FOXO_DROYA
ID FOXO_DROYA Reviewed; 628 AA.
AC B4PTD3;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 2.
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=GE24216;
OS Drosophila yakuba (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7245;
RN [1] {ECO:0000312|EMBL:EDW97632.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tai18E2 / Tucson 14021-0261.01 {ECO:0000312|EMBL:EDW97632.1};
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=EDW97632.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CM000160; EDW97632.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; XP_002097920.2; XM_002097884.2.
DR AlphaFoldDB; B4PTD3; -.
DR SMR; B4PTD3; -.
DR EnsemblMetazoa; FBtr0394701; FBpp0354003; FBgn0241347.
DR GeneID; 6537363; -.
DR KEGG; dya:Dyak_GE24216; -.
DR eggNOG; KOG2294; Eukaryota.
DR OrthoDB; 1160384at2759; -.
DR ChiTaRS; foxo; fly.
DR Proteomes; UP000002282; Chromosome 3R.
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; Transcription;
KW Transcription regulation.
FT CHAIN 1..628
FT /note="Forkhead box protein O"
FT /id="PRO_0000396513"
FT DNA_BIND 95..201
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 39..77
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 217..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 316..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 389..415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 59..77
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 182..198
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 219..233
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 252..267
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 340..359
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 44
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 75
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 190
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 259
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 263
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q95V55"
SQ SEQUENCE 628 AA; 68920 MW; 9C4C611882A072C4 CRC64;
MMDGFAQDWP TLTHTDNGLA MDQLGGDLPL DVGFEPQTRA RSNTWPCPRP ENFVEPTDEL
DSTKASNQQL APGDSQQAIQ NANAAKKNSS RRNAWGNLSY ADLITHAIGS ATDKRLTLSQ
IYEWMVQNVP YFKDKGDSNS SAGWKNSIRH NLSLHNRFMR VQNEGTGKSS WWMLNPEAKP
GKSVRRRAAS METSRYEKRR GRAKKRVEAL RQAGVVGLND ATPSPSSSVS EGLDHFPESP
LHSGGGFQLS PDFRQRASSN ASSCGRLSPI RAQDLEPDWG FPVDYQNTTM TQAHAQALEE
LTCSVADELT LCTQQQQQGF SAASGLPSQP PPPPYQPPQH QQAQQQQSPY ALNGPAPGYN
TLQPQSQCLL HRSLNCSCMH NARDGLSPNS VTTTMSPAYP NSEPSSDSLN TYSNVVLDGP
ADTAALMVQQ QQQQQQQQQQ QQQQLSASLE GQCLEVLNNE AQPIDEFNLE NFPVGNLECN
VEELLQQEMS YGGLLDINIP LATVNTNLVN SSSGPLSISN ISNISNISNL SNLSNISNIS
SNSGSSLNLN QLQAQLQQQQ QQQQAQLQQQ AQQQQQPHQQ HQQQLLLNNN NNSSSSLELA
TQTASSNLNA RVQYSQPSVV TSPPSWVH
