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Overview

Uniprot IDP43405
Protein NameTyrosine-protein kinase SYK
Gene NameSYK
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
232 KLSIPEGKKFDTLWQ

Function

Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development (PubMed:12387735, PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK (PubMed:12456653, PubMed:15388330, PubMed:34634301, PubMed:8657103). Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition (PubMed:12456653). Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Also plays a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade (By similarity). Required for the stimulation of neutrophil phagocytosis by IL15 (PubMed:15123770). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (By similarity). Also functions downstream of receptors mediating cell adhesion (PubMed:12387735). Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Also plays a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (By similarity)

Protein Sequence

10 MASSGMADSA 20 NHLPFFFGNI 30 TREEAEDYLV 40 QGGMSDGLYL 50 LRQSRNYLGG 60 FALSVAHGRK 70 AHHYTIEREL 80 NGTYAIAGGR 90 THASPADLCH 100 YHSQESDGLV 110 CLLKKPFNRP 120 QGVQPKTGPF 130 EDLKENLIRE 140 YVKQTWNLQG 150 QALEQAIISQ 160 KPQLEKLIAT 170 TAHEKMPWFH 180 GKISREESEQ 190 IVLIGSKTNG 200 KFLIRARDNN 210 GSYALCLLHE 220 GKVLHYRIDK 230 DKTGKLSIPE 240 GKKFDTLWQL 250 VEHYSYKADG 260 LLRVLTVPCQ 270 KIGTQGNVNF 280 GGRPQLPGSH 290 PATWSAGGII 300 SRIKSYSFPK 310 PGHRKSSPAQ 320 GNRQESTVSF 330 NPYEPELAPW 340 AADKGPQREA 350 LPMDTEVYES 360 PYADPEEIRP 370 KEVYLDRKLL 380 TLEDKELGSG 390 NFGTVKKGYY 400 QMKKVVKTVA 410 VKILKNEAND 420 PALKDELLAE 430 ANVMQQLDNP 440 YIVRMIGICE 450 AESWMLVMEM 460 AELGPLNKYL 470 QQNRHVKDKN 480 IIELVHQVSM 490 GMKYLEESNF 500 VHRDLAARNV 510 LLVTQHYAKI 520 SDFGLSKALR 530 ADENYYKAQT 540 HGKWPVKWYA 550 PECINYYKFS 560 SKSDVWSFGV 570 LMWEAFSYGQ 580 KPYRGMKGSE 590 VTAMLEKGER 600 MGCPAGCPRE 610 MYDLMNLCWT 620 YDVENRPGFA 630 AVELRLRNYY YDVVN

Gene Ontology

Classification GO ID Description
Cellular Component GO:0019815 B cell receptor complex
Biological Process GO:1990858 cellular response to lectin
Biological Process GO:0071396 cellular response to lipid
Biological Process GO:0071404 cellular response to low-density lipoprotein particle stimulus
Biological Process GO:0071226 cellular response to molecule of fungal origin
Biological Process GO:0042742 defense response to bacterium
Biological Process GO:0038095 Fc-epsilon receptor signaling pathway
Biological Process GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
Biological Process GO:0045087 innate immune response
Biological Process GO:0007229 integrin-mediated signaling pathway
Biological Process GO:0038156 interleukin-3-mediated signaling pathway
Biological Process GO:0035556 intracellular signal transduction
Biological Process GO:0002366 leukocyte activation involved in immune response
Biological Process GO:0007159 leukocyte cell-cell adhesion
Biological Process GO:0001945 lymph vessel development
Biological Process GO:0002281 macrophage activation involved in immune response
Biological Process GO:0002862 negative regulation of inflammatory response to antigenic stimulus
Biological Process GO:0002283 neutrophil activation involved in immune response
Biological Process GO:0030593 neutrophil chemotaxis
Biological Process GO:0018108 peptidyl-tyrosine phosphorylation
Biological Process GO:0030168 platelet activation
Biological Process GO:0045579 positive regulation of B cell differentiation
Biological Process GO:0045780 positive regulation of bone resorption
Biological Process GO:0033630 positive regulation of cell adhesion mediated by integrin
Biological Process GO:0120162 positive regulation of cold-induced thermogenesis
Biological Process GO:0032733 positive regulation of interleukin-10 production
Biological Process GO:0032735 positive regulation of interleukin-12 production
Biological Process GO:0032753 positive regulation of interleukin-4 production
Biological Process GO:0032755 positive regulation of interleukin-6 production
Biological Process GO:0032757 positive regulation of interleukin-8 production
Biological Process GO:0071639 positive regulation of monocyte chemotactic protein-1 production
Biological Process GO:0031334 positive regulation of protein-containing complex assembly
Biological Process GO:0002092 positive regulation of receptor internalization
Biological Process GO:0032930 positive regulation of superoxide anion generation
Biological Process GO:1904263 positive regulation of TORC1 signaling
Biological Process GO:0032760 positive regulation of tumor necrosis factor production
Biological Process GO:0032481 positive regulation of type I interferon production
Biological Process GO:0006606 protein import into nucleus
Biological Process GO:0006468 protein phosphorylation
Biological Process GO:0031623 receptor internalization
Biological Process GO:0090237 regulation of arachidonate secretion
Biological Process GO:0070372 regulation of ERK1 and ERK2 cascade
Biological Process GO:0043313 regulation of neutrophil degranulation
Biological Process GO:0050764 regulation of phagocytosis
Biological Process GO:0010543 regulation of platelet activation
Biological Process GO:0090330 regulation of platelet aggregation
Biological Process GO:0032928 regulation of superoxide anion generation
Biological Process GO:0006357 regulation of transcription by RNA polymerase II
Biological Process GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway
Biological Process GO:0002554 serotonin secretion by platelet
Biological Process GO:0002223 stimulatory C-type lectin receptor signaling pathway
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0032009 early phagosome
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0032991 protein-containing complex
Cellular Component GO:0042101 T cell receptor complex
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0005178 integrin binding
Molecular Function GO:0016170 interleukin-15 receptor binding
Molecular Function GO:0016301 kinase activity
Molecular Function GO:0004715 non-membrane spanning protein tyrosine kinase activity
Molecular Function GO:0019902 phosphatase binding
Molecular Function GO:0043274 phospholipase binding
Molecular Function GO:0001784 phosphotyrosine residue binding
Molecular Function GO:0004672 protein kinase activity
Molecular Function GO:0019901 protein kinase binding
Molecular Function GO:0004674 protein serine/threonine kinase activity
Molecular Function GO:0004713 protein tyrosine kinase activity
Molecular Function GO:0097110 scaffold protein binding
Molecular Function GO:0042169 SH2 domain binding
Molecular Function GO:0005102 signaling receptor binding
Molecular Function GO:0035325 Toll-like receptor binding
Biological Process GO:0002250 adaptive immune response
Biological Process GO:0097242 amyloid-beta clearance
Biological Process GO:0001525 angiogenesis
Biological Process GO:0009887 animal organ morphogenesis
Biological Process GO:0097190 apoptotic signaling pathway
Biological Process GO:0050853 B cell receptor signaling pathway
Biological Process GO:0048514 blood vessel morphogenesis
Biological Process GO:0001775 cell activation
Biological Process GO:0002752 cell surface pattern recognition receptor signaling pathway
Biological Process GO:1904646 cellular response to amyloid-beta

Reference

PMID: N/A