| Background: | 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 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-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). |
| Synonyms: | Tyrosine-protein kinase ZAP-70 (EC 2.7.10.2) (70 kDa zeta-chain associated protein) (Syk-related tyrosine kinase), Zap70, Srk, Zap-70 |
| UniProt Protein Function: | ZAP70: a tyrosine kinase of the Syk family. Associates with the T-cell antigen receptor zeta-chain after TCR stimulation. Phosphorylated by Src-family kinases following antigen receptor activation. Plays a role in lymphocyte activation.Protein type: EC 2.7.10.2; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); Kinase, protein; TK group; Syk familyCellular Component: cytoplasm; cytosol; extrinsic to internal side of plasma membrane; immunological synapse; intercellular junction; lipid raft; membrane; plasma membrane; T cell receptor complexMolecular Function: ATP binding; non-membrane spanning protein tyrosine kinase activity; phosphotyrosine binding; protein binding; protein kinase activity; protein-tyrosine kinase activity; receptor bindingBiological Process: adaptive immune response; B cell receptor signaling pathway; beta selection; immune response; inflammatory response; innate immune response; macrophage activation during immune response; negative thymic T cell selection; neutrophil activation during immune response; peptidyl-tyrosine phosphorylation; positive regulation of alpha-beta T cell differentiation; positive regulation of alpha-beta T cell proliferation; positive regulation of B cell differentiation; positive regulation of calcium-mediated signaling; positive regulation of cell adhesion mediated by integrin; positive regulation of mast cell degranulation; positive regulation of T cell differentiation; positive thymic T cell selection; protein amino acid autophosphorylation; protein amino acid phosphorylation; T cell receptor signaling pathway; thymic T cell selection; transmembrane receptor protein tyrosine kinase signaling pathway |
| UniProt Protein Details: | |
| NCBI Summary: | This gene encodes a member of the protein tyrosine kinase family. The encoded protein is essential for development of T lymphocytes and thymocytes, and functions in the initial step of T lymphocyte receptor-mediated signal transduction. A mutation in this gene causes chronic autoimmune arthritis, similar to rheumatoid arthritis in humans. Mice lacking this gene are deficient in alpha-beta T lymphocytes in the thymus. In humans, mutations in this gene cause selective T-cell defect, a severe combined immunodeficiency disease characterized by a selective absence of CD8-positive T lymphocytes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014] |
| UniProt Code: | P43404 |
| NCBI GenInfo Identifier: | 363548498 |
| NCBI Gene ID: | 22637 |
| NCBI Accession: | P43404.3 |
| UniProt Secondary Accession: | P43404,P97455, Q80VV2, Q8CHJ3 |
| UniProt Related Accession: | P43404 |
| Molecular Weight: | 35,255 Da |
| NCBI Full Name: | Tyrosine-protein kinase ZAP-70 |
| NCBI Synonym Full Names: | zeta-chain (TCR) associated protein kinase |
| NCBI Official Symbol: | Zap70Â Â |
| NCBI Official Synonym Symbols: | Srk; mur; mrtle; ZAP-70Â Â |
| NCBI Protein Information: | tyrosine-protein kinase ZAP-70 |
| UniProt Protein Name: | Tyrosine-protein kinase ZAP-70 |
| UniProt Synonym Protein Names: | 70 kDa zeta-chain associated protein; Syk-related tyrosine kinase |
| Protein Family: | Tyrosine-protein kinase |
| UniProt Gene Name: | Zap70Â Â |
| UniProt Entry Name: | ZAP70_MOUSE |
