FOXO1_XENLA
ID FOXO1_XENLA Reviewed; 631 AA.
AC Q6EUW2;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Forkhead box protein O1;
DE Short=FoxO1;
DE Short=xFoxO1;
DE AltName: Full=FoxO1A;
GN Name=foxo1 {ECO:0000303|PubMed:15567714};
GN Synonyms=foxo1a {ECO:0000250|UniProtKB:Q66JJ0};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000305, ECO:0000312|EMBL:CAH04456.1}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Tadpole {ECO:0000269|PubMed:15567714};
RX PubMed=15567714; DOI=10.1016/j.modgep.2004.08.009;
RA Pohl B.S., Schoen C., Roessner A., Knoechel W.;
RT "The FoxO-subclass in Xenopus laevis development.";
RL Gene Expr. Patterns 5:187-192(2004).
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 -!- TISSUE SPECIFICITY: Localized to the animal hemisphere during early
CC cleavage stages. At early tadpole stages, expressed in the branchial
CC arches, pronephros and liver. Within the head, expressed in the forming
CC thyroid gland and in head mesenchyme anterior to the eyes.
CC {ECO:0000269|PubMed:15567714}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Maternal expression decreases during early cleavage stages becoming
CC absent during gastrulation. Zygotic expression begins during
CC neurulation with expression levels increasing as development
CC progresses. {ECO:0000269|PubMed:15567714}.
CC -!- PTM: Phosphorylated by AKT1; insulin-induced.
CC {ECO:0000250|UniProtKB:Q9R1E0}.
CC -!- PTM: IGF1 rapidly induces phosphorylation of Thr-28, Ser-245 and Ser-
CC 308. Phosphorylation of Ser-245 decreases DNA-binding activity and
CC promotes the phosphorylation of Thr-28, and Ser-308, which leads to
CC nuclear exclusion and loss of function. Phosphorylation of Ser-318 is
CC independent of IGF1 and leads to reduced function (By similarity).
CC {ECO:0000250|UniProtKB:Q12778}.
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DR EMBL; AJ783963; CAH04456.1; -; mRNA.
DR RefSeq; NP_001086417.1; NM_001092948.1.
DR AlphaFoldDB; Q6EUW2; -.
DR SMR; Q6EUW2; -.
DR GeneID; 444991; -.
DR KEGG; xla:444991; -.
DR CTD; 444991; -.
DR Xenbase; XB-GENE-482532; foxo1.L.
DR Proteomes; UP000186698; Chromosome 2L.
DR Bgee; 444991; Expressed in spleen and 18 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: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: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: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..631
FT /note="Forkhead box protein O1"
FT /id="PRO_0000270986"
FT DNA_BIND 149..243
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..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 223..324
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 372..404
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..147
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 262..318
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 631 AA; 68468 MW; 8AE83E8A7D936845 CRC64;
MAEAPQPPPP LVEIDPDFEP FSRPRSCTWP LPRPEFNPSS SANSSPAPSL QPEPAAGNVD
FLSNLSLLEE SEDFDPAEAL GVCGDFPCQD IRQLQPPIPQ QQQQHSQQQQ EALTLLAPSV
PSALSPASSP SPLGAQQPRK SSSSRRNAWG NLSYADLISQ AIESSPEKRL TLSQIYDWMV
KSVPYFKDKG DSNSSAGWKN SIRHNLSLHS KFVRVQNEGT GKSSWWILNP EGGKNGKSPR
RRAASMDNNS KFAKSRGRAA KKKASMQSSQ DGSSDSPGSQ FSKWPGSPSS QSNDDFEAWS
TFRPRTSSNA STISGRLSPI MPEQDDLGDA DVHNLVYPSS ATKLTSTLPS LSEMGNSENM
ENLLDNLNLL TPNSSTQSSP ASMMQQSGYL FTSPNTSLGS PNSEYRKYSY AQTGISPISQ
MPMQTVPENK SGYRAVGQYP VPAGLLKELL TSDSPPHNDI LTPVDPAVSQ ANNRVLGQNS
LIGSNSIMPA YGSQPAPNKM SSHPHLHQPN HPTSINGRPI AHNPGINRLS TVKTSVQVPM
PHQPIQMTSM GSYSMNSCNG YGRVGIVSIH QEILPSDLDD MLIESLDCDV ESIIRNDLME
DGEADFNFDS ILPNQSFPHS VTTTTHSWVS G
