Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002866
UniProt IDP40763
Primary gene name(s)STAT3
Synonym gene name(s)APRF
Protein nameSignal transducer and activator of transcription 3
Protein functionSignal transducer and transcription activator that mediates cellular responses to interleukins, KITLG/SCF, LEP and other growth factors. Once activated, recruits coactivators, such as NCOA1 or MED1, to the promoter region of the target gene, PubMed:17344214. May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4. Binds to the interleukin-6, IL-6-responsive elements identified in the promoters of various acute-phase protein genes. Activated by IL31 through IL31RA. Involved in cell cycle regulation by inducing the expression of key genes for the progression from G1 to S phase, such as CCND1, PubMed:17344214. Mediates the effects of LEP on melanocortin production, body energy homeostasis and lactation, By similarity. May play an apoptotic role by transctivating BIRC5 expression under LEP activation, PubMed:18242580. Cytoplasmic STAT3 represses macroautophagy by inhibiting EIF2AK2/PKR activity. {ECO:0000250|UniProtKB:P42227, ECO:0000269|PubMed:10688651, ECO:0000269|PubMed:12359225, ECO:0000269|PubMed:12873986, ECO:0000269|PubMed:15194700, ECO:0000269|PubMed:17344214, ECO:0000269|PubMed:18242580, ECO:0000269|PubMed:23084476}.
Subcellular locationCytoplasm. Nucleus. Note=Shuttles between the nucleus and the cytoplasm. Translocated into the nucleus upon tyrosine phosphorylation and dimerization, in response to signaling by activated FGFR1, FGFR2, FGFR3 or FGFR4. Constitutive nuclear presence is independent of tyrosine phosphorylation. Predominantly present in the cytoplasm without stimuli. Upon leukemia inhibitory factor, LIF stimulation, accumulates in the nucleus. The complex composed of BART and ARL2 plays an important role in the nuclear translocation and retention of STAT3. Identified in a complex with LYN and PAG1.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P40763
Gene Ontology
(Biological Process)
Complete annatation
acute-phase response [GO:0006953];
aging [GO:0007568];
astrocyte differentiation [GO:0048708];
cell proliferation [GO:0008283];
cellular response to hormone stimulus [GO:0032870];
cellular response to leptin stimulus [GO:0044320];
cellular response to organic cyclic compound [GO:0071407];
cytokine-mediated signaling pathway [GO:0019221];
eating behavior [GO:0042755];
energy homeostasis [GO:0097009];
eye photoreceptor cell differentiation [GO:0001754];
glucose homeostasis [GO:0042593];
growth hormone receptor signaling pathway [GO:0060396];
interleukin-6-mediated signaling pathway [GO:0070102];
intracellular receptor signaling pathway [GO:0030522];
JAK-STAT cascade [GO:0007259];
JAK-STAT cascade involved in growth hormone signaling pathway [GO:0060397];
leptin-mediated signaling pathway [GO:0033210];
miRNA mediated inhibition of translation [GO:0035278];
movement of cell or subcellular component [GO:0006928];
mRNA transcription from RNA polymerase II promoter [GO:0042789];
negative regulation of apoptotic process [GO:0043066];
negative regulation of cell proliferation [GO:0008285];
negative regulation of glycolytic process [GO:0045820];
negative regulation of hydrogen peroxide biosynthetic process [GO:0010730];
negative regulation of neuron death [GO:1901215];
negative regulation of neuron migration [GO:2001223];
negative regulation of stem cell differentiation [GO:2000737];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
nervous system development [GO:0007399];
phosphorylation [GO:0016310];
positive regulation of ATP biosynthetic process [GO:2001171];
positive regulation of cell proliferation [GO:0008284];
positive regulation of gene expression [GO:0010628];
positive regulation of gene silencing by miRNA [GO:2000637];
positive regulation of growth factor dependent skeletal muscle satellite cell proliferation [GO:1902728];
positive regulation of metalloendopeptidase activity [GO:1904685];
positive regulation of Notch signaling pathway [GO:0045747];
positive regulation of pri-miRNA transcription from RNA polymerase II promoter [GO:1902895];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
positive regulation of tyrosine phosphorylation of Stat3 protein [GO:0042517];
protein import into nucleus [GO:0006606];
radial glial cell differentiation [GO:0060019];
regulation of cell cycle [GO:0051726];
regulation of feeding behavior [GO:0060259];
regulation of mitochondrial membrane permeability [GO:0046902];
regulation of multicellular organism growth [GO:0040014];
regulation of transcription, DNA-templated [GO:0006355];
regulation of transcription from RNA polymerase II promoter [GO:0006357];
response to drug [GO:0042493];
response to estradiol [GO:0032355];
response to ethanol [GO:0045471];
response to leptin [GO:0044321];
sexual reproduction [GO:0019953];
signal transduction [GO:0007165];
somatic stem cell population maintenance [GO:0035019];
temperature homeostasis [GO:0001659];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
chromatin DNA binding [GO:0031490];
DNA binding [GO:0003677];
identical protein binding [GO:0042802];
protein dimerization activity [GO:0046983];
protein kinase binding [GO:0019901];
protein phosphatase binding [GO:0019903];
RNA polymerase II core promoter proximal region sequence-specific DNA binding [GO:0000978];
RNA polymerase II repressing transcription factor binding [GO:0001103];
RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding [GO:0004879];
signal transducer activity [GO:0004871];
transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding [GO:0001077];
transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding [GO:0001228];
transcription factor activity, sequence-specific DNA binding [GO:0003700];
transcription factor binding [GO:0008134];
transcription regulatory region DNA binding [GO:0044212]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
mitochondrial inner membrane [GO:0005743];
nuclear chromatin [GO:0000790];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
RNA polymerase II transcription factor complex [GO:0090575]
Protein-protein interaction112651
Phylogenetic treeP40763
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. CD30.7749465100540090.01946930331801790.0455088926192875
AZA vs. DISU0.1388154186226610.5828290016298840.955158276076142
AZA vs. IL70.05341458230425240.7806971464631260.999311006273513
AZA vs. SAHA-0.2103642487769320.3882243576868430.751231574810201
DISU vs. CD3-0.6484857664349240.07881077134482660.154525698133704
DISU vs. IL7-0.09492548076820510.7059177972274960.924160728893139
DISU vs. SAHA-0.3468787108013490.2349968420821290.61295212997919
DMSO vs. AZA-0.05637232883985910.73589997840341
DMSO vs. CD3-0.8420010511274110.009496125939166270.0238392163428662
DMSO vs. DISU-0.1968321510070610.4193765903222410.876841758523198
DMSO vs. IL70.1169731210783320.5144768054684720.887822730765496
DMSO vs. SAHA-0.1598603000601340.4975463495849990.812534525641619
HIV vs. Mock in Activation0.1971702685547020.7512999372811060.999983755607037
HIV vs. Mock in Latency-0.005895905184127510.9714403767127760.999834320637052
IL7 vs. CD3-0.7155456439920190.02810969298589950.0689275097407618
SAHA vs. CD3-1.009152002857340.004791270619233680.013776845684383
SAHA vs. IL7-0.2661968163274070.274486678398710.521635424884285
(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 -0.357648 0.0140372
(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
0.973 0.937 0.886 0.903 1.121
(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

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
5AX3 X-ray 2.9Å B=571-582.

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

HIV Partner Interaction Type PubMed
Nef induces phosphorylation of 21886773
Nef interacts with 18443354
matrix upregulates 25704763
Tat activates 17151125
Tat upregulates 23166591
Envelope surface glycoprotein gp120 inhibits 23554973
matrix induces phosphorylation of 24736615
matrix interacts with 25704763
Tat cooperates with 20661303
matrix increases phosphorylation of 26469385
Envelope surface glycoprotein gp120 upregulates 12089333
Envelope surface glycoprotein gp120 activates 25008924
matrix recruits 26469385
Nef activates 11328823
Nef upregulates 16260903

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01521 EGFR tyrosine kinase inhibitor resistance - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04066 HIF-1 signaling pathway - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04550 Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human)
hsa04630 Jak-STAT signaling pathway - Homo sapiens (human)
hsa04659 Th17 cell differentiation - Homo sapiens (human)
hsa04917 Prolactin signaling pathway - Homo sapiens (human)
hsa04920 Adipocytokine signaling pathway - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa05145 Toxoplasmosis - Homo sapiens (human)
hsa05160 Hepatitis C - Homo sapiens (human)
hsa05161 Hepatitis B - Homo sapiens (human)
hsa05162 Measles - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05212 Pancreatic cancer - Homo sapiens (human)
hsa05221 Acute myeloid leukemia - Homo sapiens (human)
hsa05321 Inflammatory bowel disease (IBD) - Homo sapiens (human)