ID KSYK_RAT Reviewed; 629 AA. AC Q64725; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 11-DEC-2019, entry version 175. DE RecName: Full=Tyrosine-protein kinase SYK; DE EC=2.7.10.2; DE AltName: Full=Spleen tyrosine kinase; DE AltName: Full=p72Syk; GN Name=Syk; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING (ISOFORMS SYKA AND RP SYKB). RX PubMed=7759516; DOI=10.1074/jbc.270.21.12659; RA Rowley R.B., Bolen J.B., Fargnoli J.; RT "Molecular cloning of rodent p72Syk. Evidence of alternative mRNA RT splicing."; RL J. Biol. Chem. 270:12659-12664(1995). RN [2] RP FUNCTION IN PHOSPHORYLATION OF HCLS1. RX PubMed=8611520; DOI=10.1021/bi9528614; RA Ruzzene M., Brunati A.M., Marin O., Donella-Deana A., Pinna L.A.; RT "SH2 domains mediate the sequential phosphorylation of HS1 protein by RT p72syk and Src-related protein tyrosine kinases."; RL Biochemistry 35:5327-5332(1996). RN [3] RP PHOSPHORYLATION AT TYR-317 BY LYN, AND PHOSPHORYLATION AT TYR-342 AND RP TYR-346. RX PubMed=12077122; DOI=10.1074/jbc.m201362200; RA Hong J.J., Yankee T.M., Harrison M.L., Geahlen R.L.; RT "Regulation of signaling in B cells through the phosphorylation of Syk on RT linker region tyrosines. A mechanism for negative signaling by the Lyn RT tyrosine kinase."; RL J. Biol. Chem. 277:31703-31714(2002). 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 VAV1, PLCG1, PI-3-kinase, LCP2 CC and BLNK. Initially identified as essential in B-cell receptor (BCR) CC signaling, it is necessary for the maturation of B-cells most probably CC at the pro-B to pre-B transition. Activated upon BCR engagement, it CC phosphorylates and activates BLNK an adapter linking the activated BCR CC to downstream signaling adapters and effectors. It also phosphorylates CC and activates PLCG1 and the PKC signaling pathway. It also CC phosphorylates BTK and regulates its activity in B-cell antigen CC receptor (BCR)-coupled signaling. In addition to its function CC downstream of BCR plays also a role in T-cell receptor signaling. Plays CC also a crucial role in the innate immune response to fungal, bacterial CC and viral pathogens. It is for instance activated by the membrane CC lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together CC with SYK activates immune cells inducing the production of ROS. Also CC activates the inflammasome and NF-kappa-B-mediated transcription of CC chemokines and cytokines in presence of pathogens. Regulates neutrophil CC degranulation and phagocytosis through activation of the MAPK signaling CC cascade. Required for the stimulation of neutrophil phagocytosis by CC IL15 (By similarity). Also mediates the activation of dendritic cells CC by cell necrosis stimuli. Also involved in mast cells activation. CC Involved in interleukin-3/IL3-mediated signaling pathway in basophils CC (By similarity). Also functions downstream of receptors mediating cell CC adhesion. Relays for instance, integrin-mediated neutrophils and CC macrophages activation and P-selectin receptor/SELPG-mediated CC recruitment of leukocytes to inflammatory loci. Plays also a role in CC non-immune processes. It is for instance involved in vascular CC development where it may regulate blood and lymphatic vascular CC separation. It is also required for osteoclast development and CC function. Functions in the activation of platelets by collagen, CC mediating PLCG2 phosphorylation and activation. May be coupled to the CC collagen receptor by the ITAM domain-containing FCER1G. Also activated CC by the membrane lectin CLEC1B that is required for activation of CC platelets by PDPN/podoplanin. Involved in platelet adhesion being CC activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, CC enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and CC may thus have a role in the intestinal immune response (By similarity). CC {ECO:0000250|UniProtKB:P43405, ECO:0000250|UniProtKB:P48025, CC ECO:0000269|PubMed:8611520}. 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. May also be negatively regulated by CC PTPN6 through dephosphorylation. Downstream signaling adapters and CC intermediates like BLNK or RHOH may mediate positive and/or negative CC feedback regulation. Negatively regulated by CBL and CBLB through CC ubiquitination and probable degradation (By similarity). Phosphorylates CC SH3BP2 which in turn may regulate SYK through LYN (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Interacts with LYN; phosphorylates SYK. Interacts with RHOH CC (phosphorylated); regulates mast cells activation. Interacts with NFAM1 CC (phosphorylated); probably involved in BCR signaling. Interacts with CC VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR activation. CC Interacts with GAB2 (phosphorylated); probably involved in IgE Fc CC receptor signaling. Interacts (via its SH2 domains) with CD79A (via its CC phosphorylated ITAM domain); the interaction stimulates SYK CC autophosphorylation and activation. Interacts (via SH2 domains) with CC FCER1G (via ITAM domain); activates SYK and mediates neutrophils and CC macrophages integrin-mediated activation. Interaction with FCER1G in CC basophils triggers IL3-induced IL4 production (By similarity). CC Interacts with ITGB2 and FGR; involved in ITGB2 downstream signaling. CC Interacts with ITGB3; upon activation by ITGB3 promotes platelet CC adhesion. Interacts (via SH2 domains) with TYROBP (via ITAM domain); CC involved in neutrophils and macrophages integrin-mediated activation. CC Interacts with MSN and SELPLG; mediates the selectin-dependent CC activation of SYK by SELPLG. Interacts with BLNK (via SH2 domain). CC Interacts (via the second SH2 domain) with USP25 (via C-terminus); CC phosphorylates USP25 and regulates USP25 intracellular levels. CC Interacts (via SH2 domains) with CLEC1B (dimer). Interacts with CLEC7A; CC participates in leukocyte activation in presence of fungal pathogens. CC Interacts (phosphorylated) with SLA; may regulate SYK through CBL CC recruitment. Interacts with YWHAG; attenuates BCR-induced membrane CC translocation and activation of SYK (By similarity). Interacts (via SH2 CC domains) with GCSAM; the interaction increases after B-cell receptor CC stimulation, resulting in enhanced SYK autophosphorylation and activity CC (By similarity). Interacts with TNS2; leading to the phosphorylation of CC SYK (By similarity). Interacts with FLNA (via filamin repeat 5); docks CC SYK to the plasma membrane (By similarity). Interacts with CEACAM1; CC lipopolysaccharide activated neutrophils induce phosphorylation of SYK CC resulting in the formation of a complex including TLR4, phosphorylated CC form of SYK and CEACAM1, which in turn, recruits PTPN6 that CC dephosphorylates SYK, reducing the production of reactive oxygen CC species (ROS) and lysosome disruption, leading to a reduction of the CC inflammasome activity (By similarity). Interacts (via SH2 domains) with CC CEACAM20 (phosphorylated form); the interaction further enhances CC CEACAM20 phosphorylation (By similarity). Interacts with IL15RA (By CC similarity). {ECO:0000250|UniProtKB:P43405, CC ECO:0000250|UniProtKB:P48025}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}. Cytoplasm, cytosol CC {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=SykB; CC IsoId=Q64725-1; Sequence=Displayed; CC Name=SykA; CC IsoId=Q64725-2; Sequence=VSP_005011; CC -!- DOMAIN: The SH2 domains mediate the interaction of SYK with the CC phosphorylated ITAM domains of transmembrane proteins. Some proteins CC like CLEC1B have a partial ITAM domain (also called hemITAM) containing CC a single YxxL motif. The interaction with SYK requires CLEC1B CC homodimerization (By similarity). {ECO:0000250}. CC -!- PTM: Autophosphorylated. Phosphorylated on tyrosine residues by LYN CC following receptors engagement. Phosphorylation on Tyr-317 creates a CC binding site for CBL, an adapter protein that serves as a negative CC regulator of BCR-stimulated calcium ion signaling (By similarity). CC Phosphorylation at Tyr-342 creates a binding site for VAV1 (By CC similarity). Phosphorylation on Tyr-342 and Tyr-346 enhances the CC phosphorylation and activation of phospholipase C-gamma and the early CC phase of calcium ion mobilization via a phosphoinositide 3-kinase- CC independent pathway (By similarity). Phosphorylated on tyrosine CC residues in response to IL15 (By similarity). Phosphorylation on Ser- CC 291 is very common, it peaks 5 minutes after BCR stimulation, and CC creates a binding site for YWHAG (By similarity). Phosphorylation at CC Tyr-624 creates a binding site for BLNK (By similarity). CC Dephosphorylated by PTPN6 (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:P43405}. CC -!- PTM: Ubiquitinated by CBLB after BCR activation; which promotes CC proteasomal degradation. {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; U21684; AAA75167.1; -; mRNA. DR EMBL; U21683; AAA75166.1; -; mRNA. DR RefSeq; NP_036890.1; NM_012758.1. [Q64725-1] DR SMR; Q64725; -. DR BioGrid; 247220; 2. DR IntAct; Q64725; 1. DR STRING; 10116.ENSRNOP00000016942; -. DR BindingDB; Q64725; -. DR ChEMBL; CHEMBL4364; -. DR iPTMnet; Q64725; -. DR PhosphoSitePlus; Q64725; -. DR PaxDb; Q64725; -. DR PRIDE; Q64725; -. DR GeneID; 25155; -. DR KEGG; rno:25155; -. DR CTD; 6850; -. DR RGD; 3796; Syk. DR eggNOG; ENOG410IH0T; Eukaryota. DR eggNOG; COG0515; LUCA. DR HOGENOM; HOG000113264; -. DR InParanoid; Q64725; -. DR KO; K05855; -. DR OrthoDB; 796831at2759; -. DR PhylomeDB; Q64725; -. DR BRENDA; 2.7.10.2; 5301. DR Reactome; R-RNO-114604; GPVI-mediated activation cascade. DR Reactome; R-RNO-2029481; FCGR activation. DR Reactome; R-RNO-2029482; Regulation of actin dynamics for phagocytic cup formation. DR Reactome; R-RNO-2029485; Role of phospholipids in phagocytosis. DR Reactome; R-RNO-2424491; DAP12 signaling. DR Reactome; R-RNO-2454202; Fc epsilon receptor (FCERI) signaling. DR Reactome; R-RNO-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. DR Reactome; R-RNO-2871796; FCERI mediated MAPK activation. DR Reactome; R-RNO-2871809; FCERI mediated Ca+2 mobilization. DR Reactome; R-RNO-354192; Integrin alphaIIb beta3 signaling. DR Reactome; R-RNO-5621480; Dectin-2 family. DR Reactome; R-RNO-9020558; Interleukin-2 signaling. DR Reactome; R-RNO-912631; Regulation of signaling by CBL. DR Reactome; R-RNO-983695; Antigen activates B Cell Receptor (BCR) leading to generation of second messengers. DR PRO; PR:Q64725; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0019815; C:B cell receptor complex; ISO:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0032991; C:protein-containing complex; ISO:RGD. DR GO; GO:0042101; C:T cell receptor complex; ISO:RGD. DR GO; GO:0005524; F:ATP binding; ISO:RGD. DR GO; GO:0005178; F:integrin binding; ISO:RGD. DR GO; GO:0016170; F:interleukin-15 receptor binding; ISO:RGD. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0019902; F:phosphatase binding; ISO:RGD. DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD. DR GO; GO:0019904; F:protein domain specific binding; IDA:RGD. DR GO; GO:0004672; F:protein kinase activity; IDA:RGD. DR GO; GO:0019901; F:protein kinase binding; ISO:RGD. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD. DR GO; GO:0004713; F:protein tyrosine kinase activity; EXP:Reactome. DR GO; GO:0042169; F:SH2 domain binding; ISO:RGD. DR GO; GO:0035325; F:Toll-like receptor binding; ISO:RGD. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:RGD. DR GO; GO:0007257; P:activation of JUN kinase activity; ISO:RGD. DR GO; GO:0000187; P:activation of MAPK activity; ISO:RGD. DR GO; GO:0002250; P:adaptive immune response; ISS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0050853; P:B cell receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0043366; P:beta selection; ISO:RGD. DR GO; GO:0048514; P:blood vessel morphogenesis; ISS:UniProtKB. DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISO:RGD. DR GO; GO:0071404; P:cellular response to low-density lipoprotein particle stimulus; ISS:UniProtKB. DR GO; GO:0071226; P:cellular response to molecule of fungal origin; ISS:UniProtKB. DR GO; GO:0038063; P:collagen-activated tyrosine kinase receptor signaling pathway; ISO:RGD. DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB. DR GO; GO:0007167; P:enzyme linked receptor protein signaling pathway; ISO:RGD. DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB. DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0038156; P:interleukin-3-mediated signaling pathway; ISS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD. 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:0019370; P:leukotriene biosynthetic process; ISO:RGD. 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:0018105; P:peptidyl-serine phosphorylation; ISO:RGD. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISO:RGD. DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; ISO:RGD. DR GO; GO:0046641; P:positive regulation of alpha-beta T cell proliferation; ISO:RGD. DR GO; GO:0045579; P:positive regulation of B cell differentiation; ISO:RGD. DR GO; GO:0045780; P:positive regulation of bone resorption; ISS:UniProtKB. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; ISO:RGD. DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISS:UniProtKB. DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD. DR GO; GO:0050715; P:positive regulation of cytokine secretion; ISO:RGD. DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; ISO:RGD. DR GO; GO:0045425; P:positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process; ISO:RGD. DR GO; GO:0045082; P:positive regulation of interleukin-10 biosynthetic process; ISO:RGD. DR GO; GO:0045084; P:positive regulation of interleukin-12 biosynthetic process; ISO:RGD. DR GO; GO:0045401; P:positive regulation of interleukin-3 biosynthetic process; ISO:RGD. DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB. DR GO; GO:0045410; P:positive regulation of interleukin-6 biosynthetic process; ISO:RGD. DR GO; GO:0045416; P:positive regulation of interleukin-8 biosynthetic process; ISO:RGD. DR GO; GO:0051712; P:positive regulation of killing of cells of other organism; ISO:RGD. DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IMP:RGD. DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; ISO:RGD. DR GO; GO:1900086; P:positive regulation of peptidyl-tyrosine autophosphorylation; ISO:RGD. DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD. DR GO; GO:0031334; P:positive regulation of protein complex assembly; ISO:RGD. DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:RGD. DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISO:RGD. DR GO; GO:0042535; P:positive regulation of tumor necrosis factor biosynthetic process; ISO:RGD. DR GO; GO:0032481; P:positive regulation of type I interferon production; ISO:RGD. DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD. DR GO; GO:0006606; P:protein import into nucleus; ISO:RGD. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0031623; P:receptor internalization; ISS:UniProtKB. DR GO; GO:0090237; P:regulation of arachidonic acid secretion; ISS:UniProtKB. DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; ISO:RGD. DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0050776; P:regulation of immune response; IDA:RGD. 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:0010803; P:regulation of tumor necrosis factor-mediated signaling pathway; ISO:RGD. DR GO; GO:0001820; P:serotonin secretion; ISO:RGD. DR GO; GO:0002554; P:serotonin secretion by platelet; ISS:UniProtKB. DR CDD; cd09938; SH2_N-SH2_Zap70_Syk_like; 1. DR Gene3D; 1.10.930.10; -; 1. DR Gene3D; 3.30.505.10; -; 2. 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 Pfam; PF07714; Pkinase_Tyr; 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; SSF55550; SSF55550; 2. DR SUPFAM; SSF56112; SSF56112; 1. 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 Adaptive immunity; Alternative splicing; Angiogenesis; ATP-binding; KW Cell membrane; Cytoplasm; Immunity; Innate immunity; Kinase; Membrane; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat; SH2 domain; KW Transferase; Tyrosine-protein kinase; Ubl conjugation. FT CHAIN 1..629 FT /note="Tyrosine-protein kinase SYK" FT /id="PRO_0000088167" 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 365..625 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT NP_BIND 371..379 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 107..166 FT /note="Interdomain A" FT /evidence="ECO:0000250" FT REGION 259..364 FT /note="Interdomain B" FT /evidence="ECO:0000250" FT ACT_SITE 488 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 396 FT /note="ATP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 27 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 43 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 46 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 130 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 201 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 255 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 270 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P48025" FT MOD_RES 289 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 290 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 291 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 310 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 311 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 313 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 317 FT /note="Phosphotyrosine; by LYN" FT /evidence="ECO:0000269|PubMed:12077122" FT MOD_RES 339 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 342 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:12077122" FT MOD_RES 344 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 346 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:12077122" FT MOD_RES 358 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 373 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 378 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 478 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 501 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 519 FT /note="Phosphotyrosine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 520 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 524 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 540 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P48025" FT MOD_RES 573 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 576 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 623 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 624 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT MOD_RES 625 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P43405" FT VAR_SEQ 277..299 FT /note="Missing (in isoform SykA)" FT /evidence="ECO:0000305" FT /id="VSP_005011" SQ SEQUENCE 629 AA; 71529 MW; 81169A643EC6A6FE CRC64; MAGNAVDNAN HLTYFFGNIT REEAEDYLVQ GGMTDGLYLL RQSRNYLGGF ALSVAHNRKA HHYTIERELN GTYAISGGRA HASPADLCHY HSQEPEGLVC LLKKPFNRPP GVQPKTGPFE DLKENLIREY VKQTWNLQGQ ALEQAIISQK PQLEKLIATT AHEKMPWFHG NISRDESEQT VLIGSKTNGK FLIRARDNNG SFALCLLHEG KVLHYRIDRD KTGKLSIPEG KKFDTLWQLV EHYSYKPDGL LRVLTVPCQK IGVQMGHPGS SNAHPVTWSP GGIISRIKSY SFPKPGHKKP PPPQGSRPES TVSFNPYEPT GGAWGPDRGL QREALPMDTE VYESPYADPE EIRPKEVYLD RKLLTLEDNE LGSGNFGTVK KGYYQMKKVV KTVAVKILKN EANDPALKDE LLAEANVMQQ LDNPYIVRMI GICEAESWML VMEMAAWGPL NKYLQQNRHI KDKNIIELVH QVSMGMKYLE ESNFVHRDLA ARNVLLVTQH YAKISDFGLS KALRADENYY KAQTHGKWPV KWYAPECINY FKFSSKSDVW SFGVLMWEAF SYGQKPYRGM KGSEVTAMLE KGERMGCPPG CPREMYDLMF LCWTYDVENR PGFAAVELRL RNYYYDVVN //