FOXO_DROMO
ID FOXO_DROMO Reviewed; 563 AA.
AC B4KBF6;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Forkhead box protein O {ECO:0000250|UniProtKB:Q95V55};
GN Name=foxo {ECO:0000250|UniProtKB:Q95V55}; ORFNames=GI21984;
OS Drosophila mojavensis (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila.
OX NCBI_TaxID=7230;
RN [1] {ECO:0000312|EMBL:EDW16884.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tucson 15081-1352.22 {ECO:0000312|EMBL:EDW16884.1};
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}.
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DR EMBL; CH933806; EDW16884.1; -; Genomic_DNA.
DR RefSeq; XP_002001423.2; XM_002001387.2.
DR AlphaFoldDB; B4KBF6; -.
DR SMR; B4KBF6; -.
DR STRING; 7230.FBpp0171201; -.
DR GeneID; 6575413; -.
DR KEGG; dmo:Dmoj_GI21984; -.
DR eggNOG; KOG2294; Eukaryota.
DR HOGENOM; CLU_024472_1_0_1; -.
DR InParanoid; B4KBF6; -.
DR OMA; EWMMQNI; -.
DR PhylomeDB; B4KBF6; -.
DR ChiTaRS; foxo; fly.
DR Proteomes; UP000009192; 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..563
FT /note="Forkhead box protein O"
FT /id="PRO_0000396507"
FT DNA_BIND 90..196
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..72
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 177..243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 317..371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..72
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..193
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 214..228
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 335..371
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 185
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 253
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 256
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
SQ SEQUENCE 563 AA; 61986 MW; AA8D7DC2EAFCB037 CRC64;
MDDFAQEWPN LPRSDNGLQM DQLVGDLPTD GGFEPQTRAR SNTWPCPRPE PVDELDSTKA
SNQQLANGDP QQAMQNANAA KKNSSRRNAW GNLSYADLIT HAIGSATDKR LTLSQIYEWM
VQNVSYFKDK GDSNSSAGWK NSIRHNLSLH NRFMRVQNEG TGKSSWWMLN PEAKPGKSVR
RRAASMETSR YEKRRGRAKK RVEALRQAGV VGLNDATPSP SSSVSEGLDH FPESPLHSGS
YQLSPDFRQR ASSNASSCGR LSPIRALDLE PDWGFPVDYP NTTLTQAQVQ VFDQLAGSMA
DELKLHTDML QQQGFSAASG LPTQPPPPYQ PPQHPQHTQG YALNGPGLSP NSVTTTMSPA
YPNSEPSSDS LNTYSNVLLE AAADNAALLV QQQQQQQQQQ QHASTLIGQC LEALNSEPIE
EFNLENFQGG LECNVEELLH QELCYDGMLD INIPLAAVNT NATNVILTNN STNSSSSNSN
NSVAGNSSAN LQLSQLQAQL QLQQQQQQQQ QQQQQQQQQQ QQLLLSNNNN NNNNSLDTAS
ANLNARVQYT QPSVVTSPPS WVH
