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ITK (IL2-inducible T-cell kinase)

Identity

Other namesEMT
LYK
MGC126257
MGC126258
PSCTK2
HGNC (Hugo) ITK
LocusID (NCBI) 3702
Location 5q33.3
Location_base_pair Starts at 156607907 and ends at 156682109 bp from pter ( according to hg19-Feb_2009)  [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.
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615

External links

Nomenclature
HGNC (Hugo)ITK   6171
Cards
AtlasITKID43329ch5q33
Entrez_Gene (NCBI)ITK  3702  IL2-inducible T-cell kinase
GeneCards (Weizmann)ITK
Ensembl hg19 (Hinxton)ENSG00000113263 [Gene_View]  chr5:156607907-156682109 [Contig_View]  ITK [Vega]
Ensembl hg38 (Hinxton)ENSG00000113263 [Gene_View]  chr5:156607907-156682109 [Contig_View]  ITK [Vega]
ICGC DataPortalENSG00000113263
cBioPortalITK
AceView (NCBI)ITK
Genatlas (Paris)ITK
WikiGenes3702
SOURCE (Princeton)ITK
Genomic and cartography
GoldenPath hg19 (UCSC)ITK  -     chr5:156607907-156682109 +  5q31-q32   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)ITK  -     5q31-q32   [Description]    (hg38-Dec_2013)
EnsemblITK - 5q31-q32 [CytoView hg19]  ITK - 5q31-q32 [CytoView hg38]
Mapping of homologs : NCBIITK [Mapview hg19]  ITK [Mapview hg38]
OMIM186973   613011   
Gene and transcription
Genbank (Entrez)AB209622 AK303609 AK311654 AK312846 BC109077
RefSeq transcript (Entrez)NM_005546
RefSeq genomic (Entrez)AC_000137 NC_000005 NC_018916 NG_016276 NT_023133 NW_001838954 NW_004929325
Consensus coding sequences : CCDS (NCBI)ITK
Cluster EST : UnigeneHs.558348 [ NCBI ]
CGAP (NCI)Hs.558348
Alternative Splicing : Fast-db (Paris)GSHG0024407
Alternative Splicing GalleryENSG00000113263
Gene ExpressionITK [ NCBI-GEO ]     ITK [ SEEK ]   ITK [ MEM ]
SOURCE (Princeton)Expression in : [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ08881 (Uniprot)
NextProtQ08881  [Medical]
With graphics : InterProQ08881
Splice isoforms : SwissVarQ08881 (Swissvar)
Catalytic activity : Enzyme2.7.10.2 [ Enzyme-Expasy ]   2.7.10.22.7.10.2 [ IntEnz-EBI ]   2.7.10.2 [ BRENDA ]   2.7.10.2 [ KEGG ]   
Domaine 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 (EBI)Kinase-like_dom    PH_like_dom    Pleckstrin_homology    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser-Thr/Tyr_kinase_cat_dom    SH2    SH3_domain    Tyr_kinase_AS    Tyr_kinase_cat_dom    Znf_Btk_motif   
Related proteins : CluSTrQ08881
Domain families : Pfam (Sanger)BTK (PF00779)    PH (PF00169)    Pkinase_Tyr (PF07714)    SH2 (PF00017)    SH3_1 (PF00018)   
Domain families : Pfam (NCBI)pfam00779    pfam00169    pfam07714    pfam00017    pfam00018   
Domain families : Smart (EMBL)BTK (SM00107)  PH (SM00233)  SH2 (SM00252)  SH3 (SM00326)  TyrKc (SM00219)  
DMDM Disease mutations3702
Blocks (Seattle)Q08881
PDB (SRS)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   
PDB (PDBSum)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   
PDB (IMB)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   
PDB (RSDB)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   
Human Protein AtlasENSG00000113263
Peptide AtlasQ08881
HPRD01746
IPIIPI00004566   IPI00909204   IPI00973930   IPI00977543   
Protein Interaction databases
DIP (DOE-UCLA)Q08881
IntAct (EBI)Q08881
FunCoupENSG00000113263
BioGRIDITK
IntegromeDBITK
STRING (EMBL)ITK
Ontologies - Pathways
QuickGOQ08881
Ontology : AmiGOcytokine production  NK T cell differentiation  adaptive immune response  non-membrane spanning protein tyrosine kinase activity  protein binding  ATP binding  cytosol  cellular defense response  signal transduction  activation of phospholipase C activity  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  interferon-gamma production  interleukin-4 production  intracellular signal transduction  Fc-epsilon receptor signaling pathway  T cell activation  innate immune response  metal ion binding  T cell receptor signaling pathway  T cell receptor signaling pathway  
Ontology : EGO-EBIcytokine production  NK T cell differentiation  adaptive immune response  non-membrane spanning protein tyrosine kinase activity  protein binding  ATP binding  cytosol  cellular defense response  signal transduction  activation of phospholipase C activity  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  peptidyl-tyrosine phosphorylation  interferon-gamma production  interleukin-4 production  intracellular signal transduction  Fc-epsilon receptor signaling pathway  T cell activation  innate immune response  metal ion binding  T cell receptor signaling pathway  T cell receptor signaling pathway  
Pathways : BIOCARTAThe Co-Stimulatory Signal During T-cell Activation [Genes]   
Pathways : KEGGChemokine signaling pathway    T cell receptor signaling pathway    Leukocyte transendothelial migration   
REACTOMEQ08881 [protein]
REACTOME PathwaysREACT_6900 Immune System [pathway]
Protein Interaction DatabaseITK
DoCM (Curated mutations)ITK
Wikipedia pathwaysITK
Gene fusion - rearrangements
Rearrangement : TICdbITK [5q33.3]  -  SYK [17q11.2]
Polymorphisms : SNP, variants
NCBI Variation ViewerITK [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)ITK
dbVarITK
ClinVarITK
1000_GenomesITK 
Exome Variant ServerITK
SNP (GeneSNP Utah)ITK
SNP : HGBaseITK
Genetic variants : HAPMAPITK
Genomic VariantsITK  ITK [DGVbeta]
Mutations
ICGC Data PortalENSG00000113263 
Cancer Gene: CensusITK 
Somatic Mutations in Cancer : COSMICITK 
CONAN: Copy Number AnalysisITK 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)**PUBLIC** CCHMC Molecular Genetics Laboratory Mutation Database
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] 
Diseases
DECIPHER (Syndromes)5:156607907-156682109
Mutations and Diseases : HGMDITK
OMIM186973    613011   
MedgenITK
NextProtQ08881 [Medical]
GENETestsITK
Disease Genetic AssociationITK
Huge Navigator ITK [HugePedia]  ITK [HugeCancerGEM]
snp3D : Map Gene to Disease3702
DGIdb (Drug Gene Interaction db)ITK
General knowledge
Homologs : HomoloGeneITK
Homology/Alignments : Family Browser (UCSC)ITK
Phylogenetic Trees/Animal Genes : TreeFamITK
Chemical/Protein Interactions : CTD3702
Chemical/Pharm GKB GenePA29968
Clinical trialITK
Cancer Resource (Charite)ENSG00000113263
Other databases
Probes
Litterature
PubMed84 Pubmed reference(s) in Entrez
CoreMineITK
GoPubMedITK
iHOPITK

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
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/ITKID43329ch5q33.html

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