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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1 311 2
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. 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.  
7
  • UniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524] silver  
1
  • Ortholog Compara
Integrin bindingdefinition[GO:0005178]  
1
  • UniProtKB
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
17
  • IntAct
  • UniProtKB
  • BHF-UCL
Protein kinase activitydefinition[GO:0004672]  
1
  • UniProtKB
Protein kinase bindingdefinition[GO:0019901] silver  
1
  • Ortholog Compara
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • MGI
Receptor signaling protein tyrosine kinase activitydefinition[GO:0004716] silver  
1
  • Ortholog Compara
GO biological process 
Activation of JUN kinase activitydefinition[GO:0007257] silver  
1
  • Ortholog Compara
Adaptive immune responsedefinition[GO:0002250]  
2
  • RefGenome
  • Ortholog Curator
Angiogenesisdefinition[GO:0001525]  
1
  • UniProtKB KW
B cell receptor signaling pathwaydefinition[GO:0050853]  
2
  • Ortholog Curator
  • RefGenome
Beta selectiondefinition[GO:0043366] silver  
1
  • Ortholog Compara
Blood vessel morphogenesisdefinition[GO:0048514]  
1
  • Ortholog Curator
Cell proliferationdefinition[GO:0008283]  
1
  • PINC
Cellular response to molecule of fungal origindefinition[GO:0071226]  
1
  • Ortholog Curator
Defense response to bacteriumdefinition[GO:0042742]  
1
  • Ortholog Curator
Inflammatory responsedefinition[GO:0006954]  
1
  • RefGenome
Innate immune responsedefinition[GO:0045087]  
2
  • Ortholog Curator
  • RefGenome
Integrin-mediated signaling pathwaydefinition[GO:0007229]  
2
  • UniProtKB
  • Ortholog Curator
Leukocyte activation involved in immune responsedefinition[GO:0002366]  
1
  • Ortholog Curator
Leukocyte cell-cell adhesiondefinition[GO:0007159]  
1
  • UniProtKB
Leukotriene biosynthetic processdefinition[GO:0019370] silver  
1
  • Ortholog Compara
Lymph vessel developmentdefinition[GO:0001945]  
1
  • Ortholog Curator
Macrophage activation involved in immune responsedefinition[GO:0002281]  
2
  • RefGenome
  • Ortholog Curator
Neutrophil activation involved in immune responsedefinition[GO:0002283]  
2
  • Ortholog Curator
  • RefGenome
Neutrophil chemotaxisdefinition[GO:0030593]  
1
  • UniProtKB
Organ morphogenesisdefinition[GO:0009887]  
1
  • PINC
Peptidyl-tyrosine autophosphorylationdefinition[GO:0038083]  
1
  • RefGenome
Positive regulation of alpha-beta T cell differentiationdefinition[GO:0046638] silver  
1
  • Ortholog Compara
Positive regulation of alpha-beta T cell proliferationdefinition[GO:0046641]  
1
  • RefGenome
Positive regulation of B cell differentiationdefinition[GO:0045579]  
1
  • RefGenome
Positive regulation of bone resorptiondefinition[GO:0045780]  
1
  • Ortholog Curator
Positive regulation of calcium-mediated signalingdefinition[GO:0050850] silver  
1
  • Ortholog Compara
Positive regulation of cell adhesion mediated by integrindefinition[GO:0033630]  
2
  • Ortholog Curator
  • RefGenome
Positive regulation of cytokine secretiondefinition[GO:0050715] silver  
1
  • Ortholog Compara
Positive regulation of gamma-delta T cell differentiationdefinition[GO:0045588] silver  
1
  • Ortholog Compara
Positive regulation of granulocyte macrophage colony-stimulating factor biosynthetic processdefinition[GO:0045425] silver  
1
  • Ortholog Compara
Positive regulation of interleukin-3 biosynthetic processdefinition[GO:0045401] silver  
1
  • Ortholog Compara
Positive regulation of mast cell degranulationdefinition[GO:0043306]  
1
  • RefGenome
Positive regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050731] silver  
1
  • Ortholog Compara
Protein phosphorylationdefinition[GO:0006468]  
1
  • Ortholog Curator
Regulation of arachidonic acid secretiondefinition[GO:0090237]  
1
  • Ortholog Curator
Regulation of ERK1 and ERK2 cascadedefinition[GO:0070372]  
1
  • Ortholog Curator
Regulation of neutrophil degranulationdefinition[GO:0043313]  
1
  • Ortholog Curator
Regulation of phagocytosisdefinition[GO:0050764]  
1
  • Ortholog Curator
Regulation of platelet activationdefinition[GO:0010543]  
1
  • Ortholog Curator
Regulation of platelet aggregationdefinition[GO:0090330]  
2
  • Ortholog Curator
  • RefGenome
Regulation of sequence-specific DNA binding transcription factor activitydefinition[GO:0051090]  
1
  • MGI
Regulation of superoxide anion generationdefinition[GO:0032928]  
1
  • Ortholog Curator
Serotonin secretion by plateletdefinition[GO:0002554]  
1
  • Ortholog Curator
Transcription factor import into nucleusdefinition[GO:0042991]  
1
  • MGI
Transmembrane receptor protein tyrosine kinase signaling pathwaydefinition[GO:0007169]  
1
  • RefGenome
Viral processdefinition[GO:0016032]  
1
  • UniProtKB 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.  
2
  • PROSITE-ProRule
  • UniProtKB
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).  
1
  • UniProtKB
 
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:
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers  REACT_118700  
DAP12 signaling  REACT_147814  
Fc epsilon receptor (FCERI) signaling  REACT_163936  
FCERI mediated Ca+2 mobilization  REACT_163834  
FCERI mediated MAPK activation  REACT_163701  
FCGR activation  REACT_160274  
GPVI-mediated activation cascade  REACT_1695  
Integrin alphaIIb beta3 signaling  REACT_15523  
Interleukin-2 signaling  REACT_27283  
Regulation of actin dynamics for phagocytic cup formation  REACT_160086  
Regulation of signaling by CBL  REACT_23787  
Role of LAT2/NTAL/LAB on calcium mobilization  REACT_163769  
Role of phospholipids in phagocytosis  REACT_160158  
 

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