ZAP70 [The Human Chemical-Genetic Interaction Map Project]

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======= ZAP70 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: ZAP70
  * **<color #00a2e8>Official Name</color>**: zeta chain of T cell receptor associated protein kinase 70
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=7535|7535]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P43403|P43403]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=ZAP70&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20ZAP70|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/176947|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes an enzyme belonging to the protein tyrosine kinase family, and it plays a role in T-cell development and lymphocyte activation. This enzyme, which is phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation, functions in the initial step of TCR-mediated signal transduction in combination with the Src family kinases, Lck and Fyn. This enzyme is also essential for thymocyte development. Mutations in this gene cause selective T-cell defect, a severe combined immunodeficiency disease characterized by a selective absence of CD8-positive T-cells. Two transcript variants that encode different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000269|PubMed:11353765, ECO:0000269|PubMed:12051764, ECO:0000269|PubMed:1423621, ECO:0000269|PubMed:20135127, ECO:0000269|PubMed:26903241, ECO:0000269|PubMed:8124727, ECO:0000269|PubMed:8702662, ECO:0000269|PubMed:9489702}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Pkinase|
|Pkinase Tyr|
|SH2|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|T cell aggregation|
|beta selection|
|lymphocyte aggregation|
|leukocyte aggregation|
|negative thymic T cell selection|
|positive thymic T cell selection|
|negative T cell selection|
|positive regulation of alpha-beta T cell proliferation|
|thymic T cell selection|
|positive T cell selection|
|T cell migration|
|regulation of alpha-beta T cell proliferation|
|immunological synapse|
|T cell selection|
|phosphotyrosine residue binding|
|positive regulation of calcium-mediated signaling|
|non-membrane spanning protein tyrosine kinase activity|
|positive regulation of alpha-beta T cell differentiation|
|T cell differentiation in thymus|
|leukocyte cell-cell adhesion|
|alpha-beta T cell differentiation|
|positive regulation of alpha-beta T cell activation|
|alpha-beta T cell activation|
|regulation of alpha-beta T cell differentiation|
|lymphocyte migration|
|positive regulation of T cell differentiation|
|protein tyrosine kinase activity|
|regulation of alpha-beta T cell activation|
|positive regulation of lymphocyte differentiation|
|positive regulation of T cell proliferation|
|regulation of calcium-mediated signaling|
|T cell receptor complex|
|positive regulation of lymphocyte proliferation|
|positive regulation of mononuclear cell proliferation|
|T cell differentiation|
|positive regulation of leukocyte proliferation|
|regulation of T cell differentiation|
|peptidyl-tyrosine phosphorylation|
|peptidyl-tyrosine modification|
|positive regulation of leukocyte differentiation|
|B cell activation|
|regulation of T cell proliferation|
|regulation of lymphocyte differentiation|
|cell-cell junction|
|T cell receptor signaling pathway|
|positive regulation of hemopoiesis|
|protein autophosphorylation|
|positive regulation of T cell activation|
|regulation of lymphocyte proliferation|
|regulation of mononuclear cell proliferation|
|positive regulation of leukocyte cell-cell adhesion|
|regulation of leukocyte proliferation|
|membrane raft|
|T cell activation|
|lymphocyte differentiation|
|positive regulation of cell-cell adhesion|
|regulation of leukocyte differentiation|
|antigen receptor-mediated signaling pathway|
|regulation of leukocyte cell-cell adhesion|
|regulation of T cell activation|
|leukocyte differentiation|
|positive regulation of lymphocyte activation|
|leukocyte migration|
|lymphocyte activation|
|regulation of cell-cell adhesion|
|positive regulation of cell adhesion|
|positive regulation of leukocyte activation|
|positive regulation of cell activation|
|immune response-activating cell surface receptor signaling pathway|
|regulation of hemopoiesis|
|immune response-regulating cell surface receptor signaling pathway|
|cell-cell adhesion|
|regulation of lymphocyte activation|
|hemopoiesis|
|immune response-activating signal transduction|
|immune response-regulating signaling pathway|
|regulation of leukocyte activation|
|hematopoietic or lymphoid organ development|
|adaptive immune response|
|activation of immune response|
|regulation of cell activation|
|immune system development|
|regulation of cell adhesion|
|positive regulation of immune response|
|peptidyl-amino acid modification|
|positive regulation of cell population proliferation|
|leukocyte activation|
|cell adhesion|
|biological adhesion|
|cell migration|
|positive regulation of cell differentiation|
|protein phosphorylation|
|positive regulation of intracellular signal transduction|
|cell activation|
|cell motility|
|localization of cell|
|positive regulation of immune system process|
|regulation of immune response|
|phosphorylation|
|locomotion|
|positive regulation of developmental process|
|ATP binding|
|movement of cell or subcellular component|
|regulation of cell population proliferation|
|regulation of immune system process|
|positive regulation of signal transduction|
|intracellular signal transduction|
|positive regulation of multicellular organismal process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|immune response|
</modal>
\\

 === CRISPR Data ===
<button type='default' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
No hits were found.
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 1/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 12289
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.39 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='ZAP70 Expression in NALM6 Cells: 5.39'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>