FOXO_CAEEL
ID FOXO_CAEEL Reviewed; 541 AA.
AC O16850; F3NWW7; F3NWX0; G4RQR7; G4S686; G4SKG3; G4SKH0; O16849; O18676;
AC Q86S42;
DT 16-JUN-2009, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 3.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Forkhead box protein O {ECO:0000305};
DE Short=FOXO {ECO:0000303|PubMed:12750521};
DE AltName: Full=Abnormal dauer formation protein 16 {ECO:0000312|WormBase:R13H8.1h};
GN Name=daf-16 {ECO:0000312|WormBase:R13H8.1h};
GN ORFNames=R13H8.1 {ECO:0000312|WormBase:R13H8.1h};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAB84390.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C), TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAB84392.1};
RX PubMed=9353126; DOI=10.1038/40194;
RA Ogg S., Paradis S., Gottlieb S., Patterson G.I., Lee L., Tissenbaum H.A.,
RA Ruvkun G.;
RT "The Fork head transcription factor DAF-16 transduces insulin-like
RT metabolic and longevity signals in C. elegans.";
RL Nature 389:994-999(1997).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=Bristol N2;
RX PubMed=9360933; DOI=10.1126/science.278.5341.1319;
RA Lin K., Dorman J.B., Rodan A., Kenyon C.;
RT "daf-16: An HNF-3/forkhead family member that can function to double the
RT life-span of Caenorhabditis elegans.";
RL Science 278:1319-1322(1997).
RN [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [4]
RP FUNCTION.
RX PubMed=8247153; DOI=10.1038/366461a0;
RA Kenyon C., Chang J., Gensch E., Rudner A., Tabtiang R.;
RT "A C. elegans mutant that lives twice as long as wild type.";
RL Nature 366:461-464(1993).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=10880363; DOI=10.1042/0264-6021:3490629;
RA Furuyama T., Nakazawa T., Nakano I., Mori N.;
RT "Identification of the differential distribution patterns of mRNAs and
RT consensus binding sequences for mouse DAF-16 homologues.";
RL Biochem. J. 349:629-634(2000).
RN [6] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=11747821; DOI=10.1016/s0960-9822(01)00595-4;
RA Lee R.Y., Hench J., Ruvkun G.;
RT "Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2
RT insulin-like signaling pathway.";
RL Curr. Biol. 11:1950-1957(2001).
RN [7] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11747825; DOI=10.1016/s0960-9822(01)00594-2;
RA Henderson S.T., Johnson T.E.;
RT "daf-16 integrates developmental and environmental inputs to mediate aging
RT in the nematode Caenorhabditis elegans.";
RL Curr. Biol. 11:1975-1980(2001).
RN [8] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-271; THR-273 AND
RP SER-345.
RX PubMed=11381260; DOI=10.1038/88850;
RA Lin K., Hsin H., Libina N., Kenyon C.;
RT "Regulation of the Caenorhabditis elegans longevity protein DAF-16 by
RT insulin/IGF-1 and germline signaling.";
RL Nat. Genet. 28:139-145(2001).
RN [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=14622602; DOI=10.1016/s0092-8674(03)00889-4;
RA Libina N., Berman J.R., Kenyon C.;
RT "Tissue-specific activities of C. elegans DAF-16 in the regulation of
RT lifespan.";
RL Cell 115:489-502(2003).
RN [10] {ECO:0000305}
RP FUNCTION.
RX PubMed=12750521; DOI=10.1126/science.1083701;
RA Hsu A.L., Murphy C.T., Kenyon C.;
RT "Regulation of aging and age-related disease by DAF-16 and heat-shock
RT factor.";
RL Science 300:1142-1145(2003).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=15888317; DOI=10.1016/j.mad.2004.11.012;
RA Kondo M., Yanase S., Ishii T., Hartman P.S., Matsumoto K., Ishii N.;
RT "The p38 signal transduction pathway participates in the oxidative stress-
RT mediated translocation of DAF-16 to Caenorhabditis elegans nuclei.";
RL Mech. Ageing Dev. 126:642-647(2005).
RN [12]
RP INTERACTION WITH JNK-1, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=15767565; DOI=10.1073/pnas.0500749102;
RA Oh S.W., Mukhopadhyay A., Svrzikapa N., Jiang F., Davis R.J.,
RA Tissenbaum H.A.;
RT "JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear
RT translocation of forkhead transcription factor/DAF-16.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:4494-4499(2005).
RN [13]
RP INTERACTION WITH FTT-2.
RX PubMed=16777605; DOI=10.1016/j.cell.2006.04.036;
RA Berdichevsky A., Viswanathan M., Horvitz H.R., Guarente L.;
RT "C. elegans SIR-2.1 interacts with 14-3-3 proteins to activate DAF-16 and
RT extend life span.";
RL Cell 125:1165-1177(2006).
RN [14]
RP FUNCTION.
RX PubMed=17096597; DOI=10.1371/journal.pgen.0020183;
RA Troemel E.R., Chu S.W., Reinke V., Lee S.S., Ausubel F.M., Kim D.H.;
RT "p38 MAPK regulates expression of immune response genes and contributes to
RT longevity in C. elegans.";
RL PLoS Genet. 2:E183-E183(2006).
RN [15]
RP FUNCTION.
RX PubMed=16902091; DOI=10.1126/science.1124646;
RA Cohen E., Bieschke J., Perciavalle R.M., Kelly J.W., Dillin A.;
RT "Opposing activities protect against age-onset proteotoxicity.";
RL Science 313:1604-1610(2006).
RN [16]
RP SUBCELLULAR LOCATION.
RX PubMed=17551714; DOI=10.1007/s00204-007-0215-4;
RA Kampkotter A., Gombitang Nkwonkam C., Zurawski R.F., Timpel C.,
RA Chovolou Y., Watjen W., Kahl R.;
RT "Effects of the flavonoids kaempferol and fisetin on thermotolerance,
RT oxidative stress and FoxO transcription factor DAF-16 in the model organism
RT Caenorhabditis elegans.";
RL Arch. Toxicol. 81:849-858(2007).
RN [17]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17900900; DOI=10.1016/j.cub.2007.08.047;
RA Greer E.L., Dowlatshahi D., Banko M.R., Villen J., Hoang K., Blanchard D.,
RA Gygi S.P., Brunet A.;
RT "An AMPK-FOXO pathway mediates longevity induced by a novel method of
RT dietary restriction in C. elegans.";
RL Curr. Biol. 17:1646-1656(2007).
RN [18]
RP INTERACTION WITH RLE-1, AND UBIQUITINATION.
RX PubMed=17276341; DOI=10.1016/j.devcel.2006.12.002;
RA Li W., Gao B., Lee S.-M., Bennett K., Fang D.;
RT "RLE-1, an E3 ubiquitin ligase, regulates C. elegans aging by catalyzing
RT DAF-16 polyubiquitination.";
RL Dev. Cell 12:235-246(2007).
RN [19]
RP FUNCTION.
RX PubMed=17934462; DOI=10.1038/ng.2007.1;
RA Pinkston-Gosse J., Kenyon C.;
RT "DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis
RT elegans.";
RL Nat. Genet. 39:1403-1409(2007).
RN [20]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18025456; DOI=10.1073/pnas.0709613104;
RA Murphy C.T., Lee S.J., Kenyon C.;
RT "Tissue entrainment by feedback regulation of insulin gene expression in
RT the endoderm of Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:19046-19050(2007).
RN [21]
RP FUNCTION, AND PHOSPHORYLATION BY AKT-1; AKT-2 AND SGK-1.
RX PubMed=18358814; DOI=10.1016/j.cell.2008.01.030;
RA Tullet J.M., Hertweck M., An J.H., Baker J., Hwang J.Y., Liu S.,
RA Oliveira R.P., Baumeister R., Blackwell T.K.;
RT "Direct inhibition of the longevity-promoting factor SKN-1 by insulin-like
RT signaling in C. elegans.";
RL Cell 132:1025-1038(2008).
RN [22]
RP FUNCTION.
RX PubMed=18762027; DOI=10.1016/j.cmet.2008.08.007;
RA Perez C.L., Van Gilst M.R.;
RT "A 13C isotope labeling strategy reveals the influence of insulin signaling
RT on lipogenesis in C. elegans.";
RL Cell Metab. 8:266-274(2008).
RN [23]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18832074; DOI=10.1101/gad.478408;
RA Neumann-Haefelin E., Qi W., Finkbeiner E., Walz G., Baumeister R.,
RA Hertweck M.;
RT "SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to
RT modulate life span and stress response in C. elegans.";
RL Genes Dev. 22:2721-2735(2008).
RN [24]
RP FUNCTION.
RX PubMed=18245330; DOI=10.1534/genetics.107.083923;
RA Miyata S., Begun J., Troemel E.R., Ausubel F.M.;
RT "DAF-16-dependent suppression of immunity during reproduction in
RT Caenorhabditis elegans.";
RL Genetics 178:903-918(2008).
RN [25]
RP FUNCTION.
RX PubMed=18397876; DOI=10.1093/hmg/ddn109;
RA Catoire H., Pasco M.Y., Abu-Baker A., Holbert S., Tourette C., Brais B.,
RA Rouleau G.A., Parker J.A., Neri C.;
RT "Sirtuin inhibition protects from the polyalanine muscular dystrophy
RT protein PABPN1.";
RL Hum. Mol. Genet. 17:2108-2117(2008).
RN [26]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17894411; DOI=10.1002/jcp.21269;
RA Wolf M., Nunes F., Henkel A., Heinick A., Paul R.J.;
RT "The MAP kinase JNK-1 of Caenorhabditis elegans: location, activation, and
RT influences over temperature-dependent insulin-like signaling, stress
RT responses, and fitness.";
RL J. Cell. Physiol. 214:721-729(2008).
RN [27] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH HCF-1.
RX PubMed=18828672; DOI=10.1371/journal.pbio.0060233;
RA Li J., Ebata A., Dong Y., Rizki G., Iwata T., Lee S.S.;
RT "Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-
RT 16 regulator.";
RL PLoS Biol. 6:e233-e233(2008).
RN [28]
RP FUNCTION.
RX PubMed=18524954; DOI=10.1073/pnas.0707607105;
RA Bretscher A.J., Busch K.E., de Bono M.;
RT "A carbon dioxide avoidance behavior is integrated with responses to
RT ambient oxygen and food in Caenorhabditis elegans.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:8044-8049(2008).
RN [29]
RP FUNCTION.
RX PubMed=19489741; DOI=10.1111/j.1474-9726.2009.00495.x;
RA Hahm J.H., Kim S., Paik Y.K.;
RT "Endogenous cGMP regulates adult longevity via the insulin signaling
RT pathway in Caenorhabditis elegans.";
RL Aging Cell 8:473-483(2009).
RN [30]
RP FUNCTION.
RX PubMed=19103192; DOI=10.1016/j.ydbio.2008.11.019;
RA Liachko N., Davidowitz R., Lee S.S.;
RT "Combined informatic and expression screen identifies the novel DAF-16
RT target HLH-13.";
RL Dev. Biol. 327:97-105(2009).
RN [31]
RP SUBCELLULAR LOCATION.
RX PubMed=19252938; DOI=10.1007/s12263-009-0113-x;
RA Hartwig K., Heidler T., Moch J., Daniel H., Wenzel U.;
RT "Feeding a ROS-generator to Caenorhabditis elegans leads to increased
RT expression of small heat shock protein HSP-16.2 and hormesis.";
RL Genes Nutr. 4:59-67(2009).
RN [32]
RP FUNCTION, INTERACTION WITH FTT-2 AND PRMT-1, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION BY AKT, PHOSPHORYLATION AT THR-273, AND MUTAGENESIS OF
RP ARG-266; ARG-268; ARG-270; SER-271 AND THR-273.
RX PubMed=21531333; DOI=10.1016/j.cmet.2011.03.017;
RA Takahashi Y., Daitoku H., Hirota K., Tamiya H., Yokoyama A., Kako K.,
RA Nagashima Y., Nakamura A., Shimada T., Watanabe S., Yamagata K., Yasuda K.,
RA Ishii N., Fukamizu A.;
RT "Asymmetric arginine dimethylation determines life span in C. elegans by
RT regulating forkhead transcription factor DAF-16.";
RL Cell Metab. 13:505-516(2011).
RN [33]
RP FUNCTION.
RX PubMed=22081913; DOI=10.1111/j.1474-9726.2011.00768.x;
RA McCormick M., Chen K., Ramaswamy P., Kenyon C.;
RT "New genes that extend Caenorhabditis elegans' lifespan in response to
RT reproductive signals.";
RL Aging Cell 11:192-202(2012).
RN [34]
RP SUBCELLULAR LOCATION.
RX PubMed=22875284; DOI=10.1007/s00128-012-0760-2;
RA Wang Y., Jian F., Wu J., Wang S.;
RT "Stress-response protein expression and DAF-16 translocation were induced
RT in tributyltin-exposed Caenorhabditis elegans.";
RL Bull. Environ. Contam. Toxicol. 89:704-711(2012).
RN [35]
RP SUBCELLULAR LOCATION.
RX PubMed=23000058; DOI=10.1016/j.freeradbiomed.2012.08.594;
RA Shukla V., Yadav D., Phulara S.C., Gupta M.M., Saikia S.K., Pandey R.;
RT "Longevity-promoting effects of 4-hydroxy-E-globularinin in Caenorhabditis
RT elegans.";
RL Free Radic. Biol. Med. 53:1848-1856(2012).
RN [36]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=22922647; DOI=10.1038/nature11315;
RA Vilchez D., Morantte I., Liu Z., Douglas P.M., Merkwirth C.,
RA Rodrigues A.P., Manning G., Dillin A.;
RT "RPN-6 determines C. elegans longevity under proteotoxic stress
RT conditions.";
RL Nature 489:263-268(2012).
RN [37]
RP INDUCTION BY QUINIC ACID.
RX PubMed=22950425; DOI=10.1089/rej.2012.1342;
RA Zhang L., Zhang J., Zhao B., Zhao-Wilson X.;
RT "Quinic acid could be a potential rejuvenating natural compound by
RT improving survival of Caenorhabditis elegans under deleterious
RT conditions.";
RL Rejuvenation Res. 15:573-583(2012).
RN [38]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23770237; DOI=10.1016/j.celrep.2013.05.012;
RA Matilainen O., Arpalahti L., Rantanen V., Hautaniemi S., Holmberg C.I.;
RT "Insulin/IGF-1 signaling regulates proteasome activity through the
RT deubiquitinating enzyme UBH-4.";
RL Cell Rep. 3:1980-1995(2013).
RN [39]
RP INTERACTION WITH UNC-43 AND TAX-6, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP SER-319, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF SER-319.
RX PubMed=23805378; DOI=10.7554/elife.00518;
RA Tao L., Xie Q., Ding Y.H., Li S.T., Peng S., Zhang Y.P., Tan D., Yuan Z.,
RA Dong M.Q.;
RT "CAMKII and Calcineurin regulate the lifespan of Caenorhabditis elegans
RT through the FOXO transcription factor DAF-16.";
RL Elife 2:E00518-E00518(2013).
RN [40]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=24146615; DOI=10.1371/journal.ppat.1003660;
RA Zou C.G., Tu Q., Niu J., Ji X.L., Zhang K.Q.;
RT "The DAF-16/FOXO transcription factor functions as a regulator of epidermal
RT innate immunity.";
RL PLoS Pathog. 9:E1003660-E1003660(2013).
RN [41]
RP FUNCTION.
RX PubMed=25448701; DOI=10.1016/j.cmet.2014.09.006;
RA Safra M., Fickentscher R., Levi-Ferber M., Danino Y.M., Haviv-Chesner A.,
RA Hansen M., Juven-Gershon T., Weiss M., Henis-Korenblit S.;
RT "The FOXO transcription factor DAF-16 bypasses ire-1 requirement to promote
RT endoplasmic reticulum hoymeostasis.";
RL Cell Metab. 20:870-881(2014).
RN [42]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24957743; DOI=10.1007/s12263-014-0414-6;
RA Fischer M., Fitzenberger E., Kull R., Boll M., Wenzel U.;
RT "The zinc matrix metalloproteinase ZMP-2 increases survival of
RT Caenorhabditis elegans through interference with lipoprotein absorption.";
RL Genes Nutr. 9:414-414(2014).
RN [43]
RP FUNCTION (ISOFORMS A; D AND F), AND DEVELOPMENTAL STAGE (ISOFORMS A; D AND
RP F).
RX PubMed=24834345; DOI=10.1186/2046-2395-3-5;
RA Bansal A., Kwon E.S., Conte D. Jr., Liu H., Gilchrist M.J., MacNeil L.T.,
RA Tissenbaum H.A.;
RT "Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates
RT lifespan.";
RL Longev. Healthspan 3:5-5(2014).
RN [44]
RP FUNCTION.
RX PubMed=25383666; DOI=10.1038/nsmb.2915;
RA Nakagawa A., Sullivan K.D., Xue D.;
RT "Caspase-activated phosphoinositide binding by CNT-1 promotes apoptosis by
RT inhibiting the AKT pathway.";
RL Nat. Struct. Mol. Biol. 21:1082-1090(2014).
RN [45]
RP FUNCTION.
RX PubMed=24516399; DOI=10.1371/journal.pgen.1004109;
RA Tullet J.M., Araiz C., Sanders M.J., Au C., Benedetto A., Papatheodorou I.,
RA Clark E., Schmeisser K., Jones D., Schuster E.F., Thornton J.M., Gems D.;
RT "DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase
RT gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in
RT Caenorhabditis elegans.";
RL PLoS Genet. 10:E1004109-E1004109(2014).
RN [46]
RP FUNCTION.
RX PubMed=25330323; DOI=10.1371/journal.pgen.1004703;
RA Warnhoff K., Murphy J.T., Kumar S., Schneider D.L., Peterson M., Hsu S.,
RA Guthrie J., Robertson J.D., Kornfeld K.;
RT "The DAF-16 FOXO transcription factor regulates natc-1 to modulate stress
RT resistance in Caenorhabditis elegans, linking insulin/IGF-1 signaling to
RT protein N-terminal acetylation.";
RL PLoS Genet. 10:E1004703-E1004703(2014).
RN [47]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25357003; DOI=10.1371/journal.pgen.1004707;
RA Gruner M., Nelson D., Winbush A., Hintz R., Ryu L., Chung S.H., Kim K.,
RA Gabel C.V., van der Linden A.M.;
RT "Feeding state, insulin and NPR-1 modulate Chemoreceptor gene expression
RT via integration of sensory and circuit inputs.";
RL PLoS Genet. 10:E1004707-E1004707(2014).
RN [48] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26675724; DOI=10.1038/nature16483;
RA Kaletsky R., Lakhina V., Arey R., Williams A., Landis J., Ashraf J.,
RA Murphy C.T.;
RT "The C. elegans adult neuronal IIS/FOXO transcriptome reveals adult
RT phenotype regulators.";
RL Nature 529:92-96(2016).
RN [49]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=28285998; DOI=10.1016/j.cub.2017.02.015;
RA Ames K., Da Cunha D.S., Gonzalez B., Konta M., Lin F., Shechter G.,
RA Starikov L., Wong S., Buelow H.E., Melendez A.;
RT "A Non-Cell-Autonomous Role of BEC-1/BECN1/Beclin1 in Coordinating Cell-
RT Cycle Progression and Stem Cell Proliferation during Germline
RT Development.";
RL Curr. Biol. 27:905-913(2017).
RN [50]
RP FUNCTION.
RX PubMed=29523076; DOI=10.1186/s12868-018-0408-1;
RA Bennett H.L., Khoruzhik Y., Hayden D., Huang H., Sanders J., Walsh M.B.,
RA Biron D., Hart A.C.;
RT "Normal sleep bouts are not essential for C. elegans survival and FoxO is
RT important for compensatory changes in sleep.";
RL BMC Neurosci. 19:10-10(2018).
RN [51]
RP FUNCTION.
RX PubMed=29500338; DOI=10.1038/s41467-018-02934-5;
RA De Magalhaes Filho C.D., Henriquez B., Seah N.E., Evans R.M.,
RA Lapierre L.R., Dillin A.;
RT "Visible light reduces C. elegans longevity.";
RL Nat. Commun. 9:927-927(2018).
RN [52]
RP FUNCTION, AND MUTAGENESIS OF 373-TRP--LEU-541.
RX PubMed=30409788; DOI=10.1534/genetics.118.301557;
RA Flatt K.M., Beshers C., Unal C., Cohen J.D., Sundaram M.V., Schroeder N.E.;
RT "Epidermal Remodeling in Caenorhabditis elegans Dauers Requires the Nidogen
RT Domain Protein DEX-1.";
RL Genetics 211:169-183(2019).
RN [53]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30779740; DOI=10.1371/journal.pgen.1007945;
RA Peymen K., Watteyne J., Borghgraef C., Van Sinay E., Beets I., Schoofs L.;
RT "Myoinhibitory peptide signaling modulates aversive gustatory learning in
RT Caenorhabditis elegans.";
RL PLoS Genet. 15:E1007945-E1007945(2019).
CC -!- FUNCTION: Forkhead-type transcription factor (PubMed:9360933). Binds to
CC the promoters of genes that contain the daf-16/FOXO binding element
CC (DBE), TTGTTTAC, in their regulatory region (PubMed:10880363,
CC PubMed:23770237, PubMed:26675724). Functions in the Insulin/IGF-1-like
CC signaling (IIS) mediated pathway which affects lipogenesis, lifespan,
CC starvation survival, heat shock and oxidative stress responses, sleep,
CC associative memory, and dauer formation (PubMed:9360933,
CC PubMed:8247153, PubMed:11747821, PubMed:11747825, PubMed:11381260,
CC PubMed:14622602, PubMed:12750521, PubMed:17900900, PubMed:18358814,
CC PubMed:18762027, PubMed:18832074, PubMed:19103192, PubMed:21531333,
CC PubMed:22081913, PubMed:29523076, PubMed:26675724). Longevity signaling
CC predominantly arises from expression in the intestine
CC (PubMed:14622602). Transcriptional activity of daf-16/FOXO is
CC negatively regulated by interaction with host cell factor homolog hcf-
CC 1; and by cytoplasmic sequestration by association with ftt-2
CC (PubMed:11381260, PubMed:21531333, PubMed:18828672). Inhibition is
CC required for the carbon dioxide (CO2) avoidance response
CC (PubMed:18524954). Upon loss of inhibition, daf-16 translocates to the
CC nucleus to regulate genes that result in delayed reproduction and
CC growth while increasing stress resistance starvation tolerance and
CC longevity (PubMed:11747825, PubMed:21531333). Association with arginine
CC methyltransferase prmt-1 prevents phosphorylation and allows for
CC translocation to the nucleus and the subsequent transcription of
CC longevity-related genes (PubMed:21531333). Modulation of its activity
CC by cGMP levels in sensory neurons regulates lifespan (PubMed:19489741).
CC Has a protective role against muscle dystrophy (PubMed:18397876).
CC Involved in mediating protection against aberrant protein aggregation
CC proteotoxicity (PubMed:16902091). Influences transcription of genes
CC that code for proteins involved in immunity as part of a general stress
CC response (PubMed:17096597, PubMed:18245330). Targets genes that inhibit
CC and stimulate tumor growth (PubMed:17934462). Targets kinases,
CC phosphatases and transcription factors that are primarily involved in
CC signaling and gene regulation (PubMed:24516399). Thought to regulate
CC ins-7 in FOXO-to-FOXO signaling, which coordinates daf-16 expression
CC (PubMed:18025456). Activity is positively regulated by shc-1-mediated
CC inhibition of daf-2 and activation of JNK pathway (PubMed:18832074).
CC Functions by indirect interaction with jnk-1 of the mitogen-activated
CC protein kinase (MAPK) pathway (PubMed:17894411). Involved in increased
CC proteasome activity by activating expression of rpn-6.1 in response to
CC proteotoxic stress, leading to enhanced assembly of the 26S proteasome,
CC followed by higher proteasome activity (PubMed:22922647). Also
CC regulates proteasome activity in the intestine by preventing expression
CC of deubiquitinase ubh-4 (PubMed:23770237). Represses transcription of
CC natc-1 (PubMed:25330323). Involved in regulation of srh-234 expression
CC (PubMed:25357003). Binds to the promoter of the AMPK-gamma regulatory
CC subunit, aakg-4, and activates its transcription (PubMed:24516399).
CC Also activates transcription of AMPK-gamma regulatory subunit, aakg-1
CC (PubMed:24516399). Maintains endoplasmic reticulum (ER) function by
CC inducing protein degradation and elimination to remove misfolded
CC secretory proteins from the ER independently of the ire-1/xbp-1
CC unfolded protein response pathway (PubMed:25448701). Regulates
CC epidermal innate immunity to nematophagous fungal infection and
CC physical wounding which trigger bli-3 induced ROS release, leading to
CC daf-16 activation independently of daf-2 signaling (PubMed:24146615).
CC May negatively regulate resistance to stress caused by oxidized
CC cholesterol adducts by preventing the activation of daf-9 and nuclear
CC hormone receptor daf-12, two members of the steroid signaling pathway
CC (PubMed:24957743). Promotes apoptosis during embryonic development
CC (PubMed:25383666). Probably through the regulation of the autophagy
CC genes atg-18 and atg-16.2, plays a role in regulating stem cell number
CC in the germline during larval development (PubMed:28285998). Plays a
CC role in learning and memory; including associative memory, and aversive
CC gustatory associated learning known as salt avoidance learning
CC (PubMed:26675724, PubMed:30779740). Plays a role in regulating gene
CC transcription in response to white light exposure (PubMed:29500338).
CC Binds to the promoter of dex-1 to positively regulate its expression in
CC seam cells during the dauer phase (PubMed:30409788).
CC {ECO:0000269|PubMed:10880363, ECO:0000269|PubMed:11381260,
CC ECO:0000269|PubMed:11747821, ECO:0000269|PubMed:11747825,
CC ECO:0000269|PubMed:12750521, ECO:0000269|PubMed:14622602,
CC ECO:0000269|PubMed:16902091, ECO:0000269|PubMed:17096597,
CC ECO:0000269|PubMed:17894411, ECO:0000269|PubMed:17900900,
CC ECO:0000269|PubMed:17934462, ECO:0000269|PubMed:18025456,
CC ECO:0000269|PubMed:18245330, ECO:0000269|PubMed:18358814,
CC ECO:0000269|PubMed:18397876, ECO:0000269|PubMed:18524954,
CC ECO:0000269|PubMed:18762027, ECO:0000269|PubMed:18832074,
CC ECO:0000269|PubMed:19103192, ECO:0000269|PubMed:19489741,
CC ECO:0000269|PubMed:21531333, ECO:0000269|PubMed:22081913,
CC ECO:0000269|PubMed:22922647, ECO:0000269|PubMed:23770237,
CC ECO:0000269|PubMed:24146615, ECO:0000269|PubMed:24516399,
CC ECO:0000269|PubMed:24957743, ECO:0000269|PubMed:25330323,
CC ECO:0000269|PubMed:25357003, ECO:0000269|PubMed:25383666,
CC ECO:0000269|PubMed:25448701, ECO:0000269|PubMed:28285998,
CC ECO:0000269|PubMed:29500338, ECO:0000269|PubMed:30409788,
CC ECO:0000269|PubMed:30779740, ECO:0000269|PubMed:8247153,
CC ECO:0000269|PubMed:9360933}.
CC -!- FUNCTION: [Isoform a]: Functions in the Insulin/IGF-1-like signaling
CC (IIS) mediated pathway (PubMed:24834345). May play a role in lifespan
CC modulation, but less significant than that played by isoforms d and f
CC (PubMed:24834345). {ECO:0000269|PubMed:24834345}.
CC -!- FUNCTION: [Isoform d]: Functions in the Insulin/IGF-1-like signaling
CC (IIS) mediated pathway (PubMed:24834345). Transcript level in the early
CC adult may play a role in lifespan modulation, but effect is more
CC significant than that played by isoform a (PubMed:24834345).
CC {ECO:0000269|PubMed:24834345}.
CC -!- FUNCTION: [Isoform f]: Functions in the Insulin/IGF-1-like signaling
CC (IIS) mediated pathway (PubMed:24834345). Transcript level in the early
CC adult may play a role in lifespan modulation, but effect is more
CC significant than that played by isoform a (PubMed:24834345).
CC {ECO:0000269|PubMed:24834345}.
CC -!- SUBUNIT: Interacts with rle-1 (PubMed:17276341). Interacts with unc-43
CC and tax-6 (PubMed:23805378). Interacts with jnk-1 (PubMed:15767565).
CC Interacts with ftt-2 (PubMed:16777605, PubMed:21531333). Interacts with
CC prmt-1 (PubMed:21531333). Interacts with hcf-1.
CC {ECO:0000269|PubMed:15767565, ECO:0000269|PubMed:17276341,
CC ECO:0000269|PubMed:18828672, ECO:0000269|PubMed:21531333,
CC ECO:0000269|PubMed:23805378}.
CC -!- INTERACTION:
CC O16850; Q17941: akt-1; NbExp=3; IntAct=EBI-324028, EBI-1770718;
CC O16850; Q9XTG7: akt-2; NbExp=3; IntAct=EBI-324028, EBI-320656;
CC O16850; Q2PJ68: sgk-1; NbExp=3; IntAct=EBI-324028, EBI-1770776;
CC O16850; Q21921: sir-2.1; NbExp=2; IntAct=EBI-324028, EBI-966082;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11381260,
CC ECO:0000269|PubMed:11747825, ECO:0000269|PubMed:15767565,
CC ECO:0000269|PubMed:15888317, ECO:0000269|PubMed:17551714,
CC ECO:0000269|PubMed:17894411, ECO:0000269|PubMed:18832074,
CC ECO:0000269|PubMed:19252938, ECO:0000269|PubMed:21531333,
CC ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:24146615}. Cytoplasm
CC {ECO:0000269|PubMed:11381260, ECO:0000269|PubMed:11747825,
CC ECO:0000269|PubMed:15767565, ECO:0000269|PubMed:15888317,
CC ECO:0000269|PubMed:17551714, ECO:0000269|PubMed:17894411,
CC ECO:0000269|PubMed:18832074, ECO:0000269|PubMed:19252938,
CC ECO:0000269|PubMed:21531333, ECO:0000269|PubMed:23805378,
CC ECO:0000269|PubMed:24146615}. Note=Shuttles between cytoplasm and
CC nucleus (PubMed:11381260, PubMed:17894411). Nuclear translocation is
CC inhibited by phosphorylation by AKT proteins (PubMed:11381260,
CC PubMed:11747825, PubMed:21531333). Association with ftt-2 sequesters
CC daf-16 in the cytoplasm (PubMed:21531333). Association with prmt-1
CC allows for translocation to the nucleus (PubMed:21531333). Nuclear
CC translocation is promoted by phosphorylation by unc-43 and inhibited by
CC dephosphorylation by tax-6 (PubMed:23805378). Nuclear translocation is
CC promoted by jnk-1 upon heat stress and by sek-1 upon oxidative stress
CC (PubMed:15888317, PubMed:15767565). Nucleocytoplasmic shuttling is
CC induced by starvation, heat treatment, hypergravity, reactive oxygen
CC species (generated by juglone), exposure to tributyltin or 4-hydroxy-E-
CC globularinin (4-HEG) and the flavonoids kaempferol and fisetin
CC (PubMed:11381260, PubMed:17551714, PubMed:18832074, PubMed:19252938,
CC PubMed:21531333, PubMed:23805378). Nuclear localization induced by
CC nematophagous fungal infection (PubMed:24146615).
CC {ECO:0000269|PubMed:11381260, ECO:0000269|PubMed:11747825,
CC ECO:0000269|PubMed:15767565, ECO:0000269|PubMed:15888317,
CC ECO:0000269|PubMed:17551714, ECO:0000269|PubMed:17894411,
CC ECO:0000269|PubMed:18832074, ECO:0000269|PubMed:19252938,
CC ECO:0000269|PubMed:21531333, ECO:0000269|PubMed:24146615}.
CC -!- SUBCELLULAR LOCATION: [Isoform a]: Nucleus
CC {ECO:0000269|PubMed:24834345}. Cytoplasm {ECO:0000269|PubMed:24834345}.
CC Note=Ratio of nuclear to cytoplasmic localization is daf-2-dependent.
CC {ECO:0000269|PubMed:24834345}.
CC -!- SUBCELLULAR LOCATION: [Isoform d]: Nucleus
CC {ECO:0000269|PubMed:24834345}. Cytoplasm {ECO:0000269|PubMed:24834345}.
CC Note=Ratio of nuclear to cytoplasmic localization is daf-2-dependent.
CC {ECO:0000269|PubMed:24834345}.
CC -!- SUBCELLULAR LOCATION: [Isoform f]: Nucleus
CC {ECO:0000269|PubMed:24834345}. Cytoplasm {ECO:0000269|PubMed:24834345}.
CC Note=Ratio of nuclear to cytoplasmic localization is daf-2-dependent.
CC {ECO:0000269|PubMed:24834345}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=h {ECO:0000312|WormBase:R13H8.1h};
CC IsoId=O16850-8; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:R13H8.1a}; Synonyms=b
CC {ECO:0000303|PubMed:9353126};
CC IsoId=O16850-2; Sequence=VSP_053106;
CC Name=b {ECO:0000312|WormBase:R13H8.1b}; Synonyms=a2
CC {ECO:0000303|PubMed:9353126};
CC IsoId=O16850-4; Sequence=VSP_053107, VSP_053109;
CC Name=c {ECO:0000312|WormBase:R13H8.1c}; Synonyms=a1
CC {ECO:0000303|PubMed:9353126};
CC IsoId=O16850-3; Sequence=VSP_053107;
CC Name=d {ECO:0000312|WormBase:R13H8.1d};
CC IsoId=O16850-5; Sequence=VSP_053108;
CC Name=e {ECO:0000312|WormBase:R13H8.1e};
CC IsoId=O16850-6; Sequence=VSP_053105;
CC Name=f {ECO:0000312|WormBase:R13H8.1f};
CC IsoId=O16850-1; Sequence=VSP_042148;
CC Name=g {ECO:0000312|WormBase:R13H8.1g};
CC IsoId=O16850-7; Sequence=VSP_042147, VSP_042149;
CC -!- TISSUE SPECIFICITY: Isoform b and isoform c are expressed in ectoderm,
CC muscles, intestine and neurons (PubMed:9353126, PubMed:11747825,
CC PubMed:14622602, PubMed:17894411). Isoform b is also expressed in the
CC pharynx (PubMed:11747821). The intestine appears to be the primary site
CC of longevity function (PubMed:14622602). {ECO:0000269|PubMed:11747821,
CC ECO:0000269|PubMed:11747825, ECO:0000269|PubMed:14622602,
CC ECO:0000269|PubMed:17894411, ECO:0000269|PubMed:9353126}.
CC -!- DEVELOPMENTAL STAGE: Expressed in embryos, larvae, dauer larvae and
CC adults. {ECO:0000269|PubMed:9353126}.
CC -!- DEVELOPMENTAL STAGE: [Isoform a]: Expression throughout the body
CC increases slightly with age. {ECO:0000269|PubMed:24834345}.
CC -!- DEVELOPMENTAL STAGE: [Isoform d]: Expression increases substantially
CC with age. {ECO:0000269|PubMed:24834345}.
CC -!- DEVELOPMENTAL STAGE: [Isoform f]: Expression increases substantially
CC with age. {ECO:0000269|PubMed:24834345}.
CC -!- INDUCTION: Induced by quinic acid. {ECO:0000269|PubMed:22950425}.
CC -!- PTM: Phosphorylated by akt-1 and/or akt-2 (PubMed:18358814,
CC PubMed:21531333). Phosphorylated by sgk-1 (PubMed:18358814).
CC Phosphorylated by unc-43 (PubMed:23805378). Phosphorylated by jnk-1
CC (PubMed:15767565). Dephosphorylated by tax-6 in vitro
CC (PubMed:23805378). {ECO:0000269|PubMed:15767565,
CC ECO:0000269|PubMed:18358814, ECO:0000269|PubMed:21531333,
CC ECO:0000269|PubMed:23805378}.
CC -!- PTM: Ubiquitinated. Ubiquitination by rle-1 leads to proteasome-
CC mediated degradation. {ECO:0000269|PubMed:17276341}.
CC -!- PTM: Methylation by prmt-1 prevents phosphorylation and promotes
CC translocation to the nucleus to allow for daf-16-dependent
CC transcription. {ECO:0000269|PubMed:21531333}.
CC -!- DISRUPTION PHENOTYPE: Dauer defective phenotype in larvae and a reduced
CC stress phenotype in adults (PubMed:9360933). Increased carbonyl
CC accumulation and increased sensitivity to starvation (PubMed:18025456).
CC Increased expression of the srh-234 chemoreceptor during starvation
CC (PubMed:25357003). Increased sensitivity to physical injury and more
CC susceptible to death by nematophagous fungal infection
CC (PubMed:24146615). Increased lifespan (PubMed:23805378). Causes a delay
CC in apoptosis during embryonic development (PubMed:25383666). Defective
CC gustatory associative learning in response to salt cues
CC (PubMed:30779740). RNAi-mediated knock-down reduces expression of daf-
CC 16 target genes and genes up-regulated in response to nematophagous
CC fungal infection such as sod-3 (PubMed:24146615). RNAi-mediated
CC knockdown causes reduced ability of dietary restriction to extend
CC lifespan (PubMed:17900900). Simultaneous RNAi-mediated knockdown of
CC metalloproteinase zmp-2 restores normal survival upon heat stress and
CC prevents increased susceptibility to heat stress in a daf-9 or daf-12
CC mutant background (PubMed:24957743). RNAi-mediated knockdown in a daf-2
CC (e1370) mutant background restores expression of deubiquitinase ubh-4
CC in the intestine (PubMed:23770237). RNAi-mediated knockdown suppresses
CC the decreased number of mitotic nuclei in the germline of developing
CC larvae in an atg-18 (gk378) or atg-16.2 (ok3224) mutant background.
CC Suppresses associative memory, axon regeneration and fkh-9 transcript
CC levels, in a daf-2 mutant background. {ECO:0000269|PubMed:17900900,
CC ECO:0000269|PubMed:18025456, ECO:0000269|PubMed:23770237,
CC ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:24146615,
CC ECO:0000269|PubMed:24957743, ECO:0000269|PubMed:25357003,
CC ECO:0000269|PubMed:25383666, ECO:0000269|PubMed:26675724,
CC ECO:0000269|PubMed:30779740, ECO:0000269|PubMed:9360933}.
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DR EMBL; AF020342; AAB84390.1; -; mRNA.
DR EMBL; AF020343; AAB84391.1; -; mRNA.
DR EMBL; AF020344; AAB84392.1; -; mRNA.
DR EMBL; AF032112; AAC47803.1; -; mRNA.
DR EMBL; BX284601; CCD71850.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD71851.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD71852.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD71853.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD71854.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD71855.1; -; Genomic_DNA.
DR EMBL; FO080113; CCD71855.1; JOINED; Genomic_DNA.
DR EMBL; BX284601; CCD71856.1; -; Genomic_DNA.
DR EMBL; FO080113; CCD71856.1; JOINED; Genomic_DNA.
DR EMBL; BX284601; CCD71857.1; -; Genomic_DNA.
DR EMBL; FO080113; CCD71857.1; JOINED; Genomic_DNA.
DR PIR; T42234; T42234.
DR PIR; T42255; T42255.
DR RefSeq; NP_001021593.1; NM_001026422.4. [O16850-2]
DR RefSeq; NP_001021594.1; NM_001026423.4.
DR RefSeq; NP_001021595.1; NM_001026424.4.
DR RefSeq; NP_001021596.1; NM_001026425.3. [O16850-5]
DR RefSeq; NP_001021597.1; NM_001026426.2.
DR RefSeq; NP_001021598.2; NM_001026427.4. [O16850-1]
DR RefSeq; NP_001251490.1; NM_001264561.1.
DR RefSeq; NP_001251492.1; NM_001264563.1.
DR AlphaFoldDB; O16850; -.
DR SMR; O16850; -.
DR BioGRID; 38392; 70.
DR ComplexPortal; CPX-3882; daf-16-ftt-2 complex.
DR ComplexPortal; CPX-3883; daf-16-sir-2.1 complex.
DR ComplexPortal; CPX-3884; daf-16-par-5 complex.
DR DIP; DIP-25581N; -.
DR IntAct; O16850; 23.
DR STRING; 6239.R13H8.1h; -.
DR iPTMnet; O16850; -.
DR EPD; O16850; -.
DR PaxDb; O16850; -.
DR PeptideAtlas; O16850; -.
DR EnsemblMetazoa; R13H8.1a.1; R13H8.1a.1; WBGene00000912. [O16850-2]
DR EnsemblMetazoa; R13H8.1b.1; R13H8.1b.1; WBGene00000912. [O16850-4]
DR EnsemblMetazoa; R13H8.1c.1; R13H8.1c.1; WBGene00000912. [O16850-3]
DR EnsemblMetazoa; R13H8.1d.1; R13H8.1d.1; WBGene00000912. [O16850-5]
DR EnsemblMetazoa; R13H8.1e.1; R13H8.1e.1; WBGene00000912. [O16850-6]
DR EnsemblMetazoa; R13H8.1f.1; R13H8.1f.1; WBGene00000912. [O16850-1]
DR EnsemblMetazoa; R13H8.1h.1; R13H8.1h.1; WBGene00000912. [O16850-8]
DR GeneID; 172981; -.
DR UCSC; R13H8.1c; c. elegans.
DR CTD; 172981; -.
DR WormBase; R13H8.1a; CE28771; WBGene00000912; daf-16. [O16850-2]
DR WormBase; R13H8.1b; CE28772; WBGene00000912; daf-16. [O16850-4]
DR WormBase; R13H8.1c; CE28773; WBGene00000912; daf-16. [O16850-3]
DR WormBase; R13H8.1d; CE38722; WBGene00000912; daf-16. [O16850-5]
DR WormBase; R13H8.1e; CE33160; WBGene00000912; daf-16. [O16850-6]
DR WormBase; R13H8.1f; CE44821; WBGene00000912; daf-16. [O16850-1]
DR WormBase; R13H8.1g; CE44935; WBGene00000912; daf-16. [O16850-7]
DR WormBase; R13H8.1h; CE45185; WBGene00000912; daf-16. [O16850-8]
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000170843; -.
DR InParanoid; O16850; -.
DR OMA; TTDHRLN; -.
DR OrthoDB; 1160384at2759; -.
DR PhylomeDB; O16850; -.
DR Reactome; R-CEL-1181150; Signaling by NODAL.
DR Reactome; R-CEL-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-CEL-211163; AKT-mediated inactivation of FOXO1A.
DR Reactome; R-CEL-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-CEL-5689880; Ub-specific processing proteases.
DR Reactome; R-CEL-9607240; FLT3 Signaling.
DR Reactome; R-CEL-9614399; Regulation of localization of FOXO transcription factors.
DR Reactome; R-CEL-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR Reactome; R-CEL-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR Reactome; R-CEL-9617828; FOXO-mediated transcription of cell cycle genes.
DR Reactome; R-CEL-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR SignaLink; O16850; -.
DR PRO; PR:O16850; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00000912; Expressed in larva and 5 other tissues.
DR ExpressionAtlas; O16850; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0071889; F:14-3-3 protein binding; IPI:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; IPI:WormBase.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:WormBase.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:WormBase.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:WormBase.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:1990381; F:ubiquitin-specific protease binding; IPI:WormBase.
DR GO; GO:0007568; P:aging; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0034605; P:cellular response to heat; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; IGI:ParkinsonsUK-UCL.
DR GO; GO:0042994; P:cytoplasmic sequestering of transcription factor; IC:ComplexPortal.
DR GO; GO:0040024; P:dauer larval development; IGI:WormBase.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:WormBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IDA:UniProtKB.
DR GO; GO:0010286; P:heat acclimation; IGI:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IMP:WormBase.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:WormBase.
DR GO; GO:0051457; P:maintenance of protein location in nucleus; IC:ComplexPortal.
DR GO; GO:0060537; P:muscle tissue development; IMP:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IC:ComplexPortal.
DR GO; GO:0040015; P:negative regulation of multicellular organism growth; IMP:WormBase.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0002119; P:nematode larval development; IMP:UniProtKB.
DR GO; GO:0002821; P:positive regulation of adaptive immune response; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0061066; P:positive regulation of dauer larval development; IMP:WormBase.
DR GO; GO:1900426; P:positive regulation of defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:1900075; P:positive regulation of neuromuscular synaptic transmission; IGI:UniProtKB.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; IGI:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:WormBase.
DR GO; GO:0010564; P:regulation of cell cycle process; IEP:UniProtKB.
DR GO; GO:1905909; P:regulation of dauer entry; IGI:UniProtKB.
DR GO; GO:0061065; P:regulation of dauer larval development; IGI:UniProtKB.
DR GO; GO:0043620; P:regulation of DNA-templated transcription in response to stress; IMP:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0046890; P:regulation of lipid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0010883; P:regulation of lipid storage; IGI:UniProtKB.
DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; IGI:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IGI:UniProtKB.
DR GO; GO:0042594; P:response to starvation; IMP:UniProtKB.
DR GO; GO:0009411; P:response to UV; IDA:UniProtKB.
DR GO; GO:0007614; P:short-term memory; IGI:WormBase.
DR GO; GO:0030431; P:sleep; IGI:UniProtKB.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00250; Forkhead; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasm; Developmental protein; DNA-binding;
KW Growth regulation; Immunity; Innate immunity; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Stress response; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..541
FT /note="Forkhead box protein O"
FT /evidence="ECO:0000305"
FT /id="PRO_0000414886"
FT DNA_BIND 175..268
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 118..168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 252..291
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 118..158
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 273
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:21531333"
FT MOD_RES 319
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000269|PubMed:23805378"
FT VAR_SEQ 1..238
FT /note="Missing (in isoform e)"
FT /evidence="ECO:0000305"
FT /id="VSP_053105"
FT VAR_SEQ 1..221
FT /note="MQLEQKSSLHCSKCRNFLQKFSQDMQAWNCRELDSPLPSDITLHNLEPARPD
FT SGMSFSTDFDDDFFNLDLHQQERSASFGGVTQYSQQFLREKCSFSPYFHTSLETVDSGR
FT TSLYGSNEQCGQLGGASSNGSTAMLHTPDGSNSHQTSFPSDFRMSESPDDTVSGKKTTT
FT RRNAWGNMSYAELITTAIMASPEKRLTLAQVYEWMVQNVPYFRDKGDSNSS -> MNDS
FT IDDDFPPEPRGRCYTWPMQQYIYQESSATIPHHHLNQHNNPYHPMHPHHQLPHMQQLPQ
FT PLLNLNMTTLTSSGSSVASSIGGGAQCSPCASGSSTAATNSSQQQQTVGQMLAASVPCS
FT SSGMTLGMSLNLSQGGGPMPAKKKRCRKKPTDQLAQKKPNPWGEESYSDIIAKALESAP
FT DGRLKLNEIYQWFSDNIPYFGERSSPEEA (in isoform a)"
FT /evidence="ECO:0000303|PubMed:9353126"
FT /id="VSP_053106"
FT VAR_SEQ 1..217
FT /note="Missing (in isoform g)"
FT /evidence="ECO:0000305"
FT /id="VSP_042147"
FT VAR_SEQ 1..113
FT /note="MQLEQKSSLHCSKCRNFLQKFSQDMQAWNCRELDSPLPSDITLHNLEPARPD
FT SGMSFSTDFDDDFFNLDLHQQERSASFGGVTQYSQQFLREKCSFSPYFHTSLETVDSGR
FT TS -> MMEMLVDQGTDASSSASTSTSSVSRFGADTFMNTPDDVMMNDDMEPIPRDRCN
FT TWPMRRPQLEPPLNSSPIIHEQIPEEDAD (in isoform b and isoform c)"
FT /evidence="ECO:0000303|PubMed:9353126,
FT ECO:0000303|PubMed:9360933"
FT /id="VSP_053107"
FT VAR_SEQ 1..54
FT /note="Missing (in isoform d)"
FT /evidence="ECO:0000305"
FT /id="VSP_053108"
FT VAR_SEQ 1..24
FT /note="Missing (in isoform f)"
FT /evidence="ECO:0000305"
FT /id="VSP_042148"
FT VAR_SEQ 152..154
FT /note="DFR -> E (in isoform b)"
FT /evidence="ECO:0000303|PubMed:9353126"
FT /id="VSP_053109"
FT VAR_SEQ 218..225
FT /note="SNSSAGWK -> MREMSTKN (in isoform g)"
FT /evidence="ECO:0000305"
FT /id="VSP_042149"
FT MUTAGEN 266
FT /note="R->K: Decreases methylation by prmt-1; when
FT associated with K-268 and K-270."
FT /evidence="ECO:0000269|PubMed:21531333"
FT MUTAGEN 268
FT /note="R->K: Decreases methylation by prmt-1; when
FT associated with K-266 and K-270. Prevents phosphorylation
FT by akt 1 and/or 2; when associated with K-270."
FT /evidence="ECO:0000269|PubMed:21531333"
FT MUTAGEN 270
FT /note="R->K: Decreases methylation by prmt-1; when
FT associated with K-266 and K-268. Prevents phosphorylation
FT by akt 1 and/or 2; when associated with K-268."
FT /evidence="ECO:0000269|PubMed:21531333"
FT MUTAGEN 271
FT /note="S->A: Prevents phosphorylation and results in strong
FT nuclear localization. Reduces phosphorylation; when
FT associated with A-273."
FT /evidence="ECO:0000269|PubMed:11381260,
FT ECO:0000269|PubMed:21531333"
FT MUTAGEN 273
FT /note="T->A: Prevents phosphorylation and results in strong
FT nuclear localization."
FT /evidence="ECO:0000269|PubMed:11381260"
FT MUTAGEN 273
FT /note="T->A: Reduces phosphorylation in normal and starved
FT conditions. Reduces phosphorylation; when associated with
FT A-271."
FT /evidence="ECO:0000269|PubMed:21531333"
FT MUTAGEN 319
FT /note="S->A: Prevents phosphorylation and results in
FT cytoplasmic localization in unc-43 n498 gain-of-function or
FT tax-6 mutant backgrounds."
FT /evidence="ECO:0000269|PubMed:23805378"
FT MUTAGEN 319
FT /note="S->D: Phosphomimetic mutant which causes
FT constitutive nuclear localization."
FT /evidence="ECO:0000269|PubMed:23805378"
FT MUTAGEN 345
FT /note="S->A: Prevents phosphorylation and results in strong
FT nuclear localization."
FT /evidence="ECO:0000269|PubMed:11381260"
FT MUTAGEN 373..541
FT /note="Missing: In m27; defective dauer phase entry, but
FT animals are capable of entering a partial dauer state with
FT some dauer morphological characteristics. Reduces dex-1
FT expression in seam cells during the dauer phase."
FT /evidence="ECO:0000269|PubMed:30409788"
SQ SEQUENCE 541 AA; 59732 MW; 8A36A86311A32CBB CRC64;
MQLEQKSSLH CSKCRNFLQK FSQDMQAWNC RELDSPLPSD ITLHNLEPAR PDSGMSFSTD
FDDDFFNLDL HQQERSASFG GVTQYSQQFL REKCSFSPYF HTSLETVDSG RTSLYGSNEQ
CGQLGGASSN GSTAMLHTPD GSNSHQTSFP SDFRMSESPD DTVSGKKTTT RRNAWGNMSY
AELITTAIMA SPEKRLTLAQ VYEWMVQNVP YFRDKGDSNS SAGWKNSIRH NLSLHSRFMR
IQNEGAGKSS WWVINPDAKP GRNPRRTRER SNTIETTTKA QLEKSRRGAK KRIKERALMG
SLHSTLNGNS IAGSIQTISH DLYDDDSMQG AFDNVPSSFR PRTQSNLSIP GSSSRVSPAI
GSDIYDDLEF PSWVGESVPA IPSDIVDRTD QMRIDATTHI GGVQIKQESK PIKTEPIAPP
PSYHELNSVR GSCAQNPLLR NPIVPSTNFK PMPLPGAYGN YQNGGITPIN WLSTSNSSPL
PGIQSCGIVA AQHTVASSSA LPIDLENLTL PDQPLMDTMD VDALIRHELS QAGGQHIHFD
L
