ZAP70 - Tyrosine-protein kinase ZAP-70 - human protein (Function)
 
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ZAP70 »  Tyrosine-protein kinase ZAP-70   [ EC 2.7.10.2 ]
 
Protein also known as:  70 kDa zeta-chain associated protein.
Gene name:  ZAP70
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 
Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. Subsequently, ZAP70 phosphorylates at least 2 essential adapter proteins: LAT and LCP2. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface. During thymocyte development, ZAP70 promotes survival and cell-cycle progression of developing thymocytes before positive selection (when cells are still CD4/CD8 double negative). Additionally, ZAP70-dependent signaling pathway may also contribute to primary B-cells formation and activation through B-cell receptor (BCR).  
6
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • NASUniProtKB
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
1
  • TASUniProtKB
Phosphotyrosine bindingdefinition[GO:0001784] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
16
  • IPIIntAct
  • IPIUniProtKB
Protein tyrosine kinase activitydefinition[GO:0004713]  
3
  • IDAUniProtKB
GO biological process 
Adaptive immune responsedefinition[GO:0002250]  
1
  • TASUniProtKB
B cell activationdefinition[GO:0042113]  
1
  • TASUniProtKB
Beta selectiondefinition[GO:0043366] silver  
  • IEAOrtholog Compara
Immune responsedefinition[GO:0006955]  
1
  • IDAUniProtKB
Intracellular signal transductiondefinition[GO:0035556]  
1
  • NASUniProtKB
Negative thymic T cell selectiondefinition[GO:0045060] silver  
  • IEAOrtholog Compara
Peptidyl-tyrosine phosphorylationdefinition[GO:0018108]  
2
  • IMPMGI
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 calcium-mediated signalingdefinition[GO:0050850] silver  
  • IEAOrtholog Compara
Positive regulation of T cell differentiationdefinition[GO:0045582]  
1
  • IDAMGI
Positive thymic T cell selectiondefinition[GO:0045059]  
1
  • IDAMGI
Protein autophosphorylationdefinition[GO:0046777] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468]  
2
  • IDAUniProtKB
T cell activationdefinition[GO:0042110]  
1
  • TASUniProtKB
T cell aggregationdefinition[GO:0070489]  
1
  • TASUniProtKB
T cell differentiationdefinition[GO:0030217]  
1
  • NASUniProtKB
T cell migrationdefinition[GO:0072678]  
1
  • TASUniProtKB
T cell receptor signaling pathwaydefinition[GO:0050852]  
1
  • TASUniProtKB
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.  
1
  • CuratedUniProtKB
It is regulated in the following manner
Activated by phosphorylation at Tyr-493 in the activation loop. Inhibited by staurosporine.  
1
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Natural killer cell mediated cytotoxicity  hsa04650+7535  
Primary immunodeficiency  hsa05340+7535  
T cell receptor signaling pathway  hsa04660+7535  
According to Reactome, this protein belongs to the following pathway:
Immune System  REACT_6900  
 

Keywords

Biological process 
Adaptive immunity  definition   [KW-1064]
Immunity  definition   [KW-0391]
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: ZAP70
GenomeRNAi: 7535
PRO: PR:P43403
Chemistry
GuidetoPHARMACOLOGY: 2285