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Entry version 175 (23 Feb 2022)
Sequence version 3 (25 Jan 2012)
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Protein

Forkhead box protein O

Gene

daf-16

Organism
Caenorhabditis elegans
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

Forkhead-type transcription factor (PubMed:9360933).

Binds to the promoters of genes that contain the daf-16/FOXO binding element (DBE), TTGTTTAC, in their regulatory region (PubMed:10880363, PubMed:23770237, PubMed:26675724).

Functions in the Insulin/IGF-1-like signaling (IIS) mediated pathway which affects lipogenesis, lifespan, starvation survival, heat shock and oxidative stress responses, sleep, associative memory, and dauer formation (PubMed:9360933, PubMed:8247153, PubMed:11747821, PubMed:11747825, PubMed:11381260, PubMed:14622602, PubMed:12750521, PubMed:17900900, PubMed:18358814, PubMed:18762027, PubMed:18832074, PubMed:19103192, PubMed:21531333, PubMed:22081913, PubMed:29523076, PubMed:26675724).

Longevity signaling predominantly arises from expression in the intestine (PubMed:14622602).

Transcriptional activity of daf-16/FOXO is negatively regulated by interaction with host cell factor homolog hcf-1; and by cytoplasmic sequestration by association with ftt-2 (PubMed:11381260, PubMed:21531333, PubMed:18828672).

Inhibition is required for the carbon dioxide (CO2) avoidance response (PubMed:18524954).

Upon loss of inhibition, daf-16 translocates to the nucleus to regulate genes that result in delayed reproduction and growth while increasing stress resistance starvation tolerance and longevity (PubMed:11747825, PubMed:21531333).

Association with arginine methyltransferase prmt-1 prevents phosphorylation and allows for translocation to the nucleus and the subsequent transcription of longevity-related genes (PubMed:21531333).

Modulation of its activity by cGMP levels in sensory neurons regulates lifespan (PubMed:19489741).

Has a protective role against muscle dystrophy (PubMed:18397876).

Involved in mediating protection against aberrant protein aggregation proteotoxicity (PubMed:16902091).

Influences transcription of genes that code for proteins involved in immunity as part of a general stress response (PubMed:17096597, PubMed:18245330).

Targets genes that inhibit and stimulate tumor growth (PubMed:17934462).

Targets kinases, phosphatases and transcription factors that are primarily involved in signaling and gene regulation (PubMed:24516399).

Thought to regulate ins-7 in FOXO-to-FOXO signaling, which coordinates daf-16 expression (PubMed:18025456).

Activity is positively regulated by shc-1-mediated inhibition of daf-2 and activation of JNK pathway (PubMed:18832074).

Functions by indirect interaction with jnk-1 of the mitogen-activated protein kinase (MAPK) pathway (PubMed:17894411).

Involved in increased proteasome activity by activating expression of rpn-6.1 in response to proteotoxic stress, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity (PubMed:22922647).

Also regulates proteasome activity in the intestine by preventing expression of deubiquitinase ubh-4 (PubMed:23770237).

Represses transcription of natc-1 (PubMed:25330323).

Involved in regulation of srh-234 expression (PubMed:25357003).

Binds to the promoter of the AMPK-gamma regulatory subunit, aakg-4, and activates its transcription (PubMed:24516399).

Also activates transcription of AMPK-gamma regulatory subunit, aakg-1 (PubMed:24516399).

Maintains endoplasmic reticulum (ER) function by inducing protein degradation and elimination to remove misfolded secretory proteins from the ER independently of the ire-1/xbp-1 unfolded protein response pathway (PubMed:25448701).

Regulates epidermal innate immunity to nematophagous fungal infection and physical wounding which trigger bli-3 induced ROS release, leading to daf-16 activation independently of daf-2 signaling (PubMed:24146615).

May negatively regulate resistance to stress caused by oxidized cholesterol adducts by preventing the activation of daf-9 and nuclear hormone receptor daf-12, two members of the steroid signaling pathway (PubMed:24957743).

Promotes apoptosis during embryonic development (PubMed:25383666).

Probably through the regulation of the autophagy genes atg-18 and atg-16.2, plays a role in regulating stem cell number in the germline during larval development (PubMed:28285998).

Plays a role in learning and memory; including associative memory, and aversive gustatory associated learning known as salt avoidance learning (PubMed:26675724, PubMed:30779740).

Plays a role in regulating gene transcription in response to white light exposure (PubMed:29500338).

Binds to the promoter of dex-1 to positively regulate its expression in seam cells during the dauer phase (PubMed:30409788).

37 Publications

Functions in the Insulin/IGF-1-like signaling (IIS) mediated pathway (PubMed:24834345).

May play a role in lifespan modulation, but less significant than that played by isoforms d and f (PubMed:24834345).

1 Publication

Functions in the Insulin/IGF-1-like signaling (IIS) mediated pathway (PubMed:24834345).

Transcript level in the early adult may play a role in lifespan modulation, but effect is more significant than that played by isoform a (PubMed:24834345).

1 Publication

Functions in the Insulin/IGF-1-like signaling (IIS) mediated pathway (PubMed:24834345).

Transcript level in the early adult may play a role in lifespan modulation, but effect is more significant than that played by isoform a (PubMed:24834345).

1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">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 bindingi175 – 268Fork-headPROSITE-ProRule annotationAdd BLAST94

<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 functionDevelopmental protein, DNA-binding, Repressor
Biological processGrowth regulation, Immunity, Innate immunity, Stress response, Transcription, Transcription regulation

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-CEL-1181150, Signaling by NODAL
R-CEL-198693, AKT phosphorylates targets in the nucleus
R-CEL-211163, AKT-mediated inactivation of FOXO1A
R-CEL-5687128, MAPK6/MAPK4 signaling
R-CEL-5689880, Ub-specific processing proteases
R-CEL-9607240, FLT3 Signaling
R-CEL-9614399, Regulation of localization of FOXO transcription factors
R-CEL-9615017, FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-CEL-9617629, Regulation of FOXO transcriptional activity by acetylation
R-CEL-9617828, FOXO-mediated transcription of cell cycle genes
R-CEL-9634638, Estrogen-dependent nuclear events downstream of ESR-membrane signaling

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

More...
SignaLinki
O16850

<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%5Fand%5Ftaxonomy%5Fsection">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 OCurated
Short name:
FOXO1 Publication
Alternative name(s):
Abnormal dauer formation protein 16Imported
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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:daf-16Imported
ORF Names:R13H8.1Imported
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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>OrganismiCaenorhabditis elegans
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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 identifieri6239 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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 lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditinaRhabditomorphaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">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
  • UP000001940 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">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 I

Organism-specific databases

WormBase

More...
WormBasei
R13H8.1a ; CE28771 ; WBGene00000912 ; daf-16
R13H8.1b ; CE28772 ; WBGene00000912 ; daf-16
R13H8.1c ; CE28773 ; WBGene00000912 ; daf-16
R13H8.1d ; CE38722 ; WBGene00000912 ; daf-16
R13H8.1e ; CE33160 ; WBGene00000912 ; daf-16
R13H8.1f ; CE44821 ; WBGene00000912 ; daf-16
R13H8.1g ; CE44935 ; WBGene00000912 ; daf-16
R13H8.1h ; CE45185 ; WBGene00000912 ; daf-16

<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

Keywords - Cellular componenti

Cytoplasm, 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 describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

Dauer defective phenotype in larvae and a reduced stress phenotype in adults (PubMed:9360933). Increased carbonyl accumulation and increased sensitivity to starvation (PubMed:18025456). Increased expression of the srh-234 chemoreceptor during starvation (PubMed:25357003). Increased sensitivity to physical injury and more susceptible to death by nematophagous fungal infection (PubMed:24146615). Increased lifespan (PubMed:23805378). Causes a delay in apoptosis during embryonic development (PubMed:25383666). Defective gustatory associative learning in response to salt cues (PubMed:30779740). RNAi-mediated knock-down reduces expression of daf-16 target genes and genes up-regulated in response to nematophagous fungal infection such as sod-3 (PubMed:24146615). RNAi-mediated knockdown causes reduced ability of dietary restriction to extend lifespan (PubMed:17900900). Simultaneous RNAi-mediated knockdown of metalloproteinase zmp-2 restores normal survival upon heat stress and prevents increased susceptibility to heat stress in a daf-9 or daf-12 mutant background (PubMed:24957743). RNAi-mediated knockdown in a daf-2 (e1370) mutant background restores expression of deubiquitinase ubh-4 in the intestine (PubMed:23770237). RNAi-mediated knockdown suppresses the decreased number of mitotic nuclei in the germline of developing larvae in an atg-18 (gk378) or atg-16.2 (ok3224) mutant background. Suppresses associative memory, axon regeneration and fkh-9 transcript levels, in a daf-2 mutant background.11 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'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>Mutagenesisi266R → K: Decreases methylation by prmt-1; when associated with K-268 and K-270. 1 Publication1
Mutagenesisi268R → K: Decreases methylation by prmt-1; when associated with K-266 and K-270. Prevents phosphorylation by akt 1 and/or 2; when associated with K-270. 1 Publication1
Mutagenesisi270R → K: Decreases methylation by prmt-1; when associated with K-266 and K-268. Prevents phosphorylation by akt 1 and/or 2; when associated with K-268. 1 Publication1
Mutagenesisi271S → A: Prevents phosphorylation and results in strong nuclear localization. Reduces phosphorylation; when associated with A-273. 2 Publications1
Mutagenesisi273T → A: Prevents phosphorylation and results in strong nuclear localization. 1 Publication1
Mutagenesisi273T → A: Reduces phosphorylation in normal and starved conditions. Reduces phosphorylation; when associated with A-271. 1 Publication1
Mutagenesisi319S → A: Prevents phosphorylation and results in cytoplasmic localization in unc-43 n498 gain-of-function or tax-6 mutant backgrounds. 1 Publication1
Mutagenesisi319S → D: Phosphomimetic mutant which causes constitutive nuclear localization. 1 Publication1
Mutagenesisi345S → A: Prevents phosphorylation and results in strong nuclear localization. 1 Publication1
Mutagenesisi373 – 541Missing in m27; defective dauer phase entry, but animals are capable of entering a partial dauer state with some dauer morphological characteristics. Reduces dex-1 expression in seam cells during the dauer phase. 1 PublicationAdd BLAST169

<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 or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00004148861 – 541Forkhead box protein OCuratedAdd BLAST541

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 residuei273Phosphothreonine1 Publication1
Modified residuei319Phosphoserine; by CaMK21 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">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

Phosphorylated by akt-1 and/or akt-2 (PubMed:18358814, PubMed:21531333). Phosphorylated by sgk-1 (PubMed:18358814). Phosphorylated by unc-43 (PubMed:23805378). Phosphorylated by jnk-1 (PubMed:15767565). Dephosphorylated by tax-6 in vitro (PubMed:23805378).4 Publications
Ubiquitinated. Ubiquitination by rle-1 leads to proteasome-mediated degradation.1 Publication
Methylation by prmt-1 prevents phosphorylation and promotes translocation to the nucleus to allow for daf-16-dependent transcription.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

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

More...
PaxDbi
O16850

PeptideAtlas

More...
PeptideAtlasi
O16850

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
O16850

<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

Isoform b and isoform c are expressed in ectoderm, muscles, intestine and neurons (PubMed:9353126, PubMed:11747825, PubMed:14622602, PubMed:17894411). Isoform b is also expressed in the pharynx (PubMed:11747821). The intestine appears to be the primary site of longevity function (PubMed:14622602).5 Publications

<p>This subsection of the 'Expression' section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified 'at the protein level'.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

Expressed in embryos, larvae, dauer larvae and adults.1 Publication
Expression throughout the body increases slightly with age.1 Publication
Expression increases substantially with age.1 Publication
Expression increases substantially with age.1 Publication

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Induced by quinic acid.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
WBGene00000912, Expressed in adult organism and 6 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
O16850, baseline and differential

<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%5Fsection">'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%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with rle-1 (PubMed:17276341).

Interacts with unc-43 and tax-6 (PubMed:23805378).

Interacts with jnk-1 (PubMed:15767565).

Interacts with ftt-2 (PubMed:16777605, PubMed:21531333).

Interacts with prmt-1 (PubMed:21531333).

Interacts with hcf-1.

5 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">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="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
38392, 70 interactors

ComplexPortal: manually curated resource of macromolecular complexes

More...
ComplexPortali
CPX-3882, daf-16-ftt-2 complex
CPX-3883, daf-16-sir-2.1 complex
CPX-3884, daf-16-par-5 complex

Database of interacting proteins

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DIPi
DIP-25581N

Protein interaction database and analysis system

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IntActi
O16850, 23 interactors

STRING: functional protein association networks

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STRINGi
6239.R13H8.1h

<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

3D structure databases

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

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SMRi
O16850

Database of comparative protein structure models

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ModBasei
Search...

<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>Regioni118 – 168DisorderedSequence analysisAdd BLAST51
Regioni252 – 291DisorderedSequence analysisAdd BLAST40

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular type of amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi118 – 158Polar residuesSequence analysisAdd BLAST41

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG2294, Eukaryota

Ensembl GeneTree

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GeneTreei
ENSGT00940000170843

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
O16850

Identification of Orthologs from Complete Genome Data

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OMAi
PCGANSA

Database of Orthologous Groups

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OrthoDBi
1160384at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O16850

Family and domain databases

Conserved Domains Database

More...
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
IPR030456, TF_fork_head_CS_2
IPR036388, WH-like_DNA-bd_sf
IPR036390, WH_DNA-bd_sf

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF00250, Forkhead, 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%5Flength">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 (8+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">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 8 <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

This entry has 8 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform hImported (identifier: O16850-8) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><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
MQLEQKSSLH CSKCRNFLQK FSQDMQAWNC RELDSPLPSD ITLHNLEPAR
60 70 80 90 100
PDSGMSFSTD FDDDFFNLDL HQQERSASFG GVTQYSQQFL REKCSFSPYF
110 120 130 140 150
HTSLETVDSG RTSLYGSNEQ CGQLGGASSN GSTAMLHTPD GSNSHQTSFP
160 170 180 190 200
SDFRMSESPD DTVSGKKTTT RRNAWGNMSY AELITTAIMA SPEKRLTLAQ
210 220 230 240 250
VYEWMVQNVP YFRDKGDSNS SAGWKNSIRH NLSLHSRFMR IQNEGAGKSS
260 270 280 290 300
WWVINPDAKP GRNPRRTRER SNTIETTTKA QLEKSRRGAK KRIKERALMG
310 320 330 340 350
SLHSTLNGNS IAGSIQTISH DLYDDDSMQG AFDNVPSSFR PRTQSNLSIP
360 370 380 390 400
GSSSRVSPAI GSDIYDDLEF PSWVGESVPA IPSDIVDRTD QMRIDATTHI
410 420 430 440 450
GGVQIKQESK PIKTEPIAPP PSYHELNSVR GSCAQNPLLR NPIVPSTNFK
460 470 480 490 500
PMPLPGAYGN YQNGGITPIN WLSTSNSSPL PGIQSCGIVA AQHTVASSSA
510 520 530 540
LPIDLENLTL PDQPLMDTMD VDALIRHELS QAGGQHIHFD L
Length:541
Mass (Da):59,732
Last modified:January 25, 2012 - v3
<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:i8A36A86311A32CBB
GO
Isoform aImported (identifier: O16850-2) [UniParc]FASTAAdd to basket
Also known as: b1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-221: MQLEQKSSLH...FRDKGDSNSS → MNDSIDDDFP...FGERSSPEEA

Show »
Length:530
Mass (Da):57,899
Checksum:i8665FBDB428039D6
GO
Isoform bImported (identifier: O16850-4) [UniParc]FASTAAdd to basket
Also known as: a21 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-113: MQLEQKSSLH...LETVDSGRTS → MMEMLVDQGT...HEQIPEEDAD
     152-154: DFR → E

Show »
Length:508
Mass (Da):55,578
Checksum:i2C0CF97657CD6350
GO
Isoform cImported (identifier: O16850-3) [UniParc]FASTAAdd to basket
Also known as: a11 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     1-113: MQLEQKSSLH...LETVDSGRTS → MMEMLVDQGT...HEQIPEEDAD

Show »
Length:510
Mass (Da):55,867
Checksum:i52574F3F979B3583
GO
Isoform dImported (identifier: O16850-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-54: Missing.

Show »
Length:487
Mass (Da):53,518
Checksum:i6998CD8BF98A5747
GO
Isoform eImported (identifier: O16850-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-238: Missing.

Show »
Length:303
Mass (Da):32,933
Checksum:iDD1DEB2F8E1BCCAD
GO
Isoform fImported (identifier: O16850-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: Missing.

Show »
Length:517
Mass (Da):56,864
Checksum:i884488D4F43DB8D5
GO
Isoform gImported (identifier: O16850-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-217: Missing.
     218-225: SNSSAGWK → MREMSTKN

Show »
Length:324
Mass (Da):35,474
Checksum:iB1E79F5EB916A3C3
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0K3AR63A0A0K3AR63_CAEEL
Fork-head domain-containing protein
daf-16 CELE_R13H8.1, R13H8.1
485Annotation score:

Annotation score:1 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>
A0A0K3AR95A0A0K3AR95_CAEEL
Fork-head domain-containing protein
daf-16 CELE_R13H8.1, R13H8.1
407Annotation score:

Annotation score:1 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>
A0A0K3ATP5A0A0K3ATP5_CAEEL
Fork-head domain-containing protein
daf-16 CELE_R13H8.1, R13H8.1
405Annotation score:

Annotation score:1 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>
A0A0K3AWG6A0A0K3AWG6_CAEEL
Fork-head domain-containing protein
daf-16 CELE_R13H8.1, R13H8.1
515Annotation score:

Annotation score:1 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>

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_0531051 – 238Missing in isoform e. CuratedAdd BLAST238
Alternative sequenceiVSP_0531061 – 221MQLEQ…DSNSS → MNDSIDDDFPPEPRGRCYTW PMQQYIYQESSATIPHHHLN QHNNPYHPMHPHHQLPHMQQ LPQPLLNLNMTTLTSSGSSV ASSIGGGAQCSPCASGSSTA ATNSSQQQQTVGQMLAASVP CSSSGMTLGMSLNLSQGGGP MPAKKKRCRKKPTDQLAQKK PNPWGEESYSDIIAKALESA PDGRLKLNEIYQWFSDNIPY FGERSSPEEA in isoform a. 1 PublicationAdd BLAST221
Alternative sequenceiVSP_0421471 – 217Missing in isoform g. CuratedAdd BLAST217
Alternative sequenceiVSP_0531071 – 113MQLEQ…SGRTS → MMEMLVDQGTDASSSASTST SSVSRFGADTFMNTPDDVMM NDDMEPIPRDRCNTWPMRRP QLEPPLNSSPIIHEQIPEED AD in isoform b and isoform c. 2 PublicationsAdd BLAST113
Alternative sequenceiVSP_0531081 – 54Missing in isoform d. CuratedAdd BLAST54
Alternative sequenceiVSP_0421481 – 24Missing in isoform f. CuratedAdd BLAST24
Alternative sequenceiVSP_053109152 – 154DFR → E in isoform b. 1 Publication3
Alternative sequenceiVSP_042149218 – 225SNSSAGWK → MREMSTKN in isoform g. Curated8

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
AF020342 mRNA Translation: AAB84390.1
AF020343 mRNA Translation: AAB84391.1
AF020344 mRNA Translation: AAB84392.1
AF032112 mRNA Translation: AAC47803.1
BX284601 Genomic DNA Translation: CCD71850.1
BX284601 Genomic DNA Translation: CCD71851.1
BX284601 Genomic DNA Translation: CCD71852.1
BX284601 Genomic DNA Translation: CCD71853.1
BX284601 Genomic DNA Translation: CCD71854.1
BX284601, FO080113 Genomic DNA Translation: CCD71855.1
BX284601, FO080113 Genomic DNA Translation: CCD71856.1
BX284601, FO080113 Genomic DNA Translation: CCD71857.1

Protein sequence database of the Protein Information Resource

More...
PIRi
T42234
T42255

NCBI Reference Sequences

More...
RefSeqi
NP_001021593.1, NM_001026422.4 [O16850-2]
NP_001021594.1, NM_001026423.4
NP_001021595.1, NM_001026424.4
NP_001021596.1, NM_001026425.3 [O16850-5]
NP_001021597.1, NM_001026426.2
NP_001021598.2, NM_001026427.4 [O16850-1]
NP_001251490.1, NM_001264561.1
NP_001251492.1, NM_001264563.1

Genome annotation databases

Ensembl metazoan genome annotation project

More...
EnsemblMetazoai
R13H8.1a.1; R13H8.1a.1; WBGene00000912 [O16850-2]
R13H8.1b.1; R13H8.1b.1; WBGene00000912 [O16850-4]
R13H8.1b.2; R13H8.1b.2; WBGene00000912 [O16850-4]
R13H8.1c.1; R13H8.1c.1; WBGene00000912 [O16850-3]
R13H8.1c.2; R13H8.1c.2; WBGene00000912 [O16850-3]
R13H8.1d.1; R13H8.1d.1; WBGene00000912 [O16850-5]
R13H8.1e.1; R13H8.1e.1; WBGene00000912 [O16850-6]
R13H8.1f.1; R13H8.1f.1; WBGene00000912 [O16850-1]
R13H8.1g.1; R13H8.1g.1; WBGene00000912 [O16850-7]
R13H8.1h.1; R13H8.1h.1; WBGene00000912 [O16850-8]

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
172981

UCSC genome browser

More...
UCSCi
R13H8.1c, c. elegans

Keywords - Coding sequence diversityi

Alternative splicing

<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

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF020342 mRNA Translation: AAB84390.1
AF020343 mRNA Translation: AAB84391.1
AF020344 mRNA Translation: AAB84392.1
AF032112 mRNA Translation: AAC47803.1
BX284601 Genomic DNA Translation: CCD71850.1
BX284601 Genomic DNA Translation: CCD71851.1
BX284601 Genomic DNA Translation: CCD71852.1
BX284601 Genomic DNA Translation: CCD71853.1
BX284601 Genomic DNA Translation: CCD71854.1
BX284601, FO080113 Genomic DNA Translation: CCD71855.1
BX284601, FO080113 Genomic DNA Translation: CCD71856.1
BX284601, FO080113 Genomic DNA Translation: CCD71857.1
PIRiT42234
T42255
RefSeqiNP_001021593.1, NM_001026422.4 [O16850-2]
NP_001021594.1, NM_001026423.4
NP_001021595.1, NM_001026424.4
NP_001021596.1, NM_001026425.3 [O16850-5]
NP_001021597.1, NM_001026426.2
NP_001021598.2, NM_001026427.4 [O16850-1]
NP_001251490.1, NM_001264561.1
NP_001251492.1, NM_001264563.1

3D structure databases

SMRiO16850
ModBaseiSearch...

Protein-protein interaction databases

BioGRIDi38392, 70 interactors
ComplexPortaliCPX-3882, daf-16-ftt-2 complex
CPX-3883, daf-16-sir-2.1 complex
CPX-3884, daf-16-par-5 complex
DIPiDIP-25581N
IntActiO16850, 23 interactors
STRINGi6239.R13H8.1h

PTM databases

iPTMnetiO16850

Proteomic databases

PaxDbiO16850
PeptideAtlasiO16850

Genome annotation databases

EnsemblMetazoaiR13H8.1a.1; R13H8.1a.1; WBGene00000912 [O16850-2]
R13H8.1b.1; R13H8.1b.1; WBGene00000912 [O16850-4]
R13H8.1b.2; R13H8.1b.2; WBGene00000912 [O16850-4]
R13H8.1c.1; R13H8.1c.1; WBGene00000912 [O16850-3]
R13H8.1c.2; R13H8.1c.2; WBGene00000912 [O16850-3]
R13H8.1d.1; R13H8.1d.1; WBGene00000912 [O16850-5]
R13H8.1e.1; R13H8.1e.1; WBGene00000912 [O16850-6]
R13H8.1f.1; R13H8.1f.1; WBGene00000912 [O16850-1]
R13H8.1g.1; R13H8.1g.1; WBGene00000912 [O16850-7]
R13H8.1h.1; R13H8.1h.1; WBGene00000912 [O16850-8]
GeneIDi172981
UCSCiR13H8.1c, c. elegans

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
172981
WormBaseiR13H8.1a ; CE28771 ; WBGene00000912 ; daf-16
R13H8.1b ; CE28772 ; WBGene00000912 ; daf-16
R13H8.1c ; CE28773 ; WBGene00000912 ; daf-16
R13H8.1d ; CE38722 ; WBGene00000912 ; daf-16
R13H8.1e ; CE33160 ; WBGene00000912 ; daf-16
R13H8.1f ; CE44821 ; WBGene00000912 ; daf-16
R13H8.1g ; CE44935 ; WBGene00000912 ; daf-16
R13H8.1h ; CE45185 ; WBGene00000912 ; daf-16

Phylogenomic databases

eggNOGiKOG2294, Eukaryota
GeneTreeiENSGT00940000170843
InParanoidiO16850
OMAiPCGANSA
OrthoDBi1160384at2759
PhylomeDBiO16850

Enzyme and pathway databases

ReactomeiR-CEL-1181150, Signaling by NODAL
R-CEL-198693, AKT phosphorylates targets in the nucleus
R-CEL-211163, AKT-mediated inactivation of FOXO1A
R-CEL-5687128, MAPK6/MAPK4 signaling
R-CEL-5689880, Ub-specific processing proteases
R-CEL-9607240, FLT3 Signaling
R-CEL-9614399, Regulation of localization of FOXO transcription factors
R-CEL-9615017, FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes
R-CEL-9617629, Regulation of FOXO transcriptional activity by acetylation
R-CEL-9617828, FOXO-mediated transcription of cell cycle genes
R-CEL-9634638, Estrogen-dependent nuclear events downstream of ESR-membrane signaling
SignaLinkiO16850

Miscellaneous databases

Protein Ontology

More...
PROi
PR:O16850

Gene expression databases

BgeeiWBGene00000912, Expressed in adult organism and 6 other tissues
ExpressionAtlasiO16850, baseline and differential

Family and domain databases

CDDicd00059, FH, 1 hit
Gene3Di1.10.10.10, 1 hit
InterProiView protein in InterPro
IPR001766, Fork_head_dom
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
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

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 nameiFOXO_CAEEL
<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: O16850
Secondary accession number(s): F3NWW7
, F3NWX0, G4RQR7, G4S686, G4SKG3, G4SKH0, O16849, O18676, Q86S42
<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%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 16, 2009
Last sequence update: January 25, 2012
Last modified: February 23, 2022
This is version 175 of the entry and version 3 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 programCaenorhabditis annotation project

<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

Reference proteome

Documents

  1. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase
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