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    ITK IL2-inducible T-cell kinase [ Homo sapiens ]

    Gene ID: 3702, updated on 11-May-2012
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    Summary

    Official Symbol
    ITKprovided by HGNC
    Official Full Name
    IL2-inducible T-cell kinaseprovided by HGNC
    Primary source
    HGNC:6171
    See related
    Ensembl:ENSG00000113263; HPRD:01746; MIM:186973; Vega:OTTHUMG00000130245
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    EMT; LYK; PSCTK2; MGC126257; MGC126258
    Summary
    This gene encodes an intracellular tyrosine kinase expressed in T-cells. The protein contains both SH2 and SH3 domains which are often found in intracellular kinases. It is thought to play a role in T-cell proliferation and differentiation. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    5q31-q32
    Sequence :
    Chromosome: 5; NC_000005.9 (156607907..156682109)
    See ITK in Epigenomics, MapViewer

    Chromosome 5 - NC_000005.9Genomic Context describing neighboring genes Neighboring gene mediator complex subunit 7 Neighboring gene family with sequence similarity 71, member B Neighboring gene cytoplasmic FMR1 interacting protein 2 Neighboring gene fibronectin type III domain containing 9 Neighboring gene ribosomal protein L26 pseudogene 18

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells. Sela M, et al. EMBO J, 2011 Jul 1. PMID 21725281.
    2. Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. Zhizhuo H, et al. Pediatr Blood Cancer, 2012 Mar. PMID 21674762.
    3. Genome-wide association study of personality traits in bipolar patients. Alliey-Rodriguez N, et al. Psychiatr Genet, 2011 Aug. PMID 21368711.
    4. The association of a single-nucleotide polymorphism of the IL-2 inducible T-cell Kinase gene with asthma. Lee SH, et al. Ann Hum Genet, 2011 May. PMID 21323647.
    5. [Effect of Itk down regulation on cytokines production in Jurkat cell]. Yao HL, et al. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi, 2010 Oct. PMID 21280324.

    See all (64) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. No detrimental mutations were identified in ITK in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.
      Title: Screening the PRF1, UNC13D, STX11, SH2D1A, XIAP, and ITK gene mutations in Chinese children with Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis.
    2. These data suggest a sequential mechanism whereby ZAP-70-dependent priming of SLP-76 at three N-terminal sites triggers reciprocal regulatory interactions between Itk and SLP-76, which are ultimately required to couple active Itk to PLC-gamma1.
      Title: Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells.
    3. People with the -rare allele 196C>T may be more susceptible to asthma via transcriptional regulation of the ITK gene.
      Title: The association of a single-nucleotide polymorphism of the IL-2 inducible T-cell Kinase gene with asthma.
    4. Knocking down Itk expression inhibits Jurkat cell proliferation and cytokines production.
      Title: [Effect of Itk down regulation on cytokines production in Jurkat cell].
    5. TSAd, through its interaction with both Itk and Lck, primes Itk for Lck mediated phosphorylation and thereby regulates CXCL12 induced T cell migration and actin cytoskeleton rearrangements
      Title: T cell specific adapter protein (TSAd) interacts with Tec kinase ITK to promote CXCL12 induced migration of human and murine T cells.
    6. T-cell receptor (TCR)-induced association between ITK and SLP-76, recruitment and transphosphorylation of ITK, actin polarization at the T-cell contact site, and expression of Th2 cytokines
      Title: In vivo significance of ITK-SLP-76 interaction in cytokine production.
    7. Expression of patient-derived ITK in mice induces highly malignant peripheral T cell lymphomas.
      Title: The fusion kinase ITK-SYK mimics a T cell receptor signal and drives oncogenesis in conditional mouse models of peripheral T cell lymphoma.
    8. Data show that tacrolimus modified the expression levels of Foxp3-regulated T cell receptor signal related-genes, PTPN22 and Itk, in Treg cells.
      Title: Tacrolimus differentially regulates the proliferation of conventional and regulatory CD4(+) T cells.
    9. Analysis of SNPs in TCR pathway genes revealed that a haplotype that covers a major part of the coding sequence of ITK is a risk factor for seasonal allergic rhinitis.
      Title: A haplotype in the inducible T-cell tyrosine kinase is a risk factor for seasonal allergic rhinitis.
    10. The Tec family kinase Itk exists as a folded monomer in vivo.
      Title: The Tec family kinase Itk exists as a folded monomer in vivo.
    Submit: New GeneRIF Correction See all (24)
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    Phenotypes

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Genome-wide association study of personality traits in bipolar patients.

    Lymphoproliferative syndrome, EBV-associated, autosomal, 1

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_005537.3 NP_112553.1 HNRNPK    BIND  PubMed Itk interacts with hnRNPK. This interaction was modeled on a demonstrated interaction between mouse Itk and human hnRNPK. 
    NP_005537.3 NP_002257.1 KPNA2    BIND  PubMed Itk interacts with and phosphorylates Rch1-alpha. 
    NP_005537.3 NP_003736.1 SOCS1    BIND  PubMed Socs1 interacts with Itk. This interaction was modeled on a demonstrated interaction between mouse Socs1 and Itk from an unspecified species. 
    Q08881 Q8WV28 BLNK    HPRD  PubMed  
    Q08881 P51813 BMX    HPRD  PubMed  
    Q08881 Q06187 BTK    HPRD  PubMed  
    Q08881 P22681 CBL    HPRD  PubMed  
    Q08881 P10747 CD28    HPRD  PubMed  
    Q08881 P06241 FYN    HPRD  PubMed  
    Q08881 P62993 GRB2    HPRD  PubMed  
    Q08881 P61978 HNRNPK    HPRD  PubMed  
    Q08881 Q08881 ITK    HPRD  PubMed  
    Q08881 Q08881 ITK    HPRD  PubMed  
    Q08881 Q07666 KHDRBS1    HPRD  PubMed  
    Q08881 P52292 KPNA2    HPRD  PubMed  
    Q08881 O43561 LAT    HPRD  PubMed  
    Q08881 P06239 LCK    HPRD  PubMed  
    Q08881 Q13094 LCP2    HPRD  PubMed  
    Q08881 P19174 PLCG1    HPRD  PubMed  
    Q08881 P16885 PLCG2    HPRD  PubMed  
    Q08881 P62937 PPIA    HPRD  PubMed  
    Q08881 Q9NP31 SH2D2A    HPRD  PubMed  
    Q08881 Q13485 SMAD4    HPRD  PubMed  
    Q08881 O15524 SOCS1    HPRD  PubMed  
    Q08881 P36897 TGFBR1    HPRD  PubMed  
    Q08881 P42768 WAS    HPRD  PubMed  
    BioGRID:109907 BioGRID:107315 CBL    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109907 BioGRID:107352 CD2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109907 BioGRID:108810 FYN    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109907 BioGRID:109142 GRB2    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109907 BioGRID:109431 HNRNPK    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109907 BioGRID:114089 IKBKG    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109907 BioGRID:109907 ITK    BioGRID  PubMed Biochemical Activity 
    BioGRID:109907 BioGRID:115900 KHDRBS1    BioGRID  PubMed Biochemical Activity; Reconstituted Complex 
    BioGRID:109907 BioGRID:110036 KPNA2    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:109907 BioGRID:117971 LAT    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:109907 BioGRID:110129 LCP2    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:109907 BioGRID:111351 PLCG1    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity; Reconstituted Complex 
    BioGRID:109907 BioGRID:111474 PPIA    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity; Co-crystal Structure 
    BioGRID:109907 BioGRID:114203 SOCS1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109907 BioGRID:112592 SRC    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109907 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109907 BioGRID:113293 WAS    BioGRID  PubMed Reconstituted Complex 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
    • B Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      B Cell Receptor Signaling Pathway, organism-specific biosystemThe B cell receptor includes membrane ?? heavy chain molecules bound to a light chain and an Ig alpha (CD79A)/Ig beta (CD79B) heterodimer. Activation of the B cell receptor involves phosphorylation o...
    • Chemokine signaling pathway, organism-specific biosystem (from KEGG)
      Chemokine signaling pathway, organism-specific biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
    • Chemokine signaling pathway, conserved biosystem (from KEGG)
      Chemokine signaling pathway, conserved biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
    • Class I PI3K signaling events, organism-specific biosystem (from Pathway Interaction Database)
      Class I PI3K signaling events, organism-specific biosystem
      Class I PI3K signaling events
    • Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem (from Pathway Interaction Database)
      Fc-epsilon receptor I signaling in mast cells, organism-specific biosystem
      Fc-epsilon receptor I signaling in mast cells
    • Generation of second messenger molecules, organism-specific biosystem (from REACTOME)
      Generation of second messenger molecules, organism-specific biosystemIn addition to serving as a scaffold via auto-phosphorylation, ZAP-70 also phosphorylates a restricted set of substrates following TCR stimulation - including LAT and SLP-76. These substrates have be...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Leukocyte transendothelial migration, organism-specific biosystem (from KEGG)
      Leukocyte transendothelial migration, organism-specific biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
    • Leukocyte transendothelial migration, conserved biosystem (from KEGG)
      Leukocyte transendothelial migration, conserved biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
    • T Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      T Cell Receptor Signaling Pathway, organism-specific biosystem
      T Cell Receptor Signaling Pathway
    • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • T cell receptor signaling pathway, conserved biosystem (from KEGG)
      T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • TCR signaling, organism-specific biosystem (from REACTOME)
      TCR signaling, organism-specific biosystemThe TCR is a multisubunit complex that consists of clonotypic alpha/beta chains noncovalently associated with the invariant CD3 delta/epsilon/gamma and TCR zeta chains. T cell activation by antigen p...
    • TCR signaling in naive CD4+ T cells, organism-specific biosystem (from Pathway Interaction Database)
      TCR signaling in naive CD4+ T cells, organism-specific biosystem
      TCR signaling in naive CD4+ T cells

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    non-membrane spanning protein tyrosine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    NK T cell differentiation IEA
    Inferred from Electronic Annotation
    more info
    		  
    T cell activation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    T cell receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    T cell receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    activation of phospholipase C activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    adaptive immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    cellular defense response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    cytokine production ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    interferon-gamma production IEA
    Inferred from Electronic Annotation
    more info
    		  
    interleukin-4 production IEA
    Inferred from Electronic Annotation
    more info
    		  
    intracellular signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
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    General protein information

    Preferred Names
    tyrosine-protein kinase ITK/TSK
    Names
    tyrosine-protein kinase ITK/TSK
    kinase EMT
    T-cell-specific kinase
    tyrosine-protein kinase LYK
    IL-2-inducible T cell kinase
    IL-2-inducible T-cell kinase
    homolog of mouse T-cell itk/tsk
    interleukin-2-inducible T cell kinase
    interleukin-2-inducible T-cell kinase
    NP_005537.3
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    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016276.1 RefSeqGene

      Range
      5001..79203
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_189

    mRNA and Protein(s)

    1. NM_005546.3 → NP_005537.3  tyrosine-protein kinase ITK/TSK

      Status: REVIEWED

      Source sequence(s)
      D13720
      Consensus CDS
      CCDS4336.1
      UniProtKB/Swiss-Prot
      Q08881
      Related
      ENSP00000398655, OTTHUMP00000160737, ENST00000422843, OTTHUMT00000252569
      Conserved Domains (6) summary
      cd00174
      Location:175 – 228
      Blast Score: 150
      SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...
      cd05112
      Location:358 – 613
      Blast Score: 1384
      PTKc_Itk; Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase
      cl02465
      Location:113 – 148
      Blast Score: 171
      BTK; BTK motif
      cd01238
      Location:6 – 109
      Blast Score: 391
      PH_Tec; Tec pleckstrin homology (PH) domain
      cd10396
      Location:232 – 340
      Blast Score: 554
      SH2_Tec_Itk; Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk)
      pfam07714
      Location:363 – 612
      Blast Score: 978
      Pkinase_Tyr; Protein tyrosine kinase

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000005.9 Reference GRCh37.p5 Primary Assembly

      Range
      156607907..156682109
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000137.1 Alternate HuRef

      Range
      151695940..151769767
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC010609.7 (62756..136958) None
    genomic CH471062.2 EAW61608.1
    mRNA AB209622.1 BAD92859.1
    mRNA AK303609.1 BAG64622.1
    mRNA AK311654.1 None
    mRNA AK312846.1 BAG35699.1
    mRNA BC109077.2 AAI09078.1
    mRNA BC109078.1 AAI09079.1
    mRNA BX538196.1 CAD98063.1
    mRNA D13720.1 BAA02873.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q08881.1 GenPept UniProtKB/Swiss-Prot:Q08881
    Q59F39 GenPept UniProtKB/TrEMBL:Q59F39
    Q7Z318 GenPept UniProtKB/TrEMBL:Q7Z318
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

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