FOXO_DROGR
ID FOXO_DROGR Reviewed; 630 AA.
AC B4JSC2;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Forkhead box protein O {ECO:0000250|UniProtKB:Q95V55};
GN Name=foxo {ECO:0000250|UniProtKB:Q95V55}; ORFNames=GH22274;
OS Drosophila grimshawi (Hawaiian fruit fly) (Idiomyia grimshawi).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Hawaiian Drosophila.
OX NCBI_TaxID=7222;
RN [1] {ECO:0000312|EMBL:EDV94662.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tucson 15287-2541.00 {ECO:0000312|EMBL:EDV94662.1};
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; CH916373; EDV94662.1; -; Genomic_DNA.
DR RefSeq; XP_001993926.1; XM_001993890.1.
DR AlphaFoldDB; B4JSC2; -.
DR SMR; B4JSC2; -.
DR STRING; 7222.FBpp0156180; -.
DR EnsemblMetazoa; FBtr0157688; FBpp0156180; FBgn0129734.
DR GeneID; 6567837; -.
DR KEGG; dgr:6567837; -.
DR eggNOG; KOG2294; Eukaryota.
DR HOGENOM; CLU_024472_1_0_1; -.
DR InParanoid; B4JSC2; -.
DR OMA; EWMMQNI; -.
DR PhylomeDB; B4JSC2; -.
DR ChiTaRS; foxo; fly.
DR Proteomes; UP000001070; 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..630
FT /note="Forkhead box protein O"
FT /id="PRO_0000396506"
FT DNA_BIND 92..198
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 214..260
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 318..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 403..432
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 216..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..379
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 187
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 255
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 258
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 264
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
SQ SEQUENCE 630 AA; 70007 MW; AC170BFA1232B5C5 CRC64;
MDGFVQEWSN LPRSDNGLHM DQLVGELPTD GGFEPQTRAR SNTWPCPRPE NFVEPVDELD
STKASNQQLA DPQQAMQNAN AAKKNSSRRN AWGNLSYADL ITHAIGSATD KRLTLSQIYE
WMVQNVAYFK DKGDSNSSAG WKNSIRHNLS LHSRFMRVQN EGTGKSSWWM LNPDAKPGKS
VRRRAASMET SRYEKRRGRA KKRVEALRQA GAVGLNDATP SPSSSVSEGL DHFPESPLHS
GGFQLSPDFR QRASSNASSC GRLSPIRALD LEPDWGYSVD YQNTTMTQAQ AQALDQLTGS
MADELKLQND MLQQQGFSAA SGLPTQPPPP YQQQQQQQQQ QAQQQSQLPQ GYTLNGPVSA
PGYNTLQPQA QQQQQQQQQQ QQQQQQPQCL LHRSLNCGCL HSTRDGLSPN SVTTTMSPAY
PNSEPSSDSL NTYSNSILLD AASDNGSLLV QQQQQQQQQQ QQQQQQQQQL SSGLEGQCLE
ALNSEQIDEF NLENFQGGLE CNVEELLQQE MIYDGLLDIN IPLPAVNTNA TNVILTNNST
NNSSSGCNIS AGVQLSCSQL QAELQLQQQQ QQQQQQQQQQ QQQQQQQQQQ LLLSNNNNNN
NNSLELATQT ATRVQYTQPS VVTSPPSWVH
