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ITK (IL2-inducible T-cell kinase)

Identity

Other namesEMT
LYK
MGC126257
MGC126258
PSCTK2
HGNC (Hugo) ITK
Location 5q33.3
Location_base_pair Starts at 156540485 and ends at 156614687 bp from pter ( according to hg18-Mar_2006)  [Mapping]

DNA/RNA

Description centromere to telomere orientation; Exons: 17
Transcription Transcript length: 4,419 bps

Protein

 
  ITK protein
Description Number of residues: 620 residues; Molecular weight: 71 kDa; Conserved domains: PH-Tec, Tec pleckstrin homology (PH) domain; BTK, Bruton's tyrosine kinase Cys-rich motif; SH3, Src homology 3 domains; SH2, Src homology 2 domains; TyrKc, Tyrosine kinase, catalytic domain.
Function Although originally described as an important component of proximal TCR signaling pathways, the Tec family tyrosine kinase Itk has become increasingly recognized for its important role in regulating T-helper-cell differentiation. Itk has a crucial role in Th2 responses, both the protective responses to pathogenic infections in addition to the pathological responses resulting in allergic asthma. Itk is not required for Th2 differentiation per se, but effector Th2 cytokine production during recall responses is severely impaired in the absence of Itk.

Implicated in

Entity t(5;9)(q33;q22)
Disease peripheral T-cell lymphomas, unspecified (PTCL-u). ITK-SYK transcripts were detected in 5 of 30 (17%) unspecified peripheral T-cell lymphomas, but not in cases of angioimmunoblastic T-cell lymphoma (n=9) and ALK-negative anaplastic large cell lymphoma (n=7)
Hybrid/Mutated Gene N-terminal pleckstrin homology domain and proline-rich region of ITK fused to the tyrosine kinase domain of SYK.
  

External links

Nomenclature
HGNC (Hugo)ITK   6171
Entrez_Gene (NCBI)ITK  3702  IL2-inducible T-cell kinase
Cards
AtlasITKID43329ch5q33
GeneCards (Weizmann)ITK
Ensembl (Hinxton)ENSG00000113263 [Gene_View]  ITK [Vega]
AceView (NCBI)ITK
Genatlas (Paris)ITK
euGene (Indiana)3702
SOURCE (Stanford)NM_005546
Gene Expression (Array Express) ENSG00000113263
Genomic and cartography
GoldenPath (UCSC)ITK  -  5q33.3   chr5:156540485-156614687 +  5q31-q32   [Description]    (hg18-Mar_2006)
EnsemblITK - 5q31-q32 [CytoView]
Mapping of homologs : NCBIITK [Mapview]
OMIM186973   613011   
Gene and transcription
Gene : Genbank (Entrez)AB209622 AK303609 AK311654 AK312846 BC109077
Reference sequence (RefSeq transcript) :SRSNM_005546
Reference transcript : EntrezNM_005546
RefSeq genomic : SRSAC_000048 AC_000137 NC_000005 NG_016276 NT_023133 NW_001838954 NW_922784
RefSeq genomic : EntrezAC_000048 AC_000137 NC_000005 NG_016276 NT_023133 NW_001838954 NW_922784
Consensus coding sequences : CCDS NCBIITK
Cluster EST : UnigeneHs.558348 [ SRS ] Hs.558348 [ NCBI ]
Alternative Splicing : Fast-db (Paris)12506
Protein : pattern, domain, 3D structure
Protein : UniProt/SwissProtQ08881 (SRS) Q08881 (Expasy) Q08881 (Uniprot)
With graphics : InterProQ08881
Splice isoforms : VarSplice FASTAQ08881(VarSplice FASTA)
Domaine pattern : Prosite (SRS)PH_DOMAIN (PS50003)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)    SH2 (PS50001)    SH3 (PS50002)    ZF_BTK (PS51113)   
Domain pattern : Prosite (Expaxy)PH_DOMAIN (PS50003)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)    SH2 (PS50001)    SH3 (PS50002)    ZF_BTK (PS51113)   
Domains : Interpro (SRS)Kinase-like_dom    PH_type    Pleckstrin_homology    Prot_kinase_cat_dom    Protein_kinase_ATP_BS    SH2    SH3_domain    Tyr_prot_kinase    Tyr_prot_kinase_AS    Tyr_prot_kinase_cat_dom    Tyr_prot_kinase_subgr_cat_dom    Znf_Btk_motif   
Domains : Interpro (EBI)Kinase-like_dom    PH_type    Pleckstrin_homology    Prot_kinase_cat_dom    Protein_kinase_ATP_BS    SH2    SH3_domain    Tyr_prot_kinase    Tyr_prot_kinase_AS    Tyr_prot_kinase_cat_dom    Tyr_prot_kinase_subgr_cat_dom    Znf_Btk_motif   
Related proteins : CluSTrQ08881
Domain families : Pfam SRSBTK (PF00779)    PH (PF00169)    Pkinase_Tyr (PF07714)    SH2 (PF00017)    SH3_1 (PF00018)   
Domain families : Pfam SangerBTK (PF00779)    PH (PF00169)    Pkinase_Tyr (PF07714)    SH2 (PF00017)    SH3_1 (PF00018)   
Domain families : Pfam NCBIpfam00779    pfam00169    pfam07714    pfam00017    pfam00018   
Domain families : Smart EMBLBTK (SM00107)  PH (SM00233)  SH2 (SM00252)  SH3 (SM00326)  TyrKc (SM00219)  
Blocks (Seattle)Q08881
Crystal structure of protein : PDB SRS1SM2    1SNU    1SNX    2E6I    2YUQ   
Crystal structure of protein : PDBSum1SM2    1SNU    1SNX    2E6I    2YUQ   
Crystal structure of protein : IMB1SM2    1SNU    1SNX    2E6I    2YUQ   
Crystal structure of protein : PDB RSDB1SM2    1SNU    1SNX    2E6I    2YUQ   
HPRD01746
Protein Interaction databases
DIP (DOE-UCLA)Q08881
IntAct (EBI)Q08881
Polymorphism : SNP, mutations, diseases
Single Nucleotide Polymorphism (SNP) : dbSNP NCBIITK
SNP : GeneSNP UtahITK
SNP : HGBaseITK
Genetic variants : HAPMAPITK
Cancer Gene: CensusITK 
Somatic Mutations in Cancer : COSMICITK 
Translocation Breakpoints in Cancer : TICdbITK 
Mutations and Diseases : HGMDITK
Hereditary diseases : OMIM186973    613011   
Hereditary diseases : GENETests186973    613011   
Diseases : Genetic AssociationITK
General knowledge
Homologs : HomoloGeneITK
Homology/Alignments : Family Browser UCSCITK
Phylogenetic Trees/Animal Genes : TreeFamITK
Catalytic activity : Enzyme2.7.10.2 [ Enzyme-Expasy ]   2.7.10.2 [ Enzyme-SRS ]   2.7.10.2 [ IntEnz-EBI ]   2.7.10.2 [ BRENDA ]   2.7.10.2 [ KEGG ]   
Chemical/Protein Interactions : CTD3702
Keywords Ontology : AmiGOnucleotide binding  non-membrane spanning protein tyrosine kinase activity  protein binding  ATP binding  cytosol  plasma membrane  protein amino acid phosphorylation  cellular defense response  intracellular signaling cascade  zinc ion binding  transferase activity  metal ion binding  
Keywords Ontology : EGO-EBInucleotide binding  non-membrane spanning protein tyrosine kinase activity  protein binding  ATP binding  cytosol  plasma membrane  protein amino acid phosphorylation  cellular defense response  intracellular signaling cascade  zinc ion binding  transferase activity  metal ion binding  
Pathways : BIOCARTAThe Co-Stimulatory Signal During T-cell Activation [Genes]   
Pathways : KEGGT cell receptor signaling pathwayLeukocyte transendothelial migration
Other databases
Probes
Probes : ImagenesITK Related clones (RZPD - Berlin)
Literature
PubMed52 Pubmed reference(s) in Entrez
PubGeneITK

Bibliography

Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk.
Liao XC, Littman DR
Immunity. 1995 ; 3 (6) : 757-769.
PMID 8777721
 
Regulatory intramolecular association in a tyrosine kinase of the Tec family.
Andreotti AH, Bunnell SC, Feng S, Berg LJ, Schreiber SL
Nature. 1997 ; 385 (6611) : 93-97.
PMID 8985255
 
T cell receptor-initiated calcium release is uncoupled from capacitative calcium entry in Itk-deficient T cells.
Liu KQ, Bunnell SC, Gurniak CB, Berg LJ
The Journal of experimental medicine. 1998 ; 187 (10) : 1721-1727.
PMID 9584150
 
Requirement for Tec kinases Rlk and Itk in T cell receptor signaling and immunity.
Schaeffer EM, Debnath J, Yap G, McVicar D, Liao XC, Littman DR, Sher A, Varmus HE, Lenardo MJ, Schwartzberg PL
Science (New York, N.Y.). 1999 ; 284 (5414) : 638-641.
PMID 10213685
 
Tec kinases: a family with multiple roles in immunity.
Yang WC, Collette Y, Nunˆ®s JA, Olive D
Immunity. 2000 ; 12 (4) : 373-382.
PMID 10795735
 
Tec kinases: modulators of lymphocyte signaling and development.
Lewis CM, Broussard C, Czar MJ, Schwartzberg PL
Current opinion in immunology. 2001 ; 13 (3) : 317-325.
PMID 11406363
 
Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma.
Streubel B, Vinatzer U, Willheim M, Raderer M, Chott A
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2006 ; 20 (2) : 313-318.
PMID 16341044
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written04-2007Berthold Streubel
Department of Pathology, Medical University of Vienna, Waehringer, Guertel 18-20, A-1090 Vienna, Austria

Citation

This paper should be referenced as such :
Streubel B . ITK (IL2-inducible T-cell kinase). Atlas Genet Cytogenet Oncol Haematol. April 2007 .
URL : http://AtlasGeneticsOncology.org/Genes/ITKID43329ch5q33.html

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indexed on : Sat Feb 27 10:53:37 CET 2010

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