Home
GeneCards Guide
Suite
- MalaCards
- GeneALaCart
- GeneDecks
- GeneIP
- GeneLoc
Terms and Conditions
- Terms of Use
- 3rd Party Notice
About Us
User Feedback
Mirror sites

Set Analyses:

Generates a file of GeneCards annotations for your list of genes

Advanced Search

Search By

Section (entire)

for

All GeneCards Within gene subset (to enable gene prioritization):
or upload a file of gene symbols

Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

FOXO1 Gene

protein-coding GIFtS: 62
GCID: GC13M041129

forkhead box O1

(Previous name: forkhead homolog in rhabdomyosarcoma )
(Previous symbols: FKHR, FOXO1A)

Explore 62 diseases affiliated with
FOXO1 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Forkhead Box O1¹ ²		Forkhead Homolog In Rhabdomyosarcoma¹
FKHR¹ ² ³ ⁵		Forkhead Box Protein O1²
FOXO1A¹ ² ³ ⁵		Forkhead, Drosophila, Homolog Of, In Rhabdomyosarcoma²
FKH1¹ ²		Forkhead In Rhabdomyosarcoma³
Forkhead Box Protein O1A² ³

External Ids:	HGNC: 3819¹	Entrez Gene: 2308²	Ensembl: ENSG00000150907⁷	OMIM: 136533⁵	UniProtKB: Q12778³

Export aliases for FOXO1 gene to outside databases

Previous GC identifers: GC13M040028 GC13M021931

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for FOXO1:

This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead

domain. The specific function of this gene has not yet been determined; however, it may play a role in myogenic growth

and differentiation. Translocation of this gene with PAX3 has been associated with alveolar rhabdomyosarcoma.

(provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: FOXO1_HUMAN, Q12778

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 syngernistically 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 to activate the expression of genes such as IGFBP1, G6PC and

PPCK1. Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and SKT4/MST1. Promotes neural cell

death. Mediates insulin action on adipose. 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

Gene Wiki entry for FOXO1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000013.10 NC_018924.1 NT_024524.14

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the FOXO1 gene promoter:
COUP-TF1 COUP-TF AP-1 COUP HNF-4alpha1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): FOXO1 promoter sequence

Search SABiosciences Chromatin IP Primers for FOXO1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat FOXO1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 13q14.1 Ensembl cytogenetic band: 13q14.11 HGNC cytogenetic band: 13q14.1

FOXO1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
FOXO1 gene location

GeneLoc information about chromosome 13 GeneLoc Exon Structure

GeneLoc location for GC13M041129: view genomic region (about GC identifiers)

Start:	41,129,801 bp from pter	End:	41,240,734 bp from pter
Size:	110,934 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: FOXO1_HUMAN, Q12778 (See protein sequence)

Recommended Name: Forkhead box protein O1

Size: 655 amino acids; 69662 Da

Subunit: Interacts with LRPPRC. Interacts with RUNX2; the interaction inhibits RUNX2 transcriptional activity and

mediates the IGF1/insulin-dependent BGLAP expression in osteoblasts Interacts with PPP2R1A; the interaction regulates

the dephosphorylation of FOXO1 at Thr-24 and Ser-256 leading to its nuclear import (By similarity). Interacts with

NLK. Interacts with SIRT1; the interaction results in the deacetylation of FOXO1 leading to activation of

FOXO1-mediated transcription of genes involved in DNA repair and stress resistance. Binds to CDK1. Interacts with the

14-3-3 proteins, YWHAG and YWHAZ; the interactions require insulin-stimulated phosphorylation on Thr-24, promote

nuclear exit and loss of transcriptional activity. Interacts with SKP2; the interaction ubiquitinates FOXO1 leading to

its proteosomal degradation. The interaction requires the presence of KRIT1. Interacts (via the C-terminal half) with

ATF4 (via its DNA-binding domain); the interaction occurs in osteoblasts, regulates glucose homeostasis via

suppression of beta-cell proliferation and subsequent decrease in insulin production. Interacts with PRMT1; the

interaction methylates FOXO1, prevents PKB/AKT1 phosphorylation and retains FOXO1 in the nucleus. Interacts with EP300

and CREBBP; the interactions acetylate FOXO1

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

3 PDB 3D structures from and Proteopedia for FOXO1:

3CO6 (3D)

3CO7 (3D)

3COA (3D)

Secondary accessions: O43523 Q5VYC7 Q6NSK6

Explore the universe of human proteins at neXtProt for FOXO1: NX_Q12778

Post-translational modifications:

Phosphorylation by NLK promotes nuclear export and inhibits the transcriptional activity. In response to growth

factors, phosphorylation on Thr-24, Ser-256 and Ser-322 by PKB/AKT1 promotes nuclear export and inactivation of

transactivational activity. Phosphorylation on Thr-24 is required for binding 14-3-3 proteins. Phosphorylation of

Ser-256 decreases DNA-binding activity and promotes the phosphorylation of Thr-24 and Ser-319, permitting

phosphorylation of Ser-322 and Ser-325, probably by CDK1, leading to nuclear exclusion and loss of function. Stress

signals, such as response to oxygen or nitric oxide, attenuate the PKB/AKT1-mediated phosphorylation leading to

nuclear retention. Phosphorylation of Ser-329 is independent of IGF1 and leads to reduced function. Dephosphorylated

on Thr-24 and Ser-256 by PP2A in beta-cells under oxidative stress leading to nuclear retention (By similarity).

Phosphorylation of Ser-249 by CDK1 disrupts binding of 14-3-3 proteins leading to nuclear accumulation and has no

effect on DNA-binding nor transcriptional activity. Phosphorylation by STK4/MST1 on Ser-212, upon oxidative stress,

inhibits binding to 14-3-3 proteins and nuclear export¹

Ubiquitinated by SRT2. Ubiquitination leads to proteasomal degradation¹

Methylation inhibits AKT1-mediated phosphorylation at Ser-256 and is increased by oxidative stress (By similarity)¹

Once in the nucleus, acetylated by CREBBP/EP300. Acetylation diminishes the interaction with target DNA and attenuates

the transcriptional activity. It increases the phosphorylation at Ser-256. Deacetylation by SIRT1 results in

reactivation of the transcriptional activity. Oxidative stress by hydrogen peroxide treatment appears to promote

deacetylation and uncoupling of insulin-induced phosphorylation. By contrast, resveratrol acts independently of

acetylation¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_Q12778

FOXO1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_002006.2

ENSEMBL proteins:

ENSP00000368880

Reactome Protein details: Q12778
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant FOXO1 Protein
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	OriGene Purified Protein: FOXO1 OriGene Protein Over-expression Lysate: FOXO1 OriGene Custom Protein Services for FOXO1
	GenScript Custom Purified and Recombinant Proteins Services for FOXO1
	Novus Biologicals FOXO1 Proteins Novus Biologicals FOXO1 Lysate
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for FOXO1

Gene Ontology (GO): 5/7 cellular component terms (GO ID links to tree view) (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IDA	--
GO:0005654	nucleoplasm	TAS	--
GO:0005667	transcription factor complex	IBA	--
GO:0005737	cytoplasm	IDA	11237865
GO:0005739	mitochondrion	ISS	--

FOXO1 for ontologies About GeneDecksing

FOXO1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of FOXO1
	R&D Systems Antibodies for FOXO1 (FoxO1/FKHR)
	Cell Signaling Technology (CST) Antibodies for FOXO1 (FOXO1A)
	OriGene Antibodies (see all 4): FOXO1 OriGene Custom Antibody Services for FOXO1
	GenScript Superior Antibodies for FOXO1
	Novus Biologicals FOXO1 Antibodies
	Abcam antibodies for FOXO1
	Uscn Antibodies for FOXO1
	ThermoFisher Antibody for FOXO1

Assay Products for FOXO1:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for FOXO1
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for FOXO1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

FOXO1 for domains About GeneDecksing

3 InterPro domains/families:

IPR011991 WHTH_trsnscrt_rep_DNA-bd_dom

IPR018122 TF_fork_head_CS

IPR001766 TF_fork_head

Graphical View of Domain Structure for InterPro Entry Q12778

ProtoNet protein and cluster: Q12778

UniProtKB/Swiss-Prot: FOXO1_HUMAN, Q12778

Similarity: Contains 1 fork-head DNA-binding domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: