Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0005399
UniProt IDP52333
Primary gene name(s)JAK3
Synonym gene name(s)unknown
Protein nameTyrosine-protein kinase JAK3
Protein functionNon-receptor tyrosine kinase involved in various processes such as cell growth, development, or differentiation. Mediates essential signaling events in both innate and adaptive immunity and plays a crucial role in hematopoiesis during T-cells development. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors sharing the common subunit gamma such as IL2R, IL4R, IL7R, IL9R, IL15R and IL21R. Following ligand binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, upon IL2R activation by IL2, JAK1 and JAK3 molecules bind to IL2R beta, IL2RB and gamma chain, IL2RG subunits inducing the tyrosine phosphorylation of both receptor subunits on their cytoplasmic domain. Then, STAT5A AND STAT5B are recruited, phosphorylated and activated by JAK1 and JAK3. Once activated, dimerized STAT5 translocates to the nucleus and promotes the transcription of specific target genes in a cytokine-specific fashion. {ECO:0000269|PubMed:11909529, ECO:0000269|PubMed:20440074, ECO:0000269|PubMed:7662955, ECO:0000269|PubMed:8022485}.
Subcellular locationEndomembrane system {ECO:0000250};
Peripheral membrane protein {ECO:0000250}. Cytoplasm {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P52333
Gene Ontology
(Biological Process)
Complete annatation
adaptive immune response [GO:0002250];
B cell differentiation [GO:0030183];
cell migration [GO:0016477];
enzyme linked receptor protein signaling pathway [GO:0007167];
innate immune response [GO:0045087];
interleukin-4-mediated signaling pathway [GO:0035771];
intracellular signal transduction [GO:0035556];
JAK-STAT cascade involved in growth hormone signaling pathway [GO:0060397];
MAPK cascade [GO:0000165];
negative regulation of dendritic cell cytokine production [GO:0002731];
negative regulation of FasL biosynthetic process [GO:0045221];
negative regulation of interleukin-10 production [GO:0032693];
negative regulation of interleukin-12 production [GO:0032695];
negative regulation of T cell activation [GO:0050868];
negative regulation of T-helper 1 cell differentiation [GO:0045626];
negative regulation of thymocyte apoptotic process [GO:0070244];
peptidyl-tyrosine autophosphorylation [GO:0038083];
peptidyl-tyrosine phosphorylation [GO:0018108];
positive regulation of T cell proliferation [GO:0042102];
protein phosphorylation [GO:0006468];
regulation of T cell apoptotic process [GO:0070232];
response to interleukin-15 [GO:0070672];
response to interleukin-2 [GO:0070669];
response to interleukin-4 [GO:0070670];
response to interleukin-9 [GO:0071104];
STAT protein import into nucleus [GO:0007262];
T cell homeostasis [GO:0043029];
tyrosine phosphorylation of STAT protein [GO:0007260]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
non-membrane spanning protein tyrosine kinase activity [GO:0004715];
protein phosphatase binding [GO:0019903];
protein tyrosine kinase activity [GO:0004713];
Ras guanyl-nucleotide exchange factor activity [GO:0005088];
receptor binding [GO:0005102]
Gene Ontology
(Cellular Component)
Complete annatation
cytoskeleton [GO:0005856];
cytosol [GO:0005829];
endomembrane system [GO:0012505];
extrinsic component of cytoplasmic side of plasma membrane [GO:0031234]
Protein-protein interaction109921
Phylogenetic treeP52333
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
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. CD30.01904645323078430.9535690621691540.969914489473174
AZA vs. DISU0.0199320421067340.9370949732069710.995208615779092
AZA vs. IL70.1230821547346350.5212976730171450.999311006273513
AZA vs. SAHA-0.5612860966654220.02203124759683120.164242841876673
DISU vs. CD3-0.01178585579592440.9740494896043960.983839587663942
DISU vs. IL70.09410630088978370.7083416082605240.924840143472477
DISU vs. SAHA-0.5787545567394070.04787900507460390.272604641284229
DMSO vs. AZA0.05503904293361010.741967206248581
DMSO vs. CD30.02299136558609150.942632926320430.959965188603885
DMSO vs. DISU0.03300327339772680.8922245226847440.988283279918411
DMSO vs. IL70.07562503194391980.6734493177745630.932817924030342
DMSO vs. SAHA-0.6214524830705060.008725110958254790.0822055663394033
HIV vs. Mock in Activation0.1697491753482650.7847900380634380.999983755607037
HIV vs. Mock in Latency-0.2306300635703730.1610604313525070.999834320637052
IL7 vs. CD30.1103475848795050.7309352714183710.818762882038007
SAHA vs. CD3-0.6039906250976270.09000389351676750.160117893436157
SAHA vs. IL7-0.6870888511950720.005062003746843960.0387333220710283
(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) unknown
(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 -0.227655 0.154214
(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
0.815 0.352 0.469 0.785 0.331
(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
DB04716 2-(1,1-DIMETHYLETHYL)9-FLUORO-3,6-DIHYDRO-7H-BENZ[H]-IMIDAZ[4,5-F]ISOQUINOLIN-7-ONE experimental unknown unknown
DB08183 3-{(3R,4R)-4-methyl-3-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]piperidin-1-yl}-3-oxopropanenitrile experimental unknown unknown
DB08895 Tofacitinib approved, investigational yes inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1YVJ X-ray 2.5Å A=814-1103.
3LXK X-ray 2.0Å A=806-1124.
3LXL X-ray 1.7Å A=806-1124.
3PJC X-ray 2.2Å A=812-1124.
3ZC6 X-ray 2.4Å A/B/C/D=813-1100.
3ZEP X-ray 2.3Å A/B/C/D=813-1047# A/B/C/D=813-1100.
4HVD X-ray 1.8Å A=811-1124.
4HVG X-ray 2.7Å A=811-1124.
4HVH X-ray 2.3Å A=811-1124.
4HVI X-ray 2.4Å A=811-1124.
4I6Q X-ray 1.8Å A=811-1124.
4QPS X-ray 1.8Å A/C=811-1103.
4QT1 X-ray 2.4Å A=811-1124.
4RIO X-ray 2.6Å A=810-1100.
4V0G X-ray 3.0Å A/B=816-1098.
4Z16 X-ray 2.9Å A/B/C/D=811-1124.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 downregulates 9637477
Tat upregulates 23898208
Tat interacts with 24244375

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04550 Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
hsa04630 Jak-STAT signaling pathway - Homo sapiens (human)
hsa04658 Th1 and Th2 cell differentiation - Homo sapiens (human)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05340 Primary immunodeficiency - Homo sapiens (human)