Homo sapiens Protein: SYK
InnateDB Protein IDBP-75579.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol SYK
Protein Name spleen tyrosine kinase
Synonyms p72-Syk;
Species Homo sapiens
Ensembl Protein ENSP00000364898
InnateDB Gene IDBG-75571 (SYK)
Protein Structure
UniProt Annotation
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. 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. {ECO:0000269PubMed:12387735, ECO:0000269PubMed:12456653, ECO:0000269PubMed:15388330, ECO:0000269PubMed:19909739, ECO:0000269PubMed:8657103, ECO:0000269PubMed:9535867}.
Subcellular Localization Cell membrane {ECO:0000305}. Cytoplasm, cytosol {ECO:0000305}.
Disease Associations
Tissue Specificity Widely expressed in hematopoietic cells (at protein level). Within the B-cells compartment it is for instance expressed for pro-B-cells to plasma cells. {ECO:0000269PubMed:8163536}.
Number of Interactions This gene and/or its encoded proteins are associated with 173 experimentally validated interaction(s) in this database.
They are also associated with 28 interaction(s) predicted by orthology.
Experimentally validated
Total 173 [view]
Protein-Protein 170 [view]
Protein-DNA 3 [view]
Protein-RNA 0
Predicted by orthology
Total 28 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0005178 integrin binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016772 transferase activity, transferring phosphorus-containing groups
Biological Process
GO:0001525 angiogenesis
GO:0001945 lymph vessel development
GO:0002250 adaptive immune response
GO:0002281 macrophage activation involved in immune response
GO:0002283 neutrophil activation involved in immune response
GO:0002366 leukocyte activation involved in immune response
GO:0002554 serotonin secretion by platelet
GO:0006468 protein phosphorylation
GO:0007159 leukocyte cell-cell adhesion
GO:0007229 integrin-mediated signaling pathway
GO:0007596 blood coagulation
GO:0008283 cell proliferation
GO:0009887 organ morphogenesis
GO:0010543 regulation of platelet activation
GO:0016032 viral process
GO:0030168 platelet activation
GO:0030593 neutrophil chemotaxis
GO:0032928 regulation of superoxide anion generation
GO:0033630 positive regulation of cell adhesion mediated by integrin
GO:0035556 intracellular signal transduction
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0042742 defense response to bacterium
GO:0043313 regulation of neutrophil degranulation
GO:0045087 innate immune response (InnateDB)
GO:0045780 positive regulation of bone resorption
GO:0048514 blood vessel morphogenesis
GO:0050764 regulation of phagocytosis
GO:0050853 B cell receptor signaling pathway
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0071226 cellular response to molecule of fungal origin
GO:0090237 regulation of arachidonic acid secretion
GO:0090330 regulation of platelet aggregation
Cellular Component
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0032009 early phagosome
GO:0042101 T cell receptor complex
Protein Structure and Domains
InterPro IPR000719 Protein kinase domain
IPR000980 SH2 domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR012234 Tyrosine-protein kinase, non-receptor SYK/ZAP-70
IPR020635 Tyrosine-protein kinase, catalytic domain
PFAM PF00069
Post-translational Modifications
SwissProt P43405
PhosphoSite PhosphoSite-P43405
TrEMBL A0A024R244
UniProt Splice Variant
Entrez Gene 6850
UniGene Hs.371720
RefSeq NP_001167638
OMIM 600085
HPRD 02514
EMBL AL354862 BC001645 BC002962 BC011399 CH471089 L28824 X73568 Z29630
GenPept AAA36526 AAH01645 AAH02962 AAH11399 CAA51970 CAA82737 EAW62782 EAW62786