ITK (gene)

ITK
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, 4KIO, 4L7S, 4M0Y, 4M0Z, 4M12, 4M13, 4M14, 4M15, 4MF0, 4MF1, 4PP9, 4PPA, 4PPB, 4PPC, 4PQN, 4QD6, 4RFM
Identifiers
Aliases	ITK, EMT, LPFS1, LYK, PSCTK2, IL2 inducible T-cell kinase, IL2 inducible T cell kinase
External IDs	OMIM: 186973; MGI: 96621; HomoloGene: 4051; GeneCards: ITK; OMA:ITK - orthologs
Gene location (Human) Chr. Chromosome 5 (human) Band 5q33.3 Start 157,142,933 bp End 157,255,185 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11 B1.1|11 27.75 cM Start 46,215,977 bp End 46,280,342 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in granulocyte thymus blood lymph node appendix spleen epithelium of colon bone marrow cells superficial temporal artery gallbladder Top expressed in thymus mesenteric lymph nodes blood spleen granulocyte submandibular gland subcutaneous adipose tissue perirhinal cortex entorhinal cortex Ileal epithelium More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding protein kinase activity non-membrane spanning protein tyrosine kinase activity metal ion binding kinase activity protein binding protein tyrosine kinase activity signaling receptor binding ATP binding Cellular component cytoplasm cytosol cell-cell junction extrinsic component of cytoplasmic side of plasma membrane nucleus Biological process intracellular signal transduction adaptive immune response phosphorylation NK T cell differentiation transmembrane receptor protein tyrosine kinase signaling pathway immune system process cytokine production activation of phospholipase C activity Fc-epsilon receptor signaling pathway protein phosphorylation cellular defense response regulation of cell population proliferation peptidyl-tyrosine autophosphorylation T cell receptor signaling pathway T cell activation signal transduction interleukin-4 production innate immune response B cell receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3702 16428 Ensembl ENSG00000113263 ENSMUSG00000020395 UniProt Q08881 Q03526 RefSeq (mRNA) NM_005546 NM_001281965 NM_001281966 NM_001281967 NM_001281968 NM_010583 RefSeq (protein) NP_005537 NP_001268894 NP_001268895 NP_001268896 NP_001268897 NP_034713 Location (UCSC) Chr 5: 157.14 – 157.26 Mb Chr 11: 46.22 – 46.28 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Tyrosine-protein kinase ITK/TSK also known as interleukin-2-inducible T-cell kinase or simply 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.

Mice lacking ITK were shown to not be susceptible to asthma.

Structure

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

• N-terminus – PH (pleckstrin homology domain)
• TH – Tec family homology domain (including Bruton's tyrosine kinase Cys-rich motif and Proline rich region)
• SH3 – (Src homology 3)
• SH2 – (Src homology 2)
• C-terminus – tyrosine kinase, catalytic domain

Interactions

ITK (gene) has been shown to interact with:

• FYN,
• Grb2 and
• KHDRBS1,
• KPNA2,
• LAT,
• LCP2,
• PLCG1,
• PPIA, and
• WAS.

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. doi:10.1182/blood.V82.5.1561.1561. 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. S2CID 32621307.
• 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. Bibcode:1997Natur.385...93A. doi:10.1038/385093a0. PMID 8985255. S2CID 25356409.
• 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.