the gene MIPEP, was first reported by lead author Mohammad Eldomery and senior corresponding author V. Reid Sutton in 2016 in the journal Genome Medicine. The index subject was diagnosed with left ventricular non-compaction cardiomyopathy (LVNC) and Wolf-Parkinson-White syndrome at 5 1/2 months of age. In an attempt to identify the etiology of this cardiac phenotype, a series of tests were performed, including clinical whole exome sequencing. Because the clinical diagnostic laboratory did not identify pathogenic variants in known disease-associated genes, re-analysis of the exome data was performed by Dr. Mohammad Eldomery as part of the Baylor-Johns Hopkins Center for Mendelian Genomics. Biallelic variants were identified in the MIPEP gene, which was known in yeast and other organisms to be important in mitochondrial protein processing. Because LVNC is seen in other mitochondrial disorders, this was considered the best candidate gene. After interrogating the Baylor Genetic Laboratory clinical database and submitting the MIPEP gene to GeneMatcher, four other affected individuals from three families were identified with biallelic variants in MIPEP. In all cases, the phenotype is LVNC with severe hypotonia and developmental delay. All of the affected individuals, with the exception of the index case, died before 2 years of age from cardiac failure. Seizures and cataracts were also noted in some of the affected individuals. The MIPEP variants included missense variants, stop variants as well as a 1.4 Megabase deletion involving the MIPEP gene. Confirmation of the pathogenicity of these variants in MIPEP was performed in a yeast model system by Nora Vögtle and Chris Meisinger at the University of Freiburg, Germany.	MIPEP Mitochondrial intermediate peptidase is an enzyme that in humans is encoded by the MIPEP gene.[1] This protein is a critical component of human mitochondrial protein import machinery involved in the maturing process of nuclear coded mitochondrial proteins that with a mitochondrial translocation peptide, especially those OXPHOS-related proteins.[2] # Structure ## Gene The gene MIPEP encodes one metalloprotease that hydrolyzes peptide fragment of eight amino acids in lengths to process mitochondria-targeted proteins. a.[1] The human gene MIPEP has 21 Exons and locates at chromosome band13q12. Evidences showed that the human gene MIPEP is highly expressed in the heart, skeletal muscle, and pancreas, three organ systems that are frequently reported with OXPHOS disorders. ## Protein The human protein Mitochondrial intermediate peptidase is 80.6 kDa in size and composed of 713 amino acids. It contains a mitonchondria targeting peptide (Amino acid 1-35 of the peptide sequence). The mature protein has a theoretical pI of 6.03.[3] # Function Working in concert with general mitochondrial processing peptidase (MPP), MIPEP plays critical role in the maturation of a specific class of nuclear-encoded precursor proteins characterized by the motif, XRX(f)(F/L/I)XX(T/S/G)XXXX(f).[4] Initially, peptidase MPP cleaves the precursors at positions two peptide bonds from the R residue, leaving a typical octapeptide at the protein N- terminus; subsequently, MIP cleaves the octapeptide, completing the final maturation of processed protein.[5][6] A recent study showed that mitochondrial intermediate peptidase can degrade the transmembrane receptor Notch at its S5 site and assist Notch protein maturation.[7] # Clinical significance Since MIPEP plays critical roles in mitochondrial protein maturation, it has been linked to many diseases associated with mitochondrial dysfunctions. In a GWAS study of Chinese population, a significant association between high myopia and a variant at chromosome band region 13q12.12. Gene MIPEP locates in the same locus and appears to expressed in the retina and retinal pigment epithelium (RPE) and are more likely associated with high myopia.[8] Biallelic pathogenic variants in MIPEP cause the autosomal recessive disorder Eldomery-Sutton syndrome. This typically presents in infancy or early childhood with hypotonia (low muscle tone) and a rare type of cardiomyopathy, called left ventricular non-compaction. Cataracts may also be seen. In the limited number of cases reported to date, the cardiomyopathy is progressive and results in death in the first few years of life.[9] # Eldomery-Sutton syndrome Description of the human clinical phenotype of an autosomal recessive neuromuscular disorder caused by deficiency of the mitochondrial intermediate presequence protease (MIP), encoded by the gene MIPEP, was first reported by lead author Mohammad Eldomery and senior corresponding author V. Reid Sutton in 2016 in the journal Genome Medicine. The index subject was diagnosed with left ventricular non-compaction cardiomyopathy (LVNC) and Wolf-Parkinson-White syndrome at 5 1/2 months of age. In an attempt to identify the etiology of this cardiac phenotype, a series of tests were performed, including clinical whole exome sequencing. Because the clinical diagnostic laboratory did not identify pathogenic variants in known disease-associated genes, re-analysis of the exome data was performed by Dr. Mohammad Eldomery as part of the Baylor-Johns Hopkins Center for Mendelian Genomics. Biallelic variants were identified in the MIPEP gene, which was known in yeast and other organisms to be important in mitochondrial protein processing. Because LVNC is seen in other mitochondrial disorders, this was considered the best candidate gene. After interrogating the Baylor Genetic Laboratory clinical database and submitting the MIPEP gene to GeneMatcher, four other affected individuals from three families were identified with biallelic variants in MIPEP. In all cases, the phenotype is LVNC with severe hypotonia and developmental delay. All of the affected individuals, with the exception of the index case, died before 2 years of age from cardiac failure. Seizures and cataracts were also noted in some of the affected individuals. The MIPEP variants included missense variants, stop variants as well as a 1.4 Megabase deletion involving the MIPEP gene. Confirmation of the pathogenicity of these variants in MIPEP was performed in a yeast model system by Nora Vögtle and Chris Meisinger at the University of Freiburg, Germany.[9]	https://www.wikidoc.org/index.php/MIPEP
b693ec0e8774b5743f24f88d5f0aada6f474322b	wikidoc	MLANA	MLANA Protein melan-A also known as melanoma antigen recognized by T cells 1 or MART-1 is a protein that in humans is encoded by the MLANA o "MALENA" gene. A fragment of the protein, usually consisting of the nine amino acids 27 to 35, is bound by MHC class I complexes which present it to T cells of the immune system. These complexes can be found on the surface of melanoma cells. Decameric peptides (26-35) are being investigated as cancer vaccines. # Discovery and nomenclature The names MART-1 and melan-A were coined by two groups of researchers who independently sequenced the gene for this antigen in 1994. Both names are currently in common use. Kawakami et al. at the National Cancer Institute coined the term MART-1, which stands for "melanoma antigen recognized by T-cells." Coulie et al. of Belgium called the gene melan-A, presumably an abbreviation for "melanocyte antigen." # Clinical significance MART-1/melan-A is a protein antigen that is found on the surface of melanocytes. Antibodies against the antigen are used in the medical specialty of anatomic pathology in order to recognize cells of melanocytic differentiation, useful for the diagnosis of a melanoma. The same name is also used to refer to the gene which codes for the antigen. The MART-1/melan-A antigen is specific for the melanocyte lineage, found in normal skin, the retina, and melanocytes, but not in other normal tissues. It is thus useful as a marker for melanocytic tumors (melanomas) with the caveat that it is normally found in benign nevi as well. In many immunological studies melan-A peptides serve as a positive control for T-cell priming experiments. This is due to the fact that its high precursor frequency of about 1/1000 among cytotoxic T-cells makes it easy for antigen presenting cells to evoke peptide-specific responses. # Structure MART-1/melan-A is a putative 18 kDa transmembrane protein consisting of 118 amino acids. It has a single transmembrane domain. # Regulation Its expression is regulated by the Microphthalmia-associated transcription factor.	MLANA Protein melan-A also known as melanoma antigen recognized by T cells 1 or MART-1 is a protein that in humans is encoded by the MLANA o "MALENA" gene.[1] A fragment of the protein, usually consisting of the nine amino acids 27 to 35, is bound by MHC class I complexes which present it to T cells of the immune system. These complexes can be found on the surface of melanoma cells. Decameric peptides (26-35) are being investigated as cancer vaccines. # Discovery and nomenclature The names MART-1 and melan-A were coined by two groups of researchers who independently sequenced the gene for this antigen in 1994. Both names are currently in common use. Kawakami et al. at the National Cancer Institute coined the term MART-1, which stands for "melanoma antigen recognized by T-cells."[2] Coulie et al. of Belgium called the gene melan-A, presumably an abbreviation for "melanocyte antigen."[3] # Clinical significance MART-1/melan-A is a protein antigen that is found on the surface of melanocytes. Antibodies against the antigen are used in the medical specialty of anatomic pathology in order to recognize cells of melanocytic differentiation, useful for the diagnosis of a melanoma. The same name is also used to refer to the gene which codes for the antigen. The MART-1/melan-A antigen is specific for the melanocyte lineage, found in normal skin, the retina, and melanocytes, but not in other normal tissues. It is thus useful as a marker for melanocytic tumors (melanomas) with the caveat that it is normally found in benign nevi as well. In many immunological studies melan-A peptides serve as a positive control for T-cell priming experiments. This is due to the fact that its high precursor frequency of about 1/1000 among cytotoxic T-cells makes it easy for antigen presenting cells to evoke peptide-specific responses.[4] # Structure MART-1/melan-A is a putative 18 kDa transmembrane protein consisting of 118 amino acids. It has a single transmembrane domain. # Regulation Its expression is regulated by the Microphthalmia-associated transcription factor.[5][6]	https://www.wikidoc.org/index.php/MLANA
330ac5058ea190a6380ef4f4e26e5f25d83e3547	wikidoc	MMP10	MMP10 Stromelysin-2 also known as matrix metalloproteinase-10 (MMP-10) or transin-2 is an enzyme that in humans is encoded by the MMP10 gene. # Function Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The enzyme encoded by this gene degrades proteoglycans and fibronectin. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3. # Clinical significance MMP10 has been linked to cancer stem cell vitality and metastasis. MMP10 is a potential prognostic biomarker for oral cancer.	MMP10 Stromelysin-2 also known as matrix metalloproteinase-10 (MMP-10) or transin-2 is an enzyme that in humans is encoded by the MMP10 gene.[1][2] # Function Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The enzyme encoded by this gene degrades proteoglycans and fibronectin. The gene is part of a cluster of MMP genes which localize to chromosome 11q22.3.[3] # Clinical significance MMP10 has been linked to cancer stem cell vitality and metastasis.[4] MMP10 is a potential prognostic biomarker for oral cancer.[5][unreliable medical source]	https://www.wikidoc.org/index.php/MMP10
e6cd9fb4b159b7f0ca8e6c510b70824dd17ebe43	wikidoc	MMP14	MMP14 Matrix metalloproteinase-14 is an enzyme that in humans is encoded by the MMP14 gene. # Function Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Deficits in MMP14 leads to premature aging, short lifespan, and cell senescence in mice, suggesting an important role of MMP14 in extracellular matrix remodeling during aging. Most MMP's are secreted as inactive pro-proteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are tethered to the cell surface rather than secreted. "This protein activates MMP2 protein, and this activity may be involved in tumor invasion." # Interactions MMP14 has been shown to interact with TIMP2.	MMP14 Matrix metalloproteinase-14 is an enzyme that in humans is encoded by the MMP14 gene.[1] # Function Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Deficits in MMP14 leads to premature aging, short lifespan, and cell senescence in mice[2], suggesting an important role of MMP14 in extracellular matrix remodeling during aging. Most MMP's are secreted as inactive pro-proteins which are activated when cleaved by extracellular proteinases. However, the protein encoded by this gene is a member of the membrane-type MMP (MT-MMP) subfamily; each member of this subfamily contains a potential transmembrane domain suggesting that these proteins are tethered to the cell surface rather than secreted. "This protein activates MMP2 protein, and this activity may be involved in tumor invasion."[3] # Interactions MMP14 has been shown to interact with TIMP2.[4]	https://www.wikidoc.org/index.php/MMP14
a99787e60092d2f485c5a011a89cfd243c5e2264	wikidoc	MMP17	MMP17 Matrix metalloproteinase-17 (MMP-17) also known as membrane-type matrix metalloproteinase 4 (MT-MMP 4) is an enzyme that in humans is encoded by the MMP17 gene. # Function Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The protein encoded by this gene is considered a member of the membrane-type MMP (MT-MMP) subfamily. However, this protein is unique among the MT-MMP's in that it is a GPI-anchored protein rather than a transmembrane protein. The protein activates MMP2 by cleavage. In melanocytic cells MMP17 gene expression may be regulated by MITF.	MMP17 Matrix metalloproteinase-17 (MMP-17) also known as membrane-type matrix metalloproteinase 4 (MT-MMP 4) is an enzyme that in humans is encoded by the MMP17 gene.[1][2] # Function Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. The protein encoded by this gene is considered a member of the membrane-type MMP (MT-MMP) subfamily. However, this protein is unique among the MT-MMP's in that it is a GPI-anchored protein rather than a transmembrane protein. The protein activates MMP2 by cleavage.[2] In melanocytic cells MMP17 gene expression may be regulated by MITF.[3]	https://www.wikidoc.org/index.php/MMP17
37e96ee4ee1041688d692e2c54cebdb32bb5badb	wikidoc	MMP20	MMP20 Matrix metalloproteinase-20 (MMP-20) also known as enamel metalloproteinase or enamelysin is an enzyme that in humans is encoded by the MMP20 gene. # Function Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. MMP-20, also known as enamelysin, appears to be the only MMP that is tooth-specific and it is expressed by cells of different developmental origin (i.e. epithelial ameloblasts and mesenchymal odontoblasts). # Clinical significance The human MMP-20 gene contains 10 exons and is part of a cluster of matrix metalloproteinase genes that localize to human chromosome 11q22.3. A mutation in this gene, which alters the normal splice pattern and results in premature termination of the encoded protein, has been associated with amelogenesis imperfecta. Enamel in the absence of MMP-20 is hypoplastic (thin), contains less mineral (only one-third as much total mineral as wild type), and contains more protein and water. In general, MMP-20 functions in enamel are to cleave enamel matrix proteins at specific cleavage sites.	MMP20 Matrix metalloproteinase-20 (MMP-20) also known as enamel metalloproteinase or enamelysin is an enzyme that in humans is encoded by the MMP20 gene.[1][2] # Function Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMP's are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. MMP-20, also known as enamelysin, appears to be the only MMP that is tooth-specific and it is expressed by cells of different developmental origin (i.e. epithelial ameloblasts and mesenchymal odontoblasts). # Clinical significance The human MMP-20 gene contains 10 exons and is part of a cluster of matrix metalloproteinase genes that localize to human chromosome 11q22.3.[2] A mutation in this gene, which alters the normal splice pattern and results in premature termination of the encoded protein, has been associated with amelogenesis imperfecta. Enamel in the absence of MMP-20 is hypoplastic (thin), contains less mineral (only one-third as much total mineral as wild type), and contains more protein and water. In general, MMP-20 functions in enamel are to cleave enamel matrix proteins at specific cleavage sites.[3]	https://www.wikidoc.org/index.php/MMP20
2346b548b6c0293eb1d6ffe3522afd7cd974e7d2	wikidoc	MMP27	MMP27 Matrix metallopeptidase 27 also known as MMP-27 is an enzyme which in humans is encoded by the MMP27 gene. # Structure MMP-27 was discovered and cloned in 1998 by Yang and Kurkinen. Initially compared to the so-called Chicken MMP (CMMP), MMP-27 actually shows very little sequence homology with this protease. Sequence homology predicts that the human MMP-27 gene encodes the canonical domains shared by most MMPs (annotation based on Uniprot entry Q9H306): (i) a signal peptide (residues 1-17), (ii) a propeptide (18-98) containing the cysteine switch motif (89-96), (iii) a catalytic domain (99-263) containing the typical HEXXHXXGXXH motif of the metzincins (M10 and M12 families of the MEROPS database), (iv) a proline-rich hinge region (264-278) and (v) a hemopexin-like domain (279-465) folded as a four-bladed β-propeller through disulfide bond formation between the two flanking Cys residues (Cys279 and Cys465). MMP-27 could be classified in the stromelysin group of MMPs, since MMP-27 shows 51,6% homology with stromelysin-2 (MMP-10) and localizes in the cluster of MMPs located on chromosome 11. Like the six known MT-MMPs, human MMP-27 is prolonged by an additional C-terminal domain (466-513). The Spoctopus algorithm for topological prediction suggests that this C-terminal extension (CTE) includes a potential transmembrane domain (490-510). However, this sequence is less hydrophobic than in transmembrane MT-MMPs (MMP-14, -15, -16 and -24) as it contains hydrophilic/charged residues, in particular His492, Lys493, His504 and Lys507. # Function Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMPs are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases. Cominelli A. and colleagues demonstrated that MMP-27 is an unusual protease which is not secreted and is efficiently retained in the endoplasmic reticulum in three mammalian cell lines. Deletion mutants and swapping with recombinant MMP-10 demonstrate that the unique MMP-27 C-terminal extension (CTE) is necessary and sufficient for endoplasmic reticulum retention but does not provide a stable membrane anchorage. Despite sequence homology with MT-MMPs, the CTE is not a transmembrane domain and does not interact permanently with membrane. This unique feature for an MMP raises important questions about potential functions of MMP-27, which remains to be investigated. # Clinical significance Sparse information about MMP-27 expression was found in studies of gene expression profiling (micro-array) or in expression pattern analysis of MMP family members during developmental, physiological or pathological processes. MMP-27 transcript is detected in almost every tissue, except the brain, with the highest expression found in the liver during mouse development In the adult, MMP-27 mRNA is mostly abundant in anti-IgG/IgM stimulated B lymphocytes, bone and kidney but is present at lower levels in the heart. A recent investigation of the transcriptome from distinct tissue compartments of the menstrual endometrium disclosed specific MMP-27 overexpression in areas of stromal breakdown. In another transcriptomic study, MMP-27 was found to be increased in the human endometrium at the end of the secretory phase, before menstruation. Moreover, MMP-27 expression is down-regulated in macrophages when co-cultured with ovarian cancer cells but up-regulated in cartilages from patients with osteoarthritis or in abdominal aortic aneurysms. MMP-27 was also identified, at the protein level, in MDA-MB-231 breast cancer cell line and in primary human breast cancer. Recently, MMP-27 has been demonstrated to be expressed by CD163+/CD206+ macrophages in the human endometrium and in superficial endometriotic lesions.	MMP27 Matrix metallopeptidase 27 also known as MMP-27 is an enzyme which in humans is encoded by the MMP27 gene.[1] # Structure MMP-27 was discovered and cloned in 1998 by Yang and Kurkinen.[2] Initially compared to the so-called Chicken MMP (CMMP), MMP-27 actually shows very little sequence homology with this protease. Sequence homology predicts that the human MMP-27 gene encodes the canonical domains shared by most MMPs (annotation based on Uniprot entry Q9H306): (i) a signal peptide (residues 1-17), (ii) a propeptide (18-98) containing the cysteine switch motif (89-96), (iii) a catalytic domain (99-263) containing the typical HEXXHXXGXXH motif of the metzincins (M10 and M12 families of the MEROPS[2] database), (iv) a proline-rich hinge region (264-278) and (v) a hemopexin-like domain (279-465) folded as a four-bladed β-propeller through disulfide bond formation between the two flanking Cys residues (Cys279 and Cys465). MMP-27 could be classified in the stromelysin group of MMPs, since MMP-27 shows 51,6% homology with stromelysin-2 (MMP-10) and localizes in the cluster of MMPs located on chromosome 11. Like the six known MT-MMPs, human MMP-27 is prolonged by an additional C-terminal domain (466-513). The Spoctopus algorithm for topological prediction[3] suggests that this C-terminal extension (CTE) includes a potential transmembrane domain (490-510). However, this sequence is less hydrophobic than in transmembrane MT-MMPs (MMP-14, -15, -16 and -24) as it contains hydrophilic/charged residues, in particular His492, Lys493, His504 and Lys507. # Function Proteins of the matrix metalloproteinase (MMP) family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. Most MMPs are secreted as inactive proproteins which are activated when cleaved by extracellular proteinases.[4] Cominelli A. and colleagues demonstrated that MMP-27 is an unusual protease which is not secreted and is efficiently retained in the endoplasmic reticulum in three mammalian cell lines.[5] Deletion mutants and swapping with recombinant MMP-10 demonstrate that the unique MMP-27 C-terminal extension (CTE) is necessary and sufficient for endoplasmic reticulum retention but does not provide a stable membrane anchorage. Despite sequence homology with MT-MMPs, the CTE is not a transmembrane domain and does not interact permanently with membrane. This unique feature for an MMP raises important questions about potential functions of MMP-27, which remains to be investigated. # Clinical significance Sparse information about MMP-27 expression was found in studies of gene expression profiling (micro-array) or in expression pattern analysis of MMP family members during developmental, physiological or pathological processes. MMP-27 transcript is detected in almost every tissue, except the brain, with the highest expression found in the liver during mouse development[6] In the adult, MMP-27 mRNA is mostly abundant in anti-IgG/IgM stimulated B lymphocytes,[7] bone and kidney but is present at lower levels in the heart.[8] A recent investigation of the transcriptome from distinct tissue compartments of the menstrual endometrium disclosed specific MMP-27 overexpression in areas of stromal breakdown.[9] In another transcriptomic study, MMP-27 was found to be increased in the human endometrium at the end of the secretory phase, before menstruation.[10] Moreover, MMP-27 expression is down-regulated in macrophages when co-cultured with ovarian cancer cells[11] but up-regulated in cartilages from patients with osteoarthritis[12] or in abdominal aortic aneurysms.[13] MMP-27 was also identified, at the protein level, in MDA-MB-231 breast cancer cell line[14] and in primary human breast cancer.[15] Recently, MMP-27 has been demonstrated to be expressed by CD163+/CD206+ macrophages in the human endometrium and in superficial endometriotic lesions.[16]	https://www.wikidoc.org/index.php/MMP27
d6d8e15a01acbbaee65958a13fa606b1c2740d73	wikidoc	MOCS1	MOCS1 Molybdenum cofactor biosynthesis protein 1 is a protein that in humans and other animals, fungi, and cellular slime molds, is encoded by the MOCS1 gene. Both copies of this gene are defective in patients with molybdenum cofactor deficiency, type A. Molybdenum cofactor biosynthesis is a conserved pathway leading to the biological activation of molybdenum. The protein encoded by this gene is involved in molybdenum cofactor biosynthesis. (This gene was originally thought to produce a bicistronic mRNA with the potential to produce two proteins (MOCS1A and MOCS1B) from adjacent open reading frames. However, only the first open reading frame (MOCS1A) has been found to encode a protein from the putative bicistronic mRNA.) Two of the splice variants found for this gene express proteins (MOCS1A-MOCS1B) that result from a fusion between the two open reading frames.	MOCS1 Molybdenum cofactor biosynthesis protein 1 is a protein that in humans and other animals, fungi, and cellular slime molds, is encoded by the MOCS1 gene.[1][2] [3] [4] Both copies of this gene are defective in patients with molybdenum cofactor deficiency, type A.[4] Molybdenum cofactor biosynthesis is a conserved pathway leading to the biological activation of molybdenum. The protein encoded by this gene is involved in molybdenum cofactor biosynthesis. (This gene was originally thought to produce a bicistronic mRNA with the potential to produce two proteins (MOCS1A and MOCS1B) from adjacent open reading frames. However, only the first open reading frame (MOCS1A) has been found to encode a protein from the putative bicistronic mRNA.) Two of the splice variants found for this gene express proteins (MOCS1A-MOCS1B) that result from a fusion between the two open reading frames.	https://www.wikidoc.org/index.php/MOCS1
cfd33d7bb203f6d695f85c768877f63f9030b79e	wikidoc	MOCS2	MOCS2 Molybdenum cofactor synthesis protein 2A and molybdenum cofactor synthesis protein 2B are a pair of proteins that in humans are encoded from the same MOCS2 gene. These two proteins dimerize to form molybdopterin synthase. # Function Eukaryotic molybdoenzymes use a unique molybdenum cofactor (MoCo) consisting of a pterin, termed molybdopterin, and the catalytically active metal molybdenum. MoCo is synthesized from cyclic pyranopterin monophosphate (precursor Z) by the heterodimeric enzyme molybdopterin synthase. # Gene The large and small subunits of molybdopterin synthase are both encoded from the MOCS2 gene by overlapping open reading frames. The proteins were initially thought to be encoded from a bicistronic transcript. They are now thought to be encoded from monocistronic transcripts. Alternatively spliced transcripts have been found for this locus that encode the large and small subunits. The MOCS2 gene contains 7 exons. Exons 1 to 3 encode MOCS2A (the small subunit), and exons 3 to 7 encode MOCS2B (large subunit). ## Genetic disease Defects in both copies of MOCS2 cause the molybdenum cofactor deficiency disease in babies. # Protein Structure MOCS2A and MOCS2B subunits form dimers in solution. These dimers in turn dimerize to form the tetrameric molybdopterin synthase complex.	MOCS2 Molybdenum cofactor synthesis protein 2A and molybdenum cofactor synthesis protein 2B are a pair of proteins that in humans are encoded from the same MOCS2 gene.[1][2][3] These two proteins dimerize to form molybdopterin synthase. # Function Eukaryotic molybdoenzymes use a unique molybdenum cofactor (MoCo) consisting of a pterin, termed molybdopterin, and the catalytically active metal molybdenum. MoCo is synthesized from cyclic pyranopterin monophosphate (precursor Z) by the heterodimeric enzyme molybdopterin synthase.[3] # Gene The large and small subunits of molybdopterin synthase are both encoded from the MOCS2 gene by overlapping open reading frames. The proteins were initially thought to be encoded from a bicistronic transcript. They are now thought to be encoded from monocistronic transcripts. Alternatively spliced transcripts have been found for this locus that encode the large and small subunits.[3] The MOCS2 gene contains 7 exons. Exons 1 to 3 encode MOCS2A (the small subunit), and exons 3 to 7 encode MOCS2B (large subunit).[1] ## Genetic disease Defects in both copies of MOCS2 cause the molybdenum cofactor deficiency disease in babies.[4] # Protein Structure MOCS2A and MOCS2B subunits form dimers in solution. These dimers in turn dimerize to form the tetrameric molybdopterin synthase complex.[5]	https://www.wikidoc.org/index.php/MOCS2
fdfc7e2f3d007450e8bf383fdae7ea4c30f92b86	wikidoc	MPV17	MPV17 Protein MPV17 is a protein that in humans is encoded by the MPV17 gene. It is a mitochondrial inner membrane protein, which has a so far largely unknown role in mtDNA maintenance. Protein MPV17 is expressed in human pancreas, kidney, muscle, liver, lung, placenta, brain and heart. Human MPV17 is the orthologue of the mouse kidney disease gene, Mpv17. Loss of function has been shown to cause hepatocerebral mtDNA depletion syndromes (MDS) with oxidative phosphorylation failure and mtDNA depletion both in affected individuals and in Mpv17−/− mice. # Function This protein was first thought to be a peroxisomal protein, but in 2006, Spinazzola demonstrated that it is a mitochondrial inner membrane protein that is implicated in the formation of reactive oxygen species (ROS). Restoration of Mpv17 expression in a Mpv17-/- mice restore mtDNA copy number, suggesting MPV17 is involved in mtDNA copy number, and in mtDNA maintenance. MPV17 seems to be also involved in apoptosis in podocytes, and involved in ROS. # Structure ## Gene The human MPV17 gene is located on chromosome 2 at p21-23, comprising eight exons encoding 176 amino acids. ## Protein MPV17 belongs to a family of integral membrane proteins consisting of four members (PXMP2, MPV17, MP-L, and FKSG24 (MPV17L2)) in mammals and two members (Sym1 and Yor292) in yeast. The amino acid sequence of MPV17 (176 amino acids) contains four cysteine residues and three putative phosphorylation sites implies that this protein may act as a redox- and ATP-sensitive channel. # Clinical significance Mutations in this gene have been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDS), a mutation in this protein leads to an mtDNA (mitochondrial DNA) copy number decrease. By 2013, MDS caused by MPV17 mutations had been reported in 32 patients with the clinical manifestations including early progressive liver failure, neurological abnormalities, hypoglycaemia and raised blood lactate. In addition, MPV17 mutations have also been associated with autosomal recessive adult-onset neuropathy and leukoencephalopathy with multiple mtDNA deletions in skeletal muscle. Thus, MPV17 mutations can lead to recessive MDS or recessive multiple mtDNA deletion disorders. # Interactions MPV17 has been shown to interact with Prkdc protein during Adriamycin-induced nephropathy in mice.	MPV17 Protein MPV17 is a protein that in humans is encoded by the MPV17 gene.[1][2][3] It is a mitochondrial inner membrane protein, which has a so far largely unknown role in mtDNA maintenance. Protein MPV17 is expressed in human pancreas, kidney, muscle, liver, lung, placenta, brain and heart.[4] Human MPV17 is the orthologue of the mouse kidney disease gene, Mpv17. Loss of function has been shown to cause hepatocerebral mtDNA depletion syndromes (MDS) with oxidative phosphorylation failure and mtDNA depletion both in affected individuals and in Mpv17−/− mice.[2][5] # Function This protein was first thought to be a peroxisomal protein, but in 2006, Spinazzola demonstrated that it is a mitochondrial inner membrane protein that is implicated in the formation of reactive oxygen species (ROS). Restoration of Mpv17 expression in a Mpv17-/- mice restore mtDNA copy number, suggesting MPV17 is involved in mtDNA copy number, and in mtDNA maintenance.[6] MPV17 seems to be also involved in apoptosis in podocytes, and involved in ROS.[7] # Structure ## Gene The human MPV17 gene is located on chromosome 2 at p21-23, comprising eight exons encoding 176 amino acids.[3] ## Protein MPV17 belongs to a family of integral membrane proteins consisting of four members (PXMP2, MPV17, MP-L, and FKSG24 (MPV17L2)) in mammals and two members (Sym1 and Yor292) in yeast. The amino acid sequence of MPV17 (176 amino acids) contains four cysteine residues and three putative phosphorylation sites implies that this protein may act as a redox- and ATP-sensitive channel.[8] # Clinical significance Mutations in this gene have been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDS), a mutation in this protein leads to an mtDNA (mitochondrial DNA) copy number decrease.[3] By 2013, MDS caused by MPV17 mutations had been reported in 32 patients with the clinical manifestations including early progressive liver failure, neurological abnormalities, hypoglycaemia and raised blood lactate.[4] In addition, MPV17 mutations have also been associated with autosomal recessive adult-onset neuropathy and leukoencephalopathy with multiple mtDNA deletions in skeletal muscle.[9] Thus, MPV17 mutations can lead to recessive MDS or recessive multiple mtDNA deletion disorders. # Interactions MPV17 has been shown to interact with Prkdc protein during Adriamycin-induced nephropathy in mice.[10]	https://www.wikidoc.org/index.php/MPV17
68dffe46a3148a29b41cd34fcd4dc67f76632fc1	wikidoc	MRPL3	MRPL3 Mitochondrial ribosomal protein L3 is a protein that in humans is encoded by the MRPL3 gene. Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein that belongs to the L3P ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 13q. . # Clinical relevance Mutations in this gene have been shown to cause mitochondrial cardiomyopathy.	MRPL3 Mitochondrial ribosomal protein L3 is a protein that in humans is encoded by the MRPL3 gene.[1] Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 39S subunit protein that belongs to the L3P ribosomal protein family. A pseudogene corresponding to this gene is found on chromosome 13q. [provided by RefSeq, Jul 2008].[1] # Clinical relevance Mutations in this gene have been shown to cause mitochondrial cardiomyopathy.[2]	https://www.wikidoc.org/index.php/MRPL3
5c9582f4912d3061bbd3c7419db99c8e3d5f4087	wikidoc	MRPS5	MRPS5 28S ribosomal protein S5, mitochondrial is a protein that in humans is encoded by the MRPS5 gene. # Function Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that belongs to the ribosomal protein S5P family. Pseudogenes corresponding to this gene are found on chromosomes 4q, 5q, and 18q. # Model organisms Model organisms have been used in the study of MRPS5 function. A conditional knockout mouse line called Mrps5tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping	MRPS5 28S ribosomal protein S5, mitochondrial is a protein that in humans is encoded by the MRPS5 gene.[1] # Function Mammalian mitochondrial ribosomal proteins are encoded by nuclear genes and help in protein synthesis within the mitochondrion. Mitochondrial ribosomes (mitoribosomes) consist of a small 28S subunit and a large 39S subunit. They have an estimated 75% protein to rRNA composition compared to prokaryotic ribosomes, where this ratio is reversed. Another difference between mammalian mitoribosomes and prokaryotic ribosomes is that the latter contain a 5S rRNA. Among different species, the proteins comprising the mitoribosome differ greatly in sequence, and sometimes in biochemical properties, which prevents easy recognition by sequence homology. This gene encodes a 28S subunit protein that belongs to the ribosomal protein S5P family. Pseudogenes corresponding to this gene are found on chromosomes 4q, 5q, and 18q.[1] # Model organisms Model organisms have been used in the study of MRPS5 function. A conditional knockout mouse line called Mrps5tm1b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[2] Male and female animals underwent a standardized phenotypic screen[3] to determine the effects of deletion.[4][5][6][7] Additional screens performed: - In-depth immunological phenotyping[8]	https://www.wikidoc.org/index.php/MRPS5
92c9d52e7a783b4762199d331cbf79069718d1b6	wikidoc	MSTO1	MSTO1 Protein misato homolog 1 is a protein that in humans is encoded by the MSTO1 gene. The MSTO1 gene is 5134 base pairs (located in chromosome 1) and the MSTO1 protein is 570 aminoacids in length. It is located in the outer membrane of the mitochondrion, and is involved in the regulation of mitochondrial distribution and morphology. # Structure The misato protein contains an N-terminal misato segment II myosin-like domain and a central tubulin domain.	MSTO1 Protein misato homolog 1 is a protein that in humans is encoded by the MSTO1 gene.[1][2] The MSTO1 gene is 5134 base pairs (located in chromosome 1) and the MSTO1 protein is 570 aminoacids in length. It is located in the outer membrane of the mitochondrion, and is involved in the regulation of mitochondrial distribution and morphology.[3] # Structure The misato protein contains an N-terminal misato segment II myosin-like domain and a central tubulin domain.[3]	https://www.wikidoc.org/index.php/MSTO1
c2e22907e5715b3620bebd8683e48b2ae9f03f59	wikidoc	MT-TD	MT-TD Mitochondrially encoded tRNA aspartic acid also known as MT-TD is a transfer RNA which in humans is encoded by the mitochondrial MT-TD gene. # Structure The MT-TD gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 67 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function The MT-TD gene encodes for a small transfer RNA (human mitochondrial map position 7518-7585) that transfers the amino acid aspartic acid to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance MT-TD mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy. A patient with a 7526A>G mutation in the MT-TD gene exhibited gradually worsening symptoms of exercise intolerance, increased creatine kinase levels, sustained exercise leading to muscle pains and general malaise. A patient with a 7543A>G mutation also exhibited symptoms of the disease.	MT-TD Mitochondrially encoded tRNA aspartic acid also known as MT-TD is a transfer RNA which in humans is encoded by the mitochondrial MT-TD gene.[1] # Structure The MT-TD gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 67 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function The MT-TD gene encodes for a small transfer RNA (human mitochondrial map position 7518-7585) that transfers the amino acid aspartic acid to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance MT-TD mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy.[4] A patient with a 7526A>G mutation in the MT-TD gene exhibited gradually worsening symptoms of exercise intolerance, increased creatine kinase levels, sustained exercise leading to muscle pains and general malaise.[5] A patient with a 7543A>G mutation also exhibited symptoms of the disease.[6]	https://www.wikidoc.org/index.php/MT-TD
745578f3a2dc342d8e50a7e846bef84519ff6bc7	wikidoc	MT-TE	MT-TE Mitochondrially encoded tRNA glutamic acid also known as MT-TE is a transfer RNA which in humans is encoded by the mitochondrial MT-TE gene. MT-TE is a small 69 nucleotide RNA (human mitochondrial map position 14674-14742) that transfers the amino acid glutamic acid to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Structure The MT-TE gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 68 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function The MT-TE gene encodes for a transfer RNA (tRNA), which are chemical cousins of DNA responsible for assembling amino acids into functioning proteins. MT-TE codes for a specific tRNA called tRNAGlu. tRNAGlu is responsible for attaching to glutamic acid (Glu) and inserting it into the specific locations of the growing peptide during protein assembly. The tRNAGlu molecule is localized to the mitochondria, and is involved in the assembly of oxidative phosphorylation proteins. # Clinical significance Mutations in MT-TE can result in mitochondrial deficiencies and associated disorders. ## Maternally inherited diabetes and deafness A mutation in the MT-TE gene has been found in a small number of people with maternally inherited diabetes and deafness (MIDD). People with this condition have diabetes and sometimes hearing loss, particularly of high tones. Affected individuals may also have muscle weakness (myopathy) and problems with their eyes, heart, or kidneys. This mutation likely impairs the ability of mitochondria to help trigger insulin release. In affected individuals, diabetes results when the beta cells do not produce enough insulin to regulate blood sugar effectively. Researchers have not determined how such mutations lead to hearing loss or the other features of MIDD. The mutation involved in this condition replaces the DNA building block (nucleotide) thymine with the nucleotide cytosine at position 14709 (written as T14709C). A family with a mutation of 14709T>C in the MT-TE gene showed phenotypes of congenital myopathy, mental retardation, cerebellar ataxia, and diabetes mellitus. Another patient with the same mutation was found to have Diabetes mellitus type 1 with severe myopathy, a high frequency deafness (hearing impairment) which suggested maternal inheritance. ## Infantile transient mitochondrial myopathy Infantile transient mitochondrial myopathy, also known as benign COX deficiency myopathy, is a rare disease which occurs within the infantile stages of life. The myopathy is characterized by clinical manifestations such as severe muscle weakness, hypotonia (poor muscle tone), and lactic acidosis (a buildup of lactic acid in the body). Affected infants often require support from a machine for breathing and have difficulties feeding. However, the signs and symptoms have been shown to improve after several months, and most affected individuals show no symptoms of the condition by age 2 or 3. The mutations involved in infantile transient mitochondrial myopathy change single nucleotides in mitochondrial DNA. These mutations impair oxidative phosphorylation. As a result, muscle cells cannot produce enough energy, leading to the muscle problems that affect infants with infantile transient mitochondrial myopathy. It is unknown why only muscles are involved or how affected infants recover from the condition. Specific mutations of 14674T>G and 14674T>C have been observed in patients with the myopathy. ## Complex IV deficiency MT-TE mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy. A 14680C>A substitution mutation was found in a patient with the deficiency.	MT-TE Mitochondrially encoded tRNA glutamic acid also known as MT-TE is a transfer RNA which in humans is encoded by the mitochondrial MT-TE gene.[1] MT-TE is a small 69 nucleotide RNA (human mitochondrial map position 14674-14742) that transfers the amino acid glutamic acid to a growing polypeptide chain at the ribosome site of protein synthesis during translation.[2] # Structure The MT-TE gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 68 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function The MT-TE gene encodes for a transfer RNA (tRNA), which are chemical cousins of DNA responsible for assembling amino acids into functioning proteins. MT-TE codes for a specific tRNA called tRNAGlu. tRNAGlu is responsible for attaching to glutamic acid (Glu) and inserting it into the specific locations of the growing peptide during protein assembly. The tRNAGlu molecule is localized to the mitochondria, and is involved in the assembly of oxidative phosphorylation proteins.[4] # Clinical significance Mutations in MT-TE can result in mitochondrial deficiencies and associated disorders. ## Maternally inherited diabetes and deafness A mutation in the MT-TE gene has been found in a small number of people with maternally inherited diabetes and deafness (MIDD). People with this condition have diabetes and sometimes hearing loss, particularly of high tones. Affected individuals may also have muscle weakness (myopathy) and problems with their eyes, heart, or kidneys. This mutation likely impairs the ability of mitochondria to help trigger insulin release. In affected individuals, diabetes results when the beta cells do not produce enough insulin to regulate blood sugar effectively. Researchers have not determined how such mutations lead to hearing loss or the other features of MIDD.[4] The mutation involved in this condition replaces the DNA building block (nucleotide) thymine with the nucleotide cytosine at position 14709 (written as T14709C).[4] A family with a mutation of 14709T>C in the MT-TE gene showed phenotypes of congenital myopathy, mental retardation, cerebellar ataxia, and diabetes mellitus.[5] Another patient with the same mutation was found to have Diabetes mellitus type 1 with severe myopathy, a high frequency deafness (hearing impairment) which suggested maternal inheritance.[6] ## Infantile transient mitochondrial myopathy Infantile transient mitochondrial myopathy, also known as benign COX deficiency myopathy, is a rare disease which occurs within the infantile stages of life. The myopathy is characterized by clinical manifestations such as severe muscle weakness, hypotonia (poor muscle tone), and lactic acidosis (a buildup of lactic acid in the body). Affected infants often require support from a machine for breathing and have difficulties feeding. However, the signs and symptoms have been shown to improve after several months, and most affected individuals show no symptoms of the condition by age 2 or 3.[4] The mutations involved in infantile transient mitochondrial myopathy change single nucleotides in mitochondrial DNA. These mutations impair oxidative phosphorylation. As a result, muscle cells cannot produce enough energy, leading to the muscle problems that affect infants with infantile transient mitochondrial myopathy. It is unknown why only muscles are involved or how affected infants recover from the condition. Specific mutations of 14674T>G and 14674T>C have been observed in patients with the myopathy.[4] ## Complex IV deficiency MT-TE mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy.[7] A 14680C>A substitution mutation[8] was found in a patient with the deficiency.	https://www.wikidoc.org/index.php/MT-TE
adf52f4b9ca83efe3eeecd332562c294709a84fc	wikidoc	MT-TF	MT-TF Mitochondrially encoded tRNA phenylalanine also known as MT-TF is a transfer RNA which in humans is encoded by the mitochondrial MT-TF gene. # Structure The MT-TF gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 71 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function MT-TF is a small transfer RNA (human mitochondrial map position 577-647) that transfers the amino acid phenylalanine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance Mutations in MT-TF can result in mitochondrial deficiencies and associated disorders, including Myoclonic epilepsy with ragged-red fibers (MERRF), Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Juvenile myopathy, encephalopathy, lactic acidosis, and stroke. ## Myoclonic epilepsy with ragged-red fibers (MERRF) Mutations in the MT-TF gene have been associated with myoclonic epilepsy with ragged-red fibers (MERRF). Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family. Common symptoms include: - myoclonus - myopathy - spasticity - epilepsy - peripheral neuropathy - dementia - ataxia - atrophy A 611G-A transition in MT-TF was found in a patient with MERRF. ## Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a condition that affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy). The signs and symptoms of this disorder most often appear in childhood following a period of normal development, although they can begin at any age. Early symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. Most affected individuals experience stroke-like episodes beginning before age 40. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines. Repeated stroke-like episodes can progressively damage the brain, leading to vision loss, problems with movement, and a loss of intellectual function (dementia). A patient with a mutation in the 583G-A position of the MT-TF gene exhibited symptoms of acute episodes of headaches, photophobia, vomiting, and a fully recovered left arm focal motor fitting. ## Complex IV Deficiency MT-TF mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy. 622G>A mutations have been associated with the deficiency.	MT-TF Mitochondrially encoded tRNA phenylalanine also known as MT-TF is a transfer RNA which in humans is encoded by the mitochondrial MT-TF gene.[1] # Structure The MT-TF gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 71 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function MT-TF is a small transfer RNA (human mitochondrial map position 577-647) that transfers the amino acid phenylalanine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance Mutations in MT-TF can result in mitochondrial deficiencies and associated disorders, including Myoclonic epilepsy with ragged-red fibers (MERRF), Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), Juvenile myopathy, encephalopathy, lactic acidosis, and stroke.[4] ## Myoclonic epilepsy with ragged-red fibers (MERRF) Mutations in the MT-TF gene have been associated with myoclonic epilepsy with ragged-red fibers (MERRF). Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family. Common symptoms include:[4] - myoclonus - myopathy - spasticity - epilepsy - peripheral neuropathy - dementia - ataxia - atrophy A 611G-A transition in MT-TF was found in a patient with MERRF.[5] ## Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is a condition that affects many of the body's systems, particularly the brain and nervous system (encephalo-) and muscles (myopathy). The signs and symptoms of this disorder most often appear in childhood following a period of normal development, although they can begin at any age. Early symptoms may include muscle weakness and pain, recurrent headaches, loss of appetite, vomiting, and seizures. Most affected individuals experience stroke-like episodes beginning before age 40. These episodes often involve temporary muscle weakness on one side of the body (hemiparesis), altered consciousness, vision abnormalities, seizures, and severe headaches resembling migraines. Repeated stroke-like episodes can progressively damage the brain, leading to vision loss, problems with movement, and a loss of intellectual function (dementia).[6] A patient with a mutation in the 583G-A position of the MT-TF gene exhibited symptoms of acute episodes of headaches, photophobia, vomiting, and a fully recovered left arm focal motor fitting.[7] ## Complex IV Deficiency MT-TF mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy.[8] 622G>A mutations have been associated with the deficiency.[9]	https://www.wikidoc.org/index.php/MT-TF
eb6dea77d97b27d32e2e8cecc38203e73ffb7cc1	wikidoc	MT-TG	MT-TG Mitochondrially encoded tRNA glycine also known as MT-TG is a transfer RNA which in humans is encoded by the mitochondrial MT-TG gene. # Structure The MT-TG gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 68 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function MT-TG is a small 68 nucleotide transfer RNA (human mitochondrial map position 9991-10058) that transfers the amino acid glycine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance ## Myoclonic epilepsy with ragged-red fibers (MERRF) Mutations in transfer RNAs have been found to lead to marked mitochondrial energy deficiency and a hindrance of mitochondrial proliferation, and defects in oxidative phosphorylation. Such defects may result in myoclonic epilepsy with ragged-red fibers (MERRF). Myoclonic epilepsy with ragged-red fibers (MERRF) is a rare mitochondrial disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family. Common clinical manifestations include myoclonus, myopathy, spasticity,epilepsy, peripheral neuropathy, dementia, ataxia, atrophy and more. ## Familial hypertrophic cardiomyopathy Mutations in the MT-TG gene has also been associated with familial hypertrophic cardiomyopathy. Familial hypertrophic cardiomyopathy is a heart condition characterized by thickening of the heart, usually in the interventricular septum. Common phenotypes include chest pain, shortness of breath, physical exertion, palpitations, lightheadedness, dizziness and fainting. A family with a transition mutation of 9997T>C in the MT-TG gene exhibited familial hypertrophic cardiomyopathy.	MT-TG Mitochondrially encoded tRNA glycine also known as MT-TG is a transfer RNA which in humans is encoded by the mitochondrial MT-TG gene.[1] # Structure The MT-TG gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 68 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function MT-TG is a small 68 nucleotide transfer RNA (human mitochondrial map position 9991-10058) that transfers the amino acid glycine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance ## Myoclonic epilepsy with ragged-red fibers (MERRF) Mutations in transfer RNAs have been found to lead to marked mitochondrial energy deficiency and a hindrance of mitochondrial proliferation, and defects in oxidative phosphorylation. Such defects may result in myoclonic epilepsy with ragged-red fibers (MERRF). Myoclonic epilepsy with ragged-red fibers (MERRF) is a rare mitochondrial disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family. Common clinical manifestations include myoclonus, myopathy, spasticity,epilepsy, peripheral neuropathy, dementia, ataxia, atrophy and more.[4][5] ## Familial hypertrophic cardiomyopathy Mutations in the MT-TG gene has also been associated with familial hypertrophic cardiomyopathy. Familial hypertrophic cardiomyopathy is a heart condition characterized by thickening of the heart, usually in the interventricular septum. Common phenotypes include chest pain, shortness of breath, physical exertion, palpitations, lightheadedness, dizziness and fainting.[6] A family with a transition mutation of 9997T>C in the MT-TG gene exhibited familial hypertrophic cardiomyopathy.[7]	https://www.wikidoc.org/index.php/MT-TG
64b002f0e4c0f6bf6544b599dec30c5f48f997aa	wikidoc	MT-TH	MT-TH Mitochondrially encoded tRNA histidine, also known as MT-TH, is a transfer RNA which, in humans, is encoded by the mitochondrial MT-TH gene. # Structure The MT-TH gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 69 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function MT-TH is a small 69 nucleotide transfer RNA (human mitochondrial map position 12138-12206) that transfers the amino acid histidine to a growing polypeptide at the ribosomal site of protein synthesis during translation. # Clinical significance Mutations in MT-TH can result in multiple mitochondrial deficiencies and associated disorders. MT-TH is associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), cardiomyopathy, and the MELAS/MERRF overlap syndrome. ## Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) A small number of people with symptoms of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) have been found to have mutations in the MT-TH gene. MELAS is a rare mitochondrial disorder known to affect many parts of the body, especially the nervous system and the brain. Symptoms of MELAS include recurrent severe headaches, muscle weakness (myopathy), hearing loss, stroke-like episodes with a loss of consciousness, seizures, and other problems affecting the nervous system. ## MERRF/MELAS overlap syndrome MELAS syndrome may also be accompanied by another mitochondrial disorder called myoclonic epilepsy with ragged-red fibers, also known as MERRF syndrome. In addition to symptoms of MELAS syndrome, additional signs and symptoms may include muscle twitches (myoclonus), difficulty coordinating movement (ataxia), and abnormal muscle cells known as ragged-red fibers. The combination of MERRF and MELAS is called the MERRF/MELAS overlap syndrome, which is caused by mutations in the MT-TH gene. It has not been determined how such mutations alter the energy production function of the mitochondria and result in symptoms of such syndromes. A specific mutation of 12147G>A in the MT-TH gene has been found to result in the MERRF/MELAS overlap syndrome. A patient with the mutation exhibited symptoms of migrainous headache and vomiting, left hemiparesis, lateral homonymous hemianopia, and others consistent with the MERRF/MELAS overlap syndrome. The patient exhibited symptoms of MELAS first, then progressed into the overlap syndrome. ## Cardiomyopathy Mutations in the MT-TH gene may also cause cardiomyopathy, a disorder of the heart characterized by the thickening of the heart, usually in the interventricular septum, which results in a weakened heart muscle that is unable to pump blood effectively. Patients with mutations in the MT-TH gene have been found to exhibit symptoms of cardiomyopathy without other common signs of mitochondrial disease such as neurological abnormalities. It is unclear why such mutations result in the symptoms of isolated cardiomyopathy. A specific mutation of 12192G>A in the MT-TH gene has been found in multiple patients with the disorder. patients exhibited symptoms of cardiomyopathy in different forms. ## Deafness, Nonsyndromic Sensorineural, Mitochondrial Deafness has also been associated with mutations in the MT-TH gene. Heteroplasmic 12201T>C transitions in MT-TH have been found in a family exhibiting symptoms of nonsyndromic sensorineural deafness, varying in time of onset and severity.	MT-TH Mitochondrially encoded tRNA histidine, also known as MT-TH, is a transfer RNA which, in humans, is encoded by the mitochondrial MT-TH gene.[1] # Structure The MT-TH gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 69 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function MT-TH is a small 69 nucleotide transfer RNA (human mitochondrial map position 12138-12206) that transfers the amino acid histidine to a growing polypeptide at the ribosomal site of protein synthesis during translation.[4] # Clinical significance Mutations in MT-TH can result in multiple mitochondrial deficiencies and associated disorders. MT-TH is associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)[5][6], cardiomyopathy, and the MELAS/MERRF overlap syndrome.[7] ## Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) A small number of people with symptoms of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) have been found to have mutations in the MT-TH gene. MELAS is a rare mitochondrial disorder known to affect many parts of the body, especially the nervous system and the brain. Symptoms of MELAS include recurrent severe headaches, muscle weakness (myopathy), hearing loss, stroke-like episodes with a loss of consciousness, seizures, and other problems affecting the nervous system.[7] ## MERRF/MELAS overlap syndrome MELAS syndrome may also be accompanied by another mitochondrial disorder called myoclonic epilepsy with ragged-red fibers, also known as MERRF syndrome.[5] In addition to symptoms of MELAS syndrome, additional signs and symptoms may include muscle twitches (myoclonus), difficulty coordinating movement (ataxia), and abnormal muscle cells known as ragged-red fibers. The combination of MERRF and MELAS is called the MERRF/MELAS overlap syndrome, which is caused by mutations in the MT-TH gene. It has not been determined how such mutations alter the energy production function of the mitochondria and result in symptoms of such syndromes.[7] A specific mutation of 12147G>A in the MT-TH gene has been found to result in the MERRF/MELAS overlap syndrome. A patient with the mutation exhibited symptoms of migrainous headache and vomiting, left hemiparesis, lateral homonymous hemianopia, and others consistent with the MERRF/MELAS overlap syndrome. The patient exhibited symptoms of MELAS first, then progressed into the overlap syndrome.[8] ## Cardiomyopathy Mutations in the MT-TH gene may also cause cardiomyopathy, a disorder of the heart characterized by the thickening of the heart, usually in the interventricular septum, which results in a weakened heart muscle that is unable to pump blood effectively. Patients with mutations in the MT-TH gene have been found to exhibit symptoms of cardiomyopathy without other common signs of mitochondrial disease such as neurological abnormalities. It is unclear why such mutations result in the symptoms of isolated cardiomyopathy.[7] A specific mutation of 12192G>A in the MT-TH gene has been found in multiple patients with the disorder. patients exhibited symptoms of cardiomyopathy in different forms.[9] ## Deafness, Nonsyndromic Sensorineural, Mitochondrial Deafness has also been associated with mutations in the MT-TH gene. Heteroplasmic 12201T>C transitions in MT-TH have been found in a family exhibiting symptoms of nonsyndromic sensorineural deafness, varying in time of onset and severity.[10]	https://www.wikidoc.org/index.php/MT-TH
07aff9579698078072b8b4b1ce10d015ed5baaba	wikidoc	MT-TI	MT-TI Mitochondrially encoded tRNA isoleucine also known as MT-TI is a transfer RNA which in humans is encoded by the mitochondrial MT-TI gene. # Structure The MT-TI gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 69 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function MT-TI is a small 69 nucleotide RNA (human mitochondrial map position 4263-4331) that transfers the amino acid isoleucine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance Mutations in MT-TI can result in multiple mitochondrial deficiencies and associated disorders. ## Myoclonic epilepsy with ragged-red fibers (MERRF) Mutations in the MT-TI gene have been associated with myoclonic epilepsy with ragged-red fibers (MERRF). Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family. Common symptoms include, myoclonus, myopathy, spasticity, epilepsy, peripheral neuropathy, dementia, ataxia, atrophy, and more. ## Cardiomyopathy Mutations in the MT-TI gene may also cause cardiomyopathy, a disorder of the heart characterized by the thickening of the heart, usually in the interventricular septum, which results in a weakened heart muscle that is unable to pump blood effectively. It is unclear why such mutations result in the symptoms of isolated cardiomyopathy. Mutations of 4300A>G, 4295A>G, 4269A>G, and 4317A>G in the MT-TI gene have been found in patients with cardiomyopathy in varying severities and onset. ## Complex IV Deficiency MT-TI mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy. A patient with a 4269A>G mutation in MT-TI was found with the deficiency.	MT-TI Mitochondrially encoded tRNA isoleucine also known as MT-TI is a transfer RNA which in humans is encoded by the mitochondrial MT-TI gene.[1] # Structure The MT-TI gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 69 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function MT-TI is a small 69 nucleotide RNA (human mitochondrial map position 4263-4331) that transfers the amino acid isoleucine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance Mutations in MT-TI can result in multiple mitochondrial deficiencies and associated disorders. ## Myoclonic epilepsy with ragged-red fibers (MERRF) Mutations in the MT-TI gene have been associated with myoclonic epilepsy with ragged-red fibers (MERRF). Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family. Common symptoms include, myoclonus, myopathy, spasticity, epilepsy, peripheral neuropathy, dementia, ataxia, atrophy, and more.[4] ## Cardiomyopathy Mutations in the MT-TI gene may also cause cardiomyopathy, a disorder of the heart characterized by the thickening of the heart, usually in the interventricular septum, which results in a weakened heart muscle that is unable to pump blood effectively. It is unclear why such mutations result in the symptoms of isolated cardiomyopathy.[5] Mutations of 4300A>G, 4295A>G, 4269A>G, and 4317A>G in the MT-TI gene have been found in patients with cardiomyopathy in varying severities and onset.[6][7][8][9] ## Complex IV Deficiency MT-TI mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy.[10] A patient with a 4269A>G mutation in MT-TI was found with the deficiency.[11]	https://www.wikidoc.org/index.php/MT-TI
a35b700e591cbe5060bfb78988644bbc582414c8	wikidoc	MT-TK	MT-TK Mitochondrially encoded tRNA lysine also known as MT-TK is a transfer RNA which in humans is encoded by the mitochondrial MT-TK gene. # Structure The MT-TK gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 70 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function MT-TK is a small 70 nucleotide RNA (human mitochondrial map position 8295-8364) that transfers the amino acid lysine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance Mutations in MT-TK can result in multiple mitochondrial deficiencies and associated disorders. ## Myoclonic epilepsy with ragged-red fibers (MERRF) Mutations in the MT-TK gene are associated with myoclonic epilepsy and ragged-red fiber disease (MERRF). Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family. Common symptoms include, myoclonus, myopathy, spasticity, epilepsy, peripheral neuropathy, dementia, ataxia, atrophy and more. A majority of mutations in the MT-TK gene found to cause the disease were single nucleotide substitutions, such as 8344A>G. The 8344A>G mutation has been found to disable the normal functions of the mitochondria. A family of mutations 8344A>G and 16182A>C in the MT-TK gene has been found with MERRF syndrome. Another family with the syndrome exhibited mutations of 3243A>G and 16428G>A. ## MERRF/MELAS overlap syndrome MELAS syndrome may also be accompanied by another mitochondrial disorder called myoclonic epilepsy with ragged-red fibers, also known as MERRF syndrome. In addition to symptoms of MELAS syndrome, additional signs and symptoms may include muscle twitches (myoclonus), difficulty coordinating movement (ataxia), and abnormal muscle cells known as ragged-red fibers. The combination of MERRF and MELAS is called the MERRF/MELAS overlap syndrome. It has not been determined how mutations alter the energy production function of the mitochondria and result in symptoms of such syndromes. The single nucleotide substitution 8356T>C has been found to cause the syndrome. ## Maternally inherited diabetes and deafness (MIDD) A mutation in the MT-TK gene has been found in a small number of people with maternally inherited diabetes and deafness (MIDD). The disorder is characterized by diabetes combined with hearing loss, particularly of high pitches. Additional symptoms includemuscle weakness (myopathy) and various problems with a patient's eyes, heart, or kidneys. Mutations in the MT-TK gene disables the insulin release by the mitochondria. Diabetes results when the beta cells do not release enough insulin to regulate blood sugar effectively. Researchers have not determined how mutations lead to hearing loss or the other features of MIDD. The single nucleotide substitution 8296A>G has been found to cause the syndrome. ## Leigh syndrome The 8344A>G mutation in the MT-TK gene may also result in Leigh syndrome, a progressive brain disorder. Clinical manifestations, which include vomiting, seizures, delayed development, myopathy, and problems with movement, have an early onset of infancy or early childhood. Additional symptoms include heart problems, kidney problems, and breathing difficulties. The cause of the disease has not been identified. ## Cardiomyopathy The 8363G>A mutation in the MT-TK gene may also cause hypertrophic cardiomyopathy, a disorder characterized by the thickening of the heart, and hearing loss. Additional symptoms may include myopathy and ataxia. A family with abundant 8363G>A mutations of MT-TK in their muscle samples exhibited symptoms of encephalomyopathy, sensorineural hearing loss, and hypertrophic cardiomyopathy. ## Complex IV Deficiency MT-TK mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy. A patient with a 8313G>A mutation in the MT-TK gene exhibited symptoms of the deficiency accompanied by bilateral ptosis. Other variants also include 8328G>A and 8344G>A.	MT-TK Mitochondrially encoded tRNA lysine also known as MT-TK is a transfer RNA which in humans is encoded by the mitochondrial MT-TK gene.[1] # Structure The MT-TK gene is located on the p arm of the mitochondrial DNA at position 12 and it spans 70 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function MT-TK is a small 70 nucleotide RNA (human mitochondrial map position 8295-8364) that transfers the amino acid lysine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance Mutations in MT-TK can result in multiple mitochondrial deficiencies and associated disorders. ## Myoclonic epilepsy with ragged-red fibers (MERRF) Mutations in the MT-TK gene are associated with myoclonic epilepsy and ragged-red fiber disease (MERRF).[4][5] Myoclonic epilepsy with ragged-red fibers (MERRF) is a disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family. Common symptoms include, myoclonus, myopathy, spasticity, epilepsy, peripheral neuropathy, dementia, ataxia, atrophy and more.[6] A majority of mutations in the MT-TK gene found to cause the disease were single nucleotide substitutions, such as 8344A>G. The 8344A>G mutation has been found to disable the normal functions of the mitochondria.[7] A family of mutations 8344A>G and 16182A>C in the MT-TK gene has been found with MERRF syndrome. Another family with the syndrome exhibited mutations of 3243A>G and 16428G>A.[8] ## MERRF/MELAS overlap syndrome MELAS syndrome may also be accompanied by another mitochondrial disorder called myoclonic epilepsy with ragged-red fibers, also known as MERRF syndrome.[9] In addition to symptoms of MELAS syndrome, additional signs and symptoms may include muscle twitches (myoclonus), difficulty coordinating movement (ataxia), and abnormal muscle cells known as ragged-red fibers. The combination of MERRF and MELAS is called the MERRF/MELAS overlap syndrome. It has not been determined how mutations alter the energy production function of the mitochondria and result in symptoms of such syndromes.[7] The single nucleotide substitution 8356T>C has been found to cause the syndrome.[10] ## Maternally inherited diabetes and deafness (MIDD) A mutation in the MT-TK gene has been found in a small number of people with maternally inherited diabetes and deafness (MIDD). The disorder is characterized by diabetes combined with hearing loss, particularly of high pitches. Additional symptoms includemuscle weakness (myopathy) and various problems with a patient's eyes, heart, or kidneys. Mutations in the MT-TK gene disables the insulin release by the mitochondria. Diabetes results when the beta cells do not release enough insulin to regulate blood sugar effectively. Researchers have not determined how mutations lead to hearing loss or the other features of MIDD.[7] The single nucleotide substitution 8296A>G has been found to cause the syndrome.[11] ## Leigh syndrome The 8344A>G mutation in the MT-TK gene may also result in Leigh syndrome, a progressive brain disorder.[4] Clinical manifestations, which include vomiting, seizures, delayed development, myopathy, and problems with movement, have an early onset of infancy or early childhood. Additional symptoms include heart problems, kidney problems, and breathing difficulties. The cause of the disease has not been identified.[7] ## Cardiomyopathy The 8363G>A mutation in the MT-TK gene may also cause hypertrophic cardiomyopathy, a disorder characterized by the thickening of the heart, and hearing loss. Additional symptoms may include myopathy and ataxia.[7] A family with abundant 8363G>A mutations of MT-TK in their muscle samples exhibited symptoms of encephalomyopathy, sensorineural hearing loss, and hypertrophic cardiomyopathy.[12] ## Complex IV Deficiency MT-TK mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy.[13] A patient with a 8313G>A mutation in the MT-TK gene exhibited symptoms of the deficiency accompanied by bilateral ptosis.[14] Other variants also include 8328G>A[15] and 8344G>A.[16]	https://www.wikidoc.org/index.php/MT-TK
59d96450e6c74357887d655e432b54907095859f	wikidoc	MT-TN	MT-TN Mitochondrially encoded tRNA asparagine also known as MT-TN is a transfer RNA which in humans is encoded by the mitochondrial MT-TN gene. # Structure The MT-TN gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 73 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function MT-TN is a small 73 nucleotide RNA (human mitochondrial map position 5657-5729) that transfers the amino acid asparagine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance ## Ophthalmoplegia Mutations in MT-TN have been associated with isolated ophthalmoplegia. Ophthalmoplegia is a condition characterized by eye muscle weakness. Common symptoms of the disorder include hearing loss, loss of sensation in the limbs, ataxia, and neuropathy. Multiple mutations of 5692A>G and 5703G>A have been found in patients with ophthalmoplegia. Such mutations in MT-TN resulted in a failure in oxidative phosphorylation and protein synthesis of the mitochondria. In addition, a 5728A>G transition of MT-TN was found to result in a combined deficiency of complex I and IV, with symptoms of failure to thrive, renal failure, and mental retardation. ## Complex IV Deficiency MT-TN mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy. 5709T>C mutations in MT-TN have been found in patients with the deficiency.	MT-TN Mitochondrially encoded tRNA asparagine also known as MT-TN is a transfer RNA which in humans is encoded by the mitochondrial MT-TN gene.[1] # Structure The MT-TN gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 73 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function MT-TN is a small 73 nucleotide RNA (human mitochondrial map position 5657-5729) that transfers the amino acid asparagine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance ## Ophthalmoplegia Mutations in MT-TN have been associated with isolated ophthalmoplegia. Ophthalmoplegia is a condition characterized by eye muscle weakness. Common symptoms of the disorder include hearing loss, loss of sensation in the limbs, ataxia, and neuropathy.[4] Multiple mutations of 5692A>G and 5703G>A have been found in patients with ophthalmoplegia.[5][6][7] Such mutations in MT-TN resulted in a failure in oxidative phosphorylation and protein synthesis of the mitochondria. In addition, a 5728A>G transition of MT-TN was found to result in a combined deficiency of complex I and IV, with symptoms of failure to thrive, renal failure, and mental retardation.[8] ## Complex IV Deficiency MT-TN mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy.[9] 5709T>C[10][11] mutations in MT-TN have been found in patients with the deficiency.	https://www.wikidoc.org/index.php/MT-TN
a98e5c37de37bdebfcc9a9cdab054371f41e9b1b	wikidoc	MT-TP	MT-TP Mitochondrially encoded tRNA proline also known as MT-TP is a transfer RNA that in humans is encoded by the mitochondrial MT-TP gene. # Structure The MT-TP gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 68 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function MT-TP is a small 68 nucleotide RNA (human mitochondrial map position 15956-16023) that transfers the amino acid proline to a growing polypeptide chain at the ribosome site of protein synthesis during translation. MT-TP is responsible for coding the microsomal triglyceride transfer protein, which is required for the synthesis of beta-lipoproteins in the liver and intestine. Beta-lipoproteins are essential in fat, cholesterol, and fat-soluble vitamin transport from the intestine to the bloodstream for absorption. # Clinical Significance ## Abetalipoproteinemia Mutations in MT-TP have been associated with Abetalipoproteinemia. Abetalipoproteinemia is an inherited disorder characterized by an impaired absorption of fats and certain vitamins from the diet. Mutations in MT-TP cause an impaired microsomal triglyceride transfer protein and lead to reduced or absent beta-lipoprotein. The dysfunction of the microsomal triglyceride transfer protein then results in insufficient levels of fats, cholesterol, and vitamins, which are necessary for growth and development. Therefore, clinical manifestations of abetalipoproteinemia include impaired weight gain and growth, failure to thrive, diarrhea, and steatorrhea. Mutations of GLY865TER, SER590ILE, ASN780TYR, ARG540HIS, IVS9AS, and ARG215TER of the MT-TP gene have been found in patients with the disease. ## Complex I deficiency MT-TP mutations may result in complex I deficiency of the mitochondrial respiratory chain, which may cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system, the heart, and the muscles used for movement (skeletal muscles). These signs and symptoms can appear at any time from birth to adulthood. Phenotypes of the condition include encephalopathy, epilepsy, dystonia, hypotonia, myalgia, exercise intolerance, and more. A G15975A mutation has been found in a patient with the deficiency. In addition, MT-TP mutations have been associated with late-onset ataxia, retinitis, pigmentosa, deafness, leukoencephalopathy, and complex IV deficiency.	MT-TP Mitochondrially encoded tRNA proline also known as MT-TP is a transfer RNA that in humans is encoded by the mitochondrial MT-TP gene.[1] # Structure The MT-TP gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 68 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function MT-TP is a small 68 nucleotide RNA (human mitochondrial map position 15956-16023) that transfers the amino acid proline to a growing polypeptide chain at the ribosome site of protein synthesis during translation. MT-TP is responsible for coding the microsomal triglyceride transfer protein, which is required for the synthesis of beta-lipoproteins in the liver and intestine. Beta-lipoproteins are essential in fat, cholesterol, and fat-soluble vitamin transport from the intestine to the bloodstream for absorption.[4] # Clinical Significance ## Abetalipoproteinemia Mutations in MT-TP have been associated with Abetalipoproteinemia. Abetalipoproteinemia is an inherited disorder characterized by an impaired absorption of fats and certain vitamins from the diet. Mutations in MT-TP cause an impaired microsomal triglyceride transfer protein and lead to reduced or absent beta-lipoprotein. The dysfunction of the microsomal triglyceride transfer protein then results in insufficient levels of fats, cholesterol, and vitamins, which are necessary for growth and development.[4] Therefore, clinical manifestations of abetalipoproteinemia include impaired weight gain and growth, failure to thrive, diarrhea, and steatorrhea. Mutations of GLY865TER[5], SER590ILE[6], ASN780TYR[7], ARG540HIS[8], IVS9AS[9], and ARG215TER[10] of the MT-TP gene have been found in patients with the disease. ## Complex I deficiency MT-TP mutations may result in complex I deficiency of the mitochondrial respiratory chain, which may cause a wide variety of signs and symptoms affecting many organs and systems of the body, particularly the nervous system, the heart, and the muscles used for movement (skeletal muscles). These signs and symptoms can appear at any time from birth to adulthood. Phenotypes of the condition include encephalopathy, epilepsy, dystonia, hypotonia, myalgia, exercise intolerance, and more. A G15975A mutation has been found in a patient with the deficiency. In addition, MT-TP mutations have been associated with late-onset ataxia, retinitis, pigmentosa, deafness, leukoencephalopathy, and complex IV deficiency.[11][12]	https://www.wikidoc.org/index.php/MT-TP
872233a6165f4917e478d4977e434139c42a4d1b	wikidoc	MT-TR	MT-TR Mitochondrially encoded tRNA arginine also known as MT-TR is a transfer RNA which in humans is encoded by the mitochondrial MT-TR gene. # Structure The MT-TR gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 65 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function MT-TR is a small 65 nucleotide RNA (human mitochondrial map position 10405-10469) that transfers the amino acid arginine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance ## Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Mutations in MT-TR have been associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). MELAS is a rare mitochondrial disorder known to affect many parts of the body, especially the nervous system and the brain. Symptoms of MELAS include recurrent severe headaches, muscle weakness (myopathy), hearing loss, stroke-like episodes with a loss of consciousness, seizures, and other problems affecting the nervous system. Mutations in MT-TR associated with the disease have included 10450A-G and 10438A-G. ## Cytochrome c oxidase deficiency MT-TR mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy. A 10437 G>A mutation has been found with a patient with the deficiency.	MT-TR Mitochondrially encoded tRNA arginine also known as MT-TR is a transfer RNA which in humans is encoded by the mitochondrial MT-TR gene.[1] # Structure The MT-TR gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 65 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function MT-TR is a small 65 nucleotide RNA (human mitochondrial map position 10405-10469) that transfers the amino acid arginine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance ## Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) Mutations in MT-TR have been associated with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). MELAS is a rare mitochondrial disorder known to affect many parts of the body, especially the nervous system and the brain. Symptoms of MELAS include recurrent severe headaches, muscle weakness (myopathy), hearing loss, stroke-like episodes with a loss of consciousness, seizures, and other problems affecting the nervous system.[4] Mutations in MT-TR associated with the disease have included 10450A-G[5] and 10438A-G.[6] ## Cytochrome c oxidase deficiency MT-TR mutations have been associated with complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy.[7] A 10437 G>A mutation has been found with a patient with the deficiency.[8]	https://www.wikidoc.org/index.php/MT-TR
e9cd7ebde272ae8e5b40265f78f513abd0680a3b	wikidoc	MT-TT	MT-TT Mitochondrially encoded tRNA threonine also known as MT-TT is a transfer RNA which in humans is encoded by the mitochondrial MT-TT gene. # Structure The MT-TT gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 66 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function MT-TT is a small 66 nucleotide RNA (human mitochondrial map position 15888-15953) that transfers the amino acid threonine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance ## Myoclonic epilepsy with ragged-red fibers (MERRF) Mutations in MT-TT have been associated with myoclonic epilepsy with ragged-red fibers (MERRF), and cause mitochondrial energy deficiencies and reduced proliferation leading to oxidative phosphorylation. Myoclonic epilepsy with ragged-red fibers (MERRF) is a rare mitochondrial disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family. Common clinical manifestations include myoclonus, myopathy, spasticity,epilepsy, peripheral neuropathy, dementia, ataxia, atrophy and more. In addition, mutations have also been linked to lethal infantile mitochondrial myopathy, Parkinson's disease associated with a 15950G>A mutation, and a 15923A>G mutation found to result in an unconfirmed heart disease. ## Cytochrome c oxidase deficiency MT-TT mutations result in complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy. A 15915G>A mutation was found in a patient with cytochrome c oxidase deficiency with accompany symptoms of seizures, progressive hearing loss and muscle weakness.	MT-TT Mitochondrially encoded tRNA threonine also known as MT-TT is a transfer RNA which in humans is encoded by the mitochondrial MT-TT gene.[1] # Structure The MT-TT gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 66 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function MT-TT is a small 66 nucleotide RNA (human mitochondrial map position 15888-15953) that transfers the amino acid threonine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance ## Myoclonic epilepsy with ragged-red fibers (MERRF) Mutations in MT-TT have been associated with myoclonic epilepsy with ragged-red fibers (MERRF), and cause mitochondrial energy deficiencies and reduced proliferation leading to oxidative phosphorylation. Myoclonic epilepsy with ragged-red fibers (MERRF) is a rare mitochondrial disorder that affects many parts of the body, particularly the muscles and nervous system. In most cases, the signs and symptoms of this disorder appear during childhood or adolescence. The features of MERRF vary widely among affected individuals, even among members of the same family. Common clinical manifestations include myoclonus, myopathy, spasticity,epilepsy, peripheral neuropathy, dementia, ataxia, atrophy and more.[4][5] In addition, mutations have also been linked to lethal infantile mitochondrial myopathy, Parkinson's disease associated with a 15950G>A mutation[6], and a 15923A>G mutation found to result in an unconfirmed heart disease.[7][8] ## Cytochrome c oxidase deficiency MT-TT mutations result in complex IV deficiency of the mitochondrial respiratory chain, also known as the cytochrome c oxidase deficiency. Cytochrome c oxidase deficiency is a rare genetic condition that can affect multiple parts of the body, including skeletal muscles, the heart, the brain, or the liver. Common clinical manifestations include myopathy, hypotonia, and encephalomyopathy, lactic acidosis, and hypertrophic cardiomyopathy.[9] A 15915G>A mutation was found in a patient with cytochrome c oxidase deficiency with accompany symptoms of seizures, progressive hearing loss and muscle weakness.[10]	https://www.wikidoc.org/index.php/MT-TT
7d6477becb0f7f4ce77ed617440008ece36abd25	wikidoc	MT-TW	MT-TW Mitochondrially encoded tRNA tryptophan also known as MT-TW is a transfer RNA which in humans is encoded by the mitochondrial MT-TW gene. # Structure The MT-TW gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 68 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function MT-TW is a small 68 nucleotide RNA (human mitochondrial map position 5512-5579) that transfers the amino acid tryptophan to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance Mutations in MT-TW have been associated with Leigh's syndrome. Leigh's syndrome is a severe neurological disorder that usually becomes apparent in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within two to three years, usually due to respiratory failure. A small number of individuals do not develop symptoms until adulthood or have symptoms that worsen more slowly. A patient with the syndrome associated with a mutation of 5537insT in the MT-TW gene exhibited symptoms of hypotonia, nystagmus, optic atrophy and seizures. Changes in MT-TW which impair oxidate phosphorylation also cause mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). MELAS is a rare mitochondrial disorder known to affect many parts of the body, especially the nervous system and the brain. Symptoms of MELAS include recurrent severe headaches, muscle weakness (myopathy), hearing loss, stroke-like episodes with a loss of consciousness, seizures, and other problems affecting the nervous system. Variants of the gene which cause the disease have included 5556G-A, 5545C-T, and 5521G-A.	MT-TW Mitochondrially encoded tRNA tryptophan also known as MT-TW is a transfer RNA which in humans is encoded by the mitochondrial MT-TW gene.[1] # Structure The MT-TW gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 68 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function MT-TW is a small 68 nucleotide RNA (human mitochondrial map position 5512-5579) that transfers the amino acid tryptophan to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance Mutations in MT-TW have been associated with Leigh's syndrome. Leigh's syndrome is a severe neurological disorder that usually becomes apparent in the first year of life. This condition is characterized by progressive loss of mental and movement abilities (psychomotor regression) and typically results in death within two to three years, usually due to respiratory failure. A small number of individuals do not develop symptoms until adulthood or have symptoms that worsen more slowly.[4] A patient with the syndrome associated with a mutation of 5537insT in the MT-TW gene exhibited symptoms of hypotonia, nystagmus, optic atrophy and seizures.[5] Changes in MT-TW which impair oxidate phosphorylation also cause mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). MELAS is a rare mitochondrial disorder known to affect many parts of the body, especially the nervous system and the brain. Symptoms of MELAS include recurrent severe headaches, muscle weakness (myopathy), hearing loss, stroke-like episodes with a loss of consciousness, seizures, and other problems affecting the nervous system.[6] Variants of the gene which cause the disease have included 5556G-A[7], 5545C-T[8], and 5521G-A.[9]	https://www.wikidoc.org/index.php/MT-TW
c20e712912df6579786829d6a8058a1411230c2b	wikidoc	MT-TY	MT-TY Mitochondrially encoded tRNA tyrosine also known as MT-TY is a transfer RNA which in humans is encoded by the mitochondrial MT-TY gene. # Structure The MT-TY gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 66 base pairs. The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover. # Function MT-TY is a small 66 nucleotide RNA (human mitochondrial map position 5826-5891) that transfers the amino acid tyrosine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance Mutations in MT-TY have been associated with mitochondrial complex III deficiency, a genetic condition that can affect several parts of the body, including the brain, kidneys, liver, heart, and the skeletal muscles.Common clinical manifestations include muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance). Additional symptoms may also arise depending on the severity of the condition. A patient with a mutation of the gene exhibited complex III deficiency, characterized by high levels of cytochrome c oxidase–deficient fibers with symptoms of weakness and fatigue. A 5874A-G mutation was also found in a patient with the condition. Changes in MT-TY may also result in progressive external ophthalmoplegia. Progressive external ophthalmoplegia is characterized by weakness of the eye muscles. Common symptoms of the disorder include hearing loss, loss of sensation in the limbs, ataxia, and neuropathy. A 5885T deletion and 5877G-A substitution have been associated with the disease.	MT-TY Mitochondrially encoded tRNA tyrosine also known as MT-TY is a transfer RNA which in humans is encoded by the mitochondrial MT-TY gene.[1] # Structure The MT-TY gene is located on the p arm of the non-nuclear mitochondrial DNA at position 12 and it spans 66 base pairs.[2] The structure of a tRNA molecule is a distinctive folded structure which contains three hairpin loops and resembles a three-leafed clover.[3] # Function MT-TY is a small 66 nucleotide RNA (human mitochondrial map position 5826-5891) that transfers the amino acid tyrosine to a growing polypeptide chain at the ribosome site of protein synthesis during translation. # Clinical significance Mutations in MT-TY have been associated with mitochondrial complex III deficiency, a genetic condition that can affect several parts of the body, including the brain, kidneys, liver, heart, and the skeletal muscles.Common clinical manifestations include muscle weakness (myopathy) and extreme tiredness (fatigue), particularly during exercise (exercise intolerance). Additional symptoms may also arise depending on the severity of the condition.[4] A patient with a mutation of the gene exhibited complex III deficiency, characterized by high levels of cytochrome c oxidase–deficient fibers with symptoms of weakness and fatigue.[5] A 5874A-G mutation was also found in a patient with the condition.[6] Changes in MT-TY may also result in progressive external ophthalmoplegia. Progressive external ophthalmoplegia is characterized by weakness of the eye muscles. Common symptoms of the disorder include hearing loss, loss of sensation in the limbs, ataxia, and neuropathy.[7] A 5885T deletion[8] and 5877G-A substitution[9] have been associated with the disease.	https://www.wikidoc.org/index.php/MT-TY
1ad0a212ba4d478e443db3f42ddd3d77cc45631e	wikidoc	MTCH1	MTCH1 Mitochondrial carrier homolog 1 (MTCH1), also referred to as presenilin 1-associated protein (PSAP), is a protein that in humans is encoded by the MTCH1 gene on chromosome 6. MTCH1 is a proapoptotic mitochondrial protein potentially involved in Alzheimer’s disease (AD). # Structure The protein encoded by this gene is named for its structural resemblance to the members of the mitochondrial carrier protein family. The MTCH1 gene contains 12 exons and produces four isoforms. These isoforms arise from alternative splicing of exon 8 and two potential start codons, which results in the deletion of 17 amino acid residues in the hydrophilic loop between two transmembrane domains of some isoforms. Though they differ in sequence and length, the four isoforms still share a similar topological structure, including six transmembrane domains, one of which is responsible for localization to the outer mitochondrial membrane (OMM), and two N-terminal apoptotic domains. As a result, all four isoforms retain these apoptotic domains and mitochondrial localization, both of which are required for the protein’s proapoptotic function. # Function MTCH1 is a proapoptotic protein that localizes to the OMM and induces apoptosis independently of BAX and BAK. One possible mechanism proposes that its interactions with the mitochondrial permeability transition pore (MPTP) complex leads to depolarization of the mitochondrial membrane, release of cytochrome C, and activation of caspase-3. Expression of this protein is observed in 16 different tissue types, indicating that the protein may serve a housekeeping function. # Clinical Significance MTCH1 may be associated with AD and other neurodegenerative and neuroinflammatory diseases through its close interaction with presenilin. However, more research is required to confirm its clinical involvement. # Interactions MTCH1 has been shown to interact with PS1.	MTCH1 Mitochondrial carrier homolog 1 (MTCH1), also referred to as presenilin 1-associated protein (PSAP), is a protein that in humans is encoded by the MTCH1 gene on chromosome 6.[1][2][3] MTCH1 is a proapoptotic mitochondrial protein potentially involved in Alzheimer’s disease (AD).[2][3][4] # Structure The protein encoded by this gene is named for its structural resemblance to the members of the mitochondrial carrier protein family.[1][3] The MTCH1 gene contains 12 exons and produces four isoforms. These isoforms arise from alternative splicing of exon 8 and two potential start codons, which results in the deletion of 17 amino acid residues in the hydrophilic loop between two transmembrane domains of some isoforms.[5][6] Though they differ in sequence and length, the four isoforms still share a similar topological structure, including six transmembrane domains, one of which is responsible for localization to the outer mitochondrial membrane (OMM), and two N-terminal apoptotic domains. As a result, all four isoforms retain these apoptotic domains and mitochondrial localization, both of which are required for the protein’s proapoptotic function.[3][5][6] # Function MTCH1 is a proapoptotic protein that localizes to the OMM and induces apoptosis independently of BAX and BAK.[2][3] One possible mechanism proposes that its interactions with the mitochondrial permeability transition pore (MPTP) complex leads to depolarization of the mitochondrial membrane, release of cytochrome C, and activation of caspase-3.[1][3] Expression of this protein is observed in 16 different tissue types, indicating that the protein may serve a housekeeping function.[6] # Clinical Significance MTCH1 may be associated with AD and other neurodegenerative and neuroinflammatory diseases through its close interaction with presenilin.[1][4] However, more research is required to confirm its clinical involvement.[4] # Interactions MTCH1 has been shown to interact with PS1.[1]	https://www.wikidoc.org/index.php/MTCH1
b8d31b29eb9ff2f9b6ed755661754b10bc3a8355	wikidoc	MTFMT	MTFMT Mitochondrial methionyl-tRNA formyltransferase is a protein that in humans is encoded by the MTFMT gene. The protein encoded by this nuclear gene localizes to the mitochondrion, where it catalyzes the formylation of methionyl-tRNA. Recessive-type mutations in MTFMT have been shown to cause mitochondrial disease. # Model organisms Model organisms have been used in the study of MTFMT function. A conditional knockout mouse line, called Mtfmttm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty six tests were carried out on mutant mice and two significant abnormalities were observed. During gestation homozygous mutant embryos displayed lethal growth retardation and oedema. In a separate study, no homozygous animals were observed at weaning. The remaining tests were carried out on adult heterozygous mutant animals, but no further abnormalities were seen.	MTFMT Mitochondrial methionyl-tRNA formyltransferase is a protein that in humans is encoded by the MTFMT gene.[1] The protein encoded by this nuclear gene localizes to the mitochondrion, where it catalyzes the formylation of methionyl-tRNA.[1] Recessive-type mutations in MTFMT have been shown to cause mitochondrial disease.[2] # Model organisms Model organisms have been used in the study of MTFMT function. A conditional knockout mouse line, called Mtfmttm1a(KOMP)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[9][10][11] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty six tests were carried out on mutant mice and two significant abnormalities were observed.[5] During gestation homozygous mutant embryos displayed lethal growth retardation and oedema. In a separate study, no homozygous animals were observed at weaning. The remaining tests were carried out on adult heterozygous mutant animals, but no further abnormalities were seen.[5]	https://www.wikidoc.org/index.php/MTFMT
cf49749b1267ea5bffccf8daba588dc5f6adde25	wikidoc	MTUS1	MTUS1 Mitochondrial tumor suppressor 1 (MTSG1) or Microtubule-Associated Scaffold Protein 1 (MTUS1) is a candidate tumor suppressor protein encoded by the MTUS1 gene in humans. Expression levels of MTUS1 was reported to be lost in various types of human malignancies such as colon, ovarian, head-and-neck, pancreas, breast cancers, bladder, gastric, and lung cancers. # Proteins encoded by MTUS1 As a result of alternative splicing MTUS1 was shown to encode 5 different protein isoforms as listed as ATIP1, ATIP2, ATIP3a, ATIP3b and ATIP4. ATIP3a and ATIP3b was generally considered as ATIP3 and ATIP1 and ATIP3 is the major splice variants encoded by MTUS1 gene. # Function This gene encodes a protein which contains a C-terminal domain able to interact with the angiotensin II receptor type 2 (AT2) and a large coiled-coil region allowing dimerization. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the transcript variants has been shown to encode a mitochondrial protein that acts as a tumor suppressor and participates in AT2 signaling pathways. Other variants may encode nuclear or transmembrane proteins but it has not been determined whether they also participate in AT2 signaling pathways. # Interactions MTUS1 has been shown to interact with Angiotensin II receptor type 2.	MTUS1 Mitochondrial tumor suppressor 1 (MTSG1) or Microtubule-Associated Scaffold Protein 1 (MTUS1) is a candidate tumor suppressor protein encoded by the MTUS1 gene in humans.[1][2] Expression levels of MTUS1 was reported to be lost in various types of human malignancies such as colon, ovarian, head-and-neck, pancreas, breast cancers, bladder, gastric, and lung cancers.[3][4] # Proteins encoded by MTUS1 As a result of alternative splicing MTUS1 was shown to encode 5 different protein isoforms as listed as ATIP1, ATIP2, ATIP3a, ATIP3b and ATIP4. ATIP3a and ATIP3b was generally considered as ATIP3 and ATIP1 and ATIP3 is the major splice variants encoded by MTUS1 gene.[5] # Function This gene encodes a protein which contains a C-terminal domain able to interact with the angiotensin II receptor type 2 (AT2) and a large coiled-coil region allowing dimerization. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the transcript variants has been shown to encode a mitochondrial protein that acts as a tumor suppressor and participates in AT2 signaling pathways. Other variants may encode nuclear or transmembrane proteins but it has not been determined whether they also participate in AT2 signaling pathways.[6] # Interactions MTUS1 has been shown to interact with Angiotensin II receptor type 2.[7]	https://www.wikidoc.org/index.php/MTUS1
dbfaa7f6e77b6fb6cf0382283e9a4e1693b147a9	wikidoc	MUS81	MUS81 Crossover junction endonuclease MUS81 is an enzyme that in humans is encoded by the MUS81 gene. In mammalian somatic cells, MUS81 and another structure specific DNA endonuclease, XPF (ERCC4), play overlapping and essential roles in completion of homologous recombination. The significant overlap in function between these enzymes is most likely related to processing joint molecules such as D-loops and nicked Holliday junctions. # Meiosis MUS81 is a component of a minor chromosomal crossover (CO) pathway in the meiosis of budding yeast, plants and vertebrates. However, in the protozoan Tetrahymena thermophila, MUS81 appears to be part of an essential (if not the predominant) CO pathway. The MUS81 pathway also appears to be the predominant CO pathway in the fission yeast Schizosaccharomyces pombe. The relationship of the CO pathway to the overall process of meiotic recombination is illustrated in the accompanying diagram. Recombination during meiosis is often initiated by a DNA double-strand break (DSB). During recombination, sections of DNA at the 5' ends of the break are cut away in a process called resection. In the strand invasion step that follows, an overhanging 3' end of the broken DNA molecule "invades" the DNA of an homologous chromosome that is not broken forming a displacement loop (D-loop). After strand invasion, the further sequence of events may follow either of two main pathways, leading to a crossover (CO) or a non-crossover (NCO) recombinant (see Genetic recombination). The pathway leading to a CO involves a double Holliday junction (DHJ) intermediate. Holliday junctions need to be resolved for CO recombination to be completed. MU81-MMS4, in the budding yeast Saccharomyces cerevisiae, is a DNA structure-selective endonuclease that cleaves joint DNA molecules formed during homologous recombination in meiosis and mitosis. The MUS81-MMS4 endonuclease, although a minor resolvase for CO formation in S. cerevisiae, is crucial for limiting chromosome entanglements by suppressing multiple consecutive recombination events from initiating from the same DSB. Mus81 deficient mice have significant meiotic defects including the failure to repair a subset of DSBs. # Interactions MUS81 has been shown to interact with CHEK2.	MUS81 Crossover junction endonuclease MUS81 is an enzyme that in humans is encoded by the MUS81 gene.[1][2][3] In mammalian somatic cells, MUS81 and another structure specific DNA endonuclease, XPF (ERCC4), play overlapping and essential roles in completion of homologous recombination.[4] The significant overlap in function between these enzymes is most likely related to processing joint molecules such as D-loops and nicked Holliday junctions.[4] # Meiosis MUS81 is a component of a minor chromosomal crossover (CO) pathway in the meiosis of budding yeast, plants and vertebrates.[5] However, in the protozoan Tetrahymena thermophila, MUS81 appears to be part of an essential (if not the predominant) CO pathway.[5] The MUS81 pathway also appears to be the predominant CO pathway in the fission yeast Schizosaccharomyces pombe.[5] The relationship of the CO pathway to the overall process of meiotic recombination is illustrated in the accompanying diagram. Recombination during meiosis is often initiated by a DNA double-strand break (DSB). During recombination, sections of DNA at the 5' ends of the break are cut away in a process called resection. In the strand invasion step that follows, an overhanging 3' end of the broken DNA molecule "invades" the DNA of an homologous chromosome that is not broken forming a displacement loop (D-loop). After strand invasion, the further sequence of events may follow either of two main pathways, leading to a crossover (CO) or a non-crossover (NCO) recombinant (see Genetic recombination). The pathway leading to a CO involves a double Holliday junction (DHJ) intermediate. Holliday junctions need to be resolved for CO recombination to be completed. MU81-MMS4, in the budding yeast Saccharomyces cerevisiae, is a DNA structure-selective endonuclease that cleaves joint DNA molecules formed during homologous recombination in meiosis and mitosis.[6] The MUS81-MMS4 endonuclease, although a minor resolvase for CO formation in S. cerevisiae, is crucial for limiting chromosome entanglements by suppressing multiple consecutive recombination events from initiating from the same DSB.[7] Mus81 deficient mice have significant meiotic defects including the failure to repair a subset of DSBs.[8] # Interactions MUS81 has been shown to interact with CHEK2.[1]	https://www.wikidoc.org/index.php/MUS81
9a5e5ad2983027a99f19e3cdcd9298d786fd3291	wikidoc	MUTED	MUTED Protein Muted homolog is a protein that in humans is encoded by the MUTED gene. # Function This gene encodes a component of BLOC-1 (biogenesis of lysosome-related organelles complex 1). Components of this complex are involved in the biogenesis of organelles such as melanosomes and platelet-dense granules. A mouse model for Hermansky–Pudlak syndrome is mutated in the murine version of this gene. Some transcripts of the downstream gene TXNDC5 overlap this gene, but they do not contain an open reading frame for this gene. # Interactions MUTED has been shown to interact with BLOC1S2, Dysbindin and PLDN.	MUTED Protein Muted homolog is a protein that in humans is encoded by the MUTED gene.[1][2] # Function This gene encodes a component of BLOC-1 (biogenesis of lysosome-related organelles complex 1). Components of this complex are involved in the biogenesis of organelles such as melanosomes and platelet-dense granules. A mouse model for Hermansky–Pudlak syndrome is mutated in the murine version of this gene. Some transcripts of the downstream gene TXNDC5 overlap this gene, but they do not contain an open reading frame for this gene.[2] # Interactions MUTED has been shown to interact with BLOC1S2,[3] Dysbindin[3] and PLDN.[3][4]	https://www.wikidoc.org/index.php/MUTED
41c8fe78ede35377dc185addffcf8210d52f979d	wikidoc	MUTYH	MUTYH MUTYH (mutY DNA glycosylase) is a human gene that encodes a DNA glycosylase, MUTYH glycosylase. It is involved in oxidative DNA damage repair and is part of the base excision repair pathway. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a common form of oxidative DNA damage. The protein is localized to the nucleus and mitochondria. Mutations in this gene result in heritable predisposition to colon and stomach cancer. Multiple transcript variants encoding different isoforms have been found for this gene. # Location & Structure MUTYH has its locus on the short (p) arm of chromosome 1 (1p34.1), from base pair 45,464,007 to base pair 45,475,152 (45,794,835-45,806,142). The gene is composed of 16 exons and has a size of 546 amino acids. and is approximately 7.1kb. The presence of disulfide crosslinking gives rise to a complex crystal structure of the MUTY-DNA. The protein structure of the MUTYH gene has its N- terminal on the 5’ and the C-terminal on the 3’. Within the N-terminal. There is an helix-hairpin-helix and pseudo helix-hairpin-helix contained within the N-terminal, in addition to and iron cluster motif # Mechanism Repair of oxidative DNA damage is the result of a collaborative effort of MUTYH, OGG1, and MTH1. MUTYH gene acts on the adenine base that have an A to 8-oxoG pairing while OGG1 (on chromosome 3 (3p26.2) part of the base excision repair pathway) detects and acts on 8-oxoG, thereby removing it. The resultant effect of the action of the genes results in correction of transversion mutations made by the incorrect G:C, T:A pairing. TP53 transcriptionally regulates MUTYH and it can be surmised that it may potentially act as a regulator for p53. # Expression MUTYH is overexpressed in CD4-T cells, the prostate, the colon and the rectum. There is evidence of MUTYH expression in kidney, intestinal, nervous system and muscle tissues. # Protein interactions MUTYH has been shown to interact with Replication protein A1, PCNA and APEX1. The excision of the bases causes the formation of an apurinic/ apyrimidinic (AP site) gap. These gap sites are mutagenic in nature and require constant and immediate emendation and this is achieved by the active involvement of protein complexes that repair the AP gap site via short and long patch repair pathways. The short patch repair pathway employs POLB (DNA polymerase beta), APE1, XRCC1, PARP1 with the addition of either the LIG1 or LIG3 genes. When an insertion of one nucleotide occurs, the enzyme AP endonuclease (APEX/APE1) cuts out the mismatched base pairs at the AP site and this causes the evolvement of 5’dRP (5’ deoxyribose phosphate), a terminal blocking group, and 3’-OH ( 3’ hydroxyl end). POLB is required to remove the 5’dRP, and it does this by enzymatic activity, namely polymerase and dRP lyase. DNA ligase is used to seal the fragments after dRP excision causes the formation of 5’PO4 that is necessary to form the phosphodiester bonds of DNA. The purpose of PARP1 and XRCC1 in the single strand break repair pathway, is to stabilize the strands of DNA while they undergo repair, synthesis, gap-filling and ligation. PARP1 acts as a recruit agent for XRCC1. The nick sealing of the strands is accomplished by the formation of LIG1 (DNA ligase 1) and/or LIG3/ XRCCI complex that attach to processed end of the corrected strands and reinstate the original conformation of the strand. Long patch repair comes into play when more nucleotides are involved, ranging from 2 to 12. It is hypothesized that Polymerase 𝜹 (POLD) and Polymerase 𝛆 (POLE), assisted by the PCNA (proliferating cell nuclear antigen) in conjunction with replication factor C (RFC) that acts as a stabilizer and places newly synthesized nucleotides on the DNA strand. Both the polymerases repair the DNA by employing the strand displacement synthesis mechanism. This mechanism occurs downstream a DNA strand and the 5’ is transformed into a “flap intermediate” causing it to be “displaced”. FEN1 ( flap structure-specific endonuclease 1), a nuclease, removes the displaced strand and this results in a ligatable strand of DNA.Long patch repair, like short patch repair, includes the use of APE1 and PARP1 and LIG1. The repair pathway is partially determined by the amount of ATP present after the removal of the deoxyribose phosphate end. The long patch repair pathway is preferred under conditions of low ATP concentration while the short repair pathway is preferred under high concentrations of ATP. Other notable interactions include MUTYH and Replication protein A is a single strand binding protein that prevents the annealing of DNA during replication, it also plays a role as an activator for damage repair on DNA. There is a hypothetical relation between the interaction of Mismatch Repair proteins (MMR) such as MSH 2,3 and 6, MLH1, PMS1 and 2, and MUTYH in which the proposed result of their partnering is to increase susceptibility to cancer. # Chemical interactions The gene interacts with the following chemicals: a) Carbon tetrachloride : decreased expression of MUTYH mRNA b) Ethanol: When treated together with dronabinol) increased expression of MUTYH mRNA. When used alone, it has conflicting results of decreased and increased the MUTYH mRNA. c) Ethinylestradiol: When used alone it results in the increased expression of MUTYH mRNA.When treated together with tetrachlorodibenzo p dioxin, there is increased expression of MUTYH mRNA. d) Tamoxifen: affects MUTYH # Related conditions The table of the Gene-phenotype associations summarizes the diseases/conditions that arise from mutations in MUTYH Mutations in the MUTYH gene cause an autosomal recessive disorder similar to familial adenomatous polyposis (also called MUTYH-associated polyposis). Polyps caused by mutated MUTYH do not appear until adulthood and are less numerous than those found in patients with APC gene mutations. Both copies of the MYH gene are mutated in individuals who have autosomal recessive familial adenomatous polyposis i.e., the mutations for the MUTYH gene is biallelic .Mutations in this gene affect the ability of cells to correct mistakes made during DNA replication. Both copies of the MYH gene are mutated in individuals who have autosomal recessive familial adenomatous polyposis. Most reported mutations in this gene cause production of a nonfunctional or low functioning glycosylase enzyme. When base excision repair in the cell is compromised, mutations in other genes build up, leading to cell overgrowth and possibly tumor formation. The two most common mutations in Caucasian Europeans are exchanges of amino acids (the building blocks of proteins) in the enzyme. One mutation replaces the amino acid tyrosine with cysteine at position 179 (also written as p.Tyr179Cys (p.Y179C) or, when describing the nucleotide change, written as c.536A>G) The other common mutation switches the amino acid glycine with aspartic acid at position 396 (also written as p.Gly396Asp(G396D)or c.1187G>A) The association of the gene with gastric cancer is somewhat indirect and multifactorial. When a subject is infected with Helicobacter pylori (H.pylori), the bacteria cause the formation of free oxygen radicals that are present in the gastric mucosa and this increases the propensity of the genes to incur oxidative damage . A study of 95 cases of patients who had sporadic cancers, initiated by the presence of H.pylori, and two of the 95 patients had biallelic mutation of the MUTYH gene. The somatic missense mutations for the first identified cancer occurred at codon 391, in which there was a change in the nucleotide bases from CCG ( codon for amino acid proline) to TCG ( codon for amino acid serine), while the second cancer had a nucleotide base change at codon 400 from CAG ( codon for amino acid glutamine) to GGG( codon for amino acid arginine). The mutations were found to be highly conserved in the Nudix hydrolase domain of MUTYH. These amino acid mutations provide the basis for the somatic mutations in the gastric system. Pilomatricoma has been noted in a case that concerned two siblings who were the offspring of consanguineous parents. The siblings had a 2 base pair homozygous insertion on the MUTYH gene ( exon 13). Consequently, a frameshift occurred due to the insertion and a premature stop codon was read at 438 on the gene. Pilomatricoma was the phenotypic manifestation of this mutation. One of the siblings was also found to have rectal adenocarcinoma. It is worthy to note that CTNNB1, a gene associated with pilomatricoma, was also investigated. However, no mutations in this gene were found, thereby dismissing it as a possible cause for this case. There is an established correlation between aging and the elevation 8-oxoG concentrations, particularly in organs that exhibit reduced cell proliferation such as the kidneys, liver, brain and lungs. Presence of 8-oxoG also occurs in large concentrations in patients with neurological conditions such as Alzheimer’s, Parkinson’s and Huntington’s disease. MUTYH causes immoderate formation of single stranded breaks via base excision repair, under acute oxidative stress conditions. When the 8-oxoguanine species accumulate and increase in concentration in the neurons, MUTYH responds by triggering their degeneration.	MUTYH MUTYH (mutY DNA glycosylase) is a human gene that encodes a DNA glycosylase, MUTYH glycosylase. It is involved in oxidative DNA damage repair and is part of the base excision repair pathway. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a common form of oxidative DNA damage. The protein is localized to the nucleus and mitochondria. Mutations in this gene result in heritable predisposition to colon and stomach cancer. Multiple transcript variants encoding different isoforms have been found for this gene.[1] # Location & Structure MUTYH has its locus on the short (p) arm of chromosome 1 (1p34.1), from base pair 45,464,007 to base pair 45,475,152 (45,794,835-45,806,142). The gene is composed of 16 exons and has a size of 546 amino acids.[2] and is approximately 7.1kb.[3] The presence of disulfide crosslinking gives rise to a complex crystal structure of the MUTY-DNA.[4] The protein structure of the MUTYH gene has its N- terminal on the 5’ and the C-terminal on the 3’. Within the N-terminal. There is an helix-hairpin-helix and pseudo helix-hairpin-helix contained within the N-terminal, in addition to and iron cluster motif # Mechanism Repair of oxidative DNA damage is the result of a collaborative effort of MUTYH, OGG1, and MTH1. MUTYH gene acts on the adenine base that have an A to 8-oxoG pairing while OGG1 (on chromosome 3 (3p26.2) part of the base excision repair pathway) detects and acts on 8-oxoG, thereby removing it.[5][6] The resultant effect of the action of the genes results in correction of transversion mutations made by the incorrect G:C, T:A pairing. TP53 transcriptionally regulates MUTYH and it can be surmised that it may potentially act as a regulator for p53.[7] # Expression MUTYH is overexpressed in CD4-T cells, the prostate, the colon and the rectum. There is evidence of MUTYH expression in kidney, intestinal, nervous system and muscle tissues.[2] # Protein interactions MUTYH has been shown to interact with Replication protein A1,[8] PCNA[8] and APEX1.[8] The excision of the bases causes the formation of an apurinic/ apyrimidinic (AP site) gap. These gap sites are mutagenic in nature and require constant and immediate emendation and this is achieved by the active involvement of protein complexes that repair the AP gap site via short and long patch repair pathways. The short patch repair pathway employs POLB (DNA polymerase beta), APE1, XRCC1, PARP1 with the addition of either the LIG1 or LIG3 genes. When an insertion of one nucleotide occurs, the enzyme AP endonuclease (APEX/APE1) cuts out the mismatched base pairs at the AP site and this causes the evolvement of 5’dRP (5’ deoxyribose phosphate), a terminal blocking group, and 3’-OH ( 3’ hydroxyl end). POLB is required to remove the 5’dRP, and it does this by enzymatic activity, namely polymerase and dRP lyase. DNA ligase is used to seal the fragments after dRP excision causes the formation of 5’PO4 that is necessary to form the phosphodiester bonds of DNA. The purpose of PARP1 and XRCC1 in the single strand break repair pathway, is to stabilize the strands of DNA while they undergo repair, synthesis, gap-filling and ligation. PARP1 acts as a recruit agent for XRCC1. The nick sealing of the strands is accomplished by the formation of LIG1 (DNA ligase 1) and/or LIG3/ XRCCI complex that attach to processed end of the corrected strands and reinstate the original conformation of the strand. Long patch repair comes into play when more nucleotides are involved, ranging from 2 to 12. It is hypothesized that Polymerase 𝜹 (POLD) and Polymerase 𝛆 (POLE), assisted by the PCNA (proliferating cell nuclear antigen) in conjunction with replication factor C (RFC) that acts as a stabilizer and places newly synthesized nucleotides on the DNA strand. Both the polymerases repair the DNA by employing the strand displacement synthesis mechanism. This mechanism occurs downstream a DNA strand and the 5’ is transformed into a “flap intermediate” causing it to be “displaced”. FEN1 ( flap structure-specific endonuclease 1), a nuclease, removes the displaced strand and this results in a ligatable strand of DNA.Long patch repair, like short patch repair, includes the use of APE1 and PARP1 and LIG1. The repair pathway is partially determined by the amount of ATP present after the removal of the deoxyribose phosphate end. The long patch repair pathway is preferred under conditions of low ATP concentration while the short repair pathway is preferred under high concentrations of ATP.[9] Other notable interactions include MUTYH and Replication protein A is a single strand binding protein that prevents the annealing of DNA during replication, it also plays a role as an activator for damage repair on DNA. There is a hypothetical relation between the interaction of Mismatch Repair proteins (MMR) such as MSH 2,3 and 6, MLH1, PMS1 and 2, and MUTYH in which the proposed result of their partnering is to increase susceptibility to cancer.[10] # Chemical interactions The gene interacts with the following chemicals: a) Carbon tetrachloride : decreased expression of MUTYH mRNA b) Ethanol: When treated together with dronabinol) increased expression of MUTYH mRNA. When used alone, it has conflicting results of decreased and increased the MUTYH mRNA. c) Ethinylestradiol: When used alone it results in the increased expression of MUTYH mRNA.When treated together with tetrachlorodibenzo p dioxin, there is increased expression of MUTYH mRNA. d) Tamoxifen: affects MUTYH [11] # Related conditions The table of the Gene-phenotype associations summarizes the diseases/conditions that arise from mutations in MUTYH Mutations in the MUTYH gene cause an autosomal recessive disorder similar to familial adenomatous polyposis (also called MUTYH-associated polyposis). Polyps caused by mutated MUTYH do not appear until adulthood and are less numerous than those found in patients with APC gene mutations. Both copies of the MYH gene are mutated in individuals who have autosomal recessive familial adenomatous polyposis i.e., the mutations for the MUTYH gene is biallelic .Mutations in this gene affect the ability of cells to correct mistakes made during DNA replication. Both copies of the MYH gene are mutated in individuals who have autosomal recessive familial adenomatous polyposis. Most reported mutations in this gene cause production of a nonfunctional or low functioning glycosylase enzyme. When base excision repair in the cell is compromised, mutations in other genes build up, leading to cell overgrowth and possibly tumor formation. The two most common mutations in Caucasian Europeans are exchanges of amino acids (the building blocks of proteins) in the enzyme. One mutation replaces the amino acid tyrosine with cysteine at position 179 (also written as p.Tyr179Cys (p.Y179C) or, when describing the nucleotide change, written as c.536A>G) The other common mutation switches the amino acid glycine with aspartic acid at position 396 (also written as p.Gly396Asp(G396D)or c.1187G>A) The association of the gene with gastric cancer is somewhat indirect and multifactorial. When a subject is infected with Helicobacter pylori (H.pylori), the bacteria cause the formation of free oxygen radicals that are present in the gastric mucosa and this increases the propensity of the genes to incur oxidative damage . A study of 95 cases of patients who had sporadic cancers, initiated by the presence of H.pylori, and two of the 95 patients had biallelic mutation of the MUTYH gene. The somatic missense mutations for the first identified cancer occurred at codon 391, in which there was a change in the nucleotide bases from CCG ( codon for amino acid proline) to TCG ( codon for amino acid serine), while the second cancer had a nucleotide base change at codon 400 from CAG ( codon for amino acid glutamine) to GGG( codon for amino acid arginine). The mutations were found to be highly conserved in the Nudix hydrolase domain of MUTYH. These amino acid mutations provide the basis for the somatic mutations in the gastric system.[15] Pilomatricoma has been noted in a case that concerned two siblings who were the offspring of consanguineous parents. The siblings had a 2 base pair homozygous insertion on the MUTYH gene ( exon 13). Consequently, a frameshift occurred due to the insertion and a premature stop codon was read at 438 on the gene. Pilomatricoma was the phenotypic manifestation of this mutation. One of the siblings was also found to have rectal adenocarcinoma. It is worthy to note that CTNNB1, a gene associated with pilomatricoma, was also investigated. However, no mutations in this gene were found, thereby dismissing it as a possible cause for this case.[16] There is an established correlation between aging and the elevation 8-oxoG concentrations, particularly in organs that exhibit reduced cell proliferation such as the kidneys, liver, brain and lungs.[17] Presence of 8-oxoG also occurs in large concentrations in patients with neurological conditions such as Alzheimer’s, Parkinson’s and Huntington’s disease.[18] MUTYH causes immoderate formation of single stranded breaks via base excision repair, under acute oxidative stress conditions.[19][20] When the 8-oxoguanine species accumulate and increase in concentration in the neurons, MUTYH responds by triggering their degeneration.[21]	https://www.wikidoc.org/index.php/MUTYH
ae8e8ac0def66a8a21863dd7192701cf5ca73397	wikidoc	MXRA5	MXRA5 Matrix-remodelling associated 5 is a protein in humans that is encoded by the MXRA5 gene. # Function This gene encodes one of the matrix-remodelling associated proteins. This protein contains 7 leucine-rich repeats and 12 immunoglobulin-like C2-type domains related to perlecan. This gene has a pseudogene on chromosome Y. # Clinical relevance Mutations in this gene have been seen frequently mutated in cases of non-small cell lung carcinoma.	MXRA5 Matrix-remodelling associated 5 is a protein in humans that is encoded by the MXRA5 gene.[1] # Function This gene encodes one of the matrix-remodelling associated proteins. This protein contains 7 leucine-rich repeats and 12 immunoglobulin-like C2-type domains related to perlecan. This gene has a pseudogene on chromosome Y.[1] # Clinical relevance Mutations in this gene have been seen frequently mutated in cases of non-small cell lung carcinoma.[2]	https://www.wikidoc.org/index.php/MXRA5
84ddc354bf573d5759311da88f474dd876c43c3a	wikidoc	MYCBP	MYCBP C-Myc-binding protein is a protein that in humans is encoded by the MYCBP gene. # Function The MYCBP gene encodes a protein that binds to the N-terminal region of MYC (MIM 190080) and stimulates the activation of E box-dependent transcription by MYC. # Interactions MYCBP has been shown to interact with AKAP1, C3orf15 and Myc.	MYCBP C-Myc-binding protein is a protein that in humans is encoded by the MYCBP gene.[1][2] # Function The MYCBP gene encodes a protein that binds to the N-terminal region of MYC (MIM 190080) and stimulates the activation of E box-dependent transcription by MYC.[supplied by OMIM][2] # Interactions MYCBP has been shown to interact with AKAP1,[3][4] C3orf15[3] and Myc.[1]	https://www.wikidoc.org/index.php/MYCBP
4d2a47ceb24fbbff1b351ad5d179b90c7843e7a9	wikidoc	MYD88	MYD88 Myeloid differentiation primary response 88 (MYD88) is a protein that, in humans, is encoded by the MYD88 gene. # Model organisms Model organisms have been used in the study of MYD88 function. The gene was originally discovered and cloned by Dan Liebermann and Barbara Hoffman in mice. In that species it is a universal adapter protein as it is used by almost all TLRs (except TLR 3) to activate the transcription factor NF-κB. Mal (also known as TIRAP) is necessary to recruit Myd88 to TLR 2 and TLR 4, and MyD88 then signals through IRAK. It also interacts functionally with amyloid formation and behavior in a transgenic mouse model of Alzheimer's disease. A conditional knockout mouse line, called Myd88tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty-one tests were carried out on homozygous mutant animals, revealing one abnormality: male mutants had an increased susceptibility to bacterial infection. # Function The MYD88 gene provides instructions for making a protein involved in signaling within immune cells. The MyD88 protein acts as an adapter, connecting proteins that receive signals from outside the cell to the proteins that relay signals inside the cell. The human ortholog MYD88 seems to function similarly to mice, since the immunological phenotype of human cells deficient in MYD88 is similar to cells from MyD88 deficient mice. However, available evidence suggests that MYD88 is dispensable for human resistance to common viral infections and to all but a few pyogenic bacterial infections, demonstrating a major difference between mouse and human immune responses. Mutation in MYD88 at position 265 leading to a change from leucine to proline have been identified in many human lymphomas including ABC subtype of diffuse large B-cell lymphoma and Waldenstrom's macroglobulinemia. # Interactions Myd88 has been shown to interact with: - IRAK1 - IRAK2 - Interleukin 1 receptor, type I - RAC1 - TLR 4 # Gene polymorphisms Various single nucleotide polymorphisms (SNPs) of the MyD88 have been identified. and for some of them an association with susceptibility to various infectious diseases and to some autoimmune diseases like ulcerative colitis was found.	MYD88 Myeloid differentiation primary response 88 (MYD88) is a protein that, in humans, is encoded by the MYD88 gene.[1][2] # Model organisms Model organisms have been used in the study of MYD88 function. The gene was originally discovered and cloned by Dan Liebermann and Barbara Hoffman in mice.[3] In that species it is a universal adapter protein as it is used by almost all TLRs (except TLR 3) to activate the transcription factor NF-κB. Mal (also known as TIRAP) is necessary to recruit Myd88 to TLR 2 and TLR 4, and MyD88 then signals through IRAK.[4] It also interacts functionally with amyloid formation and behavior in a transgenic mouse model of Alzheimer's disease.[5] A conditional knockout mouse line, called Myd88tm1a(EUCOMM)Wtsi[9][10] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[11][12][13] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][14] Twenty-one tests were carried out on homozygous mutant animals, revealing one abnormality: male mutants had an increased susceptibility to bacterial infection. # Function The MYD88 gene provides instructions for making a protein involved in signaling within immune cells. The MyD88 protein acts as an adapter, connecting proteins that receive signals from outside the cell to the proteins that relay signals inside the cell. The human ortholog MYD88 seems to function similarly to mice, since the immunological phenotype of human cells deficient in MYD88 is similar to cells from MyD88 deficient mice. However, available evidence suggests that MYD88 is dispensable for human resistance to common viral infections and to all but a few pyogenic bacterial infections, demonstrating a major difference between mouse and human immune responses.[15] Mutation in MYD88 at position 265 leading to a change from leucine to proline have been identified in many human lymphomas including ABC subtype of diffuse large B-cell lymphoma[16] and Waldenstrom's macroglobulinemia.[17] # Interactions Myd88 has been shown to interact with: - IRAK1[18][19][20][21] - IRAK2[18][22][19] - Interleukin 1 receptor, type I[23][22] - RAC1[24] - TLR 4[25][26][27][18] # Gene polymorphisms Various single nucleotide polymorphisms (SNPs) of the MyD88 have been identified. and for some of them an association with susceptibility to various infectious diseases[28] and to some autoimmune diseases like ulcerative colitis was found.[29]	https://www.wikidoc.org/index.php/MYD88
f7801dd1ba519ba9d0c47932654e13ef13b30165	wikidoc	MYH10	MYH10 Myosin-10 also known as myosin heavy chain 10 or non-muscle myosin IIB (NM-IIB) is a protein that in humans is encoded by the MYH10 gene. Non-muscle myosins are expressed in a wide variety of tissues, but NM-IIB is the only non-muscle myosin II isoform expressed in cardiac muscle, where it localizes to adherens junctions within intercalated discs. NM-IIB is essential for normal development of cardiac muscle and for integrity of intercalated discs. Mutations in MYH10 have been identified in patients with left atrial enlargement. # Structure NM-IIB is 228.9 kDa protein composed of 1976 amino acids. NM-IIB has an N-terminal globular head that harbors the catalytically active, magnesium(Mg)-ATPase. The C-terminal rod domain is an alpha helical coiled-coil that can multimerize with other myosin molecules to form a filament. Bound to the neck region of NM-IIB are two light chains; first, MLC17 stabilizes the molecule, while the second light chain, MLC20, modulates contraction. The exception to this rule is the alternatively spliced NM-IIB2 isoform, which has a 21 amino acid inserted into loop 2, near the actin-binding domain; actomyosin MgATPase activity of this isoform is not enhanced by phosphorylation of the regulatory light chain MLC20. NM-IIB is part of the larger myosin II subfamily of proteins, which also includes skeletal muscle, cardiac muscle and smooth muscle myosins. NM-IIB, and non-muscle myosins in general, are widely expressed in every tissue in humans. # Function NM-IIB has many properties that are similar to those of smooth muscle myosins, such as the permissive nature of phosphorylation of the 20 kDa regulatory light chain for contraction. In skeletal muscle and cardiac muscle myosins, contraction is activated through thin filament proteins troponin and tropomyosin, whereas in NM-IIB and smooth muscle myosin, contraction initiates via regulatory light chain (MLC20) phosphorylation. Various functions of NM-IIB require the phosphorylation of the regulatory light chain MLC20, including cell migration and cell adhesion. The two primary kinases catalyzing this reaction are the calcium-calmodulin-dependent, myosin light chain kinase and the Rho-GTP dependent, Rho kinase (ROCK). NM-IIB is dephosphorylated by a myosin phosphatase. Detailed kinetic studies on NM-IIB show that this isoform of non-muscle myosin II has a slower actomyosin ATPase cycle relative to other myosin II isoforms, and that the markedly high affinity of NM-IIB head for ADP as well as the slow rate of ADP release can mechanistically explain affinity this finding. These data indicate that NM-IIB spends a large amount of its kinetic cycle in a configuration where it is strongly attached to actin. NM-IIB, along with the other non-muscle myosin isoforms IIA and IIC, play a role in cell-cell and cell-matrix adhesion, cell migration, cell polarity, and embryonic stem cell apoptosis. Insights into the function of NM-IIB specifically have come from studies employing transgenic animals. NM-IIB is clearly required for normal development of cardiac muscle. Targeted gene disruption of NM-IIB resulted in approximately 65% embryonic lethality, and those that survived suffered from congestive heart failure and died day 1 following birth. Feature observed in NM-IIB knockouts was an increase in the transverse diameters of cardiomyocytes, ventricular septal defects, as well as other muscular abnormalities. NM-IIB is expressed early during embryonic development in cardiomyocytes, and appears to play a role in karyokinesis; ablation of NM-IIB caused defects in chromatid segregation and mitotic spindle formation, as well as abnormal structure of centrosomes. In adult cardiomyocytes, NM-IIB redistributes from a diffuse cytoplasmic pattern in development to a localized Z-disc and intercalated disc distribution, where it colocalizes with alpha-actinin. NM-IIB is the only non-muscle myosin II isoform expressed in adult cardiac muscle (both IIa and IIB are expressed in skeletal muscle Z-discs, suggesting a specific function of NM-IIB in this cell type. NM-IIB may play a role in formation of mature sarcomeres in myofibrils. It appears that NM-IIB plays an essential role in maintaining normal adherens junction integrity and structure. A cardiac muscle-specific knockout of NM-IIB using the alpha-myosin heavy chain promoter-driven cre-recombinase develop enlarged cardiomyocytes, consistent with the defects previously observed with cytokinesis; widened adherens junctions; and progressive hypertrophic cardiomyopathy at 6 months. These data indicate that NM-IIB functions in ensuring the proper maintenance of intercalated disc structures. # Clinical Significance Single nucleotide polymorphisms in MYH10 were detected in patients with left atrial enlargement. MYH10 was identified to be a susceptibility gene using non-biased genome-wide linkage and peak-wide association analysis. # Interactions MYH10 has been shown to interact with: - MYL6 and - MYL9.	MYH10 Myosin-10 also known as myosin heavy chain 10 or non-muscle myosin IIB (NM-IIB) is a protein that in humans is encoded by the MYH10 gene.[1][2] Non-muscle myosins are expressed in a wide variety of tissues, but NM-IIB is the only non-muscle myosin II isoform expressed in cardiac muscle, where it localizes to adherens junctions within intercalated discs. NM-IIB is essential for normal development of cardiac muscle and for integrity of intercalated discs. Mutations in MYH10 have been identified in patients with left atrial enlargement. # Structure NM-IIB is 228.9 kDa protein composed of 1976 amino acids.[3] NM-IIB has an N-terminal globular head that harbors the catalytically active, magnesium(Mg)-ATPase. The C-terminal rod domain is an alpha helical coiled-coil that can multimerize with other myosin molecules to form a filament. Bound to the neck region of NM-IIB are two light chains; first, MLC17 stabilizes the molecule, while the second light chain, MLC20, modulates contraction.[4] The exception to this rule is the alternatively spliced NM-IIB2 isoform, which has a 21 amino acid inserted into loop 2, near the actin-binding domain; actomyosin MgATPase activity of this isoform is not enhanced by phosphorylation of the regulatory light chain MLC20.[5] NM-IIB is part of the larger myosin II subfamily of proteins, which also includes skeletal muscle, cardiac muscle and smooth muscle myosins. NM-IIB, and non-muscle myosins in general, are widely expressed in every tissue in humans. # Function NM-IIB has many properties that are similar to those of smooth muscle myosins, such as the permissive nature of phosphorylation of the 20 kDa regulatory light chain for contraction. In skeletal muscle and cardiac muscle myosins, contraction is activated through thin filament proteins troponin and tropomyosin, whereas in NM-IIB and smooth muscle myosin, contraction initiates via regulatory light chain (MLC20) phosphorylation.[6] Various functions of NM-IIB require the phosphorylation of the regulatory light chain MLC20, including cell migration and cell adhesion. The two primary kinases catalyzing this reaction are the calcium-calmodulin-dependent, myosin light chain kinase and the Rho-GTP dependent, Rho kinase (ROCK). NM-IIB is dephosphorylated by a myosin phosphatase.[7] Detailed kinetic studies on NM-IIB show that this isoform of non-muscle myosin II has a slower actomyosin ATPase cycle relative to other myosin II isoforms, and that the markedly high affinity of NM-IIB head for ADP as well as the slow rate of ADP release can mechanistically explain affinity this finding. These data indicate that NM-IIB spends a large amount of its kinetic cycle in a configuration where it is strongly attached to actin.[8] NM-IIB, along with the other non-muscle myosin isoforms IIA and IIC, play a role in cell-cell and cell-matrix adhesion, cell migration, cell polarity, and embryonic stem cell apoptosis.[9][10] Insights into the function of NM-IIB specifically have come from studies employing transgenic animals. NM-IIB is clearly required for normal development of cardiac muscle. Targeted gene disruption of NM-IIB resulted in approximately 65% embryonic lethality, and those that survived suffered from congestive heart failure and died day 1 following birth. Feature observed in NM-IIB knockouts was an increase in the transverse diameters of cardiomyocytes, ventricular septal defects, as well as other muscular abnormalities.[11] NM-IIB is expressed early during embryonic development in cardiomyocytes,[12] and appears to play a role in karyokinesis; ablation of NM-IIB caused defects in chromatid segregation and mitotic spindle formation, as well as abnormal structure of centrosomes.[13][14] In adult cardiomyocytes, NM-IIB redistributes from a diffuse cytoplasmic pattern in development to a localized Z-disc and intercalated disc distribution, where it colocalizes with alpha-actinin. NM-IIB is the only non-muscle myosin II isoform expressed in adult cardiac muscle (both IIa and IIB are expressed in skeletal muscle Z-discs, suggesting a specific function of NM-IIB in this cell type.[15] NM-IIB may play a role in formation of mature sarcomeres in myofibrils.[16] It appears that NM-IIB plays an essential role in maintaining normal adherens junction integrity and structure. A cardiac muscle-specific knockout of NM-IIB using the alpha-myosin heavy chain promoter-driven cre-recombinase develop enlarged cardiomyocytes, consistent with the defects previously observed with cytokinesis; widened adherens junctions; and progressive hypertrophic cardiomyopathy at 6 months.[17] These data indicate that NM-IIB functions in ensuring the proper maintenance of intercalated disc structures.[18] # Clinical Significance Single nucleotide polymorphisms in MYH10 were detected in patients with left atrial enlargement. MYH10 was identified to be a susceptibility gene using non-biased genome-wide linkage and peak-wide association analysis.[19] # Interactions MYH10 has been shown to interact with: - MYL6[4] and - MYL9.[4]	https://www.wikidoc.org/index.php/MYH10
6fe7625f17522a1837b26d3f7bb35a42e8dad8f6	wikidoc	MYH11	MYH11 Myosin-11 is a protein that in humans is encoded by the MYH11 gene. # Function Gene ID: 4629 MYH11 myosin heavy chain 11, "The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. The gene encoding a human ortholog of rat NUDE1 is transcribed from the reverse strand of this gene, and its 3' end overlaps with that of the latter. The pericentric inversion of chromosome 16 produces a chimeric transcript that encodes a protein consisting of the first 165 residues from the N terminus of core-binding factor beta in a fusion with the C-terminal portion of the smooth muscle myosin heavy chain. This chromosomal rearrangement is associated with acute myeloid leukemia of the M4Eo subtype. Alternative splicing generates isoforms that are differentially expressed, with ratios changing during muscle cell maturation. Alternatively spliced transcript variants encoding different isoforms have been identified." # Transcriptions CArG boxes are present in the promoters of smooth muscle cell (SMC) genes. "CArG box DNA sequences present within the promoters of SMC genes play a pivotal role in controlling their transcription". "Serum response factor (SRF) controls SMC gene transcription via binding to CArG box DNA sequences found within genes that exhibit SMC-restricted expression." "SMC genes examined in this study display SMC-specific histone modifications at the 5′-CArG boxes." "The SRF-CArG association is required for transcriptional activation of SMC genes the SMC genes examined in this study display SMC-specific histone modifications at the 5′-CArG boxes. enrichment of H4 and H3 acetylation were relatively low from positions –2,800 to –1,600 in the 5′ region. However, at position –1,600 to –1,200, there was a sharp rise in these modifications, which was increased even further at +400 in the coding region. We observed similar patterns for H3K4dMe and H3 Lys79 di-methylation . SRF, TFIID, and RNA polymerase II displayed enrichments that were consistent with the positions of the CArG boxes, TATA box, and coding region, respectively". The CArG boxes occur between -400 and -200 nts, between the Enhancer boxes and the TCE element. The consensus sequence of CC(A/T)6GG is confirmed. "MADS-box proteins bind to a consensus sequence, the CArG box, that has the core motif CC(A/T)6GG (15)." "Of the FLC binding sites, 69% contained at least one CArG-box motif with the core consensus sequence CCAAAAAT(G/A)G and an AAA extension at the 3′ end ." Three "other MADS-box flowering-time regulators, SOC1, SVP, and AGAMOUS-LIKE 24 (AGL24), bind to two different CArG-box motifs at 502 bp (CTAAATATGG) and 287 bp (CAATAATTGG) upstream of the translation start in the SEP3 gene (24), consistent with different specificities for the different MADS-box proteins." These together with the core motif CC(A/T)6GG (15) suggest a more general CArG-box motif of (C(C/A/T)(A/T)6(A/G)G). "Exposure of human HL-525 cells to x-rays was associated with increases in EGRI mRNA levels. Nuclear run-on assays showed that this effect is related at least in part to activation of EGRI gene transcription. Sequences responsive to ionizing radiation-induced signals were determined by deletion analysis of the EGRI promoter. The results demonstrate that x-ray inducibility of the EGRI gene is conferred by a region containing six serum response or CC(A+T-rich)6GG (CArG) motifs. Further analysis confirmed that the region encompassing the three distal or upstream CArG elements is functional in the x-ray response. Moreover, this region conferred x-ray inducibility to a minimal thymidine kinase gene promoter. Taken together, these results indicate that ionizing radiation induces EGRI transcription through CArG elements." "Positively acting, rate-limiting regulatory factors that influence tissue-specific expression of the human cardiac α-actin gene in a mouse muscle cell line are shown by in vivo competition and gel mobility-shift assays to bind to upstream regions of its promoter but to neither vector DNA nor a β-globin promoter. Although the two binding regions are distinctly separated, each corresponds to a cis region required for muscle-specific transcriptional stimulation, and each contains a core CC(A+T-rich)6GG sequence (designated CArG box), which is found in the promoter regions of several muscle-associated genes. Each site has an apparently different binding affinity for trans-acting factors, which may explain the different transcriptional stimulation activities of the two cis regions. two CArG box regions are responsible for muscle-specific transcriptional activity of the cardiac α-actin gene through a mechanism that involves their binding of a positive trans-acting factor in muscle cells." "SRF binds to an A/T-rich sequence (CCWWWWWWGG) that has been designated as the CArG box.10–12 CArG boxes were originally identified in transcriptional regulatory elements controlling expression of a set of growth- or serum-responsive genes including c-fos and egr-1.13,14 Subsequently, CArG boxes were identified in transcriptional regulatory elements controlling expression of a subset of genes encoding myogenic contractile and cytoskeletal proteins including α-cardiac actin, smooth muscle (SM)-α-actin, α-skeletal actin, and SM22α.15–19" "Functionally important CArG boxes have been identified in transcriptional regulatory elements controlling expression of sets of myogenic contractile and cytoskeletal proteins (reviewed elsewhere8,25). Of note, in cardiac and skeletal muscle cells, functionally important CArG boxes have been identified in transcriptional regulatory element controlling a relatively limited subset of myofibrillar proteins.26" "In the nucleus, MRTFs physically associate with SRF, facilitating the binding of SRF to single or dual CArG boxes, activating transcription of genes encoding cytoskeletal and myogenic proteins .39,40,53,55,56" "The binding of SRF to SMC CArG boxes is associated with specific alterations in chromatin structure including the methylation and acetylation of histones.76,79" "Both PDGF-BB and KLF-4 inhibit SRF binding to CArG boxes downregulating transcription of SMC contractile genes.92" # Variants NP_002465.1 myosin-11 isoform SM1A: "This variant (SM1A) lacks two segments in the coding region, compared to variant SM2B. The encoded isoform (SM1A) is shorter and varies in the carboxyl terminus, compared to isoform SM2B." Conserved Domains (8) summary - cd14921 (Location:99 → 771): MYSc_Myh11; class II myosin heavy chain 11, motor domain, - pfam01576 (Location:848 → 1928): Myosin_tail_1; Myosin tail, - pfam02736 (Location:33 → 71): Myosin_N; Myosin N-terminal SH3-like domain. NP_074035.1 myosin-11 isoform SM2A: "This variant (SM2A) lacks an in-frame segment of the coding region, compared to variant SM2B. It encodes a shorter isoform (SM2A), that is missing an internal segment compared to isoform SM2B." Conserved Domains (8) summary - cd14921 (Location:99 → 771): MYSc_class_II; class II myosins, motor domain, - pfam00063 (Location:87 → 771): Myosin_head; Myosin head (motor domain), - pfam01576 (Location:848 → 1928): Myosin_tail_1; Myosin tail, - pfam02736 (Location:34 → 71): Myosin_N; Myosin N-terminal SH3-like domain, - pfam09798 (Location:1819 → 1935): LCD1; DNA damage checkpoint protein, - pfam16046 (Location:990 → 1082): FAM76; FAM76 protein, - cl23717 (Location:1066 → 1124): "crotonase-like Superfamily: Crotonase/Enoyl-Coenzyme A (CoA) hydratase superfamily. This superfamily contains a diverse set of enzymes including enoyl-CoA hydratase, napthoate synthase, methylmalonyl-CoA decarboxylase, 3-hydoxybutyryl-CoA dehydratase, and dienoyl-CoA isomerase. Many of these play important roles in fatty acid metabolism. In addition to a conserved structural core and the formation of trimers (or dimers of trimers), a common feature in this superfamily is the stabilization of an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two conserved backbone NH groups in active sites that form an oxyanion hole." - cl24005 (Location:1780 → 1867): DUF2570; Protein of unknown function (DUF2570). NP_001035202.1 myosin-11 isoform SM2B: "This variant (SM2B) represents the longer transcript. It encodes the isoform SM2B." Conserved Domains (8) summary - cd01377 (Location:99 → 778): MYSc_class_II; class II myosins, motor domain, - pfam00063 (Location:87 → 778): Myosin_head; Myosin head (motor domain), - pfam01576 (Location:855 → 1935): Myosin_tail_1; Myosin tail, - pfam02736 (Location:34 → 71): Myosin_N; Myosin N-terminal SH3-like domain, - pfam09798 (Location:1826 → 1942): LCD1; DNA damage checkpoint protein, - pfam16046 (Location:997 → 1089): FAM76; FAM76 protein, - cl23717 (Location:1073 → 1131): "crotonase-like Superfamily: Crotonase/Enoyl-Coenzyme A (CoA) hydratase superfamily. This superfamily contains a diverse set of enzymes including enoyl-CoA hydratase, napthoate synthase, methylmalonyl-CoA decarboxylase, 3-hydoxybutyryl-CoA dehydratase, and dienoyl-CoA isomerase. Many of these play important roles in fatty acid metabolism. In addition to a conserved structural core and the formation of trimers (or dimers of trimers), a common feature in this superfamily is the stabilization of an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two conserved backbone NH groups in active sites that form an oxyanion hole.", - cl24005 (Location:1787 → 1874): DUF2570; Protein of unknown function (DUF2570). NP_001035203.1 myosin-11 isoform SM1B: "Transcript Variant: This variant (SM1B) lacks a segment in the coding region, which leads to a frameshift, compared to variant SM2B. The encoded isoform (SM1B) is longer and varies in the carboxyl terminus, compared to isoform SM2B." Conserved Domains (8) summary - cl14654 (Location:1027 → 1299): V_Alix_like; Protein-interacting V-domain of mammalian Alix and related domains, - cd01377 (Location:99 → 778): MYSc_class_II; class II myosins, motor domain, - pfam00063 (Location:87 → 778): Myosin_head; Myosin head (motor domain), - pfam01576 (Location:855 → 1935): Myosin_tail_1; Myosin tail, - pfam02736 (Location:34 → 71): Myosin_N; Myosin N-terminal SH3-like domain, - pfam16046 (Location:997 → 1089): FAM76; FAM76 protein, - cl23717 (Location:1073 → 1131): "crotonase-like Superfamily: Crotonase/Enoyl-Coenzyme A (CoA) hydratase superfamily. This superfamily contains a diverse set of enzymes including enoyl-CoA hydratase, napthoate synthase, methylmalonyl-CoA decarboxylase, 3-hydoxybutyryl-CoA dehydratase, and dienoyl-CoA isomerase. Many of these play important roles in fatty acid metabolism. In addition to a conserved structural core and the formation of trimers (or dimers of trimers), a common feature in this superfamily is the stabilization of an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two conserved backbone NH groups in active sites that form an oxyanion hole." - cl24005 (Location:1787 → 1874): DUF2570; Protein of unknown function (DUF2570). XP_016878739.1 myosin-11 isoform X1 Conserved Domains (8) summary - cd01377 (Location:99 → 778): MYSc_class_II; class II myosins, motor domain, - pfam00063 (Location:87 → 778): Myosin_head; Myosin head (motor domain), - pfam01576 (Location:855 → 1935): Myosin_tail_1; Myosin tail, - pfam02736 (Location:34 → 71): Myosin_N; Myosin N-terminal SH3-like domain, - pfam09798 (Location:1826 → 1942): LCD1; DNA damage checkpoint protein, - pfam16046 (Location:997 → 1089): FAM76; FAM76 protein, - cl23717 (Location:1073 → 1131): "crotonase-like Superfamily: Crotonase/Enoyl-Coenzyme A (CoA) hydratase superfamily. This superfamily contains a diverse set of enzymes including enoyl-CoA hydratase, napthoate synthase, methylmalonyl-CoA decarboxylase, 3-hydoxybutyryl-CoA dehydratase, and dienoyl-CoA isomerase. Many of these play important roles in fatty acid metabolism. In addition to a conserved structural core and the formation of trimers (or dimers of trimers), a common feature in this superfamily is the stabilization of an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two conserved backbone NH groups in active sites that form an oxyanion hole." - cl24005 (Location:1787 → 1874): DUF2570; Protein of unknown function (DUF2570). XP_011520804.1 myosin-11 isoform X2 Conserved Domains (8) summary - cd14921 (Location:99 → 771): MYSc_class_II; class II myosin heavy chain 11, motor domain, - pfam00063 (Location:87 → 771): Myosin_head; Myosin head (motor domain), - pfam01576 (Location:848 → 1928): Myosin_tail_1; Myosin tail, - pfam02736 (Location:34 → 71): Myosin_N; Myosin N-terminal SH3-like domain, - pfam09798 (Location:1826 → 1942): LCD1; DNA damage checkpoint protein, - pfam16046 (Location:990 → 1082): FAM76; FAM76 protein, - cl23717 (Location:1066 → 1124): "crotonase-like Superfamily: Crotonase/Enoyl-Coenzyme A (CoA) hydratase superfamily. This superfamily contains a diverse set of enzymes including enoyl-CoA hydratase, napthoate synthase, methylmalonyl-CoA decarboxylase, 3-hydoxybutyryl-CoA dehydratase, and dienoyl-CoA isomerase. Many of these play important roles in fatty acid metabolism. In addition to a conserved structural core and the formation of trimers (or dimers of trimers), a common feature in this superfamily is the stabilization of an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two conserved backbone NH groups in active sites that form an oxyanion hole." - cl24005 (Location:1780 → 1867): DUF2570; Protein of unknown function (DUF2570). # Clinical significance Thoracic aortic aneurysms leading to acute aortic dissections (TAAD) can be inherited in isolation or in association with genetic syndromes, such as Marfan syndrome and Loeys-Dietz syndrome. When TAAD occurs in the absence of syndromic features, it is inherited in an autosomal dominant manner with decreased penetrance and variable expression, the disease is referred to as familial TAAD. Familial TAAD exhibits significant clinical and genetic heterogeneity. Mutations in MYH11 have been described in individuals with TAAD with patent ductus arteriosus (PDA). Of individuals with TAAD, approximately 4% have mutations in TGFBR2, and approximately 1-2% have mutations in either TGFBR1 or MYH11. In addition, FBN1 mutations have also been reported in individuals with TAAD. Mutations within the SMAD3 gene have recently been reported in patients with a syndromic form of aortic aneurysms and dissections with early onset osteoarthritis. SMAD3 mutations are thought to account for approximately 2% of familial TAAD. Additionally, mutations in the ACTA2 gene are thought to account for approximately 10-14% of familial TAAD. # Acute myeloid leukemia The gene encoding a human ortholog of rat NUDE1 is transcribed from the reverse strand of this gene, and its 3' end overlaps with that of the latter. The pericentric inversion of chromosome 16 produces a chimeric transcript that encodes a protein consisting of the first 165 residues from the N-terminus of core-binding factor beta in a fusion with the C-terminal portion of the smooth muscle myosin heavy chain. This chromosomal rearrangement is associated with acute myeloid leukemia of the M4Eo subtype. # Intestinal cancer MYH11 mutations appear to contribute to human intestinal cancer.	MYH11 Associate Editor(s)-in-Chief: Henry A. Hoff Myosin-11 is a protein that in humans is encoded by the MYH11 gene.[1][2] # Function Gene ID: 4629 MYH11 myosin heavy chain 11, "The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. The gene encoding a human ortholog of rat NUDE1 is transcribed from the reverse strand of this gene, and its 3' end overlaps with that of the latter. The pericentric inversion of chromosome 16 [inv(16)(p13q22)] produces a chimeric transcript that encodes a protein consisting of the first 165 residues from the N terminus of core-binding factor beta in a fusion with the C-terminal portion of the smooth muscle myosin heavy chain. This chromosomal rearrangement is associated with acute myeloid leukemia of the M4Eo subtype. Alternative splicing generates isoforms that are differentially expressed, with ratios changing during muscle cell maturation. Alternatively spliced transcript variants encoding different isoforms have been identified."[3] # Transcriptions CArG boxes are present in the promoters of smooth muscle cell (SMC) genes. "CArG box [CC(A/T)6GG] DNA [consensus] sequences present within the promoters of SMC genes play a pivotal role in controlling their transcription".[4] "Serum response factor (SRF) controls SMC gene transcription via binding to CArG box DNA sequences found within genes that exhibit SMC-restricted expression."[4] "SMC genes examined in this study display SMC-specific histone modifications at the 5′-CArG boxes."[4] "The SRF-CArG association is required for transcriptional activation of SMC genes [...] the SMC genes examined in this study display SMC-specific histone modifications at the 5′-CArG boxes. [...] enrichment of H4 and H3 acetylation [...] were relatively low from positions –2,800 to –1,600 in the 5′ region. However, at position –1,600 to –1,200, there was a sharp rise in these modifications, which was increased even further at +400 in the coding region. We observed similar patterns for H3K4dMe and H3 Lys79 di-methylation [...]. SRF, TFIID, and RNA polymerase II displayed enrichments that were consistent with the positions of the CArG boxes, TATA box, and coding region, respectively".[4] The CArG boxes occur between -400 and -200 nts, between the Enhancer boxes and the TCE element.[4] The consensus sequence of CC(A/T)6GG is confirmed.[5] "MADS-box proteins bind to a consensus sequence, the CArG box, that has the core motif CC(A/T)6GG (15)."[6] "Of the [Flowering Locus C] FLC binding sites, 69% contained at least one CArG-box motif with the core consensus sequence CCAAAAAT(G/A)G and an AAA extension at the 3′ end [...]."[6] Three "other MADS-box flowering-time regulators, SOC1, SVP, and AGAMOUS-LIKE 24 (AGL24), bind to two different CArG-box motifs at 502 bp (CTAAATATGG) and 287 bp (CAATAATTGG) upstream of the translation start in the SEP3 gene (24), consistent with different specificities for the different MADS-box proteins."[6] These together with the core motif CC(A/T)6GG (15) suggest a more general CArG-box motif of (C(C/A/T)(A/T)6(A/G)G). "Exposure of human HL-525 cells to x-rays was associated with increases in EGRI mRNA levels. Nuclear run-on assays showed that this effect is related at least in part to activation of EGRI gene transcription. Sequences responsive to ionizing radiation-induced signals were determined by deletion analysis of the EGRI promoter. The results demonstrate that x-ray inducibility of the EGRI gene is conferred by a region containing six serum response or CC(A+T-rich)6GG (CArG) motifs. Further analysis confirmed that the region encompassing the three distal or upstream CArG elements is functional in the x-ray response. Moreover, this region conferred x-ray inducibility to a minimal thymidine kinase gene promoter. Taken together, these results indicate that ionizing radiation induces EGRI transcription through CArG elements."[7] "Positively acting, rate-limiting regulatory factors that influence tissue-specific expression of the human cardiac α-actin gene in a mouse muscle cell line are shown by in vivo competition and gel mobility-shift assays to bind to upstream regions of its promoter but to neither vector DNA nor a β-globin promoter. Although the two binding regions are distinctly separated, each corresponds to a cis region required for muscle-specific transcriptional stimulation, and each contains a core CC(A+T-rich)6GG sequence (designated CArG box), which is found in the promoter regions of several muscle-associated genes. Each site has an apparently different binding affinity for trans-acting factors, which may explain the different transcriptional stimulation activities of the two cis regions. [The] two CArG box regions are responsible for muscle-specific transcriptional activity of the cardiac α-actin gene through a mechanism that involves their binding of a positive trans-acting factor in muscle cells."[8] "SRF binds to an A/T-rich sequence (CCWWWWWWGG) that has been designated as the CArG box.10–12 CArG boxes were originally identified in transcriptional regulatory elements controlling expression of a set of growth- or serum-responsive genes including c-fos and egr-1.13,14 Subsequently, CArG boxes were identified in transcriptional regulatory elements controlling expression of a subset of genes encoding myogenic contractile and cytoskeletal proteins including α-cardiac actin, smooth muscle (SM)-α-actin, α-skeletal actin, and SM22α.15–19"[9] "Functionally important CArG boxes have been identified in transcriptional regulatory elements controlling expression of sets of myogenic contractile and cytoskeletal proteins (reviewed elsewhere8,25). Of note, in cardiac and skeletal muscle cells, functionally important CArG boxes have been identified in transcriptional regulatory element controlling a relatively limited subset of myofibrillar proteins.26"[9] "In the nucleus, MRTFs physically associate with SRF, facilitating the binding of SRF to single or dual CArG boxes, activating transcription of genes encoding cytoskeletal and myogenic proteins [...].39,40,53,55,56"[9] "The binding of SRF to SMC CArG boxes is associated with specific alterations in chromatin structure including the methylation and acetylation of histones.76,79"[9] "Both PDGF-BB and KLF-4 inhibit SRF binding to CArG boxes downregulating transcription of SMC contractile genes.92"[9] # Variants NP_002465.1 myosin-11 isoform SM1A: "This variant (SM1A) lacks two segments in the coding region, compared to variant SM2B. The encoded isoform (SM1A) is shorter and varies in the carboxyl terminus, compared to isoform SM2B."[3] Conserved Domains (8) summary - cd14921 (Location:99 → 771): MYSc_Myh11; class II myosin heavy chain 11, motor domain, - pfam01576 (Location:848 → 1928): Myosin_tail_1; Myosin tail, - pfam02736 (Location:33 → 71): Myosin_N; Myosin N-terminal SH3-like domain. NP_074035.1 myosin-11 isoform SM2A: "This variant (SM2A) lacks an in-frame segment of the coding region, compared to variant SM2B. It encodes a shorter isoform (SM2A), that is missing an internal segment compared to isoform SM2B."[3] Conserved Domains (8) summary - cd14921 (Location:99 → 771): MYSc_class_II; class II myosins, motor domain, - pfam00063 (Location:87 → 771): Myosin_head; Myosin head (motor domain), - pfam01576 (Location:848 → 1928): Myosin_tail_1; Myosin tail, - pfam02736 (Location:34 → 71): Myosin_N; Myosin N-terminal SH3-like domain, - pfam09798 (Location:1819 → 1935): LCD1; DNA damage checkpoint protein, - pfam16046 (Location:990 → 1082): FAM76; FAM76 protein, - cl23717 (Location:1066 → 1124): "crotonase-like Superfamily: Crotonase/Enoyl-Coenzyme A (CoA) hydratase superfamily. This superfamily contains a diverse set of enzymes including enoyl-CoA hydratase, napthoate synthase, methylmalonyl-CoA decarboxylase, 3-hydoxybutyryl-CoA dehydratase, and dienoyl-CoA isomerase. Many of these play important roles in fatty acid metabolism. In addition to a conserved structural core and the formation of trimers (or dimers of trimers), a common feature in this superfamily is the stabilization of an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two conserved backbone NH groups in active sites that form an oxyanion hole."[10] - cl24005 (Location:1780 → 1867): DUF2570; Protein of unknown function (DUF2570). NP_001035202.1 myosin-11 isoform SM2B: "This variant (SM2B) represents the longer transcript. It encodes the isoform SM2B."[3] Conserved Domains (8) summary - cd01377 (Location:99 → 778): MYSc_class_II; class II myosins, motor domain, - pfam00063 (Location:87 → 778): Myosin_head; Myosin head (motor domain), - pfam01576 (Location:855 → 1935): Myosin_tail_1; Myosin tail, - pfam02736 (Location:34 → 71): Myosin_N; Myosin N-terminal SH3-like domain, - pfam09798 (Location:1826 → 1942): LCD1; DNA damage checkpoint protein, - pfam16046 (Location:997 → 1089): FAM76; FAM76 protein, - cl23717 (Location:1073 → 1131): "crotonase-like Superfamily: Crotonase/Enoyl-Coenzyme A (CoA) hydratase superfamily. This superfamily contains a diverse set of enzymes including enoyl-CoA hydratase, napthoate synthase, methylmalonyl-CoA decarboxylase, 3-hydoxybutyryl-CoA dehydratase, and dienoyl-CoA isomerase. Many of these play important roles in fatty acid metabolism. In addition to a conserved structural core and the formation of trimers (or dimers of trimers), a common feature in this superfamily is the stabilization of an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two conserved backbone NH groups in active sites that form an oxyanion hole."[10], - cl24005 (Location:1787 → 1874): DUF2570; Protein of unknown function (DUF2570). NP_001035203.1 myosin-11 isoform SM1B: "Transcript Variant: This variant (SM1B) lacks a segment in the coding region, which leads to a frameshift, compared to variant SM2B. The encoded isoform (SM1B) is longer and varies in the carboxyl terminus, compared to isoform SM2B."[3] Conserved Domains (8) summary - cl14654 (Location:1027 → 1299): V_Alix_like; Protein-interacting V-domain of mammalian Alix and related domains, - cd01377 (Location:99 → 778): MYSc_class_II; class II myosins, motor domain, - pfam00063 (Location:87 → 778): Myosin_head; Myosin head (motor domain), - pfam01576 (Location:855 → 1935): Myosin_tail_1; Myosin tail, - pfam02736 (Location:34 → 71): Myosin_N; Myosin N-terminal SH3-like domain, - pfam16046 (Location:997 → 1089): FAM76; FAM76 protein, - cl23717 (Location:1073 → 1131): "crotonase-like Superfamily: Crotonase/Enoyl-Coenzyme A (CoA) hydratase superfamily. This superfamily contains a diverse set of enzymes including enoyl-CoA hydratase, napthoate synthase, methylmalonyl-CoA decarboxylase, 3-hydoxybutyryl-CoA dehydratase, and dienoyl-CoA isomerase. Many of these play important roles in fatty acid metabolism. In addition to a conserved structural core and the formation of trimers (or dimers of trimers), a common feature in this superfamily is the stabilization of an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two conserved backbone NH groups in active sites that form an oxyanion hole."[10] - cl24005 (Location:1787 → 1874): DUF2570; Protein of unknown function (DUF2570). XP_016878739.1 myosin-11 isoform X1 Conserved Domains (8) summary - cd01377 (Location:99 → 778): MYSc_class_II; class II myosins, motor domain, - pfam00063 (Location:87 → 778): Myosin_head; Myosin head (motor domain), - pfam01576 (Location:855 → 1935): Myosin_tail_1; Myosin tail, - pfam02736 (Location:34 → 71): Myosin_N; Myosin N-terminal SH3-like domain, - pfam09798 (Location:1826 → 1942): LCD1; DNA damage checkpoint protein, - pfam16046 (Location:997 → 1089): FAM76; FAM76 protein, - cl23717 (Location:1073 → 1131): "crotonase-like Superfamily: Crotonase/Enoyl-Coenzyme A (CoA) hydratase superfamily. This superfamily contains a diverse set of enzymes including enoyl-CoA hydratase, napthoate synthase, methylmalonyl-CoA decarboxylase, 3-hydoxybutyryl-CoA dehydratase, and dienoyl-CoA isomerase. Many of these play important roles in fatty acid metabolism. In addition to a conserved structural core and the formation of trimers (or dimers of trimers), a common feature in this superfamily is the stabilization of an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two conserved backbone NH groups in active sites that form an oxyanion hole."[10] - cl24005 (Location:1787 → 1874): DUF2570; Protein of unknown function (DUF2570). XP_011520804.1 myosin-11 isoform X2 Conserved Domains (8) summary - cd14921 (Location:99 → 771): MYSc_class_II; class II myosin heavy chain 11, motor domain, - pfam00063 (Location:87 → 771): Myosin_head; Myosin head (motor domain), - pfam01576 (Location:848 → 1928): Myosin_tail_1; Myosin tail, - pfam02736 (Location:34 → 71): Myosin_N; Myosin N-terminal SH3-like domain, - pfam09798 (Location:1826 → 1942): LCD1; DNA damage checkpoint protein, - pfam16046 (Location:990 → 1082): FAM76; FAM76 protein, - cl23717 (Location:1066 → 1124): "crotonase-like Superfamily: Crotonase/Enoyl-Coenzyme A (CoA) hydratase superfamily. This superfamily contains a diverse set of enzymes including enoyl-CoA hydratase, napthoate synthase, methylmalonyl-CoA decarboxylase, 3-hydoxybutyryl-CoA dehydratase, and dienoyl-CoA isomerase. Many of these play important roles in fatty acid metabolism. In addition to a conserved structural core and the formation of trimers (or dimers of trimers), a common feature in this superfamily is the stabilization of an enolate anion intermediate derived from an acyl-CoA substrate. This is accomplished by two conserved backbone NH groups in active sites that form an oxyanion hole."[10] - cl24005 (Location:1780 → 1867): DUF2570; Protein of unknown function (DUF2570). # Clinical significance Thoracic aortic aneurysms leading to acute aortic dissections (TAAD) can be inherited in isolation or in association with genetic syndromes, such as Marfan syndrome and Loeys-Dietz syndrome. When TAAD occurs in the absence of syndromic features, it is inherited in an autosomal dominant manner with decreased penetrance and variable expression, the disease is referred to as familial TAAD. Familial TAAD exhibits significant clinical and genetic heterogeneity. Mutations in MYH11 have been described in individuals with TAAD with patent ductus arteriosus (PDA). Of individuals with TAAD, approximately 4% have mutations in TGFBR2, and approximately 1-2% have mutations in either TGFBR1 or MYH11. In addition, FBN1 mutations have also been reported in individuals with TAAD. Mutations within the SMAD3 gene have recently been reported in patients with a syndromic form of aortic aneurysms and dissections with early onset osteoarthritis. SMAD3 mutations are thought to account for approximately 2% of familial TAAD. Additionally, mutations in the ACTA2 gene are thought to account for approximately 10-14% of familial TAAD.[11] # Acute myeloid leukemia The gene encoding a human ortholog of rat NUDE1 is transcribed from the reverse strand of this gene, and its 3' end overlaps with that of the latter. The pericentric inversion of chromosome 16 [inv(16)(p13q22)] produces a chimeric transcript that encodes a protein consisting of the first 165 residues from the N-terminus of core-binding factor beta in a fusion with the C-terminal portion of the smooth muscle myosin heavy chain. This chromosomal rearrangement is associated with acute myeloid leukemia of the M4Eo subtype. # Intestinal cancer MYH11 mutations appear to contribute to human intestinal cancer.[12]	https://www.wikidoc.org/index.php/MYH11
6533b507b9b32a90c19b255eb1ce3bcf68629d43	wikidoc	MYLIP	MYLIP Myosin regulatory light chain interacting protein, also known as MYLIP, is a protein that in humans is encoded by the MYLIP gene. MYLIP is also known as IDOL "Inducible Degrader of the LDL receptor" based on its involvement in cholesterol regulation. The expression of IDOL is induced by the sterol-activated liver X receptor. Increased Degradation of LDL Receptor Protein (IDOL) is a ubiquitin ligase that ubiquinates LDL receptors in endosomes and directs the receptors to the lysosomal compartment for degradation. IDOL is transcriptionally up-regulated by LXR/RXR in response to an increase in intracellular cholesterol. Pharmacologic inhibition of IDOL could reduce plasma LDL cholesterol by increasing plasma LDL receptor density. # Function The ERM protein family members ezrin, radixin, and moesin are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. Myosin regulatory light chain interacting protein (MYLIP) is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth.	MYLIP Myosin regulatory light chain interacting protein, also known as MYLIP, is a protein that in humans is encoded by the MYLIP gene.[1] MYLIP is also known as IDOL "Inducible Degrader of the LDL receptor" based on its involvement in cholesterol regulation.[2][3] The expression of IDOL is induced by the sterol-activated liver X receptor. Increased Degradation of LDL Receptor Protein (IDOL) is a ubiquitin ligase that ubiquinates LDL receptors in endosomes and directs the receptors to the lysosomal compartment for degradation. IDOL is transcriptionally up-regulated by LXR/RXR in response to an increase in intracellular cholesterol.[4] Pharmacologic inhibition of IDOL could reduce plasma LDL cholesterol by increasing plasma LDL receptor density. # Function The ERM protein family members ezrin, radixin, and moesin are cytoskeletal effector proteins linking actin to membrane-bound proteins at the cell surface. Myosin regulatory light chain interacting protein (MYLIP) is a novel ERM-like protein that interacts with myosin regulatory light chain and inhibits neurite outgrowth.[1]	https://www.wikidoc.org/index.php/MYLIP
74c905a6688219eb882d6c48a5c092949248616b	wikidoc	MYLK2	MYLK2 Myosin light chain kinase 2 also known as MYLK2 is an enzyme which in humans is encoded by the MYLK2 gene. # Function This gene encodes a myosin light chain kinase, a calcium / calmodulin dependent enzyme, that is exclusively expressed in adult skeletal muscle. The MYLK2 gene expresses skMLCK more prevalently in fast twitch muscle fibers as compared to slow twitch muscle fibers. Calmodulin is composed of two terminal domains (N,C) each containing two E-F hand motifs that bind to Ca2+. Upon saturation of Ca2+, Calmodulin undergoes a conformation change allowing it to bind with a target protein such as skMLCK. An image depicting a similar complex (sdCen/skMLCK2) is shown under myosin light chain kinase. This binding to skMLCK increases the affinity of Ca2+ and ultimately leads to a sustained muscle action. # Clinical significance Mutations in the MYLK2 gene have been linked to midventricular hypertrophic cardiomyopathy.	MYLK2 Myosin light chain kinase 2 also known as MYLK2 is an enzyme which in humans is encoded by the MYLK2 gene.[1] # Function This gene encodes a myosin light chain kinase, a calcium / calmodulin dependent enzyme, that is exclusively expressed in adult skeletal muscle.[2] The MYLK2 gene expresses skMLCK more prevalently in fast twitch muscle fibers as compared to slow twitch muscle fibers. Calmodulin is composed of two terminal domains (N,C) each containing two E-F hand motifs that bind to Ca2+. Upon saturation of Ca2+, Calmodulin undergoes a conformation change allowing it to bind with a target protein such as skMLCK. An image depicting a similar complex (sdCen/skMLCK2) is shown under myosin light chain kinase. This binding to skMLCK increases the affinity of Ca2+ and ultimately leads to a sustained muscle action.[3] # Clinical significance Mutations in the MYLK2 gene have been linked to midventricular hypertrophic cardiomyopathy.[1]	https://www.wikidoc.org/index.php/MYLK2
46713b17d4d44183eb8a4217f51ce6552688cda0	wikidoc	MYLK4	MYLK4 Myosin light chain kinase 4 also known as MYLK4 is an enzyme which in humans is encoded by the MYLK2 gene. MYLK4 is a member of the myosin light-chain kinase family of serine/threonine-specific protein kinases that phosphorylate the regulatory light chain of myosin II. This protein acts as an enzyme that catalyzes the following reaction: ATP + a protein -> ADP + a phosphoprotein. MYLK4 is also involved in protein amino acid phosphorylation meaning that it adds a phosphate group onto the molecule. Not very much is known about the specific functional characteristics of MLYK4, but it has recently been found that the gene may possibly have a role in having at least one driver mutation for cancer. MYLK4 may also be involved in transferase activity, ATP binding, protein serine/threonine kinase activity, and also nucleotide binding. Other names for MYLK4 are CaMLCK like; EG238564; MYLK4; Mylk4; Myosin light chain kinase family, member 4; SgK085; SGK085; Sgk085; Sugen kinase 85; Uncharacterized serine/threonine-protein kinase SgK085. There are other known myosin light-chain kinase enzymes.	MYLK4 Myosin light chain kinase 4 also known as MYLK4 is an enzyme which in humans is encoded by the MYLK2 gene.[2] MYLK4 is a member of the myosin light-chain kinase family of serine/threonine-specific protein kinases that phosphorylate the regulatory light chain of myosin II.[3] This protein acts as an enzyme that catalyzes the following reaction: ATP + a protein -> ADP + a phosphoprotein.[4] MYLK4 is also involved in protein amino acid phosphorylation meaning that it adds a phosphate group onto the molecule.[5] Not very much is known about the specific functional characteristics of MLYK4, but it has recently been found that the gene may possibly have a role in having at least one driver mutation for cancer.[6] MYLK4 may also be involved in transferase activity, ATP binding, protein serine/threonine kinase activity, and also nucleotide binding.[7] Other names for MYLK4 are CaMLCK like; EG238564; MYLK4; Mylk4; Myosin light chain kinase family, member 4; SgK085; SGK085; Sgk085; Sugen kinase 85; Uncharacterized serine/threonine-protein kinase SgK085.[8] There are other known myosin light-chain kinase enzymes.	https://www.wikidoc.org/index.php/MYLK4
3269086bf2727dd99d6bb32db877a5ab02a370fd	wikidoc	MYO10	MYO10 Myosin X, also known as MYO10, is a protein that in humans is encoded by the MYO10 gene. Myosin X is an actin-based motor protein known to associate at the tips of filopodia. # Model organisms Model organisms have been used in the study of MYO10 function. A conditional knockout mouse line called Myo10tm2(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping	MYO10 Myosin X, also known as MYO10, is a protein that in humans is encoded by the MYO10 gene.[1][2][3] Myosin X is an actin-based motor protein known to associate at the tips of filopodia.[4] # Model organisms Model organisms have been used in the study of MYO10 function. A conditional knockout mouse line called Myo10tm2(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[5] Male and female animals underwent a standardized phenotypic screen[6] to determine the effects of deletion.[7][8][9][10] Additional screens performed: - In-depth immunological phenotyping[11]	https://www.wikidoc.org/index.php/MYO10
064391bae2f3f93641c3a78b88505efbdb1599df	wikidoc	MYO5A	MYO5A Myosin-Va is a protein that in humans is encoded by the MYO5A gene. # Interactions MYO5A has been shown to interact with DYNLL1, RAB27A, DYNLL2 and RPGRIP1L. # Clinical significance Defects are associated with Griscelli syndrome type 1, also known as Elejalde syndrome. # Model organisms Model organisms have been used in the study of MYO5A function. A conditional knockout mouse line, called Myo5atm1e(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and three significant abnormalities were observed. Male homozygous mutants had abnormal hair cycles, coat colouration and an increased susceptibility to bacterial infection.	MYO5A Myosin-Va is a protein that in humans is encoded by the MYO5A gene.[1][2][3] # Interactions MYO5A has been shown to interact with DYNLL1,[4] RAB27A,[5][6] DYNLL2[4][7] and RPGRIP1L.[8] # Clinical significance Defects are associated with Griscelli syndrome type 1, also known as Elejalde syndrome. # Model organisms Model organisms have been used in the study of MYO5A function. A conditional knockout mouse line, called Myo5atm1e(KOMP)Wtsi[14][15] was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[16][17][18] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty five tests were carried out on mutant mice and three significant abnormalities were observed.[12] Male homozygous mutants had abnormal hair cycles, coat colouration and an increased susceptibility to bacterial infection.[12]	https://www.wikidoc.org/index.php/MYO5A
b7a3dae8f6d82aadbb42b26833b90ee3e3ddf885	wikidoc	MYO5B	MYO5B Myosin-Vb is a protein that in humans is encoded by the MYO5B gene. Recent evidence suggests that Myosin VB is related to the creation of memories by actin-dependent trafficking of AMPA receptor containing recycling endosomes in dendritic spines. Mutations of MYO5B cause microvillus inclusion disease and have been associated with bipolar disorder. # Interactions MYO5B has been shown to interact with RAB11FIP2.	MYO5B Myosin-Vb is a protein that in humans is encoded by the MYO5B gene.[1][2][3] Recent evidence suggests that Myosin VB is related to the creation of memories[4] by actin-dependent trafficking of AMPA receptor containing recycling endosomes in dendritic spines.[5] Mutations of MYO5B cause microvillus inclusion disease[6] and have been associated with bipolar disorder.[7] # Interactions MYO5B has been shown to interact with RAB11FIP2.[8]	https://www.wikidoc.org/index.php/MYO5B
5710ea74f896145aa570be2b13e6db0517448045	wikidoc	MYO7A	MYO7A Myosin VIIA is protein that in humans is encoded by the MYO7A gene. Myosin VIIA is a member of the unconventional myosin superfamily of proteins. Myosins are actin binding molecular motors that use the enzymatic conversion of ATP - ADP + inorganic phosphate (Pi) to provide the energy for movement. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. Myosin VIIA is an unconventional myosin with a very short tail. Unconventional myosins have diverse functions in eukaryotic cells and are primarily thought to be involved in the movement or linkage of intra-cellular membranes and organelles to the actin cytoskeleton via interactions mediated by their highly divergent tail domains. MYO7A is expressed in a number of mammalian tissues, including testis, kidney, lung, inner ear, retina and the ciliated epithelium of the nasal mucosa. # Clinical significance Mutations in the MYO7A gene cause the Usher syndrome type 1B, a combined deafness/blindness disorder. Affected individuals are typically profoundly deaf at birth and then undergo progressive retinal degeneration. # Model organisms Model organisms have been used in the study of MYO7A function. A spontaneous mutant mouse line, called Myo7ash1-6J was generated. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty three tests were carried out on mutant mice and ten significant abnormalities were observed. Male homozygous mutant mice displayed a decreased body weight, a decrease in body fat, improved glucose tolerance and abnormal pelvic girdle bone morphology. Homozygous mutant mice of both sex displayed various abnormalities in a modified SHIRPA test, including abnormal gait, tail dragging and an absence of pinna reflex, a decrease in grip strength, an increased thermal pain threshold, severe hearing impairment and a number of abnormal indirect calorimetry and clinical chemistry parameters.	MYO7A Myosin VIIA is protein that in humans is encoded by the MYO7A gene.[1] Myosin VIIA is a member of the unconventional myosin superfamily of proteins.[2] Myosins are actin binding molecular motors that use the enzymatic conversion of ATP - ADP + inorganic phosphate (Pi) to provide the energy for movement. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. Myosin VIIA is an unconventional myosin with a very short tail. Unconventional myosins have diverse functions in eukaryotic cells and are primarily thought to be involved in the movement or linkage of intra-cellular membranes and organelles to the actin cytoskeleton via interactions mediated by their highly divergent tail domains. MYO7A is expressed in a number of mammalian tissues, including testis, kidney, lung, inner ear, retina and the ciliated epithelium of the nasal mucosa. # Clinical significance Mutations in the MYO7A gene cause the Usher syndrome type 1B, a combined deafness/blindness disorder.[2] Affected individuals are typically profoundly deaf at birth and then undergo progressive retinal degeneration.[3] # Model organisms Model organisms have been used in the study of MYO7A function. A spontaneous mutant mouse line, called Myo7ash1-6J[15] was generated. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13][16] Twenty three tests were carried out on mutant mice and ten significant abnormalities were observed.[13] Male homozygous mutant mice displayed a decreased body weight, a decrease in body fat, improved glucose tolerance and abnormal pelvic girdle bone morphology. Homozygous mutant mice of both sex displayed various abnormalities in a modified SHIRPA test, including abnormal gait, tail dragging and an absence of pinna reflex, a decrease in grip strength, an increased thermal pain threshold, severe hearing impairment and a number of abnormal indirect calorimetry and clinical chemistry parameters.[13]	https://www.wikidoc.org/index.php/MYO7A
fed688b46d0497ce613eed3fd8ff7668d84897d2	wikidoc	MYOM1	MYOM1 Myomesin-1 is a protein that in humans is encoded by the MYOM1 gene. Myomesin-1 is expressed in muscle cells and functions to stabilize the three-dimensional conformation of the thick filament. Embryonic forms of Myomesin-1 have been detected in dilated cardiomyopathy. # Structure Alternatively spliced variants of MYOM1, including EH-myomesin, Skelemin and Myomesin-1 have been identified; with Skelemin having an additional 96 amino acids rich in serine and proline residues. Myomesin-1, like myomesin 2 and titin, is a member of a family of myosin-associated proteins containing structural modules with strong homology to either fibronectin type III (motif I) or immunoglobulin C2 (motif II) domains. Myomesin-1 bears uniqueness within this family in that it has intermediate filament core-like motifs, one near each terminus. Myomesin-1 and Myomesin-2 each have a unique N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the titin string extends into the center of the M band. Alternatively spliced, tissue-specific transcript variants encoding different isoforms have been identified. Myomesin-1 can dimerize in an anti-parallel fashion via its C-terminal region. # Function Titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to Myomesin-1 and myomesin 2. Skelemin/Myomesin-1 is concentrated at peripheral regions of M-bands, and is postulated to link myofibrils with the intermediate filament cytoskeleton. Skelemin/Myomesin-1 has been detected in the nucleus as well as the cytoskeletal, suggesting that it may play a role in gene expression. Myomesin-1 functions to mediate stretch-induced signaling, and the EH-myomesin splice variant, expressed in embryonic hearts and in dilated cardiomyopathy, can modulate its elasticity. # Clinical Significance The fetal EH-myomesin alternatively spliced form of MYOM1 has been shown to be reexpressed at an early timepoint in the progression of dilated cardiomyopathy, coincident with isoform switches in titin. MYOM1 has also been shown to be abnormally spliced in patients with myotonic dystrophy type I; specifically, exon 17a. # Interactions Skelemin/Myomesin-1 has been shown to interact with: - ITGB1 - ITGB3 - ITGA2B - MYH7 - Titin - PNKD	MYOM1 Myomesin-1 is a protein that in humans is encoded by the MYOM1 gene.[1][2] Myomesin-1 is expressed in muscle cells and functions to stabilize the three-dimensional conformation of the thick filament. Embryonic forms of Myomesin-1 have been detected in dilated cardiomyopathy. # Structure Alternatively spliced variants of MYOM1, including EH-myomesin,[3] Skelemin[4] and Myomesin-1[4][5][6] have been identified; with Skelemin having an additional 96 amino acids rich in serine and proline residues.[4] Myomesin-1, like myomesin 2 and titin, is a member of a family of myosin-associated proteins containing structural modules with strong homology to either fibronectin type III (motif I) or immunoglobulin C2 (motif II) domains. Myomesin-1 bears uniqueness within this family in that it has intermediate filament core-like motifs, one near each terminus.[7] Myomesin-1 and Myomesin-2 each have a unique N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the titin string extends into the center of the M band. Alternatively spliced, tissue-specific transcript variants encoding different isoforms have been identified.[8] Myomesin-1 can dimerize in an anti-parallel fashion via its C-terminal region.[9] # Function Titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to Myomesin-1 and myomesin 2. Skelemin/Myomesin-1 is concentrated at peripheral regions of M-bands, and is postulated to link myofibrils with the intermediate filament cytoskeleton.[7] Skelemin/Myomesin-1 has been detected in the nucleus as well as the cytoskeletal, suggesting that it may play a role in gene expression.[10] Myomesin-1 functions to mediate stretch-induced signaling,[11] and the EH-myomesin splice variant, expressed in embryonic hearts and in dilated cardiomyopathy, can modulate its elasticity.[12] # Clinical Significance The fetal EH-myomesin alternatively spliced form of MYOM1 has been shown to be reexpressed at an early timepoint in the progression of dilated cardiomyopathy, coincident with isoform switches in titin.[13] MYOM1 has also been shown to be abnormally spliced in patients with myotonic dystrophy type I; specifically, exon 17a.[14] # Interactions Skelemin/Myomesin-1 has been shown to interact with: - ITGB1[15] - ITGB3[15][16] - ITGA2B[16] - MYH7[17][18][19] - Titin[20] - PNKD[21]	https://www.wikidoc.org/index.php/MYOM1
9c43b42a13547b68e86fb6718c7d34f626dd1b9d	wikidoc	MYOM2	MYOM2 M-protein, also known as Myomesin-2 is a protein that in humans is encoded by the MYOM2 gene. M-protein is expressed in adult cardiac muscle and fast skeletal muscle, and functions to stabilize the three-dimensional arrangement of proteins comprising M-band structures. # Structure Human M-protein is 165.0 kDa and 1465 amino acids in length. MYOM2 is localized to the human chromosome 8p23.3. M-protein belong to the superfamily of cytoskeletal proteins having immunoglobulin/fibronectin repeats; M-protein contains two immunoglobulin C2-type repeats in the N-terminal region, five fibronectin type III repeats in the central region, and an additional four immunoglobulin C2-type repeats in the C-terminal region. M-protein is expressed only in striated muscle, including fast skeletal muscle and cardiac muscle. # Function M-protein exhibits a different pattern of expression in cardiac and skeletal muscle, as well as fast- versus slow-skeletal muscle during development, suggesting different regulatory mechanisms for expression quantity and temporal appearance. In cardiac muscle, expression of M-protein continues to increase from neonatal to adult; however, in skeletal muscle, M-protein mRNA expression is biophasic. M-protein is initially present in both slow- and fast-skeletal muscle embryonic fibers, then M-protein is suppressed in slow fibers. The embryonic splice variant of myomesin, termed EH-myomesin, is expressed in a complementary pattern with M-protein during development in higher vertebrates. It was also shown that the mRNA expression of M-protein is exquisitely sensitive to thyroid hormone (T3); M-protein expression, but not MYOM1 or its variant,EH-myomesin, was rapidly reduced by T3 in vivo and in vitro. The M-protein promoter is responsive to T3, and was suggested to contain thyroid hormone response elements near the transcriptional start point. The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents MYOM1 and M-protein, of apparent molecular masses of 190 kD and 165 kD, respectively. M-protein functions to stabilize the M-line cross-linking titin and myosin; the central portion of M-protein is around the M1-line, and the N-terminal and C-terminal regions are arranged along thick filaments. An animal model of thyroid hormone (T3)-induced cardiac hypertrophy showed that T3 rapidly reduced levels of M-protein; and siRNA reduction of M-protein in neonatal cardiomyocytes showed that the absence of M-protein causes significant contractile dysfunction (77% reduction in contraction velocity), thus illuminating the importance of M-protein for normal sarcomere function. M-protein can be post-translationally modified in vivo. M-protein fragments generated via cleavage by matrix metalloproteinase 2 in left ventricular myocardium have been identified as a factor in the development of pulmonary hypertension and ascites in broiler chickens. Another study demonstrated that M-protein is S-thiolated during post-ischemic reperfusion. It was also determined that domains Mp2 to Mp3 in M-protein binds myosin, and this specific interaction can be regulated by phosphorylation. # Clinical Significance # Interactions M-protein interacts with: - Titin - CKM - MYH7	MYOM2 M-protein, also known as Myomesin-2 is a protein that in humans is encoded by the MYOM2 gene.[1] M-protein is expressed in adult cardiac muscle and fast skeletal muscle, and functions to stabilize the three-dimensional arrangement of proteins comprising M-band structures. # Structure Human M-protein is 165.0 kDa and 1465 amino acids in length.[2] MYOM2 is localized to the human chromosome 8p23.3.[3] M-protein belong to the superfamily of cytoskeletal proteins having immunoglobulin/fibronectin repeats; M-protein contains two immunoglobulin C2-type repeats in the N-terminal region, five fibronectin type III repeats in the central region, and an additional four immunoglobulin C2-type repeats in the C-terminal region.[4] M-protein is expressed only in striated muscle, including fast skeletal muscle and cardiac muscle.[5][6][7] # Function M-protein exhibits a different pattern of expression in cardiac and skeletal muscle, as well as fast- versus slow-skeletal muscle during development, suggesting different regulatory mechanisms for expression quantity and temporal appearance. In cardiac muscle, expression of M-protein continues to increase from neonatal to adult; however, in skeletal muscle, M-protein mRNA expression is biophasic.[8] M-protein is initially present in both slow- and fast-skeletal muscle embryonic fibers, then M-protein is suppressed in slow fibers.[7][9] The embryonic splice variant of myomesin, termed EH-myomesin, is expressed in a complementary pattern with M-protein during development in higher vertebrates.[10] It was also shown that the mRNA expression of M-protein is exquisitely sensitive to thyroid hormone (T3); M-protein expression, but not MYOM1 or its variant,EH-myomesin, was rapidly reduced by T3 in vivo and in vitro. The M-protein promoter is responsive to T3, and was suggested to contain thyroid hormone response elements near the transcriptional start point.[11] The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents MYOM1 and M-protein, of apparent molecular masses of 190 kD and 165 kD, respectively. M-protein functions to stabilize the M-line cross-linking titin and myosin; the central portion of M-protein is around the M1-line, and the N-terminal and C-terminal regions are arranged along thick filaments.[6] An animal model of thyroid hormone (T3)-induced cardiac hypertrophy showed that T3 rapidly reduced levels of M-protein; and siRNA reduction of M-protein in neonatal cardiomyocytes showed that the absence of M-protein causes significant contractile dysfunction (77% reduction in contraction velocity), thus illuminating the importance of M-protein for normal sarcomere function.[11] M-protein can be post-translationally modified in vivo. M-protein fragments generated via cleavage by matrix metalloproteinase 2 in left ventricular myocardium have been identified as a factor in the development of pulmonary hypertension and ascites in broiler chickens.[12] Another study demonstrated that M-protein is S-thiolated during post-ischemic reperfusion.[13] It was also determined that domains Mp2 to Mp3 in M-protein binds myosin, and this specific interaction can be regulated by phosphorylation.[14] # Clinical Significance # Interactions M-protein interacts with: - Titin[15] - CKM[16] - MYH7[17][18]	https://www.wikidoc.org/index.php/MYOM2
0e4a02860d6cda92bc14d46542b84c538eb62cf3	wikidoc	MYOZ2	MYOZ2 Myozenin-2, also referred to as Calsarcin-1, is a protein that in humans is encoded by the MYOZ2 gene. The Calsarcin-1 isoform is a muscle protein expressed in cardiac muscle and slow-twitch skeletal muscle, which functions to tether calcineurin to alpha-actinin at Z-discs, and inhibit the pathological cardiac hypertrophic response. This differs from the fast-skeletal muscle isoform, calsarcin-2. # Structure Calsarcin-1 is a 29.9 kDa protein composed of 264 amino acids. Calsarcin-1 and calsarcin-2 are only 31% homologous (94 identical amino acids), exhibiting the highest homology at N- and C-termini. Calsarcin-1 binds to alpha-actinin, gamma-filamin, telethonin, ZASP/Cypher and calcineurin. The binding region of calsarcin-1 to alpha-actinin is localized to amino acids 153-200, and that of calsarcin-1 to calcineurin is amino acids 217-240. # Function The function of calsarcin-1 in cardiac and slow-skeletal muscle has been illuminated through studies in transgenic animals. Mice lacking the MYOZ2 gene (MYOZ2-/-) are generally sensitized to calcineurin signaling in both muscle types. In slow-skeletal muscle, MYOZ2-/- show increased slow-twitch muscle fibers. In cardiac, MYOZ2-/- show induction of the fetal gene program typical of pathologic hypertrophy, however there was no evidence of hypertrophied morphometry at baseline. However, upon calcineurin activation or pressure overload-induced pathologic hypertrophy, MYOZ2-/- exhibited exaggerated cardiac hypertrophy, demonstrating that calsarcin-1 negatively modulates the function of calcineurin during pathologic hypertrophic remodeling. Additional studies supported these findings in demonstrating that adenoviral overexpression of calsarcin-1 attenuated Gq alpha subunit-stimuated hypertrophy and ANP induction, by Angiotensin II, phenylephrine and endothelin-1 agonists in neonatal cardiomyocytes. Overexpression of calsarcin-1 in mice (CS1Tg) was protective against Angiotensin II-induced pathologic cardiac hypertrophy, evidenced by preserved fractional shortening and contractility, as well as a blunted induction of the fetal hypertrophic gene program and significantly reduced expression of calcineurin-stimulated MCIP1.4 gene expression. Taken together, these studies strongly support a role for calsarcin-1 in suppressing pathologic cardiac hypertrophy. # Clinical Significance Two missense mutations in MYOZ2, Ser48Pro and Ile246Met, have been shown to be causal for rare forms of familial hypertrophic cardiomyopathy.	MYOZ2 Myozenin-2, also referred to as Calsarcin-1, is a protein that in humans is encoded by the MYOZ2 gene.[1][2][3] The Calsarcin-1 isoform is a muscle protein expressed in cardiac muscle and slow-twitch skeletal muscle, which functions to tether calcineurin to alpha-actinin at Z-discs, and inhibit the pathological cardiac hypertrophic response. This differs from the fast-skeletal muscle isoform, calsarcin-2. # Structure Calsarcin-1 is a 29.9 kDa protein composed of 264 amino acids.[4][5] Calsarcin-1 and calsarcin-2 are only 31% homologous (94 identical amino acids), exhibiting the highest homology at N- and C-termini. Calsarcin-1 binds to alpha-actinin,[6] gamma-filamin,[7] telethonin,[7] ZASP/Cypher[7] and calcineurin.[6] The binding region of calsarcin-1 to alpha-actinin is localized to amino acids 153-200, and that of calsarcin-1 to calcineurin is amino acids 217-240.[6] # Function The function of calsarcin-1 in cardiac and slow-skeletal muscle has been illuminated through studies in transgenic animals. Mice lacking the MYOZ2 gene (MYOZ2-/-) are generally sensitized to calcineurin signaling in both muscle types.[8] In slow-skeletal muscle, MYOZ2-/- show increased slow-twitch muscle fibers. In cardiac, MYOZ2-/- show induction of the fetal gene program typical of pathologic hypertrophy, however there was no evidence of hypertrophied morphometry at baseline. However, upon calcineurin activation or pressure overload-induced pathologic hypertrophy, MYOZ2-/- exhibited exaggerated cardiac hypertrophy, demonstrating that calsarcin-1 negatively modulates the function of calcineurin during pathologic hypertrophic remodeling.[8] Additional studies supported these findings in demonstrating that adenoviral overexpression of calsarcin-1 attenuated Gq alpha subunit-stimuated hypertrophy and ANP induction, by Angiotensin II, phenylephrine and endothelin-1 agonists in neonatal cardiomyocytes.[9] Overexpression of calsarcin-1 in mice (CS1Tg) was protective against Angiotensin II-induced pathologic cardiac hypertrophy, evidenced by preserved fractional shortening and contractility, as well as a blunted induction of the fetal hypertrophic gene program and significantly reduced expression of calcineurin-stimulated MCIP1.4 gene expression.[9] Taken together, these studies strongly support a role for calsarcin-1 in suppressing pathologic cardiac hypertrophy. # Clinical Significance Two missense mutations in MYOZ2, Ser48Pro and Ile246Met, have been shown to be causal for rare forms of familial hypertrophic cardiomyopathy.[10]	https://www.wikidoc.org/index.php/MYOZ2

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