MGP Database

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MGP001680

UniProt Annotations

Entry Information
Gene NameIL2-inducible T-cell kinase
Protein EntryITK_HUMAN
UniProt IDQ08881
SpeciesHuman
Comments
Comment typeDescription
Catalytic ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- ProRule:PRU10028}.
CofactorName=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; Note=Binds 1 zinc ion per subunit. {ECO:0000250};
DiseaseLymphoproliferative syndrome 1 (LPFS1) [MIM:613011]: A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma. {ECO:0000269|PubMed:19425169}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe N-terminal PH domain allows ITK to be recruited to the plasma membrane by an activated PI3 kinase. This domain contains also a proline-rich region (PRR). The adjoining domain is a SH3 domain, which binds to PRR (from itself or from other proteins). Next, a SH2 domain is required for binding tyrosine-phosphorylated substrates. In the C-terminal region, the kinase domain is required for tyrosine phosphorylation. {ECO:0000269|PubMed:10795735}.
FunctionTyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. {ECO:0000269|PubMed:12186560, ECO:0000269|PubMed:12682224, ECO:0000269|PubMed:21725281}.
InductionThrough a myriad of surface receptors including the TCR/CD3 signaling complex, coreceptors, or chemokine receptors. {ECO:0000269|PubMed:8504851, ECO:0000269|PubMed:9701039}.
InteractionP04626:ERBB2; NbExp=2; IntAct=EBI-968552, EBI-641062; P48023:FASLG; NbExp=3; IntAct=EBI-968552, EBI-495538;
PtmPhosphorylated at Tyr-512 in the activation loop of the kinase domain by LCK. Subsequent autophosphorylation at Tyr-180 leads to the kinase activation. The autophosphorylated Tyr-180 lies within the substrate binding sequence of the SH3 domain. {ECO:0000269|PubMed:12573241, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:9312162}.
PtmUbiquitinated. {ECO:0000269|PubMed:20596523}.
SimilarityBelongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily. {ECO:0000255|PROSITE- ProRule:PRU00159}.
SimilarityContains 1 Btk-type zinc finger. {ECO:0000255|PROSITE- ProRule:PRU00432}.
SimilarityContains 1 PH domain. {ECO:0000255|PROSITE- ProRule:PRU00145}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
SimilarityContains 1 SH2 domain. {ECO:0000255|PROSITE- ProRule:PRU00191}.
SimilarityContains 1 SH3 domain. {ECO:0000255|PROSITE- ProRule:PRU00192}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:17060314}. Note=Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation.
SubunitHomooligomerizes; this association negatively regulates kinase activity (By similarity). Interacts with PPIA/CYPA; this interaction regulates TCR signal strength via a proline-directed conformational switch in ITK. Interacts with THEMIS (By similarity). Interacts with FASLG. Interacts with VAV1; this interaction is important for VAV1 localization and TCR-induced actin polarization. {ECO:0000250, ECO:0000269|PubMed:15308100, ECO:0000269|PubMed:15661896, ECO:0000269|PubMed:19807924}.
Tissue SpecificityT-cell lines and natural killer cell lines.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ITKID43329ch5q33.html";
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