ITK (gene)

ITK

Available structures

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

External IDs

OMIM: 186973 MGI: 96621 HomoloGene: 4051 GeneCards: ITK

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 • receptor binding • ATP binding
Cellular component	• cytoplasm • cytosol • cell-cell junction • extrinsic component of cytoplasmic side of plasma membrane
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 proliferation • peptidyl-tyrosine autophosphorylation • interferon-gamma production • T cell receptor signaling pathway • T cell activation • signal transduction • interleukin-4 production • innate immune response
Sources:Amigo / QuickGO

RNA expression pattern

More reference expression data

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_005537.3


NP_001268894.1 NP_001268895.1 NP_001268897.1 NP_034713.2

Location (UCSC)

Chr 5: 157.14 – 157.26 Mb

Chr 11: 46.33 – 46.39 Mb

PubMed search

^[1]

^[2]

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.^[3] ITK is a member of the TEC family of kinases and is highly expressed in T cells.^[4]

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.^[5]^[6] ITK is functionally important for the development and effector function of T_h2 and T_h17 cells.^[4]

Structure

This protein contains the following domains, which are often found in intracellular kinases:^[7]

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,^[8]^[9]
Grb2^[8]^[10] and
KHDRBS1,^[9]^[10]^[11]
KPNA2,^[12]
LAT,^[13]^[14]
LCP2,^[8]^[15]
PLCG1,^[11]^[16]
PPIA,^[17] and
WAS.^[9]^[18]

References

↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ 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.
1 2 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".
↑ 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.
1 2 3 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.
1 2 3 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.
1 2 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.
1 2 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.

PDB gallery

1snx: CRYSTAL STRUCTURE OF APO INTERLEUKIN-2 TYROSINE KINASE CATALYTIC DOMAIN
1snu: CRYSTAL STRUCTURE OF THE UNPHOSPHORYLATED INTERLEUKIN-2 TYROSINE KINASE CATALYTIC DOMAIN
1lum: NMR Structure of the Itk SH2 domain, Pro287trans, 20 low energy structures
1sm2: Crystal structure of the phosphorylated Interleukin-2 tyrosine kinase catalytic domain
2eu0: The NMR ensemble structure of the Itk SH2 domain bound to a phosphopeptide
2etz: The NMR minimized average structure of the Itk SH2 domain bound to a phosphopeptide
1lun: NMR Structure of the Itk SH2 domain, Pro287trans, energy minimized average structure
1lui: NMR Structures of Itk SH2 domain, Pro287cis isoform, ensemble of 20 low energy structures
1luk: NMR Structure of the Itk SH2 domain, Pro287cis, Energy minimized average structure

Protein kinases: tyrosine kinases (EC 2.7.10)

Receptor tyrosine kinases (EC 2.7.10.1)

Growth factor receptors

EGF receptor family	EGFR ERBB2 ERBB3 ERBB4

Insulin receptor family	IGF1R INSR INSRR

PDGF receptor family	CSF1R FLT3 KIT PDGFR (PDGFRA PDGFRB)

FGF receptor family	FGFR1 FGFR2 FGFR3 FGFR4

VEGF receptors family	VEGFR1 VEGFR2 VEGFR3

HGF receptor family	MET RON

Trk receptor family	NTRK1 NTRK2 NTRK3

EPH receptor family

LTK receptor family

TIE receptor family

ROR receptor family

ROR1
ROR2

DDR receptor family

DDR1
DDR2

PTK7 receptor family

PTK7

RYK receptor family

MuSK receptor family

MUSK

ROS receptor family

ROS1

AATYK receptor family

AATYK
AATYK2

AXL receptor family

RET receptor family

uncategorised

STYK1

Non-receptor tyrosine kinases (EC 2.7.10.2)

ABL family	ABL1 ARG

ACK family	ACK1 TNK1

CSK family	CSK MATK

FAK family	FAK PYK2

FES family	FES FER

FRK family	FRK BRK SRMS

JAK family	JAK1 JAK2 JAK3 TYK2

SRC-A family	SRC FGR FYN YES1

SRC-B family	BLK HCK LCK LYN

TEC family	TEC BMX BTK ITK TXK

SYK family	SYK ZAP70

Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

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ITK (gene)

Function

Structure

Interactions

References

Further reading