ZAP70 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). Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily. Expressed in T- and natural killer cells. Also present in early thymocytes and pro/pre B-cells. 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.10.2; Kinase, protein; Protein kinase, TK; Protein kinase, tyrosine (non-receptor); Syk family; TK group
Chromosomal Location of mouse Ortholog: 1 B|1 15.41 cM
Cellular Component:  cell-cell junction; cytoplasm; cytosol; extrinsic component of cytoplasmic side of plasma membrane; immunological synapse; membrane; membrane raft; plasma membrane; T cell receptor complex
Molecular Function:  ATP binding; kinase activity; non-membrane spanning protein tyrosine kinase activity; nucleotide binding; phosphotyrosine residue binding; protein binding; protein kinase activity; protein tyrosine kinase activity; signaling receptor binding; transferase activity
Biological Process:  adaptive immune response; alpha-beta T cell differentiation; beta selection; calcium-mediated signaling; cell differentiation; immune response; immune system process; innate immune response; intracellular signal transduction; negative thymic T cell selection; peptidyl-tyrosine phosphorylation; phosphorylation; positive regulation of alpha-beta T cell differentiation; positive regulation of alpha-beta T cell proliferation; positive regulation of calcium-mediated signaling; positive regulation of T cell differentiation; positive thymic T cell selection; protein autophosphorylation; protein phosphorylation; T cell differentiation; T cell receptor signaling pathway; thymic T cell selection; transmembrane receptor protein tyrosine kinase signaling pathway
Reference #:  P43404 (UniProtKB)
Alt. Names/Synonyms: 70 kDa zeta-associated protein; 70 kDa zeta-chain associated protein; 70kDa; AI327364; mrtle; mur; Srk; Syk-related tyrosine kinase; Tyrosine-protein kinase ZAP-70; TZK; ZAP-; Zap-70; Zap70; zeta-chain (TCR) associated protein kinase
Gene Symbols: Zap70
Molecular weight: 70,112 Da
Basal Isoelectric point: 8.01  Predict pI for various phosphorylation states
CST Pathways:  T Cell Receptor Signaling  |  Tyrosine Kinases & Substrates
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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ZAP70

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Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  KinBase  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene