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Q08881 (ITK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 160. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:ITK
Synonyms:EMT, LYK
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length620 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10 Ref.11 Ref.20

Catalytic activity

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

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subunit structure

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. Ref.13 Ref.14 Ref.16

Subcellular location

Cytoplasm. Note: Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation. Ref.15

Tissue specificity

T-cell lines and natural killer cell lines.

Induction

Through a myriad of surface receptors including the TCR/CD3 signaling complex, coreceptors, or chemokine receptors. Ref.1 Ref.8

Domain

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. Ref.9

Post-translational modification

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. Ref.6 Ref.7 Ref.17

Ubiquitinated. Ref.19

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.

Contains 1 Btk-type zinc finger.

Contains 1 PH domain.

Contains 1 protein kinase domain.

Contains 1 SH2 domain.

Contains 1 SH3 domain.

Ontologies

Keywords
   Biological processAdaptive immunity
Immunity
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainSH2 domain
SH3 domain
Zinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Transferase
Tyrosine-protein kinase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

NK T cell differentiation

Inferred from electronic annotation. Source: Ensembl

T cell activation

Traceable author statement Ref.10. Source: UniProtKB

T cell receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

activation of phospholipase C activity

Inferred from sequence or structural similarity. Source: UniProtKB

adaptive immune response

Inferred from sequence or structural similarity. Source: UniProtKB

cellular defense response

Traceable author statement Ref.2. Source: ProtInc

cytokine production

Inferred from sequence or structural similarity. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

interleukin-4 production

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

peptidyl-tyrosine phosphorylation

Inferred from direct assay Ref.10. Source: GOC

signal transduction

Traceable author statement Ref.2. Source: ProtInc

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from direct assay Ref.10. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.10. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ERBB2P046262EBI-968552,EBI-641062
FASLGP480233EBI-968552,EBI-495538

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 620620Tyrosine-protein kinase ITK/TSK
PRO_0000088106

Regions

Domain4 – 111108PH
Domain171 – 23161SH3
Domain239 – 338100SH2
Domain363 – 615253Protein kinase
Zinc finger113 – 14937Btk-type
Nucleotide binding369 – 3779ATP By similarity

Sites

Active site4821Proton acceptor By similarity
Metal binding1211Zinc By similarity
Metal binding1321Zinc By similarity
Metal binding1331Zinc By similarity
Metal binding1431Zinc By similarity
Binding site3911ATP By similarity

Amino acid modifications

Modified residue1801Phosphotyrosine; by autocatalysis Ref.6
Modified residue5121Phosphotyrosine; by LCK Ref.18
Modified residue5651Phosphoserine Ref.18

Natural variations

Natural variant191R → K in a metastatic melanoma sample; somatic mutation. Ref.22
VAR_041710
Natural variant231P → L in a metastatic melanoma sample; somatic mutation. Ref.22
VAR_041711
Natural variant1931R → Q.
Corresponds to variant rs17054374 [ dbSNP | Ensembl ].
VAR_051696
Natural variant3351R → W in LPFS1; shows nearly undetectable mutant ITK protein consistent with severe protein instability. Ref.23
Corresponds to variant rs121908191 [ dbSNP | Ensembl ].
VAR_063424
Natural variant4511R → Q in a gastric adenocarcinoma sample; somatic mutation. Ref.22
VAR_041712
Natural variant5811R → W. Ref.22
Corresponds to variant rs34482255 [ dbSNP | Ensembl ].
VAR_041713
Natural variant5871V → I. Ref.22
Corresponds to variant rs56005928 [ dbSNP | Ensembl ].
VAR_041714

Experimental info

Mutagenesis2881P → G: Complete loss of interaction with PPIA/CYPA. Ref.13
Sequence conflict171 – 1722PE → GS AA sequence Ref.6
Sequence conflict3311V → W in AAB28072. Ref.2

Secondary structure

......................................................................... 620
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q08881 [UniParc].

Last modified October 1, 1994. Version 1.
Checksum: DAE396BD2309319D

FASTA62071,831
        10         20         30         40         50         60 
MNNFILLEEQ LIKKSQQKRR TSPSNFKVRF FVLTKASLAY FEDRHGKKRT LKGSIELSRI 

        70         80         90        100        110        120 
KCVEIVKSDI SIPCHYKYPF QVVHDNYLLY VFAPDRESRQ RWVLALKEET RNNNSLVPKY 

       130        140        150        160        170        180 
HPNFWMDGKW RCCSQLEKLA TGCAQYDPTK NASKKPLPPT PEDNRRPLWE PEETVVIALY 

       190        200        210        220        230        240 
DYQTNDPQEL ALRRNEEYCL LDSSEIHWWR VQDRNGHEGY VPSSYLVEKS PNNLETYEWY 

       250        260        270        280        290        300 
NKSISRDKAE KLLLDTGKEG AFMVRDSRTA GTYTVSVFTK AVVSENNPCI KHYHIKETND 

       310        320        330        340        350        360 
NPKRYYVAEK YVFDSIPLLI NYHQHNGGGL VTRLRYPVCF GRQKAPVTAG LRYGKWVIDP 

       370        380        390        400        410        420 
SELTFVQEIG SGQFGLVHLG YWLNKDKVAI KTIREGAMSE EDFIEEAEVM MKLSHPKLVQ 

       430        440        450        460        470        480 
LYGVCLEQAP ICLVFEFMEH GCLSDYLRTQ RGLFAAETLL GMCLDVCEGM AYLEEACVIH 

       490        500        510        520        530        540 
RDLAARNCLV GENQVIKVSD FGMTRFVLDD QYTSSTGTKF PVKWASPEVF SFSRYSSKSD 

       550        560        570        580        590        600 
VWSFGVLMWE VFSEGKIPYE NRSNSEVVED ISTGFRLYKP RLASTHVYQI MNHCWKERPE 

       610        620 
DRPAFSRLLR QLAEIAESGL 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Sequential phosphorylation of SLP-76 at tyrosine 173 is required for activation of T and mast cells."
Sela M., Bogin Y., Beach D., Oellerich T., Lehne J., Smith-Garvin J.E., Okumura M., Starosvetsky E., Kosoff R., Libman E., Koretzky G., Kambayashi T., Urlaub H., Wienands J., Chernoff J., Yablonski D.
EMBO J. 30:3160-3172(2011) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS4336.1.
PIRS33253.
RefSeqNP_005537.3. NM_005546.3.
UniGeneHs.558348.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ08881.
SMRQ08881. Positions 1-618.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109907. 25 interactions.
DIPDIP-29974N.
IntActQ08881. 10 interactions.
MINTMINT-110502.
STRING9606.ENSP00000398655.

Chemistry

BindingDBQ08881.
ChEMBLCHEMBL2959.
GuidetoPHARMACOLOGY2046.

PTM databases

PhosphoSiteQ08881.

Polymorphism databases

DMDM585361.

Proteomic databases

MaxQBQ08881.
PaxDbQ08881.
PeptideAtlasQ08881.
PRIDEQ08881.

Protocols and materials databases

DNASU3702.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000422843; ENSP00000398655; ENSG00000113263.
GeneID3702.
KEGGhsa:3702.
UCSCuc003lwo.1. human.

Organism-specific databases

CTD3702.
GeneCardsGC05P156607.
HGNCHGNC:6171. ITK.
MIM186973. gene.
613011. phenotype.
neXtProtNX_Q08881.
Orphanet238505. Autosomal recessive lymphoproliferative disease.
PharmGKBPA29968.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233859.
HOVERGENHBG008761.
InParanoidQ08881.
KOK07363.
OMARRNEEYC.
OrthoDBEOG7KM5SC.
PhylomeDBQ08881.
TreeFamTF351634.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_6900. Immune System.
SignaLinkQ08881.

Gene expression databases

ArrayExpressQ08881.
BgeeQ08881.
CleanExHS_ITK.
GenevestigatorQ08881.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProIPR011009. Kinase-like_dom.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
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]
PfamPF00779. BTK. 1 hit.
PF00169. PH. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00109. TYRKINASE.
SMARTSM00107. BTK. 1 hit.
SM00233. PH. 1 hit.
SM00252. SH2. 1 hit.
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
SSF55550. SSF55550. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50003. 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]
ProtoNetSearch...

Other

EvolutionaryTraceQ08881.
GeneWikiITK_(gene).
GenomeRNAi3702.
NextBio14507.
PROQ08881.
SOURCESearch...

Entry information

Entry nameITK_HUMAN
AccessionPrimary (citable) accession number: Q08881
Secondary accession number(s): B2R752, Q32ML7
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: July 9, 2014
This is version 160 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM