ID KSYK_CHICK Reviewed; 613 AA. AC F1N9Y5; Q5ZJ91; DT 25-JAN-2012, integrated into UniProtKB/Swiss-Prot. DT 25-JAN-2012, sequence version 2. DT 24-JAN-2024, entry version 77. DE RecName: Full=Tyrosine-protein kinase SYK; DE EC=2.7.10.2; GN Name=SYK; ORFNames=RCJMB04_19o18; OS Gallus gallus (Chicken). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda; OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae; OC Phasianinae; Gallus. OX NCBI_TaxID=9031; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=CB; TISSUE=Bursa of Fabricius; RX PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6; RA Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P., RA Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P., RA Hayashizaki Y., Buerstedde J.-M.; RT "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene RT function analysis."; RL Genome Biol. 6:R6.1-R6.9(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Red jungle fowl; RX PubMed=15592404; DOI=10.1038/nature03154; RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P., RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B., RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C., RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V., RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O., RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W., RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D., RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K., RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L., RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B., RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M., RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K., RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E., RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M., RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M., RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S., RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M., RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M., RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A., RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S., RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J., RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J., RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E., RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M., RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A., RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M., RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O., RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E., RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S., RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E., RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R., RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R., RA Wilson R.K.; RT "Sequence and comparative analysis of the chicken genome provide unique RT perspectives on vertebrate evolution."; RL Nature 432:695-716(2004). RN [3] RP FUNCTION IN B-CELL RECEPTOR SIGNALING PATHWAY, AND FUNCTION IN RP PHOSPHORYLATION OF BLNK. RX PubMed=9697839; DOI=10.1016/s1074-7613(00)80591-9; RA Fu C., Turck C.W., Kurosaki T., Chan A.C.; RT "BLNK: a central linker protein in B cell activation."; RL Immunity 9:93-103(1998). CC -!- FUNCTION: Non-receptor tyrosine kinase which mediates signal CC transduction downstream of a variety of transmembrane receptors CC including classical immunoreceptors like the B-cell receptor (BCR). CC Regulates several biological processes including innate and adaptive CC immunity, cell adhesion, osteoclast maturation, platelet activation and CC vascular development. Assembles into signaling complexes with activated CC receptors at the plasma membrane via interaction between its SH2 CC domains and the receptor tyrosine-phosphorylated ITAM domains. The CC association with the receptor can also be indirect and mediated by CC adapter proteins containing ITAM or partial hemITAM domains. The CC phosphorylation of the ITAM domains is generally mediated by SRC CC subfamily kinases upon engagement of the receptor. More rarely signal CC transduction via SYK could be ITAM-independent. Direct downstream CC effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3- CC kinase, LCP2 and BLNK. Initially identified as essential in B-cell CC receptor (BCR) signaling, it is necessary for the maturation of B-cells CC most probably at the pro-B to pre-B transition. Activated upon BCR CC engagement, it phosphorylates and activates BLNK an adapter linking the CC activated BCR to downstream signaling adapters and effectors. CC {ECO:0000269|PubMed:9697839}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl- CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA- CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2; CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; CC -!- ACTIVITY REGULATION: Autoinhibited. Intramolecular binding of the CC interdomains A and B (also called linker region) to parts of the CC catalytic domain keep the catalytic center in an inactive conformation. CC The phosphorylation of the interdomains or the binding of the SH2 CC domains with dually phosphorylated ITAM domains on transmembrane CC proteins disrupt those intramolecular interactions allowing the kinase CC domain to adopt an active conformation. The phosphorylation of SYK and CC of the ITAM domains which is responsible for SYK activation is CC essentially mediated by SRC subfamily kinases, like LYN, upon CC transmembrane receptors engagement. Downstream signaling adapters and CC intermediates may mediate positive and/or negative feedback regulation CC (By similarity). {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}. Cytoplasm, cytosol CC {ECO:0000305}. CC -!- DOMAIN: The SH2 domains mediate the interaction of SYK with the CC phosphorylated ITAM domains of transmembrane proteins. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. SYK/ZAP-70 subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ720543; CAG32202.1; -; mRNA. DR EMBL; AADN02069860; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AADN02069861; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AADN02069862; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AADN02069863; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AADN02069864; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AADN02069865; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AADN02069866; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AADN02069867; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AADN02069868; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AADN02069869; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR RefSeq; NP_001026601.1; NM_001031430.1. DR AlphaFoldDB; F1N9Y5; -. DR SMR; F1N9Y5; -. DR BioGRID; 686612; 97. DR STRING; 9031.ENSGALP00000024509; -. DR PaxDb; 9031-ENSGALP00000024509; -. DR Ensembl; ENSGALT00000032807; ENSGALP00000032170; ENSGALG00000015216. DR Ensembl; ENSGALT00010022248.1; ENSGALP00010012784.1; ENSGALG00010009340.1. DR Ensembl; ENSGALT00015070158; ENSGALP00015043064; ENSGALG00015028988. DR GeneID; 427272; -. DR KEGG; gga:427272; -. DR CTD; 6850; -. DR VEuPathDB; HostDB:geneid_427272; -. DR eggNOG; ENOG502QT06; Eukaryota. DR GeneTree; ENSGT00940000159053; -. DR HOGENOM; CLU_000288_7_2_1; -. DR InParanoid; F1N9Y5; -. DR Reactome; R-GGA-114604; GPVI-mediated activation cascade. DR Reactome; R-GGA-2029481; FCGR activation. DR Reactome; R-GGA-2029482; Regulation of actin dynamics for phagocytic cup formation. DR Reactome; R-GGA-2029485; Role of phospholipids in phagocytosis. DR Reactome; R-GGA-2424491; DAP12 signaling. DR Reactome; R-GGA-354192; Integrin signaling. DR Reactome; R-GGA-5621480; Dectin-2 family. DR Reactome; R-GGA-912631; Regulation of signaling by CBL. DR Reactome; R-GGA-9674555; Signaling by CSF3 (G-CSF). DR Reactome; R-GGA-9705462; Inactivation of CSF3 (G-CSF) signaling. DR Reactome; R-GGA-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR PRO; PR:F1N9Y5; -. DR Proteomes; UP000000539; Chromosome Z. DR Bgee; ENSGALG00000015216; Expressed in spleen and 7 other cell types or tissues. DR ExpressionAtlas; F1N9Y5; baseline and differential. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB. DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IMP:UniProtKB. DR GO; GO:0004713; F:protein tyrosine kinase activity; IMP:AgBase. DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central. DR GO; GO:0002250; P:adaptive immune response; IMP:UniProtKB. DR GO; GO:0050853; P:B cell receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IMP:AgBase. DR GO; GO:0071226; P:cellular response to molecule of fungal origin; ISS:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB. DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB. DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro. DR GO; GO:0002366; P:leukocyte activation involved in immune response; ISS:UniProtKB. DR GO; GO:0007159; P:leukocyte cell-cell adhesion; ISS:UniProtKB. DR GO; GO:0001945; P:lymph vessel development; ISS:UniProtKB. DR GO; GO:0002281; P:macrophage activation involved in immune response; ISS:UniProtKB. DR GO; GO:0002283; P:neutrophil activation involved in immune response; ISS:UniProtKB. DR GO; GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; IMP:UniProtKB. DR GO; GO:0046641; P:positive regulation of alpha-beta T cell proliferation; IBA:GO_Central. DR GO; GO:0045579; P:positive regulation of B cell differentiation; IBA:GO_Central. DR GO; GO:0045780; P:positive regulation of bone resorption; ISS:UniProtKB. DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISS:UniProtKB. DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IBA:GO_Central. DR GO; GO:0090237; P:regulation of arachidonic acid secretion; ISS:UniProtKB. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0043313; P:regulation of neutrophil degranulation; ISS:UniProtKB. DR GO; GO:0050764; P:regulation of phagocytosis; ISS:UniProtKB. DR GO; GO:0010543; P:regulation of platelet activation; ISS:UniProtKB. DR GO; GO:0090330; P:regulation of platelet aggregation; ISS:UniProtKB. DR GO; GO:0032928; P:regulation of superoxide anion generation; ISS:UniProtKB. DR GO; GO:0002554; P:serotonin secretion by platelet; ISS:UniProtKB. DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central. DR CDD; cd05116; PTKc_Syk; 1. DR CDD; cd10401; SH2_C-SH2_Syk_like; 1. DR CDD; cd09938; SH2_N-SH2_Zap70_Syk_like; 1. DR Gene3D; 3.30.505.10; SH2 domain; 2. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR023420; Kinase_SYK/ZAP-70_inter-SH2_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR035838; SYK/ZAP-70_N_SH2. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR012234; Tyr_kinase_non-rcpt_SYK/ZAP70. DR PANTHER; PTHR24418; TYROSINE-PROTEIN KINASE; 1. DR PANTHER; PTHR24418:SF231; TYROSINE-PROTEIN KINASE SYK; 1. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF00017; SH2; 2. DR PIRSF; PIRSF000604; TyrPK_SYK; 1. DR PRINTS; PR00401; SH2DOMAIN. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00252; SH2; 2. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF55550; SH2 domain; 2. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS50001; SH2; 2. PE 1: Evidence at protein level; KW ATP-binding; Cell membrane; Cytoplasm; Immunity; Innate immunity; Kinase; KW Membrane; Nucleotide-binding; Reference proteome; Repeat; SH2 domain; KW Transferase; Tyrosine-protein kinase. FT CHAIN 1..613 FT /note="Tyrosine-protein kinase SYK" FT /id="PRO_0000415332" FT DOMAIN 14..106 FT /note="SH2 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 167..258 FT /note="SH2 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT DOMAIN 349..613 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 107..166 FT /note="Interdomain A" FT REGION 259..348 FT /note="Interdomain B" FT ACT_SITE 472 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 355..363 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 380 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT CONFLICT 188 FT /note="N -> D (in Ref. 1; CAG32202)" FT /evidence="ECO:0000305" FT CONFLICT 398 FT /note="E -> G (in Ref. 1; CAG32202)" FT /evidence="ECO:0000305" SQ SEQUENCE 613 AA; 69901 MW; 32783B7D0C8EBC82 CRC64; MASNMANPAN HLPYFFGNIT REEAEEYLMQ GGMSDGLYLL RQSRNYLGGF ALSLAYGRKV HHYTIERELS GTYAIAGGKS HASPAELINY HSEEADGLIC LLRKSFNRPP GVEPKTGPFE DLKENLIREY VKQTWNLQGH ALEQAIISQK PQLEKLIATT AHEKMPWFHG RISREESEHR ILIGSRNNGK FLIRERDSNG SYALCLLNDG KVLHYRIDRD KTGKLSIPDG KRFDTLWQLV EHYSYKPDGL LRVLSIPCPR HGSESDNVVF DTRPLPGTPS KLQTPIGAPS DDQTPFNPYV LQRARGLIGA EKGDQREALP MDTEVYESPY ADPDEIKPKN VTLDRKLLTL EEGELGSGNF GTVKKGFYKM KKGAKPVAVK ILKNESNDPA IKDELLREAN VMQQLDNPYI VRMIGICEAE AWMLVMEMAE LGPLNKFLQK NRHVTEKNIT ELVHQVSMGM KYLEENNFVH RDLAARNVLL VTQHYAKISD FGLSKALSAD ENYYKAQSHG KWPVKWYAPE CMNFYKFSSK SDVWSFGVLM WEAFSYGQKP YKGMKGGEVA QMIERGERME CPEACPVEVY DLMKLCWTYN VDDRPGFVAV ELRLRNYYYD ISH //