Human Gene ITK (uc003lwo.1) Description and Page Index
  Description: Homo sapiens IL2-inducible T-cell kinase (ITK), mRNA.
RefSeq Summary (NM_005546): 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]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: D13720.1, BC109077.2 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## RefSeq Select criteria :: based on conservation, expression, longest protein ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr5:156,607,907-156,682,109 Size: 74,203 Total Exon Count: 17 Strand: +
Coding Region
   Position: hg19 chr5:156,607,989-156,679,688 Size: 71,700 Coding Exon Count: 17 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:156,607,907-156,682,109)mRNA (may differ from genome)Protein (620 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCEUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: ITK_HUMAN
DESCRIPTION: RecName: Full=Tyrosine-protein kinase ITK/TSK; EC=2.7.10.2; AltName: Full=Interleukin-2-inducible T-cell kinase; Short=IL-2-inducible T-cell kinase; AltName: Full=Kinase EMT; AltName: Full=T-cell-specific kinase; AltName: Full=Tyrosine-protein kinase Lyk;
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.
CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
COFACTOR: Binds 1 zinc ion per subunit (By similarity).
SUBUNIT: 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.
INTERACTION: P48023:FASLG; NbExp=3; IntAct=EBI-968552, EBI-495538;
SUBCELLULAR LOCATION: Cytoplasm. Note=Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation.
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.
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.
PTM: 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.
DISEASE: Defects in ITK are the cause of lymphoproliferative syndrome EBV-associated autosomal type 1 (LPSA1) [MIM:613011]. LPSA1 is 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.
SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily.
SIMILARITY: Contains 1 Btk-type zinc finger.
SIMILARITY: Contains 1 PH domain.
SIMILARITY: Contains 1 protein kinase domain.
SIMILARITY: Contains 1 SH2 domain.
SIMILARITY: Contains 1 SH3 domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ITKID43329ch5q33.html";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): ITK
CDC HuGE Published Literature: ITK
Positive Disease Associations: Body Mass Index , Body Weight Changes , Personality
Related Studies:
  1. Body Mass Index
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
  2. Body Weight Changes
    Caroline S Fox et al. BMC medical genetics 2007, Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project., BMC medical genetics. [PubMed 17903300]
    Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC.
  3. Personality
    Ney Alliey-Rodriguez et al. Psychiatric genetics 2011, Genome-wide association study of personality traits in bipolar patients., Psychiatric genetics. [PubMed 21368711]
    After correction for the 25 subscales in TCI and four scales plus two subscales in ZKPQ, phenotype-wide significance was not reached.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: ITK
Diseases sorted by gene-association score: lymphoproliferative syndrome 1* (1228), autosomal recessive lymphoproliferative disease* (350), lymphoproliferative syndrome, ebv-associated, autosomal, 1* (100), agammaglobulinemia, x-linked 1 (17), angioimmunoblastic t-cell lymphoma (11), lymphoproliferative syndrome (10), allergic asthma (8), amphetamine abuse (7), hemophagocytic lymphohistiocytosis (3)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 8.37 RPKM in Spleen
Total median expression: 40.75 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -19.8082-0.241 Picture PostScript Text
3' UTR -741.092421-0.306 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR011993 - PH_like_dom
IPR001849 - Pleckstrin_homology
IPR000719 - Prot_kinase_cat_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

Pfam Domains:
PF00017 - SH2 domain
PF00018 - SH3 domain
PF00069 - Protein kinase domain
PF00169 - PH domain
PF00779 - BTK motif
PF07653 - Variant SH3 domain
PF07714 - Protein tyrosine kinase
PF14604 - Variant SH3 domain

SCOP Domains:
50044 - SH3-domain
50729 - PH domain-like
56112 - Protein kinase-like (PK-like)
55550 - SH2 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1SM2
- X-ray MuPIT

1SNU
- X-ray MuPIT

1SNX
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2E6I - NMR MuPIT 2YUQ - NMR MuPIT 3MIY - X-ray MuPIT
3MJ1 - X-ray MuPIT 3MJ2 - X-ray MuPIT 3QGW - X-ray MuPIT
3QGY - X-ray MuPIT 3T9T - X-ray MuPIT 3V5J - X-ray MuPIT
3V5L - X-ray MuPIT 3V8T - X-ray MuPIT 3V8W - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q08881
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
      
      
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0046872 metal ion binding
GO:0005102 receptor binding

Biological Process:
GO:0001816 cytokine production
GO:0001865 NK T cell differentiation
GO:0002250 adaptive immune response
GO:0002376 immune system process
GO:0006468 protein phosphorylation
GO:0006968 cellular defense response
GO:0007165 signal transduction
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007202 activation of phospholipase C activity
GO:0016310 phosphorylation
GO:0032609 interferon-gamma production
GO:0032633 interleukin-4 production
GO:0035556 intracellular signal transduction
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0042110 T cell activation
GO:0042127 regulation of cell proliferation
GO:0045087 innate immune response
GO:0050852 T cell receptor signaling pathway

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005911 cell-cell junction
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane


-  Descriptions from all associated GenBank mRNAs
  AB209622 - Homo sapiens mRNA for IL2-inducible T-cell kinase variant protein.
D13720 - Homo sapiens mRNA for ITK, complete cds.
BC109077 - Homo sapiens IL2-inducible T-cell kinase, mRNA (cDNA clone MGC:126257 IMAGE:40034274), complete cds.
BC109078 - Homo sapiens IL2-inducible T-cell kinase, mRNA (cDNA clone MGC:126258 IMAGE:40034276), complete cds.
L10717 - Homo sapiens T cell-specific tyrosine kinase mRNA, complete cds.
S65186 - EMT=T-cell-specific tyrosine kinase [human, mRNA, 6381 nt].
AK312846 - Homo sapiens cDNA, FLJ93288, Homo sapiens IL2-inducible T-cell kinase (ITK), mRNA.
AK303609 - Homo sapiens cDNA FLJ60388 complete cds, highly similar to Tyrosine-protein kinase ITK/TSK (EC 2.7.10.2).
KJ891492 - Synthetic construct Homo sapiens clone ccsbBroadEn_00886 ITK gene, encodes complete protein.
KR711535 - Synthetic construct Homo sapiens clone CCSBHm_00025874 ITK (ITK) mRNA, encodes complete protein.
AB590549 - Synthetic construct DNA, clone: pFN21AB6113, Homo sapiens ITK gene for IL2-inducible T-cell kinase, without stop codon, in Flexi system.
BC094701 - Homo sapiens cDNA clone IMAGE:30409823.
JD446642 - Sequence 427666 from Patent EP1572962.
AK311654 - Homo sapiens cDNA, FLJ18696.
BX538196 - Homo sapiens mRNA; cDNA DKFZp686M05208 (from clone DKFZp686M05208).
JD154749 - Sequence 135773 from Patent EP1572962.
JD310865 - Sequence 291889 from Patent EP1572962.
JD387998 - Sequence 369022 from Patent EP1572962.
JD309665 - Sequence 290689 from Patent EP1572962.
JD420255 - Sequence 401279 from Patent EP1572962.
JD081066 - Sequence 62090 from Patent EP1572962.
JD259530 - Sequence 240554 from Patent EP1572962.
JD193059 - Sequence 174083 from Patent EP1572962.
JD507618 - Sequence 488642 from Patent EP1572962.
JD267964 - Sequence 248988 from Patent EP1572962.
JD088565 - Sequence 69589 from Patent EP1572962.
JD373272 - Sequence 354296 from Patent EP1572962.
JD180396 - Sequence 161420 from Patent EP1572962.
JD511191 - Sequence 492215 from Patent EP1572962.
JD495561 - Sequence 476585 from Patent EP1572962.
JD502278 - Sequence 483302 from Patent EP1572962.
JD328618 - Sequence 309642 from Patent EP1572962.
JD373522 - Sequence 354546 from Patent EP1572962.
JD180993 - Sequence 162017 from Patent EP1572962.
JD280038 - Sequence 261062 from Patent EP1572962.
JD342853 - Sequence 323877 from Patent EP1572962.
JD313335 - Sequence 294359 from Patent EP1572962.
JD137277 - Sequence 118301 from Patent EP1572962.
JD439912 - Sequence 420936 from Patent EP1572962.
JD527450 - Sequence 508474 from Patent EP1572962.
JD540352 - Sequence 521376 from Patent EP1572962.
JD429066 - Sequence 410090 from Patent EP1572962.
JD332792 - Sequence 313816 from Patent EP1572962.
JD303691 - Sequence 284715 from Patent EP1572962.
JD086051 - Sequence 67075 from Patent EP1572962.
JD305520 - Sequence 286544 from Patent EP1572962.
JD213721 - Sequence 194745 from Patent EP1572962.
JD200962 - Sequence 181986 from Patent EP1572962.
JD253710 - Sequence 234734 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04062 - Chemokine signaling pathway
hsa04660 - T cell receptor signaling pathway
hsa04670 - Leukocyte transendothelial migration

BioCarta from NCI Cancer Genome Anatomy Project
h_ctla4Pathway - The Co-Stimulatory Signal During T-cell Activation

Reactome (by CSHL, EBI, and GO)

Protein Q08881 (Reactome details) participates in the following event(s):

R-HSA-202375 Recruitment of ITK to SLP-76
R-HSA-2730885 Recruitment of TEC kinases to p-SLP-76
R-HSA-2730833 Phosphorylation of TEC kinases by p-SYK
R-HSA-2730858 Autophosphorylation of BTK/ITK
R-HSA-2730888 Phosphorylation of PLC-gamma
R-HSA-202248 Phosphorylation of PLC-gamma1
R-HSA-2730847 Hydrolysis of PIP2 by PLCG
R-HSA-202433 Generation of second messenger molecules
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-202403 TCR signaling
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-1280218 Adaptive Immune System
R-HSA-168249 Innate Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: B2R752, EMT, ITK_HUMAN, LYK, NM_005546, NP_005537, Q08881, Q32ML7
UCSC ID: uc003lwo.1
RefSeq Accession: NM_005546
Protein: Q08881 (aka ITK_HUMAN)
CCDS: CCDS4336.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_005546.3
exon count: 17CDS single in 3' UTR: no RNA size: 4366
ORF size: 1863CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3891.00frame shift in genome: no % Coverage: 100.00
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.