ID   FOXO_DROVI              Reviewed;         609 AA.
AC   B4MB78;
DT   10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT   23-SEP-2008, sequence version 1.
DT   03-AUG-2022, entry version 70.
DE   RecName: Full=Forkhead box protein O {ECO:0000250|UniProtKB:Q95V55};
GN   Name=foxo {ECO:0000250|UniProtKB:Q95V55}; ORFNames=GJ14344;
OS   Drosophila virilis (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila.
OX   NCBI_TaxID=7244;
RN   [1] {ECO:0000312|EMBL:EDW58349.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Tucson 15010-1051.87 {ECO:0000312|EMBL:EDW58349.1};
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   ---------------------------------------------------------------------------
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; CH940656; EDW58349.1; -; Genomic_DNA.
DR   RefSeq; XP_002058381.1; XM_002058345.2.
DR   AlphaFoldDB; B4MB78; -.
DR   SMR; B4MB78; -.
DR   STRING; 7244.FBpp0228761; -.
DR   EnsemblMetazoa; FBtr0230269; FBpp0228761; FBgn0201557.
DR   eggNOG; KOG2294; Eukaryota.
DR   HOGENOM; CLU_024472_1_0_1; -.
DR   InParanoid; B4MB78; -.
DR   OMA; EWMMQNI; -.
DR   PhylomeDB; B4MB78; -.
DR   ChiTaRS; foxo; fly.
DR   Proteomes; UP000008792; 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_0000396511"
FT   DNA_BIND        94..200
FT                   /note="Fork-head"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT   REGION          1..89
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          181..263
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          321..365
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          384..411
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        60..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        249..263
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        325..339
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        386..411
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         189
FT                   /note="Phosphoserine; by PKB/AKT1"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
FT   MOD_RES         257
FT                   /note="Phosphoserine; by PKB/AKT1"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
FT   MOD_RES         260
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
FT   MOD_RES         261
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
FT   MOD_RES         266
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q95V55"
SQ   SEQUENCE   609 AA;  66919 MW;  794692F13C690D92 CRC64;
     MDGFAQDWPN LPRSDNGLHM DQLVGELPTD GGFEPQTRAR SNTWPCPRPE NFVEPVDELD
     STKASNQQLA SGDPQQAMQN ANAAKKNSSR RNAWGNLSYA DLITHAIGSA TDKRLTLSQI
     YEWMVQNVSY FKDKGDSNSS AGWKNSIRHN LSLHNRFMRV QNEGTGKSSW WMLNPEAKPG
     KSVRRRAASM ETSRYEKRRG RAKKRVEALR QGGVVGLNDA TPSPSSSVSE GLDHFPESPL
     HSGGFQLSPD FRQRASSNAS SCGRLSPIRA LDLEPDWGFS VDYQNTTMTQ AQAQQLDQLA
     GSMAEELKLQ SDMLQQQGFS AASGLPTQPP PPYQPPQQPQ LPQGYSLNGP GYAAMQPQPQ
     PQGQGQCLLH RSLNCGCLHS APVRDGLSPN SVTTTMSPAY PNSEPSSDSL NTYSNVLLDG
     SADNAALLVQ HQQQQQQQQQ QQRQQLSSGL EGQCLEALNS EQIDEFNLED FQGGLECNVE
     ELLQQEMRYD GLLDINIPLA AVNTNTNNVI LTNNSTNSGS SNAASNSSAG VQLNQLQAQL
     QLQQQQQQQQ QQQQHQQQLL MSNNNNNNNN NNNSNNSLEL ATQTATANLN ARVQYSQPSV
     VTSPPSWVH