Summary | |
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Symbol | ZAP70 |
Name | zeta-chain (TCR) associated protein kinase 70kDa |
Aliases | ZAP-70; zeta-chain (TCR) associated protein kinase (70 kD); STCD; TZK; 70 kDa zeta-associated protein; 70 kD ...... |
Chromosomal Location | 2q11-q13 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway |
Subcellular Location | Cytoplasm Cell membrane Peripheral membrane protein Note=In quiescent T-lymphocytes, it is cytoplasmic. Upon TCR activation, it is recruited at the plasma membrane by interacting with CD247/CD3Z. Colocalizes together with RHOH in the immunological synapse. RHOH is required for its proper localization to the cell membrane and cytoskeleton fractions in the thymocytes (By similarity). |
Domain |
PF07714 Protein tyrosine kinase PF00017 SH2 domain |
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). |
Biological Process |
GO:0002250 adaptive immune response GO:0002263 cell activation involved in immune response GO:0002274 myeloid leukocyte activation GO:0002275 myeloid cell activation involved in immune response GO:0002279 mast cell activation involved in immune response GO:0002281 macrophage activation involved in immune response GO:0002283 neutrophil activation involved in immune response GO:0002366 leukocyte activation involved in immune response GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002443 leukocyte mediated immunity GO:0002444 myeloid leukocyte mediated immunity GO:0002448 mast cell mediated immunity GO:0002521 leukocyte differentiation GO:0002694 regulation of leukocyte activation GO:0002696 positive regulation of leukocyte activation GO:0002697 regulation of immune effector process GO:0002699 positive regulation of immune effector process GO:0002703 regulation of leukocyte mediated immunity GO:0002705 positive regulation of leukocyte mediated immunity GO:0002757 immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0002886 regulation of myeloid leukocyte mediated immunity GO:0002888 positive regulation of myeloid leukocyte mediated immunity GO:0006887 exocytosis GO:0007159 leukocyte cell-cell adhesion GO:0007596 blood coagulation GO:0007599 hemostasis GO:0010543 regulation of platelet activation GO:0017157 regulation of exocytosis GO:0018108 peptidyl-tyrosine phosphorylation GO:0018212 peptidyl-tyrosine modification GO:0019722 calcium-mediated signaling GO:0019932 second-messenger-mediated signaling GO:0022407 regulation of cell-cell adhesion GO:0022409 positive regulation of cell-cell adhesion GO:0030098 lymphocyte differentiation GO:0030168 platelet activation GO:0030183 B cell differentiation GO:0030193 regulation of blood coagulation GO:0030217 T cell differentiation GO:0032386 regulation of intracellular transport GO:0032388 positive regulation of intracellular transport GO:0032418 lysosome localization GO:0032943 mononuclear cell proliferation GO:0032944 regulation of mononuclear cell proliferation GO:0032946 positive regulation of mononuclear cell proliferation GO:0033003 regulation of mast cell activation GO:0033005 positive regulation of mast cell activation GO:0033006 regulation of mast cell activation involved in immune response GO:0033008 positive regulation of mast cell activation involved in immune response GO:0033077 T cell differentiation in thymus GO:0033627 cell adhesion mediated by integrin GO:0033628 regulation of cell adhesion mediated by integrin GO:0033630 positive regulation of cell adhesion mediated by integrin GO:0034109 homotypic cell-cell adhesion GO:0034110 regulation of homotypic cell-cell adhesion GO:0036230 granulocyte activation GO:0038083 peptidyl-tyrosine autophosphorylation GO:0042098 T cell proliferation GO:0042102 positive regulation of T cell proliferation GO:0042110 T cell activation GO:0042113 B cell activation GO:0042116 macrophage activation GO:0042119 neutrophil activation GO:0042129 regulation of T cell proliferation GO:0043299 leukocyte degranulation GO:0043300 regulation of leukocyte degranulation GO:0043302 positive regulation of leukocyte degranulation GO:0043303 mast cell degranulation GO:0043304 regulation of mast cell degranulation GO:0043306 positive regulation of mast cell degranulation GO:0043366 beta selection GO:0043368 positive T cell selection GO:0043383 negative T cell selection GO:0045055 regulated exocytosis GO:0045058 T cell selection GO:0045059 positive thymic T cell selection GO:0045060 negative thymic T cell selection GO:0045061 thymic T cell selection GO:0045576 mast cell activation GO:0045577 regulation of B cell differentiation GO:0045579 positive regulation of B cell differentiation GO:0045580 regulation of T cell differentiation GO:0045582 positive regulation of T cell differentiation GO:0045619 regulation of lymphocyte differentiation GO:0045621 positive regulation of lymphocyte differentiation GO:0045785 positive regulation of cell adhesion GO:0045921 positive regulation of exocytosis GO:0046631 alpha-beta T cell activation GO:0046632 alpha-beta T cell differentiation GO:0046633 alpha-beta T cell proliferation GO:0046634 regulation of alpha-beta T cell activation GO:0046635 positive regulation of alpha-beta T cell activation GO:0046637 regulation of alpha-beta T cell differentiation GO:0046638 positive regulation of alpha-beta T cell differentiation GO:0046640 regulation of alpha-beta T cell proliferation GO:0046641 positive regulation of alpha-beta T cell proliferation GO:0046651 lymphocyte proliferation GO:0046777 protein autophosphorylation GO:0050670 regulation of lymphocyte proliferation GO:0050671 positive regulation of lymphocyte proliferation GO:0050817 coagulation GO:0050818 regulation of coagulation GO:0050848 regulation of calcium-mediated signaling GO:0050850 positive regulation of calcium-mediated signaling GO:0050851 antigen receptor-mediated signaling pathway GO:0050852 T cell receptor signaling pathway GO:0050853 B cell receptor signaling pathway GO:0050863 regulation of T cell activation GO:0050864 regulation of B cell activation GO:0050865 regulation of cell activation GO:0050867 positive regulation of cell activation GO:0050870 positive regulation of T cell activation GO:0050871 positive regulation of B cell activation GO:0050878 regulation of body fluid levels GO:0050900 leukocyte migration GO:0051047 positive regulation of secretion GO:0051249 regulation of lymphocyte activation GO:0051251 positive regulation of lymphocyte activation GO:0051640 organelle localization GO:0051656 establishment of organelle localization GO:0060627 regulation of vesicle-mediated transport GO:0061041 regulation of wound healing GO:0070486 leukocyte aggregation GO:0070489 T cell aggregation GO:0070527 platelet aggregation GO:0070661 leukocyte proliferation GO:0070663 regulation of leukocyte proliferation GO:0070665 positive regulation of leukocyte proliferation GO:0071593 lymphocyte aggregation GO:0071594 thymocyte aggregation GO:0072676 lymphocyte migration GO:0072678 T cell migration GO:0090330 regulation of platelet aggregation GO:1900046 regulation of hemostasis GO:1902105 regulation of leukocyte differentiation GO:1902107 positive regulation of leukocyte differentiation GO:1903034 regulation of response to wounding GO:1903037 regulation of leukocyte cell-cell adhesion GO:1903039 positive regulation of leukocyte cell-cell adhesion GO:1903305 regulation of regulated secretory pathway GO:1903307 positive regulation of regulated secretory pathway GO:1903532 positive regulation of secretion by cell GO:1903706 regulation of hemopoiesis GO:1903708 positive regulation of hemopoiesis |
Molecular Function |
GO:0001784 phosphotyrosine binding GO:0004713 protein tyrosine kinase activity GO:0004715 non-membrane spanning protein tyrosine kinase activity GO:0045309 protein phosphorylated amino acid binding GO:0051219 phosphoprotein binding |
Cellular Component |
GO:0001772 immunological synapse GO:0009898 cytoplasmic side of plasma membrane GO:0019897 extrinsic component of plasma membrane GO:0019898 extrinsic component of membrane GO:0031234 extrinsic component of cytoplasmic side of plasma membrane GO:0042101 T cell receptor complex GO:0043235 receptor complex GO:0045121 membrane raft GO:0098552 side of membrane GO:0098562 cytoplasmic side of membrane GO:0098589 membrane region GO:0098802 plasma membrane receptor complex GO:0098857 membrane microdomain |
KEGG |
hsa04014 Ras signaling pathway hsa04064 NF-kappa B signaling pathway hsa04650 Natural killer cell mediated cytotoxicity hsa04660 T cell receptor signaling pathway |
Reactome |
R-HSA-1280218: Adaptive Immune System R-HSA-202433: Generation of second messenger molecules R-HSA-168256: Immune System R-HSA-202403: TCR signaling R-HSA-202430: Translocation of ZAP-70 to Immunological synapse |
Summary | |
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Symbol | ZAP70 |
Name | zeta-chain (TCR) associated protein kinase 70kDa |
Aliases | ZAP-70; zeta-chain (TCR) associated protein kinase (70 kD); STCD; TZK; 70 kDa zeta-associated protein; 70 kD ...... |
Chromosomal Location | 2q11-q13 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Literatures that report relations between ZAP70 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells. |
Literatures describing the relation between ZAP70 and anti-tumor immunity in human cancer.
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Summary | |
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Symbol | ZAP70 |
Name | zeta-chain (TCR) associated protein kinase 70kDa |
Aliases | ZAP-70; zeta-chain (TCR) associated protein kinase (70 kD); STCD; TZK; 70 kDa zeta-associated protein; 70 kD ...... |
Chromosomal Location | 2q11-q13 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets. |
> High-throughput Screening
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Statistical results of ZAP70 in screening data sets for detecting immune reponses.
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Summary | |
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Symbol | ZAP70 |
Name | zeta-chain (TCR) associated protein kinase 70kDa |
Aliases | ZAP-70; zeta-chain (TCR) associated protein kinase (70 kD); STCD; TZK; 70 kDa zeta-associated protein; 70 kD ...... |
Chromosomal Location | 2q11-q13 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders |
Points in the above scatter plot represent the expression difference of ZAP70 in various data sets.
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Points in the above scatter plot represent the mutation difference of ZAP70 in various data sets.
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Summary | |
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Symbol | ZAP70 |
Name | zeta-chain (TCR) associated protein kinase 70kDa |
Aliases | ZAP-70; zeta-chain (TCR) associated protein kinase (70 kD); STCD; TZK; 70 kDa zeta-associated protein; 70 kD ...... |
Chromosomal Location | 2q11-q13 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of ZAP70. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene. |
Summary | |
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Symbol | ZAP70 |
Name | zeta-chain (TCR) associated protein kinase 70kDa |
Aliases | ZAP-70; zeta-chain (TCR) associated protein kinase (70 kD); STCD; TZK; 70 kDa zeta-associated protein; 70 kD ...... |
Chromosomal Location | 2q11-q13 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of ZAP70. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by ZAP70. > Immunoinhibitor > Immunostimulator > MHC molecule |
Summary | |
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Symbol | ZAP70 |
Name | zeta-chain (TCR) associated protein kinase 70kDa |
Aliases | ZAP-70; zeta-chain (TCR) associated protein kinase (70 kD); STCD; TZK; 70 kDa zeta-associated protein; 70 kD ...... |
Chromosomal Location | 2q11-q13 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of ZAP70. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor |
Summary | |
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Symbol | ZAP70 |
Name | zeta-chain (TCR) associated protein kinase 70kDa |
Aliases | ZAP-70; zeta-chain (TCR) associated protein kinase (70 kD); STCD; TZK; 70 kDa zeta-associated protein; 70 kD ...... |
Chromosomal Location | 2q11-q13 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Distribution of ZAP70 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype |
Summary | |
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Symbol | ZAP70 |
Name | zeta-chain (TCR) associated protein kinase 70kDa |
Aliases | ZAP-70; zeta-chain (TCR) associated protein kinase (70 kD); STCD; TZK; 70 kDa zeta-associated protein; 70 kD ...... |
Chromosomal Location | 2q11-q13 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Associations between ZAP70 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade |
Summary | |
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Symbol | ZAP70 |
Name | zeta-chain (TCR) associated protein kinase 70kDa |
Aliases | ZAP-70; zeta-chain (TCR) associated protein kinase (70 kD); STCD; TZK; 70 kDa zeta-associated protein; 70 kD ...... |
Chromosomal Location | 2q11-q13 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Drugs targeting ZAP70 collected from DrugBank database. |
Details on drugs targeting ZAP70.
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