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    ITK IL2 inducible T cell kinase [ Homo sapiens (human) ]

    Gene ID: 3702, updated on 14-Nov-2024

    Summary

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    Official Symbol
    ITKprovided by HGNC
    Official Full Name
    IL2 inducible T cell kinaseprovided by HGNC
    Primary source
    HGNC:HGNC:6171
    See related
    Ensembl:ENSG00000113263 MIM:186973; AllianceGenome:HGNC:6171
    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; LPFS1; PSCTK2
    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]
    Expression
    Biased expression in lymph node (RPKM 23.9), appendix (RPKM 14.7) and 9 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ITK in Genome Data Viewer
    Location:
    5q33.3
    Exon count:
    17
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (157180840..157255185)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (157699782..157774113)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (156607851..156682195)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23498 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23499 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23500 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23501 Neighboring gene mediator complex subunit 7 Neighboring gene golgi associated RAB2 interactor family member 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16556 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23502 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23503 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23504 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23505 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23506 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23507 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16557 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23508 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23509 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23510 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23511 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:156713648-156714148 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:156714149-156714649 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16558 Neighboring gene cytoplasmic FMR1 interacting protein 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:156789204-156789414 Neighboring gene fibronectin type III domain containing 9 Neighboring gene NIPAL4 divergent transcript Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr5:156817055-156818254 Neighboring gene ribosomal protein L26 pseudogene 18

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Tec kinase Itk forms membrane clusters specifically in the vicinity of recruiting receptors. Qi Q, et al. J Biol Chem, 2006 Dec 15. PMID 17060314
    2. Comparison of interleukin-2-inducible kinase (ITK) inhibitors and potential for combination therapies for T-cell lymphoma. Mamand S, et al. Sci Rep, 2018 Sep 21. PMID 30242208, Free PMC Article
    3. Human Emt tyrosine kinase is specifically expressed both in mature T-lymphocytes and T-cell associated hematopoietic malignancies. Kaukonen J, et al. Leuk Lymphoma, 1999 Feb. PMID 10048424
    4. IL-2 Inducible Kinase ITK is Critical for HIV-1 Infection of Jurkat T-cells. Hain A, et al. Sci Rep, 2018 Feb 16. PMID 29453458, Free PMC Article
    5. Interleukin-2-inducible T-cell kinase expression and relation to disease severity in systemic lupus erythematosus. Xu WD, et al. Clin Chim Acta, 2016 Dec 1. PMID 27729219

    See all (128) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Targeting kinase ITK treats autoimmune arthritis via orchestrating T cell differentiation and function.
      Title: Targeting kinase ITK treats autoimmune arthritis via orchestrating T cell differentiation and function.
    2. Inherited human ITK deficiency impairs IFN-gamma immunity and underlies tuberculosis.
      Title: Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis.
    3. ITK independent development of Th17 responses during hypersensitivity pneumonitis driven lung inflammation.
      Title: ITK independent development of Th17 responses during hypersensitivity pneumonitis driven lung inflammation.
    4. SUFU mediates EMT and Wnt/beta-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer.
      Title: SUFU mediates EMT and Wnt/β-catenin signaling pathway activation promoted by miRNA-324-5p in human gastric cancer.
    5. Interleukin-2 inducible T-cell kinase: a potential prognostic biomarker and tumor microenvironment remodeling indicator for hepatocellular carcinoma.
      Title: Interleukin-2 inducible T-cell kinase: a potential prognostic biomarker and tumor microenvironment remodeling indicator for hepatocellular carcinoma.
    6. Cytotoxic lymphocytes-related gene ITK from a systematic CRISPR screen could predict prognosis of ovarian cancer patients with distant metastasis.
      Title: Cytotoxic lymphocytes-related gene ITK from a systematic CRISPR screen could predict prognosis of ovarian cancer patients with distant metastasis.
    7. Itk Promotes the Integration of TCR and CD28 Costimulation through Its Direct Substrates SLP-76 and Gads.
      Title: Itk Promotes the Integration of TCR and CD28 Costimulation through Its Direct Substrates SLP-76 and Gads.
    8. ITK deficiency presenting as autoimmune lymphoproliferative syndrome.
      Title: ITK deficiency presenting as autoimmune lymphoproliferative syndrome.
    9. BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID-19 therapy.
      Title: BTK/ITK dual inhibitors: Modulating immunopathology and lymphopenia for COVID-19 therapy.
    10. Loss of function in ITK can result in broad dysregulation of T-cell responses to oncogenic viruses, including beta-human papillomavirus and Epstein-Barr virus.
      Title: Inherited Interleukin 2-Inducible T-Cell (ITK) Kinase Deficiency in Siblings With Epidermodysplasia Verruciformis and Hodgkin Lymphoma.
    Submit: New GeneRIF Correction See all GeneRIFs (58)

    Phenotypes

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

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Lymphoproliferative syndrome 1
    MedGen: C3552634 OMIM: 613011 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Genome-wide association study of personality traits in bipolar patients.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env Inducible T-cell kinase (ITK) affects viral entry and gp120-induced actin reorganization, but does not affect HIV-1 reverse transcription or proviral DNA integration PubMed
    Nef nef HIV-1 Nef alleles from representative M-group HIV-1 subtypes can interact with ITK. Selective ITK inhibitor blocks HIV-1 infectivity and replication in a Nef-dependent manner PubMed
    nef A cell-based bimolecular fluorescence complementation assay demonstrates that HIV-1 Nef interacts with the Tec family members Bmx, Btk, and Itk, but not with Tec or Txk in 293T cells PubMed
    Pr55(Gag) gag Tec kinase chemical inhibitors diminish the recruitment of ITK to the plasma membrane perturbing HIV-1 Gag-ITK co-localization, disrupting F-actin polymerization, and inhibiting HIV-1 release and replication PubMed
    gag HIV-1 Gag, ITK, and F-actin are located in overlapping and discrete regions of T cell-T cell contact sites PubMed
    gag HIV-1 Gag and ITK are present at regions that contain cholera toxin B in HIV-1 infected T cells, indicating that Gag and ITK co-localize in lipid raft microdomains PubMed
    gag HIV-1 Gag co-localizes with IL2-inducible T-cell kinase (ITK) at the plasma membrane of transfected HEK293T cells and HIV-1 infected T cells PubMed
    gag ITK is required for efficient transcription from the HIV-1 LTR, induces a modest increase in Gag expression, and enhances virion production PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC126257, MGC126258

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H2AXY142 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables histone H3Y41 kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables non-membrane spanning protein tyrosine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables non-membrane spanning protein tyrosine kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in B cell receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in NK T cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in T cell activation TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in T cell receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in T cell receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in adaptive immune response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in adaptive immune response ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in cellular defense response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in gamma-delta T cell activation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in intracellular signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in positive regulation of cytokine production ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cell-cell junction IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_005546.4 → NP_005537.3  tyrosine-protein kinase ITK/TSK

      See identical proteins and their annotated locations for NP_005537.3

      Status: REVIEWED

      Source sequence(s)
      AC010609, BX538196, D13720, DB150488
      Consensus CDS
      CCDS4336.1
      UniProtKB/Swiss-Prot
      B2R752, Q08881, Q32ML7
      Related
      ENSP00000398655.4, ENST00000422843.8
      Conserved Domains (4) summary
      cd05112
      Location:358 → 613
      PTKc_Itk; Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase
      cd10396
      Location:232 → 340
      SH2_Tec_Itk; Src homology 2 (SH2) domain found in Tec protein, IL2-inducible T-cell kinase (Itk)
      cd11908
      Location:174 → 229
      SH3_ITK; Src Homology 3 domain of Interleukin-2-inducible T-cell Kinase
      cd01238
      Location:7 → 148
      PH_Btk; Bruton's tyrosine kinase pleckstrin homology (PH) domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

      Range
      157180840..157255185
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060929.1 Alternate T2T-CHM13v2.0

      Range
      157699782..157774113
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q08881.1 GenPept UniProtKB/Swiss-Prot:Q08881

    Gene LinkOut

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

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