Names & Taxonomy

Uniprot ID:
P43403
Entry Name:
ZAP70_HUMAN
Status:
reviewed
Protein Names:
Tyrosine-protein kinase ZAP-70 (EC 2.7.10.2) (70 kDa zeta-chain associated protein) (Syk-related tyrosine kinase)
Gene Names:
ZAP70 SRK
Gene Names Primary:
ZAP70
Organism:
Homo sapiens (Human)

Structure

Length:
619
Sequence:
MPDPAAHLPFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEFYSRDPDGLPCNLRKPCNRPSGLEPQPGVFDCLRDAMVRDYVRQTWKLEGEALEQAIISQAPQVEKLIATTAHERMPWYHSSLTREEAERKLYSGAQTDGKFLLRPRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEYLKLKADGLIYCLKEACPNSSASNASGAAAPTLPAHPSTLTHPQRRIDTLNSDGYTPEPARITSPDKPRPMPMDTSVYESPYSDPEELKDKKLFLKRDNLLIADIELGCGNFGSVRQGVYRMRKKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGGPLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDFGLSKALGADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPYKKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRACYYSLASKVEGPPGSTQKAEAACA
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm

Function

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).
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Enzyme Regulation:
ENZYME REGULATION: Activated by phosphorylation at Tyr-493 in the activation loop. Inhibited by staurosporine.
Active Site:
ACT_SITE 461 461 Proton acceptor.
Gene Ontology Go:
cell-cell junction
cytoplasm
cytosol
extrinsic component of cytoplasmic side of plasma membrane
immunological synapse
plasma membrane
T cell receptor complex
ATP binding
non-membrane spanning protein tyrosine kinase activity
protein tyrosine kinase activity
receptor binding
adaptive immune response
B cell activation
B cell receptor signaling pathway
beta selection
immune response
innate immune response
intracellular signal transduction
macrophage activation involved in immune response
negative thymic T cell selection
neutrophil activation involved in immune response
peptidyl-tyrosine autophosphorylation
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 phosphorylation
regulation of platelet aggregation
T cell activation
T cell aggregation
T cell differentiation
T cell migration
T cell receptor signaling pathway
transmembrane receptor protein tyrosine kinase signaling pathway
Gene Ontology Biological Process:
adaptive immune response
B cell activation
B cell receptor signaling pathway
beta selection
immune response
innate immune response
intracellular signal transduction
macrophage activation involved in immune response
negative thymic T cell selection
neutrophil activation involved in immune response
peptidyl-tyrosine autophosphorylation
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 phosphorylation
regulation of platelet aggregation
T cell activation
T cell aggregation
T cell differentiation
T cell migration
T cell receptor signaling pathway
transmembrane receptor protein tyrosine kinase signaling pathway
Gene Ontology Molecular Function:
ATP binding
non-membrane spanning protein tyrosine kinase activity
protein tyrosine kinase activity
receptor binding
Gene Ontology Cellular Component:
cell-cell junction
cytoplasm
cytosol
extrinsic component of cytoplasmic side of plasma membrane
immunological synapse
plasma membrane
T cell receptor complex
Keywords:
3D-structure
ATP-binding
Acetylation
Adaptive immunity
Alternative splicing
Cell membrane
Complete proteome
Cytoplasm
Disease mutation
Immunity
Kinase
Membrane
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Repeat
SCID
SH2 domain
Transferase
Tyrosine-protein kinase
Interacts With:
P20963; P07766; P00533; P10721; P06239; P08581; Q9Y2R2; Q8BGG7

Publication

PubMed ID:
1423621 14985102 15815621 15489334 8124727 7528772 7781602 8702662 8943331 9151714 9378960 9489702 9813084 10037717 10449770 11353765 12051764 11828374 12084069 12522270 15144186 15143214 16339550 15592455 16467082 16461343 19290920 19690332 19608861 20135127 7659156 10078535 10966114 12450381 15292186 17512407 8202713 11412303 11123350 17344846 18509675