FOXO_DROWI
ID FOXO_DROWI Reviewed; 628 AA.
AC B4NFR1;
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=GK22687;
OS Drosophila willistoni (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7260;
RN [1] {ECO:0000312|EMBL:EDW83128.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tucson 14030-0811.24 {ECO:0000312|EMBL:EDW83128.1};
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; CH964251; EDW83128.1; -; Genomic_DNA.
DR RefSeq; XP_002072142.2; XM_002072106.2.
DR AlphaFoldDB; B4NFR1; -.
DR SMR; B4NFR1; -.
DR STRING; 7260.FBpp0251830; -.
DR GeneID; 6649777; -.
DR KEGG; dwi:6649777; -.
DR eggNOG; KOG2294; Eukaryota.
DR HOGENOM; CLU_024472_1_0_1; -.
DR InParanoid; B4NFR1; -.
DR OMA; EWMMQNI; -.
DR OrthoDB; 1160384at2759; -.
DR PhylomeDB; B4NFR1; -.
DR ChiTaRS; foxo; fly.
DR Proteomes; UP000007798; 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..628
FT /note="Forkhead box protein O"
FT /id="PRO_0000396512"
FT DNA_BIND 101..207
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 188..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 223..270
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 327..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 398..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 188..204
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 225..239
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 256..270
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..346
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 347..361
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 50
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 81
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 196
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 628 AA; 68745 MW; 59C05750ABB6BEB4 CRC64;
MDGFAQDWPS LTHTTDNVLT MDQLGGVSGA VGDLPGDVGF EPQTRARSNT WPCPHPEPFV
EPADELDSTK ASNQQLAAGD SQQTIQSANA AKKNSARRNA WGNLSYADLI THAIGSATDK
RLTLSQIYEW MVQNVPYFKD KGDSNSSAGW KNSIRHNLSL HNRFMRVQNE GTGKSSWWML
NPEAKPGKSV RRRAASMETS RYEKRRGRAK KRVEALRQAG VVGLNDATPS PSSSVSEGLD
HFPESPLHSG GFQLSPDFRQ RASSNASSCG RLSPIRALDL EPEWGFTVDY QNTTLTQAQS
QVLDQLAGSI ADELKLHPDM LQQQGFSAAS GLPTQPPPPP YPAPQQQQQQ QPQQQQAYTL
NGGPPGGYAS LQPQPQCLIH RSLNCSCLHN ARDGLSPNSV TTTMSPAYPN SEPSSDSLNT
YSNVVIDGSG DNGSLLVQQQ RQQQQQQQQQ QQLGSNLEGQ CLEVLNNEAQ PIDEFNLENF
PVENLECNME ELLQQEMSYD GLLDINIPLA AVSTNAPLVN LINNSSTTIS SSSNIGCSTT
TSSSSLSASA QLNQLQAQLQ QQHQQQQQQQ QQQQQQQLQQ QQQQLLLNNN NNNNNSLELA
TQTASANLNA RVQYSQPSVV TSPPSWVH
