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)
End	157,255,185 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	46,280,342 bp
RNA expression pattern
	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
	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
	3702
	16428
	ENSG00000113263
	ENSMUSG00000020395
	Q08881
	Q03526
	NM_005546
	NM_001281965; NM_001281966; NM_001281967; NM_001281968; NM_010583
	NP_005537
	NP_001268894; NP_001268895; NP_001268896; NP_001268897; NP_034713
	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.^[5] ITK is a member of the TEC family of kinases and is highly expressed in T cells.^[6]

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.^[7]^[8] ITK is functionally important for the development and effector function of T_h2 and T_h17 cells.^[6]

Mice lacking ITK were shown to not be susceptible to asthma.^[9]

Structure

This protein contains the following domains, which are often found in intracellular kinases:^[10]

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,^[11]^[12]
Grb2^[11]^[13] and
KHDRBS1,^[12]^[13]^[14]
KPNA2,^[15]
LAT,^[16]^[17]
LCP2,^[11]^[18]
PLCG1,^[14]^[19]
PPIA,^[20] and
WAS.^[12]^[21]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000113263 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020395 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Gibson S, Leung B, Squire JA, Hill M, Arima N, Goss P, Hogg D, Mills GB (September 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.
^ ^a ^b Gomez-Rodriguez J, Kraus ZJ, Schwartzberg PL (March 2011). "Tec family kinases Itk and Rlk/Txk in T lymphocytes: cross-regulation of cytokine production and T-cell fates". FEBS. 278 (12): 1980–1989. doi:10.1111/j.1742-4658.2011.08072.x. PMC 3117960. PMID 21362139.
^ Kosaka Y, Felices M, Berg LJ (October 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.
^ "Entrez Gene: ITK IL2-inducible T-cell kinase".
^ Mueller, Cynthia; August, Avery (2003-05-15). "Attenuation of immunological symptoms of allergic asthma in mice lacking the tyrosine kinase ITK". Journal of Immunology. 170 (10): 5056–5063. doi:10.4049/jimmunol.170.10.5056. ISSN 0022-1767. PMID 12734350.
^ Hawkins J, Marcy A (July 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.
^ ^a ^b ^c Bunnell SC, Diehn M, Yaffe MB, Findell PR, Cantley LC, Berg LJ (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.
^ ^a ^b ^c Bunnell SC, Henry PA, Kolluri R, Kirchhausen T, Rickles RJ, Berg LJ (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.
^ ^a ^b Andreotti AH, Bunnell SC, Feng S, Berg LJ, Schreiber SL (1997). "Regulatory intramolecular association in a tyrosine kinase of the Tec family". Nature. 385 (6611): 93–7. doi:10.1038/385093a0. PMID 8985255.
^ ^a ^b Hao S, August A (2002). "The proline rich region of the Tec homology domain of ITK regulates its activity". FEBS Lett. 525 (1–3): 53–8. doi:10.1016/S0014-5793(02)03066-1. PMID 12163161.
^ Perez-Villar JJ, O'Day K, Hewgill DH, Nadler SG, Kanner SB (2001). "Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha)". Int. Immunol. 13 (10): 1265–74. doi:10.1093/intimm/13.10.1265. PMID 11581171.
^ 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.
^ Perez-Villar JJ, Whitney GS, Sitnick MT, Dunn RJ, Venkatesan S, O'Day K, Schieven GL, Lin TA, Kanner SB (2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry. 41 (34): 10732–40. doi:10.1021/bi025554o. PMID 12186560.
^ Shim EK, Moon CS, Lee GY, Ha YJ, Chae SK, Lee JR (2004). "Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase". FEBS Lett. 575 (1–3): 35–40. doi:10.1016/j.febslet.2004.07.090. PMID 15388330.
^ Perez-Villar JJ, Kanner SB (1999). "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.
^ Brazin KN, Mallis RJ, Fulton DB, Andreotti AH (2002). "Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A". Proc. Natl. Acad. Sci. U.S.A. 99 (4): 1899–904. doi:10.1073/pnas.042529199. PMC 122291. PMID 11830645.
^ Cory GO, MacCarthy-Morrogh L, Banin S, Gout I, Brickell PM, Levinsky RJ, Kinnon C, Lovering RC (1996). "Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways". J. Immunol. 157 (9): 3791–5. PMID 8892607.

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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000113263 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000020395 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8364206-5] Gibson S, Leung B, Squire JA, Hill M, Arima N, Goss P, Hogg D, Mills GB (September 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.

[pmid21362139-6] Gomez-Rodriguez J, Kraus ZJ, Schwartzberg PL (March 2011). "Tec family kinases Itk and Rlk/Txk in T lymphocytes: cross-regulation of cytokine production and T-cell fates". FEBS. 278 (12): 1980–1989. doi:10.1111/j.1742-4658.2011.08072.x. PMC 3117960. PMID 21362139.

[pmid16931156-7] Kosaka Y, Felices M, Berg LJ (October 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.

[8] "Entrez Gene: ITK IL2-inducible T-cell kinase".

[9] Mueller, Cynthia; August, Avery (2003-05-15). "Attenuation of immunological symptoms of allergic asthma in mice lacking the tyrosine kinase ITK". Journal of Immunology. 170 (10): 5056–5063. doi:10.4049/jimmunol.170.10.5056. ISSN 0022-1767. PMID 12734350.

[pmid11437596-10] Hawkins J, Marcy A (July 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.

[pmid10636929-11] Bunnell SC, Diehn M, Yaffe MB, Findell PR, Cantley LC, Berg LJ (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.

[pmid8810341-12] Bunnell SC, Henry PA, Kolluri R, Kirchhausen T, Rickles RJ, Berg LJ (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.

[pmid8985255-13] Andreotti AH, Bunnell SC, Feng S, Berg LJ, Schreiber SL (1997). "Regulatory intramolecular association in a tyrosine kinase of the Tec family". Nature. 385 (6611): 93–7. doi:10.1038/385093a0. PMID 8985255.

[pmid12163161-14] Hao S, August A (2002). "The proline rich region of the Tec homology domain of ITK regulates its activity". FEBS Lett. 525 (1–3): 53–8. doi:10.1016/S0014-5793(02)03066-1. PMID 12163161.

[pmid11581171-15] Perez-Villar JJ, O'Day K, Hewgill DH, Nadler SG, Kanner SB (2001). "Nuclear localization of the tyrosine kinase Itk and interaction of its SH3 domain with karyopherin alpha (Rch1alpha)". Int. Immunol. 13 (10): 1265–74. doi:10.1093/intimm/13.10.1265. PMID 11581171.

[pmid10506192-16] 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.

[pmid12186560-17] Perez-Villar JJ, Whitney GS, Sitnick MT, Dunn RJ, Venkatesan S, O'Day K, Schieven GL, Lin TA, Kanner SB (2002). "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav". Biochemistry. 41 (34): 10732–40. doi:10.1021/bi025554o. PMID 12186560.

[pmid15388330-18] Shim EK, Moon CS, Lee GY, Ha YJ, Chae SK, Lee JR (2004). "Association of the Src homology 2 domain-containing leukocyte phosphoprotein of 76 kD (SLP-76) with the p85 subunit of phosphoinositide 3-kinase". FEBS Lett. 575 (1–3): 35–40. doi:10.1016/j.febslet.2004.07.090. PMID 15388330.

[pmid10586033-19] Perez-Villar JJ, Kanner SB (1999). "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.

[pmid11830645-20] Brazin KN, Mallis RJ, Fulton DB, Andreotti AH (2002). "Regulation of the tyrosine kinase Itk by the peptidyl-prolyl isomerase cyclophilin A". Proc. Natl. Acad. Sci. U.S.A. 99 (4): 1899–904. doi:10.1073/pnas.042529199. PMC 122291. PMID 11830645.

[pmid8892607-21] Cory GO, MacCarthy-Morrogh L, Banin S, Gout I, Brickell PM, Levinsky RJ, Kinnon C, Lovering RC (1996). "Evidence that the Wiskott-Aldrich syndrome protein may be involved in lymphoid cell signaling pathways". J. Immunol. 157 (9): 3791–5. PMID 8892607.

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v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

Function

Structure

Interactions

References

Further reading