ITK

IL-2-inducible T cell kinase is a member of the protein kinase superfamily, Tyr protein kinase family and TEC subfamily. It contains 1 Btk-type zinc finger, 1 PH domain, 1 protein kinase domain, 1 SH2 domain and 1 SH3 domain. As an intracellular kinase which expressed in T-cells, IL-2-inducible T cell kinase contains both SH2 and SH3 domains which are often found in intracellular kinases. It is hought to play a role in T-cell proliferation and differentiation. It regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. IL-2-inducible T cell kinase also plays an essential role in regulation of the adaptive immune response. efects in IL-2-inducible T cell kinase are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1). 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.

ITK Related Areas

Enzyme>>Protein Kinase>>Intracellular Kinase>>ITK

Signal Transduction>>Protein Kinase>>Intracellular Kinase>>ITK

ITK Alternative Names

EMT, LYK, MGC126257, MGC126258, PSCTK2, IL-2-inducible T cell kinase, IL-2-inducible T-cell kinase, T-cell-specific kinase, homolog of mouse T-cell itk/tsk, interleukin-2-inducible T cell kinase, interleukin-2-inducible T-cell kinase, kinase EMT, tyrosine-protein kinase ITK/TSK, tyrosine-protein kinase LYK [Homo sapiens]

RP23-273O7.1, Emt, Tcsk, Tsk, IL-2-inducible T-cell kinase, IL2-inducible T-cell kinase, T-cell-specific kinase, interleukin-2-inducible T cell kinase; kinase EMT, kinase TLK, tyrosine-protein kinase ITK/TSK [Mus musculus]

Summaries for ITK

Entrez Gene summary for ITK:

This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation.

OMIM - description for ITK:

ITK is the T-cell-specific homolog of Bruton tyrosine kinase (BTK), which is mutant in X-linked agammaglobulinemia (300300). Cheng et al. (1994) showed that BTK interacts with 3 protein-tyrosine kinases that get activated upon stimulation of B- and T-cell receptors. These interactions are mediated by two 10-amino acid motifs in BTK; an analogous site with the same specificity is also present in ITK.

Wikipedia summary for ITK:

Signal transduction through the T-cell receptor (TCR; see 186880) and cytokine receptors on the surface of T lymphocytes occurs largely via tyrosine phosphorylation of intracellular substrates. Signal transduction is thought to occur via association of these receptors with intracellular protein tyrosine kinases. To identify unique T-cell tyrosine kinases, Gibson et al. (1993) used PCR-based cloning with degenerate oligonucleotides directed at highly conserved motifs of tyrosine kinase domains. In this way, they cloned the complete cDNA for a unique human tyrosine kinase that is expressed mainly in T lymphocytes and natural killer (NK) cells. The cDNA predicted an open reading frame of 1,866 bp encoding a protein with a predicted size of 72 kD, which was in keeping with its size on Western blotting. A single 6.2-kb mRNA and 72-kD protein were detected in T lymphocytes and NK-like cell lines, but were not detected in other cell lineages. Sequence comparisons suggested that the protein is probably the human homolog of a murine interleukin-2-inducible T-cell kinase (ITK). However, unlike ITK, the message and protein levels for the new entity did not vary markedly on stimulation of human IL-2 responsive T cells with IL-2. They referred to the gene and its protein product as EMT ('expressed mainly in T cells'). They concluded that EMT is a member of a new family of intracellular kinases that includes BPK (the kinase mutant in X-linked agammaglobulinemia, 300300). The expression of EMT message and protein in thymocytes and mature T cells, combined with its homology to BPK and its chromosomal localization, suggested that EMT may play a role in thymic ontogeny and growth regulation of mature T cells.

Human ITK Protein General Information

 

• Protein names: Recommended name: Tyrosine-protein kinase ITK/TSK EC=2.7.10.2 Alternative name(s): Interleukin-2-inducible T-cell kinase Short name=IL-2-inducible T-cell kinase
• Sequence length: 620 AA.
• 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
• Sequence similarities: 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.
• Post-translational modification: 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.
• 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.
• Involvement in 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

General information above from UniProt

Function for ITK Protein

UniProtKB:

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

Genatlas:

• ITK is involved in regulating antigen receptor induced serum response factor (SRF) activation
• ITK is involved in T-cell proliferation and differentiation

Homology for human ITK

• homolog to murine Itk (94.35 pc) intraspecies
• homolog to rattus Itk (94.52 pc)

Phenotype Information for ITK

• Gene/Locus: ITK, EMT
• Phenotype: Lymphoproliferative syndrome, EBV-associated, autosomal, 1

Phenotype Information for ITK from OMIM (Online Mendelian Inheritance in Man)

Drugs for ITK

Target	Drug Name	Disease	Drug Status
ITK	Solifenacin	Overactive bladder	Approved
ITK	Diphemanil Methylsulfate	Peptic ulcer disease	Approved
ITK	Darifenacin	Urinary incontinence	Approved

Drugs for ITK from TTD (Therapeutic Targets Database)