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Entry version 213 (16 Oct 2019)
Sequence version 1 (01 Jun 1998)
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Protein

Forkhead box protein O3

Gene

FOXO3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:10102273, PubMed:16751106, PubMed:21329882). Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins (By similarity). Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (PubMed:10102273, PubMed:16751106). 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).By similarity4 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section specifies the position and type of each DNA-binding domain present within the protein.<p><a href='/help/dna_bind' target='_top'>More...</a></p>DNA bindingi157 – 251Fork-headPROSITE-ProRule annotationAdd BLAST95

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionActivator, DNA-binding
Biological processApoptosis, Transcription, Transcription regulation

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-1181150 Signaling by NODAL
R-HSA-198693 AKT phosphorylates targets in the nucleus
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
R-HSA-8952158 RUNX3 regulates BCL2L11 (BIM) transcription
R-HSA-9614399 Regulation of localization of FOXO transcription factors
R-HSA-9614657 FOXO-mediated transcription of cell death genes
R-HSA-9615017 FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-HSA-9617629 Regulation of FOXO transcriptional activity by acetylation
R-HSA-9617828 FOXO-mediated transcription of cell cycle genes
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
O43524

SIGNOR Signaling Network Open Resource

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SIGNORi
O43524

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Forkhead box protein O3Curated
Alternative name(s):
AF6q21 protein1 Publication
Forkhead in rhabdomyosarcoma-like 11 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:FOXO3Imported
Synonyms:FKHRL11 Publication, FOXO3A1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:3821 FOXO3

Online Mendelian Inheritance in Man (OMIM)

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MIMi
602681 gene

neXtProt; the human protein knowledge platform

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neXtProti
NX_O43524

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane, Mitochondrion, Mitochondrion outer membrane, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

A chromosomal aberration involving FOXO3 is found in secondary acute leukemias. Translocation t(6;11)(q21;q23) with KMT2A/MLL1.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi2 – 148Missing : Loss of localization to the mitochondrion outer membrane and loss of translocation into the mitochondrion following metabolic stress. 1 PublicationAdd BLAST147
Mutagenesisi2 – 30Missing : Loss of translocation into the mitochondrion following metabolic stress. 1 PublicationAdd BLAST29
Mutagenesisi12S → A in normal cells, no defect in mitochondrion import following metabolic stress. In cancer cells, defective mitochondrion import following metabolic stress and abolition of ERK-mediated phosphorylation. 1 Publication1
Mutagenesisi30S → A: Abolishes phosphorylation. Loss of localization to the mitochondrion outer membrane and loss of translocation into the mitochondrion following metabolic stress. 1 Publication1
Mutagenesisi32T → A: Abolishes YWHAZ-binding; when associated with A-253. Exclusively nuclear, induces transcription and promotes apoptosis; when associated with A-253 and A-315. 1 Publication1
Mutagenesisi80 – 108Missing : Loss of translocation into the mitochondrion following metabolic stress. 1 PublicationAdd BLAST29
Mutagenesisi179T → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-399; A-413; A-555; A-588 and A-626. 1 Publication1
Mutagenesisi209S → A: Impairs nuclear translocation upon oxidative stress. 1 Publication1
Mutagenesisi242 – 271Missing : Loss of nuclear import. 1 PublicationAdd BLAST30
Mutagenesisi242K → A: Slightly decreases DNA affinity. 2 Publications1
Mutagenesisi242K → R: Reduces acetylation, increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation; when associated with R-259; R-290 and R-569. 2 Publications1
Mutagenesisi245K → A: Decreases DNA affinity. 1 Publication1
Mutagenesisi253S → A: Abolishes YWHAZ-binding; when associated with A-32. Exclusively nuclear, induces transcription and promotes apoptosis; when associated with A-32 and A-315. 1 Publication1
Mutagenesisi259K → R: Reduces acetylation, increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation; when associated with R-242; R-290 and R-569. 1 Publication1
Mutagenesisi269K → R: Methylation levels similar to wild-type; when associated with ARG-270. 1 Publication1
Mutagenesisi270K → R: Methylation levels similar to wild-type; when associated with ARG-269. 1 Publication1
Mutagenesisi271K → R: Methylation levels strongly reduced. 1 Publication1
Mutagenesisi290K → R: Reduces acetylation, increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation; when associated with R-242; R-259 and R-569. 1 Publication1
Mutagenesisi315S → A: No effect on YWHAZ-binding. Promotes nuclear translocation. Exclusively nuclear, induces transcription and promotes apoptosis; when associated with A-32 and A-253. 1 Publication1
Mutagenesisi399S → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-179; A-413; A-555; A-588 and A-626. 1 Publication1
Mutagenesisi413S → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-179; A-399; A-555; A-588 and A-626. 1 Publication1
Mutagenesisi555S → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-179; A-399; A-413; A-588 and A-626. 1 Publication1
Mutagenesisi569K → R: Reduces acetylation, increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation; when associated with R-242; R-259 and R-290. 1 Publication1
Mutagenesisi588S → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-179; A-399; A-413; A-555 and A-626. 1 Publication1
Mutagenesisi626S → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-179; A-399; A-413; A-555 and A-588. 1 Publication1
Mutagenesisi644S → A: Loss of phosphorylation by IKKB. 1 Publication1

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNET

More...
DisGeNETi
2309

Open Targets

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OpenTargetsi
ENSG00000118689

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA28239

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
O43524

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL5778

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
FOXO3

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000918741 – 673Forkhead box protein O3Add BLAST673

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei30Phosphoserine; by AMPK1 Publication1
Modified residuei32Phosphothreonine; by PKB/AKT11 Publication1
Modified residuei46N6-methyllysine1 Publication1
Modified residuei149N6-methyllysine1 Publication1
Modified residuei179Phosphothreonine; by AMPK1 Publication1
Modified residuei209Phosphoserine; by STK4/MST11 Publication1
Modified residuei215Phosphoserine; by MAPKAPK51 Publication1
Modified residuei230N6-methyllysine1 Publication1
Modified residuei242N6-acetyllysineBy similarity1
Modified residuei253Phosphoserine; by PKB/AKT1 and MAPKAPK52 Publications1
Modified residuei262N6-methyllysine1 Publication1
Modified residuei271N6-methyllysine1 Publication1
Modified residuei280PhosphoserineCombined sources1
Modified residuei284PhosphoserineCombined sources1
Modified residuei290N6-methyllysine1 Publication1
Modified residuei294PhosphoserineBy similarity1
Modified residuei299Phosphoserine; by CaMK2ACombined sources1 Publication1
Modified residuei311PhosphoserineCombined sources1
Modified residuei315Phosphoserine; by SGK12 Publications1
Modified residuei399Phosphoserine; by AMPK1 Publication1
Modified residuei413Phosphoserine; by AMPKCombined sources1 Publication1
Modified residuei419N6-methyllysine1 Publication1
Modified residuei421PhosphoserineCombined sources1
Modified residuei551Phosphoserine; by MAPKAPK5Combined sources1 Publication1
Modified residuei555Phosphoserine; by AMPK and MAPKAPK52 Publications1
Modified residuei588Phosphoserine; by AMPK1 Publication1
Modified residuei626Phosphoserine; by AMPK1 Publication1
Modified residuei644Phosphoserine; by IKKB1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

In the presence of survival factors such as IGF-1, phosphorylated on Thr-32 and Ser-253 by AKT1/PKB (PubMed:10102273). This phosphorylated form then interacts with 14-3-3 proteins and is retained in the cytoplasm (PubMed:10102273). Survival factor withdrawal induces dephosphorylation and promotes translocation to the nucleus where the dephosphorylated protein induces transcription of target genes and triggers apoptosis (PubMed:10102273). Although AKT1/PKB doesn't appear to phosphorylate Ser-315 directly, it may activate other kinases that trigger phosphorylation at this residue (PubMed:10102273, PubMed:11154281). Phosphorylated by STK4/MST1 on Ser-209 upon oxidative stress, which leads to dissociation from YWHAB/14-3-3-beta and nuclear translocation (PubMed:16751106). Phosphorylated by PIM1 (PubMed:18593906). Phosphorylation by AMPK leads to the activation of transcriptional activity without affecting subcellular localization (PubMed:17711846). In response to metabolic stress, phosphorylated by AMPK on Ser-30 which mediates FOXO3 mitochondrial translocation (PubMed:29445193). Phosphorylation by MAPKAPK5 promotes nuclear localization and DNA-binding, leading to 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). Phosphorylated by CHUK/IKKA and IKBKB/IKKB (PubMed:15084260). TNF-induced inactivation of FOXO3 requires its phosphorylation at Ser-644 by IKBKB/IKKB which promotes FOXO3 retention in the cytoplasm, polyubiquitination and ubiquitin-mediated proteasomal degradation (PubMed:15084260). May be dephosphorylated by calcineurin A on Ser-299 which abolishes FOXO3 transcriptional activity (By similarity). In cancer cells, ERK mediated-phosphorylation of Ser-12 is required for mitochondrial translocation of FOXO3 in response to metabolic stress or chemotherapeutic agents (PubMed:29445193).By similarity8 Publications
Deacetylation by SIRT1 or SIRT2 stimulates interaction of FOXO3 with SKP2 and facilitates SCF(SKP2)-mediated FOXO3 ubiquitination and proteasomal degradation (PubMed:21841822). Deacetylation by SIRT2 stimulates FOXO3-mediated transcriptional activity in response to oxidative stress (By similarity). Deacetylated by SIRT3 (PubMed:23283301). Deacetylation by SIRT3 stimulates FOXO3-mediated mtDNA transcriptional activity in response to metabolic stress (PubMed:23283301).By similarity2 Publications
Heavily methylated by SET9 which decreases stability, while moderately increasing transcriptional activity. The main methylation site is Lys-271. Methylation doesn't affect subcellular location.1 Publication
Polyubiquitinated. Ubiquitinated by a SCF complex containing SKP2, leading to proteasomal degradation.1 Publication
The N-terminus is cleaved following import into the mitochondrion.1 Publication

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
O43524

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
O43524

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
O43524

MaxQB - The MaxQuant DataBase

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MaxQBi
O43524

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
O43524

PeptideAtlas

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PeptideAtlasi
O43524

PRoteomics IDEntifications database

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PRIDEi
O43524

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
49029 [O43524-1]
5304

PTM databases

GlyConnect protein glycosylation platform

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GlyConnecti
1253

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
O43524

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
O43524

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000118689 Expressed in 236 organ(s), highest expression level in trabecular bone tissue

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O43524 HS

Organism-specific databases

Human Protein Atlas

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HPAi
CAB004074
HPA063104

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Upon metabolic stress, forms a complex composed of FOXO3, SIRT3 and mitochondrial RNA polymerase POLRMT; the complex is recruited to mtDNA in a SIRT3-dependent manner (PubMed:23283301). Also forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT (PubMed:29445193).

Interacts with SIRT2; the interaction occurs independently of SIRT2 deacetylase activity (By similarity).

Interacts with YWHAB/14-3-3-beta and YWHAZ/14-3-3-zeta, which are required for cytosolic sequestration (PubMed:16751106). Upon oxidative stress, interacts with STK4/MST1, which disrupts interaction with YWHAB/14-3-3-beta and leads to nuclear translocation (PubMed:16751106).

Interacts with PIM1 (PubMed:18593906).

Interacts with DDIT3/CHOP (PubMed:22761832).

Interacts (deacetylated form) with SKP2 (PubMed:21841822).

Interacts with CHUK and IKBKB (PubMed:15084260, PubMed:22313691).

Interacts with CAMK2A, CAMK2B and calcineurin A (By similarity). Interacts FOXO3; this interaction represses FOXO3 transactivation (PubMed:20181828).

By similarity9 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
108598, 70 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-1123 FOXO3-MYC complex
CPX-1147 FOXO3-YWHAZ complex

CORUM comprehensive resource of mammalian protein complexes

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CORUMi
O43524

Database of interacting proteins

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DIPi
DIP-29723N

Protein interaction database and analysis system

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IntActi
O43524, 51 interactors

Molecular INTeraction database

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MINTi
O43524

STRING: functional protein association networks

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STRINGi
9606.ENSP00000385824

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
O43524

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1673
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
O43524

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

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EvolutionaryTracei
O43524

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni80 – 108Required for mitochondrial import1 PublicationAdd BLAST29
Regioni300 – 673Mediates interaction with CHUK/IKKA and IKBKB/IKKB1 PublicationAdd BLAST374

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi242 – 259Nuclear localization signal2 PublicationsAdd BLAST18

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG2294 Eukaryota
COG5025 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000159826

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000251635

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
O43524

KEGG Orthology (KO)

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KOi
K09408

Identification of Orthologs from Complete Genome Data

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OMAi
NSRRNIM

Database of Orthologous Groups

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OrthoDBi
1160384at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O43524

TreeFam database of animal gene trees

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TreeFami
TF315583

Family and domain databases

Conserved Domains Database

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CDDi
cd00059 FH, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
1.10.10.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR001766 Fork_head_dom
IPR032067 FOXO-TAD
IPR032068 FOXO_KIX-bd
IPR030456 TF_fork_head_CS_2
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf

Pfam protein domain database

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Pfami
View protein in Pfam
PF00250 Forkhead, 1 hit
PF16676 FOXO-TAD, 1 hit
PF16675 FOXO_KIX_bdg, 1 hit

Protein Motif fingerprint database; a protein domain database

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PRINTSi
PR00053 FORKHEAD

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00339 FH, 1 hit

Superfamily database of structural and functional annotation

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SUPFAMi
SSF46785 SSF46785, 1 hit

PROSITE; a protein domain and family database

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PROSITEi
View protein in PROSITE
PS00658 FORK_HEAD_2, 1 hit
PS50039 FORK_HEAD_3, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: O43524-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MAEAPASPAP LSPLEVELDP EFEPQSRPRS CTWPLQRPEL QASPAKPSGE
60 70 80 90 100
TAADSMIPEE EDDEDDEDGG GRAGSAMAIG GGGGSGTLGS GLLLEDSARV
110 120 130 140 150
LAPGGQDPGS GPATAAGGLS GGTQALLQPQ QPLPPPQPGA AGGSGQPRKC
160 170 180 190 200
SSRRNAWGNL SYADLITRAI ESSPDKRLTL SQIYEWMVRC VPYFKDKGDS
210 220 230 240 250
NSSAGWKNSI RHNLSLHSRF MRVQNEGTGK SSWWIINPDG GKSGKAPRRR
260 270 280 290 300
AVSMDNSNKY TKSRGRAAKK KAALQTAPES ADDSPSQLSK WPGSPTSRSS
310 320 330 340 350
DELDAWTDFR SRTNSNASTV SGRLSPIMAS TELDEVQDDD APLSPMLYSS
360 370 380 390 400
SASLSPSVSK PCTVELPRLT DMAGTMNLND GLTENLMDDL LDNITLPPSQ
410 420 430 440 450
PSPTGGLMQR SSSFPYTTKG SGLGSPTSSF NSTVFGPSSL NSLRQSPMQT
460 470 480 490 500
IQENKPATFS SMSHYGNQTL QDLLTSDSLS HSDVMMTQSD PLMSQASTAV
510 520 530 540 550
SAQNSRRNVM LRNDPMMSFA AQPNQGSLVN QNLLHHQHQT QGALGGSRAL
560 570 580 590 600
SNSVSNMGLS ESSSLGSAKH QQQSPVSQSM QTLSDSLSGS SLYSTSANLP
610 620 630 640 650
VMGHEKFPSD LDLDMFNGSL ECDMESIIRS ELMDADGLDF NFDSLISTQN
660 670
VVGLNVGNFT GAKQASSQSW VPG
Length:673
Mass (Da):71,277
Last modified:June 1, 1998 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iE5B4E830665A9982
GO
Isoform 2 (identifier: O43524-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-220: Missing.

Note: No experimental confirmation available.
Show »
Length:453
Mass (Da):48,406
Checksum:iE093364532E78AE1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti156 – 163AWGNLSYA → WGKPVYS in CAA04860 (PubMed:9345057).Curated8
Sequence conflicti238 – 246PDGGKSGKA → LMGEERKT in CAA04860 (PubMed:9345057).Curated9
Sequence conflicti253S → T in CAA04860 (PubMed:9345057).Curated1
Sequence conflicti271Missing in CAA04860 (PubMed:9345057).Curated1
Sequence conflicti292 – 330PGSPT…PIMAS → AWQPHVNAAVMSWMRGRTSV HAPILTPAQSVAACRPSWQV in CAA04860 (PubMed:9345057).CuratedAdd BLAST39
Sequence conflicti345 – 361PMLYS…SVSKP → AHALQHVSQPVTFSKQA in CAA04860 (PubMed:9345057).CuratedAdd BLAST17
Sequence conflicti367P → R in CAA04860 (PubMed:9345057).Curated1
Sequence conflicti371D → E in CAA04860 (PubMed:9345057).Curated1
Sequence conflicti382 – 383LT → AD in CAA04860 (PubMed:9345057).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0562251 – 220Missing in isoform 2. 1 PublicationAdd BLAST220

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AF032886 mRNA Translation: AAC39592.1
AK301304 mRNA Translation: BAG62858.1
AL096818 Genomic DNA No translation available.
AL391646 Genomic DNA No translation available.
AL365509 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW48373.1
CH471051 Genomic DNA Translation: EAW48374.1
BC020227 mRNA Translation: AAH20227.1
BC021224 mRNA Translation: AAH21224.1
BC068552 mRNA Translation: AAH68552.1
AJ001589 mRNA Translation: CAA04860.1
AJ001590 Genomic DNA Translation: CAA04861.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS5068.1 [O43524-1]

NCBI Reference Sequences

More...
RefSeqi
NP_001446.1, NM_001455.3 [O43524-1]
NP_963853.1, NM_201559.2 [O43524-1]
XP_005266925.1, XM_005266868.3 [O43524-2]
XP_011533930.1, XM_011535628.2 [O43524-2]
XP_011533931.1, XM_011535629.2 [O43524-2]
XP_016866075.1, XM_017010586.1 [O43524-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000343882; ENSP00000339527; ENSG00000118689 [O43524-1]
ENST00000406360; ENSP00000385824; ENSG00000118689 [O43524-1]
ENST00000540898; ENSP00000446316; ENSG00000118689 [O43524-2]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
2309

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:2309

UCSC genome browser

More...
UCSCi
uc003psk.3 human [O43524-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross_references_section">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF032886 mRNA Translation: AAC39592.1
AK301304 mRNA Translation: BAG62858.1
AL096818 Genomic DNA No translation available.
AL391646 Genomic DNA No translation available.
AL365509 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW48373.1
CH471051 Genomic DNA Translation: EAW48374.1
BC020227 mRNA Translation: AAH20227.1
BC021224 mRNA Translation: AAH21224.1
BC068552 mRNA Translation: AAH68552.1
AJ001589 mRNA Translation: CAA04860.1
AJ001590 Genomic DNA Translation: CAA04861.1
CCDSiCCDS5068.1 [O43524-1]
RefSeqiNP_001446.1, NM_001455.3 [O43524-1]
NP_963853.1, NM_201559.2 [O43524-1]
XP_005266925.1, XM_005266868.3 [O43524-2]
XP_011533930.1, XM_011535628.2 [O43524-2]
XP_011533931.1, XM_011535629.2 [O43524-2]
XP_016866075.1, XM_017010586.1 [O43524-2]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

More...
RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2K86NMR-A151-251[»]
2LQHNMR-B461-483[»]
2LQINMR-B461-483[»]
2UZKX-ray2.70A/C158-253[»]
6MNLNMR-A237-252[»]
SMRiO43524
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi108598, 70 interactors
ComplexPortaliCPX-1123 FOXO3-MYC complex
CPX-1147 FOXO3-YWHAZ complex
CORUMiO43524
DIPiDIP-29723N
IntActiO43524, 51 interactors
MINTiO43524
STRINGi9606.ENSP00000385824

Chemistry databases

BindingDBiO43524
ChEMBLiCHEMBL5778

PTM databases

GlyConnecti1253
iPTMnetiO43524
PhosphoSitePlusiO43524

Polymorphism and mutation databases

BioMutaiFOXO3

Proteomic databases

EPDiO43524
jPOSTiO43524
MassIVEiO43524
MaxQBiO43524
PaxDbiO43524
PeptideAtlasiO43524
PRIDEiO43524
ProteomicsDBi49029 [O43524-1]
5304

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
2309

Genome annotation databases

EnsembliENST00000343882; ENSP00000339527; ENSG00000118689 [O43524-1]
ENST00000406360; ENSP00000385824; ENSG00000118689 [O43524-1]
ENST00000540898; ENSP00000446316; ENSG00000118689 [O43524-2]
GeneIDi2309
KEGGihsa:2309
UCSCiuc003psk.3 human [O43524-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
2309
DisGeNETi2309

GeneCards: human genes, protein and diseases

More...
GeneCardsi
FOXO3
HGNCiHGNC:3821 FOXO3
HPAiCAB004074
HPA063104
MIMi602681 gene
neXtProtiNX_O43524
OpenTargetsiENSG00000118689
PharmGKBiPA28239

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG2294 Eukaryota
COG5025 LUCA
GeneTreeiENSGT00940000159826
HOGENOMiHOG000251635
InParanoidiO43524
KOiK09408
OMAiNSRRNIM
OrthoDBi1160384at2759
PhylomeDBiO43524
TreeFamiTF315583

Enzyme and pathway databases

ReactomeiR-HSA-1181150 Signaling by NODAL
R-HSA-198693 AKT phosphorylates targets in the nucleus
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-6785807 Interleukin-4 and Interleukin-13 signaling
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
R-HSA-8952158 RUNX3 regulates BCL2L11 (BIM) transcription
R-HSA-9614399 Regulation of localization of FOXO transcription factors
R-HSA-9614657 FOXO-mediated transcription of cell death genes
R-HSA-9615017 FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-HSA-9617629 Regulation of FOXO transcriptional activity by acetylation
R-HSA-9617828 FOXO-mediated transcription of cell cycle genes
R-HSA-9634638 Estrogen-dependent nuclear events downstream of ESR-membrane signaling
SignaLinkiO43524
SIGNORiO43524

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
FOXO3 human
EvolutionaryTraceiO43524

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
FOXO3

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
2309
PharosiO43524

Protein Ontology

More...
PROi
PR:O43524

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000118689 Expressed in 236 organ(s), highest expression level in trabecular bone tissue
GenevisibleiO43524 HS

Family and domain databases

CDDicd00059 FH, 1 hit
Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR001766 Fork_head_dom
IPR032067 FOXO-TAD
IPR032068 FOXO_KIX-bd
IPR030456 TF_fork_head_CS_2
IPR036388 WH-like_DNA-bd_sf
IPR036390 WH_DNA-bd_sf
PfamiView protein in Pfam
PF00250 Forkhead, 1 hit
PF16676 FOXO-TAD, 1 hit
PF16675 FOXO_KIX_bdg, 1 hit
PRINTSiPR00053 FORKHEAD
SMARTiView protein in SMART
SM00339 FH, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
PROSITEiView protein in PROSITE
PS00658 FORK_HEAD_2, 1 hit
PS50039 FORK_HEAD_3, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiFOXO3_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O43524
Secondary accession number(s): B4DVZ6
, E1P5E6, O15171, Q5T2I7, Q9BZ04
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: October 16, 2019
This is version 213 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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