Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001099
UniProt IDQ12778
Primary gene name(s)FOXO1
Synonym gene name(s)FKHR, FOXO1A
Protein nameForkhead box protein O1
Protein functionTranscription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. Binds to the insulin response element, IRE with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element, DBE with consensus sequence 5'-TT[G/A]TTTAC-3'. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity. Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP. In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC and PCK1. Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and SKT4/MST1. Promotes neural cell death. Mediates insulin action on adipose tissue. Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake. Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells. Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner. {ECO:0000250|UniProtKB:Q9R1E0, ECO:0000269|PubMed:10358076, ECO:0000269|PubMed:12228231, ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:15890677, ECO:0000269|PubMed:18356527, ECO:0000269|PubMed:19221179, ECO:0000269|PubMed:20543840, ECO:0000269|PubMed:21245099}.
Subcellular locationCytoplasm {ECO:0000250|UniProtKB:Q9R1E0}. Nucleus {ECO:0000250|UniProtKB:Q9R1E0}. Note=Shuttles between the cytoplasm and nucleus. Largely nuclear in unstimulated cells. In osteoblasts, colocalizes with ATF4 and RUNX2 in the nucleus, By similarity. Insulin-induced phosphorylation at Ser-256 by PKB/AKT1 leads, via stimulation of Thr-24 phosphorylation, to binding of 14-3-3 proteins and nuclear export to the cytoplasm where it is degraded by the ubiquitin-proteosomal pathway. Phosphorylation at Ser-249 by CDK1 disrupts binding of 14-3-3 proteins and promotes nuclear accumulation. Phosphorylation by NLK results in nuclear export. Translocates to the nucleus upon oxidative stress-induced phosphorylation at Ser-212 by STK4/MST1. SGK1-mediated phosphorylation also results in nuclear translocation. Retained in the nucleus under stress stimuli including oxidative stress, nutrient deprivation or nitric oxide. Retained in the nucleus on methylation. {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q12778
Gene Ontology
(Biological Process)
Complete annatation
apoptotic process [GO:0006915];
autophagy [GO:0006914];
blood vessel development [GO:0001568];
cellular glucose homeostasis [GO:0001678];
cellular response to cold [GO:0070417];
cellular response to dexamethasone stimulus [GO:0071549];
cellular response to DNA damage stimulus [GO:0006974];
cellular response to hydrogen peroxide [GO:0070301];
cellular response to hyperoxia [GO:0071455];
cellular response to insulin stimulus [GO:0032869];
cellular response to nitric oxide [GO:0071732];
cellular response to oxidative stress [GO:0034599];
cellular response to starvation [GO:0009267];
enamel mineralization [GO:0070166];
endocrine pancreas development [GO:0031018];
fat cell differentiation [GO:0045444];
insulin receptor signaling pathway [GO:0008286];
negative regulation of apoptotic process [GO:0043066];
negative regulation of canonical Wnt signaling pathway [GO:0090090];
negative regulation of fat cell differentiation [GO:0045599];
negative regulation of stress-activated MAPK cascade [GO:0032873];
negative regulation of transcription, DNA-templated [GO:0045892];
neuronal stem cell population maintenance [GO:0097150];
positive regulation of apoptotic process [GO:0043065];
positive regulation of autophagy [GO:0010508];
positive regulation of gluconeogenesis [GO:0045722];
positive regulation of protein catabolic process [GO:0045732];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
protein acetylation [GO:0006473];
regulation of energy homeostasis [GO:2000505];
regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter [GO:0035947];
regulation of neural precursor cell proliferation [GO:2000177];
regulation of reactive oxygen species metabolic process [GO:2000377];
response to fluoride [GO:1902617];
temperature homeostasis [GO:0001659];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
beta-catenin binding [GO:0008013];
chromatin binding [GO:0003682];
protein phosphatase 2A binding [GO:0051721];
RNA polymerase II transcription factor activity, sequence-specific DNA binding [GO:0000981];
sequence-specific DNA binding [GO:0043565];
transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding [GO:0001078];
transcription factor activity, transcription factor binding [GO:0000989];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
mitochondrion [GO:0005739];
nucleoplasm [GO:0005654];
nucleus [GO:0005634]
Protein-protein interaction108597
Phylogenetic treeQ12778
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. CD31.431874201227342.05114314081323e-050.000117815660893052
AZA vs. DISU-0.1755021724145010.4893946179244220.932280357714235
AZA vs. IL7-0.2892754616436250.1354164380723560.898662602392564
AZA vs. SAHA-0.06570381585494540.7882224385735490.9442287819058
DISU vs. CD3-1.618878114213551.72038045079814e-050.000120283000534931
DISU vs. IL7-0.1227263784600930.6270064966391040.887542218267293
DISU vs. SAHA0.1103513267919610.705787682007060.91288546904155
DMSO vs. AZA-0.08473577582957560.6155026868298631
DMSO vs. CD3-1.528099110006943.55983431021833e-062.26664851578357e-05
DMSO vs. DISU0.08891659451284940.7163579476701950.962985630444917
DMSO vs. IL7-0.1973672897975110.2758662086198390.769860685669313
DMSO vs. SAHA0.01168755220433940.9605722776305820.990894691832259
HIV vs. Mock in Activation-0.07545688428464950.9060890200680380.999983755607037
HIV vs. Mock in Latency0.06402494752218070.6995031154330810.999834320637052
IL7 vs. CD3-1.712755304867573.19001088211479e-073.48933483498667e-06
SAHA vs. CD3-1.523085791021172.72818091598959e-050.000152555422649214
SAHA vs. IL70.2187851075676310.3716394448573650.621281245622703
(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) TRUE
(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 -0.604768 0.000305467
(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
unknown unknown unknown unknown unknown
(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
202724_s_at 1.49 No downregulated in CD8+ cells

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
3CO6 X-ray 2.1Å C=151-249.
3CO7 X-ray 2.9Å C/F=151-266.
3COA X-ray 2.2Å C/F=151-266.
4LG0 X-ray 2.1Å A=143-270.
5DUI X-ray 2.3Å A/B=151-259.

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

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04152 AMPK signaling pathway - Homo sapiens (human)
hsa04211 Longevity regulating pathway - Homo sapiens (human)
hsa04213 Longevity regulating pathway - multiple species - Homo sapiens (human)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa04919 Thyroid hormone signaling pathway - Homo sapiens (human)
hsa04922 Glucagon signaling pathway - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)