ZAP70
UniProt ID: P43403
Entrez ID: 7535
Protein name: Tyrosine-protein kinase ZAP-70 (EC 2.7.10.2) (70 kDa zeta-chain associated protein) (Syk-related tyrosine kinase)
External links: UniprotKB HGNC RefSeq COSMIC
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FUNCTION: 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 pr...
FUNCTION: 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). {ECO:0000269|PubMed:11353765, ECO:0000269|PubMed:12051764, ECO:0000269|PubMed:1423621, ECO:0000269|PubMed:20135127, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:8124727, ECO:0000269|PubMed:8702662, ECO:0000269|PubMed:9489702}.
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GO - Biological processes (BP):
adaptive immune response [GO:0002250]; B cell activation [GO:0042113]; beta selection [GO:0043366]; cell differentiation [GO:0030154]; immune response [GO:0006955]; innate immune response [GO:0045087]; intracellular signal transduction [GO:0035556]; negative thymic T cell selection [GO:0045060]; pep...
adaptive immune response [GO:0002250]; B cell activation [GO:0042113]; beta selection [GO:0043366]; cell differentiation [GO:0030154]; immune response [GO:0006955]; innate immune response [GO:0045087]; intracellular signal transduction [GO:0035556]; negative thymic T cell selection [GO:0045060]; peptidyl-tyrosine phosphorylation [GO:0018108]; positive regulation of alpha-beta T cell differentiation [GO:0046638]; positive regulation of alpha-beta T cell proliferation [GO:0046641]; positive regulation of calcium-mediated signaling [GO:0050850]; positive regulation of T cell differentiation [GO:0045582]; positive thymic T cell selection [GO:0045059]; protein autophosphorylation [GO:0046777]; protein phosphorylation [GO:0006468]; T cell activation [GO:0042110]; T cell aggregation [GO:0070489]; T cell differentiation [GO:0030217]; T cell migration [GO:0072678]; T cell receptor signaling pathway [GO:0050852]; transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]
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GO - Molecular function (MF):
ATP binding [GO:0005524]; non-membrane spanning protein tyrosine kinase activity [GO:0004715]; phosphotyrosine residue binding [GO:0001784]; protein serine/threonine/tyrosine kinase activity [GO:0004712]; protein tyrosine kinase activity [GO:0004713]; signaling receptor binding [GO:0005102]...
ATP binding [GO:0005524]; non-membrane spanning protein tyrosine kinase activity [GO:0004715]; phosphotyrosine residue binding [GO:0001784]; protein serine/threonine/tyrosine kinase activity [GO:0004712]; protein tyrosine kinase activity [GO:0004713]; signaling receptor binding [GO:0005102]
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GO - Cellular component (CC):
cell-cell junction [GO:0005911]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; extrinsic component of cytoplasmic side of plasma membrane [GO:0031234]; immunological synapse [GO:0001772]; plasma membrane [GO:0005886]; T cell receptor complex [GO:0042101]...
cell-cell junction [GO:0005911]; cytoplasm [GO:0005737]; cytosol [GO:0005829]; extrinsic component of cytoplasmic side of plasma membrane [GO:0031234]; immunological synapse [GO:0001772]; plasma membrane [GO:0005886]; T cell receptor complex [GO:0042101]
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ZAP70
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*NOTE: the Kaplan plots were collected from OncoLnc