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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-Experimental evidence at protein leveli

Functioni

Forkhead-type transcription factor (PubMed:9360933). Binds to the promoters of genes that contain the daf-16 binding element (DBE), TTGTTTAC, in their regulatory region (PubMed:10880363). Functions in the Insulin/IGF-1-like signaling (IIS) mediated pathway which affects lipogenesis, lifespan, starvation survival, heat shock and oxidative stress responses, 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:22081913). Longevity signaling predominantly arises from expression in the intestine (PubMed:14622602). Daf-16 transcriptional activity is negatively regulated by cytoplasmic sequestration (PubMed:11381260). 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). 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). 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).29 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi175 – 26894Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • 14-3-3 protein binding Source: WormBase
  • activating transcription factor binding Source: UniProtKB
  • beta-catenin binding Source: ParkinsonsUK-UCL
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: WormBase
  • sequence-specific DNA binding Source: WormBase
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-specific protease binding Source: WormBase

GO - Biological processi

  • aging Source: UniProtKB
  • cellular response to DNA damage stimulus Source: UniProtKB
  • cellular response to heat Source: UniProtKB
  • cellular response to oxidative stress Source: ParkinsonsUK-UCL
  • dauer larval development Source: WormBase
  • defense response to Gram-negative bacterium Source: WormBase
  • determination of adult lifespan Source: UniProtKB
  • innate immune response Source: WormBase
  • insulin receptor signaling pathway Source: UniProtKB
  • muscle tissue development Source: UniProtKB
  • negative regulation of multicellular organism growth Source: WormBase
  • negative regulation of transcription from RNA polymerase II promoter Source: WormBase
  • nematode larval development Source: UniProtKB
  • positive regulation of adaptive immune response Source: UniProtKB
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of dauer larval development Source: WormBase
  • positive regulation of defense response to bacterium Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: WormBase
  • regulation of cell cycle process Source: UniProtKB
  • regulation of dauer larval development Source: UniProtKB
  • regulation of DNA-templated transcription in response to stress Source: UniProtKB
  • regulation of lipid biosynthetic process Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • response to starvation Source: UniProtKB
  • response to UV Source: UniProtKB
  • short-term memory Source: WormBase
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

Growth regulation, Immunity, Innate immunity, Stress response, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-CEL-198693. AKT phosphorylates targets in the nucleus.
R-CEL-211163. AKT-mediated inactivation of FOXO1A.
R-CEL-5687128. MAPK6/MAPK4 signaling.
SignaLinkiO16850.

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein OCurated
Short name:
FOXO1 Publication
Alternative name(s):
Abnormal dauer formation protein 16Imported
Gene namesi
Name:daf-16Imported
ORF Names:R13H8.1Imported
OrganismiCaenorhabditis elegans
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome I

Organism-specific databases

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.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

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). 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 knock-down causes reduced ability of dietary restriction to extend lifespan (PubMed:17900900).5 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi271 – 2711S → A: Prevents phosphorylation and results in strong nuclear localization. 1 Publication
Mutagenesisi273 – 2731T → A: Prevents phosphorylation and results in strong nuclear localization. 1 Publication
Mutagenesisi345 – 3451S → A: Prevents phosphorylation and results in strong nuclear localization. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 541541Forkhead box protein OCuratedPRO_0000414886Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei319 – 3191Phosphoserine; by CaMK21 Publication

Post-translational modificationi

Phosphorylated by akt-1, akt-2, sgk-1 (PubMed:18358814). Phosphorylated by unc-43 (PubMed:23805378). Phosphorylated by jnk-1 (PubMed:15767565).3 Publications
Ubiquitinated. Ubiquitination by rle-1 leads to proteasome-mediated degradation.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO16850.
PaxDbiO16850.
PRIDEiO16850.

PTM databases

iPTMnetiO16850.

Expressioni

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

Developmental stagei

Expressed in embryos, larvae, dauer larvae and adults.1 Publication

Inductioni

Induced by quinic acid.1 Publication

Interactioni

Subunit structurei

Interacts with rle-1 (PubMed:17276341). Interacts with unc-43 (PubMed:23805378). Interacts with jnk-1 (PubMed:15767565).3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
akt-1Q179413EBI-324028,EBI-1770718
akt-2Q9XTG73EBI-324028,EBI-320656
sgk-1Q2PJ683EBI-324028,EBI-1770776
sir-2.1Q219212EBI-324028,EBI-966082

GO - Molecular functioni

  • 14-3-3 protein binding Source: WormBase
  • activating transcription factor binding Source: UniProtKB
  • beta-catenin binding Source: ParkinsonsUK-UCL
  • ubiquitin protein ligase binding Source: UniProtKB
  • ubiquitin-specific protease binding Source: WormBase

Protein-protein interaction databases

BioGridi38392. 5 interactions.
DIPiDIP-25581N.
IntActiO16850. 22 interactions.
MINTiMINT-1069794.
STRINGi6239.R13H8.1h.

Structurei

3D structure databases

ProteinModelPortaliO16850.
SMRiO16850. Positions 171-256.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00790000123003.
HOGENOMiHOG000019698.
InParanoidiO16850.
KOiK09408.
OrthoDBiEOG79GT6N.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

Sequences (8)i

Sequence statusi: Complete.

This entry describes 8 isoformsi produced by alternative splicing. AlignAdd to basket

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

This isoform has been chosen as the 'canonical' 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
Note: No experimental confirmation available.Curated
Length:541
Mass (Da):59,732
Last modified:January 25, 2012 - v3
Checksum:i8A36A86311A32CBB
GO
Isoform a1 Publication (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 b1 Publication (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 c2 Publications (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 d1 Publication (identifier: O16850-5) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.Curated
Show »
Length:487
Mass (Da):53,518
Checksum:i6998CD8BF98A5747
GO
Isoform e1 Publication (identifier: O16850-6) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available. Derived from EST data.Curated
Show »
Length:303
Mass (Da):32,933
Checksum:iDD1DEB2F8E1BCCAD
GO
Isoform f1 Publication (identifier: O16850-1) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.Curated
Show »
Length:517
Mass (Da):56,864
Checksum:i884488D4F43DB8D5
GO
Isoform gCurated (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

Note: No experimental confirmation available.Curated
Show »
Length:324
Mass (Da):35,474
Checksum:iB1E79F5EB916A3C3
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 238238Missing in isoform e. CuratedVSP_053105Add
BLAST
Alternative sequencei1 – 221221MQLEQ…DSNSS → MNDSIDDDFPPEPRGRCYTW PMQQYIYQESSATIPHHHLN QHNNPYHPMHPHHQLPHMQQ LPQPLLNLNMTTLTSSGSSV ASSIGGGAQCSPCASGSSTA ATNSSQQQQTVGQMLAASVP CSSSGMTLGMSLNLSQGGGP MPAKKKRCRKKPTDQLAQKK PNPWGEESYSDIIAKALESA PDGRLKLNEIYQWFSDNIPY FGERSSPEEA in isoform a. 1 PublicationVSP_053106Add
BLAST
Alternative sequencei1 – 217217Missing in isoform g. CuratedVSP_042147Add
BLAST
Alternative sequencei1 – 113113MQLEQ…SGRTS → MMEMLVDQGTDASSSASTST SSVSRFGADTFMNTPDDVMM NDDMEPIPRDRCNTWPMRRP QLEPPLNSSPIIHEQIPEED AD in isoform b and isoform c. 2 PublicationsVSP_053107Add
BLAST
Alternative sequencei1 – 5454Missing in isoform d. CuratedVSP_053108Add
BLAST
Alternative sequencei1 – 2424Missing in isoform f. CuratedVSP_042148Add
BLAST
Alternative sequencei152 – 1543DFR → E in isoform b. 1 PublicationVSP_053109
Alternative sequencei218 – 2258SNSSAGWK → MREMSTKN in isoform g. CuratedVSP_042149

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.
FO081472 Genomic DNA. Translation: CCD71850.1.
FO081472 Genomic DNA. Translation: CCD71851.1.
FO081472 Genomic DNA. Translation: CCD71852.1.
FO081472 Genomic DNA. Translation: CCD71853.1.
FO081472 Genomic DNA. Translation: CCD71854.1.
FO081472, FO080113 Genomic DNA. Translation: CCD71855.1.
FO081472, FO080113 Genomic DNA. Translation: CCD71856.1.
FO081472, FO080113 Genomic DNA. Translation: CCD71857.1.
PIRiT42234.
T42255.
RefSeqiNP_001021593.1. NM_001026422.4. [O16850-2]
NP_001021594.1. NM_001026423.4. [O16850-4]
NP_001021595.1. NM_001026424.4. [O16850-3]
NP_001021596.1. NM_001026425.3. [O16850-5]
NP_001021597.1. NM_001026426.2. [O16850-6]
NP_001021598.2. NM_001026427.4. [O16850-1]
NP_001251490.1. NM_001264561.1. [O16850-8]
NP_001251492.1. NM_001264563.1. [O16850-7]
UniGeneiCel.18378.

Genome annotation databases

EnsemblMetazoaiR13H8.1h; R13H8.1h; WBGene00000912. [O16850-8]
GeneIDi172981.
KEGGicel:CELE_R13H8.1.
UCSCiR13H8.1c. c. elegans.

Keywords - Coding sequence diversityi

Alternative splicing

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.
FO081472 Genomic DNA. Translation: CCD71850.1.
FO081472 Genomic DNA. Translation: CCD71851.1.
FO081472 Genomic DNA. Translation: CCD71852.1.
FO081472 Genomic DNA. Translation: CCD71853.1.
FO081472 Genomic DNA. Translation: CCD71854.1.
FO081472, FO080113 Genomic DNA. Translation: CCD71855.1.
FO081472, FO080113 Genomic DNA. Translation: CCD71856.1.
FO081472, FO080113 Genomic DNA. Translation: CCD71857.1.
PIRiT42234.
T42255.
RefSeqiNP_001021593.1. NM_001026422.4. [O16850-2]
NP_001021594.1. NM_001026423.4. [O16850-4]
NP_001021595.1. NM_001026424.4. [O16850-3]
NP_001021596.1. NM_001026425.3. [O16850-5]
NP_001021597.1. NM_001026426.2. [O16850-6]
NP_001021598.2. NM_001026427.4. [O16850-1]
NP_001251490.1. NM_001264561.1. [O16850-8]
NP_001251492.1. NM_001264563.1. [O16850-7]
UniGeneiCel.18378.

3D structure databases

ProteinModelPortaliO16850.
SMRiO16850. Positions 171-256.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi38392. 5 interactions.
DIPiDIP-25581N.
IntActiO16850. 22 interactions.
MINTiMINT-1069794.
STRINGi6239.R13H8.1h.

PTM databases

iPTMnetiO16850.

Proteomic databases

EPDiO16850.
PaxDbiO16850.
PRIDEiO16850.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiR13H8.1h; R13H8.1h; WBGene00000912. [O16850-8]
GeneIDi172981.
KEGGicel:CELE_R13H8.1.
UCSCiR13H8.1c. c. elegans.

Organism-specific databases

CTDi172981.
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.
COG5025. LUCA.
GeneTreeiENSGT00790000123003.
HOGENOMiHOG000019698.
InParanoidiO16850.
KOiK09408.
OrthoDBiEOG79GT6N.

Enzyme and pathway databases

ReactomeiR-CEL-198693. AKT phosphorylates targets in the nucleus.
R-CEL-211163. AKT-mediated inactivation of FOXO1A.
R-CEL-5687128. MAPK6/MAPK4 signaling.
SignaLinkiO16850.

Miscellaneous databases

NextBioi877779.
PROiO16850.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans."
    Ogg S., Paradis S., Gottlieb S., Patterson G.I., Lee L., Tissenbaum H.A., Ruvkun G.
    Nature 389:994-999(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
    Strain: Bristol N2Imported.
  2. "daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans."
    Lin K., Dorman J.B., Rodan A., Kenyon C.
    Science 278:1319-1322(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), FUNCTION, DISRUPTION PHENOTYPE.
    Strain: Bristol N2.
  3. "Genome sequence of the nematode C. elegans: a platform for investigating biology."
    The C. elegans sequencing consortium
    Science 282:2012-2018(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE SPLICING.
    Strain: Bristol N2.
  4. "A C. elegans mutant that lives twice as long as wild type."
    Kenyon C., Chang J., Gensch E., Rudner A., Tabtiang R.
    Nature 366:461-464(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Identification of the differential distribution patterns of mRNAs and consensus binding sequences for mouse DAF-16 homologues."
    Furuyama T., Nakazawa T., Nakano I., Mori N.
    Biochem. J. 349:629-634(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway."
    Lee R.Y., Hench J., Ruvkun G.
    Curr. Biol. 11:1950-1957(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  7. "daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans."
    Henderson S.T., Johnson T.E.
    Curr. Biol. 11:1975-1980(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  8. "Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling."
    Lin K., Hsin H., Libina N., Kenyon C.
    Nat. Genet. 28:139-145(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-271; THR-273 AND SER-345.
  9. "Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan."
    Libina N., Berman J.R., Kenyon C.
    Cell 115:489-502(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
  10. "Regulation of aging and age-related disease by DAF-16 and heat-shock factor."
    Hsu A.L., Murphy C.T., Kenyon C.
    Science 300:1142-1145(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "The p38 signal transduction pathway participates in the oxidative stress-mediated translocation of DAF-16 to Caenorhabditis elegans nuclei."
    Kondo M., Yanase S., Ishii T., Hartman P.S., Matsumoto K., Ishii N.
    Mech. Ageing Dev. 126:642-647(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  12. "JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16."
    Oh S.W., Mukhopadhyay A., Svrzikapa N., Jiang F., Davis R.J., Tissenbaum H.A.
    Proc. Natl. Acad. Sci. U.S.A. 102:4494-4499(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH JNK-1, SUBCELLULAR LOCATION, PHOSPHORYLATION.
  13. "p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans."
    Troemel E.R., Chu S.W., Reinke V., Lee S.S., Ausubel F.M., Kim D.H.
    PLoS Genet. 2:E183-E183(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  14. "Opposing activities protect against age-onset proteotoxicity."
    Cohen E., Bieschke J., Perciavalle R.M., Kelly J.W., Dillin A.
    Science 313:1604-1610(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  15. "Effects of the flavonoids kaempferol and fisetin on thermotolerance, oxidative stress and FoxO transcription factor DAF-16 in the model organism Caenorhabditis elegans."
    Kampkotter A., Gombitang Nkwonkam C., Zurawski R.F., Timpel C., Chovolou Y., Watjen W., Kahl R.
    Arch. Toxicol. 81:849-858(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  16. "An AMPK-FOXO pathway mediates longevity induced by a novel method of dietary restriction in C. elegans."
    Greer E.L., Dowlatshahi D., Banko M.R., Villen J., Hoang K., Blanchard D., Gygi S.P., Brunet A.
    Curr. Biol. 17:1646-1656(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  17. "RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing DAF-16 polyubiquitination."
    Li W., Gao B., Lee S.-M., Bennett K., Fang D.
    Dev. Cell 12:235-246(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RLE-1, UBIQUITINATION.
  18. "DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis elegans."
    Pinkston-Gosse J., Kenyon C.
    Nat. Genet. 39:1403-1409(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  19. "Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans."
    Murphy C.T., Lee S.J., Kenyon C.
    Proc. Natl. Acad. Sci. U.S.A. 104:19046-19050(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  20. "Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like signaling in C. elegans."
    Tullet J.M., Hertweck M., An J.H., Baker J., Hwang J.Y., Liu S., Oliveira R.P., Baumeister R., Blackwell T.K.
    Cell 132:1025-1038(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PHOSPHORYLATION BY AKT-1; AKT-2 AND SGK-1.
  21. "A 13C isotope labeling strategy reveals the influence of insulin signaling on lipogenesis in C. elegans."
    Perez C.L., Van Gilst M.R.
    Cell Metab. 8:266-274(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  22. "SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to modulate life span and stress response in C. elegans."
    Neumann-Haefelin E., Qi W., Finkbeiner E., Walz G., Baumeister R., Hertweck M.
    Genes Dev. 22:2721-2735(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  23. "DAF-16-dependent suppression of immunity during reproduction in Caenorhabditis elegans."
    Miyata S., Begun J., Troemel E.R., Ausubel F.M.
    Genetics 178:903-918(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  24. "Sirtuin inhibition protects from the polyalanine muscular dystrophy protein PABPN1."
    Catoire H., Pasco M.Y., Abu-Baker A., Holbert S., Tourette C., Brais B., Rouleau G.A., Parker J.A., Neri C.
    Hum. Mol. Genet. 17:2108-2117(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  25. "The MAP kinase JNK-1 of Caenorhabditis elegans: location, activation, and influences over temperature-dependent insulin-like signaling, stress responses, and fitness."
    Wolf M., Nunes F., Henkel A., Heinick A., Paul R.J.
    J. Cell. Physiol. 214:721-729(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  26. "A carbon dioxide avoidance behavior is integrated with responses to ambient oxygen and food in Caenorhabditis elegans."
    Bretscher A.J., Busch K.E., de Bono M.
    Proc. Natl. Acad. Sci. U.S.A. 105:8044-8049(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  27. "Endogenous cGMP regulates adult longevity via the insulin signaling pathway in Caenorhabditis elegans."
    Hahm J.H., Kim S., Paik Y.K.
    Aging Cell 8:473-483(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  28. "Combined informatic and expression screen identifies the novel DAF-16 target HLH-13."
    Liachko N., Davidowitz R., Lee S.S.
    Dev. Biol. 327:97-105(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  29. "Feeding a ROS-generator to Caenorhabditis elegans leads to increased expression of small heat shock protein HSP-16.2 and hormesis."
    Hartwig K., Heidler T., Moch J., Daniel H., Wenzel U.
    Genes Nutr. 4:59-67(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  30. "New genes that extend Caenorhabditis elegans' lifespan in response to reproductive signals."
    McCormick M., Chen K., Ramaswamy P., Kenyon C.
    Aging Cell 11:192-202(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  31. "Stress-response protein expression and DAF-16 translocation were induced in tributyltin-exposed Caenorhabditis elegans."
    Wang Y., Jian F., Wu J., Wang S.
    Bull. Environ. Contam. Toxicol. 89:704-711(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  32. "Longevity-promoting effects of 4-hydroxy-E-globularinin in Caenorhabditis elegans."
    Shukla V., Yadav D., Phulara S.C., Gupta M.M., Saikia S.K., Pandey R.
    Free Radic. Biol. Med. 53:1848-1856(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  33. "RPN-6 determines C. elegans longevity under proteotoxic stress conditions."
    Vilchez D., Morantte I., Liu Z., Douglas P.M., Merkwirth C., Rodrigues A.P., Manning G., Dillin A.
    Nature 489:263-268(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  34. "Quinic acid could be a potential rejuvenating natural compound by improving survival of Caenorhabditis elegans under deleterious conditions."
    Zhang L., Zhang J., Zhao B., Zhao-Wilson X.
    Rejuvenation Res. 15:573-583(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION BY QUINIC ACID.
  35. "CAMKII and Calcineurin regulate the lifespan of Caenorhabditis elegans through the FOXO transcription factor DAF-16."
    Tao L., Xie Q., Ding Y.H., Li S.T., Peng S., Zhang Y.P., Tan D., Yuan Z., Dong M.Q.
    Elife 2:E00518-E00518(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH UNC-43, PHOSPHORYLATION BY UNC-43.
  36. "The DAF-16/FOXO transcription factor functions as a regulator of epidermal innate immunity."
    Zou C.G., Tu Q., Niu J., Ji X.L., Zhang K.Q.
    PLoS Pathog. 9:E1003660-E1003660(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
  37. "The FOXO transcription factor DAF-16 bypasses ire-1 requirement to promote endoplasmic reticulum hoymeostasis."
    Safra M., Fickentscher R., Levi-Ferber M., Danino Y.M., Haviv-Chesner A., Hansen M., Juven-Gershon T., Weiss M., Henis-Korenblit S.
    Cell Metab. 20:870-881(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  38. "DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans."
    Tullet J.M., Araiz C., Sanders M.J., Au C., Benedetto A., Papatheodorou I., Clark E., Schmeisser K., Jones D., Schuster E.F., Thornton J.M., Gems D.
    PLoS Genet. 10:E1004109-E1004109(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  39. "The DAF-16 FOXO transcription factor regulates natc-1 to modulate stress resistance in Caenorhabditis elegans, linking insulin/IGF-1 signaling to protein N-terminal acetylation."
    Warnhoff K., Murphy J.T., Kumar S., Schneider D.L., Peterson M., Hsu S., Guthrie J., Robertson J.D., Kornfeld K.
    PLoS Genet. 10:E1004703-E1004703(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  40. "Feeding state, insulin and NPR-1 modulate Chemoreceptor gene expression via integration of sensory and circuit inputs."
    Gruner M., Nelson D., Winbush A., Hintz R., Ryu L., Chung S.H., Kim K., Gabel C.V., van der Linden A.M.
    PLoS Genet. 10:E1004707-E1004707(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiFOXO_CAEEL
AccessioniPrimary (citable) accession number: O16850
Secondary accession number(s): F3NWW7
, F3NWX0, G4RQR7, G4S686, G4SKG3, G4SKH0, O16849, O18676, Q86S42
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 16, 2009
Last sequence update: January 25, 2012
Last modified: May 11, 2016
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.