Summary | |
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Symbol | FOXO1 |
Name | forkhead box O1 |
Aliases | FKH1; FKHR; FOXO1A; forkhead homolog in rhabdomyosarcoma; FKHRA; forkhead box protein O1A; forkhead, Drosoph ...... |
Chromosomal Location | 13q14.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway |
Subcellular Location | Cytoplasm Nucleus 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. |
Domain |
PF00250 Forkhead domain PF16676 Transactivation domain of FOXO protein family PF16675 KIX-binding domain of forkhead box O |
Function |
Transcription 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 STK4/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. Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity). |
Biological Process |
GO:0000302 response to reactive oxygen species GO:0001659 temperature homeostasis GO:0001678 cellular glucose homeostasis GO:0001933 negative regulation of protein phosphorylation GO:0005996 monosaccharide metabolic process GO:0006006 glucose metabolic process GO:0006094 gluconeogenesis GO:0006109 regulation of carbohydrate metabolic process GO:0006111 regulation of gluconeogenesis GO:0006473 protein acetylation GO:0006914 autophagy GO:0006979 response to oxidative stress GO:0008286 insulin receptor signaling pathway GO:0009266 response to temperature stimulus GO:0009267 cellular response to starvation GO:0009409 response to cold GO:0009894 regulation of catabolic process GO:0009896 positive regulation of catabolic process GO:0009991 response to extracellular stimulus GO:0010035 response to inorganic substance GO:0010506 regulation of autophagy GO:0010508 positive regulation of autophagy GO:0010675 regulation of cellular carbohydrate metabolic process GO:0010676 positive regulation of cellular carbohydrate metabolic process GO:0010906 regulation of glucose metabolic process GO:0010907 positive regulation of glucose metabolic process GO:0016051 carbohydrate biosynthetic process GO:0016055 Wnt signaling pathway GO:0019318 hexose metabolic process GO:0019319 hexose biosynthetic process GO:0019827 stem cell population maintenance GO:0030111 regulation of Wnt signaling pathway GO:0030178 negative regulation of Wnt signaling pathway GO:0031016 pancreas development GO:0031018 endocrine pancreas development GO:0031098 stress-activated protein kinase signaling cascade GO:0031214 biomineral tissue development GO:0031667 response to nutrient levels GO:0031668 cellular response to extracellular stimulus GO:0031669 cellular response to nutrient levels GO:0031960 response to corticosteroid GO:0032844 regulation of homeostatic process GO:0032868 response to insulin GO:0032869 cellular response to insulin stimulus GO:0032872 regulation of stress-activated MAPK cascade GO:0032873 negative regulation of stress-activated MAPK cascade GO:0033500 carbohydrate homeostasis GO:0034505 tooth mineralization GO:0034599 cellular response to oxidative stress GO:0034614 cellular response to reactive oxygen species GO:0035270 endocrine system development GO:0035947 regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter GO:0036295 cellular response to increased oxygen levels GO:0036296 response to increased oxygen levels GO:0042176 regulation of protein catabolic process GO:0042326 negative regulation of phosphorylation GO:0042475 odontogenesis of dentin-containing tooth GO:0042476 odontogenesis GO:0042542 response to hydrogen peroxide GO:0042593 glucose homeostasis GO:0042594 response to starvation GO:0043255 regulation of carbohydrate biosynthetic process GO:0043409 negative regulation of MAPK cascade GO:0043434 response to peptide hormone GO:0043543 protein acylation GO:0044262 cellular carbohydrate metabolic process GO:0044283 small molecule biosynthetic process GO:0044723 single-organism carbohydrate metabolic process GO:0045444 fat cell differentiation GO:0045598 regulation of fat cell differentiation GO:0045599 negative regulation of fat cell differentiation GO:0045722 positive regulation of gluconeogenesis GO:0045732 positive regulation of protein catabolic process GO:0045913 positive regulation of carbohydrate metabolic process GO:0046364 monosaccharide biosynthetic process GO:0048545 response to steroid hormone GO:0048871 multicellular organismal homeostasis GO:0051384 response to glucocorticoid GO:0051403 stress-activated MAPK cascade GO:0055093 response to hyperoxia GO:0060070 canonical Wnt signaling pathway GO:0060828 regulation of canonical Wnt signaling pathway GO:0061351 neural precursor cell proliferation GO:0070166 enamel mineralization GO:0070301 cellular response to hydrogen peroxide GO:0070302 regulation of stress-activated protein kinase signaling cascade GO:0070303 negative regulation of stress-activated protein kinase signaling cascade GO:0070417 cellular response to cold GO:0070482 response to oxygen levels GO:0071241 cellular response to inorganic substance GO:0071375 cellular response to peptide hormone stimulus GO:0071383 cellular response to steroid hormone stimulus GO:0071384 cellular response to corticosteroid stimulus GO:0071385 cellular response to glucocorticoid 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:0071455 cellular response to hyperoxia GO:0071496 cellular response to external stimulus GO:0071548 response to dexamethasone GO:0071549 cellular response to dexamethasone stimulus GO:0071731 response to nitric oxide GO:0071732 cellular response to nitric oxide GO:0072593 reactive oxygen species metabolic process GO:0090090 negative regulation of canonical Wnt signaling pathway GO:0097009 energy homeostasis GO:0097150 neuronal stem cell population maintenance GO:0097186 amelogenesis GO:0098727 maintenance of cell number GO:0198738 cell-cell signaling by wnt GO:1901652 response to peptide GO:1901653 cellular response to peptide GO:1901654 response to ketone GO:1901655 cellular response to ketone GO:1902170 cellular response to reactive nitrogen species GO:1902532 negative regulation of intracellular signal transduction GO:1902617 response to fluoride GO:2000177 regulation of neural precursor cell proliferation GO:2000377 regulation of reactive oxygen species metabolic process GO:2000505 regulation of energy homeostasis |
Molecular Function |
GO:0000982 transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001078 transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0001221 transcription cofactor binding GO:0001223 transcription coactivator binding GO:0001227 transcriptional repressor 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:0019902 phosphatase binding GO:0019903 protein phosphatase binding GO:0031625 ubiquitin protein ligase binding GO:0044389 ubiquitin-like protein ligase binding GO:0051721 protein phosphatase 2A binding |
Cellular Component | - |
KEGG |
hsa04068 FoxO signaling pathway hsa04152 AMPK signaling pathway hsa04910 Insulin signaling pathway hsa04919 Thyroid hormone signaling pathway hsa04922 Glucagon signaling pathway |
Reactome |
R-HSA-198693: AKT phosphorylates targets in the nucleus R-HSA-211163: AKT-mediated inactivation of FOXO1A 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-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-2219528: PI3K/AKT Signaling in Cancer R-HSA-198203: PI3K/AKT activation R-HSA-1257604: PIP3 activates AKT signaling R-HSA-186712: Regulation of beta-cell development R-HSA-210745: Regulation of gene expression in beta cells 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-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 | |
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Symbol | FOXO1 |
Name | forkhead box O1 |
Aliases | FKH1; FKHR; FOXO1A; forkhead homolog in rhabdomyosarcoma; FKHRA; forkhead box protein O1A; forkhead, Drosoph ...... |
Chromosomal Location | 13q14.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Literatures that report relations between FOXO1 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. |
Literatures describing the relation between FOXO1 and anti-tumor immunity in human cancer.
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Summary | |
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Symbol | FOXO1 |
Name | forkhead box O1 |
Aliases | FKH1; FKHR; FOXO1A; forkhead homolog in rhabdomyosarcoma; FKHRA; forkhead box protein O1A; forkhead, Drosoph ...... |
Chromosomal Location | 13q14.1 |
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
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Statistical results of FOXO1 in screening data sets for detecting immune reponses.
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Summary | |
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Symbol | FOXO1 |
Name | forkhead box O1 |
Aliases | FKH1; FKHR; FOXO1A; forkhead homolog in rhabdomyosarcoma; FKHRA; forkhead box protein O1A; forkhead, Drosoph ...... |
Chromosomal Location | 13q14.1 |
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 |
Points in the above scatter plot represent the expression difference of FOXO1 in various data sets.
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Points in the above scatter plot represent the mutation difference of FOXO1 in various data sets.
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Summary | |
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Symbol | FOXO1 |
Name | forkhead box O1 |
Aliases | FKH1; FKHR; FOXO1A; forkhead homolog in rhabdomyosarcoma; FKHRA; forkhead box protein O1A; forkhead, Drosoph ...... |
Chromosomal Location | 13q14.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FOXO1. 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. |
Summary | |
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Symbol | FOXO1 |
Name | forkhead box O1 |
Aliases | FKH1; FKHR; FOXO1A; forkhead homolog in rhabdomyosarcoma; FKHRA; forkhead box protein O1A; forkhead, Drosoph ...... |
Chromosomal Location | 13q14.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FOXO1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FOXO1. > Immunoinhibitor > Immunostimulator > MHC molecule |
Summary | |
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Symbol | FOXO1 |
Name | forkhead box O1 |
Aliases | FKH1; FKHR; FOXO1A; forkhead homolog in rhabdomyosarcoma; FKHRA; forkhead box protein O1A; forkhead, Drosoph ...... |
Chromosomal Location | 13q14.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FOXO1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor |
Summary | |
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Symbol | FOXO1 |
Name | forkhead box O1 |
Aliases | FKH1; FKHR; FOXO1A; forkhead homolog in rhabdomyosarcoma; FKHRA; forkhead box protein O1A; forkhead, Drosoph ...... |
Chromosomal Location | 13q14.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Distribution of FOXO1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype |
Summary | |
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Symbol | FOXO1 |
Name | forkhead box O1 |
Aliases | FKH1; FKHR; FOXO1A; forkhead homolog in rhabdomyosarcoma; FKHRA; forkhead box protein O1A; forkhead, Drosoph ...... |
Chromosomal Location | 13q14.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content |
Associations between FOXO1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade |
Summary | |
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Symbol | FOXO1 |
Name | forkhead box O1 |
Aliases | FKH1; FKHR; FOXO1A; forkhead homolog in rhabdomyosarcoma; FKHRA; forkhead box protein O1A; forkhead, Drosoph ...... |
Chromosomal Location | 13q14.1 |
External Links | HGNC, NCBI, Ensembl, Uniprot, GeneCards |
Content | Drugs targeting FOXO1 collected from DrugBank database. |
There is no record. |