Protein: P43405

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
P43405 (Uniprot) KSYK_HUMAN SYK Tyrosine-protein kinase SYK human No
Uniprot: 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. 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 VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. 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. 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 plays also a role in T-cell receptor signaling. Plays also 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. Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also 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). more..
MoonDB Dissimilar Functions
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0010646 regulation of cell communication 284 GO:0034641 cellular nitrogen compound metabolic process 35 1.59e-39 2.52e-03
Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
35 GO:0044271 cellular nitrogen compound biosynthetic process
35 GO:0044267 cellular protein metabolic process
35 GO:0090304 nucleic acid metabolic process
35 GO:0010468 regulation of gene expression
35 GO:0009966 regulation of signal transduction
111 GO:0006955 immune response
111 GO:0035556 intracellular signal transduction
111 GO:0009967 positive regulation of signal transduction
111 GO:0006468 protein phosphorylation
111 GO:0060255 regulation of macromolecule metabolic process
111 GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
205 GO:0071310 cellular response to organic substance
205 GO:0007167 enzyme linked receptor protein signaling pathway
205 GO:0090304 nucleic acid metabolic process
205 GO:0034654 nucleobase-containing compound biosynthetic process
205 GO:0043085 positive regulation of catalytic activity
205 GO:0031325 positive regulation of cellular metabolic process
205 GO:0010604 positive regulation of macromolecule metabolic process
205 GO:0051173 positive regulation of nitrogen compound metabolic process
205 GO:0009967 positive regulation of signal transduction
205 GO:0006468 protein phosphorylation
205 GO:2000112 regulation of cellular macromolecule biosynthetic process
205 GO:0032268 regulation of cellular protein metabolic process
205 GO:0010468 regulation of gene expression
205 GO:1902531 regulation of intracellular signal transduction
205 GO:0019219 regulation of nucleobase-containing compound metabolic process
205 GO:0042325 regulation of phosphorylation
205 GO:0051049 regulation of transport
284 GO:0009966 regulation of signal transduction
391 GO:0034645 cellular macromolecule biosynthetic process
391 GO:0090304 nucleic acid metabolic process
391 GO:0034654 nucleobase-containing compound biosynthetic process
391 GO:0060255 regulation of macromolecule metabolic process
391 GO:0019219 regulation of nucleobase-containing compound metabolic process
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
35 GO:0005829 cytosol
35 GO:0005634 nucleus
35 GO:0005886 plasma membrane
111 GO:0005829 cytosol
111 GO:0005886 plasma membrane
205 GO:0005829 cytosol
205 GO:0005634 nucleus
205 GO:0005886 plasma membrane
284 GO:0005829 cytosol
284 GO:0005886 plasma membrane
391 GO:0070013 intracellular organelle lumen
391 GO:0005634 nucleus
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0001525 angiogenesis IEA
GO:0001945 lymph vessel development ISS
GO:0002092 positive regulation of receptor internalization IEA
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0002250 adaptive immune response IBA
GO:0002281 macrophage activation involved in immune response IBA
GO:0002283 neutrophil activation involved in immune response IBA
GO:0002366 leukocyte activation involved in immune response ISS
GO:0002554 serotonin secretion by platelet ISS
GO:0006468 protein phosphorylation IDA
GO:0006954 inflammatory response IBA
GO:0007159 leukocyte cell-cell adhesion IDA
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway IBA
GO:0007229 integrin-mediated signaling pathway NAS
GO:0007257 activation of JUN kinase activity IEA
GO:0008283 cell proliferation TAS
GO:0009887 animal organ morphogenesis TAS
GO:0010543 regulation of platelet activation ISS
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway IMP
GO:0016032 viral process IEA
GO:0018105 peptidyl-serine phosphorylation IEA
GO:0019370 leukotriene biosynthetic process IEA
GO:0030168 platelet activation TAS
GO:0030593 neutrophil chemotaxis IDA
GO:0031623 receptor internalization ISS
GO:0032481 positive regulation of type I interferon production IEA
GO:0032928 regulation of superoxide anion generation ISS
GO:0033630 positive regulation of cell adhesion mediated by integrin IBA
GO:0038063 collagen-activated tyrosine kinase receptor signaling pathway IEA
GO:0038083 peptidyl-tyrosine autophosphorylation IBA
GO:0038095 Fc-epsilon receptor signaling pathway TAS
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis TAS
GO:0042742 defense response to bacterium ISS
GO:0042991 transcription factor import into nucleus IMP
GO:0043306 positive regulation of mast cell degranulation IBA
GO:0043313 regulation of neutrophil degranulation ISS
GO:0043366 beta selection IEA
GO:0045087 innate immune response IBA
GO:0045401 positive regulation of interleukin-3 biosynthetic process IEA
GO:0045425 positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic process IEA
GO:0045579 positive regulation of B cell differentiation IMP
GO:0045588 positive regulation of gamma-delta T cell differentiation IEA
GO:0045780 positive regulation of bone resorption ISS
GO:0046638 positive regulation of alpha-beta T cell differentiation IEA
GO:0046641 positive regulation of alpha-beta T cell proliferation IBA
GO:0048514 blood vessel morphogenesis ISS
GO:0050715 positive regulation of cytokine secretion IEA
GO:0050764 regulation of phagocytosis ISS
GO:0050850 positive regulation of calcium-mediated signaling IEA
GO:0050853 B cell receptor signaling pathway IBA
GO:0051090 regulation of DNA binding transcription factor activity IMP
GO:0070372 regulation of ERK1 and ERK2 cascade ISS
GO:0071226 cellular response to molecule of fungal origin ISS
GO:0071404 cellular response to low-density lipoprotein particle stimulus ISS
GO:0090237 regulation of arachidonic acid secretion ISS
GO:0090330 regulation of platelet aggregation IBA
GO:1900086 positive regulation of peptidyl-tyrosine autophosphorylation IEA
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0005634 nucleus IDA
GO:0005737 cytoplasm IDA
GO:0005829 cytosol TAS
GO:0005886 plasma membrane TAS
GO:0019815 B cell receptor complex IEA
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane IBA
GO:0032009 early phagosome ISS
GO:0042101 T cell receptor complex IDA
GO:0043234 protein complex IDA
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0005634 nucleus GO:0005886 plasma membrane 5.35e-300 7.52e-165
PMID Article Title
7513161 Cloning of the cDNA for the deleted syk kinase homologous to ZAP-70 from human basophilic leukemia cell line (KU812).
7895172 Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases.
8163536 Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex.
8168854 Molecular cloning of the human homologue to the pig protein-tyrosine kinase syk.
8590001 Solution structure of the C-terminal SH2 domain of the human tyrosine kinase Syk complexed with a phosphotyrosine pentapeptide.
8657103 Phospholipase C-gamma1 interacts with conserved phosphotyrosyl residues in the linker region of Syk and is a substrate for Syk.
8986718 Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product.
9535867 Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases.
9698567 Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide.
9857068 Cbl-mediated negative regulation of the Syk tyrosine kinase. A critical role for Cbl phosphotyrosine-binding domain binding to Syk phosphotyrosine 323.
10449770 SLAP, a dimeric adapter protein, plays a functional role in T cell receptor signaling.
10458769 Dephosphorylation of ZAP-70 and inhibition of T cell activation by activated SHP1.
11162587 Molecular cloning and characterization of SPAP1, an inhibitory receptor.
11940607 Coordinate interactions of Csk, Src, and Syk kinases with [alpha]IIb[beta]3 initiate integrin signaling to the cytoskeleton.
12387735 ITAM-based interaction of ERM proteins with Syk mediates signaling by the leukocyte adhesion receptor PSGL-1.
12456653 BLNK: molecular scaffolding through 'cis'-mediated organization of signaling proteins.
15164053 DNA sequence and analysis of human chromosome 9.
15388330 Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
18088087 Phosphoproteome of resting human platelets.
18369315 The kinase Syk as an adaptor controlling sustained calcium signalling and B-cell development.
18818202 Molecular mechanism of the Syk activation switch.
19369195 Large-scale proteomics analysis of the human kinome.
19690332 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19843936 FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B-cell receptor-mediated signaling.
19909739 Functional interaction between the ubiquitin-specific protease 25 and the SYK tyrosine kinase.
20154219 CLEC-2 activates Syk through dimerization.
20713593 A novel interaction between FlnA and Syk regulates platelet ITAM-mediated receptor signaling and function.
21269460 Initial characterization of the human central proteome.
21469132 Complex phosphorylation dynamics control the composition of the Syk interactome in B cells.
22019427 The protein-tyrosine kinase Syk interacts with the C-terminal region of tensin2.
23299888 Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation.
No results found.
Domain Name Domain ID Source
A53596 A53596 PIR
Prot_kinase_dom IPR000719 InterPro
SH2 IPR000980 InterPro
Ser-Thr/Tyr_kinase_cat_dom IPR001245 InterPro
Tyr_kinase_AS IPR008266 InterPro
Kinase-like_dom_sf IPR011009 InterPro
Tyr_kinase_non-rcpt_SYK/ZAP70 IPR012234 InterPro
Protein_kinase_ATP_BS IPR017441 InterPro
Tyr_kinase_cat_dom IPR020635 InterPro
Kinase_SYK/ZAP-70_inter-SH2_sf IPR023420 InterPro
SYK/ZAP-70_N_SH2 IPR035838 InterPro
SH2_dom_sf IPR036860 InterPro
SH2 PF00017 Pfam
Pkinase_Tyr PF07714 Pfam
TyrPK_SYK PIRSF000604 PIRSF
TYRKINASE PR00109 PRINTS
SH2DOMAIN PR00401 PRINTS
PROTEIN_KINASE_ATP PS00107 PROSITE
PROTEIN_KINASE_TYR PS00109 PROSITE
SH2 PS50001 PROSITE
PROTEIN_KINASE_DOM PS50011 PROSITE
TyrKc SM00219 SMART
SH2 SM00252 SMART
SSF55550 SSF55550 SUPFAM
SSF56112 SSF56112 SUPFAM
SH2_N-SH2_Zap70_Syk_like cd09938 CDD