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 13-NOV-2019, entry version 174. 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; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING (ISOFORMS SYKA RP AND 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 RT on linker region tyrosines. A mechanism for negative signaling by the RT Lyn 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 CC (BCR). Regulates several biological processes including innate and CC adaptive immunity, cell adhesion, osteoclast maturation, platelet CC activation and vascular development. Assembles into signaling CC complexes with activated receptors at the plasma membrane via CC interaction between its SH2 domains and the receptor tyrosine- CC phosphorylated ITAM domains. The association with the receptor can CC also be indirect and mediated by adapter proteins containing ITAM CC or partial hemITAM domains. The phosphorylation of the ITAM CC domains is generally mediated by SRC subfamily kinases upon CC engagement of the receptor. More rarely signal transduction via CC SYK could be ITAM-independent. Direct downstream effectors CC phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and CC BLNK. Initially identified as essential in B-cell receptor (BCR) CC signaling, it is necessary for the maturation of B-cells most CC probably at the pro-B to pre-B transition. Activated upon BCR CC engagement, it phosphorylates and activates BLNK an adapter CC linking the activated BCR to downstream signaling adapters and CC effectors. It also phosphorylates and activates PLCG1 and the PKC CC signaling pathway. It also phosphorylates BTK and regulates its CC activity in B-cell antigen receptor (BCR)-coupled signaling. In CC addition to its function downstream of BCR plays also a role in T- CC cell receptor signaling. Plays also a crucial role in the innate CC immune response to fungal, bacterial and viral pathogens. It is CC for instance activated by the membrane lectin CLEC7A. Upon CC stimulation by fungal proteins, CLEC7A together with SYK activates CC immune cells inducing the production of ROS. Also activates the CC inflammasome and NF-kappa-B-mediated transcription of chemokines CC and cytokines in presence of pathogens. Regulates neutrophil CC degranulation and phagocytosis through activation of the MAPK CC signaling cascade. Required for the stimulation of neutrophil CC phagocytosis by IL15 (By similarity). Also mediates the activation CC of dendritic cells by cell necrosis stimuli. Also involved in mast CC cells activation. Involved in interleukin-3/IL3-mediated signaling CC pathway in basophils (By similarity). Also functions downstream of CC receptors mediating cell adhesion. Relays for instance, integrin- CC mediated neutrophils and macrophages activation and P-selectin CC receptor/SELPG-mediated recruitment of leukocytes to inflammatory CC loci. Plays also a role in non-immune processes. It is for CC instance involved in vascular development where it may regulate CC blood and lymphatic vascular separation. It is also required for CC osteoclast development and function. Functions in the activation CC of platelets by collagen, mediating PLCG2 phosphorylation and CC activation. May be coupled to the collagen receptor by the ITAM CC domain-containing FCER1G. Also activated by the membrane lectin CC CLEC1B that is required for activation of platelets by CC PDPN/podoplanin. Involved in platelet adhesion being activated by CC ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances CC production of the cytokine CXCL8/IL-8 via the NFKB pathway and may CC thus have a role in the intestinal immune response (By CC similarity). {ECO:0000250|UniProtKB:P43405, CC ECO:0000250|UniProtKB:P48025, ECO:0000269|PubMed:8611520}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L- CC tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, CC Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; CC EC=2.7.10.2; 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 CC conformation. The phosphorylation of the interdomains or the CC binding of the SH2 domains with dually phosphorylated ITAM domains CC on transmembrane proteins disrupt those intramolecular CC interactions allowing the kinase domain to adopt an active CC conformation. The phosphorylation of SYK and of the ITAM domains CC which is responsible for SYK activation is essentially mediated by CC SRC subfamily kinases, like LYN, upon transmembrane receptors CC engagement. May also be negatively regulated by PTPN6 through CC dephosphorylation. Downstream signaling adapters and intermediates CC like BLNK or RHOH may mediate positive and/or negative feedback CC regulation. Negatively regulated by CBL and CBLB through CC ubiquitination and probable degradation (By similarity). CC Phosphorylates SH3BP2 which in turn may regulate SYK through LYN CC (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with LYN; phosphorylates SYK. Interacts with CC RHOH (phosphorylated); regulates mast cells activation. Interacts CC with NFAM1 (phosphorylated); probably involved in BCR signaling. CC Interacts with VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR CC activation. Interacts with GAB2 (phosphorylated); probably CC involved in IgE Fc receptor signaling. Interacts (via its SH2 CC domains) with CD79A (via its phosphorylated ITAM domain); the CC interaction stimulates SYK autophosphorylation and activation. CC Interacts (via SH2 domains) with FCER1G (via ITAM domain); CC activates SYK and mediates neutrophils and macrophages integrin- CC mediated activation. Interaction with FCER1G in basophils triggers CC IL3-induced IL4 production (By similarity). Interacts with ITGB2 CC and FGR; involved in ITGB2 downstream signaling. Interacts with CC ITGB3; upon activation by ITGB3 promotes platelet adhesion. CC Interacts (via SH2 domains) with TYROBP (via ITAM domain); CC involved in neutrophils and macrophages integrin-mediated CC activation. Interacts with MSN and SELPLG; mediates the selectin- CC dependent activation of SYK by SELPLG. Interacts with BLNK (via CC SH2 domain). Interacts (via the second SH2 domain) with USP25 (via CC C-terminus); phosphorylates USP25 and regulates USP25 CC intracellular levels. Interacts (via SH2 domains) with CLEC1B CC (dimer). Interacts with CLEC7A; participates in leukocyte CC activation in presence of fungal pathogens. Interacts CC (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 CC (via SH2 domains) with GCSAM; the interaction increases after B- CC cell receptor stimulation, resulting in enhanced SYK CC autophosphorylation and activity (By similarity). Interacts with CC TNS2; leading to the phosphorylation of SYK (By similarity). CC Interacts with FLNA (via filamin repeat 5); docks SYK to the CC plasma membrane (By similarity). Interacts with CEACAM1; CC lipopolysaccharide activated neutrophils induce phosphorylation of CC SYK resulting in the formation of a complex including TLR4, CC phosphorylated form of SYK and CEACAM1, which in turn, recruits CC PTPN6 that dephosphorylates SYK, reducing the production of CC reactive oxygen species (ROS) and lysosome disruption, leading to CC a reduction of the inflammasome activity (By similarity). CC Interacts (via SH2 domains) with CEACAM20 (phosphorylated form); CC the interaction further enhances CEACAM20 phosphorylation (By CC similarity). Interacts with IL15RA (By similarity). CC {ECO:0000250|UniProtKB:P43405, ECO:0000250|UniProtKB:P48025}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}. Cytoplasm, CC cytosol {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 CC proteins like CLEC1B have a partial ITAM domain (also called CC hemITAM) containing a single YxxL motif. The interaction with SYK CC requires CLEC1B homodimerization (By similarity). {ECO:0000250}. CC -!- PTM: Autophosphorylated. Phosphorylated on tyrosine residues by CC LYN following receptors engagement. Phosphorylation on Tyr-317 CC creates a binding site for CBL, an adapter protein that serves as CC a negative regulator of BCR-stimulated calcium ion signaling (By CC similarity). Phosphorylation at Tyr-342 creates a binding site for CC VAV1 (By similarity). Phosphorylation on Tyr-342 and Tyr-346 CC enhances the phosphorylation and activation of phospholipase C- CC gamma and the early phase of calcium ion mobilization via a CC phosphoinositide 3-kinase-independent pathway (By similarity). CC Phosphorylated on tyrosine residues in response to IL15 (By CC similarity). Phosphorylation on Ser-291 is very common, it peaks 5 CC minutes after BCR stimulation, and creates a binding site for CC YWHAG (By similarity). Phosphorylation at Tyr-624 creates a CC binding site for BLNK (By similarity). Dephosphorylated by PTPN6 CC (By similarity). {ECO:0000250, 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:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0019904; F:protein domain specific binding; IDA:RGD. DR GO; GO:0004672; F:protein kinase activity; IDA:RGD. DR GO; GO:0004713; F:protein tyrosine kinase activity; EXP:Reactome. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI: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:0048514; P:blood vessel morphogenesis; ISS:UniProtKB. 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: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:0038156; P:interleukin-3-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: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:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab. DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB. DR GO; GO:0043306; P:positive regulation of mast cell degranulation; IMP:RGD. DR GO; GO:0046777; P:protein autophosphorylation; IDA: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: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: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; Complete proteome; Cytoplasm; Immunity; KW Innate immunity; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; KW Reference proteome; Repeat; SH2 domain; Transferase; KW Tyrosine-protein kinase; Ubl conjugation. FT CHAIN 1 629 Tyrosine-protein kinase SYK. FT /FTId=PRO_0000088167. FT DOMAIN 14 106 SH2 1. {ECO:0000255|PROSITE- FT ProRule:PRU00191}. FT DOMAIN 167 258 SH2 2. {ECO:0000255|PROSITE- FT ProRule:PRU00191}. FT DOMAIN 365 625 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 371 379 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 107 166 Interdomain A. {ECO:0000250}. FT REGION 259 364 Interdomain B. {ECO:0000250}. FT ACT_SITE 488 488 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10028}. FT BINDING 396 396 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 27 27 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 43 43 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 46 46 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 130 130 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 201 201 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 255 255 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 270 270 Phosphoserine. FT {ECO:0000250|UniProtKB:P48025}. FT MOD_RES 289 289 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 290 290 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 291 291 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 310 310 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 311 311 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 313 313 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 317 317 Phosphotyrosine; by LYN. FT {ECO:0000269|PubMed:12077122}. FT MOD_RES 339 339 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 342 342 Phosphotyrosine. FT {ECO:0000269|PubMed:12077122}. FT MOD_RES 344 344 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 346 346 Phosphotyrosine. FT {ECO:0000269|PubMed:12077122}. FT MOD_RES 358 358 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 373 373 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 378 378 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 478 478 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 501 501 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 519 519 Phosphotyrosine; by autocatalysis. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 520 520 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 524 524 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 540 540 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P48025}. FT MOD_RES 573 573 Phosphoserine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 576 576 Phosphothreonine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 623 623 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 624 624 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT MOD_RES 625 625 Phosphotyrosine. FT {ECO:0000250|UniProtKB:P43405}. FT VAR_SEQ 277 299 Missing (in isoform SykA). {ECO:0000305}. FT /FTId=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 //