Tyrosine-protein kinase ZAP-70

Details

Name
Tyrosine-protein kinase ZAP-70
Synonyms
  • 2.7.10.2
  • 70 kDa zeta-chain associated protein
  • SRK
  • Syk-related tyrosine kinase
Gene Name
ZAP70
Organism
Humans
Amino acid sequence
>lcl|BSEQ0002606|Tyrosine-protein kinase ZAP-70
MPDPAAHLPFFYGSISRAEAEEHLKLAGMADGLFLLRQCLRSLGGYVLSLVHDVRFHHFP
IERQLNGTYAIAGGKAHCGPAELCEFYSRDPDGLPCNLRKPCNRPSGLEPQPGVFDCLRD
AMVRDYVRQTWKLEGEALEQAIISQAPQVEKLIATTAHERMPWYHSSLTREEAERKLYSG
AQTDGKFLLRPRKEQGTYALSLIYGKTVYHYLISQDKAGKYCIPEGTKFDTLWQLVEYLK
LKADGLIYCLKEACPNSSASNASGAAAPTLPAHPSTLTHPQRRIDTLNSDGYTPEPARIT
SPDKPRPMPMDTSVYESPYSDPEELKDKKLFLKRDNLLIADIELGCGNFGSVRQGVYRMR
KKQIDVAIKVLKQGTEKADTEEMMREAQIMHQLDNPYIVRLIGVCQAEALMLVMEMAGGG
PLHKFLVGKREEIPVSNVAELLHQVSMGMKYLEEKNFVHRDLAARNVLLVNRHYAKISDF
GLSKALGADDSYYTARSAGKWPLKWYAPECINFRKFSSRSDVWSYGVTMWEALSYGQKPY
KKMKGPEVMAFIEQGKRMECPPECPPELYALMSDCWIYKWEDRPDFLTVEQRMRACYYSL
ASKVEGPPGSTQKAEAACA
Number of residues
619
Molecular Weight
69871.63
Theoretical pI
7.75
GO Classification
Functions
ATP binding / non-membrane spanning protein tyrosine kinase activity / protein tyrosine kinase activity / receptor binding
Processes
adaptive immune response / B cell activation / beta selection / cell differentiation / immune response / innate immune response / intracellular signal transduction / negative thymic T cell selection / 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 calcium-mediated signaling / positive regulation of T cell differentiation / positive thymic T cell selection / protein phosphorylation / T cell activation / T cell aggregation / T cell differentiation / T cell migration / T cell receptor signaling pathway / transmembrane receptor protein tyrosine kinase signaling pathway
Components
cell-cell junction / cytoplasm / cytosol / extrinsic component of cytoplasmic side of plasma membrane / immunological synapse / plasma membrane / T cell receptor complex
General Function
Receptor binding
Specific 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).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0021292|Tyrosine-protein kinase ZAP-70 (ZAP70)
ATGCCAGACCCCGCGGCGCACCTGCCCTTCTTCTACGGCAGCATCTCGCGTGCCGAGGCC
GAGGAGCACCTGAAGCTGGCGGGCATGGCGGACGGGCTCTTCCTGCTGCGCCAGTGCCTG
CGCTCGCTGGGCGGCTATGTGCTGTCGCTCGTGCACGATGTGCGCTTCCACCACTTTCCC
ATCGAGCGCCAGCTCAACGGCACCTACGCCATTGCCGGCGGCAAAGCGCACTGTGGACCG
GCAGAGCTCTGCGAGTTCTACTCGCGCGACCCCGACGGGCTGCCCTGCAACCTGCGCAAG
CCGTGCAACCGGCCGTCGGGCCTCGAGCCGCAGCCGGGGGTCTTCGACTGCCTGCGAGAC
GCCATGGTGCGTGACTACGTGCGCCAGACGTGGAAGCTGGAGGGCGAGGCCCTGGAGCAG
GCCATCATCAGCCAGGCCCCGCAGGTGGAGAAGCTCATTGCTACGACGGCCCACGAGCGG
ATGCCCTGGTACCACAGCAGCCTGACGCGTGAGGAGGCCGAGCGCAAACTTTACTCTGGG
GCGCAGACCGACGGCAAGTTCCTGCTGAGGCCGCGGAAGGAGCAGGGCACATACGCCCTG
TCCCTCATCTATGGGAAGACGGTGTACCACTACCTCATCAGCCAAGACAAGGCGGGCAAG
TACTGCATTCCCGAGGGCACCAAGTTTGACACGCTCTGGCAGCTGGTGGAGTATCTGAAG
CTGAAGGCGGACGGGCTCATCTACTGCCTGAAGGAGGCCTGCCCCAACAGCAGTGCCAGC
AACGCCTCAGGGGCTGCTGCTCCCACACTCCCAGCCCACCCATCCACGTTGACTCATCCT
CAGAGACGAATCGACACCCTCAACTCAGATGGATACACCCCTGAGCCAGCACGCATAACG
TCCCCAGACAAACCGCGGCCGATGCCCATGGACACGAGCGTGTATGAGAGCCCCTACAGC
GACCCAGAGGAGCTCAAGGACAAGAAGCTCTTCCTGAAGCGCGATAACCTCCTCATAGCT
GACATTGAACTTGGCTGCGGCAACTTTGGCTCAGTGCGCCAGGGCGTGTACCGCATGCGC
AAGAAGCAGATCGACGTGGCCATCAAGGTGCTGAAGCAGGGCACGGAGAAGGCAGACACG
GAAGAGATGATGCGCGAGGCGCAGATCATGCACCAGCTGGACAACCCCTACATCGTGCGG
CTCATTGGCGTCTGCCAGGCCGAGGCCCTCATGCTGGTCATGGAGATGGCTGGGGGCGGG
CCGCTGCACAAGTTCCTGGTCGGCAAGAGGGAGGAGATCCCTGTGAGCAATGTGGCCGAG
CTGCTGCACCAGGTGTCCATGGGGATGAAGTACCTGGAGGAGAAGAACTTTGTGCACCGT
GACCTGGCGGCCCGCAACGTCCTGCTGGTTAACCGGCACTACGCCAAGATCAGCGACTTT
GGCCTCTCCAAAGCACTGGGTGCCGACGACAGCTACTACACTGCCCGCTCAGCAGGGAAG
TGGCCGCTCAAGTGGTACGCACCCGAATGCATCAACTTCCGCAAGTTCTCCAGCCGCAGC
GATGTCTGGAGCTATGGGGTCACCATGTGGGAGGCCTTGTCCTACGGCCAGAAGCCCTAC
AAGAAGATGAAAGGGCCGGAGGTCATGGCCTTCATCGAGCAGGGCAAGCGGATGGAGTGC
CCACCAGAGTGTCCACCCGAACTGTACGCACTCATGAGTGACTGCTGGATCTACAAGTGG
GAGGATCGCCCCGACTTCCTGACCGTGGAGCAGCGCATGCGAGCCTGTTACTACAGCCTG
GCCAGCAAGGTGGAAGGGCCCCCAGGCAGCACACAGAAGGCTGAGGCTGCCTGTGCCTGA
Chromosome Location
2
Locus
2q12
External Identifiers
ResourceLink
UniProtKB IDP43403
UniProtKB Entry NameZAP70_HUMAN
GenBank Gene IDL05148
GenAtlas IDZAP70
HGNC IDHGNC:12858
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02010StaurosporineexperimentalunknownDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails