FOXO1_XENTR
ID FOXO1_XENTR Reviewed; 626 AA.
AC Q66JJ0;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 03-AUG-2022, entry version 115.
DE RecName: Full=Forkhead box protein O1;
DE Short=FoxO1;
DE AltName: Full=FoxO1A;
GN Name=foxo1 {ECO:0000250|UniProtKB:Q6EUW2};
GN Synonyms=foxo1a {ECO:0000312|EMBL:AAH80894.1};
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1] {ECO:0000312|EMBL:AAH80894.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tail bud {ECO:0000312|EMBL:AAH80894.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Transcription factor that regulates metabolic homeostasis in
CC response to oxidative stress. Binds to the consensus sequence 5'-
CC TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE)
CC with consensus sequence 5'-TT[G/A]TTTAC-3'. Main regulator of redox
CC balance and osteoblast numbers and controls bone mass. Orchestrates the
CC endocrine function of the skeleton in regulating glucose metabolism.
CC Also acts as a key regulator of chondrogenic commitment of skeletal
CC progenitor cells in response to lipid availability: when lipids levels
CC are low, translocates to the nucleus and promotes expression of sox9,
CC which induces chondrogenic commitment and suppresses fatty acid
CC oxidation. Acts synergistically with atf4 to suppress osteocalcin/bglap
CC activity, increasing glucose levels and triggering glucose intolerance
CC and insulin insensitivity. Also suppresses the transcriptional activity
CC of runx2, an upstream activator of osteocalcin/bglap.
CC {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. {ECO:0000250|UniProtKB:Q9R1E0}.
CC -!- PTM: Phosphorylated by AKT1; insulin-induced.
CC {ECO:0000250|UniProtKB:Q9R1E0}.
CC -!- PTM: IGF1 rapidly induces phosphorylation of Thr-28, Ser-240 and Ser-
CC 303. Phosphorylation of Ser-240 decreases DNA-binding activity and
CC promotes the phosphorylation of Thr-28, and Ser-303, which leads to
CC nuclear exclusion and loss of function. Phosphorylation of Ser-313 is
CC independent of IGF1 and leads to reduced function (By similarity).
CC {ECO:0000250|UniProtKB:Q12778}.
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DR EMBL; BC080894; AAH80894.1; -; mRNA.
DR RefSeq; NP_001008016.1; NM_001008015.1.
DR AlphaFoldDB; Q66JJ0; -.
DR SMR; Q66JJ0; -.
DR DNASU; 493378; -.
DR Ensembl; ENSXETT00000101788; ENSXETP00000076822; ENSXETG00000036259.
DR GeneID; 493378; -.
DR KEGG; xtr:493378; -.
DR CTD; 2308; -.
DR Xenbase; XB-GENE-482528; foxo1.
DR InParanoid; Q66JJ0; -.
DR OrthoDB; 1160384at2759; -.
DR Reactome; R-XTR-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-XTR-211163; AKT-mediated inactivation of FOXO1A.
DR Reactome; R-XTR-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-XTR-9614399; Regulation of localization of FOXO transcription factors.
DR Reactome; R-XTR-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR Reactome; R-XTR-9617828; FOXO-mediated transcription of cell cycle genes.
DR Proteomes; UP000008143; Chromosome 2.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000036259; Expressed in liver and 12 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0070417; P:cellular response to cold; ISS:UniProtKB.
DR GO; GO:0071455; P:cellular response to hyperoxia; ISS:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0046676; P:negative regulation of insulin secretion; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006473; P:protein acetylation; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0070542; P:response to fatty acid; ISS:UniProtKB.
DR GO; GO:0001659; P:temperature homeostasis; ISS:UniProtKB.
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 2: Evidence at transcript level;
KW Cytoplasm; DNA-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation.
FT CHAIN 1..626
FT /note="Forkhead box protein O1"
FT /id="PRO_0000270987"
FT DNA_BIND 144..238
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 90..142
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 218..319
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 484..519
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..51
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 94..142
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 257..313
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 626 AA; 67806 MW; 210E6A483347B9C1 CRC64;
MAEAPLPPPP GVEVDPDFEP FSRPRSCTWP LPRPEFNPSS SANSSPAPSL QPEPAAGNVD
FLSNLSLLEE SEDFDPAEAL GVCGDFPCQD IRQLQPPVPQ QHPQQQAGTL CAPSVPSALS
PASSPSPLGA QQPRKSSSSR RNAWGNLSYA DLISQAIESS PEKRLTLSQI YDWMVKSVPY
FKDKGDSNSS AGWKNSIRHN LSLHSKFVRV QNEGTGKSSW WILNPEGGKN GKSPRRRAAS
MDNNSKFAKS RGRAAKKKAT MQSSQDGSSD SPGSQFSKWP GSPSSQSNDD FEAWSTFRPR
TSSNASTISG RLSPIMPEQD DLGDADVHNL VYPPSATKLT STLPSLSEMG NSENMENLLD
NLNLLSPNTS TQSSPASMMQ QSGYLFTSPN TSLGSPNSEY RKYSYAQTGM NPVSQMPMQT
VPENKSGYRA VGQYPVPAGL LKELLTSDSP PHNDILTPVD SAVSQANSRV LAQNSLMAPS
SVMPTYGSQP THNKMSSHPH SHQPPPNHPS VNGRTMTHNS GINRLSTVKT SVQVPMPQPI
QMTSMGSYPV NSCNGYGRVG IVSIHQEILP SDLDDMFIES LDCDMESIIR NDLMEDGEAD
FNFDSILPNQ SFPHSVTTTT HSWVSG
