TARGETID

T91761

FORMERID

TTDR00858

UNIPROID

ITK_HUMAN

TARGNAME

T-cell-specific kinase (ITK)

GENENAME

ITK

TARGTYPE

Clinical trial target

SYNONYMS

Tyrosine kinase ITK; Inducible T cell kinase; EMT

FUNCTION

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. Phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3. Tyrosine kinase that plays an essential role in regulation of the adaptive immune response.

PDBSTRUC

4RFM; 4QD6; 4PQN; 4PPC; 4PPB

BIOCLASS

Kinase

ECNUMBER

EC 2.7.10.2

SEQUENCE

MNNFILLEEQLIKKSQQKRRTSPSNFKVRFFVLTKASLAYFEDRHGKKRTLKGSIELSRIKCVEIVKSDISIPCHYKYPFQVVHDNYLLYVFAPDRESRQRWVLALKEETRNNNSLVPKYHPNFWMDGKWRCCSQLEKLATGCAQYDPTKNASKKPLPPTPEDNRRPLWEPEETVVIALYDYQTNDPQELALRRNEEYCLLDSSEIHWWRVQDRNGHEGYVPSSYLVEKSPNNLETYEWYNKSISRDKAEKLLLDTGKEGAFMVRDSRTAGTYTVSVFTKAVVSENNPCIKHYHIKETNDNPKRYYVAEKYVFDSIPLLINYHQHNGGGLVTRLRYPVCFGRQKAPVTAGLRYGKWVIDPSELTFVQEIGSGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFAAETLLGMCLDVCEGMAYLEEACVIHRDLAARNCLVGENQVIKVSDFGMTRFVLDDQYTSSTGTKFPVKWASPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDISTGFRLYKPRLASTHVYQIMNHCWKERPEDRPAFSRLLRQLAEIAESGL

DRUGINFO

JTE-051

DRUGINFO

CPI-818

DRUGINFO

PMID27774824-Compound-Figure3Example7

DRUGINFO

Pyrazolo[4,3-c]pyridine derivative 2

DRUGINFO

BMS-488516

DRUGINFO

BMS-509744

KEGGPATH

hsa04062:Chemokine signaling pathway

KEGGPATH

hsa04660:T cell receptor signaling pathway