SYK

This gene encodes a member of the family of non-receptor type Tyr protein kinases. This protein is widely expressed in hematopoietic cells and is involved in coupling activated immunoreceptors to downstream signaling events that mediate diverse cellular responses, including proliferation, differentiation, and phagocytosis. It is thought to be a modulator of epithelial cell growth and a potential tumour suppressor in human breast carcinomas. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

SYK

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: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 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 (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. 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).

Adaptive immune responseISS:UniProtKB
AngiogenesisIEA:UniProtKB-KW
Animal organ morphogenesisManual Assertion Based On ExperimentTAS:ProtInc
B cell receptor signaling pathwayManual Assertion Based On ExperimentIMP:ARUK-UCL
Beta selectionIEA:Ensembl
Blood vessel morphogenesisISS:UniProtKB
Cell activationISS:ARUK-UCL
Cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Cellular response to lectinISS:ARUK-UCL
Cellular response to lipidManual Assertion Based On ExperimentIMP:ARUK-UCL
Cellular response to low-density lipoprotein particle stimulusISS:UniProtKB
Cellular response to molecule of fungal originISS:UniProtKB
Collagen-activated tyrosine kinase receptor signaling pathwayIEA:Ensembl
Defense response to bacteriumISS:UniProtKB
Fc-epsilon receptor signaling pathwayTAS:Reactome
Fc-gamma receptor signaling pathway involved in phagocytosisTAS:Reactome
Innate immune responseISS:UniProtKB
Integrin-mediated signaling pathwayISS:UniProtKB
Interleukin-3-mediated signaling pathwayISS:UniProtKB
Intracellular signal transductionManual Assertion Based On ExperimentIDA:ARUK-UCL
Leukocyte activation involved in immune responseISS:UniProtKB
Leukocyte cell-cell adhesionManual Assertion Based On ExperimentIDA:UniProtKB
Leukotriene biosynthetic processIEA:Ensembl
Lymph vessel developmentISS:UniProtKB
Macrophage activation involved in immune responseISS:UniProtKB
Negative regulation of inflammatory response to antigenic stimulusTAS:Reactome
Neutrophil activation involved in immune responseISS:UniProtKB
Neutrophil chemotaxisManual Assertion Based On ExperimentIDA:UniProtKB
Peptidyl-serine phosphorylationIEA:Ensembl
Peptidyl-tyrosine phosphorylationManual Assertion Based On ExperimentIDA:ARUK-UCL
Platelet activationTAS:Reactome
Positive regulation of alpha-beta T cell differentiationIEA:Ensembl
Positive regulation of alpha-beta T cell proliferationManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of B cell differentiationManual Assertion Based On ExperimentIMP:CACAO
Positive regulation of bone resorptionISS:UniProtKB
Positive regulation of calcium-mediated signalingIEA:Ensembl
Positive regulation of cell adhesion mediated by integrinISS:UniProtKB
Positive regulation of cold-induced thermogenesisBy SimilarityISS:YuBioLab
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic processManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of gamma-delta T cell differentiationIEA:Ensembl
Positive regulation of granulocyte macrophage colony-stimulating factor productionIEA:Ensembl
Positive regulation of interleukin-10 productionManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of interleukin-12 productionManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of interleukin-3 productionIEA:Ensembl
Positive regulation of interleukin-4 productionISS:UniProtKB
Positive regulation of interleukin-6 productionManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of interleukin-8 productionManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of JUN kinase activityIEA:Ensembl
Positive regulation of killing of cells of another organismManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of mast cell degranulationManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of monocyte chemotactic protein-1 productionManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of peptidyl-tyrosine phosphorylationIEA:Ensembl
Positive regulation of protein-containing complex assemblyManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of receptor internalizationIEA:Ensembl
Positive regulation of superoxide anion generationManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of tumor necrosis factor productionManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of type I interferon productionIEA:Ensembl
Protein autophosphorylationIEA:Ensembl
Protein import into nucleusManual Assertion Based On ExperimentIMP:MGI
Protein phosphorylationManual Assertion Based On ExperimentIDA:CACAO
Receptor internalizationISS:UniProtKB
Regulation of arachidonic acid secretionISS:UniProtKB
Regulation of DNA-binding transcription factor activityManual Assertion Based On ExperimentIMP:MGI
Regulation of ERK1 and ERK2 cascadeISS:UniProtKB
Regulation of neutrophil degranulationISS:UniProtKB
Regulation of phagocytosisISS:UniProtKB
Regulation of platelet activationISS:UniProtKB
Regulation of platelet aggregationISS:UniProtKB
Regulation of superoxide anion generationISS:UniProtKB
Regulation of tumor necrosis factor-mediated signaling pathwayManual Assertion Based On ExperimentIMP:CACAO
Serotonin secretion by plateletISS:UniProtKB
Stimulatory C-type lectin receptor signaling pathwayISS:ARUK-UCL
Transmembrane receptor protein tyrosine kinase signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central

Cell membrane
Cytoplasm, cytosol

Immunodeficiency 82 with systemic inflammation (IMD82):
An autosomal dominant immunologic disorder with onset in early childhood. It is characterized by recurrent infections with various organisms, and multi-organ inflammation that manifests as colitis, hepatitis, arthritis and dermatitis. Patients have a propensity for the development of lymphoma, usually in adulthood. Disease severity is variable.

Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation.
Autophosphorylated. Phosphorylated on tyrosine residues by LYN following receptors engagement. Phosphorylation on Tyr-323 creates a binding site for CBL, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling. Phosphorylation at Tyr-348 creates a binding site for VAV1. Phosphorylation on Tyr-348 and Tyr-352 enhances the phosphorylation and activation of phospholipase C-gamma and the early phase of calcium ion mobilization via a phosphoinositide 3-kinase-independent pathway (By similarity).
Phosphorylated on tyrosine residues in response to IL15 (PubMed:15123770).
Phosphorylation on Ser-297 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG. Phosphorylation at Tyr-630 creates a binding site for BLNK. Dephosphorylated by PTPN6.