FOXO1_RAT
ID FOXO1_RAT Reviewed; 649 AA.
AC G3V7R4;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Forkhead box protein O1;
DE AltName: Full=Forkhead box protein O1A;
DE AltName: Full=Forkhead in rhabdomyosarcoma;
GN Name=Foxo1; Synonyms=Foxo1a;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-281 AND SER-323, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [4]
RP FUNCTION.
RX PubMed=26436652; DOI=10.1172/jci82423;
RA Huang Z.P., Kataoka M., Chen J., Wu G., Ding J., Nie M., Lin Z., Liu J.,
RA Hu X., Ma L., Zhou B., Wakimoto H., Zeng C., Kyselovic J., Deng Z.L.,
RA Seidman C.E., Seidman J.G., Pu W.T., Wang D.Z.;
RT "Cardiomyocyte-enriched protein CIP protects against pathophysiological
RT stresses and regulates cardiac homeostasis.";
RL J. Clin. Invest. 125:4122-4134(2015).
CC -!- FUNCTION: Transcription factor that is the main target of insulin
CC signaling and regulates metabolic homeostasis in response to oxidative
CC stress (By similarity). Binds to the insulin response element (IRE)
CC with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16
CC family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-
CC 3'. Activity suppressed by insulin (By similarity). Main regulator of
CC redox balance and osteoblast numbers and controls bone mass (By
CC similarity). Orchestrates the endocrine function of the skeleton in
CC regulating glucose metabolism (By similarity). Also acts as a key
CC regulator of chondrogenic commitment of skeletal progenitor cells in
CC response to lipid availability: when lipids levels are low,
CC translocates to the nucleus and promotes expression of SOX9, which
CC induces chondrogenic commitment and suppresses fatty acid oxidation (By
CC similarity). Acts synergistically with ATF4 to suppress
CC osteocalcin/BGLAP activity, increasing glucose levels and triggering
CC glucose intolerance and insulin insensitivity (By similarity). Also
CC suppresses the transcriptional activity of RUNX2, an upstream activator
CC of osteocalcin/BGLAP (By similarity). Acts as an inhibitor of glucose
CC sensing in pancreatic beta cells by acting as a transcription repressor
CC and suppressing expression of PDX1 (By similarity). In hepatocytes,
CC promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to
CC activate the expression of genes such as IGFBP1, G6PC1 and PCK1 (By
CC similarity). Also promotes gluconeogenesis by directly promoting
CC expression of PPARGC1A and G6PC1 (By similarity). Important regulator
CC of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1 (By
CC similarity). Promotes neural cell death (By similarity). Mediates
CC insulin action on adipose tissue (By similarity). Regulates the
CC expression of adipogenic genes such as PPARG during preadipocyte
CC differentiation and, adipocyte size and adipose tissue-specific gene
CC expression in response to excessive calorie intake (By similarity).
CC Regulates the transcriptional activity of GADD45A and repair of nitric
CC oxide-damaged DNA in beta-cells (By similarity). Required for the
CC autophagic cell death induction in response to starvation or oxidative
CC stress in a transcription-independent manner (By similarity). Mediates
CC the function of MLIP in cardiomyocytes hypertrophy and cardiac
CC remodeling (PubMed:26436652). Regulates endothelial cell (EC) viability
CC and apoptosis in a PPIA/CYPA-dependent manner via transcription of CCL2
CC and BCL2L11 which are involved in EC chemotaxis and apoptosis (By
CC similarity). {ECO:0000250|UniProtKB:Q12778,
CC ECO:0000250|UniProtKB:Q9R1E0, ECO:0000269|PubMed:26436652}.
CC -!- SUBUNIT: Interacts with LRPPRC. Interacts with RUNX2; the interaction
CC inhibits RUNX2 transcriptional activity and mediates the IGF1/insulin-
CC dependent BGLAP expression in osteoblasts Interacts with PPP2R1A; the
CC interaction regulates the dephosphorylation of FOXO1 at Thr-24 and Ser-
CC 250 leading to its nuclear import. Interacts with NLK. Interacts with
CC SIRT1; the interaction results in the deacetylation of FOXO1 leading to
CC activation of FOXO1-mediated transcription of genes involved in DNA
CC repair and stress resistance. Binds to CDK1. Interacts with the 14-3-3
CC proteins, YWHAG and YWHAZ; the interactions require insulin-stimulated
CC phosphorylation on Thr-24, promote nuclear exit and loss of
CC transcriptional activity. Interacts with SKP2; the interaction
CC ubiquitinates FOXO1 leading to its proteosomal degradation. The
CC interaction requires the presence of KRIT1. Interacts (via the C-
CC terminal half) with ATF4 (via its DNA binding domain); the interaction
CC occurs in osteoblasts, regulates glucose homeostasis via suppression of
CC beta-cell proliferation and subsequent decrease in insulin production.
CC Interacts with PRMT1; the interaction methylates FOXO1, prevents
CC PKB/AKT1 phosphorylation and retains FOXO1 in the nucleus. Interacts
CC with EP300 and CREBBP; the interactions acetylate FOXO1. Interacts with
CC SIRT2; the interaction is disrupted in response to oxidative stress or
CC serum deprivation, leading to increased level of acetylated FOXO1,
CC which promotes stress-induced autophagy by stimulating E1-like
CC activating enzyme ATG7. Interacts (acetylated form) with ATG7; the
CC interaction is increased in response to oxidative stress or serum
CC deprivation and promotes the autophagic process leading to cell death.
CC Interacts (acetylated form) with PPARG. Interacts with XBP1; this
CC interaction is direct and leads to FOXO1 ubiquitination and degradation
CC via the proteasome pathway (By similarity). Interacts (via the Fork-
CC head domain) with CEBPA; the interaction increases when FOXO1 is
CC deacetylated. Interacts with WDFY2. Forms a complex with WDFY2 and AKT1
CC (By similarity). Interacts with CRY1 (By similarity). Interacts with
CC PPIA/CYPA; the interaction promotes FOXO1 dephosphorylation, nuclear
CC accumulation and transcriptional activity (By similarity). Interacts
CC with TOX4; FOXO1 is required for full induction of TOX4-dependent
CC activity and the interaction is inhibited by insulin (By similarity).
CC {ECO:0000250|UniProtKB:Q12778, ECO:0000250|UniProtKB:Q9R1E0}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9R1E0}. Nucleus
CC {ECO:0000250|UniProtKB:Q9R1E0}. Note=Shuttles between the cytoplasm and
CC nucleus (By similarity). Largely nuclear in unstimulated cells (By
CC similarity). In osteoblasts, colocalizes with ATF4 and RUNX2 in the
CC nucleus. Serum deprivation increases localization to the nucleus,
CC leading to activate expression of SOX9 and subsequent chondrogenesis
CC (By similarity). Insulin-induced phosphorylation at Ser-253 by PKB/AKT1
CC leads, via stimulation of Thr-24 phosphorylation, to binding of 14-3-3
CC proteins and nuclear export to the cytoplasm where it is degraded by
CC the ubiquitin-proteosomal pathway (By similarity). Phosphorylation at
CC Ser-249 by CDK1 disrupts binding of 14-3-3 proteins and promotes
CC nuclear accumulation (By similarity). Phosphorylation by NLK results in
CC nuclear export (By similarity). Translocates to the nucleus upon
CC oxidative stress-induced phosphorylation at Ser-212 by STK4/MST1 (By
CC similarity). SGK1-mediated phosphorylation also results in nuclear
CC translocation. Retained in the nucleus under stress stimuli including
CC oxidative stress, nutrient deprivation or nitric oxide. Methylated form
CC is nuclear (By similarity). PPIA/CYPA stimulates its nuclear
CC accumulation (By similarity). Deacetylation by SIRT6, promotes its
CC translocation into the cytoplasm (By similarity).
CC {ECO:0000250|UniProtKB:Q12778, ECO:0000250|UniProtKB:Q9R1E0}.
CC -!- PTM: Phosphorylation by NLK promotes nuclear export and inhibits the
CC transcriptional activity. In response to growth factors,
CC phosphorylation on Thr-24, Ser-250 and Ser-313 by PKB/AKT1 promotes
CC nuclear export and inactivation of transactivational activity.
CC Phosphorylation on Thr-24 is required for binding 14-3-3 proteins.
CC Phosphorylation of Ser-250 decreases DNA-binding activity and promotes
CC the phosphorylation of Thr-24 and Ser-313, permitting phosphorylation
CC of Ser-316 and Ser-319, probably by CDK1, leading to nuclear exclusion
CC and loss of function. Stress signals, such as response to oxygen or
CC nitric oxide, attenuate the PKB/AKT1-mediated phosphorylation leading
CC to nuclear retention. Phosphorylation of Ser-323 is independent of IGF1
CC and leads to reduced function. Dephosphorylated on Thr-24 and Ser-250
CC by PP2A in beta-cells under oxidative stress leading to nuclear
CC retention. Phosphorylation of Ser-243 by CDK1 disrupts binding of 14-3-
CC 3 proteins leading to nuclear accumulation and has no effect on DNA
CC binding nor transcriptional activity. Phosphorylation by STK4/MST1 on
CC Ser-206, upon oxidative stress, inhibits binding to 14-3-3 proteins and
CC nuclear export (By similarity). PPIA/CYPA promotes its
CC dephosphorylation on Ser-250 (By similarity).
CC {ECO:0000250|UniProtKB:Q12778, ECO:0000250|UniProtKB:Q9R1E0}.
CC -!- PTM: Ubiquitinated by SKP2. Ubiquitination leads to proteasomal
CC degradation (By similarity). {ECO:0000250|UniProtKB:Q12778}.
CC -!- PTM: Methylation inhibits AKT1-mediated phosphorylation at Ser-250 and
CC is increased by oxidative stress. {ECO:0000250|UniProtKB:Q9R1E0}.
CC -!- PTM: Acetylation at Lys-256 and Lys-268 are necessary for autophagic
CC cell death induction. Deacetylated by SIRT2 in response to oxidative
CC stress or serum deprivation, thereby negatively regulating FOXO1-
CC mediated autophagic cell death. Once in the nucleus, acetylated by
CC CREBBP/EP300. Acetylation diminishes the interaction with target DNA
CC and attenuates the transcriptional activity. It increases the
CC phosphorylation at Ser-250. Deacetylation by SIRT1 results in
CC reactivation of the transcriptional activity. Oxidative stress by
CC hydrogen peroxide treatment appears to promote deacetylation and
CC uncoupling of insulin-induced phosphorylation. By contrast, resveratrol
CC acts independently of acetylation (By similarity). {ECO:0000250}.
CC -!- PTM: Acetylated. Acetylation at Lys-256 and Lys-268 are necessary for
CC autophagic cell death induction. Deacetylated by SIRT2 in response to
CC oxidative stress or serum deprivation, thereby negatively regulating
CC FOXO1-mediated autophagic cell death. Once in the nucleus, acetylated
CC by CREBBP/EP300. Acetylation diminishes the interaction with target DNA
CC and attenuates the transcriptional activity. It increases the
CC phosphorylation at Ser-250. Deacetylation by SIRT1 results in
CC reactivation of the transcriptional activity. Oxidative stress by
CC hydrogen peroxide treatment appears to promote deacetylation and
CC uncoupling of insulin-induced phosphorylation. By contrast, resveratrol
CC acts independently of acetylation. Acetylated at Lys-417, promoting its
CC localization to the nucleus and transcription factor activity.
CC Deacetylation at Lys-417 by SIRT6, promotes its translocation into the
CC cytoplasm, preventing its transcription factor activity. Deacetylation
CC and subsequent inhibition by SIRT6 has different effects depending on
CC cell types: it inhibits gluconeogenesis in hepatocytes, promotes
CC glucose sensing in pancreatic beta-cells and regulates lipid catabolism
CC in brown adipocytes. {ECO:0000250|UniProtKB:Q12778}.
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DR EMBL; CH474003; EDM14970.1; -; Genomic_DNA.
DR RefSeq; NP_001178775.1; NM_001191846.2.
DR AlphaFoldDB; G3V7R4; -.
DR SMR; G3V7R4; -.
DR BioGRID; 249982; 3.
DR STRING; 10116.ENSRNOP00000018244; -.
DR iPTMnet; G3V7R4; -.
DR PhosphoSitePlus; G3V7R4; -.
DR PaxDb; G3V7R4; -.
DR PRIDE; G3V7R4; -.
DR Ensembl; ENSRNOT00000018244; ENSRNOP00000018244; ENSRNOG00000013397.
DR GeneID; 84482; -.
DR KEGG; rno:84482; -.
DR CTD; 2308; -.
DR RGD; 620283; Foxo1.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000161558; -.
DR HOGENOM; CLU_023456_1_1_1; -.
DR InParanoid; G3V7R4; -.
DR OMA; KMMSPSS; -.
DR OrthoDB; 1160384at2759; -.
DR TreeFam; TF315583; -.
DR Reactome; R-RNO-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-RNO-211163; AKT-mediated inactivation of FOXO1A.
DR Reactome; R-RNO-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-RNO-9614399; Regulation of localization of FOXO transcription factors.
DR Reactome; R-RNO-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR Reactome; R-RNO-9617828; FOXO-mediated transcription of cell cycle genes.
DR PRO; PR:G3V7R4; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Proteomes; UP000234681; Chromosome 2.
DR Bgee; ENSRNOG00000013397; Expressed in ovary and 19 other tissues.
DR Genevisible; G3V7R4; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0008013; F:beta-catenin binding; ISO:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISO:RGD.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0001568; P:blood vessel development; ISO:RGD.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEP:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0071455; P:cellular response to hyperoxia; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISS:UniProtKB.
DR GO; GO:0071732; P:cellular response to nitric oxide; ISS:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
DR GO; GO:0070166; P:enamel mineralization; IEP:RGD.
DR GO; GO:0042593; P:glucose homeostasis; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; IMP:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0046676; P:negative regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0032873; P:negative regulation of stress-activated MAPK cascade; ISO:RGD.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; ISS:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0006111; P:regulation of gluconeogenesis; ISO:RGD.
DR GO; GO:2000177; P:regulation of neural precursor cell proliferation; ISO:RGD.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0070542; P:response to fatty acid; ISS:UniProtKB.
DR GO; GO:1902617; P:response to fluoride; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR032067; FOXO-TAD.
DR InterPro; IPR032068; FOXO_KIX-bd.
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 Pfam; PF16676; FOXO-TAD; 1.
DR Pfam; PF16675; FOXO_KIX_bdg; 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 Acetylation; Activator; Apoptosis; Autophagy; Cytoplasm; Differentiation;
KW DNA-binding; Methylation; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..649
FT /note="Forkhead box protein O1"
FT /id="PRO_0000419245"
FT DNA_BIND 154..248
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 112..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 205..212
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT REGION 228..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 228..231
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT REGION 277..557
FT /note="Sufficient for interaction with NLK"
FT /evidence="ECO:0000250|UniProtKB:Q9R1E0"
FT REGION 357..453
FT /note="Required for interaction with RUNX2"
FT /evidence="ECO:0000250|UniProtKB:Q9R1E0"
FT MOTIF 245..247
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 456..460
FT /note="Required for interaction with SIRT1"
FT /evidence="ECO:0000250|UniProtKB:Q9R1E0"
FT COMPBIAS 27..62
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 113..137
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..324
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 152
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT SITE 159
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT SITE 219
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 24
FT /note="Phosphothreonine; by PKB/AKT1 or PKB/AKT2 and SGK1"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 206
FT /note="Phosphoserine; by STK4/MST1"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 228
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 239
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R1E0"
FT MOD_RES 242
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9R1E0"
FT MOD_RES 243
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 245
FT /note="Omega-N-methylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:Q9R1E0"
FT MOD_RES 247
FT /note="Omega-N-methylarginine; by PRMT1"
FT /evidence="ECO:0000250|UniProtKB:Q9R1E0"
FT MOD_RES 250
FT /note="Phosphoserine; by PKB/AKT1 and SGK1"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 256
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 259
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 268
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 292
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9R1E0"
FT MOD_RES 313
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q9R1E0"
FT MOD_RES 316
FT /note="Phosphoserine; by CK1 and SGK1"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 319
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 323
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 327
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9R1E0"
FT MOD_RES 417
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
SQ SEQUENCE 649 AA; 69344 MW; 6232AA82C12F5AEA CRC64;
MAEAPQVVET DPDFEPLPRQ RSCTWPLPRP EFNQSNSTTS SPAPSGSTAA NPDATASLAS
ASAVSTDFMS NLSLLEESED FARAPGCVAV AAAAAASRGL CGDFQGPEAG CVHSAPPQPP
PTGPLSQPPP VPPAAAGPLA GQPRKTSSSR RNAWGNLSYA DLITKAIESS AEKRLTLSQI
YEWMVKSVPY FKDKGDSNSS AGWKNSIRHN LSLHSKFIRV QNEGTGKSSW WMLNPEGGKS
GKSPRRRAAS MDNNSKFAKS RGRAAKKKAS LQSGQEGPGD SPGSQFSKWP ASPGSHSNDD
FDNWSTFRPR TSSNASTISG RLSPIMTEQD DLGDGDVHSL VYPPSAAKMA STLPSLSEIS
NPENMENLLD NLNLLSSPTS LTVSTQSSPG SMMQQTPCYS FAPPNTSLNS PSPNYAKYTY
GQSSMSPVPQ MPMQTLQDSK SSYGGLNQYN CAPGLLKELL TSDSPPHNDI MSPVDPGVAQ
PNSRVLGQNV LMGPNSVMPA YGSQAPHNKM MNPSSHTHPG HAQQTSSVNG RALPHVVNTM
PHTSAMNRLT PVKTPLQVPL SHPMQMSALG NYSSVSSCNG YGRMGVLHQE KLPSDLDGMF
IERLDCDMES IIRNDLMDGD TLDFNFDNVL PNQSFPHSVK TTTHSWVSG
