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Synthyra 7

A0A644F7M7

GCP2_GIAIC

MSSVFADPRVKELLNLHRSPKLATEGKTPPSQVQDLVNKYSRLGSNVVSHPTRSSPEKTTDKPADSKPSIPPLKSESVMTRLTALSSNNTTQNVASLVTAIASHPATAALPKQEASQQPVIPTSVEKRAVTQPLSQQNMNKLMNAIDPQAAPLIEDQVAGKHTGTKPLLTLQQQQAISSLPTKSERESALNEIALNTAIQSAQHANMELSKAGITFPMWFFGVQNQSDLVSRSFISLAHIQQPMVMNDSLLQEHLLVSDCIAVLQGCMQTTYLQVSEQNKEYVVTIRKEVATELPATLVAMTQRVLVHAHARFQIVNTIYTHQVPEYGRIANAFSQALRCIIKEYDFYLADLSKKHYGKMQSSAERGSLSLQTLEVKTKQIHIILENVADLCSRLGVVRGCALLQQLETAVLQSSGLSVKEVFQYLLSESLKPLGRIMDRYINEAVIPDSDAADFFIRKSHSTELAEEQGKTTINTWMQMFKVDDAQVPLFLNNIKTHLCDIGRSTVLLKWKKKQYIDKGPNASGQELLLLSAEASGETTQGFRHGEETVASLVCGDGSTGDLELAHIRLYKQLIDINARVQTKVLDFFINPEYLDFRGHLQNIYAFYLVMAGDFLSCFVESAISELVLSRSVANILRIRSKFKMVIKTSSLANLPYNERMNVIVCPELFKHHLNSVLYPQTYVPDRATDSPDPKVLNLLGLQYDVTYPLNLVLTTPVMERLNLVFRHILRAKVSEIELQKAWTTLQRLRKLERVPHDKIEVYANALRSDKSPIIIFFGVAYKMLITMLDFIHSLQFQYVTILTECIAKFQDTLVNAKSLDDLVSGMSAFANGLIMSLGLVSNNVVNILDTLFNDCIVYSHHIVKTFCIISNEDDEFIRKIVTINEESREGKSGPRGVKGSERMTSLLKKREAIEMTRLIAIANSVYSLIVDNRGLIATLMTKFNKGVASYEQVIRNFDDR

cytoplasmic microtubule organization [GO:0031122]; meiotic cell cycle [GO:0051321]; microtubule nucleation [GO:0007020]; mitotic cell cycle [GO:0000278]; spindle assembly [GO:0051225]

centrosome [GO:0005813]; cytoplasm [GO:0005737]; equatorial microtubule organizing center [GO:0000923]; gamma-tubulin complex [GO:0000930]; microtubule [GO:0005874]; motile cilium [GO:0031514]; spindle pole [GO:0000922]

gamma-tubulin binding [GO:0043015]; microtubule minus-end binding [GO:0051011]

PF04130;PF17681;

1.20.120.1900;

TUBGCP family

SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, flagellum axoneme {ECO:0000269|PubMed:30318753}. Cytoplasm, cytoskeleton, flagellum basal body {ECO:0000269|PubMed:30318753}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:30318753}. Note=Localizes to basal bodies, axonemes and median bodies of the trophozoites during interface. Colocalizes with tubulin gamma chain. {ECO:0000269|PubMed:30318753}.

FUNCTION: Component of the gamma-tubulin small complex (gamma-TuSC) involved in microtubule (MT) nucleation for the formation of median bodies and in the biogenesis of flagella. Gamma-TuSC may be required for the correct positioning of EB1 within the trophozoites. {ECO:0000269|PubMed:30318753}.

Giardia intestinalis (strain ATCC 50803 / WB clone C6) (Giardia lamblia)

A0A649V088

BLC14_ECOLX

MVTKRVQRMMFAAAACIPLLLGSAPLYAQTSAVQQKLAALEKSSGGRLGVALIDTADNTQVLYRGDERFPMCSTSKVMAAAAVLKQSETQKQLLNQPVEIKPADLVNYNPIAEKHVNGTMTLAELSAAALQYSDNTAMNKLIAQLGGPGGVTAFARAIGDETFRLDRTEPTLNTAIPGDPRDTTTPRAMAQTLRQLTLGHALGETQRAQLVTWLKGNTTGAASIRAGLPTSWTVGDKTGSGDYGTTNDIAVIWPQGRAPLVLVTYFTQPQQNAESRRDVLASAARIIAEGL

3.5.2.6

beta-lactam antibiotic catabolic process [GO:0030655]; response to antibiotic [GO:0046677]

beta-lactamase activity [GO:0008800]

PF13354;

3.40.710.10;

Class-A beta-lactamase family

SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:A0A5R8T042}.

CATALYTIC ACTIVITY: Reaction=a beta-lactam + H2O = a substituted beta-amino acid; Xref=Rhea:RHEA:20401, ChEBI:CHEBI:15377, ChEBI:CHEBI:35627, ChEBI:CHEBI:140347; EC=3.5.2.6; Evidence={ECO:0000269|PubMed:26169409, ECO:0000269|PubMed:26282414};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=72 uM for ampicillin (at pH 7.0 and 25 degrees Celsius) {ECO:0000269|PubMed:26169409}; KM=12 uM for ampicillin (at pH 7.0 and 30 degrees Celsius) {ECO:0000269|PubMed:26282414}; KM=64 uM for cefalotin (at pH 7.0 and 25 degrees Celsius) {ECO:0000269|PubMed:26169409}; KM=93 uM for cefalotin (at pH 7.0 and 30 degrees Celsius) {ECO:0000269|PubMed:26282414}; KM=22 uM for cefuroxime (at pH 7.0 and 25 degrees Celsius) {ECO:0000269|PubMed:26169409}; KM=34 uM for cefotaxime (at pH 7.0 and 25 degrees Celsius) {ECO:0000269|PubMed:26169409}; KM=72 uM for cefotaxime (at pH 7.0 and 30 degrees Celsius) {ECO:0000269|PubMed:26282414}; KM=11 uM for nitrocefin (at pH 7.0 and 25 degrees Celsius) {ECO:0000269|PubMed:26169409}; KM=22 uM for nitrocefin (at pH 7.0 and 30 degrees Celsius) {ECO:0000269|PubMed:26282414}; KM=14 uM for ceftiofur (at pH 7.0 and 25 degrees Celsius) {ECO:0000269|PubMed:26169409}; KM=17 uM for ceftriaxone (at pH 7.0 and 25 degrees Celsius) {ECO:0000269|PubMed:26169409}; Note=kcat is 25 sec(-1) with ampicillin as substrate (at pH 7.0 and 25 degrees Celsius) (PubMed:26169409). kcat is 140 sec(-1) with ampicillin as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:26282414). kcat is 357 sec(-1) with cefalotin as substrate (at pH 7.0 and 25 degrees Celsius) (PubMed:26169409). kcat is 1626 sec(-1) with cefalotin as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:26282414). kcat is 37 sec(-1) with cefotaxime as substrate (at pH 7.0 and 25 degrees Celsius) (PubMed:26169409). kcat is 203 sec(-1) with cefotaxime as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:26282414). kcat is 114 sec(-1) with nitrocefin as substrate (at pH 7.0 and 25 degrees Celsius) (PubMed:26169409). kcat is 304 sec(-1) with nitrocefin as substrate (at pH 7.0 and 30 degrees Celsius) (PubMed:26282414). kcat is 22 sec(-1) with cefuroxime as substrate (at pH 7.0 and 25 degrees Celsius) (PubMed:26169409). kcat is 16 sec(-1) with ceftiofur as substrate (at pH 7.0 and 25 degrees Celsius) (PubMed:26169409). kcat is 42 sec(-1) with ceftriaxone as substrate (at pH 7.0 and 25 degrees Celsius) (PubMed:26169409). {ECO:0000269|PubMed:26169409, ECO:0000269|PubMed:26282414};

FUNCTION: Extended-spectrum beta-lactamase (ESBL) which confers resistance to penicillins, as well as first, second, and third-generation cephalosporins (PubMed:26169409, PubMed:26282414). Has cefotaxime-hydrolyzing activity (PubMed:26282414). {ECO:0000269|PubMed:26169409, ECO:0000269|PubMed:26282414}.

Escherichia coli

A0A6B7FMR5

VMMP3_VIPAA

MIQVLLVIICLAVFPYQVSSIILESGNINNYEVVYPQKVTALPKGAIQQLEQKYEDAMQYQFKVKGEPVVLHLEKNKDFFPEDYSETHYSPDDREITTNPPVEDHCYYYGHIQNDADSTASISACNGLKGYFTLRGVTYLIEPLKIPESEAHAIYKYENVEKEDEDPKKCEFRRAGTECRPARSECDVAEYCTGQSAECPTDVFHSNGKPCLNNFGYCYNGNCPIMYHQCYALFGPNATVGQDGCFEWNKKGESYFYCRKENDVPIPCAPEDIKCGRLFCELIKNTCKYDYSEDPDYGMVDHGTKCGDGKVCINRHCVDVTTAY

extracellular region [GO:0005576]; plasma membrane [GO:0005886]

metal ion binding [GO:0046872]; toxin activity [GO:0090729]

PF08516;PF00200;PF01562;

4.10.70.10;

Venom metalloproteinase (M12B) family, P-III subfamily, P-IIIe sub-subfamily

PTM: N-glycosylated. Exists in at least six differently N-glycosylated forms. The glycans likely have a stabilizing purpose. {ECO:0000269|PubMed:35448841}.; PTM: Cys-199 forms a disulfide bond with Cys-192 in 90% and with Cys-179 in 10% of the protein molecules; alternative disulfide bonds may have a major effect on the conformation of the protein. {ECO:0000269|PubMed:35448841}.

SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:31017792, ECO:0000269|PubMed:35448841}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Structurally relatively unstable in pure water, but more stable in various buffers between pH 5-9. Most stable in 20 mM HEPES buffer at pH 7 with the addition of 2 mM Ca(2+). {ECO:0000269|PubMed:35448841};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Unfolds at 47 degrees Celsius in pure water, but structurally more stable in various buffers up to 60 degrees Celsius. {ECO:0000269|PubMed:35448841};

FUNCTION: Abolishes platelet aggregation induced by collagen, ADP (IC(50)=292 nM) and arachidonic-acid. The inhibition of collagen-induced platelet aggregation may be due to its ability to bind collagen and block the binding site on collagen for platelets and/or to its ability to bind to the platelet alpha-2/beta-1 collagen receptor (ITGA2/ITGB1) to block its interaction with collagen and hence prevent platelet stimulation. The inhibition of ADP- or arachidonic-acid-induced platelet aggregation may be due to it acting as an antagonist of the ADP receptors or thromboxane-prostanoid receptors of the platelets, respectively. Does not interact with integrins alpha-IIb (ITGA2B) or beta-3 (ITGB3) nor platelet glycoproteins VI (GP6) or IX (GP9) in vitro, however, the detection is dependent on experimental conditions and may happen in vivo. Able to bind to platelet glycoprotein Ib alpha chain (GP1BA) receptor in vitro, although this interaction may have pathologically only limited effect in vivo as it is not able to abolish the von Willebrand factor (vWF)-dependent platelet agglutination induced by ristocetin. Does not affect blood coagulation. {ECO:0000269|PubMed:35448841}.

Vipera ammodytes ammodytes (Western sand viper)

A0A6B9HER0

PIPCL_PIPNI

MEKSGYGNDGIYRSLRPPVLFPNDPNLSVTSYLFQRSDAYPDRLALADANSGETLNFAQFKAMVQRVSHGLSRLGIKKGDVVLIFSPNSIYFPVCFLAIVALGAVVTTGNPQYTSAEITKQANDSKPKLVITVPQLWDKVNHLGLPAVFLGSKISGDGTIAPSNRNINGTVTYFSNLVELGGHVSEFPPVSIKRSDIAALLYSSGTSGTSKGVILTHRNLISTACMTTSDQEFDGEDPNVFLCFLPMSHVFGLVIICYSQLMRGNSVVSVEKFDLEMVLRSVGKYRVTYLCVVPPVMIALAKQNWGKIYDLSSLKRIICGSAPLGKEVIEECAKNYPHVPIIQGYGLTESCGIASLEIPEGVREYGSSGILFPAVEAKIVHVENLTPLPPNQLGEIWIRGPNMMQGYLNNPQATKLTIDEQGWVHTGDLGYFNGEGRLSVVDRIKELIKCKGFQVAPAELEGLLLSHQEILDAVVIPYPDAEAGEVPIAYVVRALSSTLDEEAVKKFIAEQVAPFKRLRKVTFVNSVPKSASGKILRRELIAKVRSKI

6.2.1.-

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:O24146};

aromatic compound biosynthetic process [GO:0019438]

peroxisome [GO:0005777]

ATP binding [GO:0005524]; butyrate-CoA ligase activity [GO:0047760]; CoA-ligase activity [GO:0016405]; long-chain fatty acid-CoA ligase activity [GO:0004467]

PF00501;PF13193;

3.30.300.30;3.40.50.12780;

ATP-dependent AMP-binding enzyme family

SUBCELLULAR LOCATION: Peroxisome {ECO:0000250|UniProtKB:Q9M0X9}.

CATALYTIC ACTIVITY: Reaction=a carboxylate + ATP + CoA = AMP + an acyl-CoA + diphosphate; Xref=Rhea:RHEA:24336, ChEBI:CHEBI:29067, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:58342, ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:31837062}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24337; Evidence={ECO:0000305|PubMed:31837062}; CATALYTIC ACTIVITY: Reaction=(E,E)-piperate + ATP + CoA = (E,E)-piperoyl-CoA + AMP + diphosphate; Xref=Rhea:RHEA:73571, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57287, ChEBI:CHEBI:57325, ChEBI:CHEBI:192831, ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:31837062}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:73572; Evidence={ECO:0000305|PubMed:31837062}; CATALYTIC ACTIVITY: Reaction=(E,E)-piperate + ATP + H(+) = (E,E)-piperoyl-AMP + diphosphate; Xref=Rhea:RHEA:73575, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:192831, ChEBI:CHEBI:192833; Evidence={ECO:0000269|PubMed:31837062}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:73576; Evidence={ECO:0000305|PubMed:31837062}; CATALYTIC ACTIVITY: Reaction=(E,E)-piperoyl-AMP + CoA = (E,E)-piperoyl-CoA + AMP + H(+); Xref=Rhea:RHEA:73579, ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57325, ChEBI:CHEBI:192833, ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:31837062}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:73580; Evidence={ECO:0000305|PubMed:31837062};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=43.3 uM for piperic acid {ECO:0000269|PubMed:31837062}; KM=24.3 uM for 5-phenylpentanoic acid {ECO:0000269|PubMed:31837062}; Vmax=19.6 nmol/sec/mg enzyme with piperic acid as substrate {ECO:0000269|PubMed:31837062}; Vmax=27.9 nmol/sec/mg enzyme with 5-phenylpentanoic acid as substrate {ECO:0000269|PubMed:31837062}; Note=kcat is 1.09 sec(-1) with piperic acid as substrate (PubMed:31837062). kcat is 4.17 sec(-1) with 5-phenylpentanoic acid as substrate (PubMed:31837062). {ECO:0000269|PubMed:31837062};

PATHWAY: Aromatic compound metabolism. {ECO:0000269|PubMed:31837062}.

FUNCTION: Involved in the biosynthesis of aromatic piperamides natural products such as piperine (1-piperoyl-piperidine), the pungent principle contributing, together with several terpenoids, to the aromatic properties of black pepper fruits, and displaying numerous pharmacological activities such as antiproliferative, antitumor, antiangiogenesis, antioxidant, antidiabetic, antiobesity, cardioprotective, antimicrobial, antiaging, and immunomodulatory effects (PubMed:31837062). Acts as a carboxylate--CoA ligase that catalyzes exclusively the formation of piperoyl--CoA from piperic acid and CoA (PubMed:31837062). Can also use the synthetic substrate 5-phenylpentanoic acid to form the corresponding CoA ester (PubMed:31837062). {ECO:0000269|PubMed:31837062}.

Piper nigrum (Black pepper)

A0A6J2ATK2

AMPQ_ACIJB

MGPPSSSGFYVSRAVALLLAALAAALLLALAVLAALYGRCARVQPSDLHHGGVPDAASSPRGTQEEQLPTWPPRPTREPAGTATPGHWRPPGPWDQLRLPPWLVPLHYELELWPRLRPNEFQSPTLSFTGRVNITVRCTAATARLLLHSLFLDCESAEVRGPLSSGPRDGAVGRVPVDDVWFAFDMQYMVLELGATLQPGSRYELQLSFSGLVYRDLREGLFFSIYTDQGERRALLASQMEPTFARSVFPCFDEPALKATFNITIIHHPSYGALSNMPKLGQSEKRDVNGSVWTITTFSTTPHMPTYLVALAICDYDHVSRTERGQEIRIWARKDAIANGNAAFALNITGPIFSFLEDLFNISYPLPKTDIIALPTFDNSAMENWGLLIFDESLLLMQPNDQVTDKKAVISFILSHEIGHQWFGNLVTMNWWNDIWLKEGFASYFEFGVINYFNPKFRRNEVFFSNILHHVLSEDHALVSRAVSLKVENFTETSEINELFDLFTYNKGASLARMLSSFLNENVFISALKSYLKTFSYSTAEQDDLWRHFQMVVDDQSKILLPAPVKSIMDRWTHQSGFPVITLNVSTGAMKQEPFYLGKVKNQTLLTHNDTWIVPILWIKNGITQSLVWLDKSSKIFPEMQVSDSDHDWVILNLNMTGYYRVNYDKVGWKKLKQQLEKDPKAIPVIHRLQMIDDAFSLSKNNYVEIETALDLTKYLAEEDEIIVWYAVLVNLVTKDLVFDVNNYDMYPLLKKYLLKRLISIWNMYSTVIRENVAALQDDYLALVALEKLFETACWLGLEDCLQLSRELFKNWTNHPENEIPYPIKSVVLCYGVAFGSDEEWDFLLNMYSNKTKEEERIQLTYAMSCSKDPWILHRYLEYAVTAAPFTFNETNIMEVVAESEVGRYIVKDFLINNWQAVSERYGTQSLVNLMYIIGRTISTDLQITELQQFFSNMLEEHQKLTVRAKLQTIKNKNLGNKKLNARMTAWLRKNT

3.4.11.-

COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000305}; Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:M3XFH7};

peptide catabolic process [GO:0043171]; proteolysis [GO:0006508]

cytoplasm [GO:0005737]; membrane [GO:0016020]

metalloaminopeptidase activity [GO:0070006]; peptide binding [GO:0042277]; zinc ion binding [GO:0008270]

PF11838;PF01433;PF17900;

1.25.50.20;2.60.40.1910;1.10.390.10;2.60.40.1730;

Peptidase M1 family

SUBCELLULAR LOCATION: Membrane {ECO:0000250|UniProtKB:Q6Q4G3}; Single-pass type II membrane protein {ECO:0000250|UniProtKB:Q6Q4G3}.

FUNCTION: Metalloprotease which may be important for placentation by regulating biological activity of key peptides at the embryo-maternal interface (By similarity). Involved in coat pigmentation patterns. During skin development, may be required to establish the periodicity of tabby markings, initiating a pre-pattern at or before hair follicle development (PubMed:22997338). {ECO:0000250|UniProtKB:Q6Q4G3, ECO:0000269|PubMed:22997338}.

Acinonyx jubatus (Cheetah)

A0A6J4B487

LUC5_FUSSX

MGAPNSTREPIAIVGTACRFPGGANTPSKLWDLLCEKRDVQTRIPPERFNPDAFYHRNGEKSGCTDVKKAYLLTEDIRAFDASFFKINPREAEAMDPQQRLLLETVYEATEAAGLPYEDLKGSNTAVYVGSMTGDYHEMLLRDPQDMPKYMATGTARSILSNRVSYFFDWKGPSMTIDTACSSSLVAVHEAVTALRLGVSNIACAAGTNLILGPEMMISESKLHMLSPTGRSKMWDASANGYARGEGTAAIMMKTLSQALSDGDHVYGIIRETGVNSDGHTNGITLPSSESQKTLIRQTYANAGLDLIKERCQFFEAHGTGTPAGDPIEARAIHEAFFEDAAGSSDQMFVGSVKTAIGHLEGCAGLAGLIKALEAVRRGVIPPNQLFENLNPALKPFAGNLSIPTETLPWPEVAPGTPRRASVNSFGFGGTNAHAIIESFDNTPQPAPTGGIISYPLVLSANSEKSLRRQISQLHDTLQNAGEGEVQDTLYTLAQRRSQLPARTYFSGHTQEELLKKLSAASAEDATITVASQEVTNQNSRILGVFTGQGAQWPTMGREILKSSAFAGDLITRLETSLASLQEPPTWTLSEQILADPESSRLGEAAVSQPVCTAVQLMLVELLRQAGITFSTVIGHSSGEIAAAYAAGFLTPEDAIRIAYCRGVCAKLAGGEEGQKGSMMAVGLSYEEAACFCEDHFPGCIDVAASNAPSSATLSGDKDAILEAKALLDEQGTFARVLKVDTAYHSRHMQPCAEPYMALLRESNIQLLPGDDSCEWFSSVIGERMSSFTHGQLLTGEYWVENMVKPVLFTLASELAADSKLPCHVALEVGPHPALKGPFSQTYKRATGSQLPYQGALTRNVHDVEALSDALGFIWARLGKSAVNFASHAELFSVSKTSFSTNLPSYPWDHSQSFWKESRKSANFRQRTSPPHPLLGTRSTEDATQDLRWLNILHLDDAPWLEGHKVEGLVVYPAAAYLVMAMESAKSIDETKTIQLVELFDVQILSAIQLSQDSQGVETLFTLEIDDVNSTAATARWSLFTSMVGRGSNWKCNAKGHLRVDFGSEAQDSLLPSRDPPVASLTSVNIERFYTSLAEIGLGYTGAFKHLATVQRQSGFATAKASQMNTDFSAMIHPALLDSAFQSLFAAYCWPDDGSLAAPFVPTFFKSLRIVSLDHIENGQELTIDSYLTDTNDREITADLDIFTSDSEKPLLQLQGLTCTSLLRPGPSNAKELYTQTKWEVDISCAVASLDVQQHDAAEDLDLVDLCERLSYYYLRELNRKVDRSEVPAMDWHFQRIFEWIDYLFPIIEAGKHTTIRKEWSADEGSWLLEQASKFPGQVDLLLIRAVGENLTEVVRKETTMLEHMVRNDVLNRFYKFGLGFQRANGYLSRISKQIAHRYPQMKILEIGAGTGGATKGILESLGTTFESYTFTDISTGFFEAAAEAFEPWVSKIIFKPLNVENDPVEQGFLEAQYDFIVASNVLHATKSLSTTMRNVRRLLKPGGQLLLLEVTSDIVRVRLMMSGLSGWWLGGDDGRRYAPTITVPEWDSLLRSTGFSGVDHTVNDFYDPSKYMTSVMLSQAVDDHHVDILRKPLNSALGWLPQRCITIIGGKNNEIAQQVSKTLLSMKSASLDLINHVDSFEQLASTPELPLRAVLILEDLDEPVLKSLTSEKLAGLQRTINDSRQILWVSKGCQKDEPYANMSTGLCRSLASEYPHIQLQHIDMETGLDSLAVSRIVEALIRIVYKASLKQDDDLLWSHEAELILEDEGRWLIPRILPDDKLNDHLNAGKMKVKTNASLADTPVEIQQAGSQWVISQTVPSLPISDNTDHIRIKASYSTLHAVRVRGSRVYLSYGHRVTGSTTPVIAFSETAGSIISVPESQVFDVPQGFDIDQSASLRSLVLTAIVESVLAECDHGAAIIVHEADNYLGAAFETKCREIGLKLVRTTSKSDHKDDAIFIHPLAPERVVKKALPHVEVAVVVDLSGRDYSVVDSPLRRHVPSTTKFLELSDLIGSVTCGLRDVNIQCVQDAIESSFKSPSDGPVVNISEVSGLQASETSYATVVDWSIEKPVSVQVQPLQANRLLRSDRTYLLAGCTGGLGKALCRWMVAAGVRHLALTTRNVEAIDKVWLEGLQLQGADVRLFQVDVGDKAALERAHAQVTAEMPPICGVANAAMVLSDRSFGELKVGDFDKVFGPKVRGTQNLHELFQDEPLDFFIMFSSLASVVGNRGQANYAAANLFMTAVAEQRRAKNLAASVIHIGMILGVGYVSSTGAYEATLRQYNYMPISEPDFLNMFSEAILVGQPGSSHAPELITGLNRYSLQEDAPKFFWHENMRFSHHTLEEQHQESTSTTKASISQRLAQVQTPAEMLEVVEEEFCTKLERMLQAESGTIKVSQPLMSLGVDSLIAAEIRSWFFKELDVDMPVLEILNTASVAEICSTAVASLATLAPQEQTETTTLVTSEAVQSLNAVSGNGSSSSRAPTEFNSSTLKSGAQSTQGTSVSGDKDTNSVDGSAKVERNGPLSFAQERIWFLQQYLQDATTFNVTMAYRITGPLRVNDLESAFQKVIQRHESLRTGFHMDPETTVPTQIVYEQSPFGLEQRNDSDITKEFEELQNTHYDLENGRVLKAIVLTKPDTDEHILLVGFHHIALDGFSAQILVRDLAIAYAGGNLAPLDKGYLDFAVDQRAAVYPAETLQYWKTEFETLPPALPVFDFAETKTRLPLTDYKTRVSERTLQPDVAGKAKSAARALAATPFHVYLAALQVLLSDFASTQDVCIGITDANKNDAAHMDTIGFFVNLLPLRFQLSASQTLAELVSNTKAKANGALTHSRLPFDVLLDELKIPRSTSHSPLFQVVLNFKMGSTQKVPLADCQAEVIDFKDVNNPYDLAFDIETYPDGSTSISVKSQEYLYTKNELDLILESYINLLSLFEKDSSKTLGEVSQCTPDEAQKTLTLGRGERIPSPSFDTLSHYFEDWVKRQPDAIAIRDDQGTTLSYSQLKSFVNNIAATLEKSGLTPGARVGVYCEPSIFIIASLLAIAEVGGVYVPLDPQNPIKRLQLIVDDCEPEILLFDESTKELAPKLQTNASLINIYNVRRLPSSAAITNRAQGAGMAYMFYTSGTTGVPKGVALTHANLVHHIDSITHFYDIKRGTMLQQAPLGFDMSLTQMSLSTMLGGTLVVASSEARKDPLQLAKLMLSERVTHTFMTPTLAVALIHHGYEYLVKCVGWEFSLLSGEAFRTHVISEFQRLGLPQLKLFNGYGPTEITINSSSGLNELDLAAPRDTRNPTIGFTLPNYSCYILDEDLKPVRPGHAGELFVGGAGIAVGYLRRDELNKERFLSDPFASSEDVARGWARMYRTGDKAKFLPDGRIVFLGRIAGDSQIKLRGFRIELEDIANTIVKSSGGVVSEAAVSFRQGVNGPDDGAFLVAFAIISQAHRPENPSSFLKQLLKDLSLPRYMIPAKIVQVEHLPMGPTGKLDQNALDVMPIPQDENVHEETLTTTQERLRALWFESLPAVAPDAFIGSETDFFEAGGNSLRIVMLREHIAREFGVMVSVFDLFQASTLGGMAAKIDGSTGADNQPIIWEEETRVDIPSGLETPDEPAILDGDELEVALTGATGFLGLAILRSLLKDERISRVHCLAVRSPSKARDEVFKSPRVVVYHGDLSSPRLGLSEDEFGTLSKKFDIIIHNGAEVSFLKSYQALKKANVSSTKELAQLASGRQIPFHFVSTGGVVNLTDHDGLPEISVSGFKPPIDGTEGYAASKWASEVILESHAERAHLPVWIHRPANVTGAAAPATDLMGSILQYSTTMQSLPEISNWKGSFDFVPVEQVADEIAASIHESRSSEPVYRHHCGDQKISVSELSAHLEAGIGAKMEIIGVDDWLARARSTGIDETTALLVEKMLSGENGGTVPWLRKGE

2.3.1.-; 6.3.2.-

amide biosynthetic process [GO:0043604]; fatty acid biosynthetic process [GO:0006633]; heterocycle biosynthetic process [GO:0018130]; methylation [GO:0032259]; organic cyclic compound biosynthetic process [GO:1901362]; organonitrogen compound biosynthetic process [GO:1901566]; toxin biosynthetic process [GO:0009403]

3-oxoacyl-[acyl-carrier-protein] synthase activity [GO:0004315]; fatty acid synthase activity [GO:0004312]; isomerase activity [GO:0016853]; ligase activity [GO:0016874]; methyltransferase activity [GO:0008168]; oxidoreductase activity [GO:0016491]; phosphopantetheine binding [GO:0031177]

PF00698;PF00501;PF00668;PF16197;PF00109;PF02801;PF08659;PF08242;PF07993;PF21089;PF00550;PF14765;

3.30.300.30;3.40.47.10;1.10.1200.10;3.30.559.10;3.40.366.10;3.40.50.12780;3.40.50.720;3.30.559.30;3.10.129.110;3.40.50.150;

NRP synthetase family

PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:32043422, ECO:0000269|PubMed:35484225}.

FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of the mycotoxin lucilactaene and the lucilactaene-related compound NG-391 that act as cell cycle inhibitors with potent growth inhibitory activity against malarial parasites, moderate growth inhibitory activity against cancer cells, and no activity against bacteria and fungi (PubMed:32043422, PubMed:35484225). The hybrid PKS-NRPS synthetase LUC5 is responsible for the condensation of one acetyl-coenzyme A (CoA) unit with six malonyl-CoA units and the amide linkage of the arising heptaketide and homoserine, subsequently releasing the first intermediate prelucilactaene B, as an alcohol with an open ring structure (PubMed:32043422). Lucilactaene and NG-391 lack the 7-methyl group present in fusarins which is inserted in fusarins by the C-methyltransferase (CMeT) domain of the fusarin synthetase FUS1, suggesting that the CMet domain of LUC5 does not methylate this position (PubMed:32043422). Within the pathway, both the cytochrome P450 monooxygenase LUC2 and the hydrolase LUC6 function in parallel in modification of prelucilactaene B. LUC6 may catalyze the 2-pyrrolidone ring formation to form prelucilactaene C from prelucilactaene B, followed by C-15 hydroxylation by the same enzyme to give prelucilactaene D, which is then converted to prelucilactaene E by epoxidation, and finally to prelucilactaene F by cyclization. Prelucilactane D, prelucilactaene E, and prelucilactaene F can be converted to dihydrolucilactaene, NG391, and lucilactaene, respectively, via C-20 methyl group hydroxylation by the cytochrome P450 monooxygenase LUC2. However, LUC2, unlike FUS8 in fusarin C biosynthesis, is not enough for the full oxidation of the C-20 methyl group into carboxylic acid, which is a prerequisite for the final methylation step. The aldehyde dehydrogenase LUC3 is involved in the biosynthesis by further oxidation of the C-20 alcoholic analog prelucilactaene G into a carboxylic derivative. This unidentified carboxylic derivative may be converted to demethyllucilactaene. As the last step, the methyltransferase LUC1 methylates the hydroxyl group at C-21 of demethyllucilactaene to generate lucilactaene (Probable). {ECO:0000269|PubMed:32043422, ECO:0000269|PubMed:35484225, ECO:0000305|PubMed:35484225}.

Fusarium sp

A0A6M7H989

DLMIS_ECO57

MKRSAINDILGHTRQFFSQHDVHLPPFASFSPAQWQQLDTAAWEEVFDLKLGWDVTAFGRNNFAAHGLTLFTLRNGSAKGMPYVKCYAEKIMHVRDAQVTPMHFHWRKREDIINRGGGNLIVELWNADSNEQTADSDITVVIDGCRQKHTAGSQLRLSPGESICLPPGLYHSFWAEAGFGDVLVGEVSSVNDDDHDNHFLQPLDRYNLIDEDEPAQLVLCNEYRQFR

5.3.1.15; 5.3.1.7

COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:20615418};

isomerase activity [GO:0016853]; metal ion binding [GO:0046872]

PF07385;

2.60.120.10;

D-lyxose ketol-isomerase family

CATALYTIC ACTIVITY: Reaction=D-lyxose = D-xylulose; Xref=Rhea:RHEA:14201, ChEBI:CHEBI:16789, ChEBI:CHEBI:17140; EC=5.3.1.15; Evidence={ECO:0000269|PubMed:20615418}; CATALYTIC ACTIVITY: Reaction=D-mannose = D-fructose; Xref=Rhea:RHEA:22604, ChEBI:CHEBI:4208, ChEBI:CHEBI:37721; EC=5.3.1.7; Evidence={ECO:0000269|PubMed:20615418};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=16.1 mM for D-lyxose {ECO:0000269|PubMed:20615418}; KM=19.8 mM for D-mannose {ECO:0000269|PubMed:20615418}; KM=55.2 mM for L-gulose {ECO:0000269|PubMed:20615418}; Vmax=14.1 umol/min/mg enzyme with D-lyxose as substrate {ECO:0000269|PubMed:20615418}; Vmax=13.1 umol/min/mg enzyme with D-mannose as substrate {ECO:0000269|PubMed:20615418}; Vmax=9.09 umol/min/mg enzyme with L-gulose as substrate {ECO:0000269|PubMed:20615418}; Note=kcat is 13.7 sec(-1) with D-lyxose as substrate. kcat is 12.7 sec(-1) with D-mannose as substrate. kcat is 8.78 sec(-1) with L-gulose as substrate. {ECO:0000269|PubMed:20615418};

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.5. {ECO:0000269|PubMed:20615418};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 50 degrees Celsius. {ECO:0000269|PubMed:20615418};

FUNCTION: Sugar isomerase that catalyzes the reversible isomerization of D-lyxose to D-xylulose, and D-mannose to D-fructose (PubMed:20615418). Shows similar activity toward D-lyxose and D-mannose with a turnover and catalytic efficiency for D-lyxose as a substrate only 1.1- and 1.3-fold higher than those for D-mannose, respectively (PubMed:20615418). Shows weaker activity with L-gulose, D-talose, L-ribose and L-allose (PubMed:20615418). Overexpression enables cell growth on the rare pentose D-lyxose as the sole carbon source (PubMed:20615418). {ECO:0000269|PubMed:20615418}.

Escherichia coli O157:H7

A0A6P3CW73

CYCTI_TITOB

MKFIIVLLLLTALTLTSIPVIEGILKRCKTYDDCKDVCKARKGKCEFGICKCMIKSGK

extracellular region [GO:0005576]

serine-type endopeptidase inhibitor activity [GO:0004867]

PTM: This is a cyclic peptide. {ECO:0000269|PubMed:32787139}.

SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:32787139}.

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Is very stable at high temperature. {ECO:0000269|PubMed:32787139};

FUNCTION: First cyclic scorpion trypsin inhibitor (Kd~0.5 nM). Does not inhibit chymotrypsin. {ECO:0000269|PubMed:32787139}.

Tityus obscurus (Amazonian scorpion) (Tityus cambridgei)

A0A6P3HVI0

SL9B2_BISBB

MRNQDKRAAHKDSEPSTEVNHTASSYQGRQQETGMNLRGIDGNEPTEGSNLLNNNEKMQGTPAEPNHLQRRRQIHACPPRGLLARVITNVTMVILLWAVVWSVTGSECLPGGNLFGIIMLFYCAIIGGKLFGLIKLPTLPPLPPLLGMLLAGFLIRNVPVISDNIQIKHKWSSALRSIALSVILVRAGLGLDSNALKKLKGVCVRLSLGPCLIEACTSAVLAYFLMGLPWQWGFMLGFVLGAVSPAVVVPSMLLLQEGGYGVEKGIPTLLMAAGSFDDILAITGFNTCLGMAFSTGSTVFNVLKGVLEVIIGVVTGLVLGFFIQYFPSSDQDNLVWKRAFLVLGLSVLAVFSSTYFGFPGSGGLCTLVTAFLAGRGWASTKTDVEKVIAVAWDIFQPLLFGLIGAEVLITALRPETIGLCVATLGIAVLIRILVTYLMVCFAGFNIKEKIFISFAWLPKATVQAAIGSVALDTARSHGEKQLEGYGMDVLTVAFLSIIITAPVGSLLIGLLGPRLLQKAEQNKDEEDQGETSIQV

lithium ion transport [GO:0010351]; sodium ion homeostasis [GO:0055078]; sodium ion transport [GO:0006814]

apical plasma membrane [GO:0016324]; basolateral plasma membrane [GO:0016323]; endosome membrane [GO:0010008]; lysosomal membrane [GO:0005765]; mitochondrial membrane [GO:0031966]; plasma membrane [GO:0005886]; recycling endosome [GO:0055037]; recycling endosome membrane [GO:0055038]; sperm principal piece [GO:0097228]; synaptic vesicle membrane [GO:0030672]

identical protein binding [GO:0042802]; lithium:proton antiporter activity [GO:0010348]; metal ion binding [GO:0046872]; sodium:proton antiporter activity [GO:0015385]

PF00999;

1.20.1530.20;

Monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:35173351}; Multi-pass membrane protein {ECO:0000269|PubMed:35173351}. Mitochondrion membrane {ECO:0000250|UniProtKB:Q5BKR2}; Multi-pass membrane protein {ECO:0000269|PubMed:35173351}. Endosome membrane {ECO:0000250|UniProtKB:Q5BKR2}; Multi-pass membrane protein {ECO:0000269|PubMed:35173351}. Recycling endosome membrane {ECO:0000250|UniProtKB:Q5BKR2}; Multi-pass membrane protein {ECO:0000269|PubMed:35173351}. Lysosome membrane {ECO:0000250|UniProtKB:Q5BKR2}; Multi-pass membrane protein {ECO:0000269|PubMed:35173351}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000250|UniProtKB:Q5BKR2}; Multi-pass membrane protein {ECO:0000269|PubMed:35173351}. Cell projection, cilium, flagellum membrane {ECO:0000250|UniProtKB:Q5BKR2}; Multi-pass membrane protein {ECO:0000269|PubMed:35173351}. Basolateral cell membrane {ECO:0000250|UniProtKB:Q5BKR2}; Multi-pass membrane protein {ECO:0000269|PubMed:35173351}. Apical cell membrane {ECO:0000250|UniProtKB:Q5BKR2}; Multi-pass membrane protein {ECO:0000269|PubMed:35173351}.

CATALYTIC ACTIVITY: Reaction=H(+)(in) + Li(+)(out) = H(+)(out) + Li(+)(in); Xref=Rhea:RHEA:72407, ChEBI:CHEBI:15378, ChEBI:CHEBI:49713; Evidence={ECO:0000269|PubMed:35173351}; CATALYTIC ACTIVITY: Reaction=Li(+)(in) + Na(+)(out) = Li(+)(out) + Na(+)(in); Xref=Rhea:RHEA:72415, ChEBI:CHEBI:29101, ChEBI:CHEBI:49713; Evidence={ECO:0000250|UniProtKB:Q86UD5}; CATALYTIC ACTIVITY: Reaction=H(+)(out) + Na(+)(in) = H(+)(in) + Na(+)(out); Xref=Rhea:RHEA:29419, ChEBI:CHEBI:15378, ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:35173351};

FUNCTION: Electroneutral Na(+) Li(+)/H(+) antiporter that extrudes Na(+) or Li(+) in exchange for external protons across the membrane (PubMed:35173351). Uses the proton gradient/membrane potential to extrude sodium (By similarity). Contributes to the regulation of intracellular pH and sodium homeostasis (By similarity). Also able to mediate Na(+)/Li(+) antiporter activity in kidney (By similarity). May play a physiological role in renal tubular function and blood pressure homeostasis (By similarity). Plays an important role for insulin secretion and clathrin-mediated endocytosis in beta-cells. Involved in sperm motility and fertility. It is controversial whether SLC9B2 plays a role in osteoclast differentiation or not (By similarity). {ECO:0000250|UniProtKB:Q5BKR2, ECO:0000250|UniProtKB:Q86UD5, ECO:0000269|PubMed:35173351}.

Bison bison bison (North American plains bison)

A0A6P6DKR7

APOE_OCTDE

MKVLCTVLVVTLLAGCRADVEPEPEVLEPAVWKSGQPWELALGRFWDYVRWVQTLSDQVQEELLSSQVTQELTVLMEDTMKAVKAYKSELEQELVPMAEDTKARLSKELQAAQARLGADMEEVRNRLAQYRNEMQAMLGQSADELRARLASHLRKLRKRMLRDAEDLQKRLAVYKDGASEGAERGVSAIRERLGSLVEQSRVRAALTGQPLQERAQAWGKQLRGRLEEVRGQAQDRLEEMREQMEEVRVKIEEQAEAFQTRLKGWFEPMVEDMRRQWADLIEKVQAAVGASTPVPSQKP

cholesterol catabolic process [GO:0006707]; lipid transport [GO:0006869]; lipoprotein catabolic process [GO:0042159]; melanosome organization [GO:0032438]; negative regulation of neuron apoptotic process [GO:0043524]; regulation of amyloid-beta clearance [GO:1900221]

chylomicron [GO:0042627]; extracellular exosome [GO:0070062]; high-density lipoprotein particle [GO:0034364]; intermediate-density lipoprotein particle [GO:0034363]; multivesicular body, internal vesicle [GO:0097487]; very-low-density lipoprotein particle [GO:0034361]

amyloid-beta binding [GO:0001540]; heparin binding [GO:0008201]; lipid binding [GO:0008289]; low-density lipoprotein particle receptor binding [GO:0050750]; very-low-density lipoprotein particle receptor binding [GO:0070326]

PF01442;

1.20.120.20;

Apolipoprotein A1/A4/E family

PTM: APOE exists as multiple glycosylated and sialylated glycoforms within cells and in plasma. The extent of glycosylation and sialylation are tissue and context specific. {ECO:0000250|UniProtKB:P02649}.; PTM: Glycated in plasma VLDL. {ECO:0000250|UniProtKB:P02649}.; PTM: Phosphorylated by FAM20C in the extracellular medium. {ECO:0000250|UniProtKB:P02649}.

SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:P02649}. Secreted, extracellular space {ECO:0000250|UniProtKB:P02649}. Secreted, extracellular space, extracellular matrix {ECO:0000250|UniProtKB:P02649}. Extracellular vesicle {ECO:0000250|UniProtKB:P02649}. Endosome, multivesicular body {ECO:0000250|UniProtKB:P02649}. Note=In the plasma, APOE is associated with chylomicrons, chylomicrons remnants, VLDL, LDL and HDL lipoproteins. Lipid poor oligomeric APOE is associated with the extracellular matrix in a calcium- and heparan-sulfate proteoglycans-dependent manner. Lipidation induces the release from the extracellular matrix. Colocalizes with CD63 and PMEL at exosomes and in intraluminal vesicles within multivesicular endosomes. {ECO:0000250|UniProtKB:P02649}.

FUNCTION: APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids. APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance. Apolipoproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma. As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles. Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells. A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes. APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of triglycerides and energy storage in muscle, heart and adipose tissues. By participating in the lipoprotein-mediated distribution of lipids among tissues, APOE plays a critical role in plasma and tissues lipid homeostasis. APOE is also involved in two steps of reverse cholesterol transport, the HDLs-mediated transport of cholesterol from peripheral tissues to the liver, and thereby plays an important role in cholesterol homeostasis. First, it is functionally associated with ABCA1 in the biogenesis of HDLs in tissues. Second, it is enriched in circulating HDLs and mediates their uptake by hepatocytes. APOE also plays an important role in lipid transport in the central nervous system, regulating neuron survival and sprouting. {ECO:0000250|UniProtKB:P02649}.

Octodon degus (Degu) (Sciurus degus)

A0A6P6W6H5

TPS1_COFAR

MAIINLPVPTNSSSEVNKHNHLRSCLPSGRATFTTLSAAAMRSATMAAANVREQSGQKQQLINRRSGNYEAPLWEFDYIQSLKNEYAGDIYVSRANELKEQVKMMLDEEDMKLLDCMELVDGLERLGLAYHFEGRINRLLSSDYKAIHEGNHQRNKEDLYAAALEFRIFRQNGFNVPQDIFNDFITEDGEFDESLSEDTMGLLSLYEASFLSLEGEATLDLAREFTTKHLNNYLGKENTDQNLRILVYHALELPLRWRAPRIEARWYIDAYERSPNVNPTLLELAKIDFNIVQAIHQQDLKHVSWWWKNIRIAEKLTFIRDRIVENFFWAIGAVFEPQYGSCRRMLTKVFALITMIDDIYDVYGTLEELELFTDAVDRWDVKAIDQLPDYMRVGYLGFFNSINEMAYDALKEQGVHIVEYLRKVWADLCKAYLQEAKWYYAGYTPTVEEYLENAWVSMSVPVMLMHAYAGVTNPMNKEAMDVLDTHDIVRCSSYLLRFADDLGTSPGEMKRGDVPKLVQCYMKEAGCSEEESREHVWFLLRETWKKMNKDSEWAESPFSKTFVTAAKNFGRVALVMYQYGDGHGLHSNPEAKDRILASLFSPVPPA

4.2.3.-; 4.2.3.113; 4.2.3.15; 4.2.3.47

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:A0A1C9J6A7}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250|UniProtKB:A0A1C9J6A7}; Note=Binds 3 Mg(2+) or Mn(2+) ions per subunit. {ECO:0000250|UniProtKB:A0A1C9J6A7};

alpha-pinene biosynthetic process [GO:0046248]; diterpenoid biosynthetic process [GO:0016102]; limonene biosynthetic process [GO:0046250]; monoterpenoid metabolic process [GO:0016098]

chloroplast [GO:0009507]

magnesium ion binding [GO:0000287]; myrcene synthase activity [GO:0050551]; pinene synthase activity [GO:0050550]; sabinene synthase activity [GO:0080015]

PF01397;PF03936;

1.10.600.10;1.50.10.130;

Terpene synthase family, Tpsb subfamily

SUBCELLULAR LOCATION: Plastid, chloroplast {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate = (E)-beta-farnesene + diphosphate; Xref=Rhea:RHEA:27425, ChEBI:CHEBI:10418, ChEBI:CHEBI:33019, ChEBI:CHEBI:175763; EC=4.2.3.47; Evidence={ECO:0000269|PubMed:23398891}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:27426; Evidence={ECO:0000269|PubMed:23398891}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate = diphosphate + limonene; Xref=Rhea:RHEA:68640, ChEBI:CHEBI:15384, ChEBI:CHEBI:33019, ChEBI:CHEBI:58057; Evidence={ECO:0000269|PubMed:23398891}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68641; Evidence={ECO:0000269|PubMed:23398891}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate = beta-pinene + diphosphate; Xref=Rhea:RHEA:25666, ChEBI:CHEBI:33019, ChEBI:CHEBI:50025, ChEBI:CHEBI:58057; Evidence={ECO:0000269|PubMed:23398891}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25667; Evidence={ECO:0000269|PubMed:23398891}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate = diphosphate + sabinene; Xref=Rhea:RHEA:68636, ChEBI:CHEBI:33019, ChEBI:CHEBI:50027, ChEBI:CHEBI:58057; Evidence={ECO:0000269|PubMed:23398891}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68637; Evidence={ECO:0000269|PubMed:23398891}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate = beta-myrcene + diphosphate; Xref=Rhea:RHEA:16965, ChEBI:CHEBI:17221, ChEBI:CHEBI:33019, ChEBI:CHEBI:58057; EC=4.2.3.15; Evidence={ECO:0000269|PubMed:23398891}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16966; Evidence={ECO:0000269|PubMed:23398891}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate = alpha-pinene + diphosphate; Xref=Rhea:RHEA:25662, ChEBI:CHEBI:33019, ChEBI:CHEBI:36740, ChEBI:CHEBI:58057; Evidence={ECO:0000269|PubMed:23398891}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25663; Evidence={ECO:0000269|PubMed:23398891}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate = diphosphate + terpinolene; Xref=Rhea:RHEA:25500, ChEBI:CHEBI:9457, ChEBI:CHEBI:33019, ChEBI:CHEBI:58057; EC=4.2.3.113; Evidence={ECO:0000269|PubMed:23398891}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25501; Evidence={ECO:0000269|PubMed:23398891};

PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis. {ECO:0000269|PubMed:23398891}.

FUNCTION: Monoterpene synthase (mono-TPS) involved in the biosynthesis of monoterpenes natural products, constituent of coffee beverage aroma (PubMed:23398891). Catalyzes the conversion of (2E)-geranyl diphosphate (GPP) into limonene, beta-pinene, sabinene and beta-myrcene, and, as minor products, alpha-pinene and alpha-terpinolene (PubMed:23398891). Can also, with a low efficiency, use farnesyl pyrophosphate (FPP) as substrate to produce beta-farnesene (PubMed:23398891). Not able to use geranylgeranyl pyrophosphate (GGPP) as substrate (PubMed:23398891). {ECO:0000269|PubMed:23398891}.

Coffea arabica (Arabian coffee)

A0A6S6QJ62

PLE4_RHOPP

MRIPNIFLSYLRQVAVDGTLSSCSGVKSRKPVIAFGFDDSQDSLVDENDEKILEPFGYYRHLLKGKSARTVLMHCFNAFLGLPEDWVLGVTKAIEDLHNASLLIDDIEDESALRRGSPAAHMKYGIALTMNAGNLVYFTVLQDIYDLGMRTGGTQVANAMAHIYTEEMIELHRGQGIEIWWRDQRSPPSVDQYIHMLEQKTGGLLRLGVRLLQCHPGGNNRADLSAIALRIGVYYQLRDDYINLMSTSYHDERGFAEDITEGKYTFPMLHSLKRSPDSGLREILDLKPADIALKKKAIAIMQETGSLIATRNLLGAVKNDLSGLVAEQRGDDYAMSAGLERFLEKLYIAE

2.5.1.-; 2.5.1.1; 2.5.1.10; 2.5.1.29

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q12051}; Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051};

antibiotic biosynthetic process [GO:0017000]; plastoquinone biosynthetic process [GO:0010236]; terpenoid biosynthetic process [GO:0016114]; ubiquinone biosynthetic process [GO:0006744]

mitochondrion [GO:0005739]; transferase complex [GO:1990234]

metal ion binding [GO:0046872]; prenyltransferase activity [GO:0004659]

PF00348;

1.10.600.10;

FPP/GGPP synthase family

CATALYTIC ACTIVITY: Reaction=dimethylallyl diphosphate + isopentenyl diphosphate = (2E)-geranyl diphosphate + diphosphate; Xref=Rhea:RHEA:22408, ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769; EC=2.5.1.1; Evidence={ECO:0000250|UniProtKB:Q12051}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate + isopentenyl diphosphate = (2E,6E)-farnesyl diphosphate + diphosphate; Xref=Rhea:RHEA:19361, ChEBI:CHEBI:33019, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.10; Evidence={ECO:0000250|UniProtKB:Q12051}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate = (2E,6E,10E)-geranylgeranyl diphosphate + diphosphate; Xref=Rhea:RHEA:17653, ChEBI:CHEBI:33019, ChEBI:CHEBI:58756, ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.29; Evidence={ECO:0000250|UniProtKB:Q12051};

PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis. {ECO:0000269|PubMed:28924980}.

FUNCTION: Geranylgeranyl pyrophosphate synthase; part of the gene cluster that mediates the biosynthesis of pleuromutilin, a tricyclic diterpene showing antibacterial properties (PubMed:28924980). The geranylgeranyl diphosphate (GGPP) synthase ple4 catalyzes the first step in pleuromutilin biosynthesis (PubMed:28924980). GGPP is then substrate of the premutilin synthase (PS) ple3 to yield premutilin (PubMed:28924980). Premutilin synthase is a bifunctional enzyme composed of the fusion of a class II diterpene cyclase (DTC) and a class I diterpene synthase (DTS), with the corresponding domains and active sites containing characteristic aspartate-rich motifs (By similarity). GGPP is first converted to mutildienyl-diphosphate (MPP) at the class II DTC site (By similarity). MPP is subsequently further cyclized at the class I DTS site, followed by a 1,5-hydride shift and addition of water prior to terminating deprotonation, to yield premutilin (By similarity). The cytochrome P450 monooxygenases ple5 and ple6 hydroxylate premutilin at C-11 and C-3, respectively, producing 11-hydroxypremutilin and 3-hydroxypremutilin (PubMed:28924980). The combination of the actions of both ple5 and ple6 leads to the production of 3,11-dihydroxypremutilin (PubMed:28924980). The short chain dehydrogenase ple7 further converts 3,11-dihydroxypremutilin into mutilin (PubMed:28924980). The acetyltransferase ple2 then acetylates mutilin to produce 14-O-acetylmutilin (PubMed:28924980). Finally, the cytochrome P450 monooxygenase ple1 catalyzes hydroxylation on the alpha position of the acetyl side chain of 14-O-acetylmutilin to yield pleuromutilin (PubMed:28924980). {ECO:0000250|UniProtKB:A0A2L0VXR0, ECO:0000269|PubMed:28924980}.

Rhodocybe pseudopiperita (Clitopilus pseudopiperitus)

A0A7E6FSU6

OXDD_OCTVU

MVKIAVIGAGVVGLSTALQVKQNFPFCSVTVVAEKFNTETTSDGAGGLFRPNFLTLSANPLESIKQWSQDTFSHFNNLFNSPEASDCGIALMSGFLLSNKEKLDMIEDISLGQSKMTAEQIAKMGFDCKHVTKVLTYTMECRRYMPWLTSKFLSLGGSMHHHRLKSLEELVGVYDVVVNCSGLGAKDLVPDPLVYPVKGQLIQVEAPWVKHFYFFEDDTYVIPNINRTSLGGIRIKNDYSTEVDPEISKSIWQRCTSRIPSLQKAKVLWEWAGLRPHRDPIRIEQDVMNFPKGTLKVVHNYGHGANGVSLSWGTAKHATRLVRQFLENDPELRSKL

1.4.3.1

COFACTOR: Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000269|PubMed:7915543};

D-amino acid catabolic process [GO:0019478]

peroxisomal matrix [GO:0005782]

D-aspartate oxidase activity [GO:0008445]; FAD binding [GO:0071949]

PF01266;

3.30.9.10;3.40.50.720;

DAMOX/DASOX family

SUBCELLULAR LOCATION: Peroxisome matrix {ECO:0000250|UniProtKB:Q99489}.

CATALYTIC ACTIVITY: Reaction=D-aspartate + H2O + O2 = H2O2 + NH4(+) + oxaloacetate; Xref=Rhea:RHEA:12512, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:16452, ChEBI:CHEBI:28938, ChEBI:CHEBI:29990; EC=1.4.3.1; Evidence={ECO:0000269|PubMed:7915543}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12513; Evidence={ECO:0000269|PubMed:7915543}; CATALYTIC ACTIVITY: Reaction=D-glutamate + H2O + O2 = 2-oxoglutarate + H2O2 + NH4(+); Xref=Rhea:RHEA:10028, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29986; Evidence={ECO:0000269|PubMed:7915543}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10029; Evidence={ECO:0000269|PubMed:7915543};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=4.3 mM for D-aspartate (at 25 degrees Celsius and at pH 7) {ECO:0000269|PubMed:7915543}; KM=9.7 mM for D-glutamate (at 25 degrees Celsius and at pH 7) {ECO:0000269|PubMed:7915543}; KM=47.7 mM for N-methyl D-aspartate(at 25 degrees Celsius and at pH 7) {ECO:0000269|PubMed:7915543}; KM=440 mM for D-proline (at 25 degrees Celsius and at pH 7) {ECO:0000269|PubMed:7915543}; KM=240 mM for D-asparagine (at 25 degrees Celsius and at pH 7) {ECO:0000269|PubMed:7915543}; KM=815 mM for D-glutamine (at 25 degrees Celsius and at pH 7) {ECO:0000269|PubMed:7915543}; Note=kcat is 6.8 sec(-1) with D-aspartate as substrate (at 25 degrees Celsius and at pH 7) (PubMed:7915543). kcat is 11 sec(-1) with D-glutamate as substrate (at 25 degrees Celsius and at pH 7) (PubMed:7915543). kcat is 2.4 sec(-1) with D-proline as substrate (at 25 degrees Celsius and at pH 7) (PubMed:7915543). kcat is 3.2 sec(-1) with D-proline as substrate (at 25 degrees Celsius and at pH 7) (PubMed:7915543). kcat is 1.1 sec(-1) with D-asparagine as substrate (at 25 degrees Celsius and at pH 7) (PubMed:7915543). kcat is 4.5 sec(-1) with D-glutamine as substrate (at 25 degrees Celsius and at pH 7) (PubMed:7915543). {ECO:0000269|PubMed:7915543};

FUNCTION: Selectively catalyzes the oxidative deamination of acidic amino acids (PubMed:7915543). Suppresses the level of D-aspartate in the brain, an amino acid that can act as an agonist for glutamate receptors (By similarity). Protects the organism from the toxicity of D-amino acids (By similarity). May also function in the intestine (By similarity). {ECO:0000250|UniProtKB:D3ZDM7, ECO:0000250|UniProtKB:Q922Z0, ECO:0000269|PubMed:7915543}.

Octopus vulgaris (Common octopus)

A0A7G6KN55

DFB13_CROPO

MRLLYLLFAAVMLLFLQAVPANGSYYSTLQCRNNHGHCRRLCFHGEQWIGNCNGRHQHCCK

cell chemotaxis [GO:0060326]; defense response to bacterium [GO:0042742]; defense response to fungus [GO:0050832]; killing of cells of another organism [GO:0031640]

extracellular space [GO:0005615]

CCR6 chemokine receptor binding [GO:0031731]; chemoattractant activity [GO:0042056]; identical protein binding [GO:0042802]; phosphatidic acid binding [GO:0070300]

PF00711;

Beta-defensin family

SUBCELLULAR LOCATION: Secreted {ECO:0000305|PubMed:33309943, ECO:0000305|PubMed:36859344}.

FUNCTION: Exhibits antimicrobial activity against fungi (PubMed:36859344). Antimicrobial activity in a pH-dependent manner against the yeast C.albicans; activity is salt tolerant and retains antifungal activity in NaCl concentrations of 100mM (PubMed:36859344). Permeabilizes C.albicans cell membranes via targeting plasma membrane phospholipid phosphatidic acid (PubMed:36859344). {ECO:0000269|PubMed:36859344}.

Crocodylus porosus (Saltwater crocodile) (Estuarine crocodile)

A0A7J6K7I9

WNG2_TOXGO

MMFPAVAAPPRRLPGERLQRSQNPVETSWLSFRILATRGPCVTSTFLFLTVAFLGLSWVSVAVAAHAEHPEDSATNFLFSFAENSLANREPPEDSAARPSSRSGGAERRRLDSLIPGFLKRRRIFKQLRPVDEFQLREFQEASSKVKAQFFSAGHSKVTFVDRPSAALLSFLHLEEEDVPYGVVIKAIPYDAFDFYESVAEPYIHRMFDDPRKFPYVVPVLAALRSTSKRVLYLVLPLYRELPETVDEEARSLDFVLLLAEMAMAVCQLHERNLAHRDLKEDNFLVSPEGHIVVSDLATLDITDNKSFLIGTSGYMPPETRSSYLLRKGYKRSRYGEKTDVYSLGVAFRHLAFMLEGLGVQVPHRTQLAKLIKKMTSPDPEKRPLIGEVMEDPFFASVDFRLVRQRAGKHPFKKLPGADLLAERQRARLEAREKADAAAKAADNAEVPAAKSPAGKTGGAGTLSGDRDRAGSGEKPAERAEEEKGRGRGAQTHEGNHDRTDDAGREELREGPGDQKPSGEENREGGQPPGQREEQREGTGLEEGFNKEDAQES

2.7.11.1

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:A0A7J6K7Y0};

phosphorylation [GO:0016310]

extracellular region [GO:0005576]

ATP binding [GO:0005524]; metal ion binding [GO:0046872]; protein kinase activity [GO:0004672]

PF00069;

1.10.510.10;

Protein kinase superfamily, STE Ser/Thr protein kinase family, WNG subfamily

SUBCELLULAR LOCATION: Cytoplasmic granule {ECO:0000269|PubMed:30850550}. Secreted {ECO:0000269|PubMed:30850550}. Parasitophorous vacuole lumen {ECO:0000269|PubMed:30850550}. Note=In tachyzoites, localizes to dense granules. {ECO:0000269|PubMed:30850550}.

CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:A0A7J6K7Y0}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:A0A7J6K7Y0};

FUNCTION: Probable serine/threonine-protein kinase. {ECO:0000305}.

Toxoplasma gondii

A0A7J6K7Y0

WNG1_TOXGO

MPEQDLASGFLLRFQNARPVCLSVGSFVSFRTVQPRKMRDRGWRCVWHRMAGVGALFGIFGVLCTVEAGATVAAPQVETGPLLSVRAPRSPLHLRDVDAPEVTHASSEGSPQFESSLSQQRLRRPADRGEAHNGEEPRKDAATQTVRGYGGQSTEPPPASIVPVSSEAPQDGAEQRQASSAAESLAGLDPDAGDTGLRSQEMDEEGSGAAQDMERAHAAQPTVSTWDDAHLVQVSTSHPDMFPVDGSFSKKQEGRRERRLAVRGDDSFARGHNRDRDASNGRSILRRAPGWAKIAALATGLLVSAFGYSSYKHGGPRVALRIHKLHLKRKLPISWRRYLNNLPVLDERLFPEFEDILPWLRRGARLVKRVPHVSEALADFIGLDEETRRTGIVIKVKSSTDAEARRLVYEVNAHANMVPDNPFFLPIIGAYQGASKRAVYMILPRARADVADYVRARPYDVDVRLAAAEMVYSNYILHTHGFLHRDIKAHNYFVTFDGHVVLADFEGVGVLQQRTPVVGTRGYFAPELSRATDHTEKSDVFALGQTLKRLVKYMRPTVRVPHLRELWALTKRMTAKDPEERPTLKQVMEDPYFDGIDFERLEAKDQGVPFRGDFSIDDPDAGGKMYIPPSKEQDHEQENE

2.7.11.1

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:30850550};

chromosome segregation [GO:0007059]; microtubule-based process [GO:0007017]; phosphorylation [GO:0016310]

centrosome [GO:0005813]; cortical microtubule [GO:0055028]; extracellular region [GO:0005576]; nucleus [GO:0005634]

ATP binding [GO:0005524]; metal ion binding [GO:0046872]; protein serine/threonine kinase activity [GO:0004674]

PF00069;

1.10.510.10;

Protein kinase superfamily, STE Ser/Thr protein kinase family, WNG subfamily

SUBCELLULAR LOCATION: Cytoplasmic granule {ECO:0000269|PubMed:30850550}. Secreted {ECO:0000269|PubMed:30850550}. Parasitophorous vacuole lumen {ECO:0000269|PubMed:30850550}. Note=In tachyzoites, localizes to dense granules. {ECO:0000269|PubMed:30850550}.

CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:30850550}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000269|PubMed:30850550};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=520 uM for ATP (at pH 7.5 and 30 degrees Celsius) {ECO:0000269|PubMed:30850550};

FUNCTION: Serine/threonine-protein kinase which, at the tachyzoite stage, phosphorylates several parasitophorous vacuole (PV)-resident proteins such as GRA2, GRA6 and GRA7 (PubMed:30850550). By phosphorylating GRA2 and GRA6, regulates the formation of a functional intravacuolar network (IVN); IVN is composed of membranous tubules that bud from the PV membrane into the vacuolar lumen (PubMed:30850550). Plays a role in the establishement of chronic infection in the host by controlling cyst formation in the host tissues (PubMed:27165797). {ECO:0000269|PubMed:27165797, ECO:0000269|PubMed:30850550}.

Toxoplasma gondii

A0A7L8UVC9

FFSA_ASPFV

MATTTAPTTQGHNQPSREPIAIVGSACRFPGGASSPSKLWKLLEHPRDVLKEIPPDRFSVDGFYHPDNMHHGTSNVRHSYILDDDIRVFDAQFFGIKPVEANSIDPQQRLLMETVYEGIESAGLQLNKMKGSQTGVYVGLMSNDYADMLGNDQESFPTYFATGTARSIVSNRVSYFFDWHGPSMTIDTACSSSLVAMHQAVQYLRSGDGSDVAIAAGTNILLNPDQYIAESKLKMLSPDGRSQMWDEKANGYARGDGIAVVVLKTLSQALRDGDHIECIVRETHINQDGKTKGITMPSATAQTALIRSTYKNAGLDITKPSDRPQFFEAHGTGTPAGDPIEAEAIHTAFFGYKGLSKEIEPLSVGSIKTIIGHTEGTAGLAAVLKASLALQAGVIPPNLLFDKVNPKVKPFYGNLQIQTQAKSWPSLAPGAVRRASVNSFGFGGANAHAILEAYEPSSTPTVGTPANVFTALNVSAMSETALRGTLKKYVEYLKEEPSVDLRSLALTVNTRRSTFPVRTSVFGTSVEELSQRLSERSEAEGKTLTPVAPTSLSSSPKILGVFTGQGAQWKQMGAVLLATSPRVVAILDQLEKSLAELPDGPSWSIKGEILADEDSRVNEAVISQPLCTAVQIVLVDLLQSAGVQFHTVVGHSSGEIGAAYAAGYLSASDAIRIAYYRGLHLYLAQGPNGQQGAMMAVGTSFEDAQELCDLPAFRGRISIAASNSSASVTLSGDLNAIEWAKDVFDDEKKFARLLKVDKAYHSHHMLACSDAYRKSMTDCGITVLQPARNGTTWISSVYGEDALDYRHEMNAEYWISNMVSPVLFSQAIEFAMADQGPFDIGIECGPHPALKGPALQVIQEMLGSSIPYTGLLSRGRPDTQALAEGISYLWQALGADVVNYTSFDRFIAGPDASEPQVLANLPSYAWDHDRAFWHESRQYWANRTKEDPPHEILGTKCPDGTDQQHRWRNMLRPREIPWIAGHQIQEQMVFPAAGYVSAAIEAVQMVTRGQSLGAIEIEDFVIGQAIAFNDEYASVETQFTLTDISVEKDIWSASFFFYSASPKSSRSLDLNASGKLKVTLGEPKDDFLPPHLSPEFNMIDVDSERFYDALKKLGFGYTGPFKALGSLKRRMGVATGTITNPTSTDPAHDLLLHPATFDNAIQSIILAYCYPNDGRLWSVQLPTGIKKIKINPVLCNRYAGKKALLCFKASTSDDRSAEIGGDVDIYDEQGNNALMQLEGLQTKPLANATAANDSPLFLETIWDIESPSREAAVADRPDMQPKTELSFDVERVAFFYLRHLDSVATREEREKAESHHKIFFEYIDHTVANVKSGTAQFAKREWMYDTHDEILDIISKYPDSLDMKLMHAVGEHLLPVIRGETTMLEYMREDNLLNDFYVHAIGFDEYTENLAQQVSQFSHRYPHMNILEIGAGTGGATKRIFSKLGKRFGSYTYTDISAGFFEKTRETFREYEHMMTFKALNIEKDPVEQGFTEQSYDLVVASLVLHATHEMETTMRNVRRLLKPGGYLIMLELGDYIEMRTGLIFGSLPGWWMGYDDGRKLSPCMSEEDWSVCMQKTGFSGVDAIVPRQSELPISLAVLTGQAVDDHVNFLRDPLTPGSIDFVESNLTIIGGTTSKVSAMVEEAAKSLGRFYEKIVTATSLAELDTTEVPFMGSVLFLTDLDEPIFENVTEDALTALKQLFKQSRTCLWVTQGARDDNPFQNMSVGLGRVVKLEMTHLRLQSLDFDVETEPSAPTIMQRLLQFEAMAQWEQSGESKDLLWSVEPEIGYDHGKAIIPRLMPNPVRNARYNSSRRLITKYMEPTSANLSLRWSGKSYDIHEGEPSGATSLVMDGRVQLEVSHSTLDAIGVTATDYAYLVLGKNVKSQQQVIALTPKSDSIVRVFDSWTVPYSMAEDDALRLLPVVYTNLMALSVISRLSSGETLVLVEPEEAFAQTLSRLATERAISVVTLTSRMDVKNSDWIYLHVNSPKRLVRSTVPRNASWVIADRDQGGLAANVLQCLPANCKILATESLTSKQPKLDTFSSMAFIPSILRTAFVRAHDIKATLELPSVVAAADISSDNQPSTEATFFSWTASPSVPVQVTPVDHGTLFSSEKTYWLVGLSGGLGLSLCDWMVKHGAKYIVITSRNPQVDARWEQHMKAQGAVVRVYANDITDRESVSSVCKKIRDELPPVGGIAQGAMVLADTMFVDMDLPRVQKVVGPKVNGSIHLHEMFVEVDLEFFVFFSSMAYVTGNQGQSIYAAANAYMTALAAQRRKRGLAGSAINIGTIIGNGYVTRQLTIAQQEYLTHMGNVFMSEQDFHQIFAEAVVAGRPTSKDIPEIMTGLRLAHLDDSDKVTWFHNPKFSHCVLWPEEQGGKAVMSKQNVTVRAQLLLATTADEAREIIEESLAAKLRSSLQIDATVSVINMNADQLGLDSLVAVDIRSWFIKELNVEMPVLKILGGYTVAEMVAAAQEKLSPSLIPNLGKEVDPSLKAVVKAQVEKPVAAAEEKPIVTEKAEYADFDDENEEEGIPTEDSLPEITVSDESSELSDREPAKFNFNGPGFKKVGFSPGPQTPLSEDDRSKWSSYGSPFDSDSDNASIRKSRTSAATSVTALDEYFSKPDHTIFERTLPMSFGQTRFWFLKFYMEDQTTFNITTSISLAGKLDVGRFSRAVHHLGRRHEALRTAFFTDSNNQPMQAVLKEPVLRLEHARGEANVASEYRRIKNHQYDIGRGETMKITLLSLSEKLHQLIIGYHHINMDGISLEVIIRDLQQLYDGKSLAPVSIQYPDFSIMQYKEHSSGQWDDELTFWKSEFADIPEPLPILPPSTKAVRTPLSIYSSNTVKFEVGAELSSQIENACKRTKTSPFNFYLATFKVLLYRLAEGKATDICIGMADGGRNNDLVSQSVGFFLNLLPLRFKQQSSQMFSDALKEARSKVITALANSKVPFDVLLNEVNAPRTATLSPLFQAFINYRQGVQEKRQFCGCESEATKFDGSQTAYDLSLDILGNPGSGIVYLAGQSSLYSQSDVETIAQSYYALLKAFAKNPALRISRPSLYDPQAVDHALAKGKGPTNVGTWPETLVHRVDEIVKAHGSKVALKSATAKLTYTQMAERVNAIASTLQSNGINKCSRVGVFQDPSTDFFCTILAVLRIGAVFVPLEPRLTAPRLATMVQDSDLNAIVYDKANQKTLAELGSNSKKINVSLVLAKSSAVVSNQATPGATAIILYTSGSTGKPKGILLSHSAWRNQIESSSRAWEVPTGTGVHLQQSSWSFDISISQTFVALANGASLIITPKTMRGDSSAITKTIVSDQVTHVQATPSELSSWLRFGDLAALRASKWQFAMTGGERMTPALIDGFRKLAKNDLKLFNAYGPAETTLAVGSSEVDYMTSDDLDTPFTLFPNYSVYILDGQKQPVPAGIPGEVYIGGAGVAQGYLNQDSLTAKRFLPDTFGTTEYTHFGWTKMHRSGDRGHLSEDGHLVLEGRIDGDTQVKLRGIRIDLQDIESAMVQQANGALTEAVVSVCKLQETEYLVAHVVISPTFTGNTESFLDQLRASLPVPQYMQPAIAVTLDALPVNHSGKVDRKAIAALPILPKATQPGATSQPRDSTEKLKDIWTQVLGQGMTSLHHIDAQSDFFHVGGSSLALVEVQAKIKTIFQVEVSLVQLFENPTLGAMARMVDPTAFSAPVNANLTIPAEVATAISAPTTSINTAPKEIDWEEETALTDDFYDIEIDPTPKDQGLPYKTVVITGATGFLGKALLRRMLDDNHIDKIHAITLRRSRSDLPGIFSDPKVHLHRGDLNAPRLGLSETAAAEIFAETDAVIHNGADVSFMKTYRTLSKTNVGSTRELVKLCLPHRIPIHYISSASVVHLSGLESYGEASVSSFEPPQDGTDGYTASKWASERFLERVSEKFSVPIWIHRPSSITGEDAPTLDLMTNMLSFSKKLRKAPTSPAWQGTLDFVDVEKVATEIVEEVKNDSAHPGGLVKYMYESGDLEIAVDDMKGSLERETGQAFQTLSLEEWTKAAAEEVTNELGICCSK

2.3.1.-; 6.3.2.-

amide biosynthetic process [GO:0043604]; fatty acid biosynthetic process [GO:0006633]; heterocycle biosynthetic process [GO:0018130]; methylation [GO:0032259]; organic cyclic compound biosynthetic process [GO:1901362]; organonitrogen compound biosynthetic process [GO:1901566]; toxin biosynthetic process [GO:0009403]

3-oxoacyl-[acyl-carrier-protein] synthase activity [GO:0004315]; fatty acid synthase activity [GO:0004312]; isomerase activity [GO:0016853]; ligase activity [GO:0016874]; methyltransferase activity [GO:0008168]; oxidoreductase activity [GO:0016491]; phosphopantetheine binding [GO:0031177]

PF00698;PF00501;PF00668;PF16197;PF00109;PF02801;PF08659;PF08242;PF07993;PF21089;PF00550;PF14765;

3.30.300.30;3.40.47.10;1.10.1200.10;3.30.559.10;3.40.366.10;3.40.50.12780;3.40.50.720;3.30.559.30;3.10.129.110;3.40.50.150;

NRP synthetase family

PATHWAY: Mycotoxin biosynthesis. {ECO:0000305|PubMed:32913332}.

FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of the cytotoxic leucine-containing cytochalasans, including aspochalasin C, aspochalasin E, TMC-169, flavichalasine F, aspergillin PZ, aspochalasin M and flavichalasine G (PubMed:32913332). The first step in the pathway is catalyzed by the hybrid PKS-NRPS ffsA that utilizes 8 units of malonyl-CoA to iteratively assemble the octaketide chain before addition of L-leucine by the C-terminal NRPS modules (PubMed:32913332). Because ffsA lacks a designated enoylreductase (ER) domain, the required activity is provided the enoyl reductase fssC (Probable). The methyltransferase (MT) domain of ffsA catalyzes the alpha-methylation at C10 and C14 using S-adenosyl-L-methionine as the methyl-donating cosubstrate (Probable). Reduction by the hydrolyase ffsE, followed by dehydration and intra-molecular Diels-Alder cyclization by the Diels-Alderase ffsF then yield the required isoindolone-fused macrocycle (By similarity). A number of oxidative steps catalyzed by the tailoring cytochrome P450 monooxygenase ffsD, the FAD-linked oxidoreductase ffsJ and the short-chain dehydrogenase/reductase ffsI, are further required to afford the final products (Probable). {ECO:0000250|UniProtKB:Q0V6Q6, ECO:0000269|PubMed:32913332, ECO:0000305|PubMed:32913332}.

Aspergillus flavipes

A0A7L9EYL1

XENE_XENSI

MSGQDPVKESGQREPIAVVGSGFRFPGSSNNPSKLWDLLVKPRDLLTKIPENRFNSDAFYHPKPFHHGTSDVRESYFLEEDHRQFDAAFFNIKPVEVHAIDPQQRILMEAVYESLEAAGLSMESLAGSRTGVYVGLMCADYVDLLNNDVNSLPTYTPTGTARSIMSNRISYFFDWHGPSMTIDTACSSSLVAVHQAVQLLRSGDSDVAVAAGANLMLGPLPYIAESKLQMLSSNSRSRMWDIDASGYARGEGVAAVVLKRLSSAIADGDQIECIIRESGINQDGRTKGITMPSSVAQADLISRTYAKAGLNPRDPTERCQYFEAHGTGTAAGDPKEAEAISKAFFHPGEDISGKTDPLYVGSIKTVIGHTEGTAGLAGLLKASLAVQHGIVPPNLLFNQLSPAVEPFYTNLEVLTSPRPWPKLAEGTPRRASINSFGFGGTNAHCIIENYIPSPAHTDRAITTRQFTPFNFSAASEKSLRGILTDYSNYLRLNPEVSLQDLSYTLYARRSEHAVRVHISAGSTTDLYTRIDDLLQVPSSGGNAQSIGTRSKILSRPVRALGVFTGQGAQWPSMGRELVLNSPYAKEVVQKLDLVLQSLPEPERPDWSLMYELTCDASQSRLNTAVIAQPLCTVVQIILFDLLSSAGVKLQAVVGHSSGEIAAAYAAGYLTREDALKIAYYRGYFTNLTPSDRPGAMMAIGTSAEDAEELCSLPMFQGRLAVAAVNSSSSVTISGDRDAIEQAKEVLEDEKKFARLLKVDKAYHSSHMVPCAEGYLEALKNSEIHPLSGTDDCVWHSSTHKNKYSHGDGALAGQYWADNMIQPVLFSHAVEAAASAGDAFDIAIEVGPHPALKGPALQTLQEVQKDTIPYTGLLNRGKDDIEALSDALGYLWTQFTPSLIDFRGFDLLASGGEQRSLIRNLPTYHWDHDKIFWHKSRAVKAFLGQKNIPNPLLGSRTTDVMEQEIRWRNLLRLSELPWVRGHQLQGQVIYPATAYISTAVEAARFLVPKGDNIALIEVEDFSLGKPLVFAEDAAGIETVFTLSDIAKENDTTYSASFIYHASTNAETEQLSTHAIGRVIVITGETSSHWLPSRQKDLPNLVDIPEDRFYASLEPLGYAYSGYFKTMSSIKRRLNFSSTKIRVPPQDDEPEKMLLHPALLDTALQGIFLAYCWPGDGSLEQLHVPTGIKNFRVNVGLCQQVLTPETDVSSCTQLTGNPLATKHLNGDVEIYADDGAGLVQMEGLRVVAFAEQTEDADRAIFSEHVWDVLAPNCERAMGGKRATLQDYEFAYGMERVVVYYMKQLVTLFPESLRKIMNLEWHFECMFAFFTDVLTTLEAGERRTARREWLQDTAADVEGIKARYAHTVDMQLTCAVGDNLPAVLRGESTILQHLTKDNLLNRFYEVGLGLKEVSGYLGKIVEQVVHRHPRMKILEIGKSGTGGATKVIMRGIGRSFSSYTYTDISPNFFESAQEVFSAVADKMIFKTLDVEKDITEQSFEEHSYDLVVASLVLHATTNLKRTLTNARRLLKPGGYLIFQEICDNDIARVGFLICAVPGWWLGQDDGRKLSPCVSTSEWHNLLLETGFSGADSPMPEYDAAPYPLAVIVSQAVDDRIALLREPLSLVQNDASVGEPWDLVLVGGQTSKTAMIIEQISGLITSSGVTHSVFKTIDEVDGTRISPTTAILCLADLDEPVFKGLSSTTLEGLQRLFETQRTVLWITQGCRSEDPWMNMSVGLGRTLVLENPDLALQFLDLEPGVEPNPRQLLEVLLRLRQSDIWEKEGKFDDVLWTNEHELAYDKGDLTLSRVHLSGALNDRYNAAKRTVLEAKNPQETPLNLSLGPSLKQFLVLDDVLVAKTLSSWELKDDSETLIKVTHSLLMPALAAPTPLYLILGTINKTKKSVLSIADNNGSYALVASNKVLAIDVPAGQESQLLSLFNTRLQVDSMLSLCESDSTLLIHEPSPDLASAIAACGSSGKINVVFTTSTSSGDSTWTRIDAYSTQRAIRSLLPENVSVFIDCSAGSQSRRTASLIASCLLPSCFQTTISGVQSLQRIRGLSPTDLCQKLNDALAWASKELAAPSNPGTLPSIKLETLIDDSAVASTTQAVVDWSTATSVPVQVSTVDNHVTFKGNNTYVLFGLTSDLAQSICDWMVSRGARNIVLTSRNPKIDSNWIELLKGAGVRLEAFANDITNKDALSSLVHHIRKNFPPIAGVAHGAMVLDDVSFFEMPYEKMTKVLGPKVQGAILLDEIFQDTSLDFFVFFSSVTAIAGNRGQSAYTSANMFMTSLASQRRDKGLAASILHLGAVMGVGYINRGFSDAFFTTLRRAGFMMMSERGLHLLFGEAVLASNPHSGRNPEVITALELSRLGDKPPLWTKFPRFQHCLQADDGANKRAKKKTAAVSTKLKLAEATTAEEILEIVQDAFYLKLQVALQIPDETDKSQVLASGTDDLGIDSLVAVEIRSWFLKELETEIPVFKVLSGGSVTQLVEYAIGSMPAELTPNRADSAKASEPEPEAPATLMPPPDSVSSSPSSLPKTSASGSSQQMSEGSSKTSEQGDAQDKKEESPSESVNDISELTYEKVLPVSPGQSRFWFLKHLLEDQTTANNTIWVSIQGTIRLNDLEMAIRKVAARHEALRTSFFMDENQKPIQAISETSRLYLEKKTLSSGSQAEREFEGLKKHVYDIEHGECMRLVYLEVTDTESYLLIGSHHIIMDGISLEVFLKDIEKAYNGQSLSNQVYQYSDYSEKLRQELEQGTMQEEINYWKSEFADVPSPLPLLPFAAEKQRKSLAAYSHTSVSRLVDPRVARQISNTCHKLKANVFHFYLGVFEVLLFKLFGNNDVCIGMADANRWNEKVSQSIGMYLNLLPLRFHLDGRQSFEAMLKDTRRKAYLAMSNSRLPFDVLLDNVICERSSAFSPLFQAFINYRQGVNEKRVLGNATGATKELSLPRAGYDISLDIIENPGNDTRVTVMLQKALYSDNESSRVLDLYFKLLNDLSSSSKKMLEEVSLFTEQEISNSIQLGQGPVLPSQWPETLVHRIDAMIAVHTDKVALKEITGKSWTYLQLEEEINRVSSVLIQANVTSGSTVAIYQEASPNFVFSLLAVLRIGAIYVPLDCNLPEGRLRLVLAECKPSALLADGKTLSQIGSLGLSPSVTILDVSRLPAASASISPVFTKAANPAAILFTSGSTGVPKGVVLSHGSLRNHVEALVHTHGFGSETVLQQSSVGFDMSMNQVFMALANGGSLVIVPESLRKDSSAIAKILLEQNITYTSATPSEYFAWLRHGSDDLLRNKSWKYATAGGEKFTPKLLQAFQKLKSAFSHSFHAFNAYGPTECSMSSNELEVNLDGHSAQFITAGRALPNYAVYIVDENATPQTIEIPGEICIAGAGVALEYLNNPVETAKKFLKDPFASVSAIERGWNRMYRTGDKGVLRPDGTLEILGRIEGDTQIKLRGLRIEMQDIEQSILKAGEGRVKEAIVTPRGDPTILVAHAVVSPIVSIDNEREYLRGLAASLPLPQYMRPAAIIPIATMPLNASGKIDRRALQNLDIPSTLQQKTRSKRKLTDTESKLAQIWVEVLPQQLQEVYAIDETSDFFQVGGNSMLLIELRELVKKRFQVHLPLLRFFEHSTLGAMAAAIQDTSPGEKLEINWDVETEVPSAYSELNTQEPAQSHSSHKTIVLTGATGFLGKYLLNLLTEAPDVDKIHCIAIRNREKLANFTNSAKVVIHDGDLASPRCGLSEADATSVFGSANVIIHNGADVSFLKTYSSLRASNVLSTKELVKLALPHHIPIHYISTATVGKLNKSDSLAPESLAQYPPGPSFVDGYAASKWASEVFLEKTTRQFGLPTFIHRPSSITGDGAGENDIVPSVLKYSAMIKALPDSSKWTGYIDLITVEKAAAGIADSVLQGRLVNVTATEAEYLHHAGEKVIPAQSIKTILTADDGPQWESVSMKNWVEKAIQNGMNPLVGEFLLSIDKGQGMQIGQKLLSKTDGSKNEF

2.3.1.-; 6.3.2.-

amide biosynthetic process [GO:0043604]; fatty acid biosynthetic process [GO:0006633]; heterocycle biosynthetic process [GO:0018130]; methylation [GO:0032259]; organic cyclic compound biosynthetic process [GO:1901362]; organonitrogen compound biosynthetic process [GO:1901566]; toxin biosynthetic process [GO:0009403]

3-oxoacyl-[acyl-carrier-protein] synthase activity [GO:0004315]; fatty acid synthase activity [GO:0004312]; ligase activity [GO:0016874]; methyltransferase activity [GO:0008168]; oxidoreductase activity [GO:0016491]; phosphopantetheine binding [GO:0031177]

PF00698;PF00501;PF00668;PF16197;PF00109;PF02801;PF08659;PF08242;PF07993;PF21089;PF00550;PF14765;

3.30.300.30;3.40.47.10;1.10.1200.10;3.30.559.10;3.40.366.10;3.40.50.12780;3.40.50.720;3.30.559.30;3.10.129.110;3.40.50.150;

NRP synthetase family

PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:34900544}.

FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of xenoacremones such as xenoacremone A, a compound that shows inhibitory activity toward the PI3K/AKT signaling pathway and which has the ability to induce apoptosis of A549 lung cancer cells (PubMed:34900544). Within the pathway, cooperation of the hybrid PKS-NRPS xenE and the trans-acting enoyl reductase xenG is responsible for the formation of the reduced tyrosine-nonaketide derivative (PubMed:34900544). The PKS module of xenE acted in combination with the trans-acting enoyl reductase xenG to produce a double-methylated nonaketide attached to the ACP domain (PubMed:34900544). In parallel, the adenylation (A) domain of the NRPS module activated L-tyrosine, which was then transferred to the ACP domain (PubMed:34900544). The condensation (C) domain subsequently linked this group to the polyketide chain, forming an enzyme-bound amide (PubMed:34900544). Reductive release by the C-terminal R domain afforded the aldehyde derivative (PubMed:34900544). The alpha/beta hydrolase xenA then accelerates intramolecular nucleophilic attack to give a pyrrolidone derivative (PubMed:34900544). Subsequently, three enzymes, xenF, xenD, and xenC, coordinately participate in the conversion to xenoacremone B (PubMed:34900544). XenF catalyzes sigmatropic rearrangement to form an A-ring, which leads to an unusual intermediate with a hexane ring, which is required for the formation of the tricarbocyclic product (PubMed:34900544). Epoxidation catalyzed by xenD and the formation of the paracyclophane ether catalyzed by xenC initiate a spontaneous intramolecular Diels-Alder (IMDA) reaction to yield xenoacremone B (PubMed:34900544). Spontaneous hydration of xenoacremone B leads to the formation of xenoacremone A, which undergoes subsequent methylation to afford xenoacremone C (PubMed:34900544). {ECO:0000269|PubMed:34900544}.

Xenoacremonium sinensis (Endophyte fungus)

A0A7U9P668

CDAS_GEOTM

MRKEAIHHRSTDNFAYAYDSETLHLRLQTKKNDVDHVELLFGDPYEWHDGAWQFQTMPMRKTGSDGLFDYWLAEVKPPYRRLRYGFVLRAGGEKLVYTEKGFYHEAPSDDTAYYFCFPFLHRVDLFQAPDWVKDTVWYQIFPERFANGNPAISPKGARPWGSEDPTPTSFFGGDLQGIIDHLDYLADLGITGIYLTPIFRAPSNHKYDTADYFEIDPHFGDKETLKTLVKRCHEKGIRVMLDAVFNHCGYEFGPFQDVLKNGAASRYKDWFHIREFPLQTEPRPNYDTFAFVPQMPKLNTAHPEVKRYLLDVATYWIREFDIDGWRLDVANEIDHQFWREFRQAVKALKPDVYILGEIWHDAMPWLRGDQFDAVMNYPLADAALRFFAKEDMSASEFADRLMHVLHSYPKQVNEAAFNLLGSHDTPRLLTVCGGDVRKVKLLFLFQLTFTGSPCIYYGDEIGMTGGNDPECRKCMVWDPEKQNKELYEHVKQLIALRKQYRALRRGDVAFLAADDEVNHLVYAKTDGNETVMIIINRSNEAAEIPMPIDARGKWLVNLLTGERFAAEAETLCVSLPPYGFVLYAVESW

3.2.1.54

pullulan catabolic process [GO:0051678]

cyclomaltodextrinase activity [GO:0047798]; identical protein binding [GO:0042802]; protein homodimerization activity [GO:0042803]

PF00128;PF02903;PF16657;

3.20.20.80;2.60.40.1180;2.60.40.10;

Glycosyl hydrolase 13 family

CATALYTIC ACTIVITY: Reaction=cyclomaltodextrin + H2O = linear maltodextrin; Xref=Rhea:RHEA:23980, Rhea:RHEA-COMP:14584, Rhea:RHEA-COMP:14707, ChEBI:CHEBI:15377, ChEBI:CHEBI:17623, ChEBI:CHEBI:18398; EC=3.2.1.54; Evidence={ECO:0000269|PubMed:31212108}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23981; Evidence={ECO:0000269|PubMed:31212108};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.8 mM for alpha-cyclodextrin {ECO:0000269|PubMed:31212108}; KM=0.6 mM for beta-cyclodextrin {ECO:0000269|PubMed:31212108}; KM=0.4 mM for gamma-cyclodextrin {ECO:0000269|PubMed:31212108}; Vmax=1200 umol/min/mg enzyme with alpha-cyclodextrin as substrate {ECO:0000269|PubMed:31212108}; Vmax=735 umol/min/mg enzyme with beta-cyclodextrin as substrate {ECO:0000269|PubMed:31212108}; Vmax=360 umol/min/mg enzyme with gamma-cyclodextrin as substrate {ECO:0000269|PubMed:31212108}; Vmax=105 umol/min/mg enzyme with pullulan as substrate {ECO:0000269|PubMed:31212108}; Note=kcat is 2739 sec(-1) with alpha-cyclodextrin as substrate. kcat is 1678 sec(-1) with beta-cyclodextrin as substrate. kcat is 821 sec(-1) with gamma-cyclodextrin as substrate. kcat value calculations are based on the dimeric enzyme. {ECO:0000269|PubMed:31212108};

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 6.0 for hydrolysis of alpha-cyclodextrin. {ECO:0000269|PubMed:31212108};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 55 degrees Celsius for hydrolysis of alpha-cyclodextrin. Thermostable. No significant loss of catalytic activity even after overnight incubation at 65 degrees. EDTA enhances the thermostability, the half-life being 90 minutes at 70 degrees Celsius in the absence of EDTA, increasing to 360 minutes in the presence of 10 mM EDTA. However, overnight incubation at 4 degrees Celsius is first required for enhancement of thermostability. Activity decreases drastically at 75 degrees Celsius. {ECO:0000269|PubMed:31212108};

FUNCTION: Hydrolyzes alpha-, beta- and gamma-cyclodextrins with the highest activity with alpha-cyclodextrin (cyclomaltohexaose). Pullulan is the preferred substrate from linear substrates. Maltose is a major product of these reactions. Is also able to hydrolyze maltotriose and acarbose, and transglycosylate their hydrolytic products. Major reaction products of maltotriose and of acarbose are maltose and glucose, and glucose and pseudotrisaccharide, respectively. No activity with glucose or maltose as substrate. {ECO:0000269|PubMed:31212108}.

Geobacillus thermopakistaniensis (strain MAS1)

A0A858E6N7

GGDPS_MELLI

MKPLPSTNGKVNGNGKHHDSSLSSTSSTSSSSSSDTQFNISDRYGDFLHRLDTLDTWPKSNEQILLEPYTYLNNIPGKEIRSMMIDAFNHWLQIPRPALEIIKKIVGQLHTASLLMDDVEDDSDLRRGVPVTHKIYGIPQTINTANYVYFLAYQELSKLKPCLSSNASTDLWSLVNDELLQLHRGQGMDLYWRDSLTCPTEEEYLQMVNNKTGGLFRIAIKLMIALSPLTETPDYLPLVNLVGIIFQIRDDLLNLSSVYTKNKGFCEDLTEGKFSFPIVHSIRADSSNHQLMNILRQKPTDIGTKTFAVSYMKDQTKSLQYTREVLTCLEEQAIEEVTRLGGNPALESIFELMHVLPSPPATDQH

2.5.1.-; 2.5.1.1; 2.5.1.10; 2.5.1.29

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q12051}; Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051};

isoprenoid biosynthetic process [GO:0008299]; plastoquinone biosynthetic process [GO:0010236]; ubiquinone biosynthetic process [GO:0006744]

mitochondrion [GO:0005739]; transferase complex [GO:1990234]

lyase activity [GO:0016829]; metal ion binding [GO:0046872]; prenyltransferase activity [GO:0004659]

PF00348;

1.10.600.10;

FPP/GGPP synthase family

CATALYTIC ACTIVITY: Reaction=dimethylallyl diphosphate + isopentenyl diphosphate = (2E)-geranyl diphosphate + diphosphate; Xref=Rhea:RHEA:22408, ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769; EC=2.5.1.1; Evidence={ECO:0000269|PubMed:32913319}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22409; Evidence={ECO:0000269|PubMed:32913319}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate + isopentenyl diphosphate = (2E,6E)-farnesyl diphosphate + diphosphate; Xref=Rhea:RHEA:19361, ChEBI:CHEBI:33019, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.10; Evidence={ECO:0000269|PubMed:32913319}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19362; Evidence={ECO:0000269|PubMed:32913319}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate = (2E,6E,10E)-geranylgeranyl diphosphate + diphosphate; Xref=Rhea:RHEA:17653, ChEBI:CHEBI:33019, ChEBI:CHEBI:58756, ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.29; Evidence={ECO:0000269|PubMed:32913319}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17654; Evidence={ECO:0000269|PubMed:32913319};

FUNCTION: Geranylgeranyl pyrophosphate synthase that catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate (PubMed:32913319). Does not show any monoterpene nor sesquiterpene synthase activity (PubMed:32913319). {ECO:0000269|PubMed:32913319}.

Melampsora lini (Rust fungus)

A0A858E7G0

GGDPS_MELLP

MKPVPSTNGKVDDKVEHHNLSSSSSSSSSSSSSDTKFNISNRYGNFLQRLEALDIWPESNEQILLEPYTYLTNIPGKEIRSMMIDAFNHWLQVPRPALEIIKKIVGQLHTASLLMDDVEDDSDLRRGVPVTHKIYGIPQTINTANYVYFLAYQELTKLKPCLRSDATTDLWSLVNDELLQLHRGQGMDLYWRDSLTCPTEEEYLQMVNNKTGGLFRIAIKLMIALSPIPETPDYLPLVNLVGIIFQIRDDLLNLSSVYTKNKGFCEDLTEGKFSFPIVHSIRSDSTNHQLMNILRQKPTDIGTKAFAVSYMKDRTKSLEYTRGVLICLEEQAIEEVTRLGGNPALESIFELMHVLPSPPATDQN

2.5.1.-; 2.5.1.1; 2.5.1.10; 2.5.1.29

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q12051}; Note=Binds 2 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051};

isoprenoid biosynthetic process [GO:0008299]; plastoquinone biosynthetic process [GO:0010236]; ubiquinone biosynthetic process [GO:0006744]

mitochondrion [GO:0005739]; transferase complex [GO:1990234]

lyase activity [GO:0016829]; metal ion binding [GO:0046872]; prenyltransferase activity [GO:0004659]

PF00348;

1.10.600.10;

FPP/GGPP synthase family

CATALYTIC ACTIVITY: Reaction=dimethylallyl diphosphate + isopentenyl diphosphate = (2E)-geranyl diphosphate + diphosphate; Xref=Rhea:RHEA:22408, ChEBI:CHEBI:33019, ChEBI:CHEBI:57623, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769; EC=2.5.1.1; Evidence={ECO:0000269|PubMed:32913319}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22409; Evidence={ECO:0000269|PubMed:32913319}; CATALYTIC ACTIVITY: Reaction=(2E)-geranyl diphosphate + isopentenyl diphosphate = (2E,6E)-farnesyl diphosphate + diphosphate; Xref=Rhea:RHEA:19361, ChEBI:CHEBI:33019, ChEBI:CHEBI:58057, ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.10; Evidence={ECO:0000269|PubMed:32913319}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19362; Evidence={ECO:0000269|PubMed:32913319}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate + isopentenyl diphosphate = (2E,6E,10E)-geranylgeranyl diphosphate + diphosphate; Xref=Rhea:RHEA:17653, ChEBI:CHEBI:33019, ChEBI:CHEBI:58756, ChEBI:CHEBI:128769, ChEBI:CHEBI:175763; EC=2.5.1.29; Evidence={ECO:0000269|PubMed:32913319}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17654; Evidence={ECO:0000269|PubMed:32913319};

FUNCTION: Geranylgeranyl pyrophosphate synthase that catalyzes the trans-addition of the three molecules of IPP onto DMAPP to form geranylgeranyl pyrophosphate (PubMed:32913319). Does not show any monoterpene nor sesquiterpene synthase activity (PubMed:32913319). {ECO:0000269|PubMed:32913319}.

Melampsora larici-populina (strain 98AG31 / pathotype 3-4-7) (Poplar leaf rust fungus)

A0A8B7DWS6

ACTL1_HYDVU

MLLYICLVNLLLPLSVGAASGAALGVIAKVGVDAALQQIDDVWKGKTVRYWKCAVENRSSKTLYALGTTQESGSMTTVFADIPPKSTGVFVWEKSRGAAKGAVGVVHYKYGNKVLNIMASIPYDWNLYKAWANVHLSDHKESFSDLYKGKNGAKYPTRAGNWGEVDGTKFFLTEKSHAEFKVIFSG

cytolysis in another organism [GO:0051715]; monoatomic cation transport [GO:0006812]; pore complex assembly [GO:0046931]

extracellular region [GO:0005576]; nematocyst [GO:0042151]; other organism cell membrane [GO:0044218]; pore complex [GO:0046930]

channel activity [GO:0015267]; toxin activity [GO:0090729]

PF06369;

2.60.270.20;

Actinoporin family, HALT subfamily

SUBCELLULAR LOCATION: Nematocyst {ECO:0000269|PubMed:31513812}. Secreted {ECO:0000250|UniProtKB:B9W5G6}. Target cell membrane {ECO:0000250|UniProtKB:B9W5G6}. Note=Is found in differentiating stenoteles (one type of nematocyst) (PubMed:31513812). Forms an alpha-helical membrane channel in the prey (By similarity). {ECO:0000250|UniProtKB:B9W5G6, ECO:0000269|PubMed:31513812}.

FUNCTION: Pore-forming protein that forms hydrophilic pores and causes cytolysis (PubMed:24768765, PubMed:31513812). Compared to equinatoxin-2 (AC P61914), it reveals lower cytolysis activity (5-12-fold difference, tested on erythrocytes), a larger pore size (probably 2-3 nm) and different affinity to membrane lipids (100-fold lower affinity to sphingomyelin) (PubMed:24768765). Binds to sulfatides (SFT) as well as to the two sphingolipids, lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) (PubMed:31513812). It seems to bind more strongly to LPA than to S1P and SFT (PubMed:31513812). Shows cytolytic activity on HeLa cells, with a different potency than its paralogs (from most potent to less potent: HALT-4>HALT-6~HALT-1>HALT-3>HALT-7>HALT-2) (PubMed:31513812). Pore formation is a multi-step process that involves specific recognition of membrane lipid by a protein aromatic residues rich region, firm binding to the membrane (mainly driven by hydrophobic interactions) accompanied by the transfer of the N-terminal region to the lipid-water interface and finally pore formation after oligomerization of monomers (By similarity) (PubMed:31513812). In vitro, binds to the folate receptor alpha (FOLR1), a GPI-anchored membrane protein that plays a major role in the uptake of folate/folic acid into cells via endocytosis, suggesting a possible involvement of this receptor in the mechanism of HALT-1-induced cell lysis (PubMed:28478056). In vivo, does not cause visible paralysis in larvae of the blowfly Sarcophaga faculata, the most common arthropod prey of Hydra (PubMed:24768765). {ECO:0000250|UniProtKB:B9W5G6, ECO:0000269|PubMed:24768765, ECO:0000269|PubMed:28478056, ECO:0000269|PubMed:31513812}.

Hydra vulgaris (Hydra) (Hydra attenuata)

A0A8H8CMW1

CUBA_PSICU

MSTEQFVLPDLLESCPLKDATNPYYKEAAAESRAWINGYDIFTDRKRAEFIQGQNELLCSHVYWYAGREQLRTTCDFVNLLFVVDEVSDEQNGKGARETGQVFFKAMKYPDWDDGSILAKVTKEFMARFTRLAGPRNTKRFIDLCESYTACVGEEAELRERSELLDLASYIPLRRQNSAVLLCFALVEYILGIDLADEVYEDEMFMKAYWAACDQVCWANDIYSYDMEQSKGLAGNNIVSILMNENGTNLQETADYIGERCGEFVSDYISAKSQISPSLGPEALQFIDFVGYWMIGNIEWCFETPRYFGSRHLEIKETRVVHLRPKEVPEGLSSEDCIESDDE

4.2.3.-; 4.2.3.127; 4.2.3.128; 4.2.3.129; 4.2.3.91; 4.2.3.98

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9UR08};

metal ion binding [GO:0046872]; terpene synthase activity [GO:0010333]

PF19086;

1.10.600.10;

Terpene synthase family

CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate + H2O = cubebol + diphosphate; Xref=Rhea:RHEA:31823, ChEBI:CHEBI:15377, ChEBI:CHEBI:33019, ChEBI:CHEBI:63446, ChEBI:CHEBI:175763; EC=4.2.3.91; Evidence={ECO:0000269|PubMed:37614035}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:31824; Evidence={ECO:0000269|PubMed:37614035}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate = beta-copaene + diphosphate; Xref=Rhea:RHEA:33111, ChEBI:CHEBI:33019, ChEBI:CHEBI:64799, ChEBI:CHEBI:175763; EC=4.2.3.127; Evidence={ECO:0000269|PubMed:37614035}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33112; Evidence={ECO:0000269|PubMed:37614035}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate = delta-cadinene + diphosphate; Xref=Rhea:RHEA:56556, ChEBI:CHEBI:33019, ChEBI:CHEBI:140564, ChEBI:CHEBI:175763; Evidence={ECO:0000269|PubMed:37614035}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56557; Evidence={ECO:0000269|PubMed:37614035}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate = diphosphate + germacrene D; Xref=Rhea:RHEA:68716, ChEBI:CHEBI:33019, ChEBI:CHEBI:49045, ChEBI:CHEBI:175763; Evidence={ECO:0000269|PubMed:37614035}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68717; Evidence={ECO:0000269|PubMed:37614035}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate = (+)-sativene + diphosphate; Xref=Rhea:RHEA:33119, ChEBI:CHEBI:33019, ChEBI:CHEBI:64800, ChEBI:CHEBI:175763; EC=4.2.3.129; Evidence={ECO:0000269|PubMed:37614035}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33120; Evidence={ECO:0000269|PubMed:37614035}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate + H2O = (+)-T-muurolol + diphosphate; Xref=Rhea:RHEA:32011, ChEBI:CHEBI:15377, ChEBI:CHEBI:33019, ChEBI:CHEBI:63704, ChEBI:CHEBI:175763; EC=4.2.3.98; Evidence={ECO:0000269|PubMed:37614035}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32012; Evidence={ECO:0000269|PubMed:37614035}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate = beta-cubebene + diphosphate; Xref=Rhea:RHEA:32019, ChEBI:CHEBI:10363, ChEBI:CHEBI:33019, ChEBI:CHEBI:175763; EC=4.2.3.128; Evidence={ECO:0000269|PubMed:37614035}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32020; Evidence={ECO:0000269|PubMed:37614035}; CATALYTIC ACTIVITY: Reaction=(2E,6E)-farnesyl diphosphate = (1S,2S,4R)-beta-elemene + diphosphate; Xref=Rhea:RHEA:68712, ChEBI:CHEBI:33019, ChEBI:CHEBI:62855, ChEBI:CHEBI:175763; Evidence={ECO:0000269|PubMed:37614035}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68713; Evidence={ECO:0000269|PubMed:37614035};

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.0. {ECO:0000269|PubMed:37614035};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 29 degrees Celsius. {ECO:0000269|PubMed:37614035};

FUNCTION: Terpene cyclase that catalyzes the cyclization of farnesyl diphosphate (FPP) to various sesquiterpenes, including cubebol as the major product and beta-copaene, delta-cadinene, germacrene D, germacrene D-4-ol, sativene, tau-muurolol, beta-cubebene and beta-elemene as minor compounds, along with minute amounts of further sesquiterpenoids. {ECO:0000269|PubMed:37614035}.

Psilocybe cubensis (Psychedelic mushroom) (Stropharia cubensis)

A0A8I3NFE2

SHIP2_CANLF

MASACGAPGPGGAGPGGALGSPAPAWYHRDLSRAAAEELLARAGRDGSFLVRDSESVAGAFALCVLYQKHVHTYRILPDGEDFLAVQTSQGVPVRRFQTLGELIGLYAQPNQGLVCALLLPVEREREPDPPDDRDVSDGEDEKPPLPPRSGSTSISAPVGPGSPPAAPETPTTPAAESAPNGLSTVSHEYLKGSYGLDLEAVRGGASNLPHLTRTLATSCRRLHSEVDKVLAGLEILSKVFDQQSSPMVTRLLQQQNPAQTGEQELESLVLKLSVLKDFLSGIQKKALKVLQDMSSTAPPAPPQPAIRKAKTVPVQAFEVKLDVTLGDLTKIGKSQKFTLSVDVEGGRLVLLRRQRDSQEDWTTFTHDRIRQLIKSQRVQNKLGVVFEKEKDRTQRKDFIFVSARKREAFCQLLQLMKNKHSKQDEPDMISVFIGSWNMGSVPPPKNVTSWFTSKGLGKTLDEVTVTIPHDIYVFGTQENSVGDREWLDLLRGGLKELTDLDYRPIAMQSLWNIKVAVLVKPEHENRISHVSTSSVKTGIANTLGNKGAVGVSFMFNGTSFGFVNCHLTSGNEKTARRNQNYLDILRLLSLGDRQLSAFDISLRFTHLFWFGDLNYRLDMDIQEILNYISRKEFEPLLRVDQLNLEREKHKVFLRFSEEEISFPPTYRYERGSRDTYAWHKQKPTGVRTNVPSWCDRILWKSYPETHIICNSYGCTDDIVTSDHSPVFGTFEVGVTSQFISKKGLSKTSDQAYIEFESIEAIVKTASRTKFFIEFYSTCLEEYKKSFENDAQSSDNINFLKVQWSSRQLPTLKPILADIEYLQDQHLLLTVKSMDGYESYGECVVALKSMIGSTAQQFLTFLSHRGEETGNIRGSMKVRVPTERLGTRERLYEWISIDKDEAGAKSKAPSVSRGSQDPRSGNRKPAPAEASCPLSKLFEEPEKPPPTGRPPAPPRAASREEPLTPRLKAEGAPEPEGVAAPPPKNSFNNPAYYVLEGVPHQLLPPEPPSPARAPVPPATKNKVAITVPAPQLGRHRPPRVGEGSSSDEESGGTLPPPDFPPPPLPDSAIFLPPSLDPLPGPVVRGRSGGEARGPPPPKAHPRPPLPPGPSPTSTFLGEVASGDDRSCSVLQMAKTLSEVDYAPAGPGRSVLLPGPLELQPPRGLPSDYGRPLSFPPPRIRESIQEDLAEEAPCPQGGRAGGLGEAGMGAWLRAIGLERYEEGLVHNGWDDLEFLSDITEEDLEEAGVQDPAHKRLLLDTLQLSK

3.1.3.86

immune system process [GO:0002376]; negative regulation of insulin-like growth factor receptor signaling pathway [GO:0043569]; phosphatidylinositol dephosphorylation [GO:0046856]; regulation of immune response [GO:0050776]

basal plasma membrane [GO:0009925]; cytosol [GO:0005829]; filopodium [GO:0030175]; lamellipodium [GO:0030027]; nuclear speck [GO:0016607]; spindle pole [GO:0000922]

actin binding [GO:0003779]; inositol-polyphosphate 5-phosphatase activity [GO:0004445]; SH3 domain binding [GO:0017124]

PF00536;PF00017;

3.60.10.10;3.30.505.10;1.10.150.50;

Inositol 1,4,5-trisphosphate 5-phosphatase family

PTM: Tyrosine phosphorylated by the members of the SRC family after exposure to a diverse array of extracellular stimuli such as insulin, growth factors such as EGF or PDGF, chemokines, integrin ligands and hypertonic and oxidative stress. May be phosphorylated upon IgG receptor FCGR2B-binding. Phosphorylated at Tyr-992 following cell attachment and spreading. Phosphorylated at Tyr-1168 following EGF signaling pathway stimulation. Phosphorylated at Thr-964 in response to PDGF. {ECO:0000250|UniProtKB:O15357}.

SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:O15357}. Membrane {ECO:0000250|UniProtKB:O15357}; Peripheral membrane protein. Cell projection, filopodium {ECO:0000250|UniProtKB:O15357}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:O15357}. Basal cell membrane {ECO:0000269|PubMed:27926875}. Nucleus {ECO:0000250|UniProtKB:D7PF45}. Nucleus speckle {ECO:0000250|UniProtKB:D7PF45}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:27926875}. Note=Translocates to membrane ruffles when activated, translocation is probably due to different mechanisms depending on the stimulus and cell type (By similarity). Partly translocated via its SH2 domain which mediates interaction with tyrosine phosphorylated receptors such as the FC-gamma-RIIB receptor (FCGR2B). Tyrosine phosphorylation may also participate in membrane localization. Insulin specifically stimulates its redistribution from the cytosol to the plasma membrane. Recruited to the membrane following M-CSF stimulation. In activated spreading platelets, localizes with actin at filopodia, lamellipodia and the central actin ring (By similarity). {ECO:0000250|UniProtKB:O15357, ECO:0000250|UniProtKB:Q6P549}.

CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:25528, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57658, ChEBI:CHEBI:57836; EC=3.1.3.86; Evidence={ECO:0000250|UniProtKB:O15357}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25529; Evidence={ECO:0000250|UniProtKB:O15357}; CATALYTIC ACTIVITY: Reaction=1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = 1,2-dioctanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:43548, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83416, ChEBI:CHEBI:83417; Evidence={ECO:0000250|UniProtKB:O15357}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43549; Evidence={ECO:0000250|UniProtKB:O15357}; CATALYTIC ACTIVITY: Reaction=1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:43556, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:83420, ChEBI:CHEBI:83422; Evidence={ECO:0000250|UniProtKB:O15357}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43557; Evidence={ECO:0000250|UniProtKB:O15357};

FUNCTION: Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways (By similarity). Required for correct mitotic spindle orientation and therefore progression of mitosis (PubMed:27926875). Plays a central role in regulation of PI3K-dependent insulin signaling, although the precise molecular mechanisms and signaling pathways remain unclear (By similarity). While overexpression reduces both insulin-stimulated MAP kinase and Akt activation, its absence does not affect insulin signaling or GLUT4 trafficking (By similarity). Confers resistance to dietary obesity (By similarity). May act by regulating AKT2, but not AKT1, phosphorylation at the plasma membrane. Part of a signaling pathway that regulates actin cytoskeleton remodeling (By similarity). Required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation (By similarity). Participates in regulation of cortical and submembraneous actin by hydrolyzing PtdIns(3,4,5)P3 thereby regulating membrane ruffling (By similarity). Regulates cell adhesion and cell spreading (By similarity). Required for HGF-mediated lamellipodium formation, cell scattering and spreading (By similarity). Acts as a negative regulator of EPHA2 receptor endocytosis by inhibiting via PI3K-dependent Rac1 activation (By similarity). Acts as a regulator of neuritogenesis by regulating PtdIns(3,4,5)P3 level and is required to form an initial protrusive pattern, and later, maintain proper neurite outgrowth (By similarity). Acts as a negative regulator of the FC-gamma-RIIA receptor (FCGR2A) (By similarity). Mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems (By similarity). Involved in EGF signaling pathway (By similarity). Upon stimulation by EGF, it is recruited by EGFR and dephosphorylates PtdIns(3,4,5)P3 (By similarity). Plays a negative role in regulating the PI3K-PKB pathway, possibly by inhibiting PKB activity (By similarity). Down-regulates Fc-gamma-R-mediated phagocytosis in macrophages independently of INPP5D/SHIP1 (By similarity). In macrophages, down-regulates NF-kappa-B-dependent gene transcription by regulating macrophage colony-stimulating factor (M-CSF)-induced signaling (By similarity). Plays a role in the localization of AURKA and NEDD9/HEF1 to the basolateral membrane at interphase in polarized cysts, thereby mediates cell cycle homeostasis, cell polarization and cilia assembly (PubMed:27926875). Additionally promotion of cilia growth is also facilitated by hydrolysis of (PtdIns(3,4,5)P3) to PtdIns(3,4)P2 (PubMed:27926875). Promotes formation of apical membrane-initiation sites during the initial stages of lumen formation via Rho family-induced actin filament organization and CTNNB1 localization to cell-cell contacts (PubMed:27926875). May also hydrolyze PtdIns(1,3,4,5)P4, and could thus affect the levels of the higher inositol polyphosphates like InsP6. Involved in endochondral ossification (By similarity). {ECO:0000250|UniProtKB:O15357, ECO:0000250|UniProtKB:Q6P549, ECO:0000250|UniProtKB:Q9WVR3, ECO:0000269|PubMed:27926875}.

Canis lupus familiaris (Dog) (Canis familiaris)

A0A8I3P7X4

CCD47_CANLF

MKASLAFCVVLLVFGSVSEAKFDDFEDEEDIVEYDDNDFAEFEDVTEDSVTESPQRVITTEDDEDETTVELEGQDENQEGDFEDADTQEGDTESEPYDDEEFEGYEDKPDTSSSKNKDPITIVDVPAHLQNSWESYYLEILMVTGLLAYIMNYIIGKNKNSRLAQAWFNTHRELLESNFTLVGDDGTNKEATSTGKLNQENEHIYNLWCSGRVCCEGMLIQLRFLKRQDLLNVLARMMRPVSDQVQIKVTMNDEDMDTYVFAVGTRKALVRLQKEMQDLSEFCSDKPKSGAKYGLPDSLAILSEMGEVTEGMMDTKMVHFLTHYADKIESVHFSDQFSGPKIMQEEGQPLKLPDTKRTLLFTFNVPGSGNTYPKDMEALLPLMNMVIYSIDKAKKFRLNREGKQKADKNRARVEENFLKLTHVQRQEAAQSRREEKKRAEKERIMNEEDPEKQRRLEEAALRREQKKLEKKQMKMKQIKVKAM

endoplasmic reticulum calcium ion homeostasis [GO:0032469]; multi-pass transmembrane protein insertion into ER membrane [GO:0160063]

endoplasmic reticulum membrane [GO:0005789]; multi-pass translocon complex [GO:0160064]; rough endoplasmic reticulum membrane [GO:0030867]

calcium ion binding [GO:0005509]

PF07946;

CCDC47 family

SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:36261528}; Single-pass type I membrane protein {ECO:0000269|PubMed:36261528}. Rough endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9D024}; Single-pass type I membrane protein {ECO:0000269|PubMed:36261528}.

FUNCTION: Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (PubMed:36261528). The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (PubMed:36261528). Within the MPT complex, the PAT subcomplex sequesters any highly polar regions in the transmembrane domains away from the non-polar membrane environment until they can be buried in the interior of the fully assembled protein (PubMed:36261528). Within the PAT subcomplex, CCDC47 occludes the lateral gate of the SEC61 complex (PubMed:36261528). Involved in the regulation of calcium ion homeostasis in the ER (By similarity). Required for proper protein degradation via the ERAD (ER-associated degradation) pathway (By similarity). Has an essential role in the maintenance of ER organization during embryogenesis (By similarity). {ECO:0000250|UniProtKB:Q96A33, ECO:0000250|UniProtKB:Q9D024, ECO:0000269|PubMed:36261528}.

Canis lupus familiaris (Dog) (Canis familiaris)

A0A8I3PDQ1

CASL_CANLF

MWARNLMARALYDNVPECAEELAFRKGDILTVIEQNTGGLEGWWLCSLHGRQGIVPGNRVKLLIGPIQETPSGQDQPTSGLMHQTFGQQKLYQVPNPHSAPRDTIYQVPPSYQHQGIYQVPTSHGIQEQDVYQVPPSVQRSIGAANGPHLSKKVVTPVRTGQGYVYEYPSRHQKDIYDIPPSHTTQGVYDIPPSSVKVPVFSLPVGEIKPQGVYDIPPTKGLYAIPPSACRDEAGLREKEYDFPPPMRQAGRLDVRPEGVYDIPPTSTKPTGKDLHIKYNCDAPGAAELATRRHQSVLLNHAPSQLGQSPGAQNDAYDVPRGVQFLEPPAETSEKANPEERDGVYDVPLHNPPDAKGSQDVVDGMNRLSFSSTGSTRSNMSTSSTTSKESSVSASPSQDKRLLLDPDTAIERLHRLQQTLEVGVSSLMALVTTDWRCYGYMDRHINEIRTSVDKVELFVRDYLHFARGAVANASCLPELTLHNKMKRELQRVEDSHQILSQTSHDLNECSWSLNILAVNKPQNKCDDLDRFVMVAKTVPDDAKQLTTTINTNAEALFRPGPGSSHVKSGSENIMNSTEYPHAASQMPLLHPGDHKAQGLNKPLPPSLGKDQPPDCSSSDGSERSWMDDYDYVHLQGKEEFERQQKELLEKENIIKQNKLQLEHHQLSQFQLLEQEITKPVENDISKWKPSQSLPTTNSSVGAQDRQLLCFYYDQCETHYISLLNAIDALFSCVSSAQPPRIFVAHSKFVILSAHKLVFIGDTLTRQVAAQDICHKVMNSSNQLCEQLKTIVMATKMAALHYPSTTALQEMVHQVTDLSRNAQLFKRSLLEMATF

cell adhesion [GO:0007155]; cell cycle [GO:0007049]; cell division [GO:0051301]; cell migration [GO:0016477]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]

basolateral plasma membrane [GO:0016323]; cell cortex [GO:0005938]; cilium [GO:0005929]; focal adhesion [GO:0005925]; Golgi apparatus [GO:0005794]; lamellipodium [GO:0030027]; nucleus [GO:0005634]; spindle pole [GO:0000922]

PF12026;PF08824;PF14604;

1.20.120.230;1.20.120.830;2.30.30.40;

CAS family

PTM: Polyubiquitinated by ITCH/AIP4, leading to proteasomal degradation. {ECO:0000250|UniProtKB:Q14511}.; PTM: PTK2/FAK1 phosphorylates the protein at the YDYVHL motif (conserved among all cas proteins) following integrin stimulation (By similarity). The SRC family kinases (FYN, SRC, LCK and CRK) are recruited to the phosphorylated sites and can phosphorylate other tyrosine residues (By similarity). Ligation of either integrin beta-1 or B-cell antigen receptor on tonsillar B-cells and B-cell lines promotes tyrosine phosphorylation and both integrin and BCR-mediated tyrosine phosphorylation requires an intact actin network (By similarity). Phosphorylation is required to recruit NEDD9 to T-cell receptor microclusters at the periphery of newly formed immunological synapses (By similarity). In fibroblasts transformation with oncogene v-ABL results in an increase in tyrosine phosphorylation. Transiently phosphorylated following CD3 cross-linking and this phosphorylated form binds to CRKL and C3G (By similarity). A mutant lacking the SH3 domain is phosphorylated upon CD3 cross-linking but not upon integrin beta-1 cross-linking. Tyrosine phosphorylation occurs upon stimulation of the G-protein coupled C1a calcitonin receptor. Calcitonin-stimulated tyrosine phosphorylation is mediated by calcium- and protein kinase C-dependent mechanisms and requires the integrity of the actin cytoskeleton. Phosphorylation at Ser-369 induces proteasomal degradation (By similarity). Phosphorylated by LYN (By similarity). Phosphorylation at Ser-780 by CSNK1D or CSNK1E, or phosphorylation of Thr-804 by CSNK1E enhances the interaction of NEDD9 with PLK1 (By similarity). {ECO:0000250|UniProtKB:O35177, ECO:0000250|UniProtKB:Q14511}.

SUBCELLULAR LOCATION: Cytoplasm, cell cortex {ECO:0000250|UniProtKB:Q14511}. Nucleus {ECO:0000250|UniProtKB:Q14511}. Golgi apparatus {ECO:0000250|UniProtKB:Q14511}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:Q14511}. Cytoplasm {ECO:0000250|UniProtKB:Q14511}. Cell junction, focal adhesion {ECO:0000250|UniProtKB:Q14511}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q14511}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:27926875}. Cell projection, cilium {ECO:0000250|UniProtKB:Q14511}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000250|UniProtKB:Q14511}. Basolateral cell membrane {ECO:0000269|PubMed:27926875}.

FUNCTION: Negatively regulates embryonic fibroblast migration (By similarity). May play an important role in integrin beta-1 or B cell antigen receptor (BCR) mediated signaling in B- and T-cells. Integrin beta-1 stimulation leads to recruitment of various proteins including CRKl and SHPTP2 to the tyrosine phosphorylated form (By similarity). Promotes adhesion and migration of lymphocytes; as a result required for the correct migration of lymphocytes to the spleen and other secondary lymphoid organs (By similarity). Plays a role in the organization of T-cell F-actin cortical cytoskeleton and the centralization of T-cell receptor microclusters at the immunological synapse (By similarity). Negatively regulates cilia outgrowth in polarized cysts (PubMed:27926875). Modulates cilia disassembly via activation of AURKA-mediated phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (By similarity). In conjunction with NKX2-5, positively regulates transcription of genes such as COL3A1 and MMP2, resulting in increased pulmonary endothelial fibrosis in response to hypoxia (By similarity). Positively regulates RANKL-induced osteoclastogenesis (By similarity). Required for the maintenance of hippocampal dendritic spines in the dentate gyrus and CA1 regions, thereby involved in spatial learning and memory (By similarity). {ECO:0000250|UniProtKB:O35177, ECO:0000250|UniProtKB:Q14511, ECO:0000269|PubMed:27926875}.

Canis lupus familiaris (Dog) (Canis familiaris)

A0A8I3PI99

TMCO1_CANLF

MSTMFADTLLIVFISVCTALLAEGITWVLVYRTDKYKRLKAEVEKQSKKLEKKKETITESAGRQQKKKIERQEEKLKNNNRDLSMVRMKSMFAIGFCFTALMGMFNSIFDGRVVAKLPFTPLSYIQGLSHRNLLGDDTTDCSFIFLYILCTMSIRQNIQKILGLAPSRAATKQAGGFLGPPPPSGKFS

endoplasmic reticulum calcium ion homeostasis [GO:0032469]; multi-pass transmembrane protein insertion into ER membrane [GO:0160063]

endoplasmic reticulum membrane [GO:0005789]; Golgi membrane [GO:0000139]; multi-pass translocon complex [GO:0160064]

calcium channel activity [GO:0005262]

PF01956;

TMCO1 family

SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:36261528}; Multi-pass membrane protein {ECO:0000269|PubMed:36261528}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q9UM00}; Multi-pass membrane protein {ECO:0000269|PubMed:36261528}. Note=The first transmembrane region is required for localization to the endoplasmic reticulum. {ECO:0000250|UniProtKB:Q9UM00}.

FUNCTION: Calcium-selective channel required to prevent calcium stores from overfilling, thereby playing a key role in calcium homeostasis (By similarity). In response to endoplasmic reticulum (ER) overloading, assembles into a homotetramer, forming a functional calcium-selective channel, regulating the calcium content in endoplasmic reticulum store (By similarity). Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (PubMed:36261528). The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (PubMed:36261528). Within the MPT complex, the GEL subcomplex may mediate insertion of transmembrane regions into the membrane (PubMed:36261528). {ECO:0000250|UniProtKB:Q9UM00, ECO:0000269|PubMed:36261528}.

Canis lupus familiaris (Dog) (Canis familiaris)

A0A8I3S724

AURKA_CANLF

MDKSKENCIAGPVKTAIALGDGPKRVLVTQQVPSQNPLSANSGQAQRVLCPSNSSQRVPPQTQKLVSSHKPAQNLKQKQLQATGVPRPASRSLNNTQKSEQPSSSAPGNNSEKELATKQKNEESKKRQWALEDFEIGRPLGKGKFGNVYLAREKQSKFILAIKVLFKAQLEKAGVEHQLRREVEIQSHLRHPNILRLYGYFHDATRVYLILEYAPLGAVYRELQKLSKFDEQRTATYITELADALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGWSVHAPSSRRTTLCGTLDYLPPEMIEGRMHDEKVDLWSLGVLCYEFLVGKPPFEASTYQETYKRISRVEFTFPDFVPEGARDLISRLLKHNPSQRPTLKDVLEHPWIMANSSKPSSSQKSKDSTSKQS

2.7.11.1

cell division [GO:0051301]; meiotic spindle organization [GO:0000212]; mitotic centrosome separation [GO:0007100]; mitotic spindle organization [GO:0007052]; phosphorylation [GO:0016310]; positive regulation of mitotic cell cycle [GO:0045931]; regulation of cytokinesis [GO:0032465]

basolateral plasma membrane [GO:0016323]; centriole [GO:0005814]; chromosome passenger complex [GO:0032133]; cilium [GO:0005929]; cytoplasm [GO:0005737]; kinetochore [GO:0000776]; neuron projection [GO:0043005]; spindle microtubule [GO:0005876]; spindle midzone [GO:0051233]; spindle pole [GO:0000922]; spindle pole centrosome [GO:0031616]

ATP binding [GO:0005524]; protein serine/threonine kinase activity [GO:0004674]

PF00069;

1.10.510.10;

Protein kinase superfamily, Ser/Thr protein kinase family, Aurora subfamily

PTM: Activated by phosphorylation at Thr-289; this brings about a change in the conformation of the activation segment (By similarity). Phosphorylation at Thr-289 varies during the cell cycle and is highest during M phase (By similarity). Autophosphorylated at Thr-289 upon TPX2 binding (By similarity). Thr-289 can be phosphorylated by several kinases, including PAK and PKA. Protein phosphatase type 1 (PP1) binds AURKA and inhibits its activity by dephosphorylating Thr-289 during mitosis (By similarity). Phosphorylation at Ser-343 decreases the kinase activity (By similarity). PPP2CA controls degradation by dephosphorylating Ser-52 at the end of mitosis (By similarity). {ECO:0000250|UniProtKB:O14965}.; PTM: Ubiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL7) during mitosis, leading to its degradation by the proteasome (By similarity). Ubiquitinated by CHFR, leading to its degradation by the proteasome (By similarity). Ubiquitinated by the anaphase-promoting complex (APC), leading to its degradation by the proteasome (By similarity). Ubiquitinated by the CUL3-KLHL18 ligase leading to its activation at the centrosome which is required for initiating mitotic entry (By similarity). Ubiquitination mediated by CUL3-KLHL18 ligase does not lead to its degradation by the proteasome (By similarity). {ECO:0000250|UniProtKB:O14965, ECO:0000250|UniProtKB:P97477}.

SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250|UniProtKB:O14965}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000269|PubMed:27926875}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole {ECO:0000250|UniProtKB:P97477}. Cell projection, neuron projection {ECO:0000250|UniProtKB:P97477}. Cell projection, cilium {ECO:0000250|UniProtKB:O14965}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000250|UniProtKB:P97477}. Basolateral cell membrane {ECO:0000269|PubMed:27926875}. Note=Detected at the neurite hillock in developing neurons (By similarity). Localizes at the centrosome in mitotic cells from early prophase until telophase, but also localizes to the spindle pole MTs from prophase to anaphase (By similarity). Moves to the midbody during both telophase and cytokinesis (By similarity). Associates with both the pericentriolar material (PCM) and centrioles (By similarity). Colocalized with SIRT2 at centrosome. The localization to the spindle poles is regulated by AAAS (By similarity). {ECO:0000250|UniProtKB:O14965}.

CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:O14965}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:O14965};

FUNCTION: Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression (By similarity). Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis (PubMed:27926875). Required for normal spindle positioning during mitosis and for the localization of NUMA1 and DCTN1 to the cell cortex during metaphase (By similarity). Required for initial activation of CDK1 at centrosomes (By similarity). Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2 (By similarity). Regulates KIF2A tubulin depolymerase activity (By similarity). Important for microtubule formation and/or stabilization (By similarity). Required for normal axon formation (By similarity). Plays a role in microtubule remodeling during neurite extension (By similarity). Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and destabilizing p53/TP53 (By similarity). Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity (By similarity). Inhibits cilia outgrowth (PubMed:27926875). Required for cilia disassembly via phosphorylation of HDAC6 and subsequent deacetylation of alpha-tubulin (By similarity). Regulates protein levels of the anti-apoptosis protein BIRC5 by suppressing the expression of the SCF(FBXL7) E3 ubiquitin-protein ligase substrate adapter FBXL7 through the phosphorylation of the transcription factor FOXP1 (By similarity). {ECO:0000250|UniProtKB:O14965, ECO:0000269|PubMed:27926875}.

Canis lupus familiaris (Dog) (Canis familiaris)

A0A8I3S9V6

RCAF1_CANLF

MSGGRRKEEPPQPQLANGALKVSVWSKVLRSDAAWEDKDEFLDVIYWFRQIIAVVLGVIWGVLPLRGFLGIAGFCVINAGVLYLYFSNYLQIDEEEYGGTWELTKEGFMTSFALFMVIWIIFYTAIHYD

mitochondrial respirasome assembly [GO:0097250]; multi-pass transmembrane protein insertion into ER membrane [GO:0160063]

endoplasmic reticulum membrane [GO:0005789]; mitochondrial inner membrane [GO:0005743]; multi-pass translocon complex [GO:0160064]

PF07019;

EMC6 family

SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:36261528}; Multi-pass membrane protein {ECO:0000269|PubMed:36261528}. Mitochondrion inner membrane {ECO:0000250|UniProtKB:Q9BUV8}; Multi-pass membrane protein {ECO:0000255}.

FUNCTION: Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (PubMed:36261528). The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (PubMed:36261528). Within the MPT complex, the GEL subcomplex may mediate insertion of transmembrane regions into the membrane (PubMed:36261528). In addition to its role in multi-pass membrane insertion, RAB5IF/OPTI also acts as an assembly factor for mitochondrial respiratory complexes (By similarity). {ECO:0000250|UniProtKB:Q9BUV8, ECO:0000269|PubMed:36261528}.

Canis lupus familiaris (Dog) (Canis familiaris)

A0A8I5ZN27

CNGB1_RAT

MLGWVQRVLPQPPGTPQKTEEGAGPQPETESKPEANPQPEPEVQPEPEPEPEPAPEEAAPEVQTLPPEEPVEGEDVAEAGPSLQETQEADPPQPTSQAQVAVVKVNRPSSWMLSWFWKGMEKVVPQPVYSSSGGQNLAAGEGGPDQDGAQTLEPCGTGDPGSEDGSDKTSKTQDTEPSLWLLRWLELNLEKVLPQPPTPSQAWKVEPEGAVLEPDPPGTPMEVEPTENPSQPNPGPVEPEEEPAAEPQPGFQASSLPPPGDPVRLIEWLLHRLEMALPQPVLHGKAAEQEPSCPGTCDVQTISILPVEQAEHDLVLEDVDSCWEDTQQEDGASLQETELAPIYEDESEAMVEMPRELPQIQEEEEEEKEEKEEKEEEEEKEEEEKREEEKKKEKEEEKKEKEKEEKEEKEEKEEEEKEEKEEEEKEEKEEEEKEEKEEEEEEEEEEEEEEPIVLLDSCLVVQADVDQCQLERAQPETASIQELPEEEEEKEEEKKEEEEEKEEEEEKEEEEEKEEEGEATNSTVPATKEHPELQVEDTDAEAGPLIPEETIPPPERPPVSPAKSDTLAVPGAATHRKKLPSQDDEAEELKALSPAESPVVAWSDPTTPQEADGEDRAASTASQNSAIINDRLQELVKMFKERTEKVKEKLIDPDVTSDEESPKPSPAKKAPDSAPAQKPAEAEAAEEEHYCDMLCCKFKRRPWKMYQFPQSIDPLTNLMYILWLFFVVLAWNWNCWLIPVRWAFPYQRADNIHLWLLMDYLCDFIYLLDITVFQMRLQFVKGGDIITDKKEMRNNYLKSQRFKMDLLCLLPLDFLYLKLGVNPLLRLPRCLKYMAFFEFNNRLEAILSKAYVYRVIRTTAYLLYSLHLNSCLYYWASAFQGIGSTHWVYDGVGNSYIRCYYWAVKTLITIGGLPDPQTLFEIVFQLLNYFTGVFAFSVMIGQMRDVVGAATAGQTYYRSCMDSTVKYMNFYKIPRSVQNRVKTWYEYTWHSQGMLDESELMVQLPDKMRLDLAIDVNYNIVSKVALFQGCDRQMIFDMLKRLRSVVYLPNDYVCKKGEIGREMYIIQAGQVQVLGGPDGKAVLVTLKAGSVFGEISLLAVGGGNRRTANVVAHGFTNLFILDKKDLNEILVHYPESQKLLRKKARRMLRNNNKPKEEKSVLILPPRAGTPKLFNAALAAAGKMGPRGAKGGKLAHLRARLKELAALEAAARQQQLLEQAKSSQEAGGEEGSGATDQPAPQEPSEPKEPPEPPAPSSPPPASAKPEGSTEEAAGPPEPSVRIRVSPGPDPGEQTLSVEMLEEKKEEVE

detection of chemical stimulus involved in sensory perception of smell [GO:0050911]; detection of light stimulus involved in visual perception [GO:0050908]; ion channel modulating, G protein-coupled receptor signaling pathway [GO:0099105]; membrane depolarization [GO:0051899]; monoatomic cation transmembrane transport [GO:0098655]; monoatomic cation transport [GO:0006812]; olfactory nerve maturation [GO:0021630]; photoreceptor cell maintenance [GO:0045494]; photoreceptor cell outer segment organization [GO:0035845]; phototransduction [GO:0007602]; positive regulation of gene expression [GO:0010628]; protein localization to organelle [GO:0033365]; regulation of cytosolic calcium ion concentration [GO:0051480]; response to odorant [GO:1990834]; retina homeostasis [GO:0001895]; sensory perception of smell [GO:0007608]

intracellular cyclic nucleotide activated cation channel complex [GO:0017071]; membrane [GO:0016020]; photoreceptor outer segment [GO:0001750]; plasma membrane [GO:0005886]; terminal bouton [GO:0043195]; transmembrane transporter complex [GO:1902495]

cAMP binding [GO:0030552]; cGMP binding [GO:0030553]; cyclic nucleotide-activated monoatomic ion channel activity [GO:0043855]; intracellularly cAMP-activated cation channel activity [GO:0005222]; intracellularly cGMP-activated cation channel activity [GO:0005223]; intracellularly cyclic nucleotide-activated monoatomic cation channel activity [GO:0005221]; protein-containing complex binding [GO:0044877]

PF00027;

1.10.287.70;1.10.287.630;2.60.120.10;

Cyclic nucleotide-gated cation channel (TC 1.A.1.5) family, CNGB1 subfamily

SUBCELLULAR LOCATION: [Isoform 2]: Cell projection, cilium membrane {ECO:0000269|PubMed:10377344}; Multi-pass membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:9878057}; CATALYTIC ACTIVITY: Reaction=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963, ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:10377344}; CATALYTIC ACTIVITY: Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103; Evidence={ECO:0000269|PubMed:10377344}; CATALYTIC ACTIVITY: Reaction=NH4(+)(in) = NH4(+)(out); Xref=Rhea:RHEA:28747, ChEBI:CHEBI:28938; Evidence={ECO:0000250|UniProtKB:Q28181}; CATALYTIC ACTIVITY: Reaction=Rb(+)(in) = Rb(+)(out); Xref=Rhea:RHEA:78547, ChEBI:CHEBI:49847; Evidence={ECO:0000250|UniProtKB:Q9NQW8}; CATALYTIC ACTIVITY: Reaction=Li(+)(in) = Li(+)(out); Xref=Rhea:RHEA:78551, ChEBI:CHEBI:49713; Evidence={ECO:0000250|UniProtKB:Q9NQW8}; CATALYTIC ACTIVITY: Reaction=Cs(+)(in) = Cs(+)(out); Xref=Rhea:RHEA:78555, ChEBI:CHEBI:49547; Evidence={ECO:0000250|UniProtKB:Q28181};

FUNCTION: Pore-forming subunit of the rod cyclic nucleotide-gated channel. Mediates rod photoresponses at dim light converting transient changes in intracellular cGMP levels into electrical signals. In the dark, cGMP levels are high and keep the channel open enabling a steady inward current carried by Na(+) and Ca(2+) ions that leads to membrane depolarization and neurotransmitter release from synaptic terminals. Upon photon absorption cGMP levels decline leading to channel closure and membrane hyperpolarization that ultimately slows neurotransmitter release and signals the presence of light, the end point of the phototransduction cascade. Conducts cGMP- and cAMP-gated ion currents, with permeability for monovalent and divalent cations. The selectivity for Ca(2+) over Na(+) increases with cGMP concentrations, whereas the selectivity among monovalent ions is independent of the cGMP levels. {ECO:0000250|UniProtKB:Q28181}.; FUNCTION: [Isoform 2]: Pore-forming subunit of the olfactory cyclic nucleotide-gated channel. Operates in the cilia of olfactory sensory neurons where chemical stimulation of the odorant is converted to an electrical signal. Mediates odorant-induced cAMP-dependent Ca(2+) influx triggering neuron depolarization. The rise of intracellular Ca(2+) levels potentiates the olfactory response by activating Ca(2+)-dependent Cl(-) channels, but it also serves as a negative feedback signal to desensitize the channel for rapid adaptation to odorants. {ECO:0000269|PubMed:10377344, ECO:0000269|PubMed:15134638, ECO:0000269|PubMed:27405959, ECO:0000269|PubMed:9539801, ECO:0000269|PubMed:9878057}.

Rattus norvegicus (Rat)

A0A8I5ZNK2

OXSR1_RAT

MSEDSSALPWSINRDDYELQEVIGSGATAVVQAAYCAPKKERVAIKRINLEKCQTSMDELLKEIQAMSQCHHPNIVSYYTSFVVKDELWLVMKLLSGGSVLDIIKHIVAKGEHKGGVLDESTIATILREVLEGLEYLHKNGQIHRDVKAGNILLGEDGSVQIADFGVSAFLATGGDITRNKVRKTFVGTPCWMAPEVMEQVRGYDFKADIWSFGITAIELATGAAPYHKYPPMKVLMLTLQNDPPSLDTGVQDKEMLKKYGKSFRKMISLCLQKDPEKRPTAAELLRHKFFQKAKNKEFLQEKILQRAPTISERSKKVRRVPGSSGRLHKTEDGGWEWSDDEFDEESEEGKAAISQLRSCPTQQHCLCLLQLFSAADPMGTLLQVPEQISAHLPQPASQMPTQPAQVSLLPPAEPAKPAQARSSGERSQETKVPISLVLRLRNSKKELNDIRFEFTPGRDTAEGVSQELISAGLVDGRDLVIVAANLQKIVEEPQSNRSVTFKLASGVEGSDIPDDGKLIGFAQLSIS

2.7.11.1

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:O95747};

cell volume homeostasis [GO:0006884]; cellular hyperosmotic response [GO:0071474]; cellular hypotonic response [GO:0071476]; cellular response to chemokine [GO:1990869]; chemokine (C-C motif) ligand 21 signaling pathway [GO:0038116]; chemokine (C-X-C motif) ligand 12 signaling pathway [GO:0038146]; intracellular signal transduction [GO:0035556]; negative regulation of potassium ion transmembrane transport [GO:1901380]; osmosensory signaling pathway [GO:0007231]; phosphorylation [GO:0016310]; positive regulation of T cell chemotaxis [GO:0010820]; renal sodium ion absorption [GO:0070294]; response to oxidative stress [GO:0006979]; response to xenobiotic stimulus [GO:0009410]; signal transduction [GO:0007165]

cytoplasm [GO:0005737]; cytosol [GO:0005829]

ATP binding [GO:0005524]; identical protein binding [GO:0042802]; magnesium ion binding [GO:0000287]; protein kinase binding [GO:0019901]; protein serine/threonine kinase activity [GO:0004674]

PF12202;PF00069;

1.10.510.10;

Protein kinase superfamily, STE Ser/Thr protein kinase family, STE20 subfamily

PTM: Phosphorylation at Thr-185 by WNK kinases (WNK1, WNK2, WNK3 or WNK4) is required for activation (PubMed:16083423). Autophosphorylated; promoting its activity (By similarity). {ECO:0000250|UniProtKB:O95747, ECO:0000269|PubMed:16083423}.

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O95747}.

CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:O95747}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:O95747};

FUNCTION: Effector serine/threonine-protein kinase component of the WNK-SPAK/OSR1 kinase cascade, which is involved in various processes, such as ion transport, response to hypertonic stress and blood pressure (PubMed:22544747). Specifically recognizes and binds proteins with a RFXV motif (By similarity). Acts downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4): following activation by WNK kinases, catalyzes phosphorylation of ion cotransporters, such as SLC12A1/NKCC2, SLC12A2/NKCC1, SLC12A3/NCC, SLC12A5/KCC2 or SLC12A6/KCC3, regulating their activity (By similarity). Mediates regulatory volume increase in response to hyperosmotic stress by catalyzing phosphorylation of ion cotransporters SLC12A1/NKCC2, SLC12A2/NKCC1 and SLC12A6/KCC3 downstream of WNK1 and WNK3 kinases (By similarity). Phosphorylation of Na-K-Cl cotransporters SLC12A2/NKCC1 and SLC12A2/NKCC1 promote their activation and ion influx; simultaneously, phosphorylation of K-Cl cotransporters SLC12A5/KCC2 and SLC12A6/KCC3 inhibit their activity, blocking ion efflux (PubMed:22544747). Acts as a regulator of NaCl reabsorption in the distal nephron by mediating phosphorylation and activation of the thiazide-sensitive Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney downstream of WNK4 (By similarity). Also acts as a regulator of angiogenesis in endothelial cells downstream of WNK1 (By similarity). Acts as an activator of inward rectifier potassium channels KCNJ2/Kir2.1 and KCNJ4/Kir2.3 downstream of WNK1: recognizes and binds the RXFXV/I variant motif on KCNJ2/Kir2.1 and KCNJ4/Kir2.3 and regulates their localization to the cell membrane without mediating their phosphorylation (By similarity). Phosphorylates RELL1, RELL2 and RELT (By similarity). Phosphorylates PAK1. Phosphorylates PLSCR1 in the presence of RELT (By similarity). {ECO:0000250|UniProtKB:O95747, ECO:0000269|PubMed:22544747}.

Rattus norvegicus (Rat)

A0A8I6G705

RBPMS_RAT

MNGGGKAEKENTPSEANLQEEEVRTLFVSGLPLDIKPRELYLLFRPFKGYEGSLIKLTSKQPVGFVSFDSRSEAEAAKNALNGIRFDPEIPQTLRLEFAKANTKMAKNKLVGTPNPSTPLPNTVPQFIAREPYELTVPALYPSSPEVWAPYPLYPAELAPALPPPAAFTYPASLHAQMRWLPPSEATSQGWKSRQFC

protein-containing complex assembly [GO:0065003]; regulation of alternative mRNA splicing, via spliceosome [GO:0000381]; response to oxidative stress [GO:0006979]; SMAD protein signal transduction [GO:0060395]

cytoplasm [GO:0005737]; cytoplasmic stress granule [GO:0010494]; cytosol [GO:0005829]; nucleus [GO:0005634]; P-body [GO:0000932]

identical protein binding [GO:0042802]; molecular adaptor activity [GO:0060090]; mRNA 3'-UTR binding [GO:0003730]; mRNA binding [GO:0003729]; mRNA CDS binding [GO:1990715]; pre-mRNA binding [GO:0036002]; pre-mRNA intronic binding [GO:0097157]; protein homodimerization activity [GO:0042803]; RNA binding [GO:0003723]; transcription coactivator activity [GO:0003713]

PF00076;

3.30.70.330;

SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q93062}. Cytoplasm {ECO:0000250|UniProtKB:Q93062}. Cytoplasm, Stress granule {ECO:0000250|UniProtKB:Q93062}. Cytoplasm, P-body {ECO:0000250|UniProtKB:Q93062}.

FUNCTION: [Isoform 1]: RNA binding protein that mediates pre-mRNA alternative splicing (AS) regulation (PubMed:31283468, PubMed:37548402). Acts either as activator (FLNB, HSPG2, LIPA1, MYOCD, PTPRF and PPFIBP1) or repressor (TPM1, ACTN1, ITGA7, PIEZO1, LSM14B, MBNL1 and MBML2) of splicing events on specific pre-mRNA targets (PubMed:31283468, PubMed:37548402). Together with RNA binding proteins RBFOX2 and MBNL1/2, activates a splicing program associated with differentiated contractile vascular smooth muscle cells (SMC) by regulating AS of numerous pre-mRNA involved in actin cytoskeleton and focal adhesion machineries, suggesting a role in promoting a cell differentiated state (PubMed:31283468, PubMed:37548402). Binds to introns, exons and 3'-UTR associated with tandem CAC trinucleotide motifs separated by a variable spacer region, at a minimum as a dimer. The minimal length of RNA required for RBPMS-binding tandem CAC motifs is 15 nt, with spacing ranging from 1 to 9 nt. Can also bind to CA dinucleotide repeats (By similarity). Mediates repression of TPM1 exon 3 by binding to CAC tandem repeats in the flanking intronic regions, followed by higher-order oligomerization and heterotypic interactions with other splicing regulators including MBNL1 and RBFOX2, which prevents assembly of ATP-dependent splicing complexes (PubMed:37548402). {ECO:0000250|UniProtKB:Q93062, ECO:0000269|PubMed:31283468, ECO:0000269|PubMed:37548402}.; FUNCTION: [Isoform 2]: Acts as a regulator of pre-mRNA alternative splicing (AS) (PubMed:31283468). Binds mRNA (By similarity). Regulates AS of ACTN1, FLNB, although with lower efficiency than isoform 1 (PubMed:31283468). Acts as coactivator of SMAD transcriptional activity in a TGFB1-dependent manner, possibly through increased phosphorylation of SMAD2 and SMAD3 at the C-terminal SSXS regions and promotion of the nuclear accumulation of SMAD proteins (By similarity). {ECO:0000250|UniProtKB:Q93062, ECO:0000269|PubMed:31283468}.

Rattus norvegicus (Rat)

A0A8M1NHK4

RBM47_DANRE

MTAEDSASAVAMSNPSPSSSSKSSSGHPQHHCTVPEGVAGAPNEAALVSLMERSGYGMVQENGQRKYGPPPGWQGTSPPRGCEIFVGKIPRDVYEDELVPVFESVGRIYEMRLMMDFDGKNRGYAFVMYTQKHEAKRAVRELNNFEIRPGRLLGVCSSVDNCRLFIGGIPKTKKREEILEEVSKVTEGVLDVIVYASAADKMKNRGFAFVEYESHRAAAMARRKLMPGRIQLWGHQIAVDWAEPEIDVDEDVMETVKILYVRNLMIETSEEILRQTFGQFNPGCVERVKKIRDYAFVHFASRDDAVVAMDNLNGTEIEGSRIEVTLAKPVDKEQYTRYQKASKGTAAATTVESTQQSYVYQCDPYTLAYYGYPYNTLIGPNRDYFIKGTVRGRGRAGASSRGPGPRGSYLGGYSAGRGIYSRYHEGKTKLPDKPYEIMSNLELAAVNPVGIKPGTMALPALGAQYPTVFSAAPATKLMEEGKIHPVEHLINPLALQHDPTAASATAAVIPAVSTPPPFQGRPITPVYAMAHNIQRIPAAAASLYGAGYMPIAAHANTATLAALQKNAAVAAAYGGYAGYMPQAFPAATFQMPIHDVYQTY

antiviral innate immune response [GO:0140374]; head development [GO:0060322]; lysosomal protein catabolic process [GO:1905146]; mRNA processing [GO:0006397]; regulation of anterior head development [GO:2000742]; RNA splicing [GO:0008380]

lysosome [GO:0005764]; nucleus [GO:0005634]

mRNA binding [GO:0003729]

PF00076;

3.30.70.330;

RRM RBM47 family

SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:A0AV96}. Cytoplasm {ECO:0000250|UniProtKB:A0AV96}.

FUNCTION: Single-stranded RNA-binding protein that functions in a variety of RNA processes, including alternative splicing, RNA stabilization, and RNA editing (By similarity). Independently of its RNA-binding activity, could negatively regulate MAVS by promoting its lysosomal degradation (PubMed:32859727). {ECO:0000250|UniProtKB:A0AV96, ECO:0000269|PubMed:32859727}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0A8M2

L14AA_XENLA

MSGGTPYIGSKISLISKAEIRYEGILYTIDTENSTVALAKVRSFGTEDRPTDRPIPPRDEIFEYIIFRGSDIKDLTVCEPPKPQCSLPQDPAIVQSSLGSSSASSFQSVSSYGPFGRMPAYSQFNTGPLVGPQFGAVGVGSSLTSFGAETTSSTSLPPSSAVGTSFTQEARTLKTQSSQGQSSSPLDSLRKSPNIEQAVQTAAAPHAPSTATVGRRSPVLSRPVPSSIQKTAESPEQRKGELHKMQRPDIDQLKNDKNDPSKRQPVLSALQPRRGRGGNRGGRGRFGVRRDGPMKFEKDFDFESANAQFNKEEIDREFHNKLKIKDDKPEKPVNGEDKTDSVVDTQNSEGNAEEEEVLAGGVCYYDKTKSFFDNISCDDNRDRRQTWAEERRINVETFGLPLRSNRGRGGFRGRGGGMGFRGGRGRGGERRGAPGGGGFGPARGFRGGFRGGRGGREFADYEYRKDNKVAA

negative regulation of translation [GO:0017148]; P-body assembly [GO:0033962]; stress granule assembly [GO:0034063]

cytoplasm [GO:0005737]; cytoplasmic stress granule [GO:0010494]; P-body [GO:0000932]; protein-containing complex [GO:0032991]; ribonucleoprotein complex [GO:1990904]

DEAD/H-box RNA helicase binding [GO:0017151]; mRNA binding [GO:0003729]; RNA binding [GO:0003723]

PF09532;PF12701;

2.30.30.100;

LSM14 family

PTM: Phosphorylated. {ECO:0000269|PubMed:17074753}.

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17074753}. Cytoplasm, P-body {ECO:0000250|UniProtKB:Q8ND56}. Cytoplasm, Stress granule {ECO:0000250|UniProtKB:Q8ND56}. Note=Localizes to cytoplasmic particles in stage VI oocytes and eggs. {ECO:0000269|PubMed:17074753}.

FUNCTION: RNA-binding component of messenger ribonucleoprotein complexes (mRNPs), storage particles that mask maternal mRNAs from the translational apparatus during oocyte maturation (PubMed:17074753). Acts as a repressor of mRNA translation (PubMed:17074753). Probably involved in the storage of translationally inactive mRNAs in the cytoplasm in order to prevent their degradation (PubMed:17074753). {ECO:0000269|PubMed:17074753}.

Xenopus laevis (African clawed frog)

A0A8M3B525

BRCC3_DANRE

MWKCSTVINKNKLIKAEYHTFYTLLFAMAVNAVHLESDAFLVCMNHALSTEKEEVMGLCIGEVDTNRIVHIHSVIILRRSDKRKDRVEISPEQLSAASTEAERLAEMTGRPMRVVGWYHSHPHITVWPSHVDVRTQAMYQMMDQGFVGLIFSCFIEDKNTKTGRVLYTCFQSVQAQKGSEYERIEIPIHVVPHEAIGKVCLESAVELPRILCQEEQDTYRRIHSLTHLDPITKIHNGSVFTKNLCSQMSAISGPLLQWLEDRLEQNKQSIITLQKEKELLTQELAAL

3.4.19.-

COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000255|RuleBase:RU367116, ECO:0000269|PubMed:26344097}; Note=Binds 1 zinc ion per subunit. {ECO:0000255|RuleBase:RU367116, ECO:0000269|PubMed:26344097};

angiogenesis [GO:0001525]; cell cycle [GO:0007049]; cell division [GO:0051301]; double-strand break repair [GO:0006302]; proteolysis [GO:0006508]

BRCA1-A complex [GO:0070531]; BRISC complex [GO:0070552]; cytoplasm [GO:0005737]; spindle pole [GO:0000922]

cysteine-type deubiquitinase activity [GO:0004843]; metal ion binding [GO:0046872]; metallopeptidase activity [GO:0008237]; polyubiquitin modification-dependent protein binding [GO:0031593]

PF18110;PF01398;

3.40.140.10;

Peptidase M67A family, BRCC36 subfamily

SUBCELLULAR LOCATION: Nucleus {ECO:0000255|RuleBase:RU367116}. Cytoplasm {ECO:0000255|RuleBase:RU367116}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000255|RuleBase:RU367116}.

FUNCTION: Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains, leaving the last ubiquitin chain attached to its substrates (By similarity). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates; brcc3 does not have activity by itself, but needs to be associated into a higher-order assembly, for minimal in vitro activity (PubMed:26344097). {ECO:0000250|UniProtKB:E2AXC7, ECO:0000269|PubMed:26344097}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0A8M9PFP2

CSTN3_DANRE

MARMSFLSFLLFCLTSVAHGNKANKHKPWIETEYQGIVMENDNTVLLNPPLFALDKDAPLHYAGEICGFRVHNGPGGSGSAQFEAVVLDRSTGEGLVRSKEPLDCESQKEHSFTIQAYDCGEGPDGTNSKKSHKATVHVRVNDVNEFSPVFVERRYEASVPEGRLFDRIVRVEAVDADCSPQYSQICFYDIITPNVPFTIDNDGNIKNTEPLDSKRQRVHSFWVTAFDCGKNRAQADAQVIVTVKPSCKPGWIGWTKRIEYTPGSGSIPLFPNLHLETCEETVWNIQATVELQTSHIGKGCDRDSYSDRSVRRLCGAVRGEVDLLPPPSPATNWTAALPTLPSSDSSLVFSFNGSTHVAVVPDSVASAVSGDHFTLQLWMRRGGASTQPPANQARGTRKEEETIVCSTVKNDDSYSHYSLSVHGCRLSLFYWPDVSAARPVKFLWKLEQVCDSEWHHLSLSVQFPSVTLYVDGVTFDPALIHDNGAIPNPAPHQRLVIGACWEPEEKPKDIVNNTMPENKDTGKFVSGYKGLLSGVTVRPGNVEPHSVVECLYACREGLDFGDLETLGSGMKVHVNPSQSVLVLEGDDIESFNRAVQQVTYRNSLRFATPGVRPLKLTTSLRCFSEESCLSLRQLEGYLVVLQPDAPQISLSGVGPHLARPAAEFEGPQGVPLFPELRIVCSLSHAVNTAAQGMEGGALMSDAVAHTLDGCEVQPLGEELNTEREELLVDMESLRERGLDIINTTAYIAITGAESISVYEDVLRSIHYRLAKGSARFERRFRLSCSEMNGRYTSNELTLEVNFLHSLDSLYHPSHLLASQQQFLHPSHHTGELSGHTLPNPHRNSVVPGAATVIIMVCVGFLVVMVILGVFRIRSIHRRGEGARGGGKEGGNQWDDSALTIIVNPMETYENRMGITTDMEGECEDEEEVVDSPDDTSDDQRIIIKKEGRDSAPRRY

excitatory synapse assembly [GO:1904861]; homophilic cell adhesion via plasma membrane adhesion molecules [GO:0007156]; inhibitory synapse assembly [GO:1904862]; negative regulation of excitatory synapse assembly [GO:1904890]; positive regulation of inhibitory synapse assembly [GO:1905704]; positive regulation of synapse assembly [GO:0051965]; positive regulation of synaptic transmission [GO:0050806]; regulation of excitatory synapse assembly [GO:1904889]

cell surface [GO:0009986]; endoplasmic reticulum membrane [GO:0005789]; Golgi membrane [GO:0000139]; postsynaptic membrane [GO:0045211]

amyloid-beta binding [GO:0001540]; calcium ion binding [GO:0005509]; cell-cell adhesion mediator activity [GO:0098632]; kinesin binding [GO:0019894]; neurexin family protein binding [GO:0042043]; X11-like protein binding [GO:0042988]

PF00028;PF19699;

2.60.120.200;2.60.40.60;

Calsyntenin family

SUBCELLULAR LOCATION: Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q99JH7}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q99JH7}; Single-pass type I membrane protein {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q99JH7}; Single-pass type I membrane protein {ECO:0000255}. Note=Most prominent in the postsynaptic specializations of asymmetric (type I) synapses. {ECO:0000250|UniProtKB:Q99JH7}.

FUNCTION: Synaptic adhesion molecule (PubMed:25463516). Promotes synapse development by acting as a cell adhesion molecule at the postsynaptic membrane, which associates with presynaptic neurexins (By similarity). {ECO:0000250|UniProtKB:Q99JH7, ECO:0000269|PubMed:25463516}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0A8V1ABE9

DSD1_CHICK

MWLGALLDTLPTPALTIDRTTAHRNAERMRERCRALGVRLRPHVKTHKTLEGGLLATGGTRRGIAVSTLAEARFFADGGFDDILLAYPVPTARLEECAGLARRLDAFHVLLDRPEALASLRQRPLGHGKRWLVWLKLDCGNGRAGVRPTDPAALELAQAIANDAPEEVTLVGVYAHCGNTYGCSGADTIQAIARTTTNAVLSFVAALRQAGVPCPQASIGSTPSCSHPIPEMSQLTELHPGNYIFYDLQQTQLGSCQPQDVAIRVLTRVIGHYAHRGQLLVDCGWAALSLHGAGAGQGPQGCAAIDGHPELRLVGLTQEHGLLEHAGGQMDFGRFPVGSVLALIPYHACATAAMHPVYYVHEEGKVVALWHPVRGW

4.3.1.18

COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000269|PubMed:17977854}; COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:21676877};

D-serine catabolic process [GO:0036088]

cytoplasm [GO:0005737]; dendrite [GO:0030425]

D-serine ammonia-lyase activity [GO:0008721]; pyridoxal phosphate binding [GO:0030170]; zinc ion binding [GO:0008270]

PF01168;PF14031;

3.20.20.10;2.40.37.20;

DSD1 family

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24529545}. Cell projection, dendrite {ECO:0000269|PubMed:24529545}.

CATALYTIC ACTIVITY: Reaction=D-serine = NH4(+) + pyruvate; Xref=Rhea:RHEA:13977, ChEBI:CHEBI:15361, ChEBI:CHEBI:28938, ChEBI:CHEBI:35247; EC=4.3.1.18; Evidence={ECO:0000269|PubMed:17977854, ECO:0000269|PubMed:21676877, ECO:0000305|PubMed:24529545}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13978; Evidence={ECO:0000269|PubMed:17977854, ECO:0000269|PubMed:21676877};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=131 uM for D-serine (at pH 7.8 and 37 degrees Celsius) {ECO:0000269|PubMed:17977854}; KM=830 uM for D-serine (at pH 7.5, 37 degrees Celsius and in presence of Zn(2+)) {ECO:0000269|PubMed:21676877}; KM=340 uM for D-serine (at pH 7.5, 37 degrees Celsius and in presence of Mn(2+)) {ECO:0000269|PubMed:21676877}; KM=312 uM for D-threonine (at pH 7.8 and 37 degrees Celsius) {ECO:0000269|PubMed:17977854}; Note=kcat is 0.811 sec(-1) with D-serine as substrate (at pH 7.8 and 37 degrees Celsius) (PubMed:17977854). kcat is 2.08 sec(-1) with D-serine as substrate (at pH 7.5, 37 degrees Celsius and in presence of Zn(2+)) (PubMed:21676877). kcat is 0.244 sec(-1) with D-serine as substrate (at pH 7.5, 37 degrees Celsius and in presence of Mn(2+)) (PubMed:21676877). kcat is 0.0512 sec(-1) with D-threonine as substrate (at pH 7.8 and 37 degrees Celsius) (PubMed:17977854). {ECO:0000269|PubMed:17977854, ECO:0000269|PubMed:21676877};

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8.5 (at 37 degrees Celsius). {ECO:0000269|PubMed:17977854};

FUNCTION: Catalyzes the conversion of D-serine, an allosteric activator of the N-methyl-D-aspartate (NMDA) receptor for L-glutamate, to pyruvate and ammonia. {ECO:0000269|PubMed:17977854, ECO:0000269|PubMed:21676877}.

Gallus gallus (Chicken)

A0AAR7

CCAMK_LOTJA

MGYDQTRKLSDEYEISEILGRGGFSVVRKGTKKSGNEKTQVAIKTLRRLGSSPSGTGGGQKSTATVMGFPSLRQVSVSDALLTNEILVMRRIVENVSPHPNVIDLYDVCEDSNGVHLVLELCSGGELFDRIVAQDKYAETEAAAVVRQIAAGLEAVHKADIVHRDLKPENCLFLDSRKDSPLKIMDFGLSSVEEFTDPVVGLFGSIDYVSPEALSQGKITAKSDMWSLGVILYILLSGYPPFIAQNNRQKQQMIINGNFSFYEKTWKGITQSAKQLISSLLTVDPSKRPSAQELLSHPWVRGDKAKDEQMDPEIVSRLQSFNARRKLRAAAIASVWSSTIFLRTKKLRSLVGTYDLKEEEIESLRIHFKKICGNGDNATLSEFVEVLKAMKMPSLIPLAPRIFDLFDNNRDGTIDMREILCGFSSLKNSKGDDALRLCFQMYDTDRSGCITKEEVASMLCALPEECLPADITEPGKLDEIFDLMDANSDGKVTFEEFKAAMQRDSSLQDMLLSSLRPS

2.7.11.17

intracellular signal transduction [GO:0035556]; nodulation [GO:0009877]; protein autophosphorylation [GO:0046777]; response to symbiont [GO:0009608]

cytoplasm [GO:0005737]; nucleus [GO:0005634]

ATP binding [GO:0005524]; calcium ion binding [GO:0005509]; calcium-dependent protein serine/threonine kinase activity [GO:0009931]; calmodulin binding [GO:0005516]; calmodulin-dependent protein kinase activity [GO:0004683]; protein serine kinase activity [GO:0106310]

PF13202;PF13499;PF00069;

1.10.238.10;1.10.510.10;

Protein kinase superfamily, CAMK Ser/Thr protein kinase family, CaMK subfamily

PTM: Autophosphorylation stimulated by calcium. Occurs probably by an intermolecular mechanism. {ECO:0000269|PubMed:16810257}.

SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19074278, ECO:0000269|PubMed:21209278}.

CATALYTIC ACTIVITY: Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.17; Evidence={ECO:0000269|PubMed:25868982}; CATALYTIC ACTIVITY: Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.17; Evidence={ECO:0000269|PubMed:16810257};

FUNCTION: Calcium- and calmodulin-dependent protein kinase necessary and sufficient for dedifferentiation of root cortical cells into nodule initials. Not required for calcium spiking (PubMed:16810257). Acts as central regulator of the nodule organogenesis program. Required for root hair curling and infection thread (IT) formation upon rhizobial infection, and arbuscule formation during arbuscular mycorrhiza (AM) fungal infection. Phosphorylates the downstream target IPD3, a protein required for root infection by symbiotic rhizobia and AM fungi (PubMed:19074278). Phosphorylates the downstream target CIP73, a protein required for root nodule organogenesis (PubMed:21209278). Mediates the phosphorylation of leghemoglobins (e.g. LB1) to modulate their oxygen O(2) affinity, thus regulating the diffusion of oxygen to the bacteroids in nodules (PubMed:25868982). {ECO:0000269|PubMed:16810257, ECO:0000269|PubMed:19074278, ECO:0000269|PubMed:21209278, ECO:0000269|PubMed:25868982}.

Lotus japonicus (Lotus corniculatus var. japonicus)

A0AUJ5

POLG_BVY3

MPTRYRGADRYGNLGYDKVLQSKADAAKRRGLLFDHGSETYECPRCGEIWRNLDDYMAEGGKMHPKKCLPEECDSDEEQISSCNAALIHEKWGDLDSDTSSKLSEFYKEPSILTYTTRTHCVVEKMRSMTAPQCIEDIVGVRLHGRTAWFFSKDPTLQYGHHPIYYDTHPWNDELDKYLGGAKYNTALVQVYDGTRDLPYHKDDEPCYDITNNPIRTVNVTGTGDLCISKDKRRLYETIPMTSGTVITFPATMQENFYHAVRNPSAGRISITFRNQIRTVERQVAHSANKRWVPIVEARVTTNESRRGDNKQFQEAQSKLQTKTTINFGEFAAEVDGYYPTLSQDHKPALPKIIPELGLPTVDFIYVGNMRVPIDFKKNNVPAIVDTARHVAKIIDSQALTSEPIKVFTEQREVVGNVVTCTGTGFSVADAKEAKALLNGLMYNRASNLFICPSCSDAAVLPEALLTLEHKRSCELASMKKISLARNMQVHVKQEAVARLISQQNSISVPIATLSSCVRGSADTTQVSLHIDEEDSIVDAIHLPNDFITCDHEHAFETDSASDNDVETMKKSEKRRKRRKRNPPPVRQVITRAPVSNIICDVILTCLETQIPVEFIGKSCITFKPVRVGPVHTVGIQLKHQLHKTGFEVDDLPDRETTSDIILAATRALRRLRHAHSNAQQVHNSDITFGTSGAILPWSWLAHDVIVEGPVQDSLVVRGRNVVSGHVTNALNLQQDCLADDYLQYSEELQPLHDDLSELKPLNVINNELIRQNMHITTLYSNMSKLQNDALATKAEMKLPLFGVAQLVVNQLKYNTTTHEWGERGDYVRKFVGKFFADFPTTQVPKQYMTRTTNGHIRITAYKALSLTSDPEIMMSRRMTQPMLTTAKQADCVFQSTTGATCTSASCTTNSSGVVLSNKCADPAPNTLRVRTMWDDIIIELPLQGGRVHVPLEGLCFSTIFLHMYLLVPDESVKLFHRTVTERAMPSLGQWPTLRHLATWVLNLVAMFPVLSTTPMPEILVHHESQSVHIPDCLGTATSGYHRLNIVTPYDFIIFATEIGRNGCQEYRVGGFAHDIKYTVSLMQDKRKLLHELMLTPTWAFYALSSPTLLKILYRSGALKRTYEHAVMANHNAVDLVHELNFLPERVSRAQTLQDEITAWEANVGRVLQQVDGYLTRNHDPPLQRWYADASARLQHLKIDVDLLKNGFRSSQREHVEKKEQLLCDSFERLYNEQNSSLESLKTRCGMGSARALIKPSGKCESPEPAKQLSCKDLICSTKDKYALMLYTQADALKRKIVAGSQSAFTTVCAGVAYRATKVMLRTPFNLLNALNTYSLLIAAVNVMVLVQNYRRDQRKRAQYVNNLETQSMIRHYFAHLEQYIVNYVPRDEQFEVIKAKFDEEFPEYNVMFKEVYKERIQFQSADEGKNMCKIFASAILVMMVFDAHRADLMYKSFSQVRALFNTLYDSGNPFNIIFQAERTIAPTMDVIIQEPKPAIPSTSSCTFETWFRNCVNANNVIPVIPECDLLDFTRDTASSVVATLTSSVKREFVIRGFVGSGKSTYLPHLLTKHGKVLLCEPVRVLASNVFEALSGSPFYQSPTLLMRGTTKFGSGKITVATSGYAANYYNANRHRLNEFAYIIFDESHQHTAHNFLLRSILDVIGYEGTVLHVSATPIGKEIPFRTMHPVEVVNMSTLSFEDFAIGQRKQVRCDVFNKGANILVYVASYNDVDRMSTLLLERGLRVKKIDARTVANVNNITCDGSDGEPLYLVATNIVENGVTLNVDVVVDFGLCVKPVINALQRRVDYVKTPITWGQRIQRNGRVGRYKNGFCLNVGDVYKTPPIISEDVALESALMCFAANVPPIFDNVDPALFGQVTRPQVQTAQMFELPIYITTPMISDAGALQSDIYQVIKKFVLREGSIQLTQDATYLSNMSNWKTIADYFPDISDTHAMRHEKVPFFVKDFGENSYIALAEAIRKARNKSLGARGKLYGDVDATALLLQTDPGSLDRSIMIVETELVAQRSKLEDLNHHVHESTGMFQRYVSHLNHCLRGRYQTDQIQKNIEVLSNMRSTLVGYRQVVDKVEPEEIPHFVQQNPNITMIIDFQSDRTKADGFVKHGINGIYNYTKIASDTFSLLLIACVVIYYVVQYFFREMKSHITFEASGSRRNRLHLRDNKLIKGGYTWAGPSDDMEREFGPEYALKRDKFSEKKARKHMRERIQPRTNMGVKLAPFQVFYGFDVADYDVLQLFDPITGVKIDMDPRATAKEITEEVEDTPFNKEVWSDTHMPEKIQATFVKKGGVNREDVLKQVRVDMTTHNPTMVTGSGGIMGYPEHKGDFRQTGPPKFSIVPEGRSTIKSGNNIAPFISAMGTIKNVYMNGDFDTLACTQIGNKLVVNAHIFMEPVKKQELILQHGVYELPNNGTINIKHVPGIDMVIQTLPMDVPLARQIKAYRGPIPGELIRLLKIERNTKTNSTSLSDPGTARVGPGTIWYHNITTKHGDCGSLVLSEKDNKIVGIHTGQQDGTNLNLFAPITKDAIVAIETVLPGELNDWVFTPDMLDVGSNNAIRKQASDPFPVVKKLLEGITFQNNRTTTTDSVSNTAILPARKYWVASDLPVNIKYQCDMPTFFNTRHTYEGESQPFMAYLRECGDAETFFRPLLSHYIPSNLNGDAFKKDFFKYGKPVPVGLVHGPSFKIASDRVIKRFERVGYERHSIPFEFDAEAIRDDLNKHAAMGAQYVGKKEQHLDGISEEQFCDEFVASCCRLANNCDGVWKGSLKAELRSKEKVQENKTRVFTSAPYDVLLGGKACVMHFNKKFYANNTKGPWTVGINKLGLGWHRLLKSLPEGFVYGTGDGSQFDSSLTPLLINEVCRIRMYFMQDDELGQAMLRGLYRQIIWTLISMPDGSVVRKAKGNPSGQPSTVDDNTIMVMLAVEYVFAYLGITQEEMDTIFKYYANGDDLIFAIHPDRESILNEFTHLFAHLGLNYIFEDRTRNRAELEYMSLTGIEREGFYIPKLSRERISSIVQWRRKGDTRAMFDALNAAILESWGYDDLTYWLRKYYEWLIINRYDIDLPEGEKLPYHTETAVETLYTCDDNTTVYDGRYDFEVPTDASGGVFIIDFQSSSGTDTPPVIPPATSEPALQPVLTRQTSRPPTPPNTILTGQQQQQLMPKSSQPYQLEPLLAPTGVQQPTFGTFGMPQAQQTTTEPVVAAARVRGKQKEGDTSLSQVRDHRRLSPERIVRHDDDLAPPNESTSGESSHYDELTLPDVPRDKRKGLGARLKGKPIITQTQIYNYRPAFGSIHNNKATDIELEAWKKQIADYFQVDDVSTLILGFMAYVIENGTSPEIFTNQKFVMATSSGEQREYPLAPFRSRSVELRKIMRRFSEEAIDYIQIQREHNPQYVPRQAVVRNVKRAIYFPYCFDFIDETILTPDALEIVHQMKAAALESASSKVLGLDGGSARAIDTERHTTEDATARTHNLRGAAMMA

2.7.7.48; 3.4.-.-; 3.4.22.44; 3.4.22.45; 3.6.4.-

COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000255|PROSITE-ProRule:PRU00805}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000255|PROSITE-ProRule:PRU00805};

DNA-templated transcription [GO:0006351]; proteolysis [GO:0006508]; viral RNA genome replication [GO:0039694]; virus-mediated perturbation of host defense response [GO:0019049]

helical viral capsid [GO:0019029]; host cell cytoplasmic vesicle [GO:0044161]

ATP binding [GO:0005524]; cysteine-type endopeptidase activity [GO:0004197]; dioxygenase activity [GO:0051213]; helicase activity [GO:0004386]; hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides [GO:0016818]; metal ion binding [GO:0046872]; RNA binding [GO:0003723]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type peptidase activity [GO:0008236]; structural molecule activity [GO:0005198]

PF00270;PF00271;PF00863;PF00851;PF01577;PF00767;PF08440;PF13608;PF00680;

3.30.70.270;2.60.120.590;3.90.70.150;3.40.50.300;2.40.10.10;

Potyviridae genome polyprotein family

PTM: [Viral genome-linked protein]: VPg is uridylylated by the polymerase and is covalently attached to the 5'-end of the genomic RNA. This uridylylated form acts as a nucleotide-peptide primer for the polymerase (By similarity). {ECO:0000250|UniProtKB:P09814}.; PTM: [Genome polyprotein]: Genome polyprotein of potyviruses undergoes post-translational proteolytic processing by the main proteinase NIa-pro resulting in the production of at least ten individual proteins. The P1 proteinase and the HC-pro cleave only their respective C-termini autocatalytically. 6K1 is essential for proper proteolytic separation of P3 from CI (By similarity). {ECO:0000250}.

SUBCELLULAR LOCATION: [6 kDa protein 1]: Host cytoplasmic vesicle. Note=Probably colocalizes with 6K2-induced vesicles associated with host chloroplasts. {ECO:0000250|UniProtKB:P13529}.; SUBCELLULAR LOCATION: [6 kDa protein 2]: Host cytoplasmic vesicle {ECO:0000250|UniProtKB:P09814}. Note=6K-induced vesicles associate with host chloroplasts. {ECO:0000250|UniProtKB:P09814}.; SUBCELLULAR LOCATION: [Capsid protein]: Virion {ECO:0000305}.

CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: Reaction=Hydrolyzes glutaminyl bonds, and activity is further restricted by preferences for the amino acids in P6 - P1' that vary with the species of potyvirus, e.g. Glu-Xaa-Xaa-Tyr-Xaa-Gln-|-(Ser or Gly) for the enzyme from tobacco etch virus. The natural substrate is the viral polyprotein, but other proteins and oligopeptides containing the appropriate consensus sequence are also cleaved.; EC=3.4.22.44; Evidence={ECO:0000250|UniProtKB:P04517}; CATALYTIC ACTIVITY: Reaction=Hydrolyzes a Gly-|-Gly bond at its own C-terminus, commonly in the sequence -Tyr-Xaa-Val-Gly-|-Gly, in the processing of the potyviral polyprotein.; EC=3.4.22.45; Evidence={ECO:0000250|UniProtKB:P04517};

FUNCTION: [Helper component proteinase]: Required for aphid transmission and also has proteolytic activity. Only cleaves a Gly-Gly dipeptide at its own C-terminus. Interacts with virions and aphid stylets. Acts as a suppressor of RNA-mediated gene silencing, also known as post-transcriptional gene silencing (PTGS), a mechanism of plant viral defense that limits the accumulation of viral RNAs. May have RNA-binding activity. {ECO:0000250|UniProtKB:P04517}.; FUNCTION: [Cytoplasmic inclusion protein]: Has helicase activity. It may be involved in replication.; FUNCTION: [6 kDa protein 1]: Indispensable for virus replication. {ECO:0000250|UniProtKB:P13529}.; FUNCTION: [6 kDa protein 2]: Indispensable for virus replication. {ECO:0000250|UniProtKB:P09814}.; FUNCTION: [Viral genome-linked protein]: Mediates the cap-independent, EIF4E-dependent translation of viral genomic RNAs (By similarity). Binds to the cap-binding site of host EIF4E and thus interferes with the host EIF4E-dependent mRNA export and translation (By similarity). VPg-RNA directly binds EIF4E and is a template for transcription (By similarity). Also forms trimeric complexes with EIF4E-EIF4G, which are templates for translation (By similarity). {ECO:0000250|UniProtKB:P18247}.; FUNCTION: [Nuclear inclusion protein A]: Has RNA-binding and proteolytic activities. {ECO:0000250|UniProtKB:P04517}.; FUNCTION: [Nuclear inclusion protein B]: An RNA-dependent RNA polymerase that plays an essential role in the virus replication.; FUNCTION: [Capsid protein]: Involved in aphid transmission, cell-to-cell and systemis movement, encapsidation of the viral RNA and in the regulation of viral RNA amplification. {ECO:0000250|UniProtKB:P04517}.

Blackberry virus Y (isolate Blackberry plant/USA:Arkansas/C3ARK/2005) (BVY)

A0AV02

S12A8_HUMAN

MTQMSQVQELFHEAAQQDALAQPQPWWKTQLFMWEPVLFGTWDGVFTSCMINIFGVVLFLRTGWLVGNTGVLLGMFLVSFVILVALVTVLSGIGVGERSSIGSGGVYSMISSVLGGQTGGTIGLLYVFGQCVAGAMYITGFAESISDLLGLGNIWAVRGISVAVLLALLGINLAGVKWIIRLQLLLLFLLAVSTLDFVVGSFTHLDPEHGFIGYSPELLQNNTLPDYSPGESFFTVFGVFFPAATGVMAGFNMGGDLREPAASIPLGSLAAVGISWFLYIIFVFLLGAICTREALRYDFLIAEKVSLMGFLFLLGLYISSLASCMGGLYGAPRILQCIAQEKVIPALACLGQGKGPNKTPVAAICLTSLVTMAFVFVGQVNVLAPIVTINFMLTYVAVDYSYFSLSMCSCSLTPVPEPVLREGAEGLHCSEHLLLEKAPSYGSEGPAQRVLEGTLLEFTKDMDQLLQLTRKLESSQPRQGEGNRTPESQKRKSKKATKQTLQDSFLLDLKSPPSFPVEISDRLPAASWEGQESCWNKQTSKSEGTQPEGTYGEQLVPELCNQSESSGEDFFLKSRLQEQDVWRRSTSFYTHMCNPWVSLLGAVGSLLIMFVIQWVYTLVNMGVAAIVYFYIGRASPGLHLGSASNFSFFRWMRSLLLPSCRSLRSPQEQIILAPSLAKVDMEMTQLTQENADFATRDRYHHSSLVNREQLMPHY

cell volume homeostasis [GO:0006884]; chloride ion homeostasis [GO:0055064]; chloride transmembrane transport [GO:1902476]; potassium ion homeostasis [GO:0055075]; potassium ion import across plasma membrane [GO:1990573]

membrane [GO:0016020]

potassium:chloride symporter activity [GO:0015379]

PF00324;

1.20.1740.10;

SLC12A transporter family

SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.

FUNCTION: Cation/chloride cotransporter that may play a role in the control of keratinocyte proliferation. {ECO:0000269|PubMed:11863360}.

Homo sapiens (Human)

A0AV96

RBM47_HUMAN

MTAEDSTAAMSSDSAAGSSAKVPEGVAGAPNEAALLALMERTGYSMVQENGQRKYGGPPPGWEGPHPQRGCEVFVGKIPRDVYEDELVPVFEAVGRIYELRLMMDFDGKNRGYAFVMYCHKHEAKRAVRELNNYEIRPGRLLGVCCSVDNCRLFIGGIPKMKKREEILEEIAKVTEGVLDVIVYASAADKMKNRGFAFVEYESHRAAAMARRKLMPGRIQLWGHQIAVDWAEPEIDVDEDVMETVKILYVRNLMIETTEDTIKKSFGQFNPGCVERVKKIRDYAFVHFTSREDAVHAMNNLNGTELEGSCLEVTLAKPVDKEQYSRYQKAARGGGAAEAAQQPSYVYSCDPYTLAYYGYPYNALIGPNRDYFVKAGSIRGRGRGAAGNRAPGPRGSYLGGYSAGRGIYSRYHEGKGKQQEKGYELVPNLEIPTVNPVAIKPGTVAIPAIGAQYSMFPAAPAPKMIEDGKIHTVEHMISPIAVQPDPASAAAAAAAAAAAAAAVIPTVSTPPPFQGRPITPVYTVAPNVQRIPTAGIYGASYVPFAAPATATIATLQKNAAAAAAMYGGYAGYIPQAFPAAAIQVPIPDVYQTY

3'-UTR-mediated mRNA stabilization [GO:0070935]; cytidine to uridine editing [GO:0016554]; hematopoietic progenitor cell differentiation [GO:0002244]; mRNA processing [GO:0006397]; positive regulation of interleukin-10 production [GO:0032733]; positive regulation of type I interferon-mediated signaling pathway [GO:0060340]; regulation of alternative mRNA splicing, via spliceosome [GO:0000381]; RNA splicing [GO:0008380]

apolipoprotein B mRNA editing enzyme complex [GO:0030895]; cytoplasm [GO:0005737]; nucleus [GO:0005634]

enzyme binding [GO:0019899]; enzyme-substrate adaptor activity [GO:0140767]; mRNA 3'-UTR binding [GO:0003730]; mRNA binding [GO:0003729]; RNA binding [GO:0003723]

PF00076;

3.30.70.330;

RRM RBM47 family

SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24038582, ECO:0000269|PubMed:24916387}. Cytoplasm {ECO:0000269|PubMed:24916387}.

FUNCTION: Single-stranded RNA-binding protein that functions in a variety of RNA processes, including alternative splicing, RNA stabilization, and RNA editing (PubMed:24038582, PubMed:24916387, PubMed:27050523, PubMed:30844405, PubMed:31358901, PubMed:34160127). Functions as an enzyme-substrate adapter for the cytidine deaminase APOBEC1. With APOBEC1 forms an mRNA editing complex involved into cytidine to uridine editing of a variety of mRNA molecules (PubMed:24038582, PubMed:24916387, PubMed:30844405). Through the binding of their 3'UTR, also stabilizes a variety of mRNAs and regulates the expression of genes such as the interferon alpha/beta receptor and interleukin-10 (PubMed:34160127). Also involved in the alternative splicing of several genes including TJP1. Binds the pre-mRNA (U)GCAUG consensus sequences in downstream intronic regions of alternative exons, regulating their exclusion and inclusion into mRNAs (PubMed:27050523, PubMed:31358901). Independently of its RNA-binding activity, could negatively regulate MAVS by promoting its lysosomal degradation (By similarity). {ECO:0000250|UniProtKB:A0A8M1NHK4, ECO:0000269|PubMed:24038582, ECO:0000269|PubMed:24916387, ECO:0000269|PubMed:27050523, ECO:0000269|PubMed:30844405, ECO:0000269|PubMed:31358901, ECO:0000269|PubMed:34160127}.

Homo sapiens (Human)

A0AVF1

IFT56_HUMAN

MMLSRAKPAVGRGVQHTDKRKKKGRKIPKLEELLSKRDFTGAITLLEFKRHVGEEEEDTNLWIGYCAFHLGDYKRALEEYENATKEENCNSEVWVNLACTYFFLGMYKQAEAAGFKASKSRLQNRLLFHLAHKFNDEKKLMSFHQNLQDVTEDQLSLASIHYMRSHYQEAIDIYKRILLDNREYLALNVYVALCYYKLDYYDVSQEVLAVYLQQIPDSTIALNLKACNHFRLYNGRAAEAELKSLMDNASSSFEFAKELIRHNLVVFRGGEGALQVLPPLVDVIPEARLNLVIYYLRQDDVQEAYNLIKDLEPTTPQEYILKGVVNAALGQEMGSRDHMKIAQQFFQLVGGSASECDTIPGRQCMASCFFLLKQFDDVLIYLNSFKSYFYNDDIFNFNYAQAKAATGNTSEGEEAFLLIQSEKMKNDYIYLSWLARCYIMNKKPRLAWELYLKMETSGESFSLLQLIANDCYKMGQFYYSAKAFDVLERLDPNPEYWEGKRGACVGIFQMIIAGREPKETLREVLHLLRSTGNTQVEYMIRIMKKWAKENRVSI

axoneme assembly [GO:0035082]; cilium assembly [GO:0060271]; intraciliary anterograde transport [GO:0035720]; intraciliary transport [GO:0042073]; intraciliary transport involved in cilium assembly [GO:0035735]; manchette assembly [GO:1905198]; protein localization to cilium [GO:0061512]; protein transport [GO:0015031]; smoothened signaling pathway [GO:0007224]

centrosome [GO:0005813]; ciliary basal body [GO:0036064]; ciliary base [GO:0097546]; ciliary tip [GO:0097542]; cilium [GO:0005929]; intraciliary transport particle B [GO:0030992]; neuron projection [GO:0043005]

intraciliary transport particle B binding [GO:0120170]

PF12895;

1.25.40.10;

IFT56 family

SUBCELLULAR LOCATION: Cell projection, cilium {ECO:0000250|UniProtKB:Q8BS45}. Note=Localizes at the base to the ciliary transition zone. {ECO:0000250|UniProtKB:Q8BS45}.

FUNCTION: Component of the intraflagellar transport (IFT) complex B required for transport of proteins in the motile cilium. Required for transport of specific ciliary cargo proteins related to motility, while it is neither required for IFT complex B assembly or motion nor for cilium assembly. Required for efficient coupling between the accumulation of GLI2 and GLI3 at the ciliary tips and their dissociation from the negative regulator SUFU. Plays a key role in maintaining the integrity of the IFT complex B and the proper ciliary localization of the IFT complex B components. Not required for IFT complex A ciliary localization or function. Essential for maintaining proper microtubule organization within the ciliary axoneme. {ECO:0000269|PubMed:31595528}.

Homo sapiens (Human)

A0AVI4

TM129_HUMAN

MDSPEVTFTLAYLVFAVCFVFTPNEFHAAGLTVQNLLSGWLGSEDAAFVPFHLRRTAATLLCHSLLPLGYYVGMCLAASEKRLHALSQAPEAWRLFLLLAVTLPSIACILIYYWSRDRWACHPLARTLALYALPQSGWQAVASSVNTEFRRIDKFATGAPGARVIVTDTWVMKVTTYRVHVAQQQDVHLTVTESRQHELSPDSNLPVQLLTIRVASTNPAVQAFDIWLNSTEYGELCEKLRAPIRRAAHVVIHQSLGDLFLETFASLVEVNPAYSVPSSQELEACIGCMQTRASVKLVKTCQEAATGECQQCYCRPMWCLTCMGKWFASRQDPLRPDTWLASRVPCPTCRARFCILDVCTVR

2.3.2.27

ERAD pathway [GO:0036503]; protein polyubiquitination [GO:0000209]; protein ubiquitination [GO:0016567]; response to unfolded protein [GO:0006986]; retrograde protein transport, ER to cytosol [GO:0030970]; ubiquitin-dependent protein catabolic process [GO:0006511]

endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]

metal ion binding [GO:0046872]; ubiquitin protein ligase activity [GO:0061630]

PF10272;

TMEM129 family

SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:24807418}; Multi-pass membrane protein {ECO:0000269|PubMed:24807418}.

CATALYTIC ACTIVITY: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;

PATHWAY: Protein modification; protein ubiquitination.

FUNCTION: E3 ubiquitin-protein ligase involved in ER-associated protein degradation, preferentially associates with the E2 enzyme UBE2J2. Exploited by viral US11 proteins to mediate HLA class I proteins degradation. {ECO:0000269|PubMed:24807418}.

Homo sapiens (Human)

A0AVK6

E2F8_HUMAN

MENEKENLFCEPHKRGLMKTPLKESTTANIVLAEIQPDFGPLTTPTKPKEGSQGEPWTPTANLKMLISAVSPEIRNRDQKRGLFDNRSGLPEAKDCIHEHLSGDEFEKSQPSRKEKSLGLLCHKFLARYPNYPNPAVNNDICLDEVAEELNVERRRIYDIVNVLESLHMVSRLAKNRYTWHGRHNLNKTLGTLKSIGEENKYAEQIMMIKKKEYEQEFDFIKSYSIEDHIIKSNTGPNGHPDMCFVELPGVEFRAASVNSRKDKSLRVMSQKFVMLFLVSTPQIVSLEVAAKILIGEDHVEDLDKSKFKTKIRRLYDIANVLSSLDLIKKVHVTEERGRKPAFKWTGPEISPNTSGSSPVIHFTPSDLEVRRSSKENCAKNLFSTRGKPNFTRHPSLIKLVKSIESDRRKINSAPSSPIKTNKAESSQNSAPFPSKMAQLAAICKMQLEEQSSESRQKVKVQLARSGPCKPVAPLDPPVNAEMELTAPSLIQPLGMVPLIPSPLSSAVPLILPQAPSGPSYAIYLQPTQAHQSVTPPQGLSPTVCTTHSSKATGSKDSTDATTEKAANDTSKASASTRPGSLLPAPERQGAKSRTREPAGERGSKRASMLEDSGSKKKFKEDLKGLENVSATLFPSGYLIPLTQCSSLGAESILSGKENSSALSPNHRIYSSPIAGVIPVTSSELTAVNFPSFHVTPLKLMVSPTSVAAVPVGNSPALASSHPVPIQNPSSAIVNFTLQHLGLISPNVQLSASPGSGIVPVSPRIESVNVAPENAGTQQGRATNYDSPVPGQSQPNGQSVAVTGAQQPVPVTPKGSQLVAESFFRTPGGPTKPTSSSCMDFEGANKTSLGTLFVPQRKLEVSTEDVH

cell cycle comprising mitosis without cytokinesis [GO:0033301]; chorionic trophoblast cell differentiation [GO:0060718]; fibroblast proliferation [GO:0048144]; hepatocyte differentiation [GO:0070365]; negative regulation of cytokinesis [GO:0032466]; negative regulation of transcription by RNA polymerase II [GO:0000122]; placenta development [GO:0001890]; positive regulation of DNA endoreduplication [GO:0032877]; positive regulation of transcription by RNA polymerase II [GO:0045944]; regulation of transcription by RNA polymerase II [GO:0006357]; sprouting angiogenesis [GO:0002040]; trophoblast giant cell differentiation [GO:0060707]

chromatin [GO:0000785]; cytosol [GO:0005829]; nucleolus [GO:0005730]; nucleoplasm [GO:0005654]; RNA polymerase II transcription regulator complex [GO:0090575]

cis-regulatory region sequence-specific DNA binding [GO:0000987]; DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; DNA-binding transcription repressor activity [GO:0001217]; DNA-binding transcription repressor activity, RNA polymerase II-specific [GO:0001227]; identical protein binding [GO:0042802]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific double-stranded DNA binding [GO:1990837]

PF02319;

1.10.10.10;

E2F/DP family

SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15897886}.

FUNCTION: Atypical E2F transcription factor that participates in various processes such as angiogenesis and polyploidization of specialized cells. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1: component of a feedback loop in S phase by repressing the expression of E2F1, thereby preventing p53/TP53-dependent apoptosis. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene. {ECO:0000269|PubMed:15897886, ECO:0000269|PubMed:16179649, ECO:0000269|PubMed:18202719, ECO:0000269|PubMed:22903062}.

Homo sapiens (Human)

A0AVT1

UBA6_HUMAN

MEGSEPVAAHQGEEASCSSWGTGSTNKNLPIMSTASVEIDDALYSRQRYVLGDTAMQKMAKSHVFLSGMGGLGLEIAKNLVLAGIKAVTIHDTEKCQAWDLGTNFFLSEDDVVNKRNRAEAVLKHIAELNPYVHVTSSSVPFNETTDLSFLDKYQCVVLTEMKLPLQKKINDFCRSQCPPIKFISADVHGIWSRLFCDFGDEFEVLDTTGEEPKEIFISNITQANPGIVTCLENHPHKLETGQFLTFREINGMTGLNGSIQQITVISPFSFSIGDTTELEPYLHGGIAVQVKTPKTVFFESLERQLKHPKCLIVDFSNPEAPLEIHTAMLALDQFQEKYSRKPNVGCQQDSEELLKLATSISETLEEKPDVNADIVHWLSWTAQGFLSPLAAAVGGVASQEVLKAVTGKFSPLCQWLYLEAADIVESLGKPECEEFLPRGDRYDALRACIGDTLCQKLQNLNIFLVGCGAIGCEMLKNFALLGVGTSKEKGMITVTDPDLIEKSNLNRQFLFRPHHIQKPKSYTAADATLKINSQIKIDAHLNKVCPTTETIYNDEFYTKQDVIITALDNVEARRYVDSRCLANLRPLLDSGTMGTKGHTEVIVPHLTESYNSHRDPPEEEIPFCTLKSFPAAIEHTIQWARDKFESSFSHKPSLFNKFWQTYSSAEEVLQKIQSGHSLEGCFQVIKLLSRRPRNWSQCVELARLKFEKYFNHKALQLLHCFPLDIRLKDGSLFWQSPKRPPSPIKFDLNEPLHLSFLQNAAKLYATVYCIPFAEEDLSADALLNILSEVKIQEFKPSNKVVQTDETARKPDHVPISSEDERNAIFQLEKAILSNEATKSDLQMAVLSFEKDDDHNGHIDFITAASNLRAKMYSIEPADRFKTKRIAGKIIPAIATTTATVSGLVALEMIKVTGGYPFEAYKNCFLNLAIPIVVFTETTEVRKTKIRNGISFTIWDRWTVHGKEDFTLLDFINAVKEKYGIEPTMVVQGVKMLYVPVMPGHAKRLKLTMHKLVKPTTEKKYVDLTVSFAPDIDGDEDLPGPPVRYYFSHDTD

6.2.1.45

amygdala development [GO:0021764]; dendritic spine development [GO:0060996]; DNA damage response [GO:0006974]; hippocampus development [GO:0021766]; learning [GO:0007612]; locomotory behavior [GO:0007626]; protein ubiquitination [GO:0016567]; ubiquitin-dependent protein catabolic process [GO:0006511]

cytoplasm [GO:0005737]; cytosol [GO:0005829]; nucleus [GO:0005634]

ATP binding [GO:0005524]; FAT10 activating enzyme activity [GO:0019780]; nucleotidyltransferase activity [GO:0016779]; thiosulfate sulfurtransferase activity [GO:0004792]; ubiquitin activating enzyme activity [GO:0004839]

PF16191;PF16190;PF09358;PF00899;PF10585;

3.40.50.720;2.40.30.180;3.50.50.80;3.40.50.12550;1.10.10.2660;3.10.290.60;

Ubiquitin-activating E1 family

CATALYTIC ACTIVITY: Reaction=ATP + ubiquitin + [E1 ubiquitin-activating enzyme]-L-cysteine = AMP + diphosphate + S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine.; EC=6.2.1.45; Evidence={ECO:0000250|UniProtKB:P22314};

PATHWAY: Protein modification; protein ubiquitination. {ECO:0000250|UniProtKB:P22314}.

FUNCTION: Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP. Specific for ubiquitin, does not activate ubiquitin-like peptides. Differs from UBE1 in its specificity for substrate E2 charging. Does not charge cell cycle E2s, such as CDC34. Essential for embryonic development. Required for UBD/FAT10 conjugation. Isoform 2 may play a key role in ubiquitin system and may influence spermatogenesis and male fertility. {ECO:0000269|PubMed:15202508, ECO:0000269|PubMed:17597759, ECO:0000269|PubMed:17889673}.

Homo sapiens (Human)

A0AVX7

CHP3_CHICK

MGSAQSVPPEMRALAERTGFTSEQIEQLHRRFKQLNHNRKTIRKEDFDTIPDLEFNPIRARIVHAFFDKRNLRKAPAGLAEEINFEDFLTIMSYFRPIEMDMDEERLESFRKEKLKFLFHMYDADYDGIITLQEYKNVLDELMSGNPHLEKESLRAIAEGAMLEAASACMARTGPDEVYEGITFEDFLKVWKGIDIETKMHVRFLTMEAIAHCY

cell differentiation [GO:0030154]; cellular response to retinoic acid [GO:0071300]; positive regulation of granulocyte differentiation [GO:0030854]; positive regulation of sodium:proton antiporter activity [GO:0032417]; protein localization to plasma membrane [GO:0072659]; protein maturation [GO:0051604]; protein stabilization [GO:0050821]; regulation of cell adhesion mediated by integrin [GO:0033628]

cytoplasm [GO:0005737]; lamellipodium [GO:0030027]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; ruffle [GO:0001726]; ruffle membrane [GO:0032587]

calcium ion binding [GO:0005509]; magnesium ion binding [GO:0000287]; phosphatase inhibitor activity [GO:0019212]; protein homodimerization activity [GO:0042803]; protein kinase inhibitor activity [GO:0004860]

1.10.238.10;

Calcineurin regulatory subunit family, CHP subfamily

SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:19345287}. Cytoplasm {ECO:0000269|PubMed:19345287}. Membrane {ECO:0000250|UniProtKB:Q96BS2}; Lipid-anchor {ECO:0000250|UniProtKB:Q96BS2}. Cell membrane {ECO:0000250|UniProtKB:Q96BS2}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:Q96BS2}. Cell projection, ruffle membrane {ECO:0000250|UniProtKB:Q9JKL5}. Note=Expressed in both the nucleus and cytoplasm of the embryonic testis. {ECO:0000269|PubMed:19345287}.

FUNCTION: Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Promotes the induction of hematopoietic stem cell differentiation toward megakaryocytic lineage. Essential for the coupling of ERK cascade activation with the expression of ETS family genes in megakaryocytic differentiation. Also involved in granulocytic differentiation in a ERK-dependent manner. Inhibits the phosphatase activity of calcineurin (By similarity). {ECO:0000250}.

Gallus gallus (Chicken)

A0FGR8

ESYT2_HUMAN

MTANRDAALSSHRHPGCAQRPRTPTFASSSQRRSAFGFDDGNFPGLGERSHAPGSRLGARRRAKTARGLRGHRQRGAGAGLSRPGSARAPSPPRPGGPENPGGVLSVELPGLLAQLARSFALLLPVYALGYLGLSFSWVLLALALLAWCRRSRGLKALRLCRALALLEDEERVVRLGVRACDLPAWVHFPDTERAEWLNKTVKHMWPFICQFIEKLFRETIEPAVRGANTHLSTFSFTKVDVGQQPLRINGVKVYTENVDKRQIILDLQISFVGNCEIDLEIKRYFCRAGVKSIQIHGTMRVILEPLIGDMPLVGALSIFFLRKPLLEINWTGLTNLLDVPGLNGLSDTIILDIISNYLVLPNRITVPLVSEVQIAQLRFPVPKGVLRIHFIEAQDLQGKDTYLKGLVKGKSDPYGIIRVGNQIFQSRVIKENLSPKWNEVYEALVYEHPGQELEIELFDEDPDKDDFLGSLMIDLIEVEKERLLDEWFTLDEVPKGKLHLRLEWLTLMPNASNLDKVLTDIKADKDQANDGLSSALLILYLDSARNLPSGKKISSNPNPVVQMSVGHKAQESKIRYKTNEPVWEENFTFFIHNPKRQDLEVEVRDEQHQCSLGNLKVPLSQLLTSEDMTVSQRFQLSNSGPNSTIKMKIALRVLHLEKRERPPDHQHSAQVKRPSVSKEGRKTSIKSHMSGSPGPGGSNTAPSTPVIGGSDKPGMEEKAQPPEAGPQGLHDLGRSSSSLLASPGHISVKEPTPSIASDISLPIATQELRQRLRQLENGTTLGQSPLGQIQLTIRHSSQRNKLIVVVHACRNLIAFSEDGSDPYVRMYLLPDKRRSGRRKTHVSKKTLNPVFDQSFDFSVSLPEVQRRTLDVAVKNSGGFLSKDKGLLGKVLVALASEELAKGWTQWYDLTEDGTRPQAMT

endocytosis [GO:0006897]; endoplasmic reticulum-plasma membrane tethering [GO:0061817]; lipid transport [GO:0006869]

cytoplasmic side of plasma membrane [GO:0009898]; cytosol [GO:0005829]; endoplasmic reticulum membrane [GO:0005789]; endoplasmic reticulum-plasma membrane contact site [GO:0140268]; extrinsic component of cytoplasmic side of plasma membrane [GO:0031234]; membrane [GO:0016020]; organelle membrane contact site [GO:0044232]; plasma membrane [GO:0005886]

cadherin binding [GO:0045296]; calcium ion binding [GO:0005509]; calcium-dependent phospholipid binding [GO:0005544]; identical protein binding [GO:0042802]; phosphatidylcholine binding [GO:0031210]; phosphatidylethanolamine binding [GO:0008429]; phosphatidylinositol binding [GO:0035091]

PF00168;PF17047;

2.60.40.150;

Extended synaptotagmin family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:29469807}; Peripheral membrane protein {ECO:0000269|PubMed:17360437}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:29469807}; Multi-pass membrane protein {ECO:0000255}. Note=Localizes to endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:23791178, PubMed:27044890, PubMed:29469807, PubMed:30220461). Recruited to the cell membrane via the third C2 domain (PubMed:17360437). {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:29469807, ECO:0000269|PubMed:30220461}.

FUNCTION: Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex. Promotes the localization of SACM1L at endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:27044890). {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24847877, ECO:0000269|PubMed:27044890}.

Homo sapiens (Human)

A0FGR9

ESYT3_HUMAN

MRAEEPCAPGAPSALGAQRTPGPELRLSSQLLPELCTFVVRVLFYLGPVYLAGYLGLSITWLLLGALLWMWWRRNRRGKLGRLAAAFEFLDNEREFISRELRGQHLPAWIHFPDVERVEWANKIISQTWPYLSMIMESKFREKLEPKIREKSIHLRTFTFTKLYFGQKCPRVNGVKAHTNTCNRRRVTVDLQICYIGDCEISVELQKIQAGVNGIQLQGTLRVILEPLLVDKPFVGAVTVFFLQKPHLQINWTGLTNLLDAPGINDVSDSLLEDLIATHLVLPNRVTVPVKKGLDLTNLRFPLPCGVIRVHLLEAEQLAQKDNFLGLRGKSDPYAKVSIGLQHFRSRTIYRNLNPTWNEVFEFMVYEVPGQDLEVDLYDEDTDRDDFLGSLQICLGDVMTNRVVDEWFVLNDTTSGRLHLRLEWLSLLTDQEVLTEDHGGLSTAILVVFLESACNLPRNPFDYLNGEYRAKKLSRFARNKVSKDPSSYVKLSVGKKTHTSKTCPHNKDPVWSQVFSFFVHNVATERLHLKVLDDDQECALGMLEVPLCQILPYADLTLEQRFQLDHSGLDSLISMRLVLRFLQVEERELGSPYTGPEALKKGPLLIKKVATNQGPKAQPQEEGPTDLPCPPDPASDTKDVSRSTTTTTSATTVATEPTSQETGPEPKGKDSAKRFCEPIGEKKSPATIFLTVPGPHSPGPIKSPRPMKCPASPFAWPPKRLAPSMSSLNSLASSCFDLADISLNIEGGDLRRRQLGEIQLTVRYVCLRRCLSVLINGCRNLTPCTSSGADPYVRVYLLPERKWACRKKTSVKRKTLEPLFDETFEFFVPMEEVKKRSLDVAVKNSRPLGSHRRKELGKVLIDLSKEDLIKGFSQWYELTPNGQPRS

endoplasmic reticulum-plasma membrane tethering [GO:0061817]; lipid transport [GO:0006869]

cytoplasmic side of plasma membrane [GO:0009898]; endoplasmic reticulum membrane [GO:0005789]; endoplasmic reticulum-plasma membrane contact site [GO:0140268]; extrinsic component of cytoplasmic side of plasma membrane [GO:0031234]; organelle membrane contact site [GO:0044232]; plasma membrane [GO:0005886]

calcium ion binding [GO:0005509]; calcium-dependent phospholipid binding [GO:0005544]; phosphatidylcholine binding [GO:0031210]; phosphatidylethanolamine binding [GO:0008429]; phosphatidylinositol binding [GO:0035091]

PF00168;PF17047;

2.60.40.150;

Extended synaptotagmin family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:29469807}; Peripheral membrane protein {ECO:0000269|PubMed:17360437}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:29469807}; Multi-pass membrane protein {ECO:0000255}. Note=Localizes to endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:29469807, PubMed:30220461). Recruited to the cell membrane via the third C2 domain. {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:29469807, ECO:0000269|PubMed:30220461}.

FUNCTION: Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport (By similarity). Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. {ECO:0000250, ECO:0000269|PubMed:23791178}.

Homo sapiens (Human)

A0FI79

INP5E_PANTR

MPSKAENLRPSEPAPQPPEGRTLQGQLPGAPLAQRAGSPPDVPGSESPALACSTPATPSGEDPPARAAPIAPRPPARPRLERALSLDDKGWRRRRFRGSQEDLEARNGTSPSRGSVQSEGPGAPAHSCSPPCLSTSLQEIPKSRGVLSSERGSPSSGGNPLSGVASSSPNLPHRDAAVAGSSPRLPSLLPPRPPPALSLDIASDSLRTANKVDSDLADYKLRAQPLLVRAHSSLGPGRPRSPLACDDCSLRSAKSSFSLLAPIRSKDVRSRSYLEGSLLASGALLGADELARYFPDRNVALFVATWNMQGQKELPPSLDEFLLPAEADYAQDLYVIGVQEGCSDRREWETRLQETLGPHYVLLSSAAHGVLYMSLFIRRDLIWFCSEVECSTVTTRIVSQIKTKGALGISFTFFGTSFLFITSHFTSGDGKVAERLLDYTRTVQALALPRNVPDTNPYRSSAADVTTRFDEVFWFGDFNFRLSGGRTVVDALLCQGLVVDVPALLQHDQLIREMRKGSIFKGFQEPDIHFLPSYKFDIGKDTYDSTSKQRTPSYTDRVLYRSRHKGDICPVSYSSCPGIKTSDHRPVYGLFRVKVRPGRDNIPLAAGKFDRELYLLGIKRRISKEIQRQQALQSQNSSTICSVS

3.1.3.36; 3.1.3.86

phosphatidylinositol dephosphorylation [GO:0046856]

axoneme [GO:0005930]; Golgi apparatus [GO:0005794]; Golgi cisterna membrane [GO:0032580]; nucleus [GO:0005634]; plasma membrane [GO:0005886]; ruffle [GO:0001726]

inositol-polyphosphate 5-phosphatase activity [GO:0004445]; phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase activity [GO:0034485]; phosphatidylinositol-3,5-bisphosphate 5-phosphatase activity [GO:0043813]; phosphatidylinositol-4,5-bisphosphate 5-phosphatase activity [GO:0004439]

3.60.10.10;

Inositol polyphosphate 5-phosphatase family

SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium axoneme {ECO:0000250|UniProtKB:Q9JII1}. Golgi apparatus, Golgi stack membrane {ECO:0000250|UniProtKB:Q9JII1}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9JII1}; Cytoplasmic side {ECO:0000250|UniProtKB:Q9JII1}. Cell membrane {ECO:0000250|UniProtKB:Q9WVR1}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9WVR1}; Cytoplasmic side {ECO:0000250|UniProtKB:Q9WVR1}. Cell projection, ruffle {ECO:0000250|UniProtKB:Q9WVR1}. Cytoplasm {ECO:0000250|UniProtKB:Q9WVR1}. Nucleus {ECO:0000250|UniProtKB:Q9JII1}. Note=Peripheral membrane protein associated with Golgi stacks. {ECO:0000250|UniProtKB:Q9JII1}.

CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + phosphate; Xref=Rhea:RHEA:22764, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:58178, ChEBI:CHEBI:58456; EC=3.1.3.36; Evidence={ECO:0000250|UniProtKB:Q9NRR6}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22765; Evidence={ECO:0000250|UniProtKB:Q9NRR6}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + phosphate; Xref=Rhea:RHEA:25528, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57658, ChEBI:CHEBI:57836; EC=3.1.3.86; Evidence={ECO:0000250|UniProtKB:Q9NRR6}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25529; Evidence={ECO:0000250|UniProtKB:Q9NRR6}; CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + phosphate; Xref=Rhea:RHEA:32955, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57923, ChEBI:CHEBI:58088; Evidence={ECO:0000250|UniProtKB:Q9JII1}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32956; Evidence={ECO:0000250|UniProtKB:Q9JII1};

FUNCTION: Phosphatidylinositol (PtdIns) phosphatase that specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3), phosphatidylinositol 4,5-bisphosphate(PtdIns(4,5)P2) and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Specific for lipid substrates, inactive towards water soluble inositol phosphates (By similarity). Plays an essential role in the primary cilium by controlling ciliary growth and phosphoinositide 3-kinase (PI3K) signaling and stability (By similarity). {ECO:0000250|UniProtKB:Q9JII1, ECO:0000250|UniProtKB:Q9NRR6}.

Pan troglodytes (Chimpanzee)

A0FIN4

IRF1_PIG

MPITRMRMRPWLEMQINSNQIPGLIWINKEEMIFQIPWKHAAKHGWDINKDACLFRSWAIHTGRYKAGEKEPDPKTWKANFRCAMNSLPDIEEVKDQSRNKGSSAVRVYRMLPPLTKNQRKERKSKSSRDAKCKAKKKSCGESSPDTFSDGLSSSTLPDDHSSYTAQGYIGQDLDIEQALTPALSPCAISSTLPEWRIPVEIVPDSTSDLYNFQVSPMPSTSEAATDEDEEGKLTEDIMKLLEQSGWQQTNVDGKGYLLNEPGAQPTAVYGDFSCKEEPEVESPGGYTGLISSDLKNVDTSWLDNLLTPVRLPSIQAIPCAP

apoptotic process [GO:0006915]; CD8-positive, alpha-beta T cell differentiation [GO:0043374]; cellular response to interferon-beta [GO:0035458]; cellular response to mechanical stimulus [GO:0071260]; defense response to virus [GO:0051607]; immune system process [GO:0002376]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of regulatory T cell differentiation [GO:0045590]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of interferon-beta production [GO:0032728]; positive regulation of interleukin-12 production [GO:0032735]; positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of type I interferon production [GO:0032481]; regulation of CD8-positive, alpha-beta T cell proliferation [GO:2000564]; regulation of cell cycle [GO:0051726]; regulation of MyD88-dependent toll-like receptor signaling pathway [GO:0034124]; regulation of transcription by RNA polymerase II [GO:0006357]; transcription by RNA polymerase II [GO:0006366]; type II interferon-mediated signaling pathway [GO:0060333]

chromatin [GO:0000785]; cytoplasm [GO:0005737]; nucleus [GO:0005634]

DNA-binding transcription activator activity, RNA polymerase II-specific [GO:0001228]; DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; transcription cis-regulatory region binding [GO:0000976]

PF00605;

1.10.10.10;

IRF family

PTM: Phosphorylated by CK2 and this positively regulates its activity. {ECO:0000250|UniProtKB:P10914}.; PTM: Sumoylation represses the transcriptional activity and displays enhanced resistance to protein degradation (By similarity). Sumolyated by UBE2I/UBC9 and SUMO1 (By similarity). Inactivates the tumor suppressor activity (By similarity). Elevated levels in tumor cells. Major site is Lys-276 (By similarity). Sumoylation is enhanced by PIAS3 (By similarity). Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites (By similarity). {ECO:0000250|UniProtKB:P10914, ECO:0000250|UniProtKB:P15314}.; PTM: Ubiquitinated in a SPOP-depedent manner. Appears to compete with sumoylation on C-terminal sites (By similarity). {ECO:0000250|UniProtKB:P10914}.

SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P15314}. Cytoplasm {ECO:0000250|UniProtKB:P15314}. Note=MYD88-associated IRF1 migrates into the nucleus more efficiently than non-MYD88-associated IRF1. {ECO:0000250|UniProtKB:P15314}.

FUNCTION: Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses (By similarity). Regulates transcription of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage (By similarity). Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon-stimulated response element (ISRE) in their promoters (By similarity). Binds to a consensus sequence in gene promoters (By similarity). Its target genes for transcriptional activation activity include: genes involved in anti-viral response, such as IFN-alpha/beta, RIGI, TNFSF10/TRAIL, ZBP1, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as GBP2, GBP5 and NOS2/INOS; anti-proliferative response, such as p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M and MHC class II expression, such as CIITA; metabolic enzymes, such as ACOD1/IRG1 (By similarity). Represses genes involved in anti-proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4 (By similarity). Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53 (By similarity). Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells (By similarity). Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development (By similarity). Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells (By similarity). {ECO:0000250|UniProtKB:P10914}.

Sus scrofa (Pig)

A0FKE6

TD1_SOLLC

MEVLRFTAVKSLNSCVRPEFTAMSSVIVPISTVKVSGTRKSKKKALICAKATEILSSPATVTEPLKAEPAEAPVPLLRVSPSSLQCEPGYLLPNSPVLGTGGVTGYEYLTNILSSKVYDVAYETPLQKAPKLSERLGVNVWLKREDLQPVFSFKIRGAYNMMAKLPKEQLEKGVICSSAGNHAQGVALSAQRLGCDAVIVMPVTTPDIKWKSVKRLGATVVLVGDSYDEAQAYAKKRAESEGRTFIPPFDHPDVIVGQGTVGMEINRQLKDNIHAIFVPVGGGGLIAGIAAYLKRVAPDIKIIGVEPLDANALALSLHHGQRVMLDQVGGFADGVAVKVVGEETYRLCEELIDGVVLVGRDAICASIKDMFEEKRSILEPAGALALAGAEAYCKYYGLKGENVVAITSGANMNFDRLRLVTELADVGRQREAVLATFMPEDPGSFKKFAEMVGPMNITEFKYRYNSDKERALVLYSVGLHTILELEGMVERMESADLQTINLTDNDLVKDHLRHLMGGRTNVHNELLCRFTFPEKPGALMKFLDAFSPRWNISLFHYRAQGDTGANVLVGIQVPPDEVVEFEGRADSLGYEYAMESLNEAYQLIMH

4.3.1.19

COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000255|RuleBase:RU362012};

amino acid biosynthetic process [GO:0008652]; isoleucine biosynthetic process [GO:0009097]; L-serine catabolic process [GO:0006565]; threonine catabolic process [GO:0006567]

chloroplast [GO:0009507]

L-serine ammonia-lyase activity [GO:0003941]; pyridoxal phosphate binding [GO:0030170]; threonine deaminase activity [GO:0004794]

PF00291;PF00585;

3.40.50.1100;

Serine/threonine dehydratase family

SUBCELLULAR LOCATION: Plastid, chloroplast {ECO:0000305}.

CATALYTIC ACTIVITY: Reaction=L-threonine = 2-oxobutanoate + NH4(+); Xref=Rhea:RHEA:22108, ChEBI:CHEBI:16763, ChEBI:CHEBI:28938, ChEBI:CHEBI:57926; EC=4.3.1.19; Evidence={ECO:0000255|RuleBase:RU362012, ECO:0000269|PubMed:21436043};

PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; 2-oxobutanoate from L-threonine: step 1/1. {ECO:0000255|RuleBase:RU362012}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Active at alkaline pH. {ECO:0000269|PubMed:21436043};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 16 degrees Celsius. Not active at temperatures above 55 degrees Celsius. Complete loss of activity by incubation at 55 degrees Celsius for 1 minute. {ECO:0000269|PubMed:21436043};

FUNCTION: Has a housekeeping role in isoleucine biosynthesis (Probable). {ECO:0000305|PubMed:17416643}.

Solanum lycopersicum (Tomato) (Lycopersicon esculentum)

A0FKN5

S26A5_CHICK

MEDAQESGECLVQNQKYCVERPIYNQEILQGQLHKRERTPQSLRQKIEHSCRCSSKKAKSHLYSFLPILKWLPRYPVKEYLLGDIISGISTGVMQLPQGLAYALLAAVPPVFGLYSSFYPVFLYTFFGTSKHISIGTFAVISMMVGGVAVRQVPDEVISVGYNSTNATDASDYYSLRDDKRVQVAVTLAFLSGIIQLCLGFLRFGFVAIYLTEPLVRGFTTAAAVHVFTSQLKYLLGVKTSRYSGPLSVVYSLVAVFSKITTTNIAALIVGLTCIALLLIGKEINLRFKKKLPVPIPMEIIVVIIGTGVSAGMNLTESYGVDVVGKIPQGLSAPAVPEIQLIPAIFIDAVAIAIVGFSMAVSMAKIFALKHGYTIDGNQELIALGICNSVGSFFQSFPITCSMSRSLVQESTGGKTQIAGALSSIMVLLVIVAIGYLFEPLPQTVLAAIVMVNLKGMFKQFADVAHFWRTSKIELAIWVVAFVASLFLGLDYGLLTAVAFAMITVIYRTQRPQYRILGQIPDTDIYCDVEEYEEVKEYPGIKIFQANTSLYFANSESYTSALKKKTGVDPCAILAARRKAQKKHAREIKKANKVKKKAVLKLVNSSTNDVEASVKHEIANDGLPANGKFAFVDAGVQDGSPDELEHFVEPKTNVHSLILDFAPVNFVDSVGAKTLKSVIKEYNEVGVCVCIASCSGPVMNELTRLNFFDNTVTRELLFHSIHDAVLACQGKDRSASQTALDH

plasma membrane [GO:0005886]

bicarbonate transmembrane transporter activity [GO:0015106]; chloride transmembrane transporter activity [GO:0015108]; metal ion binding [GO:0046872]; oxalate transmembrane transporter activity [GO:0019531]; oxalate:chloride antiporter activity [GO:0160046]; sulfate transmembrane transporter activity [GO:0015116]; sulfate:chloride antiporter activity [GO:0160044]

PF01740;PF00916;

3.30.750.24;

SLC26A/SulP transporter (TC 2.A.53) family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17442754}; Multi-pass membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=chloride(out) + oxalate(in) = chloride(in) + oxalate(out); Xref=Rhea:RHEA:72263, ChEBI:CHEBI:17996, ChEBI:CHEBI:30623; Evidence={ECO:0000269|PubMed:17442754, ECO:0000269|PubMed:24710176}; CATALYTIC ACTIVITY: Reaction=chloride(in) + sulfate(out) = chloride(out) + sulfate(in); Xref=Rhea:RHEA:75295, ChEBI:CHEBI:16189, ChEBI:CHEBI:17996; Evidence={ECO:0000269|PubMed:17442754, ECO:0000269|PubMed:24710176};

FUNCTION: Electrogenic antiporter that exchanges sulfate or oxalate for chloride ion in a strictly coupled manner with a 1:1 stoichiometry (PubMed:17442754, PubMed:22399806, PubMed:24710176). Adopts a dynamic conformation, which alternates between the exposure of the central binding site to the extra- and intracellular solutions leading to an inward-to-outward conformational transition during the transport cycle (PubMed:24710176). {ECO:0000269|PubMed:17442754, ECO:0000269|PubMed:22399806, ECO:0000269|PubMed:24710176}.

Gallus gallus (Chicken)

A0JJU1

TENS_BEABA

MSPMKQNESESHSVSEPIAIIGSAYRFPGGCNTPSKLWDLLRQPRDILKEIDPERLNLRRYYHPDGETHGSTDVANKAYTLEEDISRFDASFFGISPLEAASMDPQQRTLLEVVYESTETAGIPLDKLRGSLTSVHVGVMTTDWAQMQRRDPETMPQYTATGIASSIISNRISYIFDLKGASETIDTACSSSLVALHNAARALQSGDCEKAIVAGVNLILDPDPFIYESKLHMLSPDARSRMWDAAANGYARGEGAAAVVLKTLGHALRDGDRIEGVIRSTFVNSDGLSSGLTMPSSAAQTALIRQTYRKAGLDPVRDRPQFFECHGTGTKAGDPVEARAISDAFLPPSHRTNGAATTVDAPLYVGSIKTVVGHLEGCAGLAGLVKVLLSLKHGIIPPNLWFDKLNPEIARYYGPLQIPTKAIPWPKLAPGTPLRASVNSFGFGGTNAHAIIERYDASQSYCSQWRRNMTEEKTIARTQNNESIEIPVPLVLTAKTGRALWRTVDAYAQHLRQHPKLRVTNLSQFMHSRRSTHRVRASFSGASREELVENMAKFVQAHAADAKSPASQNRIGYSPLHIDPKEAPGILGVFTGQGAQWPAMGRDMMHQSPLFRKTIADCESVLQALPAKDAPVWSLSEELKKDASTSRLGEAEISQPLCTAVQLALVNVLLASGVHFDAVVGHSSGEIAATYASGIINLEAAMQIAYYRGLYAKLARGETDAAGGMMAAGLSMNDAVKLCRLPEFEGRIHVAASNAPQSVTLSGDKEAIKAAKAKLDADGVFARELKVDTAYHSHHMLPCAEPYLKALLACDIQVSAPTTTPGRKCMWSSSVRGDAELLRHDRNLDSLKGPYWVANMVQTVLFSRAVQSTIWHGGPFDLAVEVGPHPALKGPTEQTLKAVYGSAPLYTGVLSRGANDAVAFSTAIGNIWSHLGPAFVDITGYQSIFSSTCEGHGGGSAAPFISDLPLYPWDHDEEYWRESRISRRHRTGKDESHELLGRRTPDDNEREIRWRNLLKVSELPWTQGHRVLGEVLLPGAAYISMAIEAGRRLALDQGREARLLEVSDVDILRPVVVADNKEGTETLFTVRLLDEYASTGKKSDELITASFSFYIYNSPASTSIVHTCEGRIAVQLGAKLGSEAGANSMPQLPHREPSISNLQQLDCEKLYSVFETIGLEYSGAFRRIVSSSRCLGHATATASWPTTDLNDCYLIHPAILDVAFQTIFVARAHPDSGQLSSALLPSRIERVRVVPSLAMGSKLQNNENFNAAIDSWALNQTASSLTGNINVYDAESGRALIQVEGFEVRAVGEPDASKDRLLFYETVWGRDISIMGLSDPIRDETSDAMVHNLSEAIERVSLFYVRQLMGELSTADRRQANWYHTRMLAAFDYHLAKVHEETHLHLRPEWLADDWAVIQTIDEAYPDAVELQMLHAVGQNVADVIRGKKHLLEVLRVDNLLDRLYTEDKGMHMANLFLANALEEITFKFPRCKILEIGAGTGATTWAALSAIGEAFDTYTYTDLSVGFFENAVERFSAFRHRMVFRALDIEKDPASQSFDLNSYDIIIATNVLHATRNLGVTLGNVRALLKPGGYLLLNEKTGPESLRATFNFGGLEGWWLAEEKERQLSPLMSPDGWDAQLQKASFSGVDHIVHDVQEDQQDKQQNSMIMSQAVDDTFYARLSPLSEMANLLPMNEPLLIIGGQTTATLKMIKEIQKLLPRQWRHKVRLIASVDHVEAEGLPAHSDVICLQELDRGLFTTAMTSKCLDALKTLFINTRNLLWVTNAQNSSSMTPRASMFRGITRVLDGEVPHIRTQVLGIEPRETPSATARTLLEAFLRLRSDDGRHAGNVDEDGADGSSQQVLWLHEPEAELLSNGTMMVPRVKARKSLNDTYLASTRAISTTVDARCVSVQAVAGPAKMLLRPVEDFAGEHAISNQTSDSKVHIQVESTLHIPEALDGTCLYLVCGWTRTAETSVPVIALSANNASMVAVESKAVAMIDEVDVKPETLLRVFQHMAMQALDSAVKRHGQGQSTALIYGADEELAKLTSERFAVRESKVYFASSRTFAPGDWLKVQPLLSKFALSQMIPADVEVFIDCLGDTESFDACRTLQSCLSTTRTVQHRLDACLLSQMSRCSPDALVDAYSYAKTQSNAEFSWNGYVKTFTAAELAGKLSHSLIHSVYMTNWQKKDSILVTVPPLQTRGLFKSDRTYLMVGAAGGLGTSICRWMVRNGARHVVVTSRNPKADPEMLNEAERYGAAVQVVPMDACSKDSVQTVVDMIRATMPPIAGVCNAAMVLRDKLFLDMNVDHMKDVLGPKMQGTEHLDSIFAQEPLDFFVLLSSSAAILNNTGQSNYHCANLYMDSLVTNRRSRGLAASIIHVGHVCDTGYVARLVDDTKVQMSLGTTRVMSVSETDVHHAFAEAVRGGQPDSRSGSHNIIMGIEPPTKPLDLTKRKPVWISDPRLGPCLPFSTLENQMMASEQAAAASAVDSLAQQVSEATTDEEAAVAALKGFATKLEGILLLPLGSIGEDSAGRPVTDLGIDSLVAVEIRTWFLKQLRVDVPVMKILGGSTVGQLSALAAKLARQDAKKRAQLEEPSGNQPVALPSPPPKDKAGGLNKNGKSPKLPEIAQVDTVVERMEPLVLEASDRGGSSTANLTTSSSVSELDDSLHESTLQSSDNNGESTPSKSSNCNSDSGSDNQAPKEIPSNGFFTQPAATARPNVLREAPMSPAQSRIWFLSKHIAEPDAYNMVFHYRVRGPLSMVRLRHALQTVTNHHECLCMCFYASADNGQPMQGLLASSAFQMTHVPGGEEQDVQRELRKLKTRVWSVESGQTLELVVLGPRPGTAAAAEEEEEEFSLLFGYHHIVMDAISFYIFLADLDKAYRMLPLDKASAGSHLDLAAHQRQQERAGAWEESLEFWRAEFETIPEMLPSLSVALPTLHRGAVGTHRVLRELAHEQGGDAAIKKMCKHLRVSPFNLHIAVLQVVIARLASIEDVCVGIVDANRSDSRASRMVGCFVNMLPVRSRILPTATLADVARAASSKALAAFAHGQVPLDSILDKVKAPRPAGSTPLFQVALNYRPAAAIASKQALGGECEMELLADDFKDAENPFEISVLVSEMSGGRIAVEVVCQKSRYTMQATEALLDAYLNVLAGFLSDSAQSVGDCVVHDQSKVEHALDLGRGAQKSFGWPRTLSERVMSICQQHSTKSAIKDGRNELSYAQLASRVNRTASAILGTGCSVGSRIAVLCNPSIDAIVAMLAILHIGGVYVPLDTSLPEARHQSLASNCTPSLIISHAATRERAHKLSAAISAPGHEPARELTLDDLSPPEETGYMAPLNAEPNAPAILLYTSGSTGTPKGVLLTQANFGNHIALKTDILGLQRGECVLQQSSLGFDMSLVQVFCALANGGCLVIVRQDVRRDPVELTTLMTQHKVSLTIATPSEYLAWLQYGSDALAQATSWKNLCMGGEPIPPLLKDELRRRLERKDLVVTNCYGPTETTAAISFQSVALDSEHGHELPGESELAQYAVGKALPNYSIRIRDSAGGAWLPVNHTGEIVIGGAGVALGYLDMPEETRARFLQTPGEEDGMMLYRTGDKGRLLSDGTLLCFGRITGDYQVKLRGLRIELGEVEAALLQASHGLIHTAVVSRRGDVLVAHCARSHESSRETTGGGEQQDATAILRRVSELLPQYSVPAAIALLPSLPTNANGKLDRKAIAALPLSPQDEAAAATSPSNNNINNNTPSGGGGEKMTVRQGELRLLWERVLPRDAATTTTNSVRITPESDFFLRGGNSLLLMKLQAAIRESMGVRVSTKALYQASTLSGMARCVAEQRSDDDEAEEDIDWAAEVAVPPSMLAQIEKLQHSSASSSSSSSSSSSAGSSSTQRPRKTSGLEILLTGATGFLGGQLLERLVQSPRVSTVHCVAVPVDEQSLLEPFLQQQADGTRRKVRCYIGNLAAPALGLTAADQTALSQTADVIVHAGSMGHCLNTYATLAAPNFASTRHLCSLALSRSPPIPLAFASSNRVALLTGSTAPPPASAAAFPPPPGAQGFTASKWASEAFLEKLAASIMTSKTKSTTTTTTTTVPWRVSIHRPCALISDRAPNSDALNAILRYSTSMRCVPSLPEHRAEGYLDFGQVDKVVEEMVGDILGLADERQQEGPAVVYRHHSGGVKVPIHEFREHMESVYGGRFESVELGQWIVRAVDAGMDPLISAYLETFLEGDASMVFPYMGEQAV

2.3.1.-; 6.3.2.-

amide biosynthetic process [GO:0043604]; fatty acid biosynthetic process [GO:0006633]; heterocycle biosynthetic process [GO:0018130]; methylation [GO:0032259]; organic cyclic compound biosynthetic process [GO:1901362]; organonitrogen compound biosynthetic process [GO:1901566]; toxin biosynthetic process [GO:0009403]

fatty acid synthase activity [GO:0004312]; ligase activity [GO:0016874]; methyltransferase activity [GO:0008168]; oxidoreductase activity [GO:0016491]; phosphopantetheine binding [GO:0031177]

PF00698;PF00501;PF00668;PF16197;PF00109;PF02801;PF08659;PF08242;PF07993;PF21089;PF00550;PF14765;

3.30.300.30;3.30.70.3290;3.40.47.10;1.10.1200.10;3.30.559.10;3.40.366.10;3.40.50.12780;3.40.50.720;3.30.559.30;3.10.129.110;3.40.50.150;

NRP synthetase family

PATHWAY: Secondary metabolite biosynthesis. {ECO:0000269|PubMed:17216664, ECO:0000269|PubMed:18266306, ECO:0000269|PubMed:20575135, ECO:0000269|PubMed:34903054}.

FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that mediates the biosynthesis of tenellin-type 2-pyridones, iron-chelating compounds involved in iron stress tolerance, competition with the natural competitor fungus Metarhizium robertsii and insect hosts infection (PubMed:17216664, PubMed:18266306, PubMed:20575135, PubMed:34903054). TenS catalyzes the assembly of the polyketide-amino acid backbone (PubMed:18266306, PubMed:34903054). Because tenS lacks a designated enoylreductase (ER) domain, the required activity is provided the enoyl reductase tenC (PubMed:18266306, PubMed:34903054). Upon formation of the polyketide backbone on the thiotemplate, the triketide is transferred to the NRPS module and linked to tyrosine to produce the pyrrolidine-2-dione intermediates, including pretellinin A, 11-hydropretellenin A, 12-hydropretellenin A, 13-hydropretellenin A, 14-hydropretellenin A, 12-oxopretellenin A and prototellinin D (PubMed:18266306, PubMed:34903054). The pathway begins with the assembly of the polyketide-amino acid backbone by the hybrid PKS-NRPS tenS with the help of the enoyl reductase tenC. These enzymes catalyze the synthesis of the pyrrolidine-2-dione intermediates pretellinin A, 11-hydropretellenin A, 12-hydropretellenin A, 13-hydropretellenin A, 14-hydropretellenin A, 12-oxopretellenin A and prototellinin D. The cytochrome P450 monooxygenase tenA then catalyzes an oxidative ring expansion of pretenellin A and 14-hydropretellenin A to form the 2-pyridone core, leading to pretenellin B and pyridovericin, respectively. The cytochrome P450 monooxygenase tenB is then required for the selective N-hydroxylation of the 2-pyridone nitrogen of yield tellinin and 15-hydroxytellenin (15-HT), respectively. The UDP-glucosyltransferase GT1 and the methyltransferase MT1, located outside the tenS gene cluster, contribute to the stepwise glycosylation and methylation of 15-HT to obtain the glycoside pyridovericin-N-O-(4-O-methyl-beta-D-glucopyranoside) (PMGP). Additional related compounds such as 1-O-methyl-15-HT, (8Z)-1-O-methyl-15-HT, and O-methyltenellin A are also produced but the enzymes involved in their biosynthesis have still to be determined (PubMed:34903054). {ECO:0000269|PubMed:17216664, ECO:0000269|PubMed:18266306, ECO:0000269|PubMed:20575135, ECO:0000269|PubMed:34903054}.

Beauveria bassiana (White muscardine disease fungus) (Tritirachium shiotae)

A0JLT2

MED19_HUMAN

MENFTALFGAQADPPPPPTALGFGPGKPPPPPPPPAGGGPGTAPPPTAATAPPGADKSGAGCGPFYLMRELPGSTELTGSTNLITHYNLEQAYNKFCGKKVKEKLSNFLPDLPGMIDLPGSHDNSSLRSLIEKPPILSSSFNPITGTMLAGFRLHTGPLPEQCRLMHIQPPKKKNKHKHKQSRTQDPVPPETPSDSDHKKKKKKKEEDPDRKRKKKEKKKKKNRHSPDHPGMGSSQASSSSSLR

positive regulation of transcription by RNA polymerase II [GO:0045944]; positive regulation of transcription elongation by RNA polymerase II [GO:0032968]; positive regulation of transcription initiation by RNA polymerase II [GO:0060261]; RNA polymerase II preinitiation complex assembly [GO:0051123]

core mediator complex [GO:0070847]; mediator complex [GO:0016592]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]

transcription coregulator activity [GO:0003712]

PF10278;

Mediator complex subunit 19 family

SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.

FUNCTION: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.

Homo sapiens (Human)

A0JMD4

TPC2_DANRE

MEEEPLLAGSINQGSGDYGAHSESCLHYPDEHTPRSRRLSYSVTDDSCNVEEDADADLYVQQAVVFIEDAIKYRSINHRVDSGSLRLYRWYYSNLCQWGLGLTIAVVLALAFIERPSSLTYTSDIRVKPKPWEPPCGMTEGIEIVCLCIFILDVTAKGYLIGWEEFRMNKWLLAYLIVITASVIDWMLSISMLCDENLRVRRLIRPFFLLQNSSLMKKTLKCIKRTLPEIASVILLLALHICLFTMIGMLIFAKSDDPKQNGEWQTYFRNLPKALSSLLVLLTTANNPDVMIPAYSLNRGYSIFFILFSVFGTYLLMNLMTAIIYNQFRGYLLMSVQTSIIRRRLGIRAAFEVLCCPGRGHTSTQAEGHVERVAVSMFLKVMERVHMKSYCRQAIVKAARRFPDGFISGEDFQRLFNELDKDFVKEHPPKPEYSSSGLQHIQYVYSHYYISVLGNAVALANVICICTVLVLNAEKSASEKNYFYMEIINCIFILYYLIEMLLKIVAFGWKGYLSYRNNIFDGFLTVLLLAIQIVIFITFKIPYVDVDPVPRHVMALWEMIRLVNMLIVFRFLRIIPEIKLMAVVASTIVDLVKNLRAFAGILLVVYYMFAVLGIWLFQGAISPPSNMSLVSNSSLENITGPYSMECGTFEQLEYWPNNFDDFASSLILLYNIMVVNNWHVFTDAYARYTTDWSLVYFVVWWLTSSVMWVNLFVALILENFTYKWDRSNGLSVEDVERIAYQSTVQLMFKEHVKEPTEEELLAQLHQHPHLHLSW

calcium-mediated signaling [GO:0019722]; endocytosis involved in viral entry into host cell [GO:0075509]; regulation of myotome development [GO:2000290]; skeletal myofibril assembly [GO:0014866]; smooth muscle contraction [GO:0006939]; sodium ion transmembrane transport [GO:0035725]

late endosome membrane [GO:0031902]; lysosomal membrane [GO:0005765]; lysosome [GO:0005764]; monoatomic ion channel complex [GO:0034702]

identical protein binding [GO:0042802]; intracellularly phosphatidylinositol-3,5-bisphosphate-gated monatomic cation channel activity [GO:0097682]; ligand-gated sodium channel activity [GO:0015280]; NAADP-sensitive calcium-release channel activity [GO:0072345]; phosphatidylinositol-3,5-bisphosphate binding [GO:0080025]; voltage-gated calcium channel activity [GO:0005245]

PF00520;

1.10.287.70;1.20.120.350;

Calcium channel alpha-1 subunit (TC 1.A.1.11) family, Two pore calcium channel subfamily

PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q8BWC0}.

SUBCELLULAR LOCATION: Late endosome membrane {ECO:0000250|UniProtKB:Q8NHX9}; Multi-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q8NHX9}; Multi-pass membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963, ChEBI:CHEBI:29101; Evidence={ECO:0000250|UniProtKB:Q8NHX9}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:34965; Evidence={ECO:0000250|UniProtKB:Q8NHX9}; CATALYTIC ACTIVITY: Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, ChEBI:CHEBI:29108; Evidence={ECO:0000250|UniProtKB:Q8NHX9}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:29673; Evidence={ECO:0000250|UniProtKB:Q8NHX9};

FUNCTION: Intracellular channel initially characterized as a non-selective Ca(2+)-permeable channel activated by NAADP (nicotinic acid adenine dinucleotide phosphate), it is also a highly-selective Na(+) channel activated directly by PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate). Localizes to the lysosomal and late endosome membranes where it regulates organellar membrane excitability, membrane trafficking, and pH homeostasis. {ECO:0000250|UniProtKB:Q8NHX9}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0JMQ9

ZRN1B_DANRE

MTDLGLKWSCEYCTYENWPSAIKCTMCRAQRHNAPIITEEPFKSSSSLDPSLCTTQGGSTLLICPDSSARPRVRIADELPETSSKWSCHMCTYLNWPRAIRCTQCLSQRQQGSQQHSPLSPSETPQTSGSRPSPVTSDPCEEYNDRNRLNMHAQRWPCSACTYENWPKSLRCVVCDHPKPSGSPETPQQDSEAESATSPSIVNEQERENVRTAGGGGGGSRGRLRKLSPPMCKGQAEVKIELASGAVGSDNEQEADFKKLKQIRNRMRRSDWLFLNACAGVVEGDLAAVEAYKSSGGDIARQLTADEVRILNRPSAFDAGFTLVHLAIRFQRQDMLAVLLTEVSQQTAKCIPALVCPELTEQIRREVAAALHRRKGEFPCYFFTDLVTFTLPADIEDLPPNVQEKLFDEVLDRDVQKELEEESPIINWSLELGTRLDSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKSLNDSLHDCSHWFYTRWKEWESWYSQSFGLHFSLREEQWQEDWAFILSLASQPGASLEQTHVFVLAHILRRPIIVYGVKYYKSFRGETLGYTRFQGVYLPLLWEQSFCWKSPIALGYTRGHFSALVAMENDGYDNRGAGANLNTDDDVTVTFLPLVDSERKLLHIHFLSAQEMGTEEQQERMLRQWMDCCVTEGGVLVAMQKSSRRRNHPLVTQMVEKWLDGYRQLAACPTLSDGEEEEEDEDE

3.4.19.12

brain development [GO:0007420]; cell migration [GO:0016477]; central nervous system morphogenesis [GO:0021551]; cytoskeleton organization [GO:0007010]; positive regulation of Wnt signaling pathway [GO:0030177]; protein K29-linked deubiquitination [GO:0035523]; protein K33-linked deubiquitination [GO:1990168]; protein K63-linked deubiquitination [GO:0070536]; proteolysis [GO:0006508]; regulation of cell morphogenesis [GO:0022604]; Wnt signaling pathway [GO:0016055]

cytoplasm [GO:0005737]; nucleus [GO:0005634]

cysteine-type deubiquitinase activity [GO:0004843]; K63-linked polyubiquitin modification-dependent protein binding [GO:0070530]; metal ion binding [GO:0046872]

PF18418;PF02338;PF00641;

1.25.40.560;4.10.1060.10;2.30.30.380;

Peptidase C64 family

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UGI0}. Nucleus {ECO:0000250|UniProtKB:Q9UGI0}. Note=Enriched in punctate localization in the cytoplasm. {ECO:0000250|UniProtKB:Q9UGI0}.

CATALYTIC ACTIVITY: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:Q9UGI0};

FUNCTION: Ubiquitin thioesterase, which specifically hydrolyzes 'Lys-29'-linked and 'Lys-33'-linked diubiquitin (By similarity). Also cleaves 'Lys-63'-linked chains, but with 40-fold less efficiency compared to 'Lys-29'-linked ones (By similarity). Positive regulator of the Wnt signaling pathway that deubiquitinates apc protein, a negative regulator of Wnt-mediated transcription (By similarity). Acts as a regulator of autophagy by mediating deubiquitination of pik3c3/vps34, thereby promoting autophagosome maturation (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization (By similarity). Required in the stress fiber dynamics and cell migration (By similarity). {ECO:0000250|UniProtKB:Q9UGI0}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0JN54

DGKA_BOVIN

MAKERGLISPSDFAQLQKYMEYSTKKVSDVLKLFEDGEMAEYLQGDAIGYEGFQQFLKIYLEVDNVPDHLSQALFQSFQTGYYIEDTVREDVVCLSDVSCYFSLLEGGRPEDKLEFTFKLYDTDRNGILDSSEVDRIIIQMMRMAEYLDWDVSELRPILQEMMKEIDYDGSGSVSLAEWLRAGATTVPLLVLLGLEMTLKDNGQHMWRPKRFPRPVYCNLCESSIGLGKQGLSCNLCKYIVHDQCAMKALPCEVSTYAKSRKDIGVQSHVWVRGGCESGRCDRCQKKIRIYHSLVGLHCVWCHLEIHDDCLPAMGHECDCGLLRDHILPPSSIYPSVLASGQERKTSKISQKTMDDLSLSTSEALRIDPVSNTHPLLVFVNPKSGGKQGERVLWKFQYLLNPRQVFNLLKDGPEPGLRFFRDVPDYRILVCGGDGTVGWILESIDKANLPFVPPVAVLPLGTGNDLARCLRWGGGYEGQNLGKILKDLETSKVVHMDRWSVEVIPQQTEEKSDPVPFQIINNYFSIGVDASIAHRFHIMREKYPEKFNSRMKNKLWYFEFATSESIFSTCKKLEESLTVEICGKPLDLSNLSLEGIAVLNIPSTHGGSNLWGDTKRPHGDIHGINQALGATAKVITDPDILKTCVPDLSDKRLEVVGLEGAIEIGQIYTKLKNAGHRLAKCSEITFHTTKTLPMQIDGEPWMQTPCTIKITHRNQMPMLVGPPPRSSNFFGFLC

2.7.1.107; 2.7.1.93

diacylglycerol metabolic process [GO:0046339]; intracellular signal transduction [GO:0035556]; lipid phosphorylation [GO:0046834]; phosphatidic acid biosynthetic process [GO:0006654]; protein kinase C-activating G protein-coupled receptor signaling pathway [GO:0007205]

cytosol [GO:0005829]; plasma membrane [GO:0005886]

alkylglycerol kinase activity [GO:0047649]; ATP binding [GO:0005524]; ATP-dependent diacylglycerol kinase activity [GO:0004143]; calcium ion binding [GO:0005509]

PF00130;PF14513;PF00609;PF00781;PF13499;

2.60.200.40;3.30.60.20;1.10.238.110;1.10.238.10;

Eukaryotic diacylglycerol kinase family

SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P23743}.

CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycerol + ATP = a 1,2-diacyl-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:10272, ChEBI:CHEBI:15378, ChEBI:CHEBI:17815, ChEBI:CHEBI:30616, ChEBI:CHEBI:58608, ChEBI:CHEBI:456216; EC=2.7.1.107; Evidence={ECO:0000250|UniProtKB:P23743}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10273; Evidence={ECO:0000250|UniProtKB:P23743}; CATALYTIC ACTIVITY: Reaction=1-O-alkyl-sn-glycerol + ATP = 1-O-alkyl-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:16937, ChEBI:CHEBI:15378, ChEBI:CHEBI:15850, ChEBI:CHEBI:30616, ChEBI:CHEBI:58014, ChEBI:CHEBI:456216; EC=2.7.1.93; Evidence={ECO:0000250|UniProtKB:P51556}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16938; Evidence={ECO:0000250|UniProtKB:P51556}; CATALYTIC ACTIVITY: Reaction=1-O-alkyl-2-acyl-sn-glycerol + ATP = 1-O-alkyl-2-acyl-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:44072, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:52595, ChEBI:CHEBI:73332, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P23743}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:44073; Evidence={ECO:0000250|UniProtKB:P23743}; CATALYTIC ACTIVITY: Reaction=1,2-dihexadecanoyl-sn-glycerol + ATP = 1,2-dihexadecanoyl-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:63324, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:72859, ChEBI:CHEBI:82929, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P23743}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63325; Evidence={ECO:0000250|UniProtKB:P23743}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycerol + ATP = 1-hexadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:43416, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:64839, ChEBI:CHEBI:75466, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P23743}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43417; Evidence={ECO:0000250|UniProtKB:P23743}; CATALYTIC ACTIVITY: Reaction=2-(9Z-octadecenoyl)-glycerol + ATP = 2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:63328, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:73990, ChEBI:CHEBI:77593, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P23743}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63329; Evidence={ECO:0000250|UniProtKB:P23743}; CATALYTIC ACTIVITY: Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycerol + ATP = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:40327, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:52333, ChEBI:CHEBI:74546, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P23743}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40328; Evidence={ECO:0000250|UniProtKB:P23743}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:40323, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:75728, ChEBI:CHEBI:77091, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P23743}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40324; Evidence={ECO:0000250|UniProtKB:P23743}; CATALYTIC ACTIVITY: Reaction=1,2-didecanoyl-sn-glycerol + ATP = 1,2-didecanoyl-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:43428, ChEBI:CHEBI:15378, ChEBI:CHEBI:18155, ChEBI:CHEBI:30616, ChEBI:CHEBI:78227, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P20192}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43429; Evidence={ECO:0000250|UniProtKB:P20192}; CATALYTIC ACTIVITY: Reaction=1-O-hexadecyl-2-acetyl-sn-glycerol + ATP = 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:41676, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:75936, ChEBI:CHEBI:78385, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P51556}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41677; Evidence={ECO:0000250|UniProtKB:P51556}; CATALYTIC ACTIVITY: Reaction=1-O-hexadecyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycerol + ATP = 1-O-hexadecyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:40403, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77184, ChEBI:CHEBI:77186, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P23743}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40404; Evidence={ECO:0000250|UniProtKB:P23743}; CATALYTIC ACTIVITY: Reaction=1-O-hexadecyl-2-(9Z-octadecenoyl)-sn-glycerol + ATP = 1-O-hexadecyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:40407, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:77185, ChEBI:CHEBI:77187, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P23743}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40408; Evidence={ECO:0000250|UniProtKB:P23743}; CATALYTIC ACTIVITY: Reaction=1-O-hexadecyl-sn-glycerol + ATP = 1-O-hexadecyl-sn-glycero-3-phosphate + ADP + H(+); Xref=Rhea:RHEA:41672, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:34115, ChEBI:CHEBI:77580, ChEBI:CHEBI:456216; Evidence={ECO:0000250|UniProtKB:P51556}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41673; Evidence={ECO:0000250|UniProtKB:P51556};

PATHWAY: Lipid metabolism; glycerolipid metabolism. {ECO:0000250|UniProtKB:P23743}.

FUNCTION: Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids. Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes. Also plays an important role in the biosynthesis of complex lipids. Can also phosphorylate 1-alkyl-2-acylglycerol in vitro as efficiently as diacylglycerol provided it contains an arachidonoyl group. Also involved in the production of alkyl-lysophosphatidic acid, another bioactive lipid, through the phosphorylation of 1-alkyl-2-acetyl glycerol. {ECO:0000250|UniProtKB:P23743}.

Bos taurus (Bovine)

A0JNB0

FYN_BOVIN

MGCVQCKDKEATKLTEERDGSLNQSSGYRYGTDPTPQHYPSFGVTSIPNYNNFHGAGGQGLTVFGGVNSSSHTGTLRTRGGTGVTLFVALYDYEARTEDDLSFHKGEKFQILNSSEGDWWEARSLTTGETGYIPSNYVAPVDSIQAEEWYFGKLGRKDAERQLLSFGNPRGTFLIRESETTKGAYSLSIRDWDDMKGDHVKHYKIRKLDNGGYYITTRAQFETLQQLVQHYSERAAGLCCRLVVPCHKGMPRLTDLSVKTKDVWEIPRESLQLIKRLGNGQFGEVWMGTWNGNTKVAIKTLKPGTMSPESFLEEAQIMKKLKHDKLVQLYAVVSEEPIYIVTEYMNKGSLLDFLKDGEGRALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANILVGNGLICKIADFGLARLIEDNEYTARQGAKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELMIHCWKKDPEERPTFEYLQGFLEDYFTATEPQYQPGENL

2.7.10.2

COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};

adaptive immune response [GO:0002250]; cell differentiation [GO:0030154]; innate immune response [GO:0045087]; peptidyl-tyrosine phosphorylation [GO:0018108]; T cell receptor signaling pathway [GO:0050852]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]

cytoplasm [GO:0005737]; extrinsic component of cytoplasmic side of plasma membrane [GO:0031234]; nucleus [GO:0005634]; perikaryon [GO:0043204]

ATP binding [GO:0005524]; metal ion binding [GO:0046872]; non-membrane spanning protein tyrosine kinase activity [GO:0004715]; protein tyrosine kinase activity [GO:0004713]; signaling receptor binding [GO:0005102]

PF07714;PF00017;PF00018;

3.30.505.10;2.30.30.40;1.10.510.10;

Protein kinase superfamily, Tyr protein kinase family, SRC subfamily

PTM: Autophosphorylated at Tyr-420 (By similarity). Phosphorylation on the C-terminal tail at Tyr-531 by CSK maintains the enzyme in an inactive state. PTPRC/CD45 dephosphorylates Tyr-531 leading to activation. Ultraviolet B (UVB) strongly increase phosphorylation at Thr-12 and kinase activity, and promotes translocation from the cytoplasm to the nucleus. Dephosphorylation at Tyr-420 by PTPN2 negatively regulates T-cell receptor signaling (By similarity). Phosphorylated at tyrosine residues, which can be enhanced by NTN1 (By similarity). {ECO:0000250|UniProtKB:P06241, ECO:0000250|UniProtKB:P39688}.; PTM: Palmitoylated. Palmitoylation at Cys-3 and Cys-6, probably by ZDHHC21, regulates subcellular location. {ECO:0000250|UniProtKB:P39688}.

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P06241}. Nucleus {ECO:0000250|UniProtKB:P06241}. Cell membrane {ECO:0000250|UniProtKB:P06241}. Perikaryon {ECO:0000250|UniProtKB:Q62844}. Note=Present and active in lipid rafts (By similarity). Palmitoylation is crucial for proper trafficking (By similarity). {ECO:0000250|UniProtKB:P06241}.

CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:10930415};

FUNCTION: Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1. In mast cells, phosphorylates CLNK after activation of immunoglobulin epsilon receptor signaling (By similarity). {ECO:0000250|UniProtKB:P06241, ECO:0000250|UniProtKB:P39688, ECO:0000269|PubMed:10930415}.

Bos taurus (Bovine)

A0JNC1

CDS2_BOVIN

MTELRQRVAREPEAPPEDKESESEAKADGETASDSESRVEAVTQPPSADDTPEVLNRALSNLSSRWKNWWVRGILTLAMIAFFFIIIYLGPMVLMMIVMCVQIKCFHEIITIGYNVYHSYDLPWFRTLSWYFLLCVNYFFYGETVTDYFFTLVQREEPLRILSKYHRFISFTLYLTGFCMFVLSLVKKHYRLQFYMFGWTHVTLLIVVTQSHLVIHNLFEGMIWFIVPISCVICNDIMAYMFGFFFGRTPLIKLSPKKTWEGFIGGFFATVVFGLLLSYVMSGYRCFVCPVEYNNDTNSFTVDCEPSGLFRLQEYNIPGVIQSIIGWKTVRMYPFQIHSIALSTFASLIGPFGGFFASGFKRAFKIKDFANTIPGHGGIMDRFDCQYLMATFVNVYIASFIRGPNPSKLVQQFLTLRPDQQLHIFNTLKSHLTDKGMLTAATEDK

2.7.7.41

CDP-diacylglycerol biosynthetic process [GO:0016024]; lipid droplet formation [GO:0140042]

endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]; membrane [GO:0016020]

phosphatidate cytidylyltransferase activity [GO:0004605]

PF01148;

CDS family

SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:O95674}; Multi-pass membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=a 1,2-diacyl-sn-glycero-3-phosphate + CTP + H(+) = a CDP-1,2-diacyl-sn-glycerol + diphosphate; Xref=Rhea:RHEA:16229, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:58332, ChEBI:CHEBI:58608; EC=2.7.7.41; Evidence={ECO:0000250|UniProtKB:O95674}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16230; Evidence={ECO:0000250|UniProtKB:O95674}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-cytidine-5'-diphosphate + diphosphate; Xref=Rhea:RHEA:45648, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:77091, ChEBI:CHEBI:85349; Evidence={ECO:0000250|UniProtKB:O95674}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45649; Evidence={ECO:0000250|UniProtKB:O95674}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1-octadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-cytidine-5'-diphosphate + diphosphate; Xref=Rhea:RHEA:45660, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:77098, ChEBI:CHEBI:85352; Evidence={ECO:0000250|UniProtKB:O95674}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45661; Evidence={ECO:0000250|UniProtKB:O95674}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-cytidine-5'-diphosphate + diphosphate; Xref=Rhea:RHEA:45652, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:72864, ChEBI:CHEBI:85350; Evidence={ECO:0000250|UniProtKB:O95674}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45653; Evidence={ECO:0000250|UniProtKB:O95674}; CATALYTIC ACTIVITY: Reaction=1,2-di-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphate + CTP + H(+) = 1,2-di-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-cytidine-5'-diphosphate + diphosphate; Xref=Rhea:RHEA:45656, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:77126, ChEBI:CHEBI:85351; Evidence={ECO:0000250|UniProtKB:O95674}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45657; Evidence={ECO:0000250|UniProtKB:O95674}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1-octadecanoyl-2-(9Z-octadecenoyl)-sn-glycero-3-cytidine-5'-diphosphate + diphosphate; Xref=Rhea:RHEA:45664, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:74560, ChEBI:CHEBI:85353; Evidence={ECO:0000250|UniProtKB:O95674}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45665; Evidence={ECO:0000250|UniProtKB:O95674}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1-octadecanoyl-2-(4Z,7Z,10Z,13Z,16Z,19Z-docosahexaenoyl)-sn-glycero-3-cytidine-5'-diphosphate + diphosphate; Xref=Rhea:RHEA:45668, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:77130, ChEBI:CHEBI:85354; Evidence={ECO:0000250|UniProtKB:O95674}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45669; Evidence={ECO:0000250|UniProtKB:O95674}; CATALYTIC ACTIVITY: Reaction=1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-cytidine-5'-diphosphate + diphosphate; Xref=Rhea:RHEA:45672, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:77128, ChEBI:CHEBI:85355; Evidence={ECO:0000250|UniProtKB:O95674}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45673; Evidence={ECO:0000250|UniProtKB:O95674}; CATALYTIC ACTIVITY: Reaction=1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphate + CTP + H(+) = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-cytidine-5'-diphosphate + diphosphate; Xref=Rhea:RHEA:45676, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:74546, ChEBI:CHEBI:85356; Evidence={ECO:0000250|UniProtKB:O95674}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45677; Evidence={ECO:0000250|UniProtKB:O95674};

PATHWAY: Phospholipid metabolism; CDP-diacylglycerol biosynthesis; CDP-diacylglycerol from sn-glycerol 3-phosphate: step 3/3.

FUNCTION: Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol (By similarity). Exhibits specificity for the nature of the acyl chains at the sn-1 and sn-2 positions in the substrate, PA and the preferred acyl chain composition is 1-stearoyl-2-arachidonoyl-sn-phosphatidic acid (By similarity). Plays an important role in regulating the growth and maturation of lipid droplets which are storage organelles at the center of lipid and energy homeostasis (By similarity). {ECO:0000250|UniProtKB:O95674}.

Bos taurus (Bovine)

A0JNC4

ELOV7_BOVIN

MAFSDLTSRTVRLYDNWIKDADPRVEDWLLMSSPLPQTIILGFYVYFVTSLGPKLMENRKPFELKKVMITYNFSIVLFSVYMFYEFIMSGWGTGYSFRCDIVDYSQSPTALRMVRTCWLYYFSKFIELLDTIFFILRKKNSQVTFLHVFHHTIMPWTWWFGVKFAAGGLGTFHAFLNTAVHVVMYSYYGLCALGPDYQKYLWWKKYLTSLQLIQFVLITIHISQFFFMEDCKYQFPVFQYIIMSYGCIFLLLFLHFWYRAYTKGQRLPKTVKHGICKNKDH

2.3.1.199

fatty acid elongation, monounsaturated fatty acid [GO:0034625]; fatty acid elongation, polyunsaturated fatty acid [GO:0034626]; fatty acid elongation, saturated fatty acid [GO:0019367]; long-chain fatty-acyl-CoA biosynthetic process [GO:0035338]; sphingolipid biosynthetic process [GO:0030148]; unsaturated fatty acid biosynthetic process [GO:0006636]; very long-chain fatty acid biosynthetic process [GO:0042761]

endoplasmic reticulum [GO:0005783]; endoplasmic reticulum membrane [GO:0005789]

fatty acid elongase activity [GO:0009922]

PF01151;

ELO family, ELOVL7 subfamily

SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000255|HAMAP-Rule:MF_03207}; Multi-pass membrane protein {ECO:0000255|HAMAP-Rule:MF_03207}.

CATALYTIC ACTIVITY: Reaction=a very-long-chain acyl-CoA + H(+) + malonyl-CoA = a very-long-chain 3-oxoacyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:32727, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:90725, ChEBI:CHEBI:90736; EC=2.3.1.199; Evidence={ECO:0000255|HAMAP-Rule:MF_03207}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32728; Evidence={ECO:0000250|UniProtKB:A1L3X0}; CATALYTIC ACTIVITY: Reaction=eicosanoyl-CoA + H(+) + malonyl-CoA = 3-oxodocosanoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:35327, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57380, ChEBI:CHEBI:57384, ChEBI:CHEBI:71451; Evidence={ECO:0000250|UniProtKB:A1L3X0}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35328; Evidence={ECO:0000250|UniProtKB:A1L3X0}; CATALYTIC ACTIVITY: Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoyl-CoA + H(+) + malonyl-CoA = (7Z,10Z,13Z,16Z)-3-oxodocosatetraenoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:36475, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57368, ChEBI:CHEBI:57384, ChEBI:CHEBI:73852; Evidence={ECO:0000250|UniProtKB:A1L3X0}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36476; Evidence={ECO:0000250|UniProtKB:A1L3X0}; CATALYTIC ACTIVITY: Reaction=(6Z,9Z,12Z)-octadecatrienoyl-CoA + H(+) + malonyl-CoA = (8Z,11Z,14Z)-3-oxoeicosatrienoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:35379, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57363, ChEBI:CHEBI:57384, ChEBI:CHEBI:71481; Evidence={ECO:0000250|UniProtKB:A1L3X0}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35380; Evidence={ECO:0000250|UniProtKB:A1L3X0}; CATALYTIC ACTIVITY: Reaction=(9Z,12Z)-octadecadienoyl-CoA + H(+) + malonyl-CoA = (11Z,14Z)-3-oxoicosa-11,14-dienoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:36503, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57383, ChEBI:CHEBI:57384, ChEBI:CHEBI:74012; Evidence={ECO:0000250|UniProtKB:A1L3X0}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36504; Evidence={ECO:0000250|UniProtKB:A1L3X0}; CATALYTIC ACTIVITY: Reaction=(9Z)-octadecenoyl-CoA + H(+) + malonyl-CoA = (11Z)-3-oxoicosenoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:36511, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:57387, ChEBI:CHEBI:74011; Evidence={ECO:0000250|UniProtKB:A1L3X0}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36512; Evidence={ECO:0000250|UniProtKB:A1L3X0}; CATALYTIC ACTIVITY: Reaction=H(+) + malonyl-CoA + octadecanoyl-CoA = 3-oxoeicosanoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:35319, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:57394, ChEBI:CHEBI:65115; Evidence={ECO:0000250|UniProtKB:A1L3X0}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35320; Evidence={ECO:0000250|UniProtKB:A1L3X0}; CATALYTIC ACTIVITY: Reaction=H(+) + hexadecanoyl-CoA + malonyl-CoA = 3-oxooctadecanoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:35315, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57384, ChEBI:CHEBI:71407; Evidence={ECO:0000250|UniProtKB:A1L3X0}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:35316; Evidence={ECO:0000250|UniProtKB:A1L3X0}; CATALYTIC ACTIVITY: Reaction=(9Z,12Z,15Z)-octadecatrienoyl-CoA + H(+) + malonyl-CoA = (11Z,14Z,17Z)-3-oxoeicosatrienoyl-CoA + CO2 + CoA; Xref=Rhea:RHEA:36523, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57384, ChEBI:CHEBI:74034, ChEBI:CHEBI:74054; Evidence={ECO:0000250|UniProtKB:A1L3X0}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36524; Evidence={ECO:0000250|UniProtKB:A1L3X0};

PATHWAY: Lipid metabolism; fatty acid biosynthesis. {ECO:0000255|HAMAP-Rule:MF_03207}.

FUNCTION: Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme with higher activity toward C18 acyl-CoAs, especially C18:3(n-3) acyl-CoAs and C18:3(n-6)-CoAs. Also active toward C20:4-, C18:0-, C18:1-, C18:2- and C16:0-CoAs, and weakly toward C20:0-CoA. Little or no activity toward C22:0-, C24:0-, or C26:0-CoAs. May participate in the production of saturated and polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. {ECO:0000255|HAMAP-Rule:MF_03207}.

Bos taurus (Bovine)

A0JNH9

APLF_BOVIN

MSGGFELQPQDGGPRVALAPGETVIGRGPLLGLHRNPCYYQSSEKSQLLPLKTNIWCWLNPGDHFSLLVDKYIFCVLSTHSEMEMECTLRNSQMLDEDDILNEIPKSSSADLPDKTPSAPRRERSTETAKPQAAANNMSFIGESRDLSKQQPNPSERKRILPAWMLTENSSDQNLSVISGGNNVTWESEKERVCKDKTQVNITQPGKKRLISSGSSESTSAKQDTGKKCKNDDQEESIISSKEMPQSFSAAMLHNTEIDNTKTNPQRSKVPVEALGKVSEHKIITKGSSNEDSTARSCSESYSSTQSKSFCDKPQKSHPEPSSNPPSPECVQAKATDSVPNGSEENKVQRTSCMYGANCYRKNPVHFQHFSHPGDSDYGGVNITCQDEADDRPECPYGASCYRKNPQHKIEYRHSTFPVRSISDEDDNVGQPNEYNLNDSFIDDEEEEYEPTDEDSDWEPEKEDLEKEDMEGLLKEAKKFMKRKK

3.1.1.-

DNA damage response [GO:0006974]; DNA repair-dependent chromatin remodeling [GO:0140861]; double-strand break repair [GO:0006302]; double-strand break repair via nonhomologous end joining [GO:0006303]; embryo implantation [GO:0007566]; regulation of epithelial to mesenchymal transition [GO:0010717]; single strand break repair [GO:0000012]

cytosol [GO:0005829]; nucleus [GO:0005634]; site of DNA damage [GO:0090734]; site of double-strand break [GO:0035861]

3'-5' exonuclease activity [GO:0008408]; ADP-D-ribose modification-dependent protein binding [GO:0160002]; DNA endonuclease activity [GO:0004520]; DNA-(apurinic or apyrimidinic site) endonuclease activity [GO:0003906]; histone binding [GO:0042393]; histone chaperone activity [GO:0140713]; metal ion binding [GO:0046872]; nucleotide binding [GO:0000166]; poly-ADP-D-ribose binding [GO:0072572]

PF10283;

2.60.200.20;

APLF family

PTM: Poly-ADP-ribosylated. In addition to binding non covalently poly-ADP-ribose via its PBZ-type zinc fingers, the protein is also covalently poly-ADP-ribosylated by PARP1. {ECO:0000250|UniProtKB:Q8IW19}.; PTM: Phosphorylated in an ATM-dependent manner upon double-strand DNA break. {ECO:0000250|UniProtKB:Q8IW19}.

SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9D842}. Chromosome {ECO:0000250|UniProtKB:Q8IW19}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9D842}. Note=Localizes to DNA damage sites. Accumulates at single-strand breaks and double-strand breaks via the PBZ-type zinc fingers. {ECO:0000250|UniProtKB:Q8IW19}.

FUNCTION: Histone chaperone involved in single-strand and double-strand DNA break repair. Recruited to sites of DNA damage through interaction with branched poly-ADP-ribose chains, a polymeric post-translational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions (By similarity). Following recruitment to DNA damage sites, acts as a histone chaperone that mediates histone eviction during DNA repair and promotes recruitment of histone variant MACROH2A1 (By similarity). Also has a nuclease activity: displays apurinic-apyrimidinic (AP) endonuclease and 3'-5' exonuclease activities in vitro. Also able to introduce nicks at hydroxyuracil and other types of pyrimidine base damage (By similarity). Together with PARP3, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ). Also acts as a negative regulator of cell pluripotency by promoting histone exchange. Required for the embryo implantation during the epithelial to mesenchymal transition in females (By similarity). {ECO:0000250|UniProtKB:Q8IW19, ECO:0000250|UniProtKB:Q9D842}.

Bos taurus (Bovine)

A0JNI4

SRR_BOVIN

MCDQYCISFADVEKAHINIRDFIHLTPVLTSSILNQITGRNLFFKCELFQKTGSFKIRGALNAIRGLISAHPEEKPRAVVAHSSGNHGQALSFAARLEGIPAYVIVPETAPNCKKLAIQAYGASIVYSEQSEESRENITKRIAEETEGIMVHPNQEPAVIAGQGTIAMEVLNQVPLVDALVVPVGGGGMLAGIAVTVKALRPSVKVYAAEPLNADDCYQSKLKGELTPNPYPPETIADGIKSSIGLNTWPIIRDLVDDVFTVTEDEIKYATQLVWERMKLLIEPTAGVGVAVVLSQHFRTVPAEVKNICIVLSGGNVDLTSLTWVKKQDEKAAP

4.3.1.17; 4.3.1.18; 5.1.1.18

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q9GZT4}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250|UniProtKB:Q9GZT4}; Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250|UniProtKB:Q9GZT4}; COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000250|UniProtKB:Q9QZX7};

D-serine biosynthetic process [GO:0070179]; D-serine metabolic process [GO:0070178]; L-serine metabolic process [GO:0006563]

cytoplasm [GO:0005737]

ATP binding [GO:0005524]; D-serine ammonia-lyase activity [GO:0008721]; L-serine ammonia-lyase activity [GO:0003941]; magnesium ion binding [GO:0000287]; pyridoxal phosphate binding [GO:0030170]; serine racemase activity [GO:0030378]; threonine racemase activity [GO:0018114]

PF00291;

3.40.50.1100;

Serine/threonine dehydratase family

PTM: S-nitrosylated, leading to decrease the enzyme activity. {ECO:0000250|UniProtKB:Q9QZX7}.

CATALYTIC ACTIVITY: Reaction=L-serine = D-serine; Xref=Rhea:RHEA:10980, ChEBI:CHEBI:33384, ChEBI:CHEBI:35247; EC=5.1.1.18; Evidence={ECO:0000250|UniProtKB:Q9QZX7}; CATALYTIC ACTIVITY: Reaction=L-serine = NH4(+) + pyruvate; Xref=Rhea:RHEA:19169, ChEBI:CHEBI:15361, ChEBI:CHEBI:28938, ChEBI:CHEBI:33384; EC=4.3.1.17; Evidence={ECO:0000250|UniProtKB:Q9QZX7}; CATALYTIC ACTIVITY: Reaction=D-serine = NH4(+) + pyruvate; Xref=Rhea:RHEA:13977, ChEBI:CHEBI:15361, ChEBI:CHEBI:28938, ChEBI:CHEBI:35247; EC=4.3.1.18; Evidence={ECO:0000250|UniProtKB:Q9QZX7};

FUNCTION: Catalyzes the synthesis of D-serine from L-serine. D-serine is a key coagonist with glutamate at NMDA receptors. Has dehydratase activity towards both L-serine and D-serine (By similarity). {ECO:0000250|UniProtKB:Q9QZX7}.

Bos taurus (Bovine)

A0JNM1

OSTB_BOVIN

MNYSEKLTGAPPMTEVPLELLEEMLWFFRVEDATPWNCSMFVLAALVAIISFILLGRNIQANRNQKKLPPEKQTPEVLYLAEGGNKDDKNLTSLTETLLSEKPTLAQGEMEAKCSDVPRVHLPDPQEPES

bile acid and bile salt transport [GO:0015721]; bile acid secretion [GO:0032782]; positive regulation of protein exit from endoplasmic reticulum [GO:0070863]; positive regulation of protein glycosylation [GO:0060050]; positive regulation of protein targeting to membrane [GO:0090314]; regulation of protein stability [GO:0031647]

basolateral plasma membrane [GO:0016323]; membrane [GO:0016020]; plasma membrane [GO:0005886]; protein-containing complex [GO:0032991]

bile acid transmembrane transporter activity [GO:0015125]; protein heterodimerization activity [GO:0046982]

PF15048;

OST-beta family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Note=Mainly restricted to the lateral and basal membranes of ileal enterocytes. {ECO:0000250}.

CATALYTIC ACTIVITY: Reaction=taurocholate(out) = taurocholate(in); Xref=Rhea:RHEA:71703, ChEBI:CHEBI:36257; Evidence={ECO:0000250|UniProtKB:Q86UW1}; CATALYTIC ACTIVITY: Reaction=estrone 3-sulfate(out) = estrone 3-sulfate(in); Xref=Rhea:RHEA:71835, ChEBI:CHEBI:60050; Evidence={ECO:0000250|UniProtKB:Q86UW2}; CATALYTIC ACTIVITY: Reaction=dehydroepiandrosterone 3-sulfate(out) = dehydroepiandrosterone 3-sulfate(in); Xref=Rhea:RHEA:71839, ChEBI:CHEBI:57905; Evidence={ECO:0000250|UniProtKB:Q86UW2}; CATALYTIC ACTIVITY: Reaction=tauroursodeoxycholate(out) = tauroursodeoxycholate(in); Xref=Rhea:RHEA:71843, ChEBI:CHEBI:132028; Evidence={ECO:0000250|UniProtKB:Q80WK2}; CATALYTIC ACTIVITY: Reaction=glycoursodeoxycholate(out) = glycoursodeoxycholate(in); Xref=Rhea:RHEA:71847, ChEBI:CHEBI:132030; Evidence={ECO:0000250|UniProtKB:Q80WK2}; CATALYTIC ACTIVITY: Reaction=glycocholate(out) = glycocholate(in); Xref=Rhea:RHEA:71851, ChEBI:CHEBI:29746; Evidence={ECO:0000250|UniProtKB:Q80WK2}; CATALYTIC ACTIVITY: Reaction=taurochenodeoxycholate(out) = taurochenodeoxycholate(in); Xref=Rhea:RHEA:71855, ChEBI:CHEBI:9407; Evidence={ECO:0000250|UniProtKB:Q80WK2}; CATALYTIC ACTIVITY: Reaction=glycochenodeoxycholate(out) = glycochenodeoxycholate(in); Xref=Rhea:RHEA:71859, ChEBI:CHEBI:36252; Evidence={ECO:0000250|UniProtKB:Q80WK2}; CATALYTIC ACTIVITY: Reaction=taurodeoxycholate(out) = taurodeoxycholate(in); Xref=Rhea:RHEA:71863, ChEBI:CHEBI:36261; Evidence={ECO:0000250|UniProtKB:Q80WK2}; CATALYTIC ACTIVITY: Reaction=glycodeoxycholate(out) = glycodeoxycholate(in); Xref=Rhea:RHEA:71867, ChEBI:CHEBI:82982; Evidence={ECO:0000250|UniProtKB:Q80WK2}; CATALYTIC ACTIVITY: Reaction=prostaglandin E2(out) = prostaglandin E2(in); Xref=Rhea:RHEA:50984, ChEBI:CHEBI:606564; Evidence={ECO:0000250|UniProtKB:Q90YM5};

FUNCTION: Essential component of the Ost-alpha/Ost-beta complex, a heterodimer that acts as the intestinal basolateral transporter responsible for bile acid export from enterocytes into portal blood. The Ost-alpha/Ost-beta complex efficiently transports the major species of bile acids (taurocholate). Taurine conjugates are transported more efficiently across the basolateral membrane than glycine-conjugated bile acids (By similarity). Can also transport steroids such as estrone 3-sulfate and dehydroepiandrosterone 3-sulfate, therefore playing a role in the enterohepatic circulation of sterols (By similarity). Able to transport eicosanoids such as prostaglandin E2 (By similarity). Modulates SLC51A glycosylation, membrane trafficking and stability activities (By similarity). {ECO:0000250|UniProtKB:Q80WK2, ECO:0000250|UniProtKB:Q86UW1, ECO:0000250|UniProtKB:Q90YM5}.

Bos taurus (Bovine)

A0JNT9

BICL1_MOUSE

MSAFCLGLAGRASAPAEPDSACCMELPAGAGDAVRSPATAAALVSFPGGPGELELALEEELALLAAGERSSEPGEHPQAEPESPVEGHGPPLPPPPTQDPELLSVIRQKEKDLVLAARLGKALLERNQDMSRQYEQMHKELTDKLEHLEQEKHELRRRFENREGEWEGRVSELETDVKQLQDELERQQLHLREADREKTRAVQELSEQNQRLLDQLSRASEVERQLSMQVHALKEDFREKNSSTNQHIIRLESLQAEIKMLSDRKRELEHRLSATLEENDLLQGTVEELQDRVLILERQGHDKDLQLHQSQLELQEVRLSYRQLQGKVEELTEERSLQSSAATSTSLLSEIEQSMEAEELEQEREQLRLQLWEAYCQVRYLCSHLRGNDSADSAVSTDSSMDESSETSSAKDVPAGSLRTALNDLKRLIQSIVDGVEPTVTLLSVEMTALKEERDRLRVTSEDKEPKEQLQKAIRDRDEAIAKKNAVELELAKCKMDMMSLNSQLLDAIQQKLNLSQQLEAWQDDMHRVIDRQLMDTHLKEQSRPAAAAFPRGHGVGRGQEPSTADGKRLFSFFRKI

Golgi to secretory granule transport [GO:0055107]; neuron projection development [GO:0031175]; vesicle transport along microtubule [GO:0047496]

centrosome [GO:0005813]; cytoplasm [GO:0005737]

dynactin binding [GO:0034452]; small GTPase binding [GO:0031267]

BICDR family

SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton {ECO:0000305|PubMed:36071160}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:20360680}. Note=Localizes around the centrosome.

FUNCTION: Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Predominantly recruits 2 dyneins, which increases both the force and speed of the microtubule motor (PubMed:29420470, PubMed:33734450, PubMed:36071160). Component of secretory vesicle machinery in developing neurons that acts as a regulator of neurite outgrowth. Regulates the secretory vesicle transport by controlling the accumulation of Rab6-containing secretory vesicles in the pericentrosomal region restricting anterograde secretory transport during the early phase of neuronal differentiation, thereby inhibiting neuritogenesis. {ECO:0000269|PubMed:20360680, ECO:0000269|PubMed:29420470, ECO:0000269|PubMed:33734450, ECO:0000269|PubMed:36071160}.

Mus musculus (Mouse)

A0JNU3

LPP60_MOUSE

MARAMGPERRLLAIYTGGTIGMRSEGGVLVPGRGLAAVLKTLHMFHDEEYAQAHSLPEDTLVLPPASPDQRIIYTVLECQPLFDSSDMTITEWVQIAQTIERHYAQYQGFVVIHGTDTMAFAASVLSFMLENLQKPVVLTGAQVPIHALWSDGRENLLGALLMAGQYVIPEVCLFFQNQLFRGNRTTKVDARRFAAFCSPNLPPLATVGADVTINRELVRKACGKSHLVVHSSMEPDVGLLRLYPGIPASLVRTFLQPPLKGVVMETFGSGNGPTKPDLLQELRVAAEQGLIIVNCTHCLQGAVTSDYASGMAMAGAGIVSGFDMTSEAALAKLSYVLGQPGLSLNDRKKLLAKDLRGEMTLPATDVLLQDGMLGCRVAWLLSMNGSQEADTMKDVLLPGLALAAAHAGDLDTLQAFVELDRDLNLKDYSGQTPLHVAARRGHAAVVTMLLQRGADVDARNEDGQSPLLLAVRGRHQSVIGLLRAAGARLSPQELEDVGTELCRLASRGDSEGLRAWWQAGADLGQPDYDGHCALQVAEAAGNADVVALLQSFKDSVCAQPQPH

3.1.1.47; 3.1.1.5; 3.5.1.1

asparagine metabolic process [GO:0006528]; lipid catabolic process [GO:0016042]; phospholipid metabolic process [GO:0006644]

cytosol [GO:0005829]

1-alkyl-2-acetylglycerophosphocholine esterase activity [GO:0003847]; acyltransferase activity, transferring groups other than amino-acyl groups [GO:0016747]; asparaginase activity [GO:0004067]; lysophospholipase activity [GO:0004622]; phosphatidyl phospholipase B activity [GO:0102545]

PF12796;PF00710;PF17763;

3.40.50.40;1.25.40.20;3.40.50.1170;

Asparaginase 1 family

CATALYTIC ACTIVITY: Reaction=a 1-acyl-sn-glycero-3-phosphocholine + H2O = a fatty acid + H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:15177, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:28868, ChEBI:CHEBI:58168; EC=3.1.1.5; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15178; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=H2O + L-asparagine = L-aspartate + NH4(+); Xref=Rhea:RHEA:21016, ChEBI:CHEBI:15377, ChEBI:CHEBI:28938, ChEBI:CHEBI:29991, ChEBI:CHEBI:58048; EC=3.5.1.1; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21017; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-alkyl-sn-glycero-3-phosphocholine + acetate + H(+); Xref=Rhea:RHEA:17777, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30089, ChEBI:CHEBI:30909, ChEBI:CHEBI:36707; EC=3.1.1.47; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17778; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) + hexadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40435, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:72998; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40436; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=2 1-hexadecanoyl-sn-glycero-3-phosphocholine = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40879, ChEBI:CHEBI:16870, ChEBI:CHEBI:72998, ChEBI:CHEBI:72999; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40880; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=1-octadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) + octadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40887, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:25629, ChEBI:CHEBI:73858; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40888; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = (9Z)-octadecenoate + H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40807, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:28610, ChEBI:CHEBI:30823; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40808; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-sn-glycero-3-phosphoethanolamine + H2O = H(+) + hexadecanoate + sn-glycero-3-phosphoethanolamine; Xref=Rhea:RHEA:40891, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:73004, ChEBI:CHEBI:143890; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40892; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = (9Z)-octadecenoate + H(+) + sn-glycero-3-phosphoethanolamine; Xref=Rhea:RHEA:40895, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:74971, ChEBI:CHEBI:143890; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40896; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + 1-hexadecanoyl-sn-glycero-3-phosphoethanolamine = 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40899, ChEBI:CHEBI:16870, ChEBI:CHEBI:72998, ChEBI:CHEBI:73004, ChEBI:CHEBI:73005; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40900; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine + H2O = (5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40827, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:32395, ChEBI:CHEBI:76079; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40828; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=2-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = H(+) + hexadecanoate + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40903, ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16870, ChEBI:CHEBI:76078; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40904; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=2 2-hexadecanoyl-sn-glycero-3-phosphocholine = 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40907, ChEBI:CHEBI:16870, ChEBI:CHEBI:72999, ChEBI:CHEBI:76078; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40908; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=1-O-(9Z)-octadecenoyl-2-O-acetyl-sn-glycero-3-phosphocholine + H2O = (9Z)-octadecenoate + 2-acetyl-sn-glycero-3-phosphocholine + H(+); Xref=Rhea:RHEA:41320, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30823, ChEBI:CHEBI:78044, ChEBI:CHEBI:78045; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41321; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=1-hexadecanoyl-sn-glycero-3-phosphocholine + a 1-acyl-sn-glycero-3-phospho-(1D-myo-inositol) = a 1-acyl-2-hexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol) + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:41352, ChEBI:CHEBI:16870, ChEBI:CHEBI:64771, ChEBI:CHEBI:64874, ChEBI:CHEBI:72998; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41353; Evidence={ECO:0000250|UniProtKB:O88202}; CATALYTIC ACTIVITY: Reaction=2 2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phosphocholine = 1,2-di-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + sn-glycerol 3-phosphocholine; Xref=Rhea:RHEA:40959, ChEBI:CHEBI:16870, ChEBI:CHEBI:60657, ChEBI:CHEBI:76079; Evidence={ECO:0000250|UniProtKB:O88202}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40960; Evidence={ECO:0000250|UniProtKB:O88202};

FUNCTION: Exhibits lysophospholipase, transacylase, PAF acetylhydrolase and asparaginase activities (By similarity). Can catalyze three types of transacylation reactions: (1) acyl transfer from 1-acyl-sn-glycero-3-phosphocholine (1-acyl-GPC) to the sn-1(3) positions of glycerol and 2-acylglycerol (sn-1 to -1(3) transfer), (2) acyl transfer from 1-acyl-GPC to the sn-2 positions of 1-acyl-GPC, 1-acyl-sn-glycero-3-phosphoethanolamine (1-acyl-GPE), and other lysophospholipids (sn-1 to -2 transfer) and (3) acyl transfer from 2-acyl-GPC to the sn-1 position of 2-acyl-GPC and 2-acyl-GPE (sn-2 to -1 transfer) (By similarity). Mediates the synthesis of 1-arachidonoyl species of phospholipids by transferring the arachidonoyl residue from 2-arachidonoyl lysophospholipid to the sn-1 position of 2-acyl lysophospholipid (By similarity). {ECO:0000250|UniProtKB:O88202}.

Mus musculus (Mouse)

A0JNW5

BLT3B_HUMAN

MAGIIKKQILKHLSRFTKNLSPDKINLSTLKGEGELKNLELDEEVLQNMLDLPTWLAINKVFCNKASIRIPWTKLKTHPICLSLDKVIMEMSTCEEPRSPNGPSPIATASGQSEYGFAEKVVEGISVSVNSIVIRIGAKAFNASFELSQLRIYSVNAHWEHGDLRFTRIQDPQRGEVLTFKEINWQMIRIEADATQSSHLEIMCAPVRLITNQSKIRVTLKRRLKDCNVIATKLVLILDDLLWVLTDSQLKAMVQYAKSLSEAIEKSTEQRKSMAPEPTQSSTVVASAQQVKTTQTSNAPDVNDAIVKLFNDFDVKETSHHLVISHLDLHICDDIHAKEKESNRRITGGAMQLSFTQLTIDYYPYHKAGDSCNHWMYFSDATKTKNGWANELLHEFECNVEMLKQAVKDHNVGSPPKSPTHASPQHTQTEKDYPLKGTCRTPSVLSQQSKAKLMSSSVVVRLADFNIYQVSTAEQCRSSPKSMICCNKKSLYLPQEMSAVYIEFTEYYYPDGKDFPIPSPNLYSQLNALQFTVDERSILWLNQFLLDLKQSLNQFMAVYKLNDNSKSDEHVDVRVDGLMLKFVIPSEVKSECHQDQPRAISIQSSEMIATNTRHCPNCRHSDLEALFQDFKDCDFFSKTYTSFPKSCDNFNLLHPIFQRHAHEQDTKMHEIYKGNITPQLNKNTLKTSAATDVWAVYFSQFWIDYEGMKSGKGRPISFVDSFPLSIWICQPTRYAESQKEPQTCNQVSLNTSQSESSDLAGRLKRKKLLKEYYSTESEPLTNGGQKPSSSDTFFRFSPSSSEADIHLLVHVHKHVSMQINHYQYLLLLFLHESLILLSENLRKDVEAVTGSPASQTSICIGILLRSAELALLLHPVDQANTLKSPVSESVSPVVPDYLPTENGDFLSSKRKQISRDINRIRSVTVNHMSDNRSMSVDLSHIPLKDPLLFKSASDTNLQKGISFMDYLSDKHLGKISEDESSGLVYKSGSGEIGSETSDKKDSFYTDSSSILNYREDSNILSFDSDGNQNILSSTLTSKGNETIESIFKAEDLLPEAASLSENLDISKEETPPVRTLKSQSSLSGKPKERCPPNLAPLCVSYKNMKRSSSQMSLDTISLDSMILEEQLLESDGSDSHMFLEKGNKKNSTTNYRGTAESVNAGANLQNYGETSPDAISTNSEGAQENHDDLMSVVVFKITGVNGEIDIRGEDTEICLQVNQVTPDQLGNISLRHYLCNRPVGSDQKAVIHSKSSPEISLRFESGPGAVIHSLLAEKNGFLQCHIENFSTEFLTSSLMNIQHFLEDETVATVMPMKIQVSNTKINLKDDSPRSSTVSLEPAPVTVHIDHLVVERSDDGSFHIRDSHMLNTGNDLKENVKSDSVLLTSGKYDLKKQRSVTQATQTSPGVPWPSQSANFPEFSFDFTREQLMEENESLKQELAKAKMALAEAHLEKDALLHHIKKMTVE

early endosome to Golgi transport [GO:0034498]; intermembrane lipid transfer [GO:0120009]

cytosol [GO:0005829]; early endosome [GO:0005769]

GARP complex binding [GO:0062069]; lipid transfer activity [GO:0120013]; protein homodimerization activity [GO:0042803]

PF12624;

SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:20163565}. Early endosome {ECO:0000269|PubMed:20163565, ECO:0000269|PubMed:35499567}. Note=Localizes on a subpopulation of vesicle clusters in the early endocytic pathway. {ECO:0000269|PubMed:35499567}.

FUNCTION: Tube-forming lipid transport protein which mediates the transfer of lipids between membranes at organelle contact sites (PubMed:35499567). Required for retrograde traffic of vesicle clusters in the early endocytic pathway to the Golgi complex (PubMed:20163565, PubMed:35499567). {ECO:0000269|PubMed:20163565, ECO:0000269|PubMed:35499567}.

Homo sapiens (Human)

A0JP26

POTB3_HUMAN

MVAEVCSMPAASAVKKPFDLRSKMGKWCHHRFPCCRGSGKSNMGTSGDHDDSFMKTLRSKMGKCCHHCFPCCRGSGTSNVGTSGDHDNSFMKTLRSKMGKWCCHCFPCCRGSGKSNVGTWGDYDDSAFMEPRYHVRREDLDKLHRAAWWGKVPRKDLIVMLRDTDMNKRDKQKRTALHLASANGNSEVVQLLLDRRCQLNVLDNKKRTALIKAVQCQEDECVLMLLEHGADGNIQDEYGNTALHYAIYNEDKLMAKALLLYGADIESKNKCGLTPLLLGVHEQKQQVVKFLIKKKANLNALDRYGRTALILAVCCGSASIVNLLLEQNVDVSSQDLSGQTAREYAVSSHHHVICELLSDYKEKQMLKISSENSNPEQDLKLTSEEESQRLKVSENSQPEKMSQEPEINKDCDREVEEEIKKHGSNPVGLPENLTNGASAGNGDDGLIPQRKSRKPENQQFPDTENEEYHSDEQNDTQKQLSEEQNTGISQDEILTNKQKQIEVAEKEMNSKLSLSHKKEEDLLRENSMLREEIAMLRLELDETKHQNQLRENKILEEIESVKEKLLKAIQLNEEALTKTSI

PF12796;PF14915;

1.25.40.20;

POTE family

Homo sapiens (Human)

A0JP82

TET3_XENTR

MDTQPAPVPHVLPQDVYEFPDDQESLGRLRVSEMPAELNGGGGGGSAAAFAMELPEQSNKKRKRCGVCVPCLRKEPCGACYNCVNRSTSHQICKMRKCEQLKKKRVVPMKGVENCSESILVDGPKTDQMEAGPVNHVQEGRLKQECDSTLPSKGCEDLANQLLMEANSWLSNTAAPQDPCNKLNWDKPTIPNHAANNNSNLEDAKNLVAFSAVAEAMSTYGMPASGTPSSVSLQLYEKFNYETNRDNSGHLEGNAPSCPEDLNTLKAALALAKHGVKPPNCNCDGPECPDYLEWLENKIKSTVKGSQESPFPNLGQVSKELVQKQYPKEQVLNLENKNSTCPSGNLPFSQNALSLAKEKNISLQTAIAIEALTQLSSALPQTNNECPNAPSQPLINPHDQLTHFPSAKGNQLPMLPVARNELFQNQQSQLYTGKNALPVPQSPRQTSWEQNKKSSYQEGQYIPENLSHSSSVLPSDASTPQKPEFLQQWVQNADLLKSPSDPMTGLKQLLGNTDEYIKSVFKGPEALPNKKNVKPKHTIKSIKKESTEFLKMSPDQQLSQLLQTNEFHRNTQAALQQHLHHKRNLFVDPNAMEACTQEQQNWWVPSSQQAPVSKTTEKPVKERKKRRQSPSQKQVEPKPKPQRKQVQIKKPKVKEGSAVFMPVSQISLDTFRRVEKEENQGKEMDAENSLPNNVQTELLESQSLQLTGSQANPDDRKTVNTQEMCNENQSNIGKANNFALCVNRANSFVAKDQCPTPSTHDTSSSSGQGDSANQHTNVSDVPGQNDLSCLDDKLEDLIRQFEAEFGEDFSLPGSAVPSQNGEGPPKQTPSGDPQFKLPFPSQLLPPENSTKPATHSNPALSNNPVSREVSNNLDSLFSSKSPKQIKIESSGAITVVSTTCFYSEENQHLDGTPTKSDLPFNPTLSGFLDSPLKYLTSPTKSLIDTPAKKAQAEFPTCDCVEQINEKDEGPYYTHLGSGPTVASIRELMEERFGQKGDAIRIEKVIYTGKEGKSSRGCPIAKWVIRRQSEDEKLMCLVRQRAGHHCENAVIIILIMAWEGIPRSLGDSLYNDITETITKYGNPTSRRCGLNDDRTCACQGKDPNTCGASFSFGCSWSMYFNGCKYARSKTPRKFRLIGENPKEEDGLKDNFQNLATKVAPVYKMLAPQAYQNQVNNEDIAIDCRLGLKEGRPFSGVTACMDFCAHAHKDQHNLYNGCTVVCTLTKEDNRMIGRVAEDEQLHVLPLYKVSTTDEFGSEEGQLEKIKKGGIHVLSSFPREVRKLSEPAKSCRQRQLEAKKAAAEKKKLQKEKLVSPDKTKQEPSDKKTCQQNPGVPQQQTKPCIKVEPSNHYNNFKYNGNGVVESYSVLGSCRPSDPYSMNSVYSYHSFYAQPNLPSVNGFHSKYALPPFGFYGFPNNPVVPNQFMNYGTSDARNSGWMNNCFEKKPELQSLADGMNQSYGSELSEQSFRRSSEVPHHYSLQNPSSQKSVNVPHRTTPAPVETTPYSNLPCYNKVIKKEPGSDPLVDSFQRANSVHSHSPGVNHSLQASDLPISYKANGALSSSGRTNAESPCSMFMPNDKNGLEKKDYFGVHSNAPGLKDKQWPPYGTDVSVRQHDSLDSQSPGKVWSSCKLSDSSAALPSSASTQDKNWNGRQVSLNQGMKESALFQEKLWNSVAASDRCSATPSDRSSITPCSELQDKNWGSFPNPTVNSLKTDSSQNHWDPYSLDDNMDDGQSKSVKEEDDEEIWSDSEHNFLDENIGGVAVAPGHGSILIECARRELHATTPLKKPNRCHPTRISLVFYQHKNLNQPNHGLALWEAKMKQLAERARAREEEAAKLGIKQEVKSLGKKRKWGGAATTETPPVEKKDYTPTRQAATILTDSATTSFSYAYTKVTGPYSRFI

1.14.11.80

COFACTOR: Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250|UniProtKB:Q6N021}; Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250|UniProtKB:Q6N021}; COFACTOR: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:Q6N021}; Note=The zinc ions have a structural role. {ECO:0000250|UniProtKB:Q6N021};

5-methylcytosine catabolic process [GO:0006211]; DNA demethylation [GO:0080111]; eye development [GO:0001654]; positive regulation of gene expression via CpG island demethylation [GO:0044029]; positive regulation of transcription by RNA polymerase II [GO:0045944]

chromosome [GO:0005694]; nucleus [GO:0005634]

5-methylcytosine dioxygenase activity [GO:0070579]; methyl-CpG binding [GO:0008327]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; zinc ion binding [GO:0008270]

PF12851;PF02008;

TET family

SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23217707}. Chromosome {ECO:0000269|PubMed:23217707}. Note=Detected on chromatin, where it binds to target gene promoters. {ECO:0000269|PubMed:23217707}.

CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + a 5-methyl-2'-deoxycytidine in DNA + O2 = a 5-hydroxymethyl-2'-deoxycytidine in DNA + CO2 + succinate; Xref=Rhea:RHEA:52636, Rhea:RHEA-COMP:11370, Rhea:RHEA-COMP:13315, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:85454, ChEBI:CHEBI:136731; EC=1.14.11.80; Evidence={ECO:0000269|PubMed:23217707}; CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + a 5-hydroxymethyl-2'-deoxycytidine in DNA + O2 = a 5-formyl-2'-deoxycytidine in DNA + CO2 + H2O + succinate; Xref=Rhea:RHEA:53828, Rhea:RHEA-COMP:13315, Rhea:RHEA-COMP:13656, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:136731, ChEBI:CHEBI:137731; EC=1.14.11.80; Evidence={ECO:0000250|UniProtKB:Q6N021}; CATALYTIC ACTIVITY: Reaction=2-oxoglutarate + a 5-formyl-2'-deoxycytidine in DNA + O2 = a 5-carboxyl-2'-deoxycytidine in DNA + CO2 + H(+) + succinate; Xref=Rhea:RHEA:53832, Rhea:RHEA-COMP:13656, Rhea:RHEA-COMP:13657, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031, ChEBI:CHEBI:137731, ChEBI:CHEBI:137732; EC=1.14.11.80; Evidence={ECO:0000250|UniProtKB:Q6N021};

FUNCTION: Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming during embryonic development. Conversion of 5mC into 5hmC probably constitutes the first step in cytosine demethylation. Selectively binds to the promoter region of target genes and contributes to regulate the expression of numerous developmental genes, including pax6, rax, sox9 and six3. May also contribute to the regulation of target genes in ways that do not require its enzyme activity. {ECO:0000269|PubMed:23217707}.

Xenopus tropicalis (Western clawed frog) (Silurana tropicalis)

A0JPF9

ISPD_DANRE

MGTVTIQLSCLRHIRKLCFSCPWEGRRLFKMLLQFHHETQRPLDPGCLLPQDAERSADQPGRAVVDFPVAAVLPAGGSGERMGLTTPKQFCSIFNRPLISYTIQAFERLPWIVMVVVVVAKDNHDLMLNIVRKFNHTKVKVVHGGTTRHRSIYNGLQAFSDSTDSSTPKPKVVIIHDAVRPFVEEDLLLKITLAAKEQGASGAIRPLVSTVIATTSESYLDHSLERAKYRASEMPQGFLYDIIFQAYQRCSEFDLEFGTECLHLALQYCGTNARLIEGPPTLWKVTYKRDLAAAEAIIKETLSVSACIIAEAEEEAVELAKTLQKNLNMMETDVIPCGKESNVQYLSKTRNFIHISASASSSLWVLEMVKCFEDIDHARLYPVVIVWVQLSMTKQSADSQETDEFMALASEVKQRNVLLYGIKIDHSKELEQWQRSLERLGQITLVLIRDRNMALTGQMLHV

2.7.7.40

brain morphogenesis [GO:0048854]; isoprenoid biosynthetic process [GO:0008299]; muscle cell development [GO:0055001]; protein O-linked mannosylation [GO:0035269]; regulation of protein glycosylation [GO:0060049]

cytosol [GO:0005829]

cytidylyltransferase activity [GO:0070567]; D-ribitol-5-phosphate cytidylyltransferase activity [GO:0047349]; protein homodimerization activity [GO:0042803]

PF01128;PF18706;

IspD/TarI cytidylyltransferase family, IspD subfamily

SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:A4D126}.

CATALYTIC ACTIVITY: Reaction=CTP + D-ribitol 5-phosphate + H(+) = CDP-L-ribitol + diphosphate; Xref=Rhea:RHEA:12456, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:57608, ChEBI:CHEBI:57695; EC=2.7.7.40; Evidence={ECO:0000250|UniProtKB:A4D126}; CATALYTIC ACTIVITY: Reaction=CTP + D-ribose 5-phosphate + H(+) = CDP-D-ribose + diphosphate; Xref=Rhea:RHEA:53872, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:78346, ChEBI:CHEBI:137525; Evidence={ECO:0000250|UniProtKB:A4D126}; CATALYTIC ACTIVITY: Reaction=CTP + D-ribulose 5-phosphate + H(+) = CDP-D-ribulose + diphosphate; Xref=Rhea:RHEA:53612, ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:37563, ChEBI:CHEBI:58121, ChEBI:CHEBI:137524; Evidence={ECO:0000250|UniProtKB:A4D126};

PATHWAY: Protein modification; protein glycosylation. {ECO:0000250|UniProtKB:A4D126}.

FUNCTION: Cytidylyltransferase required for protein O-linked mannosylation (PubMed:22522421). Catalyzes the formation of CDP-ribitol nucleotide sugar from D-ribitol 5-phosphate (By similarity). CDP-ribitol is a substrate of FKTN during the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (By similarity). Shows activity toward other pentose phosphate sugars and mediates formation of CDP-ribulose or CDP-ribose using CTP and ribulose-5-phosphate or ribose-5-phosphate, respectively (By similarity). Not involved in dolichol production (By similarity). {ECO:0000250|UniProtKB:A4D126, ECO:0000269|PubMed:22522421}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0JPL0

ZN382_RAT

MNCHSVPLQGPVSFKDVTVDFTQEEWQRLDPAQKALYRDVMLENYCHFISVGFHITKPDMIRKLEQGEELWTERMFPSQSYLEDEEVLVKFRDYQDKPPTSIVIINHKKLIKERNNVYEKTLGNNHIISKTLFEYKSDGKVLKNISDFISRDINPVMGTLGDSSEWEESVLTSEQEKTHPVPTLYKQIGRNLSSSLELAQHQKTQIPEQRFECDECDSSFLMTEVAFPHDRAHRGVRDFNCSKDEIAFFEKSDLGIHPHNLMEKKCSTYNKYGKLLCRKSVFVMHPRSQVDERPFQCPYCGNSFRRKSYLIEHQRIHTGEKPYICSQCGKAFRQKTALTLHEKTHTDGKPYLCVDCGKSFRQKATLTRHHKTHTGEKAYECTQCGSAFGKKSYLIDHQRTHTGEKPYQCAECGKAFIQKTTLTVHQRTHTGEKPYMCSECGKSFCQKTTLTLHQRIHTGEKPYVCSDCGKSFRQKAILTVHYRIHTGEKSNGCPQCGKAFSRKSNLIRHQKTHTGEKPYECHECGKFFSCKSNLVAHQKTHKAETVRFQ

negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; regulation of cell growth [GO:0001558]; regulation of transcription by RNA polymerase II [GO:0006357]

nucleus [GO:0005634]

DNA-binding transcription factor activity [GO:0003700]; DNA-binding transcription repressor activity, RNA polymerase II-specific [GO:0001227]; metal ion binding [GO:0046872]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]

PF01352;PF00096;

6.10.140.140;3.30.160.60;

Krueppel C2H2-type zinc-finger protein family

SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11154279, ECO:0000269|PubMed:9835615}.

FUNCTION: Functions as a sequence-specific transcriptional repressor. {ECO:0000269|PubMed:11154279, ECO:0000269|PubMed:9835615}.

Rattus norvegicus (Rat)

A0JPN2

S39A4_RAT

MMLPKSLTQGLLLAMLVGTAAMVQPYHLLSLLTSGQGALDRTALDGLLNTLVARVHCTDGPCEKCLSVETALALGKPDKPQLAPESVLESRYITYLSAAAALYLNDPEKTCKDIRAGLLASHVDDYLAKLESPEAMTLGLSQLLQKIEAHDASQPTREETCVDVPQLLEEAEEAGVSRSPGLVLTALLDHVLNGSCFQGLPSPQYFVDFVFRQLSSKPRNITLPELEDLMHHLGVGGEDHSDHGDHVDHSHLDREANHQDSELHATHNSSSSVWDTLCLSAKDVMAVYGLSEEAGVSPQAWAQLTPALVQQQLSEACSSSPIIHVQDQLSQAERYLYGSLATLLICLCAVFGLLLLTCAKCSTATHYIMQTFLSLAVGALTGDALLHLIPKVLGLHTHSGEVHSHEEESIGGQSTWRLLAVLGGFYIFFLFESFFNLLLPRDQDHEKDGPCSHGGHSHGISLQLSPSNLRQSKQPHESSRSDLVTEETPELLNPDTRRLRAELRMLPYLITLGDAVHNFADGLAVGAAFSSTWKTGLATSLAVFCHELPHELGDFAALLHAGLTVKRALLLNLASALTAFAGLYVALAVGVGEEGETWILAVATGLFLYVALCDMLPAMMNVRDQRPWLLFLLHNVGLLGGWTILLLLSLYEDSITF

cellular response to zinc ion starvation [GO:0034224]; intracellular zinc ion homeostasis [GO:0006882]; zinc ion import across plasma membrane [GO:0071578]; zinc ion transmembrane transport [GO:0071577]

apical plasma membrane [GO:0016324]; cytoplasmic vesicle [GO:0031410]; plasma membrane [GO:0005886]; recycling endosome membrane [GO:0055038]

identical protein binding [GO:0042802]; metal ion binding [GO:0046872]; monoatomic cation:bicarbonate symporter activity [GO:0140410]; zinc ion binding [GO:0008270]; zinc ion sensor activity [GO:0106219]; zinc ion sequestering activity [GO:0140486]; zinc ion transmembrane transporter activity [GO:0005385]

PF21116;PF02535;PF18292;

ZIP transporter (TC 2.A.5) family

PTM: The extracellular N-terminal ectodomain is cleaved when cells are Zn(2+) deficient, N-terminally cleaved SLC39A4 is internalized at a faster rate. {ECO:0000250|UniProtKB:Q78IQ7}.; PTM: Under excess Zn(2+) conditions, SLC39A4 on the cell surface is rapidly endocytosed, ubiquitinated and degraded. {ECO:0000250|UniProtKB:Q6P5W5}.; PTM: Glycosylated. {ECO:0000250|UniProtKB:Q6P5W5}.

SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q78IQ7}; Multi-pass membrane protein {ECO:0000250|UniProtKB:A0A0H3LM39}. Recycling endosome membrane {ECO:0000250|UniProtKB:Q78IQ7}; Multi-pass membrane protein {ECO:0000250|UniProtKB:A0A0H3LM39}. Apical cell membrane {ECO:0000250|UniProtKB:Q78IQ7}; Multi-pass membrane protein {ECO:0000250|UniProtKB:A0A0H3LM39}. Note=Colocalized with TFRC in the recycling endosomes. Cycles between endosomal compartments and the plasma membrane in response to zinc availability. Translocates to the apical membrane during zinc deficiency. Expressed on the apical surface of the intestinal wall. {ECO:0000250|UniProtKB:Q78IQ7}.

CATALYTIC ACTIVITY: Reaction=Zn(2+)(in) = Zn(2+)(out); Xref=Rhea:RHEA:29351, ChEBI:CHEBI:29105; Evidence={ECO:0000250|UniProtKB:Q6P5W5};

FUNCTION: Selective transporter that mediates the uptake of Zn(2+). Plays an essential role for dietary zinc uptake from small intestine (By similarity). The Zn(2+) uniporter activity is regulated by zinc availability. Exhibits also polyspecific binding and transport of Cu(2+), Cd(2+) and possibly Ni(2+) but at higher concentrations (By similarity). {ECO:0000250|UniProtKB:Q6P5W5, ECO:0000250|UniProtKB:Q78IQ7}.

Rattus norvegicus (Rat)

A0JPN4

ZC12A_RAT

MSDPCGKKLVQEISPTMSLWGLEDRHSCQGQPQPDQDPVAKEASASELQMKVDFFRKLGYSSSEIHSALQKLGVQADTNTVLGELVKHGSATERECQASTDPCPQPPLVPRGGSTPKPSTVEPSLPEEDKESSDLRPVVIDGSNVAMSHGNKEVFSCRGILLAVNWFLERGHTDITVFVPSWRKEQPRPDVPITDQHILRELEKKKILVFTPSRRVGGKRVVCYDDRFIVKLAYESDGVVVSNDTYRDLQGERQEWKRFIEERLLMYSFVNDKFMPPDDPLGRHGPSLDNFLRKKPLPSEHRKQPCPYGRKCTYGIKCRFFHPERPSRPQRSVADELRANALLSPPRTPVKDKSSQRPSPASQPNSMSLEAEPGSPDGKKLGTRSSPGPHQEGSTQTCAPAGRSLPVSGGSFGPTEWLPHTLDSLPYTSQECLDSGIGSLESQMSELWGLRGGSPGESGPTRGPYTGYQTYGSKLPAAPAFSPFRQAIGTGHFSVPTDYVPPPPTYPAREYWSEPYPLPPPTPVLQEPQRPRPRASGDPWGRVSDLAKERAGVYTKLCGVFPPHLVEAVMGRFPQLLDPQQLAAEILSYKSQHLSE

3.1.-.-

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:Q5D1E7}; Note=Mg(2+) is required for RNase activity. {ECO:0000250|UniProtKB:Q5D1E7};

3'-UTR-mediated mRNA destabilization [GO:0061158]; angiogenesis [GO:0001525]; apoptotic process [GO:0006915]; cell differentiation [GO:0030154]; cellular response to chemokine [GO:1990869]; cellular response to glucose starvation [GO:0042149]; cellular response to ionomycin [GO:1904637]; cellular response to lipopolysaccharide [GO:0071222]; cellular response to oxidative stress [GO:0034599]; cellular response to sodium arsenite [GO:1903936]; cellular response to tumor necrosis factor [GO:0071356]; cellular response to virus [GO:0098586]; DNA damage response [GO:0006974]; immune response-activating signaling pathway [GO:0002757]; inflammatory response [GO:0006954]; miRNA catabolic process [GO:0010587]; mRNA catabolic process [GO:0006402]; negative regulation by host of viral genome replication [GO:0044828]; negative regulation of canonical NF-kappaB signal transduction [GO:0043124]; negative regulation of cardiac muscle contraction [GO:0055118]; negative regulation of cytokine production involved in inflammatory response [GO:1900016]; negative regulation of gene expression [GO:0010629]; negative regulation of interleukin-1 beta production [GO:0032691]; negative regulation of interleukin-6 production [GO:0032715]; negative regulation of muscle cell apoptotic process [GO:0010656]; negative regulation of nitric oxide biosynthetic process [GO:0045019]; negative regulation of non-canonical NF-kappaB signal transduction [GO:1901223]; negative regulation of protein phosphorylation [GO:0001933]; negative regulation of T-helper 17 cell differentiation [GO:2000320]; negative regulation of tumor necrosis factor production [GO:0032720]; negative regulation of type II interferon production [GO:0032689]; nervous system development [GO:0007399]; positive regulation of angiogenesis [GO:0045766]; positive regulation of autophagy [GO:0010508]; positive regulation of defense response to virus by host [GO:0002230]; positive regulation of endothelial cell migration [GO:0010595]; positive regulation of execution phase of apoptosis [GO:1900119]; positive regulation of fat cell differentiation [GO:0045600]; positive regulation of gene expression [GO:0010628]; positive regulation of lipid storage [GO:0010884]; positive regulation of miRNA catabolic process [GO:2000627]; positive regulation of mRNA catabolic process [GO:0061014]; positive regulation of p38MAPK cascade [GO:1900745]; positive regulation of protein deubiquitination [GO:1903003]; positive regulation of protein import into nucleus [GO:0042307]; positive regulation of reactive oxygen species metabolic process [GO:2000379]; positive regulation of transcription by RNA polymerase II [GO:0045944]; protein complex oligomerization [GO:0051259]; regulation of gene expression [GO:0010468]; T cell receptor signaling pathway [GO:0050852]

cytoplasm [GO:0005737]; cytoplasmic ribonucleoprotein granule [GO:0036464]; cytoskeleton [GO:0005856]; nucleoplasm [GO:0005654]; nucleus [GO:0005634]; P-body [GO:0000932]; protein-containing complex [GO:0032991]; rough endoplasmic reticulum [GO:0005791]; rough endoplasmic reticulum membrane [GO:0030867]

chromatin binding [GO:0003682]; cysteine-type deubiquitinase activity [GO:0004843]; DNA binding [GO:0003677]; metal ion binding [GO:0046872]; miRNA binding [GO:0035198]; mRNA 3'-UTR AU-rich region binding [GO:0035925]; mRNA 3'-UTR binding [GO:0003730]; mRNA binding [GO:0003729]; nuclease activity [GO:0004518]; ribosome binding [GO:0043022]; RNA binding [GO:0003723]; RNA endonuclease activity [GO:0004521]; RNA exonuclease activity [GO:0004532]; RNA nuclease activity [GO:0004540]; RNA stem-loop binding [GO:0035613]

PF18561;PF11977;PF18039;

3.40.50.11980;

ZC3H12 family

PTM: Phosphorylated by IRAK1; phosphorylation is necessary for subsequent phosphorylation by the I-kappa-B-kinase (IKK) complex. Phosphorylated by I-kappa-B-kinases (IKKs) at Ser-435 and Ser-439 upon lipopolysaccharide (LPS) or IL1B stimulation in macrophages through the MyD88-dependent signaling pathway; these phosphorylations promote rapid ubiquitin proteasome-mediated degradation of ZC3H12A in macrophages and hence allows its target mRNAs, such as IL6, to escape from degradation and accumulate during the inflammatory response. {ECO:0000250|UniProtKB:Q5D1E7}.; PTM: Ubiquitinated; ubiquitination is induced in response to interleukin IL1 receptor stimuli in a IKBKB/IKKB and IRAK1-dependent manner, leading to proteasome-mediated degradation. {ECO:0000250|UniProtKB:Q5D1E7}.; PTM: Proteolytically cleaved between Arg-111 and Arg-214 by MALT1 in activated T-cells; cleavage at Arg-111 is critical for promoting ZC3H12A degradation in response to T-cell receptor (TCR) stimulation, and hence is necessary for prolonging the stability of a set of mRNAs controlling T-cell activation and Th17 cell differentiation. {ECO:0000250|UniProtKB:Q5D1E7}.

SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q5D1E7}. Cytoplasm {ECO:0000250|UniProtKB:Q5D1E7}. Rough endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q5D1E7}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q5D1E7}; Cytoplasmic side {ECO:0000250|UniProtKB:Q5D1E7}. Cytoplasmic granule {ECO:0000250|UniProtKB:Q5D1E7}. Cytoplasm, P-body {ECO:0000250|UniProtKB:Q5D1E8}. Note=Predominantly localized in the cytoplasm. Colocalizes with GW182 on many granule-like structures, probably corresponding to cytoplasmic GW bodies (GWBs), also called processing bodies (P bodies). Colocalizes with calnexin on the surface of the rough endoplasmic reticulum (RER) membrane and with translationally active polysomes. Colocalizes with ZC3H12D in cytoplasmic mRNA processing P-body, also known as GW bodies (GWBs). {ECO:0000250|UniProtKB:Q5D1E7, ECO:0000250|UniProtKB:Q5D1E8}.

FUNCTION: Endoribonuclease involved in various biological functions such as cellular inflammatory response and immune homeostasis, glial differentiation of neuroprogenitor cells, cell death of cardiomyocytes, adipogenesis and angiogenesis. Functions as an endoribonuclease involved in mRNA decay. Modulates the inflammatory response by promoting the degradation of a set of translationally active cytokine-induced inflammation-related mRNAs, such as IL6 and IL12B, during the early phase of inflammation. Prevents aberrant T-cell-mediated immune reaction by degradation of multiple mRNAs controlling T-cell activation, such as those encoding cytokines (IL6 and IL2), cell surface receptors (ICOS, TNFRSF4 and TNFR2) and transcription factor (REL). Inhibits cooperatively with ZC3H12A the differentiation of helper T cells Th17 in lungs. They repress target mRNA encoding the Th17 cell-promoting factors IL6, ICOS, REL, IRF4, NFKBID and NFKBIZ. The cooperation requires RNA-binding by RC3H1 and the nuclease activity of ZC3H12A (By similarity). Together with RC3H1, destabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR (By similarity). Self regulates by destabilizing its own mRNA. Cleaves mRNA harboring a stem-loop (SL), often located in their 3'-UTRs, during the early phase of inflammation in a helicase UPF1-dependent manner (By similarity). Plays a role in the inhibition of microRNAs (miRNAs) biogenesis (By similarity). Cleaves the terminal loop of a set of precursor miRNAs (pre-miRNAs) important for the regulation of the inflammatory response leading to their degradation, and thus preventing the biosynthesis of mature miRNAs (By similarity). Also plays a role in promoting angiogenesis in response to inflammatory cytokines by inhibiting the production of antiangiogenic microRNAs via its anti-dicer RNase activity (By similarity). Affects the overall ubiquitination of cellular proteins. Positively regulates deubiquitinase activity promoting the cleavage at 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains on TNF receptor-associated factors (TRAFs), preventing JNK and NF-kappa-B signaling pathway activation, and hence negatively regulating macrophage-mediated inflammatory response and immune homeostasis (By similarity). Induces also deubiquitination of the transcription factor HIF1A, probably leading to its stabilization and nuclear import, thereby positively regulating the expression of proangiogenic HIF1A-targeted genes. Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB activation through the deubiquitination of IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (By similarity). Prevents stress granules (SGs) formation and promotes macrophage apoptosis under stress conditions, including arsenite-induced oxidative stress, heat shock, and energy deprivation. Plays a role in the regulation of macrophage polarization; promotes IL4-induced polarization of macrophages M1 into anti-inflammatory M2 state. May also act as a transcription factor that regulates the expression of multiple genes involved in inflammatory response, angiogenesis, adipogenesis and apoptosis (By similarity). Functions as a positive regulator of glial differentiation of neuroprogenitor cells through an amyloid precursor protein (APP)-dependent signaling pathway (By similarity). Attenuates septic myocardial contractile dysfunction in response to lipopolysaccharide (LPS) by reducing I-kappa-B-kinase (IKK)-mediated NF-kappa-B activation, and hence myocardial pro-inflammatory cytokine production (By similarity). {ECO:0000250|UniProtKB:Q5D1E7, ECO:0000250|UniProtKB:Q5D1E8}.

Rattus norvegicus (Rat)

A0JPQ4

TRI72_RAT

MSTAPGLLRQELSCPLCLQLFDAPVTAECGHSFCRACLIRVAGEPADDGTVACPCCQASTRPQALSTNLQLARLVEGLAQVPQGHCEEHLDPLSIYCEQDRTLVCGVCASLGSHRGHRLLPAAEAHARLKTQLPQQKAQLQEACMRKEKSVAVLEHQLVEVEETVRQFRGAVGEQLGKMRMFLAALESSLDREAERVRGEAGVALRRELSSLNSYLEQLRQMEKVLEEVADKPQTEFLMKFCLVTSRLQKILSESPPPARLDIQLPVISDDFKFQVWKKMFRALMPELEELTFDPSSAHPSLVVSASGRRVECSEQKAPPAGEDTCQFDKTVAVVAKQLLSQGEHYWEVEVGDKPRWALGVMAADASRRGRLHAVPSQGLWLLGLRDGKILEAHVEAKEPRALRTPERPPARIGLYLSFADGVLTFYDASNTDALTPLFSFHERLPGPVYPMFDVCWHDKGKNSQPLLLVGPDSEQA

exocytosis [GO:0006887]; muscle organ development [GO:0007517]; muscle system process [GO:0003012]; negative regulation of insulin receptor signaling pathway [GO:0046627]; negative regulation of insulin-like growth factor receptor signaling pathway [GO:0043569]; negative regulation of myotube differentiation [GO:0010832]; plasma membrane repair [GO:0001778]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]; protein homooligomerization [GO:0051260]; protein ubiquitination [GO:0016567]

cytoplasm [GO:0005737]; cytoplasmic vesicle membrane [GO:0030659]; sarcolemma [GO:0042383]

identical protein binding [GO:0042802]; mitogen-activated protein kinase kinase kinase binding [GO:0031435]; phosphatidylserine binding [GO:0001786]; ubiquitin conjugating enzyme binding [GO:0031624]; ubiquitin protein ligase activity [GO:0061630]; zinc ion binding [GO:0008270]

PF13765;PF00622;PF00643;PF15227;

2.60.120.920;3.30.160.60;3.30.40.10;

TRIM/RBCC family

PTM: Disulfide bond formation at Cys-242 occurs in case of membrane damage that cause the entry of the oxidized milieu of the extracellular space, resulting in homooligomerization. {ECO:0000250}.; PTM: S-nitrosylation at Cys-144 stabilizes TRIM72 and protects against oxidation-induced protein degradation and cell death. {ECO:0000250|UniProtKB:Q6ZMU5}.

SUBCELLULAR LOCATION: Cell membrane, sarcolemma {ECO:0000250}. Cytoplasmic vesicle membrane {ECO:0000250}. Note=Tethered to plasma membrane and cytoplasmic vesicles via its interaction with phosphatidylserine. {ECO:0000250}.

FUNCTION: Muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at injury sites. Specifically binds phosphatidylserine. Acts as a sensor of oxidation: upon membrane damage, entry of extracellular oxidative environment results in disulfide bond formation and homooligomerization at the injury site. This oligomerization acts as a nucleation site for recruitment of TRIM72-containing vesicles to the injury site, leading to membrane patch formation. Probably acts upstream of the Ca(2+)-dependent membrane resealing process. Required for transport of DYSF to sites of cell injury during repair patch formation. Regulates membrane budding and exocytosis. May be involved in the regulation of the mobility of KCNB1-containing endocytic vesicles (By similarity). {ECO:0000250}.

Rattus norvegicus (Rat)

A0JQ18

SOP14_ARATH

MAAKTSNLVALLLSLFLLLLSISSQVGLGEAKRNLRNNLRLDCVSHPSPPPPHRSMAPPIFVPPSTSHKGQGP

defense response [GO:0006952]; defense response to bacterium [GO:0042742]; response to bacterium [GO:0009617]; response to cold [GO:0009409]; response to ethylene [GO:0009723]; response to jasmonic acid [GO:0009753]; response to salicylic acid [GO:0009751]; response to salt stress [GO:0009651]; response to water deprivation [GO:0009414]

apoplast [GO:0048046]; plasma membrane [GO:0005886]

LRR domain binding [GO:0030275]; receptor serine/threonine kinase binding [GO:0033612]

Serine rich endogenous peptide (SCOOP) phytocytokine family

SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:31001913}. Secreted, extracellular space, apoplast {ECO:0000269|PubMed:31001913}. Note=The precursor of SCOOP14, PROSCOOP14, accumulates at the plasma membrane and is proteolytically cleaved to release the SCOOP14 in the apoplasm. {ECO:0000269|PubMed:31001913}.

FUNCTION: Brassicaceae-specific phytocytokine (plant endogenous peptide released into the apoplast) perceived by MIK2 in a BAK1/SERK3 and SERK4 coreceptors-dependent manner, that modulates various physiological and antimicrobial processes including growth prevention and reactive oxygen species (ROS) response regulation (PubMed:31001913, PubMed:33514716, PubMed:34535661). Inhibits root growth and regulates root meristems (PubMed:31001913, PubMed:34535661). Prevents general growth and development (PubMed:31001913). Exhibits antibacterial effects against Pseudomonas syringae pv. tomato DC3000, Ralstonia solanacearum, Bacillus subtilis and Agrobacterium tumefaciens, thus being an antimicrobial peptide (AMP) (PubMed:31001913). {ECO:0000269|PubMed:31001913, ECO:0000269|PubMed:33514716, ECO:0000269|PubMed:34535661}.

Arabidopsis thaliana (Mouse-ear cress)

A0KEL1

FADB_AERHH

MIYQGETLTVSYLEDGIAELRFDAPGSVNKLDRATLLSLSEAIAALQQERELKGLILTSGKDAFIVGADITEFLELFDLPQADLLGWLKKANDIFSAIEDLPVPTLSAIKGHALGGGCETILSTDFRLADTSAKIGLPETKLGIMPGFGGTVRLPRVIGADNALEWITTGKDYRADDALKVGAIDAVVAPDALQSAAVQMIKDAVKGKLDWQGRRAAKKAPLRLSKLEAMMSFTTAAGMVAAVAGKHYPAPMTAVKTVEAAAGMSRDEALAVEAQGFIKLAKTDVAKALVGIFLNDQHIKALAKKAAKQAAKATSHAAVLGAGIMGGGIAYQSASKGIPAVMKDINEKALALGMGEATKLLNGQLEKGRIDGIKMGQVLSAITPTLSYDNVKHVDVVVEAVVENPKVKAAVLGEVEGIIGEDAVLASNTSTIPISLLAKELKRPQNFCGMHFFNPVHRMPLVEIIRGEQTSDETINRVVAYAAAMGKSPVVVNDCPGFFVNRVLFPYFFGFNKLVADGADFAAVDKVMEKEFGWPMGPAYLLDVVGIDTGHHAGDVMAQGFPARMSKEGRTAIDVMYEVNRFGQKNGKGFYAYEQDKKGKPKKVADAASYELLAPIAKPKQDFDKDAIIARMMIPMINEVVLCLEEGIVATPAEADIALVYGLGFPPFRGGVFRYLDTIGLDRYVAMADQYADLGPLYRVSDKLREMAAQGKTFY

1.1.1.35; 4.2.1.17; 5.1.2.3; 5.3.3.8

fatty acid beta-oxidation [GO:0006635]

fatty acid beta-oxidation multienzyme complex [GO:0036125]

3-hydroxyacyl-CoA dehydrogenase activity [GO:0003857]; 3-hydroxybutyryl-CoA epimerase activity [GO:0008692]; delta(3)-delta(2)-enoyl-CoA isomerase activity [GO:0004165]; enoyl-CoA hydratase activity [GO:0004300]; NAD+ binding [GO:0070403]

PF00725;PF02737;PF00378;

1.10.1040.50;3.40.50.720;

Enoyl-CoA hydratase/isomerase family; 3-hydroxyacyl-CoA dehydrogenase family

CATALYTIC ACTIVITY: Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35; Evidence={ECO:0000255|HAMAP-Rule:MF_01621}; CATALYTIC ACTIVITY: Reaction=a (3S)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O; Xref=Rhea:RHEA:16105, ChEBI:CHEBI:15377, ChEBI:CHEBI:57318, ChEBI:CHEBI:58856; EC=4.2.1.17; Evidence={ECO:0000255|HAMAP-Rule:MF_01621}; CATALYTIC ACTIVITY: Reaction=a 4-saturated-(3S)-3-hydroxyacyl-CoA = a (3E)-enoyl-CoA + H2O; Xref=Rhea:RHEA:20724, ChEBI:CHEBI:15377, ChEBI:CHEBI:58521, ChEBI:CHEBI:137480; EC=4.2.1.17; Evidence={ECO:0000255|HAMAP-Rule:MF_01621}; CATALYTIC ACTIVITY: Reaction=(3S)-3-hydroxybutanoyl-CoA = (3R)-3-hydroxybutanoyl-CoA; Xref=Rhea:RHEA:21760, ChEBI:CHEBI:57315, ChEBI:CHEBI:57316; EC=5.1.2.3; Evidence={ECO:0000255|HAMAP-Rule:MF_01621}; CATALYTIC ACTIVITY: Reaction=a (3Z)-enoyl-CoA = a 4-saturated (2E)-enoyl-CoA; Xref=Rhea:RHEA:45900, ChEBI:CHEBI:85097, ChEBI:CHEBI:85489; EC=5.3.3.8; Evidence={ECO:0000255|HAMAP-Rule:MF_01621}; CATALYTIC ACTIVITY: Reaction=a (3E)-enoyl-CoA = a 4-saturated (2E)-enoyl-CoA; Xref=Rhea:RHEA:45228, ChEBI:CHEBI:58521, ChEBI:CHEBI:85097; EC=5.3.3.8; Evidence={ECO:0000255|HAMAP-Rule:MF_01621};

PATHWAY: Lipid metabolism; fatty acid beta-oxidation. {ECO:0000255|HAMAP-Rule:MF_01621}.

FUNCTION: Involved in the aerobic and anaerobic degradation of long-chain fatty acids via beta-oxidation cycle. Catalyzes the formation of 3-oxoacyl-CoA from enoyl-CoA via L-3-hydroxyacyl-CoA. It can also use D-3-hydroxyacyl-CoA and cis-3-enoyl-CoA as substrate. {ECO:0000255|HAMAP-Rule:MF_01621}.

Aeromonas hydrophila subsp. hydrophila (strain ATCC 7966 / DSM 30187 / BCRC 13018 / CCUG 14551 / JCM 1027 / KCTC 2358 / NCIMB 9240 / NCTC 8049)

A0KLG5

BSR_AERHH

MHKKTLLATLILGLLAGQAVAAPYLPLASDHRNGEVQTASNAWLEVDLGAFEHNIQTLKDRLGDKGPKICAIMKADAYGHGIDLLVPSVVKAGIPCIGIASNEEARVAREKGFTGRLMRVRAATPAEVEQALPYKMEELIGSLVSAQGIADIAQRHHTNIPVHIALNSAGMSRNGIDLRLADSKEDALAMLKLKGITPVGIMTHFPVEEKEDVKMGLAQFKLDSQWLLEAGKLDRSKITIHAANSFATLEVPDAYFDMVRPGGLLYGDSIPSYTEYKRVMAFKTQVASVNHYPAGNTVGYDRTFTLKRDSWLANLPLGYSDGYRRALSNKAYVLIQGQKVPVVGKTSMNTIMVDVTDLKGVKPGDEVVLFGRQGEAEVKQADLEEYNGALLADMYTIWGYTNPKKIKR

5.1.1.10

COFACTOR: Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; Evidence={ECO:0000255|HAMAP-Rule:MF_02212, ECO:0000269|PubMed:24419381};

peptidoglycan biosynthetic process [GO:0009252]

cytosol [GO:0005829]; periplasmic space [GO:0042597]

alanine racemase activity [GO:0008784]; arginine racemase activity [GO:0047679]; lysine racemase activity [GO:0018113]; methionine racemase activity [GO:0018111]; pyridoxal phosphate binding [GO:0030170]; serine racemase activity [GO:0030378]

PF00842;PF01168;

3.20.20.10;

Alanine racemase family, Bsr subfamily

SUBCELLULAR LOCATION: Periplasm {ECO:0000250|UniProtKB:Q9KSE5, ECO:0000255|HAMAP-Rule:MF_02212}.

CATALYTIC ACTIVITY: Reaction=an L-alpha-amino acid = a D-alpha-amino acid; Xref=Rhea:RHEA:18317, ChEBI:CHEBI:59869, ChEBI:CHEBI:59871; EC=5.1.1.10; Evidence={ECO:0000255|HAMAP-Rule:MF_02212, ECO:0000269|PubMed:24419381}; CATALYTIC ACTIVITY: Reaction=L-lysine = D-lysine; Xref=Rhea:RHEA:22864, ChEBI:CHEBI:32551, ChEBI:CHEBI:32557; Evidence={ECO:0000255|HAMAP-Rule:MF_02212, ECO:0000269|PubMed:24419381}; CATALYTIC ACTIVITY: Reaction=L-arginine = D-arginine; Xref=Rhea:RHEA:18069, ChEBI:CHEBI:32682, ChEBI:CHEBI:32689; Evidence={ECO:0000255|HAMAP-Rule:MF_02212, ECO:0000269|PubMed:24419381}; CATALYTIC ACTIVITY: Reaction=L-alanine = D-alanine; Xref=Rhea:RHEA:20249, ChEBI:CHEBI:57416, ChEBI:CHEBI:57972; Evidence={ECO:0000269|PubMed:24419381}; CATALYTIC ACTIVITY: Reaction=L-serine = D-serine; Xref=Rhea:RHEA:10980, ChEBI:CHEBI:33384, ChEBI:CHEBI:35247; Evidence={ECO:0000269|PubMed:24419381}; CATALYTIC ACTIVITY: Reaction=L-methionine = D-methionine; Xref=Rhea:RHEA:12492, ChEBI:CHEBI:57844, ChEBI:CHEBI:57932; Evidence={ECO:0000269|PubMed:24419381}; CATALYTIC ACTIVITY: Reaction=L-leucine = D-leucine; Xref=Rhea:RHEA:59396, ChEBI:CHEBI:57427, ChEBI:CHEBI:143079; Evidence={ECO:0000269|PubMed:24419381}; CATALYTIC ACTIVITY: Reaction=L-cysteine = D-cysteine; Xref=Rhea:RHEA:59272, ChEBI:CHEBI:35235, ChEBI:CHEBI:35236; Evidence={ECO:0000269|PubMed:24419381}; CATALYTIC ACTIVITY: Reaction=L-glutamine = D-glutamine; Xref=Rhea:RHEA:59276, ChEBI:CHEBI:58000, ChEBI:CHEBI:58359; Evidence={ECO:0000269|PubMed:24419381}; CATALYTIC ACTIVITY: Reaction=L-asparagine = D-asparagine; Xref=Rhea:RHEA:59280, ChEBI:CHEBI:58048, ChEBI:CHEBI:74337; Evidence={ECO:0000269|PubMed:24419381}; CATALYTIC ACTIVITY: Reaction=L-histidine = D-histidine; Xref=Rhea:RHEA:59188, ChEBI:CHEBI:57595, ChEBI:CHEBI:142967; Evidence={ECO:0000269|PubMed:24419381};

FUNCTION: Amino-acid racemase able to utilize a broad range of substrates. Reversibly racemizes ten of the 19 natural chiral amino acids known, including both non-beta-branched aliphatic amino acids (Ala, Leu, Met, Ser, Cys, Gln and Asn) and positively charged amino acids (His, Lys and Arg). Is not active on negatively charged (Glu and Asp) or aromatic (Tyr, Trp and Phe) amino acids and displays minimal activity towards beta-branched aliphatic (Ile, Val and Thr) substrates (PubMed:24419381). Enables bacteria to produce and release extracellular non-canonical D-amino acids (NCDAAs) that regulate diverse cellular processes (By similarity). {ECO:0000250|UniProtKB:Q9KSE5, ECO:0000269|PubMed:24419381}.

Aeromonas hydrophila subsp. hydrophila (strain ATCC 7966 / DSM 30187 / BCRC 13018 / CCUG 14551 / JCM 1027 / KCTC 2358 / NCIMB 9240 / NCTC 8049)

A0KR50

FADB_SHESA

MIYQSPTIQVELLEDNIAKLCFNAPGSVNKFDRETLASLDAALDSIKQQSNIQALVLTSGKDTFIVGADITEFLGLFAQDDAVLLSWIEQANAVFNKLEDLPFPTASAIKGFALGGGCETILATDFRIADTTAKIGLPETKLGIIPGFGGTVRLPRVIGADNALEWITTGKDQRPEDALKVGAVDAVVAPEALEAAAIQMLKDAVAEKLDWQARRQRKMSPLTLPKLEAMMSFTTAKGMVFAVAGKHYPAPMAAVSVVEQAATKGRSDALQIEHQAFIKLAKTDVAKALIGIFLNDQLVKGKAKKAGKLAKDVKSAAVLGAGIMGGGIAYQSASKGTPIVMKDIAQPALDLGLGEAAKLLSAQVARGRSTPEKMAKVLNNITPALDYAPVKHADVVVEAVVEHPKVKAQVLAEVEQYVSEDAIIASNTSTISINLLAKSMKKPERFCGMHFFNPVHKMPLVEVIRGEHSSEETIASVVAYASKMGKTPIVVNDCPGFFVNRVLFPYFAGFNGLLAEGGDFAAIDKVMEKQFGWPMGPAYLLDVVGLDTGHHAQAVMAEGFPDRMGKSGNDAIDVMFENKRLGQKNGKGFYAYSVDSRGKPKKDVDPTSYELLKAAFGEQKAFDADEIIARTMIPMIIETVRCLEEGIVASPAEADMGLVYGLGFPPFRGGVFRYLDTMGVANFVALADKYAHLGGLYQVTDAMRALAANNGSYYQA

1.1.1.35; 4.2.1.17; 5.1.2.3; 5.3.3.8

fatty acid beta-oxidation [GO:0006635]

fatty acid beta-oxidation multienzyme complex [GO:0036125]

3-hydroxyacyl-CoA dehydrogenase activity [GO:0003857]; 3-hydroxybutyryl-CoA epimerase activity [GO:0008692]; delta(3)-delta(2)-enoyl-CoA isomerase activity [GO:0004165]; enoyl-CoA hydratase activity [GO:0004300]; NAD+ binding [GO:0070403]

PF00725;PF02737;PF00378;

1.10.1040.50;3.40.50.720;

Enoyl-CoA hydratase/isomerase family; 3-hydroxyacyl-CoA dehydrogenase family

CATALYTIC ACTIVITY: Reaction=a (3S)-3-hydroxyacyl-CoA + NAD(+) = a 3-oxoacyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:22432, ChEBI:CHEBI:15378, ChEBI:CHEBI:57318, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:90726; EC=1.1.1.35; Evidence={ECO:0000255|HAMAP-Rule:MF_01621}; CATALYTIC ACTIVITY: Reaction=a (3S)-3-hydroxyacyl-CoA = a (2E)-enoyl-CoA + H2O; Xref=Rhea:RHEA:16105, ChEBI:CHEBI:15377, ChEBI:CHEBI:57318, ChEBI:CHEBI:58856; EC=4.2.1.17; Evidence={ECO:0000255|HAMAP-Rule:MF_01621}; CATALYTIC ACTIVITY: Reaction=a 4-saturated-(3S)-3-hydroxyacyl-CoA = a (3E)-enoyl-CoA + H2O; Xref=Rhea:RHEA:20724, ChEBI:CHEBI:15377, ChEBI:CHEBI:58521, ChEBI:CHEBI:137480; EC=4.2.1.17; Evidence={ECO:0000255|HAMAP-Rule:MF_01621}; CATALYTIC ACTIVITY: Reaction=(3S)-3-hydroxybutanoyl-CoA = (3R)-3-hydroxybutanoyl-CoA; Xref=Rhea:RHEA:21760, ChEBI:CHEBI:57315, ChEBI:CHEBI:57316; EC=5.1.2.3; Evidence={ECO:0000255|HAMAP-Rule:MF_01621}; CATALYTIC ACTIVITY: Reaction=a (3Z)-enoyl-CoA = a 4-saturated (2E)-enoyl-CoA; Xref=Rhea:RHEA:45900, ChEBI:CHEBI:85097, ChEBI:CHEBI:85489; EC=5.3.3.8; Evidence={ECO:0000255|HAMAP-Rule:MF_01621}; CATALYTIC ACTIVITY: Reaction=a (3E)-enoyl-CoA = a 4-saturated (2E)-enoyl-CoA; Xref=Rhea:RHEA:45228, ChEBI:CHEBI:58521, ChEBI:CHEBI:85097; EC=5.3.3.8; Evidence={ECO:0000255|HAMAP-Rule:MF_01621};

PATHWAY: Lipid metabolism; fatty acid beta-oxidation. {ECO:0000255|HAMAP-Rule:MF_01621}.

FUNCTION: Involved in the aerobic and anaerobic degradation of long-chain fatty acids via beta-oxidation cycle. Catalyzes the formation of 3-oxoacyl-CoA from enoyl-CoA via L-3-hydroxyacyl-CoA. It can also use D-3-hydroxyacyl-CoA and cis-3-enoyl-CoA as substrate. {ECO:0000255|HAMAP-Rule:MF_01621}.

Shewanella sp. (strain ANA-3)

A0LFF8

MDH_SYNFM

MAKKPVRVTVTGAAGQIGYALLFRVASGQMLGPDQPIILQMLELPIDKVQAALKGVMMELEDCAFPLLADMIGTGDPKVAFKDSDYALLVGARPRGPGMERKDLLLENAKIFIEQGKAMNAVASRDIRVIVVGNPANTNAWIAMKSAPDLPKGNFTAMLRLDHNRAKSQLATRTGKPVASVEKMIVWGNHSPTMYPDIRFCTVDGQPAVKLVNDEAWYRNEYIPKVGKRGAAIIEARGLSSAASAANAAIDHMHDWALGTNGKWVTMGLPSDGSYGIPEGTMYGVPVTCTPGKYERVKGLEIDAFSREKMDFTLKELTEEQAGVKEMVK

1.1.1.37

malate metabolic process [GO:0006108]; NADH metabolic process [GO:0006734]; oxaloacetate metabolic process [GO:0006107]; tricarboxylic acid cycle [GO:0006099]

L-malate dehydrogenase activity [GO:0030060]

PF02866;PF00056;

3.90.110.10;3.40.50.720;

LDH/MDH superfamily, MDH type 2 family

CATALYTIC ACTIVITY: Reaction=(S)-malate + NAD(+) = H(+) + NADH + oxaloacetate; Xref=Rhea:RHEA:21432, ChEBI:CHEBI:15378, ChEBI:CHEBI:15589, ChEBI:CHEBI:16452, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.37; Evidence={ECO:0000255|HAMAP-Rule:MF_01517, ECO:0000269|PubMed:8900056};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=50 uM for oxaloacetate (at 37 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:8900056}; KM=30 uM for NADH (at 37 degrees Celsius and pH 7.5) {ECO:0000269|PubMed:8900056}; KM=4 mM for L-malate (at 37 degrees Celsius and pH 9.0) {ECO:0000269|PubMed:8900056}; KM=1.1 mM for NAD (at 37 degrees Celsius and pH 9.0) {ECO:0000269|PubMed:8900056};

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 8.5 with oxaloacetate as substrate. {ECO:0000269|PubMed:8900056};

BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 60 degrees Celsius with oxaloacetate as substrate. {ECO:0000269|PubMed:8900056};

FUNCTION: Catalyzes the reversible oxidation of malate to oxaloacetate. Catalyzes the reduction of oxaloacetate more efficiently than the oxidation of malate. {ECO:0000269|PubMed:8900056}.

Syntrophobacter fumaroxidans (strain DSM 10017 / MPOB)

A0LNN5

SFMCT_SYNFM

MADQQTTMPRWVPLLLGLLGSTTCGMLLYAWSVFIKPLNAEFGWSRAEIAMAFAICCLIFGLMTFPAGRLSDKMGPRKVVMTGGVLLAIGFILSGFIQSKYQLYITYGVIAGFGGGMIYLPPIATAPKWWPDRRALATGFAVVGLGLGSFLMGPLATYIIEKPGMGWRYVFWYCGVAMGIMALIAGAFLEPPPAGWKPAGYTPPAPPAGAAAPKVTRDWTYEEAKGDTKFWLLYLAYFCGSFAGLMVIGHLAGFGRDAGLTAMAAAGAVSSLAFSNAATRILSGWFVDKIGIRVYFAALFALQTAAMIAIFQLGGSVVGLSIVAIVIGWNYGAMFTLFPATCLQFYGPTAQGSNYGLLFTACGLAGFAGPWVGGWLKDTTGTYYLPFLCAAALCALGTAIVFMTKPPEKKHA

plasma membrane [GO:0005886]

symporter activity [GO:0015293]

PF07690;

1.20.1250.20;

Major facilitator superfamily, Monocarboxylate porter (TC 2.A.1.13) family

SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:31201333}; Multi-pass membrane protein {ECO:0000255}.

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=233 uM for L-lactate {ECO:0000269|PubMed:31201333};

FUNCTION: Proton-coupled L-lactate specific transporter. {ECO:0000269|PubMed:31201333}.

Syntrophobacter fumaroxidans (strain DSM 10017 / MPOB)

A0LU48

DOP_ACIC1

MHRVMGIETEYGISVPHQPNANAMAASSQVVNAYAPIGAPAQRQARWDFEEENPLRDARGFEVAREAADPSQLTDEDLGLANVILTNGARLYVDHAHPEYSTPEVTNPRDAVLWDKAGERIMAEAARRAADLPMGWTIQLYKNNTDNKGASYGCHENYLMNRSTPFADIVRHLIPFFVTRQVFCGAGRVGIGADGRGEGFQLSQRADFFEVEVGLETTLKRPIINTRDEPHADPEKYRRLHVIIGDANMSEIATYLKLGTTALVLAMIEDGFLSQDFSVESPVGALRAVSHDPTLRYQLRLHDGRRLTAVQLQMEYLEQARKYVEDRFGTDVDDMTRDVLDRWETTLVRLADDPMQLSRDLDWVAKLSILEGYRQRENLPWSAHKLQLVDLQYHDVRPDRGLYNRLVARGRMNLLVDEAAVRTAMHEPPNDTRAYFRGRCLAKFGAEIAAASWDSVIFDLPGRDSLQRVPTLEPLRGTRAHVGDLLDRCRSATELVAALTGGR

3.4.-.-

COFACTOR: Name=ATP; Xref=ChEBI:CHEBI:30616; Evidence={ECO:0000250}; Note=ATP is required for the deamidation and depupylation reactions but is not hydrolyzed during the reactions. {ECO:0000250};

modification-dependent protein catabolic process [GO:0019941]; proteasomal protein catabolic process [GO:0010498]; protein pupylation [GO:0070490]

ATP binding [GO:0005524]; hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides [GO:0016811]; metal ion binding [GO:0046872]; peptidase activity [GO:0008233]

PF03136;

Pup ligase/Pup deamidase family, Pup deamidase subfamily

PATHWAY: Protein degradation; proteasomal Pup-dependent pathway.

FUNCTION: Displays depupylase (DPUP) activity, removing conjugated Pup from target proteins; is thus involved in the recycling of Pup and may function similarly to deubiquitinases (DUBs) in eukaryotes to prevent or promote proteasomal degradation of certain proteins. Is also able to catalyze the deamidation of the C-terminal glutamine to glutamate in a variant of the prokaryotic ubiquitin-like protein Pup; however, since Pup from A.cellulolyticus possesses a C-terminal glutamate, this deamidase activity may be of no significance in vivo. {ECO:0000269|PubMed:22910360}.

Acidothermus cellulolyticus (strain ATCC 43068 / DSM 8971 / 11B)

A0M8Q6

IGLC7_HUMAN

GQPKAAPSVTLFPPSSEELQANKATLVCLVSDFNPGAVTVAWKADGSPVKVGVETTKPSKQSNNKYAASSYLSLTPEQWKSHRSYSCRVTHEGSTVEKTVAPAECS

adaptive immune response [GO:0002250]; B cell receptor signaling pathway [GO:0050853]; immunoglobulin mediated immune response [GO:0016064]

extracellular region [GO:0005576]; extracellular space [GO:0005615]; IgA immunoglobulin complex [GO:0071745]; IgD immunoglobulin complex [GO:0071738]; IgE immunoglobulin complex [GO:0071742]; IgG immunoglobulin complex [GO:0071735]; IgM immunoglobulin complex [GO:0071753]; plasma membrane [GO:0005886]

antigen binding [GO:0003823]

PF07654;

2.60.40.10;

SUBCELLULAR LOCATION: Secreted {ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}. Cell membrane {ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}.

FUNCTION: Constant region of immunoglobulin light chains. Immunoglobulins, also known as antibodies, are membrane-bound or secreted glycoproteins produced by B lymphocytes. In the recognition phase of humoral immunity, the membrane-bound immunoglobulins serve as receptors which, upon binding of a specific antigen, trigger the clonal expansion and differentiation of B lymphocytes into immunoglobulins-secreting plasma cells. Secreted immunoglobulins mediate the effector phase of humoral immunity, which results in the elimination of bound antigens (PubMed:20176268, PubMed:22158414). The antigen binding site is formed by the variable domain of one heavy chain, together with that of its associated light chain. Thus, each immunoglobulin has two antigen binding sites with remarkable affinity for a particular antigen. The variable domains are assembled by a process called V-(D)-J rearrangement and can then be subjected to somatic hypermutations which, after exposure to antigen and selection, allow affinity maturation for a particular antigen (PubMed:17576170, PubMed:20176268). {ECO:0000303|PubMed:17576170, ECO:0000303|PubMed:20176268, ECO:0000303|PubMed:22158414}.

Homo sapiens (Human)

A0M8R5

CAV2_PAPAN

MGLETEKADVQLFMDDDSYSHHSGLEYADPEKFADSGQDRDPHRLNSHLKLGFEDVIAEPVTTHSFDKVWICSHALFEISKYVMYKFLTVFLAIPLAFIAGILFATLSCLHIWILMPFVKTCLMVLPSVQTIWKSVTDVFIAPLCTSIGRSFSSVSLQLSQD

caveola assembly [GO:0070836]; endoplasmic reticulum organization [GO:0007029]; insulin receptor signaling pathway [GO:0008286]; mitochondrion organization [GO:0007005]; negative regulation of endothelial cell proliferation [GO:0001937]; positive regulation of dopamine receptor signaling pathway [GO:0060161]; positive regulation of MAPK cascade [GO:0043410]; regulation of cytosolic calcium ion concentration [GO:0051480]; skeletal muscle fiber development [GO:0048741]; vesicle docking [GO:0048278]; vesicle fusion [GO:0006906]

caveola [GO:0005901]; cytoplasmic vesicle [GO:0031410]; focal adhesion [GO:0005925]; Golgi membrane [GO:0000139]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane raft [GO:0044853]; sarcolemma [GO:0042383]

D1 dopamine receptor binding [GO:0031748]; molecular adaptor activity [GO:0060090]; protein kinase binding [GO:0019901]

PF01146;

Caveolin family

PTM: Phosphorylated on serine and tyrosine residues. CAV1 promotes phosphorylation on Ser-23 which then targets the complex to the plasma membrane, lipid rafts and caveolae. Phosphorylation on Ser-36 appears to modulate mitosis in endothelial cells (By similarity). Phosphorylation on both Tyr-19 and Tyr-27 is required for insulin-induced 'Ser-727' phosphorylation of STAT3 and its activation. Phosphorylation on Tyr-19 is required for insulin-induced phosphorylation of MAPK1 and DNA binding of STAT3. Tyrosine phosphorylation is induced by both EGF and insulin (By. similarity). {ECO:0000250}.

SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Golgi apparatus membrane; Peripheral membrane protein. Cell membrane; Peripheral membrane protein. Membrane, caveola; Peripheral membrane protein. Note=Potential hairpin-like structure in the membrane. Membrane protein of caveolae. Tyr-19-phosphorylated form is enriched at sites of cell-cell contact and is translocated to the nucleus in complex with MAPK1 in response to insulin (By similarity). Tyr-27-phosphorylated form is located both in the cytoplasm and plasma membrane. CAV1-mediated Ser-23-phosphorylated form locates to the plasma membrane. Ser-36-phosphorylated form resides in intracellular compartments. {ECO:0000250}.

FUNCTION: May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. Acts as an accessory protein in conjunction with CAV1 in targeting to lipid rafts and driving caveolae formation. The Ser-36 phosphorylated form has a role in modulating mitosis in endothelial cells. Positive regulator of cellular mitogenesis of the MAPK signaling pathway. Required for the insulin-stimulated nuclear translocation and activation of MAPK1 and STAT3, and the subsequent regulation of cell cycle progression (By similarity). {ECO:0000250}.

Papio anubis (Olive baboon)

A0M8R6

CAV1_PAPAN

MSGGKYVDSEGHLYTVPIREQGNIYKPNNKAMADELSEKQVYDAHTKEIDLVNRDPKHLNDDVVKIDFEDVIAEPEGTHSFDGIWKASFTTFTVTKYWFYRLLSALFGIPMALVWGIYFAILSFLHIWAVVPCIKSFLIEIQCISRVYSIYVHTVCDPLFEAVGKIFSNVRINLQKEI

caveola assembly [GO:0070836]; cell differentiation [GO:0030154]; negative regulation of endothelial cell proliferation [GO:0001937]; receptor internalization [GO:0031623]; regulation of cytosolic calcium ion concentration [GO:0051480]; T cell costimulation [GO:0031295]

caveola [GO:0005901]; endosome [GO:0005768]; focal adhesion [GO:0005925]; Golgi membrane [GO:0000139]; membrane raft [GO:0045121]; perinuclear region of cytoplasm [GO:0048471]; sarcolemma [GO:0042383]

molecular adaptor activity [GO:0060090]; oxysterol binding [GO:0008142]; protein kinase binding [GO:0019901]; transmembrane transporter binding [GO:0044325]

PF01146;

Caveolin family

PTM: Phosphorylated at Tyr-14 by ABL1 in response to oxidative stress. {ECO:0000250|UniProtKB:Q03135}.; PTM: Ubiquitinated. Undergo monoubiquitination and multi- and/or polyubiquitination. Monoubiquitination of N-terminal lysines promotes integration in a ternary complex with UBXN6 and VCP which promotes oligomeric CAV1 targeting to lysosomes for degradation. Ubiquitinated by ZNRF1; leading to degradation and modulation of the TLR4-mediated immune response. {ECO:0000250|UniProtKB:Q03135}.

SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Membrane, caveola {ECO:0000250|UniProtKB:P49817}; Peripheral membrane protein {ECO:0000250}. Membrane raft {ECO:0000250|UniProtKB:Q03135}. Note=Colocalized with DPP4 in membrane rafts. Potential hairpin-like structure in the membrane. Membrane protein of caveolae (By similarity). {ECO:0000250}.

FUNCTION: May act as a scaffolding protein within caveolar membranes. Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the recruitment of CAVIN proteins (CAVIN1/2/3/4) to the caveolae (By similarity). Interacts directly with G-protein alpha subunits and can functionally regulate their activity (By similarity). Involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (By similarity). Recruits CTNNB1 to caveolar membranes and may regulate CTNNB1-mediated signaling through the Wnt pathway (By similarity). Negatively regulates TGFB1-mediated activation of SMAD2/3 by mediating the internalization of TGFBR1 from membrane rafts leading to its subsequent degradation (By similarity). Binds 20(S)-hydroxycholesterol (20(S)-OHC) (By similarity). {ECO:0000250|UniProtKB:P49817, ECO:0000250|UniProtKB:Q03135}.

Papio anubis (Olive baboon)

A0M8R7

MET_PAPAN

MKAPAVLVPGILVLLFTLVQRSNGECKEALAKSEMNVNMKYQLPNFTAETAIQNVILHEHHIFLGATNYIYVLNEEDLQKVAEYKTGPVLEHPDCFPCQDCSSKANLSGGVWKDNINMALVVDTYYDDQLISCGSVNRGTCQRHVFPHNHTADIQSEVHCIFSPQIEEPSQCPDCVVSALGAKVLSSVKDRFINFFVGNTINSSYFPHHPLHSISVRRLKETKDGFMFLTDQSYIDVLPEFRDSYPIKYIHAFESNNFIYFLTVQRETLNAQTFHTRIIRFCSLNSGLHSYMEMPLECILTEKRKKRSTKKEVFNILQAAYVSKPGAQLARQIGASLNDDILFGVFAQSKPDSAEPMDRSAMCAFPIKYVNDFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEARRDEYRAEFTTALQRVDLFMGQFSEVLLTSISTFVKGDLTIANLGTSEGRFMQVVVSRSGPSTPHVNFLLDSHPVSPEVIVEHPLNQNGYTLVVTGKKITKIPLNGLGCRHFQSCSQCLSAPPFVQCGWCHDKCVRSEECPSGTWTQQICLPAIYKVFPTSAPLEGGTRLTICGWDFGFRRNNKFDLKKTRVLLGNESCTLTLSESTMNILKCTVGPAMNKHFNMSIIISNGHGTTQYSTFSYVDPIITSISPKYGPMAGGTLLTLTGNYLNSGNSRHISIGGKTCTLKSVSNSILECYTPAQTISTEFAVKLKIDLANRETSIFSYREDPIVYEIHPTKSFISGGSTITGVGKNLHSVSVPRMVINVHEAGRNFTVACQHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGILSKYFDLIYVHNPVFKPFEKPVMISMGNENVLEIKGNDIDPEAVKGEVLKVGNKSCENIHLHSEAVLCTVPNDLLKLNSELNIEWKQAISSTVLGKVIVQPDQNFTGLIAGVVSISIALLLLLGLFLWLKKRKQIKDLGSELVRYDARVHTPHLDRLVSARSVSPTTEMVSNESVDYRATFPEDQFPNSSQNGSCRQVQYPLTDMSPILTSGDSDISSPLLQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHFNEVIGRGHFGCVYHGTLLDNDGKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVLSLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKFVHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCWHPKAEMRPSFSELVSRISAIFSTFIGEHYVHVNATYVNVKCVAPYPSLLSSEDNADDEVDT

2.7.10.1

phosphorylation [GO:0016310]; positive chemotaxis [GO:0050918]; positive regulation of endothelial cell chemotaxis [GO:2001028]; semaphorin-plexin signaling pathway [GO:0071526]; semaphorin-plexin signaling pathway involved in axon guidance [GO:1902287]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]

membrane [GO:0016020]; semaphorin receptor complex [GO:0002116]

ATP binding [GO:0005524]; semaphorin receptor activity [GO:0017154]; transmembrane receptor protein tyrosine kinase activity [GO:0004714]

PF07714;PF01437;PF01403;PF01833;

2.60.40.10;1.10.510.10;2.130.10.10;

Protein kinase superfamily, Tyr protein kinase family

PTM: Autophosphorylated in response to ligand binding on Tyr-1234 and Tyr-1235 in the kinase domain leading to further phosphorylation of Tyr-1349 and Tyr-1356 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365. Dephosphorylated by PTPN1 and PTPN2 (By similarity). {ECO:0000250|UniProtKB:P08581}.; PTM: Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:P08581}.; PTM: O-mannosylation of IPT/TIG domains by TMEM260 is required for protein maturation. O-mannosylated residues are composed of single mannose glycans that are not elongated or modified. {ECO:0000250|UniProtKB:P08581}.

SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.

CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};

FUNCTION: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells (By similarity). {ECO:0000250}.

Papio anubis (Olive baboon)

A0M8S6

CAV2_FELCA

MGLETEKADVQLFMDDDSYSRHSGVDYADPDKFADSGSDRDPHRLNSNLKVGFEDVIAEPVSTHSFDKVWICSHALFEISKYVIYKFLTLFLAIPLAFAAGILFATLSCLHIWIIMPFVKTCLMVLPSVQTIWKSITDVVIAPLCTSVGRSFSSVSLQLSHD

caveola assembly [GO:0070836]; cell differentiation [GO:0030154]; endoplasmic reticulum organization [GO:0007029]; insulin receptor signaling pathway [GO:0008286]; mitochondrion organization [GO:0007005]; negative regulation of endothelial cell proliferation [GO:0001937]; positive regulation of dopamine receptor signaling pathway [GO:0060161]; positive regulation of MAPK cascade [GO:0043410]; regulation of cytosolic calcium ion concentration [GO:0051480]; skeletal muscle fiber development [GO:0048741]; vesicle docking [GO:0048278]; vesicle fusion [GO:0006906]

caveola [GO:0005901]; cytoplasmic vesicle [GO:0031410]; focal adhesion [GO:0005925]; Golgi apparatus [GO:0005794]; Golgi membrane [GO:0000139]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; plasma membrane raft [GO:0044853]; sarcolemma [GO:0042383]

D1 dopamine receptor binding [GO:0031748]; molecular adaptor activity [GO:0060090]; protein kinase binding [GO:0019901]

PF01146;

Caveolin family

PTM: Phosphorylated on serine and tyrosine residues. CAV1 promotes phosphorylation on Ser-23 which then targets the complex to the plasma membrane, lipid rafts and caveolae. Phosphorylation on Ser-36 appears to modulate mitosis in endothelial cells (By similarity). Phosphorylation on both Tyr-19 and Tyr-27 is required for insulin-induced 'Ser-727' phosphorylation of STAT3 and its activation. Phosphorylation on Tyr-19 is required for insulin-induced phosphorylation of MAPK1 and DNA binding of STAT3. Tyrosine phosphorylation is induced by both EGF and insulin (By. similarity). {ECO:0000250}.

SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}. Golgi apparatus membrane; Peripheral membrane protein. Cell membrane; Peripheral membrane protein. Membrane, caveola; Peripheral membrane protein. Note=Potential hairpin-like structure in the membrane. Membrane protein of caveolae. Tyr-19-phosphorylated form is enriched at sites of cell-cell contact and is translocated to the nucleus in complex with MAPK1 in response to insulin (By similarity). Tyr-27-phosphorylated form is located both in the cytoplasm and plasma membrane. CAV1-mediated Ser-23-phosphorylated form locates to the plasma membrane. Ser-36-phosphorylated form resides in intracellular compartments. {ECO:0000250}.

FUNCTION: May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. Acts as an accessory protein in conjunction with CAV1 in targeting to lipid rafts and driving caveolae formation. The Ser-36 phosphorylated form has a role in modulating mitosis in endothelial cells. Positive regulator of cellular mitogenesis of the MAPK signaling pathway. Required for the insulin-stimulated nuclear translocation and activation of MAPK1 and STAT3, and the subsequent regulation of cell cycle progression (By similarity). {ECO:0000250}.

Felis catus (Cat) (Felis silvestris catus)

A0M8S7

CAV1_FELCA

MSGGKYVDSEGHLYTVPIREQGNIYKPNNKAMAEEINEKQVYDAHTKEIDLVNRDPKHLNDDVVKIDFEDVIAEPEGTHSFDGIWKASFTTFTVTKYWFYRLLSALFGIPMALIWGIYFAILSFLHIWAVVPCIKSFLIEIQCISRVYSIYVHTFCDPFFEAVGKIFSNIRINMQKEI

caveola assembly [GO:0070836]; cell differentiation [GO:0030154]; negative regulation of endothelial cell proliferation [GO:0001937]; receptor internalization [GO:0031623]; regulation of cytosolic calcium ion concentration [GO:0051480]; T cell costimulation [GO:0031295]

caveola [GO:0005901]; cytoplasmic vesicle [GO:0031410]; endosome [GO:0005768]; focal adhesion [GO:0005925]; Golgi apparatus [GO:0005794]; Golgi membrane [GO:0000139]; membrane raft [GO:0045121]; perinuclear region of cytoplasm [GO:0048471]; sarcolemma [GO:0042383]

molecular adaptor activity [GO:0060090]; oxysterol binding [GO:0008142]; protein kinase binding [GO:0019901]; transmembrane transporter binding [GO:0044325]

PF01146;

Caveolin family

PTM: Phosphorylated at Tyr-14 by ABL1 in response to oxidative stress. {ECO:0000250|UniProtKB:Q03135}.; PTM: Ubiquitinated. Undergo monoubiquitination and multi- and/or polyubiquitination. Monoubiquitination of N-terminal lysines promotes integration in a ternary complex with UBXN6 and VCP which promotes oligomeric CAV1 targeting to lysosomes for degradation. Ubiquitinated by ZNRF1; leading to degradation and modulation of the TLR4-mediated immune response. {ECO:0000250|UniProtKB:Q03135}.

SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Membrane, caveola {ECO:0000250|UniProtKB:P49817}; Peripheral membrane protein {ECO:0000250}. Membrane raft {ECO:0000250|UniProtKB:Q03135}. Note=Colocalized with DPP4 in membrane rafts. Potential hairpin-like structure in the membrane. Membrane protein of caveolae (By similarity). {ECO:0000250}.

FUNCTION: May act as a scaffolding protein within caveolar membranes. Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the recruitment of CAVIN proteins (CAVIN1/2/3/4) to the caveolae (By similarity). Interacts directly with G-protein alpha subunits and can functionally regulate their activity (By similarity). Involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (By similarity). Recruits CTNNB1 to caveolar membranes and may regulate CTNNB1-mediated signaling through the Wnt pathway (By similarity). Negatively regulates TGFB1-mediated activation of SMAD2/3 by mediating the internalization of TGFBR1 from membrane rafts leading to its subsequent degradation (By similarity). Binds 20(S)-hydroxycholesterol (20(S)-OHC) (By similarity). {ECO:0000250|UniProtKB:P49817, ECO:0000250|UniProtKB:Q03135}.

Felis catus (Cat) (Felis silvestris catus)

A0M8S8

MET_FELCA

MKAPAVLAPGILVLLFTLVQKSYGECREALVKSEMNVNMKYQLPNFTAETPIQNVVLHKHHIYLGAVNYIYVLNDKDLQKVAEYKTGPVLEHPDCFPCQDCSHKANLSGGVWKDNINMALLIDTYYDDQLISCGSVHRGTCQRHVLPPSNTADILSKVHCMYSPQADEESSHCPDCVVSALGTKVLISEKGRFINFFVGNTINSSYLTDHSLHSISVRRLKETQDGFKFLTDQSYIDVLPEFRDSYPIKYIHAFESNRFIYFLTVQRETLDAQTFHTRIIRFCSVDSGLHSYMEMPLECILTEKRRKRSTREEVFNILQAAYVSKPGAHLAKQIGANLNDDILYGVFAQSKPDSAEPMNRSAVCAFPIKYVNEFFNKIVNKNNVRCLQHFYGPNHEHCFNRTLLRNSSGCEVRSDEYRTEFTTALQRVDLFMGQFNQVLLTSISTFIKGDLTIANLGTSEGRFMQVVVSRSGSSTPHVNFRLDSHPVSSEAIVEHPLNQNGYTLVVTGKKITKIPLNGLGCEHFQSCSQCLSAPPFVQCGWCHDKCVQLEECPSGTWTQEICLPTIYEVFPTSAPLEGGTMLTVCGWDFGFRRNNKFDLKKTRVFLGNESCTLTLSESTTNMLKCTVGPAVNEHFNISIIISNGRGTAQYSTFSYVDPVITSIFPSYGPKTGGTLLTLTGKYLNSGNSRHISIGGKTCTLKSVSDSILECYTPAQTIPTEFPIKLKIDLANREMNSFSYQEDPIVYAIHPTKSFISGGSTITAVGKNLNSVSVLRMVISVHETRRNFTVACHHRSNSEIICCTTPSLQQLNLQLPLKTKAFFMLDGIHSKYFDLIYVHNPVFKPFEKPVMISIGNENVLEIKGNDIDPEAVKGEVLKVGNKSCETIYSDSEAVLCKVPNDLLKLNNELNIEWKQAVSSTILGKVIVQPDQNFTGLIVGVISISIILLLLLGVFLWLKKRKQIKDLGSELVRYDARVHTPHLDRLVSARSVSPTTEMVSNESVDYRATFPEDQFPNSSQNGSCRQVQYPLTDLSPMLNSGDSDISSPLLQNTVHIDLSALNPELVQAVQHVVIGPSSLIVHFNEVIGRGHFGCVYHGTLLDSDDKKIHCAVKSLNRITDIGEVSQFLTEGIIMKDFSHPNVLSLLGICLRSEGSPLVVLPYMKHGDLRNFIRNETHNPTVKDLIGFGLQVAKGMKYLASKKFVHRDLAARNCMLDEKFTVKVADFGLARDMYDKEYYSVHNKTGAKLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVNTFDITVYLLQGRRLLQPEYCPDPLYEVMLKCWHPKAELRPSFSELVSRISAIFSTFIGEHYVHVNATYVNVKCVAPYPSLLSSQDNIDGEGDT

2.7.10.1

branching morphogenesis of an epithelial tube [GO:0048754]; cell migration [GO:0016477]; endothelial cell morphogenesis [GO:0001886]; establishment of skin barrier [GO:0061436]; liver development [GO:0001889]; negative regulation of hydrogen peroxide-mediated programmed cell death [GO:1901299]; negative regulation of Rho protein signal transduction [GO:0035024]; negative regulation of stress fiber assembly [GO:0051497]; negative regulation of thrombin-activated receptor signaling pathway [GO:0070495]; nervous system development [GO:0007399]; neuron differentiation [GO:0030182]; pancreas development [GO:0031016]; phagocytosis [GO:0006909]; phosphorylation [GO:0016310]; positive chemotaxis [GO:0050918]; positive regulation of endothelial cell chemotaxis [GO:2001028]; positive regulation of microtubule polymerization [GO:0031116]; positive regulation of transcription by RNA polymerase II [GO:0045944]; semaphorin-plexin signaling pathway [GO:0071526]; semaphorin-plexin signaling pathway involved in axon guidance [GO:1902287]

basal plasma membrane [GO:0009925]; receptor complex [GO:0043235]; semaphorin receptor complex [GO:0002116]

ATP binding [GO:0005524]; hepatocyte growth factor receptor activity [GO:0005008]; identical protein binding [GO:0042802]; protein phosphatase binding [GO:0019903]; semaphorin receptor activity [GO:0017154]

PF07714;PF01437;PF01403;PF01833;

2.60.40.10;1.10.510.10;2.130.10.10;

Protein kinase superfamily, Tyr protein kinase family

PTM: Autophosphorylated in response to ligand binding on Tyr-1235 and Tyr-1236 in the kinase domain leading to further phosphorylation of Tyr-1350 and Tyr-1357 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1350 and Tyr-1366. Dephosphorylated by PTPN1 and PTPN2 (By similarity). {ECO:0000250|UniProtKB:P08581}.; PTM: Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:P08581}.; PTM: O-mannosylation of IPT/TIG domains by TMEM260 is required for protein maturation. O-mannosylated residues are composed of single mannose glycans that are not elongated or modified. {ECO:0000250|UniProtKB:P08581}.

SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.

CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};

FUNCTION: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells (By similarity). {ECO:0000250}.

Felis catus (Cat) (Felis silvestris catus)

A0MD28

RPOA_PRRSS

MSGTFSRCMCTPAARVFWNAGQVFCTRCLSARPLLSPELQDTDLGVVGLFYKPKDKIHWKVPIGIPQVECTPSGCCWLSAVFPLARMTSGNHNFLQRLVKVADVLYRDGCLAPRHLRELQVYERGCSWYPITGPVPGMGLFANSMHVSDQPFPGATHVLTNSPLPQRACRQPFCPFEEAHSDVYRWKKFVIFTDSSPNGRFRMMWTPESDDSAALEVLPPELERQVEILTRSFPAHHPINLADWELTESPENGFSFGTSHSCGHIVQNPNVFDGKCWLTCFLGQSAEVCYHEEHLANALGYQTKWGVHGKYLQRRLQVRGMRAVVDPDGPIHVEALSCSQSWVRHLTLNNDVTPGFVRLTSIRIVSNTEPTAFRIFRFGAHKWYGAAGKRARAKRATKSGKDSALAPKIAPPVPTCGITTYSPPTDGSCGWHVLAAIVNRMINGDFTSPLPQYNRPEDDWASDYDLAQAIQCLQLPATVVRNRACPNAKYLIKLNGVHWEVEVRSGMAPRSLSRECVVGVCSEGCVAPPYPADGLPKRALEALASAYRLPSDCVSSGIADFLADPPPQEFWTLDKMLTSPSPERSGFSSLYKLLLEVVPQKCGATEGAFVYAVERMLKDCPSPEQAMALLAKIKVPSSKAPSVSLDECFPAGVPADFEPAFQERPRSPGAAVALCSPDAKGFEGTASEEAQESGHKAVHAVPLAEGPNNEQVQVVAGEQLELGGCGLAIGSAQSSSDSKRENMHNSREDEPLDLSHPAPAATTTLVGEQTPDNPGSDASALPIAVRGFVPTGPILRHVEHCGTESGDSSSPLDLSFAQTLDQPLDLSLAAWPVKATASDPGWVRGRCEPVFLKPRKAFSDGDSALQFGELSESSSVIEFDQTKDTLVADAPVDLTTSNEALSAVDPSEFVELRRPRHSAQALIDRGGPLADVHAKIKNRVYEQCLQACEPGSRATPATREWLDKMWDRVDMKTWRCTSQFQAGRILASLKFLPDMIQDTPPPVPRKNRASDNAGLKQLVARWDKKLSVTPPPKSAGLVLDQTVPPPTDIQQEDATPSDGLSHASDFSSRVSTSWSWKGLMLSGTRLAGSAGQRLMTWVFEVYSHLPAFILTLFSPRGSMAPGDWLFAGVVLLALLLCRSYPILGCLPLLGVFSGSLRRVRLGVFGSWMAFAVFLFSTPSNPVGSSCDHDSPECHAELLALEQRQLWEPVRGLVVGPSGLLCVILGKLLGGSRHLWHVILRLCMLTDLALSLVYVVSQGRCHKCWGKCIRTAPAEVALNVFPFSRATRNSLTSLCDRFQTPKGVDPVHLATGWRGCWRGESPIHQPHQKPIAYANLDEKKISAQTVVAVPYDPSQAIKCLKVLQAGGAIVDQPTPEVVRVSEIPFSAPFFPKVPVNPDCRIVVDSDTFVAAVRCGYSTAQLVLGRGNFAKLNQTPLRDSASTKTTGGASYTLAVAQVSVWTLVHFILGLWFTSPQVCGRGTADPWCSNPFSYPAYGPGVVCSSRLCVSADGVTLPLFSAVAQLSGREVGIFILVLVSLTALAHRLALKADMLVVFSAFCAYAWPMSSWLICFFPILLKWVTLHPLTMLWVHSFLVFCMPAAGILSLGITGLLWAVGRFTQVAGIITPYDIHQYTSGPRGAAAVATAPEGTYMAAVRRAALTGRTLIFTPSAVGSLLEGAFRTHKPCLNTVNVVGSSLGSGGVFTIDGRKTVVTAAHVLNGDTARVTGDSYNRMHTFKTSGDYAWSHADDWQGVAPVVKVAKGYRGRAYWQTSTGVEPGVIGEGFAFCFTNCGDSGSPVISESGDLIGIHTGSNKLGSGLVTTPEGETCAIKETKLSDLSRHFAGPSVPLGDIKLSPAIVPDVTSIPSDLASLLASVPVMEGGLSTVQLLCVFFLLWRMMGHAWTPIVAVGFFLLNEILPAVLVRAVFSFALFILAWATPWSAQVLMIRLLTASLNRNKLSLAFYALGGVVGLAAEIGAFAGRLPELSQALSTYCFLPRVLAMASYVPIIIIGGLHALGVILWLFKYRCLHNMLVGDGSFSSAFFLRYFAEGNLRKGVSQSCGMSNESLTAALACKLSQADLDFLSSLTNFKCFVSASNMKNAAGQYIEAAYAKALRQELASLVQVDKMKGILSKLEAFAETATPSLDAGDVVVLLGQHPHGSILDINVGTERKTVSVQETRSLGGSKFSVCTVVSNTPVDALTGIPLQTPTPLFENGPRHRGEEDDLRVERMKKHCVSLGFHNINGKVYCKIWDKSTGDTFYTDDSRYTQDLAFQDRSADYRDRDYEGVQTAPQQGFDPKSETPIGTVVIGGITYNRYLIKGKEVLVPKPDNCLEAAKLSLEQALAGMGQTCDLTAAEVEKLRRIISQLQGLTTEQALNCLLAASGLTRCGRGGLVVTETAVKIVKYHSRTFTLGPLDLKVTSEAEVKKSTEQGHAVVANLCSGVILMRPHPPSLVDVLLKPGLDTKPGIQPGHGAGNMGVDGSTWDFETAPTKAELELSKQIIQACEVRRGDAPNLQLPYKLYPVRGDPERHGGRLINTRFGDLSYKTPQDTKSAIHAACCLHPNGAPVSDGKSTLGTTLQHGFELYVPTVPYSVMEYLDSRPDTPFMCTKHGTSKAAAEDLQKYDLSTQGFVLPGVLRLVRRFIFGHIGKAPPLFLPSTYPAKNSMAGINGQRFPTKDVQSIPEIDEMCARAVKENWQTVTPCTLKKQYCSKPKTRTILGTNNFIALAHRSALSGVTQAFMKKAWKSPIALGKNKFKELHCTVAGRCLEADLASCDRSTPAIVRWFVANLLYELAGCEEYLPSYVLNCCHDLVATQDGAFTKRGGLSSGDPVTSVSNTVYSLIIYAQHMVLSALKMGHEIGLKFLEEQLKFEDLLEIQPMLVYSDDLVLYAERPTFPNYHWWVEHLDLMLGFRTDPKKTVITDKPSFLGCRIEAGRQLVPNRDRILAALAYHMKAQNASEYYASAAAILMDSCACIDHDPEWYEDLICGIARCARQDGYSFPGPAFFMSMWEKLRSHNEGKKFRHCGICDAKADHASACGLDLCLFHSHFHQHCPVTLSCGHHAGSRECSQCQSPVGAGRSPLDAVLKQIPYKPPRTVIMKVGNKTTALDPGRYQSRRGLVAVKRGIAGNEVDLPDGDYQVVPLLPTCKDINMVKVACNVLLSKFIVGPPGSGKTTWLLSQVQDDDVIYTPTHQTMFDIVSALKVCRYSIPGASGLPFPPPARSGPWVRLVASGHVPGRTSYLDEAGYCNHLDILRLLSKTPLVCLGDLQQLHPVGFDSYCYVFDQMPQKQLTTIYRFGPNICAAIQPCYREKLESKARNTRVVFTTWPVAFGQVLTPYHKDRIGSAITIDSSQGATFDIVTLHLPSPKSLNKSRALVAITRARHGLFIYDPHNQLQEFFNLIPERTDCNLVFSRGDDLVVLSADNAVTTVAKALGTGPSRFRVSDPRCKSLLAACSASLEGSCMPLPQVAHNLGFYFSPDSPAFAPLPKELAPHWPVVTHQNNRAWPDRLVASMRPIDARYSKPMVGAGYVVGPSTFLGTPGVVSYYLTLYIRGEPQALPETLVSTGRIATDCREYLDAAEEEAAKELPHAFIGDVKGTTVGGCHHITSKYLPRTLPKDSVAVVGVSSPGRAAKAMCTLTDVYLPELRPYLQPETASKCWKLKLDFRDVRLMVWKGATAYFQLEGLTWSALPDYARFIQLPKDAVVYIDPCIGPATANRKVVRTTDWRADLAVTPYDYGAQNILTTAWFEDLGPQWKILGLQPFRRAFGFENTEDWAILARRMSDGKDYTDYNWDCVRERPHAIYGRARDHTYHFAPGTELQVELGKPRLPPGREP

2.7.7.48; 3.4.19.12; 3.4.21.-; 3.4.22.-; 3.6.4.12; 3.6.4.13; 4.6.1.-

DNA-templated transcription [GO:0006351]; proteolysis [GO:0006508]; symbiont-mediated perturbation of host protein ubiquitination [GO:0039648]; symbiont-mediated suppression of host ISG15-protein conjugation [GO:0039579]; symbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT1 activity [GO:0039563]; symbiont-mediated suppression of host PKR/eIFalpha signaling [GO:0039580]; symbiont-mediated suppression of host type I interferon-mediated signaling pathway [GO:0039502]; viral protein processing [GO:0019082]; viral RNA genome replication [GO:0039694]; virus-mediated perturbation of host defense response [GO:0019049]

host cell endoplasmic reticulum [GO:0044165]; host cell membrane [GO:0033644]; host cell nucleus [GO:0042025]; host cell perinuclear region of cytoplasm [GO:0044220]; membrane [GO:0016020]

ATP binding [GO:0005524]; ATP hydrolysis activity [GO:0016887]; cysteine-type deubiquitinase activity [GO:0004843]; cysteine-type endopeptidase activity [GO:0004197]; endonuclease activity [GO:0004519]; lyase activity [GO:0016829]; protein serine/threonine kinase inhibitor activity [GO:0030291]; RNA binding [GO:0003723]; RNA helicase activity [GO:0003724]; RNA nuclease activity [GO:0004540]; RNA-dependent RNA polymerase activity [GO:0003968]; serine-type endopeptidase activity [GO:0004252]; zinc ion binding [GO:0008270]

PF16749;PF14757;PF14758;PF05410;PF05411;PF05412;PF05579;PF00680;PF01443;

3.90.70.160;4.10.80.390;3.30.1330.220;2.30.31.30;3.90.70.70;3.40.50.300;3.90.70.60;2.40.10.10;

Arteriviridae polyprotein family

PTM: [Replicase polyprotein 1ab]: Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. Nsp1 is autocleaved into two subunits, Nsp1-alpha and Nsp1-beta. There are two alternative pathways for processing. Either nsp4-5 is cleaved, which represents the major pathway or the nsp5-6 and nsp6-7 are processed, which represents the minor pathway. The major pathway occurs when nsp2 acts as a cofactor for nsp4. {ECO:0000269|PubMed:22258855}.

SUBCELLULAR LOCATION: [Nsp1]: Host nucleus {ECO:0000250|UniProtKB:Q04561}. Host cytoplasm {ECO:0000250|UniProtKB:Q04561}.; SUBCELLULAR LOCATION: [Nsp1-alpha papain-like cysteine proteinase]: Host nucleus {ECO:0000250|UniProtKB:Q04561}. Host cytoplasm {ECO:0000250|UniProtKB:Q04561}.; SUBCELLULAR LOCATION: [Nsp1-beta papain-like cysteine proteinase]: Host nucleus {ECO:0000250|UniProtKB:A6YQT5}. Host cytoplasm {ECO:0000250|UniProtKB:A6YQT5}. Note=Accumulates mainly in the host cytoplasm in early infection and then mostly in the host nucleus. {ECO:0000250|UniProtKB:A6YQT5}.; SUBCELLULAR LOCATION: [Nsp2 cysteine proteinase]: Host cytoplasm {ECO:0000269|PubMed:23043113}. Host membrane {ECO:0000250|UniProtKB:Q04561}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q04561}.; SUBCELLULAR LOCATION: [Non-structural protein 5-6-7]: Host endoplasmic reticulum {ECO:0000250|UniProtKB:Q04561}. Host membrane {ECO:0000250|UniProtKB:Q04561}; Multi-pass membrane protein {ECO:0000250|UniProtKB:Q04561}.; SUBCELLULAR LOCATION: [Serine protease nsp4]: Host cytoplasm {ECO:0000250|UniProtKB:Q04561}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm {ECO:0000250|UniProtKB:Q04561}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:Q04561}.; SUBCELLULAR LOCATION: [Helicase nsp10]: Host cytoplasm {ECO:0000250|UniProtKB:Q04561}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:Q04561}.; SUBCELLULAR LOCATION: [Uridylate-specific endoribonuclease nsp11]: Host cytoplasm {ECO:0000250|UniProtKB:Q04561}. Host nucleus {ECO:0000250|UniProtKB:Q04561}.; SUBCELLULAR LOCATION: [Non-structural protein 12]: Host cytoplasm {ECO:0000250|UniProtKB:Q04561}.

CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: [Helicase nsp10]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12; Evidence={ECO:0000250|UniProtKB:Q04561}; CATALYTIC ACTIVITY: [Helicase nsp10]: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000250|UniProtKB:Q04561}; CATALYTIC ACTIVITY: [Nsp2 cysteine proteinase]: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000250|UniProtKB:Q04561}; CATALYTIC ACTIVITY: [Uridylate-specific endoribonuclease nsp11]: Reaction=uridylyl-uridylyl-ribonucleotide-RNA = a 3'-end uridylyl-2',3'-cyclophospho-uridine-RNA + a 5'-end dephospho-ribonucleoside-RNA; Xref=Rhea:RHEA:67732, Rhea:RHEA-COMP:13936, Rhea:RHEA-COMP:17334, Rhea:RHEA-COMP:17335, ChEBI:CHEBI:138284, ChEBI:CHEBI:173079, ChEBI:CHEBI:173080; Evidence={ECO:0000250|UniProtKB:P19811};

FUNCTION: [Replicase polyprotein 1ab]: Contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.; FUNCTION: [Nsp1-alpha papain-like cysteine proteinase]: Inhibits host IFN-beta production. Plays a role in the degradation of the host transcriptional activator CREBBP protein. The degradation of host CREBBP which is a key component of the IFN enhanceosome is likely responsible for the inhibition of interferon mediated by Nsp1-alpha. Participates also in the inhibition of host NF-kappa-B activation by counteracting LUBAC-dependent induction of NF-kappa-B. Reduces host NEMO ubiquitination by blocking the interaction between the two LUBAC complex components RNF31 and SHARPIN. {ECO:0000250|UniProtKB:Q04561}.; FUNCTION: [Nsp1-beta papain-like cysteine proteinase]: Plays a role in blocking host mRNA nuclear export to the cytoplasm and subversion of host protein synthesis (By similarity). Additionally, inhibits the interferon-activated JAK/STAT signal transduction by mediating the ubiquitination and subsequent proteasomal degradation of host KPNA1 (By similarity). Repurposes the host antiviral stress granules into a proviral platform to counteract the EIF2AK2/PKR restriction, thereby regulating the host inflammatory response (By similarity). {ECO:0000250|UniProtKB:A6YQT5, ECO:0000250|UniProtKB:Q04561, ECO:0000250|UniProtKB:Q9WJB2}.; FUNCTION: [Nsp2 cysteine proteinase]: Multifunctional protein that acts as a viral protease and as a viral antagonist of host immune response (PubMed:20504922, PubMed:22258253). Cleaves the nsp2/nsp3 site in the viral polyprotein. Displays deubiquitinating activity that cleaves both ubiquitinated and ISGylated products and therefore inhibits ubiquitin and ISG15-dependent host innate immunity (PubMed:20504922, PubMed:22258253). Deubiquitinates also host NFKBIA, thereby interfering with NFKBIA degradation and impairing subsequent NF-kappa-B activation (PubMed:20504922). {ECO:0000269|PubMed:20504922, ECO:0000269|PubMed:22258253}.; FUNCTION: [Non-structural protein 3]: Plays a role in the inhibition of the immune response by interacting with host IFITM1. This interaction leads to the proteasomal degradation of the IFN-induced antiviral protein IFITM1. {ECO:0000250|UniProtKB:Q04561}.; FUNCTION: [Serine protease nsp4]: Cleaves the majority of cleavage sites present in the C-terminus of the polyprotein. Triggers host apoptosis through caspase-3, -8, and -9 activations. Subverts host innate immune responses through its protease activity. Targets the NF-kappa-B essential modulator NEMO and mediates its cleavage. Blocks host interferon beta induction and downstream signaling by cleaving mitochondrial MAVS, dislodging it from the mitochondria. Impairs host defense by cleaving host mRNA-decapping enzyme DCP1A to attenuate its antiviral activity. {ECO:0000250|UniProtKB:Q04561}.; FUNCTION: [Non-structural protein 5-6-7]: Plays a role in the initial induction of autophagosomes from host reticulum endoplasmic. {ECO:0000250|UniProtKB:Q04561}.; FUNCTION: [Non-structural protein 5]: Plays a role in the inhibition of host STAT3 signaling pathway by inducing the degradation of STAT3. {ECO:0000250|UniProtKB:Q04561}.; FUNCTION: [RNA-directed RNA polymerase]: Responsible for replication and transcription of the viral RNA genome. {ECO:0000250|UniProtKB:Q04561}.; FUNCTION: [Helicase nsp10]: Displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. {ECO:0000250|UniProtKB:Q04561}.; FUNCTION: [Uridylate-specific endoribonuclease nsp11]: Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, PKR (By similarity) and NLRP3 inflammasome (By similarity). Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) (By similarity). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors (By similarity). Also plays a role in the inhibition of host type I interferon production by recruiting host OTULIN to promote removal of linear ubiquitination targeting host NEMO (By similarity). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000250|UniProtKB:P19811, ECO:0000250|UniProtKB:Q04561}.

Porcine reproductive and respiratory syndrome virus (isolate Pig/United States/SD 01-08/2001) (PRRSV)

A0MES8

ABI4_ARATH

MDPLASQHQHNHLEDNNQTLTHNNPQSDSTTDSSTSSAQRKRKGKGGPDNSKFRYRGVRQRSWGKWVAEIREPRKRTRKWLGTFATAEDAARAYDRAAVYLYGSRAQLNLTPSSPSSVSSSSSSVSAASSPSTSSSSTQTLRPLLPRPAAATVGGGANFGPYGIPFNNNIFLNGGTSMLCPSYGFFPQQQQQQNQMVQMGQFQHQQYQNLHSNTNNNKISDIELTDVPVTNSTSFHHEVALGQEQGGSGCNNNSSMEDLNSLAGSVGSSLSITHPPPLVDPVCSMGLDPGYMVGDGSSTIWPFGGEEEYSHNWGSIWDFIDPILGEFY

abscisic acid-activated signaling pathway [GO:0009738]; defense response [GO:0006952]; ethylene-activated signaling pathway [GO:0009873]; lateral root development [GO:0048527]; mitochondria-nucleus signaling pathway [GO:0031930]; positive regulation of DNA-templated transcription [GO:0045893]; regulation of L-ascorbic acid biosynthetic process [GO:2000082]; regulation of protein localization [GO:0032880]; regulation of stomatal movement [GO:0010119]; regulation of triglyceride catabolic process [GO:0010896]; response to glucose [GO:0009749]; response to osmotic stress [GO:0006970]; response to sucrose [GO:0009744]; response to trehalose [GO:0010353]; response to water deprivation [GO:0009414]; root meristem growth [GO:0010449]; seed development [GO:0048316]; starch catabolic process [GO:0005983]; sugar mediated signaling pathway [GO:0010182]

nucleus [GO:0005634]

DNA binding [GO:0003677]; DNA-binding transcription factor activity [GO:0003700]; sequence-specific DNA binding [GO:0043565]; transcription cis-regulatory region binding [GO:0000976]

PF00847;

3.30.730.10;

AP2/ERF transcription factor family, ERF subfamily

SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00366, ECO:0000255|PROSITE-ProRule:PRU00768, ECO:0000269|PubMed:24451981}.

FUNCTION: Transcription regulator that probably binds to the GCC-box pathogenesis-related promoter element. Binds also to the S-box (5'-CACTTCCA-3') photosynthesis-associated nuclear genes-related (PhANGs-related) promoter element, and thus acts as a transcription inhibitor. Involved in the regulation of gene expression by stress factors and by components of stress signal transduction pathways. May have a function in the deetiolation process. Confers sensitivity to abscisic acid (ABA), and regulates the ABA signaling pathway during seed germination, upon nitrate-mediated lateral root inhibition, in hexokinase-dependent sugar responses (including feed-back regulation of photosynthesis and mobilization of storage lipid during germination), and in response to osmotic stress mediated by NaCl, KCl or mannitol. Plays a role in sucrose sensing or signaling, especially at low fluence far red light. Also involved in plant response to glucose treatment, especially at low concentration and in young seedlings. Required for the trehalose-mediated root inhibition and starch accumulation in cotyledons, probably by inhibiting starch breakdown. However, seems to not be involved in sugar-mediated senescence. Required for the ABA-dependent beta-amino-butyric acid (BABA) signaling pathway. BABA primes ABA synthesis and promotes resistance to drought and salt, and leads to a prime callose accumulation that confers resistance against necrotrophic pathogens such as A.brassicicola and P.cucumerina. Seems to be involved in resistance to S.sclerotiorum probably by regulating the ABA-mediated stomatal closure apparently by antagonistic interaction with oxalate. Negative regulator of low water potential-induced Pro accumulation whose effect is decreased by high levels of sugar. {ECO:0000269|PubMed:10629000, ECO:0000269|PubMed:10950871, ECO:0000269|PubMed:10972884, ECO:0000269|PubMed:10972885, ECO:0000269|PubMed:11115891, ECO:0000269|PubMed:11172073, ECO:0000269|PubMed:11439129, ECO:0000269|PubMed:11851911, ECO:0000269|PubMed:11996676, ECO:0000269|PubMed:12136027, ECO:0000269|PubMed:12529517, ECO:0000269|PubMed:12857824, ECO:0000269|PubMed:15053765, ECO:0000269|PubMed:15118859, ECO:0000269|PubMed:15502012, ECO:0000269|PubMed:16098105, ECO:0000269|PubMed:16113213, ECO:0000269|PubMed:16339784, ECO:0000269|PubMed:16844907, ECO:0000269|PubMed:17031512, ECO:0000269|PubMed:9144963, ECO:0000269|PubMed:9418043, ECO:0000269|PubMed:9634591}.

Arabidopsis thaliana (Mouse-ear cress)

A0MGZ7

H6S3B_DANRE

MNDKPNKWIFIPILAILFVMIGYQYVCPAGGQACHFRTGDKLVRIAPLATPDPTTDDLYREQDPEEDNPPKCASKFNFTERDLTRDVDFNIKGDDVIVFLHIQKTGGTTFGRHLVRNIRLEQPCDCKAGQKKCTCHRPGKQESWLFSRFSTGWSCGLHADWTELTNCVPVIMDKRQPPKRKRNFYYITMLRDPVSRYLSEWKHVQRGATWKTSLHMCDGRSPTQDELPTCYNGDDWSGVTLHDFMDCPSNLANNRQVRMLADLSLVGCYNLSTMNESERNPILLASAKSNLKNMAFYGLTEFQRKTQYLFERTFHLRFISAFTQINSTRAANVELRDDMRSRIEQLNMLDMQLYEFAKDLFLQRYQFVRQRERQEERLKRREERRWIRERRVNQSKEPIVENQTRVTTTEDYASQVVRW

2.8.2.-

heparan sulfate proteoglycan biosynthetic process, enzymatic modification [GO:0015015]

membrane [GO:0016020]

3'-phosphoadenosine 5'-phosphosulfate binding [GO:0050656]; heparan sulfate 6-O-sulfotransferase activity [GO:0017095]; oligosaccharide binding [GO:0070492]; sulfotransferase activity [GO:0008146]

PF03567;

3.40.50.300;

Sulfotransferase 6 family

SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass type II membrane protein {ECO:0000255}.

CATALYTIC ACTIVITY: Reaction=3'-phosphoadenylyl sulfate + alpha-D-glucosaminyl-[heparan sulfate](n) = 6-sulfo-alpha-D-glucosaminyl-[heparan sulfate](n) + adenosine 3',5'-bisphosphate + H(+); Xref=Rhea:RHEA:56604, Rhea:RHEA-COMP:9830, Rhea:RHEA-COMP:14621, ChEBI:CHEBI:15378, ChEBI:CHEBI:58339, ChEBI:CHEBI:58343, ChEBI:CHEBI:58388, ChEBI:CHEBI:140604; Evidence={ECO:0000269|PubMed:28103688};

FUNCTION: 6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate. {ECO:0000269|PubMed:28103688}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0MLS4

GHRL_PAPHA

MPSPGTVCSLLLLGMLWLDLAMAGSSFLSPEHQRAQQRKESKKPPAKLQPRALGGWLRPEDGDQAEGAEDELEIQFNAPFDVGIKLSGVQYQQHSQALGKFLQDILWEEAKEAPADK

actin polymerization or depolymerization [GO:0008154]; decidualization [GO:0046697]; dendrite development [GO:0016358]; gastric acid secretion [GO:0001696]; negative regulation of apoptotic process [GO:0043066]; negative regulation of endothelial cell proliferation [GO:0001937]; negative regulation of inflammatory response [GO:0050728]; negative regulation of insulin secretion [GO:0046676]; negative regulation of interleukin-1 beta production [GO:0032691]; negative regulation of interleukin-6 production [GO:0032715]; negative regulation of tumor necrosis factor production [GO:0032720]; positive regulation of cytosolic calcium ion concentration [GO:0007204]; positive regulation of growth hormone secretion [GO:0060124]; positive regulation of insulin secretion [GO:0032024]; positive regulation of MAPK cascade [GO:0043410]; positive regulation of response to food [GO:0032097]; positive regulation of synapse assembly [GO:0051965]; regulation of cell population proliferation [GO:0042127]; regulation of response to food [GO:0032095]; response to estrogen [GO:0043627]; response to hormone [GO:0009725]

axon [GO:0030424]; extracellular region [GO:0005576]; extracellular space [GO:0005615]

ghrelin receptor binding [GO:0031768]; growth hormone-releasing hormone activity [GO:0016608]; hormone activity [GO:0005179]; protein tyrosine kinase activator activity [GO:0030296]

PF04643;PF04644;

Motilin family

PTM: O-octanoylated by GOAT/MBOAT4 (By similarity). O-octanoylation is essential for ghrelin activity. {ECO:0000250, ECO:0000250|UniProtKB:Q9EQX0}.; PTM: Amidation of Leu-98 is essential for obestatin activity. {ECO:0000250}.

SUBCELLULAR LOCATION: Secreted {ECO:0000250}.

FUNCTION: [Ghrelin]: Ghrelin is the ligand for growth hormone secretagogue receptor type 1 (GHSR). Induces the release of growth hormone from the pituitary. Has an appetite-stimulating effect, induces adiposity and stimulates gastric acid secretion. Involved in growth regulation (By similarity). {ECO:0000250}.; FUNCTION: [Obestatin]: Obestatin may be the ligand for GPR39. May have an appetite-reducing effect resulting in decreased food intake. May reduce gastric emptying activity and jejunal motility (By similarity). {ECO:0000250}.

Papio hamadryas (Hamadryas baboon)

A0MLS5

BMAL1_HORSE

MADQRMDISSTISDFMSPGATDLLSSPLGTSGMDCNRKRKGSSTDYQESMDTDKDDPHGRLEYTEHQGRIKNAREAHSQIEKRRRDKMNSFIDELASLVPTCNAMSRKLDKLTVLRMAVQHMKTLRGATNPYTEANYKPTFLSDDELKHLILRAADGFLFVVGCDRGKILFVSESVFKILNYSQNDLIGQSLFDYLHPKDIAKVKEQLSSSDTAPRERLIDAKTGLPVKTDITPGPSRLCSGARRSFFCRMKCNRPSVKVEDKDFPSTCSKKKADRKSFCTIHSTGYLKSWPPTKMGLDEDNEPDNEGCNLSCLVAIGRLHSHVVPQPVNGEIRVKSMEYVSRHAIDGKFVFVDQRATAILAYLPQELLGTSCYEYFHQDDIGHLAECHRQVLQTREKITTNCYKFKIKDGSFITLRSRWFSFMNPWTKEVEYIVSTNTVVLANVLEGGDPTFPQLTASPHSMDSMLPSGEGGPKRTHPTVPGIPGGTRAGAGKIGRMIAEEVMEIHRIRGSSPSSCGSSPLNITSTPPPDASSPGGKKILNGGTPDIPSSGLPPGQAQENPGYPYSDSSSILGENPHIGIDMIDNDQGSSSPSNDEAAMAVIMSLLEADAGLGGPVDFSDLPWPL

circadian regulation of gene expression [GO:0032922]; circadian rhythm [GO:0007623]; negative regulation of DNA-templated transcription [GO:0045892]; negative regulation of fat cell differentiation [GO:0045599]; negative regulation of glucocorticoid receptor signaling pathway [GO:2000323]; negative regulation of TOR signaling [GO:0032007]; oxidative stress-induced premature senescence [GO:0090403]; positive regulation of canonical Wnt signaling pathway [GO:0090263]; positive regulation of circadian rhythm [GO:0042753]; positive regulation of DNA-templated transcription [GO:0045893]; positive regulation of protein acetylation [GO:1901985]; positive regulation of skeletal muscle cell differentiation [GO:2001016]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]; regulation of cell cycle [GO:0051726]; regulation of cellular senescence [GO:2000772]; regulation of DNA-templated transcription [GO:0006355]; regulation of hair cycle [GO:0042634]; regulation of insulin secretion [GO:0050796]; regulation of neurogenesis [GO:0050767]; regulation of transcription by RNA polymerase II [GO:0006357]; regulation of type B pancreatic cell development [GO:2000074]; spermatogenesis [GO:0007283]

aryl hydrocarbon receptor complex [GO:0034751]; chromatoid body [GO:0033391]; nucleus [GO:0005634]; PML body [GO:0016605]; transcription regulator complex [GO:0005667]

DNA-binding transcription factor activity, RNA polymerase II-specific [GO:0000981]; E-box binding [GO:0070888]; protein dimerization activity [GO:0046983]; RNA polymerase II cis-regulatory region sequence-specific DNA binding [GO:0000978]; sequence-specific DNA binding [GO:0043565]; transcription cis-regulatory region binding [GO:0000976]

PF00010;PF00989;PF14598;

4.10.280.10;3.30.450.20;

PTM: Ubiquitinated, leading to its proteasomal degradation. Deubiquitinated by USP9X. {ECO:0000250|UniProtKB:Q9WTL8}.; PTM: O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents protein degradation by inhibiting ubiquitination. It also stabilizes the CLOCK-BMAL1 heterodimer thereby increasing CLOCK-BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2/3 and CRY1/2 (By similarity). {ECO:0000250|UniProtKB:Q9WTL8}.; PTM: Acetylated on Lys-538 by CLOCK during the repression phase of the circadian cycle. Acetylation facilitates recruitment of CRY1 protein and initiates the repression phase of the circadian cycle. Acetylated at Lys-538 by KAT5 during the activation phase of the cycle, leading to recruitment of the positive transcription elongation factor b (P-TEFb) and BRD4, followed by productive elongation of circadian transcripts. Deacetylated by SIRT1, which may result in decreased protein stability. {ECO:0000250|UniProtKB:Q9WTL8}.; PTM: Phosphorylated upon dimerization with CLOCK. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the CLOCK-BMAL1 heterodimer by promoting its degradation. Phosphorylation shows circadian variations in the liver with a peak between CT10 to CT14. Phosphorylation at Ser-90 by CK2 is essential for its nuclear localization, its interaction with CLOCK and controls CLOCK nuclear entry. Dephosphorylation at Ser-78 is important for dimerization with CLOCK and transcriptional activity. {ECO:0000250|UniProtKB:O00327, ECO:0000250|UniProtKB:Q9WTL8}.; PTM: Sumoylated on Lys-259 upon dimerization with CLOCK. Predominantly conjugated to poly-SUMO2/3 rather than SUMO1 and the level of these conjugates undergo rhythmic variation, peaking at CT9-CT12. Sumoylation localizes it exclusively to the PML body and promotes its ubiquitination in the PML body, ubiquitin-dependent proteasomal degradation and the transcriptional activity of the CLOCK-BMAL1 heterodimer (By similarity). {ECO:0000250|UniProtKB:Q9WTL8}.; PTM: Undergoes lysosome-mediated degradation in a time-dependent manner in the liver. {ECO:0000250|UniProtKB:Q9WTL8}.

SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981}. Cytoplasm {ECO:0000250}. Nucleus, PML body {ECO:0000250}. Note=Shuttles between the nucleus and the cytoplasm and this nucleocytoplasmic shuttling is essential for the nuclear accumulation of CLOCK, target gene transcription and the degradation of the CLOCK-BMAL1 heterodimer. The sumoylated form localizes in the PML body (By similarity). {ECO:0000250}.

FUNCTION: Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1, NR1D2, RORA, RORB and RORG, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. BMAL1 positively regulates myogenesis and negatively regulates adipogenesis via the transcriptional control of the genes of the canonical Wnt signaling pathway. Plays a role in normal pancreatic beta-cell function; regulates glucose-stimulated insulin secretion via the regulation of antioxidant genes NFE2L2/NRF2 and its targets SESN2, PRDX3, CCLC and CCLM. Negatively regulates the mTORC1 signaling pathway; regulates the expression of MTOR and DEPTOR. Controls diurnal oscillations of Ly6C inflammatory monocytes; rhythmic recruitment of the PRC2 complex imparts diurnal variation to chemokine expression that is necessary to sustain Ly6C monocyte rhythms. Regulates the expression of HSD3B2, STAR, PTGS2, CYP11A1, CYP19A1 and LHCGR in the ovary and also the genes involved in hair growth. Plays an important role in adult hippocampal neurogenesis by regulating the timely entry of neural stem/progenitor cells (NSPCs) into the cell cycle and the number of cell divisions that take place prior to cell-cycle exit. Regulates the circadian expression of CIART. The CLOCK-BMAL1 heterodimer regulates the circadian expression of SERPINE1/PAI1, VWF, B3, CCRN4L/NOC, NAMPT, DBP, MYOD1, PPARGC1A, PPARGC1B, SIRT1, GYS2, F7, NGFR, GNRHR, BHLHE40/DEC1, ATF4, MTA1 and also genes implicated in glucose and lipid metabolism. Promotes rhythmic chromatin opening, regulating the DNA accessibility of other transcription factors. The NPAS2-BMAL1 heterodimer positively regulates the expression of MAOA, F7 and LDHA and modulates the circadian rhythm of daytime contrast sensitivity by regulating the rhythmic expression of adenylate cyclase type 1 (ADCY1) in the retina. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking adenine nucleotide at the 3-prime end of the canonical 6-nucleotide E-box sequence. CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3'. The CLOCK-BMAL1 heterodimer also recognizes the non-canonical E-box motifs 5'-AACGTGA-3' and 5'-CATGTGA-3'. Essential for the rhythmic interaction of CLOCK with ASS1 and plays a critical role in positively regulating CLOCK-mediated acetylation of ASS1. Plays a role in protecting against lethal sepsis by limiting the expression of immune checkpoint protein CD274 in macrophages in a PKM2-dependent manner (By similarity). Regulates the diurnal rhythms of skeletal muscle metabolism via transcriptional activation of genes promoting triglyceride synthesis (DGAT2) and metabolic efficiency (COQ10B) (By similarity). {ECO:0000250|UniProtKB:O00327, ECO:0000250|UniProtKB:Q9WTL8}.

Equus caballus (Horse)

A0MQA3

ASP5_TOXGO

MEAGAMGGSSFLSFSSGPSAETSPSSLSPPTSSSPSPSPQLVSDSVESLHAKRPLAQSSRSSSRTAASTCFCWQGEGQENEAAPTISQEERRGGSMTAASAGHLETAREEAARCLGCSYTGEERRGASSATSVLSLGGERGRPPSRSSSLWTFSGLLSPLAFRSRRCCPQFSSSSSPLSPLPHPRGAPASACGSAVITDRAGRPASPLSFSRLASPVSDPSGVCPPRVVAARVWRLLSSVLFSLVNCARLFPRRLSRRPDPLRKPRAQVWSASSRSLQALLLATVALFAACSSLHGSSLLGAQAASPTPPFLSLSSSPRSLASDSAKKGSNAPEQSREQRGEREGERQRPDKGEENGETEETFPAASGVVPAPGLKVADLPRTGPPVDLLGLPIRKKVFRARLYGSMFSYAYYFLDILVGTPPQRASVILDTGSSLLAFPCAGCSECGQHLDPAMDTSRSATGEWIDCKEQERCFGSCSGGTPLGGLGGGGVSSMRRCMYTQTYSEGSAIRGIYFSDVVALGEVEQKNPPVRYDFVGCHTQETNLFVTQKAAGIFGISFPKGHRQPTLLDVMFGHTNLVDKKMFSVCISEDGGLLTVGGYEPTLLVAPPESESTPATEALRPVAGESASRRISEKTSPHHAALLTWTSIISHSTYRVPLSGMEVEGLVLGSGVDDFGNTMVDSGTDLSSIFPPIKVSFGDEKNSQVWWWPEGYLYRRTGGYFCDGLDDNKVSASVLGLSFFKNKQVLFDREQDRVGFAAAKCPSFFLDQRPRGPDSGDGPKGRPTAPFTVPPLRVPVPMDGGGVPGDAKQPEGLPLSPQQLWVAAALVVVAILIAVTVILLHTIKRPSRSSAVVPAPSAPRLPFAQNSKSAGRFARGLGHGALGVGNPVYVQRTQRYREVQEAQPHTADAYYDVEEDRFTGEDDGDFFGDDSVPSAEEQETAPSLSLREESSPFSASQSTLLDLPLGGE

3.4.23.-

proteolysis [GO:0006508]

Golgi membrane [GO:0000139]

aspartic-type endopeptidase activity [GO:0004190]

PF14541;PF14543;

2.40.70.10;

Peptidase A1 family

PTM: May be auto-cleaved to produce a 55 kDa form. {ECO:0000269|PubMed:26576949}.

SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000269|PubMed:26473595, ECO:0000269|PubMed:26576949}; Single-pass type I membrane protein {ECO:0000305}.

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 5.5. {ECO:0000269|PubMed:26576949};

FUNCTION: In tachyzoites, plays an essential role in the export of several dense granule proteins into the host cell by cleaving the localization motif RRLxx (termed Toxoplasma export element (TEXEL)) located downstream of the N-terminal secretory signal sequence (PubMed:26270241, PubMed:26473595, PubMed:26576949, PubMed:30377279). However, can also regulate the export of proteins that lack the TEXEL motif, such as GRA24 (PubMed:26270241, PubMed:26473595, PubMed:26576949). Requires Arg at P3 and P2, and Leu at P1 in the substrate TEXEL motif and, specifically, cleaves after Leu (PubMed:26576949). Cleaves GRA16; proteolytic cleavage is essential for the correct trafficking of GRA16 from the parasite into the infected host nucleus (PubMed:26270241, PubMed:26473595, PubMed:26576949). Cleaves GRA19 and GRA20 (PubMed:26473595). Cleaves MYR1 (PubMed:26576949). Cleaves LCAT, GRA44, GRA46, GRA46, ROP35/WNG1 and ROP34/WNG2 (PubMed:30377279). By regulating the export of dense granule proteins into the host cell, regulates multiple processes during tachyzoite infection of host cells, including recruitment of host mitochondria to the parasitophorous vacuole (PV), formation of the nanotubular network (NTN) or intravacuolar network (IVN) which are membranous tubules that bud from the PV membrane into the vacuolar lumen and, up-regulation of host cell genes to facilitate the parasite infection and modulate the host innate immune response (PubMed:26473595, PubMed:26576949). At the bradyzoite stage, also involved in the formation of the cyst wall (PubMed:26473595). {ECO:0000269|PubMed:26270241, ECO:0000269|PubMed:26473595, ECO:0000269|PubMed:26576949, ECO:0000269|PubMed:30377279}.

Toxoplasma gondii

A0MQH0

DICER_CRIGR

MKSPALQPLSMAGLQLMTPASSPMGPFFGLPWQQEAIHDNIYTPRKYQVELLEAALDHNTIVCLNTGSGKTFIAVLLTKELAHQIRGDLNPRAKRTVFLVNSANQVAQQVSAVRTHSDLKVGEYSNLEVNASWTKERWSQEFTKHQVLIMTCYVALNVLKNGYLSLSDINLLVFDECHLAILDHPYREIMKLCESCPSCPRILGLTASILNGKCDPEELEEKIQKLEKILKSNAETATDLVVLDRYASQPCEIVVDCGPFTDRSGLYERLLMELEEAINFINDCNVSVHSKERDSTLISKQILSDCRAVLVVLGPWCADKVAGMMVRELQKYIKHEQEELHRKFLLFTDTLLRKIHALCEEHFSPASLDLKYVTPKVMKLLEILRKYKPYERQQFESVEWYNNRNQDNYVSWSDSEDDDDDEEIEEKEKPETNFPSPFTNILCGIIFVERRYTAVVLNRLIKEAGKQDPELAYISSNFITGHGIGKNQPRSKQMEAEFRKQEEVLRKFRAHETNLLIATSVVEEGVDIPKCNLVVRFDLPTEYRSYVQSKGRARAPISNYVMLADTDKIQSFEEDLKTYKAIEKILRNKCSKSVDGAEADVDAVVDDDDVFPPYVLRPDDGGPRVTINTAIGHVNRYCARLPSDPFTHLAPKCRTQELPDGTFYSTLYLPINSPLRASIVGPPMGCVRLAERVVALICCEKLHKIGELDEHLMPVGKETVKYEEELDLHDEEETSVPGRPGSTKRRQCYPKAIPECLRESYPKPDQPCYLYVIGMVLTTPLPDELNFRRRKLYPPEDTTRCFGILTAKPIPQIPHFPVYTRSGEVTISIELKKSGFTLSQQMLELITRLHQYIFSHILRLEKPALEFKPTGAESAYCVLPLNVVNDSSTLDIDFTFMEDIEKSEARIGIPSTKYSKETPFVFKLEDYQDAVIIPRYRNFDQPHRFYVADVYTDLTPLSKFPSPEYETFAEYYKTKYNLDLTNLNQPLLDVDHTSSRLNLLTPRHLNQKGKALPLSSAEKRKAKWESLQNKQILVPELCAIHPIPASLWRKAVCLPSILYRLHCLLTAEELRAQTASDAGVGVRSLPADFRYPNLDFGWKKSIDSKSFISTCNSSLAENDNYCKHSTIIVPENAAHQGATRTPLENHDQMSVNCRRLPAESSGKLQIEVSTDLTAINGLSYNKNLANGSYDLVNRDFCQGNQLNYFKQEIPVQPTTSYPIQNLYHYENQPKPSNECTLLSNKYLDGNANTSTSDGSPAVSTMPAVMSAGRALKDRMDSEQSPSAGYSSRTLGPNPGLILQALTLSNASDGFNLERLEMLGDSFLKHAITTYLFCTYPDAHEGRLSYMRSKKVSNCNLYRLGKKKGLPSRMVVSIFDPPVNWLPPGYVVNQDKSNAEKWEKDEMTKDCLLANGKLGKDCEEEEALTWRAPKEEAEYEDDFLEYDQEHIQFIDSMLMGSGAFVKKISLSPFSTSDSAYEWKMPKKSSLGSMPFSSDLEDFDYSSWDAMCYLDPSKAVEEDDFVVGFWNPSEENCGVDTGKQSISYDLHTEQCIADKSIADCVEALLGCYLTSCGERAAQLFLCSLGLKVLPVIKRTSREKALYPAQENFSSQQKSLSGSCAATAASPRSSAGKDLEYGCLKIPPRCMFDHPDAEKTLNHLISGFENFEKKINYRFKNKAYLLQAFTHASYHYNTITDCYQRLEFLGDAILDYLITKHLYEDPRQHSPGVLTDLRSALVNNTIFASLAVKYDYHKYFKAVSPELFHVIDDFVQFQLEKNEMQGMDSELRRSEEDEEKEEDIEVPKAMGDIFESLAGAIYMDSGMSLEVVWQVYYPMMRPLIEKFSANVPRSPVRELLEMEPETAKFSPAERTYDGKVRVTVEVVGKGKFKGVGRSYRIAKSAAARRALRSLKANQPQVPNS

3.1.26.3

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250}; Note=Binds 2 magnesium or manganese ions per subunit. {ECO:0000250};

apoptotic DNA fragmentation [GO:0006309]; global gene silencing by mRNA cleavage [GO:0098795]; negative regulation of tumor necrosis factor production [GO:0032720]; negative regulation of tumor necrosis factor-mediated signaling pathway [GO:0010804]; pre-miRNA processing [GO:0031054]; RISC complex assembly [GO:0070922]; siRNA processing [GO:0030422]

extracellular exosome [GO:0070062]; nucleus [GO:0005634]; perinuclear region of cytoplasm [GO:0048471]; RISC complex [GO:0016442]; RISC-loading complex [GO:0070578]

ATP binding [GO:0005524]; deoxyribonuclease I activity [GO:0004530]; DNA binding [GO:0003677]; double-stranded RNA binding [GO:0003725]; helicase activity [GO:0004386]; metal ion binding [GO:0046872]; pre-miRNA binding [GO:0070883]; protein domain specific binding [GO:0019904]; ribonuclease III activity [GO:0004525]; siRNA binding [GO:0035197]

PF03368;PF20932;PF20930;PF20931;PF00271;PF02170;PF04851;PF00636;

3.30.160.20;3.30.160.380;3.40.50.300;2.170.260.10;1.10.1520.10;

Helicase family, Dicer subfamily

SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9UPY3}.

CATALYTIC ACTIVITY: Reaction=Endonucleolytic cleavage to 5'-phosphomonoester.; EC=3.1.26.3;

FUNCTION: Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-induced silencing complex (RISC) to complementary RNAs to degrade them or prevent their translation. Gene silencing mediated by siRNAs, also called RNA interference, controls the elimination of transcripts from mobile and repetitive DNA elements of the genome but also the degradation of exogenous RNA of viral origin for instance. The miRNA pathway on the other side is a mean to specifically regulate the expression of target genes (By similarity). {ECO:0000250|UniProtKB:Q9UPY3}.

Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus)

A0MSJ1

CRA1B_DANRE

MEPDNTPSSRLRAAGVGGRAVFFCMVLYCTCCLRLAQAQSADVDVLQRLGLVGKRPPQGFIPIKSGVILTTRARIDVPVSSVIPVSLGSTFSIILSVCSHRINNAFLFTIVTKRKRLHLGVQFIPGQILVYLGQNSSVNFDYNVHNGQWHNLALEIQGQKVTLYTSCGNTSIQANLDFQNEETLDSEGSFRLGKMSQNSVQFEGAICQFDIHPSAQAAHNYCKYIKKQCREADTYRPNLPPLLPLLPLDPNRSTIQTPKVVTDINERHLSLTRDKMNINHEGQTTVPPMITQPTLQLPLQTTAQTTASIRNRTSQISPKPTQQNRKKAKKERNKLHILKEHQISVTDSPTSQQQNQVDIPTTTTPELSSTFRVSEMTTLAAQRPLPKETSFFEAKATFFESVTPAAMDGLQTFDLEPTQYSLLELTGLKGEPGLPGPPGPPGQPGLPGKRGPRGPSGPHGKPGPPGTPGPKGKKGNPGISPGRAPSGIKGDPGLVGLPGQPGQPGRKGQKGHPGPSGHPGDQGIRGPDGSPGAKGYPGRQGLPGPIGNMGPKGVRGFIGIPGIFGLPGADGERGLPGVPGKKGKMGRPGFPGDFGERGPPGPDGNPGEIGAPGPVGIPGFIGDMGPVGMVGPPGLIGPKGVPGNPGEPGLKGDKGELGLPGEPGEPGFQGDKGIQGSPGLPGVQGKPGPQGKIGDRGPDGLPGPLGPEGFPGDIGPPGQNGVEGPKGNAGVRGIPGPGGLPGLEGDQGPVGPAGAPGLEGRPGRKGISGNPGEEGMKGEPGMTGNPGMLGERGPVGFVGPFGEMGLAGEKGDRGETGQPGPPGEKGAMGHPGAPGERGLSGPAGAPGPHGSRGLSGTRGPKGTRGARGPDGPVGEKGMMGMKGPEGPPGKQGLSGQMGKIGETGEAGPTGFTGVQGPTGPPGAKGILGEPGPQGSPGVLGPLGEIGAIGLPGKAGDQGLPGEPGEKGAVGSPGNIGEQGLIGPRGDPGVDGEAGPSGPDGAKGEQGDVGLEGESGEKGVIGFKGTEGRTGDPGLIGVKGPEGKPGKIGERGKPGEKGSKGHQGQLGEMGALGEQGDTGFIGPKGSRGTTGFMGAPGKMGQQGEPGLVGYEGHQGPQGSLGSPGPKGEKGEQGDDGKVEGPPGPSGDIGPVGNRGDRGEPGDPGYPGLEGVQGERGKEGAPGVPGNSGPRGFPGPKGSKGNKGPKGKNSPRGESGNRGSPGPVGVPGPRGVIGREGFEGEPGLDGAAGKDGAKGMPGDLGRDGDVGLPGKPGPQGNAGAPGLPGVQGSFGPKGERGITGHSGPPGKRGLNGGMGFPGKQGDQGFKGQPGDAGEQGFPGVLGIFGPQGPPGDFGPVGIQGPKGPQGLMGMQGAIGPVGIIGPSGNPGPQGDKGNKGEMGVQGPRGPPGPRGPPGPPGLPAVAFSHENEALGAALHVFDSRSALRSEMYQDTDLPLLDQGSEIFKTLHYLSILIHSIKNPLGTQENPARMCRDLLECEHRLNDGTYWIDPNLGCSSDNIEVTCSFTSGGQTCLKPVTASKLEIGVSLIQMNFIHLLSSEAVQIITVHCLNVSVWASEDSKTPSSSMVYFKAWDGQIIEAGGFIEPDLLKDECWITDGRWHQTQFIFRTQDPNLLPIVEIYNLPSTKPGSHYHLEVGPVCFL

bone mineralization [GO:0030282]; extracellular matrix organization [GO:0030198]; notochord morphogenesis [GO:0048570]; skeletal system development [GO:0001501]

collagen trimer [GO:0005581]; collagen-containing extracellular matrix [GO:0062023]; extracellular space [GO:0005615]

extracellular matrix structural constituent conferring tensile strength [GO:0030020]; metal ion binding [GO:0046872]

PF01410;PF01391;

2.60.120.1000;2.60.120.200;

Fibrillar collagen family

SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix {ECO:0000255|PROSITE-ProRule:PRU00793}.

FUNCTION: May play a role during the calcification of cartilage and the transition of cartilage to bone (By similarity). Together with col27a1a, plays a role in development of the notochord and axial skeleton. {ECO:0000250, ECO:0000269|PubMed:20041163}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0MTA1

APEX1_DANRE

MPKRAKKNEEGVDGEADNGTAAAKKEKKGKEPEAPILYEDPPEKLTSKDGRAANMKITSWNVDGLRAWVKKNGLDWVRKEDPDILCLQETKCAEKALPADITGMPEYPHKYWAGSEDKEGYSGVAMLCKTEPLNVTYGIGKEEHDKEGRVITAEFPDFFLVTAYVPNASRGLVRLDYRKTWDVDFRAYLCGLDARKPLVLCGDLNVAHQEIDLKNPKGNRKNAGFTPEEREGFTQLLEAGFTDSFRELYPDQAYAYTFWTYMMNARSKNVGWRLDYFVLSSALLPGLCDSKIRNTAMGSDHCPITLFLAV

3.1.11.2; 3.1.21.-

COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250|UniProtKB:P27695}; Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250|UniProtKB:P27695}; Note=Probably binds two magnesium or manganese ions per subunit. {ECO:0000250|UniProtKB:P27695};

base-excision repair [GO:0006284]; heart contraction [GO:0060047]; heart looping [GO:0001947]; negative regulation of apoptotic process [GO:0043066]; positive regulation of gene expression [GO:0010628]; positive regulation of gene expression via CpG island demethylation [GO:0044029]

endoplasmic reticulum [GO:0005783]; mitochondrion [GO:0005739]; nuclear speck [GO:0016607]; nucleolus [GO:0005730]; nucleus [GO:0005634]

class II DNA-(apurinic or apyrimidinic site) endonuclease activity [GO:0052720]; DNA-(abasic site) binding [GO:0140431]; DNA-(apurinic or apyrimidinic site) endonuclease activity [GO:0003906]; double-stranded DNA 3'-5' DNA exonuclease activity [GO:0008311]; metal ion binding [GO:0046872]; phosphoric diester hydrolase activity [GO:0008081]; RNA binding [GO:0003723]

PF03372;

3.60.10.10;

DNA repair enzymes AP/ExoA family

SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00764}. Nucleus, nucleolus {ECO:0000250}. Nucleus speckle {ECO:0000255|PROSITE-ProRule:PRU00764}. Endoplasmic reticulum {ECO:0000250}. Cytoplasm {ECO:0000255|PROSITE-ProRule:PRU00764}. Mitochondrion {ECO:0000250}.

CATALYTIC ACTIVITY: Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield nucleoside 5'-phosphates.; EC=3.1.11.2; Evidence={ECO:0000250|UniProtKB:P27695};

FUNCTION: Functions as an apurinic/apyrimidinic (AP) endodeoxyribonuclease in the DNA base excision repair (BER) pathway of DNA lesions induced by oxidative and alkylating agents (PubMed:16966376). Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends (PubMed:16966376). Has 3'-5' exoribonuclease activity on mismatched deoxyribonucleotides at the 3' termini of nicked or gapped DNA molecules during short-patch BER (By similarity). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (By similarity). Required for passage through the mid-blastula transition MBT (PubMed:16966376). May also act as an endoribonuclease involved in the control of single-stranded RNA metabolism (By similarity). Has no redox activity (PubMed:18579163). Binds DNA and RNA (By similarity). {ECO:0000250|UniProtKB:P27695, ECO:0000269|PubMed:16966376, ECO:0000269|PubMed:18579163}.

Danio rerio (Zebrafish) (Brachydanio rerio)

A0MTQ2

BAPA_SPHMI

MHYLKFPAIIAGMLLAGAASAEGPRARDLGVPFAGKPGANNAITDVAGVEVGYVSLISGEGKLERGKGPVRTGVTAVLPRGKESRTPVYAGWETSNAAGEMTGTVWLEERGYFDGPMMITNTHSVGVVRDAVVGWLADVKWPGAWFTPVVAETYDGMLNDINGFHVKPEHALRAIQTAASGPVAEGNVGGGVGMQCFGFKGGTGTASRVVEMDGKSYTVGVLVQCNFGMRPWLRVAGAPVGEELAGKYLPETRGTQTAAATNNGVAPGDGSIIVVMATDAPMLPHQLKRLAKRAAAGMGRMGDAGSNGSGDIFVAFSTANANVQSVGGNVISVETMPNDKLTLIFEAATQATEEAITNVLVAADTLTGVNGYTIQRLPHAELRAILKKYRRLAAAK

3.4.11.25

proteolysis [GO:0006508]

periplasmic space [GO:0042597]

aminopeptidase activity [GO:0004177]

PF03576;

3.60.70.12;

Peptidase S58 family

PTM: Autoproteolytic processing to generate the alpha and beta subunit is required for self-activation and is proposed to use a similar mechanism as substrate cleavage. {ECO:0000250|UniProtKB:Q52VH2}.

SUBCELLULAR LOCATION: Periplasm {ECO:0000250|UniProtKB:Q52VH2}.

CATALYTIC ACTIVITY: Reaction=Cleaves N-terminal beta-homoamino acids from peptides composed of 2 to 6 amino acids.; EC=3.4.11.25; Evidence={ECO:0000269|PubMed:17064315};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=39 mM for beta-homoVal-beta-homoAla-beta-homoLeu; KM=41 mM for beta-homoAla-beta-homoLeu; KM=4.4 mM for beta-3homoAla-pNA; Vmax=0.84 umol/min/mg enzyme with beta-homoVal-beta-homoAla-beta-homoLeu as substrate; Vmax=3.1 umol/min/mg enzyme with beta-homoAla-beta-homoLeu as substrate; Vmax=0.063 umol/min/mg enzyme with carnosine as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.047 umol/min/mg enzyme with beta-homoGly-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.45 umol/min/mg enzyme with beta-homoVal-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.38 umol/min/mg enzyme with beta-homoVal-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.46 umol/min/mg enzyme with beta-homoPhe-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.21 umol/min/mg enzyme with beta-homoTyr-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.04 umol/min/mg enzyme with beta-homoTrp-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.4 umol/min/mg enzyme with beta-homoSer-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.05 umol/min/mg enzyme with beta-homoThr-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.011 umol/min/mg enzyme with beta-homoHis-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.015 umol/min/mg enzyme with beta-homoLys-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.011 umol/min/mg enzyme with beta-homoArg-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315}; Vmax=0.016 umol/min/mg enzyme with D-beta-homoVal-Ile-beta-homoTyr as substrate {ECO:0000269|PubMed:17064315};

BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 10. {ECO:0000269|PubMed:17064315};

FUNCTION: Beta-aminopeptidase that can cleave synthetic beta-peptides which consist of backbone-elongated beta-amino acid residues that are not processed by common proteolytic enzymes. Can cleave the beta-peptides beta-homoVal-beta-homoAla-beta-homoLeu and beta-homoAla-beta-homoLeu. Requires a beta-amino acid at the N-terminus of peptide substrates and cleaves the peptide bond between the N-terminal beta-amino acid and the amino acid at the second position of tripeptidic substrates of the general structure H-betahXaa-Ile-betahTyr-OH according to the following preferences with regard to the side chain of the N-terminal beta-amino acid: aliphatic and aromatic > OH-containing > hydrogen, basic and polar. beta-homoVal-beta-homoAla-beta-homoLeu and beta-homoAla-beta-homoLeu. {ECO:0000269|PubMed:17064315}.

Sphingosinicella microcystinivorans

A0MZ66

SHOT1_HUMAN

MNSSDEEKQLQLITSLKEQAIGEYEDLRAENQKTKEKCDKIRQERDEAVKKLEEFQKISHMVIEEVNFMQNHLEIEKTCRESAEALATKLNKENKTLKRISMLYMAKLGPDVITEEINIDDEDSTTDTDGAAETCVSVQCQKQIKELRDQIVSVQEEKKILAIELENLKSKLVEVIEEVNKVKQEKTVLNSEVLEQRKVLEKCNRVSMLAVEEYEEMQVNLELEKDLRKKAESFAQEMFIEQNKLKRQSHLLLQSSIPDQQLLKALDENAKLTQQLEEERIQHQQKVKELEEQLENETLHKEIHNLKQQLELLEEDKKELELKYQNSEEKARNLKHSVDELQKRVNQSENSVPPPPPPPPPLPPPPPNPIRSLMSMIRKRSHPSGSGAKKEKATQPETTEEVTDLKRQAVEEMMDRIKKGVHLRPVNQTARPKTKPESSKGCESAVDELKGILGTLNKSTSSRSLKSLDPENSETELERILRRRKVTAEADSSSPTGILATSESKSMPVLGSVSSVTKTALNKKTLEAEFNSPSPPTPEPGEGPRKLEGCTSSKVTFQPPSSIGCRKKYIDGEKQAEPVVVLDPVSTHEPQTKDQVAEKDPTQHKEDEGEIQPENKEDSIENVRETDSSNC

actin filament bundle retrograde transport [GO:0061573]; axonogenesis [GO:0007409]; Cdc42 protein signal transduction [GO:0032488]; cytoplasmic actin-based contraction involved in cell motility [GO:0060327]; endoplasmic reticulum polarization [GO:0061163]; netrin-activated signaling pathway [GO:0038007]; neuron projection morphogenesis [GO:0048812]; positive regulation of axon extension [GO:0045773]; positive regulation of neuron migration [GO:2001224]; Ras protein signal transduction [GO:0007265]; regulation of establishment of cell polarity [GO:2000114]; substrate-dependent cell migration, cell extension [GO:0006930]

axon [GO:0030424]; axonal growth cone [GO:0044295]; cell leading edge [GO:0031252]; cytoplasm [GO:0005737]; filopodium [GO:0030175]; growth cone [GO:0030426]; lamellipodium [GO:0030027]; microtubule [GO:0005874]; microtubule associated complex [GO:0005875]; microtubule cytoskeleton [GO:0015630]; perikaryon [GO:0043204]; perinuclear region of cytoplasm [GO:0048471]

actin filament binding [GO:0051015]; cadherin binding [GO:0045296]; identical protein binding [GO:0042802]; kinesin binding [GO:0019894]

1.20.5.1160;

Shootin family

PTM: Phosphorylated on Ser-101 and Ser-249 by PAK1 through a CDC42- and RAC1-dependent signaling pathway, which enhances its association with F-actin retrograde flow in filopodia and lamellipodia of axonal growth cones. Phosphorylation on Ser-101 and Ser-249 is increased by netrin-1. {ECO:0000250|UniProtKB:A0MZ67}.

SUBCELLULAR LOCATION: Perikaryon {ECO:0000250|UniProtKB:Q8K2Q9}. Cell projection, axon {ECO:0000250|UniProtKB:Q8K2Q9}. Cell projection, growth cone {ECO:0000250|UniProtKB:Q8K2Q9}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q8K2Q9}. Cell projection, filopodium {ECO:0000250|UniProtKB:A0MZ67}. Cell projection, lamellipodium {ECO:0000250|UniProtKB:A0MZ67}. Note=Localizes in multiple growth cones at neurite tips before the neuronal symmetry-breaking step. Accumulates in growth cones of a single nascent axon in a neurite length-dependent manner during the neuronal symmetry-breaking step; when absent from the nascent axon's siblings, probably due to competitive transport, prevents the formation of surplus axons. Transported anterogradely from the soma to the axon growth cone in an actin and myosin-dependent manner and passively diffuses back to the cell bodies. Colocalized with L1CAM in close apposition with actin filaments in filopodia and lamellipodia of axonal growth cones in hippocampal neurons. Exhibits retrograde movements in filopodia and lamellopodia of axonal growth cones. Colocalized with KIF20B along microtubules to the tip of the growing cone in primary hippocampal neurons. Recruited to the growth cone of developing axon in a KIF20B- and microtubule-dependent manner. {ECO:0000250|UniProtKB:A0MZ67, ECO:0000250|UniProtKB:Q8K2Q9}.

FUNCTION: Involved in the generation of internal asymmetric signals required for neuronal polarization and neurite outgrowth. Mediates netrin-1-induced F-actin-substrate coupling or 'clutch engagement' within the axon growth cone through activation of CDC42, RAC1 and PAK1-dependent signaling pathway, thereby converting the F-actin retrograde flow into traction forces, concomitantly with filopodium extension and axon outgrowth. Plays a role in cytoskeletal organization by regulating the subcellular localization of phosphoinositide 3-kinase (PI3K) activity at the axonal growth cone. Also plays a role in regenerative neurite outgrowth. In the developing cortex, cooperates with KIF20B to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex. Involved in the accumulation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the growth cone of primary hippocampal neurons. {ECO:0000250|UniProtKB:A0MZ67, ECO:0000250|UniProtKB:Q8K2Q9}.

Homo sapiens (Human)

A0MZ67

SHOT1_RAT

MNSSDEEKQLQLITSLKEQAIGEYEDLRAENQKTKETCDKIRQERDEAVKKLEEFQKISHMVIEEVNFMQNHLEIEKTCRESAEALATKLNKENKTLKRISMLYMAKLGPDVITEEINIDDDDPGTDTDAAAETCVSVQCQKQIKELRDQIVSVQEEKKVLAIELESLKSKLGEVMEEVNKVKQEKAVLNSEVLEQRKVLEKCNRVSVLAVEEYEELQVNLELEKDLRKKAESFAQEMFIEQNKLKRQSHLLLQSSLPDQQLLKALDENAKLIQQLEEERIQHQQKVKELEERLENEALHKEIHNLRQQLELLEDDKRELEQKYQSSEEKARNLKHSVDELQKRVNQSENSVPPPPPPPPPLPPPPPNPIRSLMSMIRKRSHPSGGSTKKEKATQPETAEEVTDLKRQAVEEMMDRIKKGVHLRPVNQTARPKAKPDSLKGSESAVDELKGILGTLNKSTSSRSLKSLGPENSETELERILRRRKLTAEADSSSPTGILATSESKSMPVLGSVSSVTKSALNKKTLEAEFNNPCPLTPEPGEGPRKLEGCTNSKVTFQPPSKGGYRRKCVGSENQSEPVVVLDPVSTHEPQTKDQAAEKDPTQCKEEERGETQPEFKEDSSGGKTGETDSSNC

actin filament bundle retrograde transport [GO:0061573]; axonogenesis [GO:0007409]; Cdc42 protein signal transduction [GO:0032488]; cytoplasmic actin-based contraction involved in cell motility [GO:0060327]; endoplasmic reticulum polarization [GO:0061163]; netrin-activated signaling pathway [GO:0038007]; neuron projection morphogenesis [GO:0048812]; positive regulation of axon extension [GO:0045773]; positive regulation of neuron migration [GO:2001224]; Ras protein signal transduction [GO:0007265]; regulation of establishment of cell polarity [GO:2000114]; regulation of neuron migration [GO:2001222]; substrate-dependent cell migration, cell extension [GO:0006930]

axon [GO:0030424]; axonal growth cone [GO:0044295]; cell leading edge [GO:0031252]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; filopodium [GO:0030175]; growth cone [GO:0030426]; lamellipodium [GO:0030027]; microtubule associated complex [GO:0005875]; microtubule cytoskeleton [GO:0015630]; perikaryon [GO:0043204]; perinuclear region of cytoplasm [GO:0048471]

actin filament binding [GO:0051015]; cell adhesion molecule binding [GO:0050839]; kinesin binding [GO:0019894]

Shootin family

PTM: Phosphorylated on Ser-101 and Ser-249 by PAK1 through a CDC42- and RAC1-dependent signaling pathway, which enhances its association with F-actin retrograde flow in filopodia and lamellipodia of axonal growth cones (PubMed:23453953). Phosphorylation on Ser-101 and Ser-249 is increased by netrin-1 (PubMed:23453953). {ECO:0000269|PubMed:23453953}.

SUBCELLULAR LOCATION: Perikaryon {ECO:0000269|PubMed:17030985, ECO:0000269|PubMed:20664640}. Cell projection, axon {ECO:0000269|PubMed:17030985, ECO:0000269|PubMed:20664640}. Cell projection, growth cone {ECO:0000269|PubMed:17030985, ECO:0000269|PubMed:18519736, ECO:0000269|PubMed:20664640, ECO:0000269|PubMed:23453953}. Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q8K2Q9}. Cell projection, filopodium {ECO:0000269|PubMed:18519736, ECO:0000269|PubMed:23453953}. Cell projection, lamellipodium {ECO:0000269|PubMed:18519736, ECO:0000269|PubMed:23453953}. Note=Localizes in multiple growth cones at neurite tips before the neuronal symmetry-breaking step (PubMed:23453953). Accumulates in growth cones of a single nascent axon in a neurite length-dependent manner during the neuronal symmetry-breaking step; when absent from the nascent axon's siblings, probably due to competitive transport, prevents the formation of surplus axons (PubMed:17030985, PubMed:23453953). Transported anterogradely from the soma to the axon growth cone in an actin and myosin-dependent manner and passively diffuses back to the cell bodies (PubMed:23453953). Colocalized with L1CAM in close apposition with actin filaments in filopodia and lamellipodia of axonal growth cones in hippocampal neurons (PubMed:18519736). Exhibits retrograde movements in filopodia and lamellopodia of axonal growth cones (PubMed:18519736). Colocalized with KIF20B along microtubules to the tip of the growing cone in primary hippocampal neurons. Recruited to the growth cone of developing axon in a KIF20B- and microtubule-dependent manner (By similarity). {ECO:0000250|UniProtKB:Q8K2Q9, ECO:0000269|PubMed:17030985, ECO:0000269|PubMed:18519736, ECO:0000269|PubMed:23453953}.

FUNCTION: Involved in the generation of internal asymmetric signals required for neuronal polarization and neurite outgrowth (PubMed:17030985, PubMed:17439943, PubMed:18519736, PubMed:20664640). Mediates netrin-1-induced F-actin-substrate coupling or 'clutch engagement' within the axon growth cone through activation of CDC42, RAC1 and PAK1-dependent signaling pathway, thereby converting the F-actin retrograde flow into traction forces, concomitantly with filopodium extension and axon outgrowth (PubMed:18519736, PubMed:23453953). Plays a role in cytoskeletal organization by regulating the subcellular localization of phosphoinositide 3-kinase (PI3K) activity at the axonal growth cone (PubMed:17030985). Also plays a role in regenerative neurite outgrowth (PubMed:20664640). In the developing cortex, cooperates with KIF20B to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex. Involved in the accumulation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the growth cone of primary hippocampal neurons (By similarity). {ECO:0000250|UniProtKB:Q8K2Q9, ECO:0000269|PubMed:17030985, ECO:0000269|PubMed:17439943, ECO:0000269|PubMed:18519736, ECO:0000269|PubMed:20664640, ECO:0000269|PubMed:23453953}.

Rattus norvegicus (Rat)

A0NLY7

ISAHY_ROSAI

MSAQSALSGLGAKLLSGEVEVVDCTGVLGPNTPILQLPPDFAKNTPKVEIHKISEYDSDGPFFAWNWMVLGEHSGTHFDAPHHWITGKDYSDGFTDTLDVQRLIAPVNVIDCSKESAADPDFLLTADLIKAWEAEHGEIGAGEWVVMRTDWDKRAGDEAAFLNADETGPHSPGPTPDAIEYLLSKKIVGWGSQCIGTDAGQAGGMEPPFPAHNLLHRDNCFGLASLANLDKLPAKGAILIAAPLKIERGTGSPIRALALVPKA

3.5.2.20

COFACTOR: Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000269|PubMed:24917679}; Note=Binds 1 manganese ion per subunit. {ECO:0000269|PubMed:24917679};

tryptophan catabolic process to kynurenine [GO:0019441]

arylformamidase activity [GO:0004061]; hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides [GO:0016812]; manganese ion binding [GO:0030145]

PF04199;

3.50.30.50;

Cyclase 1 superfamily

CATALYTIC ACTIVITY: Reaction=H2O + isatin = H(+) + isatinate; Xref=Rhea:RHEA:43232, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:27539, ChEBI:CHEBI:82904; EC=3.5.2.20; Evidence={ECO:0000269|PubMed:24917679};

BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=4.8 uM for isatin {ECO:0000269|PubMed:24917679}; Vmax=0.24 umol/sec/mg enzyme {ECO:0000269|PubMed:24917679}; Note=kcat is 24 sec(-1) for isatin as substrate. {ECO:0000269|PubMed:24917679};

FUNCTION: Involved in the degradation of the plant hormone indole-3-acetic acid (IAA). Catalyzes the hydrolysis of the cyclic amide bond (lactam) of isatin (1H-indole-2,3-dione) to yield isatinate (2-(2-aminophenyl)-2-oxoacetate). {ECO:0000269|PubMed:24917679}.

Roseibium aggregatum (strain ATCC 25650 / DSM 13394 / JCM 20685 / NBRC 16684 / NCIMB 2208 / IAM 12614 / B1) (Stappia aggregata)