InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SYK

Summary

InnateDB Protein

IDBP-75575.7

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

ENSP00000364904

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}.

Comments

Interactions

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
DNA-DNA	0
RNA-RNA	0
DNA-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

PDB ID

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
PF00017
PF14633
PF07714

PRINTS

PR00401
PR00109

PIRSF

PIRSF000604

SMART

SM00252
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References