ITK (gene)

IL2-inducible T-cell kinase
1LUI
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1SM2, 1SNU, 1SNX, 2E6I, 2LMJ, 2YUQ, 3MIY, 3MJ1, 3MJ2, 3QGW, 3QGY, 3T9T, 3V5J, 3V5L, 3V8T, 3V8W, 4HCT, 4HCU, 4HCV
Identifiers
Symbols	ITK; EMT; LPFS1; LYK; PSCTK2
External IDs	OMIM: 186973 MGI: 96621 HomoloGene: 4051 ChEMBL: 2959 GeneCards: ITK Gene
EC number	2.7.10.2
Gene Ontology Molecular function • non-membrane spanning protein tyrosine kinase activity • protein binding • ATP binding • phospholipid binding • metal ion binding Cellular component • cytosol Biological process • cytokine production • NK T cell differentiation • adaptive immune response • cellular defense response • signal transduction • activation of phospholipase C activity • interferon-gamma production • interleukin-4 production • intracellular signal transduction • T cell activation • T cell receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Protein domains
Orthologs
Species	Human	Mouse
Entrez	3702	16428
Ensembl	ENSG00000113263	ENSMUSG00000020395
UniProt	Q08881	Q03526
RefSeq (mRNA)	NM_005546	NM_010583
RefSeq (protein)	NP_005537	NP_034713
Location (UCSC)	Chr 5: 156.57 – 156.68 Mb	Chr 11: 46.33 – 46.39 Mb
PubMed search	[1]	[2]

IL2-inducible T-cell kinase, also known as ITK, is a protein that in humans is encoded by the ITK gene. ITK is a member of the TEC family of kinases and is highly expressed in T cells.

Function

This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein is thought to play a role in T-cell proliferation and differentiation. ITK is functionally important for the development and effector function of T_h2 and T_h17 cells.

Structure

This protein contains the following domains, which are often found in intracellular kinases:

• N-terminus – PH (pleckstrin homology domain)
• BTK – Bruton's tyrosine kinase Cys-rich motif
• SH3 – (Src homology 3)
• SH2 – (Src homology 2)
• C-terminus – tyrosine kinase, catalytic domain

Interactions

ITK (gene) has been shown to interact with FYN, Wiskott-Aldrich syndrome protein, KHDRBS1, PLCG1, Lymphocyte cytosolic protein 2, Linker of activated T cells, Karyopherin alpha 2, Grb2 and Peptidylprolyl isomerase A.

Further reading

• Kosaka Y, Felices M, Berg LJ (2006). "Itk and Th2 responses: action but no reaction.". Trends Immunol. 27 (10): 453–60. doi:10.1016/j.it.2006.08.006. PMID 16931156. 
• Janis EM, Siliciano JD, Isaac DD, et al. (1995). "Mapping of the gene for the tyrosine kinase Itk to a region of conserved synteny between mouse chromosome 11 and human chromosome 5q.". Genomics 23 (1): 269–71. doi:10.1006/geno.1994.1492. PMID 7829087. 
• Gibson S, Leung B, Squire JA, et al. (1993). "Identification, cloning, and characterization of a novel human T-cell-specific tyrosine kinase located at the hematopoietin complex on chromosome 5q.". Blood 82 (5): 1561–72. PMID 8364206. 
• Tanaka N, Asao H, Ohtani K, et al. (1993). "A novel human tyrosine kinase gene inducible in T cells by interleukin 2.". FEBS Lett. 324 (1): 1–5. doi:10.1016/0014-5793(93)81520-A. PMID 8504851. 
• Bunnell SC, Henry PA, Kolluri R, et al. (1996). "Identification of Itk/Tsk Src homology 3 domain ligands.". J. Biol. Chem. 271 (41): 25646–56. doi:10.1074/jbc.271.41.25646. PMID 8810341. 
• Andreotti AH, Bunnell SC, Feng S, et al. (1997). "Regulatory intramolecular association in a tyrosine kinase of the Tec family.". Nature 385 (6611): 93–7. doi:10.1038/385093a0. PMID 8985255. 
• Heyeck SD, Wilcox HM, Bunnell SC, Berg LJ (1997). "Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity.". J. Biol. Chem. 272 (40): 25401–8. doi:10.1074/jbc.272.40.25401. PMID 9312162. 
• Kaukonen J, Savolainen ER, Palotie A (1999). "Human Emt tyrosine kinase is specifically expressed both in mature T-lymphocytes and T-cell associated hematopoietic malignancies.". Leuk. Lymphoma 32 (5-6): 513–22. doi:10.3109/10428199909058409. PMID 10048424. 
• Shan X, Wange RL (1999). "Itk/Emt/Tsk activation in response to CD3 cross-linking in Jurkat T cells requires ZAP-70 and Lat and is independent of membrane recruitment.". J. Biol. Chem. 274 (41): 29323–30. doi:10.1074/jbc.274.41.29323. PMID 10506192. 
• Su YW, Zhang Y, Schweikert J, et al. (1999). "Interaction of SLP adaptors with the SH2 domain of Tec family kinases.". Eur. J. Immunol. 29 (11): 3702–11. doi:10.1002/(SICI)1521-4141(199911)29:11<3702::AID-IMMU3702>3.0.CO;2-R. PMID 10556826. 
• Perez-Villar JJ, Kanner SB (2000). "Regulated association between the tyrosine kinase Emt/Itk/Tsk and phospholipase-C gamma 1 in human T lymphocytes.". J. Immunol. 163 (12): 6435–41. PMID 10586033. 
• Rajagopal K, Sommers CL, Decker DC, et al. (2000). "RIBP, a novel Rlk/Txk- and itk-binding adaptor protein that regulates T cell activation.". J. Exp. Med. 190 (11): 1657–68. doi:10.1084/jem.190.11.1657. PMC 2195727. PMID 10587356. 
• Bunnell SC, Diehn M, Yaffe MB, et al. (2000). "Biochemical interactions integrating Itk with the T cell receptor-initiated signaling cascade.". J. Biol. Chem. 275 (3): 2219–30. doi:10.1074/jbc.275.3.2219. PMID 10636929. 
• Shan X, Czar MJ, Bunnell SC, et al. (2000). "Deficiency of PTEN in Jurkat T cells causes constitutive localization of Itk to the plasma membrane and hyperresponsiveness to CD3 stimulation.". Mol. Cell. Biol. 20 (18): 6945–57. doi:10.1128/MCB.20.18.6945-6957.2000. PMC 88770. PMID 10958690. 
• Hawkins J, Marcy A (2001). "Characterization of Itk tyrosine kinase: contribution of noncatalytic domains to enzymatic activity.". Protein Expr. Purif. 22 (2): 211–9. doi:10.1006/prep.2001.1447. PMID 11437596.