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. [provided by RefSeq, Jul 2008]

Full Name

IL2 Inducible T Cell Kinase

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 (PubMed:12186560, PubMed:12682224, PubMed:21725281).
Required for TCR-mediated calcium response in gamma-delta T-cells, may also be involved in the modulation of the transcriptomic signature in the Vgamma2-positive subset of immature gamma-delta T-cells (By similarity).
Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3 (By similarity).

Biological Process

Activation of phospholipase C activityISS:UniProtKB
Adaptive immune responseISS:UniProtKB
B cell receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Cellular defense responseManual Assertion Based On ExperimentTAS:ProtInc
Gamma-delta T cell activationISS:UniProtKB
Intracellular signal transductionIEA:InterPro
NK T cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Peptidyl-tyrosine autophosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of cytokine productionISS:UniProtKB
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
T cell activationManual Assertion Based On ExperimentTAS:UniProtKB
T cell receptor signaling pathwayISS:UniProtKB

Cellular Location

Cytoplasm; Nucleus. Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation.

Involvement in disease

Lymphoproliferative syndrome 1 (LPFS1):
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.

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.
Ubiquitinated.