FOXO_DROPE
ID FOXO_DROPE Reviewed; 629 AA.
AC B4G4S8;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 2.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Forkhead box protein O {ECO:0000250|UniProtKB:Q95V55};
GN Name=foxo {ECO:0000250|UniProtKB:Q95V55}; ORFNames=GL24235;
OS Drosophila persimilis (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7234;
RN [1] {ECO:0000312|EMBL:EDW24594.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MSH-3 / Tucson 14011-0111.49 {ECO:0000312|EMBL:EDW24594.1};
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 -!- SEQUENCE CAUTION:
CC Sequence=EDW24594.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AAIZ01000342; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH479179; EDW24594.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_002013608.1; XM_002013572.1.
DR AlphaFoldDB; B4G4S8; -.
DR SMR; B4G4S8; -.
DR STRING; 7234.FBpp0188342; -.
DR eggNOG; KOG2294; Eukaryota.
DR ChiTaRS; foxo; fly.
DR Proteomes; UP000008744; 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..629
FT /note="Forkhead box protein O"
FT /id="PRO_0000396508"
FT DNA_BIND 98..204
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 185..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 220..274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 321..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 394..417
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 563..597
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 185..201
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 222..236
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..270
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 344..368
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 78
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 193
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 262
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 265
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 271
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
SQ SEQUENCE 629 AA; 69129 MW; 48A2EF1D7B5E95C6 CRC64;
MMDSFAQDWP TLTHTDNGLA MDQLSGVVGG GDLPGDVGFE PQTRARSNTW PCPRPENFVE
QADELDSTKA SNQQLADSQQ AIQNANAAKK NSSRRNAWGN LSYADLITHA IGSATDKRLT
LSQIYEWMVQ NVPYFKDKGD SNSSAGWKNS IRHNLSLHNR FMRVQNEGTG KSSWWMLNPE
AKPGKSVRRR AASMETSRYE KRRGRAKKRV EALRQAGVVG LNDATPSPSS SVSEGLDHFP
ESPLHSGGGF QLSPDFRQRA SSNASSCGRL SPIRAQDLEP QDLWGFPVDY QNTTMTQAHA
QALEELTGSM ADELTLCNQQ QQQFSAASGL PSQPPPPPYQ PPQLQQQQQQ QPSYSLNGPA
PGGYQTLQPQ SQSQCLLHRS LNCSCLHNAR DGLSPNSVTT TMSPAYPNSE PSSDSLNTYS
NVVLDGSSDL LVQQQQQQQL QQQQVKVEFE GQCLEVLNNE AQPIDEFNLE NFPVGNLECN
VEELLQQEMS YDGLLDINIP LANVSTNAPL VSLVNNSTTL SSSSSNLSGS TTTLSSSSLS
AAVQLNQLQA QLQQQQQQQQ QQQHLQQQQQ QHHQHQQQLL LNNNNNNNNN NSSNSSLDLA
TQTAATNLNA ARVQYSQPSV VTSPPSWVH
