Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001471
UniProt IDQ08881
Primary gene name(s)ITK
Synonym gene name(s)EMT, LYK
Protein nameTyrosine-protein kinase ITK/TSK
Protein functionTyrosine 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. {ECO:0000269|PubMed:12186560, ECO:0000269|PubMed:12682224, ECO:0000269|PubMed:21725281}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:17060314}. Note=Localizes in the vicinity of cell surface receptors in the plasma membrane after receptor stimulation.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q08881
Gene Ontology
(Biological Process)
Complete annatation
activation of phospholipase C activity [GO:0007202];
adaptive immune response [GO:0002250];
cellular defense response [GO:0006968];
cytokine production [GO:0001816];
Fc-epsilon receptor signaling pathway [GO:0038095];
innate immune response [GO:0045087];
interferon-gamma production [GO:0032609];
interleukin-4 production [GO:0032633];
intracellular signal transduction [GO:0035556];
NK T cell differentiation [GO:0001865];
peptidyl-tyrosine autophosphorylation [GO:0038083];
regulation of cell proliferation [GO:0042127];
signal transduction [GO:0007165];
T cell activation [GO:0042110];
T cell receptor signaling pathway [GO:0050852];
transmembrane receptor protein tyrosine kinase signaling pathway [GO:0007169]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
metal ion binding [GO:0046872];
non-membrane spanning protein tyrosine kinase activity [GO:0004715]
Gene Ontology
(Cellular Component)
Complete annatation
cell-cell junction [GO:0005911];
cytosol [GO:0005829];
extrinsic component of cytoplasmic side of plasma membrane [GO:0031234]
Protein-protein interaction109907
Phylogenetic treeQ08881
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.4191091973611770.2039249912862470.309522403692478
AZA vs. DISU0.06438875904253640.7985423182317340.982911011425006
AZA vs. IL70.1897130643586440.3220612854814060.999311006273513
AZA vs. SAHA-0.0252531395845970.9173151539395720.981377475548978
DISU vs. CD3-0.3677946216401750.3141698793801710.446688998469789
DISU vs. IL70.1163723123177190.6432578692259480.89539357142947
DISU vs. SAHA-0.08816849671376920.7616862851060610.933099972131921
DMSO vs. AZA0.01982502059832430.9053478542517681
DMSO vs. CD3-0.4116765126875470.20099743069870.300310055883756
DMSO vs. DISU-0.04659316238868850.8481561153565790.982583769983649
DMSO vs. IL70.177188363740480.3226590046986220.799721223986312
DMSO vs. SAHA-0.05160823638123070.8262310182116780.9527541217637
HIV vs. Mock in Activation0.1714819719123320.7833451412778050.999983755607037
HIV vs. Mock in Latency-0.04962789534511730.7632719185882370.999834320637052
IL7 vs. CD3-0.2218118600671950.4932221216050910.623947716236135
SAHA vs. CD3-0.4692331515543030.1871932405873750.28674549051146
SAHA vs. IL7-0.2186783014501290.3681054982589820.617977757072713
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.223539 0.105635
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.93 1.589 0.668 0.487 1.586
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB02010 Staurosporine experimental unknown unknown
DB06589 Pazopanib approved unknown inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1SM2 X-ray 2.3Å A/B=357-620.
1SNU X-ray 2.5Å A/B=357-620.
1SNX X-ray 3.2Å A/B=357-620.
2E6I NMR - A=113-169.
2LMJ NMR - A=171-231.
2YUQ NMR - A=162-239.
3MIY X-ray 1.6Å A/B=357-620.
3MJ1 X-ray 1.7Å A=357-620.
3MJ2 X-ray 1.9Å A=357-620.
3QGW X-ray 2.1Å A/B=357-620.
3QGY X-ray 2.1Å A/B=357-620.
3T9T X-ray 1.6Å A=354-620.
3V5J X-ray 2.5Å A/B=357-620.
3V5L X-ray 1.8Å A/B/C/D=357-620.
3V8T X-ray 2.0Å A/B=357-620.
3V8W X-ray 2.2Å A/B=357-620.
4HCT X-ray 1.4Å A=354-620.
4HCU X-ray 1.4Å A=354-620.
4HCV X-ray 1.4Å A=354-620.
4KIO X-ray 2.1Å A/B/C/D=357-620.
4L7S X-ray 2.0Å A/B=357-620.
4M0Y X-ray 1.7Å A=354-620.
4M0Z X-ray 2.0Å A=354-620.
4M12 X-ray 2.1Å A=354-620.
4M13 X-ray 1.8Å A=354-620.
4M14 X-ray 1.5Å A=354-620.
4M15 X-ray 1.5Å A=354-620.
4MF0 X-ray 2.6Å A/B=357-620.
4MF1 X-ray 2.1Å A/B=357-620.
4PP9 X-ray 2.5Å A/B=357-620.
4PPA X-ray 2.6Å A/B=357-620.
4PPB X-ray 2.8Å A/B=357-620.
4PPC X-ray 2.9Å A/B=357-620.
4PQN X-ray 1.7Å A=357-620.
4QD6 X-ray 2.4Å A/B=357-620.
4RFM X-ray 2.1Å A=357-620.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Nef interacts with 24722985
24722985
Pr55(Gag) co-localizes with 23260110
23260110
23260110
23260110
Envelope surface glycoprotein gp120 modulated by 18443296
20842205
Pr55(Gag) upregulated by 18443296

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04660 T cell receptor signaling pathway - Homo sapiens (human)
hsa04670 Leukocyte transendothelial migration - Homo sapiens (human)
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