SYK - Tyrosine-protein kinase SYK - human protein (Function)
 
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SYK »  Tyrosine-protein kinase SYK   [ EC 2.7.10.2 ]
 
Protein also known as:  Spleen tyrosine kinase.
Gene name:  SYK
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
6
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524] silver  
  • IEAOrtholog Compara
Integrin bindingdefinition[GO:0005178]  
1
  • IPIUniProtKB
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
16
  • IPIUniProtKB
  • IPIBHF-UCL
  • IPIIntAct
Protein kinase activitydefinition[GO:0004672]  
1
  • NASUniProtKB
Protein kinase bindingdefinition[GO:0019901] silver  
  • IEAOrtholog Compara
Receptor signaling protein tyrosine kinase activitydefinition[GO:0004716] silver  
  • IEAOrtholog Compara
GO biological process 
Activation of JUN kinase activitydefinition[GO:0007257] silver  
  • IEAOrtholog Compara
Adaptive immune responsedefinition[GO:0002250]  
  • ISSOrtholog Curator
Angiogenesisdefinition[GO:0001525]  
  • IEAUniProtKB KW
B cell receptor signaling pathwaydefinition[GO:0050853]  
  • ISSOrtholog Curator
Beta selectiondefinition[GO:0043366] silver  
  • IEAOrtholog Compara
Blood vessel morphogenesisdefinition[GO:0048514]  
  • ISSOrtholog Curator
Cell proliferationdefinition[GO:0008283]  
1
  • TASPINC
Cellular response to molecule of fungal origindefinition[GO:0071226]  
  • ISSOrtholog Curator
Defense response to bacteriumdefinition[GO:0042742]  
  • ISSOrtholog Curator
Enzyme linked receptor protein signaling pathwaydefinition[GO:0007167] silver  
  • IEAOrtholog Compara
Innate immune responsedefinition[GO:0045087]  
  • ISSOrtholog Curator
Integrin-mediated signaling pathwaydefinition[GO:0007229]  
1
  • NASUniProtKB
  • ISSOrtholog Curator
Leukocyte activation involved in immune responsedefinition[GO:0002366]  
  • ISSOrtholog Curator
Leukocyte cell-cell adhesiondefinition[GO:0007159]  
1
  • IDAUniProtKB
Leukotriene biosynthetic processdefinition[GO:0019370] silver  
  • IEAOrtholog Compara
Lymph vessel developmentdefinition[GO:0001945]  
  • ISSOrtholog Curator
Macrophage activation involved in immune responsedefinition[GO:0002281]  
  • ISSOrtholog Curator
Neutrophil activation involved in immune responsedefinition[GO:0002283]  
  • ISSOrtholog Curator
Neutrophil chemotaxisdefinition[GO:0030593]  
1
  • IDAUniProtKB
Organ morphogenesisdefinition[GO:0009887]  
1
  • TASPINC
Positive regulation of alpha-beta T cell differentiationdefinition[GO:0046638] silver  
  • IEAOrtholog Compara
Positive regulation of alpha-beta T cell proliferationdefinition[GO:0046641] silver  
  • IEAOrtholog Compara
Positive regulation of B cell differentiationdefinition[GO:0045579] silver  
  • IEAOrtholog Compara
Positive regulation of bone resorptiondefinition[GO:0045780]  
  • ISSOrtholog Curator
Positive regulation of calcium-mediated signalingdefinition[GO:0050850] silver  
  • IEAOrtholog Compara
Positive regulation of cell adhesion mediated by integrindefinition[GO:0033630]  
  • ISSOrtholog Curator
Positive regulation of cytokine secretiondefinition[GO:0050715] silver  
  • IEAOrtholog Compara
Positive regulation of gamma-delta T cell differentiationdefinition[GO:0045588] silver  
  • IEAOrtholog Compara
Positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic processdefinition[GO:0045425] silver  
  • IEAOrtholog Compara
Positive regulation of interleukin-3 biosynthetic processdefinition[GO:0045401] silver  
  • IEAOrtholog Compara
Positive regulation of mast cell degranulationdefinition[GO:0043306] silver  
  • IEAOrtholog Compara
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731] silver  
  • IEAOrtholog Compara
Protein autophosphorylationdefinition[GO:0046777] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468]  
  • ISSOrtholog Curator
Regulation of arachidonic acid secretiondefinition[GO:0090237]  
  • ISSOrtholog Curator
Regulation of ERK1 and ERK2 cascadedefinition[GO:0070372]  
  • ISSOrtholog Curator
Regulation of neutrophil degranulationdefinition[GO:0043313]  
  • ISSOrtholog Curator
Regulation of phagocytosisdefinition[GO:0050764]  
  • ISSOrtholog Curator
Regulation of platelet activationdefinition[GO:0010543]  
  • ISSOrtholog Curator
Regulation of platelet aggregationdefinition[GO:0090330]  
  • ISSOrtholog Curator
Regulation of superoxide anion generationdefinition[GO:0032928]  
  • ISSOrtholog Curator
Serotonin secretion by plateletdefinition[GO:0002554]  
  • ISSOrtholog Curator
Viral processdefinition[GO:0016032]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
  • CuratedUniProtKB
It is regulated in the following manner
Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement. May also be negatively regulated by PTPN6 through dephosphorylation. Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN (By similarity).  
4
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
B cell receptor signaling pathway  hsa04662+6850  
Fc epsilon RI signaling pathway  hsa04664+6850  
Fc gamma R-mediated phagocytosis  hsa04666+6850  
Natural killer cell mediated cytotoxicity  hsa04650+6850  
Osteoclast differentiation  hsa04380+6850  
Tuberculosis  hsa05152+6850  
According to Reactome, this protein belongs to the following pathways:
Hemostasis  REACT_604  
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Adaptive immunity  definition   [KW-1064]
Angiogenesis  definition   [KW-0037]
Host-virus interaction  definition   [KW-0945]
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Molecular function 
Kinase  definition   [KW-0418]
Transferase  definition   [KW-0808]
Tyrosine-protein kinase  definition   [KW-0829]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Syk
GenomeRNAi: 6850
PRO: PR:P43405
Chemistry
GuidetoPHARMACOLOGY: 2230