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Q08881

- ITK_HUMAN

UniProt

Q08881 - ITK_HUMAN

Protein

Tyrosine-protein kinase ITK/TSK

Gene

ITK

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 162 (01 Oct 2014)
      Sequence version 1 (01 Oct 1994)
      Previous versions | rss
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    Functioni

    Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates the development, function and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen presenting cells (APC) activate T-cell receptor (TCR), a series of phosphorylation lead to the recruitment of ITK to the cell membrane, in the vicinity of the stimulated TCR receptor, where it is phosphorylated by LCK. Phosphorylation leads to ITK autophosphorylation and full activation. Once activated, phosphorylates PLCG1, leading to the activation of this lipase and subsequent cleavage of its substrates. In turn, the endoplasmic reticulum releases calcium in the cytoplasm and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional duty. Phosphorylates 2 essential adapter proteins: the linker for activation of T-cells/LAT protein and LCP2. Then, a large number of signaling molecules such as VAV1 are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation.3 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotations

    Cofactori

    Binds 1 zinc ion per subunit.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi121 – 1211ZincBy similarity
    Metal bindingi132 – 1321ZincBy similarity
    Metal bindingi133 – 1331ZincBy similarity
    Metal bindingi143 – 1431ZincBy similarity
    Binding sitei391 – 3911ATPPROSITE-ProRule annotations
    Active sitei482 – 4821Proton acceptorPROSITE-ProRule annotations

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri113 – 14937Btk-typePROSITE-ProRule annotationsAdd
    BLAST
    Nucleotide bindingi369 – 3779ATPPROSITE-ProRule annotations

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW
    3. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
    4. protein binding Source: UniProtKB

    GO - Biological processi

    1. activation of phospholipase C activity Source: UniProtKB
    2. adaptive immune response Source: UniProtKB
    3. cellular defense response Source: ProtInc
    4. cytokine production Source: UniProtKB
    5. Fc-epsilon receptor signaling pathway Source: Reactome
    6. innate immune response Source: Reactome
    7. interferon-gamma production Source: Ensembl
    8. interleukin-4 production Source: Ensembl
    9. intracellular signal transduction Source: InterPro
    10. NK T cell differentiation Source: Ensembl
    11. peptidyl-tyrosine phosphorylation Source: GOC
    12. signal transduction Source: ProtInc
    13. T cell activation Source: UniProtKB
    14. T cell receptor signaling pathway Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Biological processi

    Adaptive immunity, Immunity

    Keywords - Ligandi

    ATP-binding, Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 2681.
    ReactomeiREACT_12623. Generation of second messenger molecules.
    REACT_163834. FCERI mediated Ca+2 mobilization.
    SignaLinkiQ08881.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase ITK/TSK (EC:2.7.10.2)
    Alternative name(s):
    Interleukin-2-inducible T-cell kinase
    Short name:
    IL-2-inducible T-cell kinase
    Kinase EMT
    T-cell-specific kinase
    Tyrosine-protein kinase Lyk
    Gene namesi
    Name:ITK
    Synonyms:EMT, LYK
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

    Organism-specific databases

    HGNCiHGNC:6171. ITK.

    Subcellular locationi

    Cytoplasm 1 Publication
    Note: Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation.

    GO - Cellular componenti

    1. cytosol Source: Reactome

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Involvement in diseasei

    Lymphoproliferative syndrome 1 (LPFS1) [MIM:613011]: A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Inadequate immune response to EBV can have a fatal outcome. Clinical features include splenomegaly, lymphadenopathy, anemia, thrombocytopenia, pancytopenia, recurrent infections. There is an increased risk for lymphoma.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti335 – 3351R → W in LPFS1; shows nearly undetectable mutant ITK protein consistent with severe protein instability. 1 Publication
    Corresponds to variant rs121908191 [ dbSNP | Ensembl ].
    VAR_063424

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi288 – 2881P → G: Complete loss of interaction with PPIA/CYPA. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi613011. phenotype.
    Orphaneti238505. Autosomal recessive lymphoproliferative disease.
    PharmGKBiPA29968.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 620620Tyrosine-protein kinase ITK/TSKPRO_0000088106Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei180 – 1801Phosphotyrosine; by autocatalysis2 Publications
    Modified residuei512 – 5121Phosphotyrosine; by LCK2 Publications
    Modified residuei565 – 5651Phosphoserine2 Publications

    Post-translational modificationi

    Phosphorylated at Tyr-512 in the activation loop of the kinase domain by LCK. Subsequent autophosphorylation at Tyr-180 leads to the kinase activation. The autophosphorylated Tyr-180 lies within the substrate binding sequence of the SH3 domain.3 Publications
    Ubiquitinated.1 Publication

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ08881.
    PaxDbiQ08881.
    PeptideAtlasiQ08881.
    PRIDEiQ08881.

    PTM databases

    PhosphoSiteiQ08881.

    Expressioni

    Tissue specificityi

    T-cell lines and natural killer cell lines.

    Inductioni

    Through a myriad of surface receptors including the TCR/CD3 signaling complex, coreceptors, or chemokine receptors.2 Publications

    Gene expression databases

    ArrayExpressiQ08881.
    BgeeiQ08881.
    CleanExiHS_ITK.
    GenevestigatoriQ08881.

    Interactioni

    Subunit structurei

    Homooligomerizes; this association negatively regulates kinase activity By similarity. Interacts with PPIA/CYPA; this interaction regulates TCR signal strength via a proline-directed conformational switch in ITK. Interacts with THEMIS By similarity. Interacts with FASLG. Interacts with VAV1; this interaction is important for VAV1 localization and TCR-induced actin polarization.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ERBB2P046262EBI-968552,EBI-641062
    FASLGP480233EBI-968552,EBI-495538

    Protein-protein interaction databases

    BioGridi109907. 25 interactions.
    DIPiDIP-29974N.
    IntActiQ08881. 10 interactions.
    MINTiMINT-110502.
    STRINGi9606.ENSP00000398655.

    Structurei

    Secondary structure

    1
    620
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi127 – 1337
    Beta strandi148 – 1525
    Beta strandi171 – 1733
    Beta strandi175 – 1806
    Beta strandi187 – 1893
    Beta strandi197 – 2059
    Beta strandi208 – 2125
    Beta strandi214 – 2163
    Beta strandi218 – 2214
    Helixi223 – 2253
    Beta strandi226 – 2283
    Helixi360 – 3623
    Beta strandi363 – 3719
    Beta strandi372 – 3743
    Beta strandi376 – 3827
    Turni383 – 3853
    Beta strandi386 – 3938
    Turni395 – 3973
    Helixi400 – 41112
    Beta strandi421 – 4255
    Beta strandi427 – 43610
    Helixi443 – 4486
    Turni449 – 4524
    Helixi456 – 47520
    Helixi485 – 4873
    Beta strandi488 – 4903
    Helixi492 – 4943
    Beta strandi496 – 4983
    Helixi503 – 5064
    Helixi510 – 5134
    Helixi522 – 5243
    Helixi527 – 5326
    Helixi537 – 55216
    Turni553 – 5553
    Turni558 – 5614
    Helixi564 – 5729
    Beta strandi581 – 5833
    Helixi585 – 59410
    Helixi599 – 6013
    Helixi605 – 61713

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1SM2X-ray2.30A/B357-620[»]
    1SNUX-ray2.50A/B357-620[»]
    1SNXX-ray3.20A/B357-620[»]
    2E6INMR-A113-169[»]
    2LMJNMR-A171-231[»]
    2YUQNMR-A162-239[»]
    3MIYX-ray1.67A/B357-620[»]
    3MJ1X-ray1.72A357-620[»]
    3MJ2X-ray1.90A357-620[»]
    3QGWX-ray2.10A/B357-620[»]
    3QGYX-ray2.10A/B357-620[»]
    3T9TX-ray1.65A354-620[»]
    3V5JX-ray2.59A/B357-620[»]
    3V5LX-ray1.86A/B/C/D357-620[»]
    3V8TX-ray2.00A/B357-620[»]
    3V8WX-ray2.27A/B357-620[»]
    4HCTX-ray1.48A354-620[»]
    4HCUX-ray1.43A354-620[»]
    4HCVX-ray1.48A354-620[»]
    4KIOX-ray2.18A/B/C/D357-620[»]
    4L7SX-ray2.03A/B357-620[»]
    4M0YX-ray1.70A354-620[»]
    4M0ZX-ray2.00A354-620[»]
    4M12X-ray2.15A354-620[»]
    4M13X-ray1.85A354-620[»]
    4M14X-ray1.55A354-620[»]
    4M15X-ray1.52A354-620[»]
    4MF0X-ray2.67A/B357-620[»]
    4MF1X-ray2.11A/B357-620[»]
    4PP9X-ray2.58A/B357-620[»]
    4PPAX-ray2.67A/B357-620[»]
    4PPBX-ray2.82A/B357-620[»]
    4PPCX-ray2.95A/B357-620[»]
    ProteinModelPortaliQ08881.
    SMRiQ08881. Positions 1-618.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ08881.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini4 – 111108PHPROSITE-ProRule annotationsAdd
    BLAST
    Domaini171 – 23161SH3PROSITE-ProRule annotationsAdd
    BLAST
    Domaini239 – 338100SH2PROSITE-ProRule annotationsAdd
    BLAST
    Domaini363 – 615253Protein kinasePROSITE-ProRule annotationsAdd
    BLAST

    Domaini

    The N-terminal PH domain allows ITK to be recruited to the plasma membrane by an activated PI3 kinase. This domain contains also a proline-rich region (PRR). The adjoining domain is a SH3 domain, which binds to PRR (from itself or from other proteins). Next, a SH2 domain is required for binding tyrosine-phosphorylated substrates. In the C-terminal region, the kinase domain is required for tyrosine phosphorylation.1 Publication

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.PROSITE-ProRule annotations
    Contains 1 Btk-type zinc finger.PROSITE-ProRule annotations
    Contains 1 PH domain.PROSITE-ProRule annotations
    Contains 1 protein kinase domain.PROSITE-ProRule annotations
    Contains 1 SH2 domain.PROSITE-ProRule annotations
    Contains 1 SH3 domain.PROSITE-ProRule annotations

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri113 – 14937Btk-typePROSITE-ProRule annotationsAdd
    BLAST

    Keywords - Domaini

    SH2 domain, SH3 domain, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233859.
    HOVERGENiHBG008761.
    InParanoidiQ08881.
    KOiK07363.
    OMAiRRNEEYC.
    OrthoDBiEOG7KM5SC.
    PhylomeDBiQ08881.
    TreeFamiTF351634.

    Family and domain databases

    Gene3Di2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProiIPR011009. Kinase-like_dom.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR001562. Znf_Btk_motif.
    [Graphical view]
    PfamiPF00779. BTK. 1 hit.
    PF00169. PH. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    PR00109. TYRKINASE.
    SMARTiSM00107. BTK. 1 hit.
    SM00233. PH. 1 hit.
    SM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS50003. PH_DOMAIN. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    PS51113. ZF_BTK. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Sequencei

    Sequence statusi: Complete.

    Q08881-1 [UniParc]FASTAAdd to Basket

    « Hide

    MNNFILLEEQ LIKKSQQKRR TSPSNFKVRF FVLTKASLAY FEDRHGKKRT    50
    LKGSIELSRI KCVEIVKSDI SIPCHYKYPF QVVHDNYLLY VFAPDRESRQ 100
    RWVLALKEET RNNNSLVPKY HPNFWMDGKW RCCSQLEKLA TGCAQYDPTK 150
    NASKKPLPPT PEDNRRPLWE PEETVVIALY DYQTNDPQEL ALRRNEEYCL 200
    LDSSEIHWWR VQDRNGHEGY VPSSYLVEKS PNNLETYEWY NKSISRDKAE 250
    KLLLDTGKEG AFMVRDSRTA GTYTVSVFTK AVVSENNPCI KHYHIKETND 300
    NPKRYYVAEK YVFDSIPLLI NYHQHNGGGL VTRLRYPVCF GRQKAPVTAG 350
    LRYGKWVIDP SELTFVQEIG SGQFGLVHLG YWLNKDKVAI KTIREGAMSE 400
    EDFIEEAEVM MKLSHPKLVQ LYGVCLEQAP ICLVFEFMEH GCLSDYLRTQ 450
    RGLFAAETLL GMCLDVCEGM AYLEEACVIH RDLAARNCLV GENQVIKVSD 500
    FGMTRFVLDD QYTSSTGTKF PVKWASPEVF SFSRYSSKSD VWSFGVLMWE 550
    VFSEGKIPYE NRSNSEVVED ISTGFRLYKP RLASTHVYQI MNHCWKERPE 600
    DRPAFSRLLR QLAEIAESGL 620
    Length:620
    Mass (Da):71,831
    Last modified:October 1, 1994 - v1
    Checksum:iDAE396BD2309319D
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti19 – 191R → K in a metastatic melanoma sample; somatic mutation. 1 Publication
    VAR_041710
    Natural varianti23 – 231P → L in a metastatic melanoma sample; somatic mutation. 1 Publication
    VAR_041711
    Natural varianti193 – 1931R → Q.
    Corresponds to variant rs17054374 [ dbSNP | Ensembl ].
    VAR_051696
    Natural varianti335 – 3351R → W in LPFS1; shows nearly undetectable mutant ITK protein consistent with severe protein instability. 1 Publication
    Corresponds to variant rs121908191 [ dbSNP | Ensembl ].
    VAR_063424
    Natural varianti451 – 4511R → Q in a gastric adenocarcinoma sample; somatic mutation. 1 Publication
    VAR_041712
    Natural varianti581 – 5811R → W.1 Publication
    Corresponds to variant rs34482255 [ dbSNP | Ensembl ].
    VAR_041713
    Natural varianti587 – 5871V → I.1 Publication
    Corresponds to variant rs56005928 [ dbSNP | Ensembl ].
    VAR_041714

    Sequence conflict

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti171 – 1722PE → GS AA sequence (PubMed:12573241)Curated
    Sequence conflicti331 – 3311V → W in AAB28072. (PubMed:8364206)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D13720 mRNA. Translation: BAA02873.1.
    L10717 mRNA. Translation: AAA36748.1.
    S65186 mRNA. Translation: AAB28072.2.
    AK312846 mRNA. Translation: BAG35699.1.
    CH471062 Genomic DNA. Translation: EAW61608.1.
    BC109077 mRNA. Translation: AAI09078.1.
    BC109078 mRNA. Translation: AAI09079.1.
    CCDSiCCDS4336.1.
    PIRiS33253.
    RefSeqiNP_005537.3. NM_005546.3.
    UniGeneiHs.558348.

    Genome annotation databases

    EnsembliENST00000422843; ENSP00000398655; ENSG00000113263.
    GeneIDi3702.
    KEGGihsa:3702.
    UCSCiuc003lwo.1. human.

    Polymorphism databases

    DMDMi585361.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D13720 mRNA. Translation: BAA02873.1 .
    L10717 mRNA. Translation: AAA36748.1 .
    S65186 mRNA. Translation: AAB28072.2 .
    AK312846 mRNA. Translation: BAG35699.1 .
    CH471062 Genomic DNA. Translation: EAW61608.1 .
    BC109077 mRNA. Translation: AAI09078.1 .
    BC109078 mRNA. Translation: AAI09079.1 .
    CCDSi CCDS4336.1.
    PIRi S33253.
    RefSeqi NP_005537.3. NM_005546.3.
    UniGenei Hs.558348.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1SM2 X-ray 2.30 A/B 357-620 [» ]
    1SNU X-ray 2.50 A/B 357-620 [» ]
    1SNX X-ray 3.20 A/B 357-620 [» ]
    2E6I NMR - A 113-169 [» ]
    2LMJ NMR - A 171-231 [» ]
    2YUQ NMR - A 162-239 [» ]
    3MIY X-ray 1.67 A/B 357-620 [» ]
    3MJ1 X-ray 1.72 A 357-620 [» ]
    3MJ2 X-ray 1.90 A 357-620 [» ]
    3QGW X-ray 2.10 A/B 357-620 [» ]
    3QGY X-ray 2.10 A/B 357-620 [» ]
    3T9T X-ray 1.65 A 354-620 [» ]
    3V5J X-ray 2.59 A/B 357-620 [» ]
    3V5L X-ray 1.86 A/B/C/D 357-620 [» ]
    3V8T X-ray 2.00 A/B 357-620 [» ]
    3V8W X-ray 2.27 A/B 357-620 [» ]
    4HCT X-ray 1.48 A 354-620 [» ]
    4HCU X-ray 1.43 A 354-620 [» ]
    4HCV X-ray 1.48 A 354-620 [» ]
    4KIO X-ray 2.18 A/B/C/D 357-620 [» ]
    4L7S X-ray 2.03 A/B 357-620 [» ]
    4M0Y X-ray 1.70 A 354-620 [» ]
    4M0Z X-ray 2.00 A 354-620 [» ]
    4M12 X-ray 2.15 A 354-620 [» ]
    4M13 X-ray 1.85 A 354-620 [» ]
    4M14 X-ray 1.55 A 354-620 [» ]
    4M15 X-ray 1.52 A 354-620 [» ]
    4MF0 X-ray 2.67 A/B 357-620 [» ]
    4MF1 X-ray 2.11 A/B 357-620 [» ]
    4PP9 X-ray 2.58 A/B 357-620 [» ]
    4PPA X-ray 2.67 A/B 357-620 [» ]
    4PPB X-ray 2.82 A/B 357-620 [» ]
    4PPC X-ray 2.95 A/B 357-620 [» ]
    ProteinModelPortali Q08881.
    SMRi Q08881. Positions 1-618.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109907. 25 interactions.
    DIPi DIP-29974N.
    IntActi Q08881. 10 interactions.
    MINTi MINT-110502.
    STRINGi 9606.ENSP00000398655.

    Chemistry

    BindingDBi Q08881.
    ChEMBLi CHEMBL2959.
    GuidetoPHARMACOLOGYi 2046.

    PTM databases

    PhosphoSitei Q08881.

    Polymorphism databases

    DMDMi 585361.

    Proteomic databases

    MaxQBi Q08881.
    PaxDbi Q08881.
    PeptideAtlasi Q08881.
    PRIDEi Q08881.

    Protocols and materials databases

    DNASUi 3702.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000422843 ; ENSP00000398655 ; ENSG00000113263 .
    GeneIDi 3702.
    KEGGi hsa:3702.
    UCSCi uc003lwo.1. human.

    Organism-specific databases

    CTDi 3702.
    GeneCardsi GC05P156607.
    HGNCi HGNC:6171. ITK.
    MIMi 186973. gene.
    613011. phenotype.
    neXtProti NX_Q08881.
    Orphaneti 238505. Autosomal recessive lymphoproliferative disease.
    PharmGKBi PA29968.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233859.
    HOVERGENi HBG008761.
    InParanoidi Q08881.
    KOi K07363.
    OMAi RRNEEYC.
    OrthoDBi EOG7KM5SC.
    PhylomeDBi Q08881.
    TreeFami TF351634.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 2681.
    Reactomei REACT_12623. Generation of second messenger molecules.
    REACT_163834. FCERI mediated Ca+2 mobilization.
    SignaLinki Q08881.

    Miscellaneous databases

    EvolutionaryTracei Q08881.
    GeneWikii ITK_(gene).
    GenomeRNAii 3702.
    NextBioi 14507.
    PROi Q08881.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q08881.
    Bgeei Q08881.
    CleanExi HS_ITK.
    Genevestigatori Q08881.

    Family and domain databases

    Gene3Di 2.30.29.30. 1 hit.
    3.30.505.10. 1 hit.
    InterProi IPR011009. Kinase-like_dom.
    IPR001849. PH_domain.
    IPR011993. PH_like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR001452. SH3_domain.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR001562. Znf_Btk_motif.
    [Graphical view ]
    Pfami PF00779. BTK. 1 hit.
    PF00169. PH. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    PR00109. TYRKINASE.
    SMARTi SM00107. BTK. 1 hit.
    SM00233. PH. 1 hit.
    SM00252. SH2. 1 hit.
    SM00326. SH3. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 1 hit.
    SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi PS50003. PH_DOMAIN. 1 hit.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    PS51113. ZF_BTK. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "A novel human tyrosine kinase gene inducible in T cells by interleukin 2."
      Tanaka N., Asao H., Ohtani K., Nakamura M., Sugamura K.
      FEBS Lett. 324:1-5(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], INDUCTION.
    2. "Identification, cloning, and characterization of a novel human T-cell-specific tyrosine kinase located at the hematopoietin complex on chromosome 5q."
      Gibson S., Leung B., Squire J.A., Hill M., Arima N., Goss P., Hogg D., Mills G.B.
      Blood 82:1561-1572(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Thymus.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Thymus.
    4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    6. "Identification of phosphorylation sites within the SH3 domains of Tec family tyrosine kinases."
      Nore B.F., Mattsson P.T., Antonsson P., Backesjo C.-M., Westlund A., Lennartsson J., Hansson H., Low P., Ronnstrand L., Smith C.I.E.
      Biochim. Biophys. Acta 1645:123-132(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 171-192, PHOSPHORYLATION AT TYR-180.
    7. "Lck phosphorylates the activation loop tyrosine of the Itk kinase domain and activates Itk kinase activity."
      Heyeck S.D., Wilcox H.M., Bunnell S.C., Berg L.J.
      J. Biol. Chem. 272:25401-25408(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION BY LCK.
    8. "CD2-mediated activation of the Tec-family tyrosine kinase ITK is controlled by proline-rich stretch-4 of the CD2 cytoplasmic tail."
      King P.D., Sadra A., Teng J.M., Bell G.M., Dupont B.
      Int. Immunol. 10:1009-1016(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION.
    9. "Tec kinases: a family with multiple roles in immunity."
      Yang W.C., Collette Y., Nunes J.A., Olive D.
      Immunity 12:373-382(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAIN.
    10. "Phosphorylation of the linker for activation of T-cells by Itk promotes recruitment of Vav."
      Perez-Villar J.J., Whitney G.S., Sitnick M.T., Dunn R.J., Venkatesan S., O'Day K., Schieven G.L., Lin T.A., Kanner S.B.
      Biochemistry 41:10732-10740(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF LAT.
    11. "Inducible T cell tyrosine kinase regulates actin-dependent cytoskeletal events induced by the T cell antigen receptor."
      Grasis J.A., Browne C.D., Tsoukas C.D.
      J. Immunol. 170:3971-3976(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
      Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
      Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    13. "Cyclophilin A regulates TCR signal strength in CD4+ T cells via a proline-directed conformational switch in Itk."
      Colgan J., Asmal M., Neagu M., Yu B., Schneidkraut J., Lee Y., Sokolskaja E., Andreotti A., Luban J.
      Immunity 21:189-201(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PPIA/CYPA, MUTAGENESIS OF PRO-288.
    14. "Kinase-independent functions for Itk in TCR-induced regulation of Vav and the actin cytoskeleton."
      Dombroski D., Houghtling R.A., Labno C.M., Precht P., Takesono A., Caplen N.J., Billadeau D.D., Wange R.L., Burkhardt J.K., Schwartzberg P.L.
      J. Immunol. 174:1385-1392(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH VAV1.
    15. "Tec kinase Itk forms membrane clusters specifically in the vicinity of recruiting receptors."
      Qi Q., Sahu N., August A.
      J. Biol. Chem. 281:38529-38534(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    16. "Identification of SH3 domain interaction partners of human FasL (CD178) by phage display screening."
      Voss M., Lettau M., Janssen O.
      BMC Immunol. 10:53-53(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FASLG.
    17. "SH2-dependent autophosphorylation within the Tec family kinase Itk."
      Joseph R.E., Severin A., Min L., Fulton D.B., Andreotti A.H.
      J. Mol. Biol. 391:164-177(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: AUTOPHOSPHORYLATION.
    18. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-512 AND SER-565, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    19. "Development and validation of a method for profiling post-translational modification activities using protein microarrays."
      Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B., Spruck C.
      PLoS ONE 5:E11332-E11332(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION.
    20. Cited for: FUNCTION IN PHOSPHORYLATION OF LCP2.
    21. "Solution structure of the BTK motif and the SH3 domain of tyrosine-protein kinase ITK from human."
      RIKEN structural genomics initiative (RSGI)
      Submitted (OCT-2007) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 113-239.
    22. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-19; LEU-23; GLN-451; TRP-581 AND ILE-587.
    23. "Girls homozygous for an IL-2-inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation."
      Huck K., Feyen O., Niehues T., Rueschendorf F., Huebner N., Laws H.-J., Telieps T., Knapp S., Wacker H.-H., Meindl A., Jumaa H., Borkhardt A.
      J. Clin. Invest. 119:1350-1358(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT LPFS1 TRP-335, CHARACTERIZATION OF VARIANT LPSA1 TRP-335.

    Entry informationi

    Entry nameiITK_HUMAN
    AccessioniPrimary (citable) accession number: Q08881
    Secondary accession number(s): B2R752, Q32ML7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1994
    Last sequence update: October 1, 1994
    Last modified: October 1, 2014
    This is version 162 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

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