ZAP70

Zeta-chain (TCR) associated protein kinase 70kDa
PDB rendering based on 1m61.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1FBV, 1M61, 1U59, 2CBL, 2OQ1, 2OZO, 2Y1N, 3ZNI, 4A4B, 4A4C, 4K2R
Identifiers
Symbols	ZAP70 ; SRK; STCD; STD; TZK; ZAP-70
External IDs	OMIM: 176947 MGI: 99613 HomoloGene: 839 ChEMBL: 2803 GeneCards: ZAP70 Gene
EC number	2.7.10.2
Gene ontology Molecular function • phosphotyrosine binding • protein tyrosine kinase activity • non-membrane spanning protein tyrosine kinase activity • receptor binding • protein binding • ATP binding Cellular component • immunological synapse • cytoplasm • cytosol • plasma membrane • cell-cell junction • extrinsic component of cytoplasmic side of plasma membrane • T cell receptor complex • membrane raft Biological process • adaptive immune response • protein phosphorylation • immune response • transmembrane receptor protein tyrosine kinase signaling pathway • peptidyl-tyrosine phosphorylation • cell differentiation • T cell differentiation • intracellular signal transduction • peptidyl-tyrosine autophosphorylation • T cell activation • B cell activation • beta selection • positive thymic T cell selection • negative thymic T cell selection • innate immune response • positive regulation of T cell differentiation • positive regulation of alpha-beta T cell differentiation • positive regulation of alpha-beta T cell proliferation • positive regulation of calcium-mediated signaling • T cell receptor signaling pathway • T cell aggregation • T cell migration Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7535	22637
Ensembl	ENSG00000115085	ENSMUSG00000026117
UniProt	P43403	P43404
RefSeq (mRNA)	NM_001079	NM_001289612
RefSeq (protein)	NP_001070	NP_001276541
Location (UCSC)	Chr 2: 97.71 – 97.74 Mb	Chr 1: 36.76 – 36.78 Mb
PubMed search	[1]	[2]

ZAP-70 (Zeta-chain-associated protein kinase 70) is a protein normally expressed near the surface membrane of T cells and natural killer cells. It is part of the T cell receptor, and plays a critical role in T-cell signaling. Its molecular weight is 70 kDa, and it is a member of the protein-tyrosine kinase family.

Clinical significance

ZAP-70 in B cells is used as a prognostic marker in identifying different forms of chronic lymphocytic leukemia (CLL). DNA analysis has distinguished two major types of CLL, with different survival times. CLL that is positive for the marker ZAP-70 has an average survival of 8 years. CLL that is negative for ZAP-70 has an average survival of more than 25 years. Many patients, especially older ones, with slowly progressing disease can be reassured and may not need any treatment in their lifetimes.

In systemic lupus erythematosus, the Zap-70 receptor pathway is missing and Syk takes its place.

ZAP70 deficiency results in a form of immune deficiency.

Function

T lymphocytes are activated by engagement of the T cell receptor with processed antigen fragments presented by professional antigen presenting cells (i.e. macrophages, dendritic cells and B cells) via the MHC. Upon this activation, the TCR co-receptor CD4 or CD8 binds to the MHC, activating the co-receptor associated tyrosine kinase Lck. Lck phosphorylates the intracellular portions of the CD3 complex (called ITAMs), creating a docking site for ZAP-70. The most important member of the CD3 family is CD3-zeta, to which ZAP-70 binds (hence the abbreviation). The tandem SH2-domains of ZAP-70 are engaged by the doubly phosphorylated ITAMs of CD3-zeta, which positions ZAP-70 to phosphorylate the transmembrane protein linker of activated T cells (LAT). Phosphorylated LAT, in turn, serves as a docking site to which a number of signaling proteins bind including SLP-76. The final outcome of T cell activation is the transcription of several gene products which allow the T cells to differentiate, proliferate and secrete a number of cytokines.

Interactions

ZAP-70 has been shown to interact with:

• Cbl gene,
• Drebrin-like,
• FYN,
• Lck,
• LAT,
• SHB, and
• SHC1.

See also

• Lck
• Syk

External links

• GeneReviews/NIH/NCBI/UW entry on ZAP70-Related Severe Combined Immunodeficiency
• ZAP-70 Protein at the US National Library of Medicine Medical Subject Headings (MeSH)