FOXO3_XENLA
ID FOXO3_XENLA Reviewed; 657 AA.
AC Q6EUW1; Q5XG59;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Forkhead box protein O3 {ECO:0000305};
DE Short=FoxO3 {ECO:0000303|PubMed:15567714};
DE Short=xFoxO3 {ECO:0000303|PubMed:15567714};
GN Name=foxo3 {ECO:0000303|PubMed:15567714};
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]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC TISSUE=Tadpole;
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).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Kidney;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Transcriptional activator that recognizes and binds to the
CC DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes,
CC such as apoptosis and autophagy. Acts as a positive regulator of
CC autophagy in skeletal muscle: in starved cells, enters the nucleus
CC following dephosphorylation and binds the promoters of autophagy genes,
CC thereby activating their expression, resulting in proteolysis of
CC skeletal muscle proteins (By similarity). Triggers apoptosis in the
CC absence of survival factors, including neuronal cell death upon
CC oxidative stress (By similarity). In response to metabolic stress,
CC translocates into the mitochondria where it promotes mtDNA
CC transcription. Also acts as a key regulator of chondrogenic commitment
CC of skeletal progenitor cells in response to lipid availability: when
CC lipids levels are low, translocates to the nucleus and promotes
CC expression of sox9, which induces chondrogenic commitment and
CC suppresses fatty acid oxidation (By similarity). Also acts as a key
CC regulator of regulatory T-cells (Treg) differentiation (By similarity).
CC {ECO:0000250|UniProtKB:O43524, ECO:0000250|UniProtKB:Q9WVH4}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O43524}. Nucleus {ECO:0000250|UniProtKB:O43524}.
CC Note=Retention in the cytoplasm contributes to its inactivation (By
CC similarity). Translocates to the nucleus upon oxidative stress and in
CC the absence of survival factors (By similarity).
CC {ECO:0000250|UniProtKB:O43524}.
CC -!- TISSUE SPECIFICITY: Localized to the animal hemisphere during early
CC cleavage stages. At the late neurula, localized in the anterior neural
CC plate, neural crest cells and in the hatching gland (PubMed:15567714).
CC As development progresses, expression becomes less localized, being
CC observed in a variety of organs and tissues including the head,
CC branchial arches and somites by stage 32 (PubMed:15567714).
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 (PubMed:15567714). Zygotic expression begins
CC during neurulation and expression levels decrease rapidly through the
CC early tadpole stages before becoming enhanced again up till stage 39
CC (PubMed:15567714). {ECO:0000269|PubMed:15567714}.
CC -!- PTM: Dephosphorylation may promote translocation to the nucleus where
CC the protein induces transcription of target genes and triggers
CC apoptosis. {ECO:0000250|UniProtKB:O43524}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AJ783964; CAH04457.1; -; mRNA.
DR EMBL; BC084603; AAH84603.1; -; mRNA.
DR RefSeq; NP_001086418.1; NM_001092949.1.
DR AlphaFoldDB; Q6EUW1; -.
DR SMR; Q6EUW1; -.
DR PRIDE; Q6EUW1; -.
DR GeneID; 444992; -.
DR KEGG; xla:444992; -.
DR CTD; 444992; -.
DR Xenbase; XB-GENE-945076; foxo3.L.
DR OrthoDB; 1160384at2759; -.
DR Proteomes; UP000186698; Chromosome 5L.
DR Bgee; 444992; Expressed in muscle tissue and 19 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0014737; P:positive regulation of muscle atrophy; ISS:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; 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:0006357; P:regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0070542; P:response to fatty acid; ISS:UniProtKB.
DR GO; GO:0042594; P:response to starvation; ISS:UniProtKB.
DR GO; GO:0033209; P:tumor necrosis factor-mediated signaling pathway; 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 Activator; Apoptosis; Cytoplasm; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..657
FT /note="Forkhead box protein O3"
FT /id="PRO_0000270988"
FT DNA_BIND 142..236
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..71
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 216..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 27..53
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 259..287
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 294..311
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 21
FT /note="G -> E (in Ref. 2; AAH84603)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="G -> GGGQQ (in Ref. 2; AAH84603)"
FT /evidence="ECO:0000305"
FT CONFLICT 287
FT /note="K -> E (in Ref. 2; AAH84603)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 657 AA; 70384 MW; D4C60C71AD4EC7A9 CRC64;
MAEALPPRSP PDDVDIDPDF GPQSRPRSCT WPLQRLDSQG SPGKPNSGAG EAADTSSMIP
EEEDDDYEGA ASTATVLGTA GDKGTLVLLS GGESGQLAVL ASPVGGVETL QVSLGGEGAG
GAVSGAGGQQ QQRKCSSRRN AWGNMSYADL ITRAIESTQD KRLTLSQIYD WMVRSVPYFK
DKGDSNSSAG WKNSIRHNLS LHSRFIRVQN EGSGKSSWWM INPEGGKGGK APRRRAVSMD
NSNKYTKSRG RAAKKKASLQ ASSDATDDSP SQLSKWPGSP TSRSSDKLDT WTDFRSRTNS
NASTISGRLS PIPATTELDD VQDDDSPLSP MLYNSPGSLS PSISKPCTVE MPRITDMAET
MNLNDGLPEN LMDDLLDDIS LTSSQQSSPG VLMQRSSSFT YGTKGSGIGS PSNNFNNTGS
FNFPLTSLRQ SPMQTIQENK QATFSSMNHY SNQSLQDLLN TDTLSHSDVL MTQSDPLMSQ
ASTAVTAQNS RRNIILRNDP MMSFAAQPNQ GGNLVNQNSL HQQQSLNSFQ GGSRALSNNL
SNTGLNDSSI LESTKHQQQS SVSHSMQTIS DTLSGSLYSS GVTLPTLGHE KFPTDLDLDI
FNGSLECDME TIIRNDLMDA DGLDFNFDTL ISAQNVSLSV GSFTGAKQTS SQSWVPG
