Browse FOXO3

Summary
SymbolFOXO3
Nameforkhead box O3
Aliases AF6q21; FOXO2; FKHRL1; FOXO3A; FKHRL1P2; FOXO2A; forkhead box O3A; forkhead homolog (rhabdomyosarcoma) like ......
Chromosomal Location6q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm, cytosol Nucleus Mitochondrion matrix Mitochondrion outer membrane Peripheral membrane protein Cytoplasmic side Note=Retention in the cytoplasm contributes to its inactivation (PubMed:10102273, PubMed:15084260, PubMed:16751106). Translocates to the nucleus upon oxidative stress and in the absence of survival factors (PubMed:10102273, PubMed:16751106). Translocates in a AMPK-dependent manner into the mitochondrion in response to metabolic stress (PubMed:23283301, PubMed:29445193).
Domain PF00250 Forkhead domain
PF16676 Transactivation domain of FOXO protein family
PF16675 KIX-binding domain of forkhead box O
Function

Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (PubMed:10102273, PubMed:16751106). Recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' (PubMed:21329882). Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation (PubMed:21329882). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription (PubMed:23283301).

> Gene Ontology
 
Biological Process GO:0000302 response to reactive oxygen species
GO:0001541 ovarian follicle development
GO:0001542 ovulation from ovarian follicle
GO:0001544 initiation of primordial ovarian follicle growth
GO:0001547 antral ovarian follicle growth
GO:0001556 oocyte maturation
GO:0001666 response to hypoxia
GO:0001678 cellular glucose homeostasis
GO:0002262 myeloid cell homeostasis
GO:0006417 regulation of translation
GO:0006979 response to oxidative stress
GO:0007281 germ cell development
GO:0007292 female gamete generation
GO:0007548 sex differentiation
GO:0007568 aging
GO:0008406 gonad development
GO:0008585 female gonad development
GO:0009743 response to carbohydrate
GO:0009746 response to hexose
GO:0009749 response to glucose
GO:0009991 response to extracellular stimulus
GO:0009994 oocyte differentiation
GO:0010035 response to inorganic substance
GO:0010421 hydrogen peroxide-mediated programmed cell death
GO:0010608 posttranscriptional regulation of gene expression
GO:0010721 negative regulation of cell development
GO:0016055 Wnt signaling pathway
GO:0019827 stem cell population maintenance
GO:0021700 developmental maturation
GO:0022412 cellular process involved in reproduction in multicellular organism
GO:0022602 ovulation cycle process
GO:0030099 myeloid cell differentiation
GO:0030111 regulation of Wnt signaling pathway
GO:0030178 negative regulation of Wnt signaling pathway
GO:0030218 erythrocyte differentiation
GO:0030330 DNA damage response, signal transduction by p53 class mediator
GO:0030728 ovulation
GO:0031667 response to nutrient levels
GO:0031960 response to corticosteroid
GO:0032844 regulation of homeostatic process
GO:0032846 positive regulation of homeostatic process
GO:0033209 tumor necrosis factor-mediated signaling pathway
GO:0033500 carbohydrate homeostasis
GO:0034101 erythrocyte homeostasis
GO:0034248 regulation of cellular amide metabolic process
GO:0034284 response to monosaccharide
GO:0034599 cellular response to oxidative stress
GO:0034612 response to tumor necrosis factor
GO:0034614 cellular response to reactive oxygen species
GO:0035902 response to immobilization stress
GO:0036293 response to decreased oxygen levels
GO:0036294 cellular response to decreased oxygen levels
GO:0036473 cell death in response to oxidative stress
GO:0036474 cell death in response to hydrogen peroxide
GO:0038034 signal transduction in absence of ligand
GO:0042542 response to hydrogen peroxide
GO:0042593 glucose homeostasis
GO:0042698 ovulation cycle
GO:0042770 signal transduction in response to DNA damage
GO:0043523 regulation of neuron apoptotic process
GO:0043525 positive regulation of neuron apoptotic process
GO:0045137 development of primary sexual characteristics
GO:0045637 regulation of myeloid cell differentiation
GO:0045639 positive regulation of myeloid cell differentiation
GO:0045646 regulation of erythrocyte differentiation
GO:0045648 positive regulation of erythrocyte differentiation
GO:0045665 negative regulation of neuron differentiation
GO:0046545 development of primary female sexual characteristics
GO:0046660 female sex differentiation
GO:0048469 cell maturation
GO:0048477 oogenesis
GO:0048511 rhythmic process
GO:0048545 response to steroid hormone
GO:0048599 oocyte development
GO:0048608 reproductive structure development
GO:0048854 brain morphogenesis
GO:0048872 homeostasis of number of cells
GO:0050768 negative regulation of neurogenesis
GO:0051384 response to glucocorticoid
GO:0051385 response to mineralocorticoid
GO:0051402 neuron apoptotic process
GO:0051412 response to corticosterone
GO:0051961 negative regulation of nervous system development
GO:0060070 canonical Wnt signaling pathway
GO:0060828 regulation of canonical Wnt signaling pathway
GO:0061351 neural precursor cell proliferation
GO:0061458 reproductive system development
GO:0070301 cellular response to hydrogen peroxide
GO:0070482 response to oxygen levels
GO:0070997 neuron death
GO:0071322 cellular response to carbohydrate stimulus
GO:0071326 cellular response to monosaccharide stimulus
GO:0071331 cellular response to hexose stimulus
GO:0071333 cellular response to glucose stimulus
GO:0071356 cellular response to tumor necrosis factor
GO:0071383 cellular response to steroid hormone stimulus
GO:0071384 cellular response to corticosteroid stimulus
GO:0071385 cellular response to glucocorticoid stimulus
GO:0071386 cellular response to corticosterone stimulus
GO:0071389 cellular response to mineralocorticoid stimulus
GO:0071396 cellular response to lipid
GO:0071407 cellular response to organic cyclic compound
GO:0071417 cellular response to organonitrogen compound
GO:0071453 cellular response to oxygen levels
GO:0071456 cellular response to hypoxia
GO:0071548 response to dexamethasone
GO:0072331 signal transduction by p53 class mediator
GO:0072577 endothelial cell apoptotic process
GO:0072593 reactive oxygen species metabolic process
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:0097150 neuronal stem cell population maintenance
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand
GO:0097468 programmed cell death in response to reactive oxygen species
GO:0098727 maintenance of cell number
GO:0198738 cell-cell signaling by wnt
GO:1900407 regulation of cellular response to oxidative stress
GO:1900409 positive regulation of cellular response to oxidative stress
GO:1901031 regulation of response to reactive oxygen species
GO:1901033 positive regulation of response to reactive oxygen species
GO:1901214 regulation of neuron death
GO:1901216 positive regulation of neuron death
GO:1901298 regulation of hydrogen peroxide-mediated programmed cell death
GO:1901300 positive regulation of hydrogen peroxide-mediated programmed cell death
GO:1901652 response to peptide
GO:1901653 cellular response to peptide
GO:1901654 response to ketone
GO:1901655 cellular response to ketone
GO:1902882 regulation of response to oxidative stress
GO:1902884 positive regulation of response to oxidative stress
GO:1903201 regulation of oxidative stress-induced cell death
GO:1903205 regulation of hydrogen peroxide-induced cell death
GO:1903209 positive regulation of oxidative stress-induced cell death
GO:1903409 reactive oxygen species biosynthetic process
GO:1903426 regulation of reactive oxygen species biosynthetic process
GO:1903428 positive regulation of reactive oxygen species biosynthetic process
GO:1903706 regulation of hemopoiesis
GO:1903708 positive regulation of hemopoiesis
GO:1904019 epithelial cell apoptotic process
GO:1904035 regulation of epithelial cell apoptotic process
GO:1904037 positive regulation of epithelial cell apoptotic process
GO:1904645 response to beta-amyloid
GO:1904646 cellular response to beta-amyloid
GO:1905206 positive regulation of hydrogen peroxide-induced cell death
GO:1990089 response to nerve growth factor
GO:1990090 cellular response to nerve growth factor stimulus
GO:1990785 response to water-immersion restraint stress
GO:2000177 regulation of neural precursor cell proliferation
GO:2000351 regulation of endothelial cell apoptotic process
GO:2000353 positive regulation of endothelial cell apoptotic process
GO:2000377 regulation of reactive oxygen species metabolic process
GO:2000379 positive regulation of reactive oxygen species metabolic process
Molecular Function GO:0001047 core promoter binding
GO:0001221 transcription cofactor binding
GO:0001227 transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003682 chromatin binding
GO:0008013 beta-catenin binding
GO:0008134 transcription factor binding
GO:0031490 chromatin DNA binding
GO:0043566 structure-specific DNA binding
Cellular Component -
> KEGG and Reactome Pathway
 
KEGG hsa04062 Chemokine signaling pathway
hsa04068 FoxO signaling pathway
hsa04151 PI3K-Akt signaling pathway
hsa04152 AMPK signaling pathway
hsa04722 Neurotrophin signaling pathway
hsa04917 Prolactin signaling pathway
Reactome R-HSA-198693: AKT phosphorylates targets in the nucleus
R-HSA-1280218: Adaptive Immune System
R-HSA-5674400: Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-8862803: Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-186763: Downstream signal transduction
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-180292: GAB1 signalosome
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-6785807: Interleukin-4 and 13 signaling
R-HSA-5683057: MAPK family signaling cascades
R-HSA-5687128: MAPK6/MAPK4 signaling
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-8863678: Neurodegenerative Diseases
R-HSA-2219528: PI3K/AKT Signaling in Cancer
R-HSA-198203: PI3K/AKT activation
R-HSA-1257604: PIP3 activates AKT signaling
R-HSA-2730905: Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-449147: Signaling by Interleukins
R-HSA-1181150: Signaling by NODAL
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF
Summary
SymbolFOXO3
Nameforkhead box O3
Aliases AF6q21; FOXO2; FKHRL1; FOXO3A; FKHRL1P2; FOXO2A; forkhead box O3A; forkhead homolog (rhabdomyosarcoma) like ......
Chromosomal Location6q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between FOXO3 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 

There is no record.

Summary
SymbolFOXO3
Nameforkhead box O3
Aliases AF6q21; FOXO2; FKHRL1; FOXO3A; FKHRL1P2; FOXO2A; forkhead box O3A; forkhead homolog (rhabdomyosarcoma) like ......
Chromosomal Location6q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of FOXO3 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR Second most enriched score: 0.53 Sensitive to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolFOXO3
Nameforkhead box O3
Aliases AF6q21; FOXO2; FKHRL1; FOXO3A; FKHRL1P2; FOXO2A; forkhead box O3A; forkhead homolog (rhabdomyosarcoma) like ......
Chromosomal Location6q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of FOXO3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.0310.878
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.2070.854
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0960.906
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.0280.93
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.210.933
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.2010.948
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.1730.631
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.3710.828
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0730.97
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.2340.837
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.9370.559
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.0360.667
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of FOXO3 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.703.70.27
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.703.70.314
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91606.2-6.21
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59011.1-11.11
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.63.7-1.11
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolFOXO3
Nameforkhead box O3
Aliases AF6q21; FOXO2; FKHRL1; FOXO3A; FKHRL1P2; FOXO2A; forkhead box O3A; forkhead homolog (rhabdomyosarcoma) like ......
Chromosomal Location6q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FOXO3. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolFOXO3
Nameforkhead box O3
Aliases AF6q21; FOXO2; FKHRL1; FOXO3A; FKHRL1P2; FOXO2A; forkhead box O3A; forkhead homolog (rhabdomyosarcoma) like ......
Chromosomal Location6q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FOXO3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FOXO3.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolFOXO3
Nameforkhead box O3
Aliases AF6q21; FOXO2; FKHRL1; FOXO3A; FKHRL1P2; FOXO2A; forkhead box O3A; forkhead homolog (rhabdomyosarcoma) like ......
Chromosomal Location6q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FOXO3. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolFOXO3
Nameforkhead box O3
Aliases AF6q21; FOXO2; FKHRL1; FOXO3A; FKHRL1P2; FOXO2A; forkhead box O3A; forkhead homolog (rhabdomyosarcoma) like ......
Chromosomal Location6q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of FOXO3 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolFOXO3
Nameforkhead box O3
Aliases AF6q21; FOXO2; FKHRL1; FOXO3A; FKHRL1P2; FOXO2A; forkhead box O3A; forkhead homolog (rhabdomyosarcoma) like ......
Chromosomal Location6q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between FOXO3 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolFOXO3
Nameforkhead box O3
Aliases AF6q21; FOXO2; FKHRL1; FOXO3A; FKHRL1P2; FOXO2A; forkhead box O3A; forkhead homolog (rhabdomyosarcoma) like ......
Chromosomal Location6q21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting FOXO3 collected from DrugBank database.
> Drugs from DrugBank database
 

There is no record.