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FLASH GENE
Symbol ITK contributors: mct/npt/pgu - updated : 01-03-2013
HGNC name IL2-inducible T-cell kinase
HGNC id 6171
Location 5q33.3      Physical location : 156.607.906 - 156.682.109
Synonym name
  • kinase EMT
  • tyrosine-protein kinase ITK/TSK
  • homolog of mouse T-cell itk/tsk
  • Synonym symbol(s) EMT, LYK, PSCTK2, MGC126257, MGC126258
    EC.number 2.7.10.2
    DNA
    TYPE functioning gene
    STRUCTURE 74.20 kb     17 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    FLJ11526 5q33.2 hypothetical protein FLJ11526 HAND1 5q32 heart and neural crest derivatives expressed 1 LOC389339 5 LOC389339 LARP 5q33.2 likely ortholog of mouse la related protein C5orf4 5q31-q32 chromosome 5 open reading frame 4 CNOT8 5q31-q33 CCR4-NOT transcription complex, subunit 8 GEMIN5 5q33.3 gem (nuclear organelle) associated protein 5 MRPL22 5q33.1-q33.3 mitochondrial ribosomal protein L22 LOC285643 5q33.2 similar to Chromosome-associated kinesin KIF4A (Chromokinesin) LOC391842 5 similar to 60S ribosomal protein L6 (TAX-responsive enhancer element binding protein 107) (TAXREB107) (Neoplasm-related protein C140) LOC389340 5 LOC389340 SGCD 5q33 sarcoglycan, delta (35kDa dystrophin-associated glycoprotein) LOC153743 5q33.3 similar to protein phosphatase 1, regulatory (inhibitor) subunit 2 LOC91937 5q33.3 hypothetical protein BC008988 HAVCR1 5q33.2 hepatitis A virus cellular receptor 1 HAVCR2 5q34 hepatitis A virus cellular receptor 2 CRSP9 5q33.2 cofactor required for Sp1 transcriptional activation, subunit 9, 33kDa MGC26988 5q33.3 hypothetical protein MGC26988 ITK 5q33.1 IL2-inducible T-cell kinase CYFIP2 5q34 cytoplasmic FMR1 interacting protein 2 LOC348938 5q33.3 hypothetical protein LOC348938 ADAM19 5q32-q33 a disintegrin and metalloproteinase domain 19 (meltrin beta) SOX30 5q33 a disintegrin and metalloproteinase domain 19 (meltrin beta) LOC389341 5 similar to RIKEN cDNA 4921536K21 FLJ20546 5q33.3 hypothetical protein FLJ20546 LSM11 5q33.3 U7 snRNA-associated Sm-like protein ENTH 5q23.1-q33.3 U7 snRNA-associated Sm-like protein LOC391843 5 similar to 60S acidic ribosomal protein P2 LOC345471 5q33.3 similar to Hsp90 co-chaperone Cdc37 (Hsp90 chaperone protein kinase-targeting subunit) (p50Cdc37) LOC285721 5q33.3 hypothetical LOC285721 EBF 5q34 early B-cell factor FLJ31951 5q33.3 hypothetical protein FLJ31951 MGC10067 5q33.3 hypothetical protein MGC10067 IL12B 5q31.1-q33.1 interleukin 12B (natural killer cell stimulatory factor 2, cytotoxic lymphocyte maturation factor 2, p40)
    RNA
    TRANSCRIPTS type
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 4366 - 620 - 2006 16631752
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  lowly
     pharynx   lowly
    Endocrinethyroid   lowly
    Lymphoid/Immunespleen   lowly
     thymus   predominantly Homo sapiensAdult
    Respiratoryrespiratory tracttrachea  lowly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immuneactivated B lymphocyte
    Lymphoid/ImmuneT cell Homo sapiensAdult
    cell lineage hematopoietic
    cell lines
    fluid/secretion blood
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an intracellular tyrosine kinase with SH2, SH3 domains
  • a Bruton's tyrosine kinase (Btk)-type zinc finger
  • three aromatic AAs, termed the FYF motif, located in the inner walls of the phospholipid-binding pocket of the ITK PH domain, are conserved in the PH domains of all Tec kinases
  • a zinc binding regions within its Tec homology domain to interacting with GNA13
  • HOMOLOGY
    interspecies homolog to rattus Itk (94.52 pc)
    homolog to murine Itk (94.35 pc)
    Homologene
    FAMILY
  • protein kinase superfamily
  • Tyr protein kinase family
  • TEC subfamily
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • tyrosine kinase
  • involved in regulating antigen receptor induced serum response factor (SRF) activation
  • critical role for ITK and TXK in conventional CD8(+) T cell development in the thymus
  • ITK and TXK are required for efficient positive selection of conventional CD4+ and CD8+ T cells in the thymus
  • important role for ITK and TXK in the development of conventional as opposed to innate CD4(+) and CD8(+) T cells
  • play critical roles in helping shape immune responses via their effects on the differentiation and function of distinct cytokine-producing, effector T-cell populations
  • serves as a modulator, or rheostat, critically fine-tuning the T cell response
  • required for efficient replication of influenza virus in infected T-cells
  • Tec-family kinase that regulates the spatiotemporal organization of components of T cell signaling pathways and CDC42-dependent actin polymerization
  • ITK signaling promotes IRF4 up-regulation following CD8(+) T-cell activation and that this signaling pathway normally suppresses EOMES expression, thereby regulating the differentiation pathway of CD8(+) T cells
  • critical for the recruitment of the kinase to the plasma membrane and its co-localization with the TCR-CD3 molecular complex
  • catalyzes phosphorylation on tyrosine residues within a number of its natural substrates, including the well-characterized gamma783 of PLCG1
  • involved in T-cell proliferation and differentiation
  • important for the activation of T cells via the T cell Receptor (TCR)
  • CELLULAR PROCESS cell life, differentiation
    cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling signal transduction
  • possible cross talk between ITK and G-protein signaling downstream of the TCR
  • ITK signaling is required to prevent the expansion of gammadelta NKT cells in the adult thymus, to block their emigration, and to promote terminal NKT cell maturation
  • a component
  • ITK-SYK exists in the active conformation state and is therefore capable of signaling without SRC family kinases or stimulation of the T cell receptor
  • INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
  • Zinc
  • ATP
  • protein
  • ongoing physical interaction between LCP2 and ITK is required to maintain ITK in an active conformation
  • SH2D2A is required for tyrosine phosphorylation of the LCK substrate ITK
  • ITK-LCP2 interaction in cytokine production
  • controlled the central localization of DEF6, which may contribute to the activation of CDC42 at the center of the interface (PMId: 21971040)
  • plays a domineering role in the T-cell development, differentiation and production of pro-inflammatory cytokines such as IL2, IL4, IL5, IL10, IL13 and IL17
  • modulates T-cell signaling by activating PLCG1 and regulating the extent of Ca2+ flux
  • both interacts with DEF6 and phosphorylates DEF6 at tyrosine residues Tyr(210) and Tyr(222)
  • IRF4 is transiently up-regulated during thymic development as cells undergo positive selection and ITK is required for optimal IRF4 expression
  • ITK signaling promotes IRF4 up-regulation following CD8+ T-cell activation and this signaling pathway normally suppresses EOMES expression, thereby regulating the differentiation pathway of CD8+ T cells
  • a specific docking interaction between the kinase domain of ITK and the C-terminal Src homology 2 (SH2C) domain of PLCG1 that promotes substrate specificity for this enzyme/substrate pair
  • LCP2 is critical for ITK-SYK activation and is particularly required for the ITK-SYK-dependent phosphorylation of SYK activation loop tyrosines
  • ITK interacts with GNA13 during TCR triggering
  • cell & other
    REGULATION
    induced by interleukin-2 inducible
    repressed by intermolecular clustering and disruption of this clustering leads to increased ITK kinase activity following TCR stimulation
    Other regulated by the peptidyl prolyl cis-trans isomerase PPIB
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    inhibitors of ITK are potential therapeutic candidates for the treatment of various inflammatory disease
    ANIMAL & CELL MODELS