ID   FOXO_DROER              Reviewed;         615 AA.
AC   B3P0K6;
DT   10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT   10-AUG-2010, sequence version 2.
DT   03-AUG-2022, entry version 66.
DE   RecName: Full=Forkhead box protein O {ECO:0000250|UniProtKB:Q95V55};
GN   Name=foxo {ECO:0000250|UniProtKB:Q95V55}; ORFNames=GG16833;
OS   Drosophila erecta (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7220;
RN   [1] {ECO:0000312|EMBL:EDV48832.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tucson 14021-0224.01 {ECO:0000312|EMBL:EDV48832.1};
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=EDV48832.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; CH954181; EDV48832.1; ALT_SEQ; Genomic_DNA.
DR   RefSeq; XP_001979874.2; XM_001979838.2.
DR   AlphaFoldDB; B3P0K6; -.
DR   SMR; B3P0K6; -.
DR   eggNOG; KOG2294; Eukaryota.
DR   ChiTaRS; foxo; fly.
DR   Proteomes; UP000008711; 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; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..615
FT                   /note="Forkhead box protein O"
FT                   /id="PRO_0000396505"
FT   DNA_BIND        95..201
FT                   /note="Fork-head"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT   REGION          39..77
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          182..205
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          217..269
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          318..359
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          389..409
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        59..77
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        182..198
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        219..233
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        252..267
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        338..359
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         44
FT                   /note="Phosphothreonine; by PKB/AKT1"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
FT   MOD_RES         75
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
FT   MOD_RES         190
FT                   /note="Phosphoserine; by PKB/AKT1"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
FT   MOD_RES         259
FT                   /note="Phosphoserine; by PKB/AKT1"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
FT   MOD_RES         262
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
FT   MOD_RES         263
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
FT   MOD_RES         268
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
SQ   SEQUENCE   615 AA;  67270 MW;  CE33DED57A74ADA5 CRC64;
     MMDGFAQDWP TLTHTDNGLA MDQLGGDLPL DVGFEPQTRA RSNTWPCPRP ENFVEPTDEL
     DSTKASNQQL APGDSQQAIQ NANAAKKNSS RRNAWGNLSY ADLITHAIGS ATDKRLTLSQ
     IYEWMVQNVP YFKDKGDSNS SAGWKNSIRH NLSLHNRFMR VQNEGTGKSS WWMLNPEAKP
     GKSVRRRAAS METSRYEKRR GRAKKRVEAL RQAGVVGLND ATPSPSSSVS EGLDHFPESP
     LHSGGGFQLS PDFRQRASSN ASSCGRLSPI RAQDLEPDWG FPVDYQNTTM TQAHAQALDE
     LTGTMADELT LCPQQQGFSA ASGLPSQPPP PPYQPPQHQQ AQQQQQQSPY ALNGPAPGYN
     TLQPQSQCLL HRSLNCSCMH NARDGLSPNS VTTTMSPAYP NSEPSSDSLN TYSNVVLDGP
     ADTAALMVQQ QQQQQQMSAS LEGQCLEVLN NEAQPIDEFN LENFPVGNLE CNVEELLQQE
     MSYGGLLDIN IPLATVNTNL VNSSSGPLSI SNISNLSNLS NISNISNISS NSGSSLSLNQ
     LQAQLQQQQQ QQAQQQQAQQ QQQAHQQHQQ QLLLNNNNNS SSSLELATQT ASANLNARVQ
     YSQPSVVTSP PSWVH