FOXO_DROSE
ID FOXO_DROSE Reviewed; 609 AA.
AC B4HF64;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 2.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Forkhead box protein O {ECO:0000250|UniProtKB:Q95V55};
GN Name=foxo {ECO:0000250|UniProtKB:Q95V55}; ORFNames=GM24148;
OS Drosophila sechellia (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7238;
RN [1] {ECO:0000312|EMBL:EDW42238.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Rob3c / Tucson 14021-0248.25 {ECO:0000312|EMBL:EDW42238.1};
RX PubMed=17994087; DOI=10.1038/nature06341;
RG Drosophila 12 genomes consortium;
RT "Evolution of genes and genomes on the Drosophila phylogeny.";
RL Nature 450:203-218(2007).
CC -!- FUNCTION: Transcription factor involved in the regulation of the
CC insulin signaling pathway. Consistently activates both the downstream
CC target Thor\d4EBP and the feedback control target InR. Involved in
CC negative regulation of the cell cycle, modulating cell growth and
CC proliferation. In response to cellular stresses, such as nutrient
CC deprivation or increased levels of reactive oxygen species, foxo is
CC activated and inhibits growth through the action of target genes such
CC as Thor. Foxo activated in the adult fat body can regulate lifespan in
CC adults; an insulin peptide itself may function as one secondary
CC messenger of insulin-regulated aging. Also regulates Lip4, homolog of
CC human acid lipases, thereby acting as a key modulator of lipid
CC metabolism by insulin signaling and integrates insulin responses to
CC glucose and lipid homeostasis (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with melt. {ECO:0000250|UniProtKB:Q95V55}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q95V55}. Nucleus
CC {ECO:0000250|UniProtKB:Q95V55, ECO:0000255|PROSITE-ProRule:PRU00089}.
CC Note=When phosphorylated, translocated from nucleus to cytoplasm.
CC Dephosphorylation triggers nuclear translocation (By similarity).
CC {ECO:0000250|UniProtKB:Q95V55}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EDW42238.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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; CH480815; EDW42238.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_002031252.1; XM_002031216.1.
DR AlphaFoldDB; B4HF64; -.
DR SMR; B4HF64; -.
DR STRING; 7238.B4HF64; -.
DR ChiTaRS; foxo; fly.
DR Proteomes; UP000001292; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS: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 3: Inferred from homology;
KW Activator; Cell cycle; Cytoplasm; Developmental protein; Differentiation;
KW DNA-binding; Growth regulation; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..609
FT /note="Forkhead box protein O"
FT /id="PRO_0000396510"
FT DNA_BIND 94..200
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 38..89
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 181..204
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 216..264
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 316..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..89
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 181..197
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..232
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 337..358
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 43
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 189
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 258
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
SQ SEQUENCE 609 AA; 66893 MW; B4DA5D1569978D93 CRC64;
MDGYAQEWPR LTHTDNGLAM DQLGGDLPLD VGFEPQTRAR SNTWPCPRPE NFVEPTDELD
STKASNQQLA PGDSQQAIQN ANAAKKNSSR RNAWGNLSYA DLITHAIGSA ADKRLTLSQI
YEWMVQNVPY FKDKGDSNSS AGWKNSIRHN LSLHNRFMRV QNEGTGKSSW WMLNPEAKPG
KSVRRRAASM ETSRYEKRRG RAKKRVEALR QAGVVGLNDA TPSPSSSVSE GLDHFPESPL
HSGGGFQLSP DFRQRASSNA SSCGRLSPIR ALDLEPDWGF PVDYQNTTMT QAHAQALEEL
TGTMADELTL CTQQQQGFSA ASGLPSQPPH PPYQPPQHQQ GQQQQQSPYA LNGPAPGYNT
LQPQSQCLLH RSLNCSCMHN ARDGLSPNSV TTTMSPAYPN SEPSSDSLNT YSNVVLDGPA
DTAALMVQQQ QQQQQQQMST SLEGQCLEVL NNEAQPIDEF NLENFPVGNL ECNVEELLQQ
EMSYGGLLDI NIPLATVNTN VVNSSSGPLS ISNISNLSNI SSNSGSSLSL NQLQAQLQQQ
QQQAQQQQQQ QAQQQQQQHQ QHQQQLLLNN NNNGSSSLEL ATQTVSTNLN ARVQYSQPSV
VTSPPSWVH
