FOXO_DROPS
ID FOXO_DROPS Reviewed; 644 AA.
AC Q298W7;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 2.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Forkhead box protein O {ECO:0000250|UniProtKB:Q95V55};
GN Name=foxo {ECO:0000250|UniProtKB:Q95V55}; ORFNames=GA16248;
OS Drosophila pseudoobscura pseudoobscura (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=46245;
RN [1] {ECO:0000312|EMBL:EAL27838.2}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MV2-25 / Tucson 14011-0121.94;
RX PubMed=15632085; DOI=10.1101/gr.3059305;
RA Richards S., Liu Y., Bettencourt B.R., Hradecky P., Letovsky S.,
RA Nielsen R., Thornton K., Hubisz M.J., Chen R., Meisel R.P., Couronne O.,
RA Hua S., Smith M.A., Zhang P., Liu J., Bussemaker H.J., van Batenburg M.F.,
RA Howells S.L., Scherer S.E., Sodergren E., Matthews B.B., Crosby M.A.,
RA Schroeder A.J., Ortiz-Barrientos D., Rives C.M., Metzker M.L., Muzny D.M.,
RA Scott G., Steffen D., Wheeler D.A., Worley K.C., Havlak P., Durbin K.J.,
RA Egan A., Gill R., Hume J., Morgan M.B., Miner G., Hamilton C., Huang Y.,
RA Waldron L., Verduzco D., Clerc-Blankenburg K.P., Dubchak I., Noor M.A.F.,
RA Anderson W., White K.P., Clark A.G., Schaeffer S.W., Gelbart W.M.,
RA Weinstock G.M., Gibbs R.A.;
RT "Comparative genome sequencing of Drosophila pseudoobscura: chromosomal,
RT gene, and cis-element evolution.";
RL Genome Res. 15:1-18(2005).
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; CM000070; EAL27838.2; -; Genomic_DNA.
DR RefSeq; XP_001358695.2; XM_001358658.3.
DR AlphaFoldDB; Q298W7; -.
DR SMR; Q298W7; -.
DR STRING; 7237.FBpp0282082; -.
DR EnsemblMetazoa; FBtr0283644; FBpp0282082; FBgn0076264.
DR KEGG; dpo:Dpse_GA16248; -.
DR eggNOG; KOG2294; Eukaryota.
DR HOGENOM; CLU_024472_1_0_1; -.
DR InParanoid; Q298W7; -.
DR OMA; EWMMQNI; -.
DR ChiTaRS; foxo; fly.
DR Proteomes; UP000001819; Genome assembly.
DR Bgee; FBgn0076264; Expressed in insect adult head and 2 other tissues.
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..644
FT /note="Forkhead box protein O"
FT /id="PRO_0000396509"
FT DNA_BIND 100..206
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 39..75
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 187..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 222..276
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 329..386
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 412..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 578..612
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 187..203
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 224..238
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 257..272
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 329..347
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 362..386
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 49
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 195
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 264
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 273
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
SQ SEQUENCE 644 AA; 70843 MW; 218BB2B8C25AD24C CRC64;
MMDGFAQDWP TLTHTDNGLA MDQLSGVVGG GDLPGDVGFE PQTRARSNTW PCPRPENFVE
PPDELDSTKA SNQQLAAGDS QQAIQNANAA KKNSSRRNAW GNLSYADLIT HAIGSATDKR
LTLSQIYEWM VQNVPYFKDK GDSNSSAGWK NSIRHNLSLH NRFMRVQNEG TGKSSWWMLN
PEAKPGKSVR RRAASMETSR YEKRRGRAKK RVEALRQAGV VGLNDATPSP SSSVSEGLDH
FPESPLHSGG GFQLSPDFRQ RASSNASSCG RLSPIRAQDL EPQDLWGFPV DYQNTTMTQA
HAQALEELTG SMADELTLCN QQQQQQQQQQ QQQQQQQQQQ GFSAASGLPS QPPPPPYQPP
QLQQQQQQQP SYSLNGPAPG GYQTLQPQSQ SQCLLHRSLN CSCLHNARDG LSPNSVTTTM
SPAYPNSEPS SDSLNTYSNV VLDGSSDLLV QQQQQQQLQQ QQVKVEFEGQ CLEVLNNEAQ
PIDEFNLENF PVGNLECNVE ELLQQEMSYD GLLDINIPLA NVSTNAPLVN LVNNSTTLSS
SSSNLSGSTT TLSSSSLSAA VQLNQLQAQL QQQQQQQQQH LQQQQQHHQH QQQLLLNNNN
NNNNNNSSNS SLDLATQTAA TNLNAARVQY SQPSVVTSPP SWVH
