ID:ITK_HUMAN DESCRIPTION: RecName: Full=Tyrosine-protein kinase ITK/TSK; EC=2.7.10.2; AltName: Full=Interleukin-2-inducible T-cell kinase; Short=IL-2-inducible T-cell kinase; AltName: Full=Kinase EMT; AltName: Full=T-cell-specific kinase; AltName: Full=Tyrosine-protein kinase Lyk; FUNCTION: Tyrosine 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. CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. COFACTOR: Binds 1 zinc ion per subunit (By similarity). SUBUNIT: Homooligomerizes; 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. INTERACTION: P48023:FASLG; NbExp=3; IntAct=EBI-968552, EBI-495538; SUBCELLULAR LOCATION: Cytoplasm. Note=Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation. TISSUE SPECIFICITY: T-cell lines and natural killer cell lines. INDUCTION: Through a myriad of surface receptors including the TCR/CD3 signaling complex, coreceptors, or chemokine receptors. DOMAIN: The 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. PTM: Phosphorylated 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. DISEASE: Defects in ITK are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1) [MIM:613011]. LPSA1 is 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. SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily. SIMILARITY: Contains 1 Btk-type zinc finger. SIMILARITY: Contains 1 PH domain. SIMILARITY: Contains 1 protein kinase domain. SIMILARITY: Contains 1 SH2 domain. SIMILARITY: Contains 1 SH3 domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ITKID43329ch5q33.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q08881
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
