| Protein Name :
Tyrosine-protein kinase SYK
UniProtKB / Swiss-Prot ID : KSYK_HUMAN
Gene Name (Synonyms) :
Species : Homo sapiens (Human).
Subcellular Localization : Cell membrane (Probable). Cytoplasm, cytosol (Probable).
Protein 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. Beside 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.
|Predicted Secondary Structure
|45||R -> H (in dbSNP:rs16906862). VAR_033838|
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| Overview of Protein Modification Sites with Functional and Structural Information
|Accessible Surface Area (ASA)|
Experimental PTM Sites
|Predicted PTM Sites|
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Experimental Post-Translational Modification Sites
|There are no disease associations of PTM sites.|
|D09347|| Fostamatinib (USAN)|
|D09348|| Fostamatinib disodium (USAN)|
|There are no disease associations of PTM sites.|
|Related Literatures of Post-Translational Modification|
|"Profiling of tyrosine phosphorylation pathways in human cells usingmass spectrometry.";|
Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T.,Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.;
Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-348 AND TYR-352, ANDMASS SPECTROMETRY.
|"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";|
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-296; TYR-323; TYR-348;TYR-352 AND TYR-526, AND MASS SPECTROMETRY.
|"Multiple reaction monitoring for robust quantitative proteomicanalysis of cellular signaling networks.";|
Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M.;
Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-323, AND MASSSPECTROMETRY.
|"The kinase Syk as an adaptor controlling sustained calcium signallingand B-cell development.";|
Kulathu Y., Hobeika E., Turchinovich G., Reth M.;
EMBO J. 27:1333-1344(2008).
Cited for: INTERACTION WITH BLNK, ENZYME REGULATION, MUTAGENESIS OF TYR-630, ANDPHOSPHORYLATION AT TYR-630.
|"Phosphoproteome of resting human platelets.";|
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,Schuetz C., Walter U., Gambaryan S., Sickmann A.;
J. Proteome Res. 7:526-534(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-297, AND MASSSPECTROMETRY.
|"Large-scale proteomics analysis of the human kinome.";|
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-295; TYR-296; SER-319;TYR-323 AND TYR-352, AND MASS SPECTROMETRY.
|"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals system-wide modulation of protein-protein interactions.";|
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,Rodionov V., Han D.K.;
Sci. Signal. 2:RA46-RA46(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-28, AND MASSSPECTROMETRY.
|"Complex phosphorylation dynamics control the composition of the Sykinteractome in B cells.";|
Bohnenberger H., Oellerich T., Engelke M., Hsiao H.H., Urlaub H.,Wienands J.;
Eur. J. Immunol. 41:1550-1562(2011).
Cited for: PHOSPHORYLATION AT TYR-28; SER-44; TYR-47; TYR-131; SER-202; THR-256;SER-295; TYR-296; SER-297; SER-316; THR-317; SER-319; TYR-323;THR-345; TYR-348; SER-350; TYR-352; TYR-364; SER-379; THR-384;TYR-484; TYR-507; TYR-525; TYR-526; THR-530; SER-579; THR-582;TYR-629; TYR-630 AND TYR-631, INTERACTION WITH YWHAG, AND MUTAGENESISOF SER-297.
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