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Protein

Forkhead box protein O

Gene

foxo

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor involved in the regulation of the insulin signaling pathway. Consistently activates both the downstream target Thor\d4EBP and the feedback control target InR. Involved in negative regulation of the cell cycle, modulating cell growth and proliferation. In response to cellular stresses, such as nutrient deprivation or increased levels of reactive oxygen species, foxo is activated and inhibits growth through the action of target genes such as Thor. Foxo activated in the adult fat body can regulate lifespan in adults; an insulin peptide itself may function as one secondary messenger of insulin-regulated aging. Also regulates Lip4, homolog of human acid lipases, thereby acting as a key modulator of lipid metabolism by insulin signaling and integrates insulin responses to glucose and lipid homeostasis.5 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi95 – 201107Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • chromatin DNA binding Source: FlyBase
  • DNA binding Source: FlyBase
  • sequence-specific DNA binding Source: FlyBase
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: FlyBase
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

  • cAMP biosynthetic process Source: FlyBase
  • cell cycle Source: UniProtKB-KW
  • cellular response to amino acid starvation Source: FlyBase
  • cellular response to DNA damage stimulus Source: FlyBase
  • cellular response to oxidative stress Source: FlyBase
  • cellular response to starvation Source: FlyBase
  • circadian rhythm Source: FlyBase
  • compound eye morphogenesis Source: FlyBase
  • dendrite morphogenesis Source: FlyBase
  • determination of adult lifespan Source: FlyBase
  • ecdysone biosynthetic process Source: FlyBase
  • female germ-line stem cell population maintenance Source: FlyBase
  • glucose homeostasis Source: UniProtKB
  • glycogen metabolic process Source: FlyBase
  • imaginal disc-derived wing morphogenesis Source: FlyBase
  • insulin receptor signaling pathway Source: FlyBase
  • locomotor rhythm Source: FlyBase
  • microtubule bundle formation Source: FlyBase
  • multicellular organism aging Source: UniProtKB
  • myoblast fusion Source: FlyBase
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of cell size Source: FlyBase
  • negative regulation of insulin receptor signaling pathway Source: UniProtKB
  • negative regulation of lipid storage Source: FlyBase
  • negative regulation of multicellular organism growth Source: FlyBase
  • negative regulation of transcription, DNA-templated Source: FlyBase
  • positive regulation of cellular response to insulin stimulus Source: FlyBase
  • positive regulation of feeding behavior Source: FlyBase
  • positive regulation of octopamine signaling pathway Source: FlyBase
  • positive regulation of transcription, DNA-templated Source: FlyBase
  • positive regulation of transcription from RNA polymerase II promoter Source: FlyBase
  • regulation of activin receptor signaling pathway Source: FlyBase
  • regulation of autophagy Source: FlyBase
  • regulation of cell growth Source: FlyBase
  • regulation of growth Source: FlyBase
  • regulation of hemocyte proliferation Source: FlyBase
  • regulation of insulin receptor signaling pathway Source: FlyBase
  • regulation of lipid metabolic process Source: UniProtKB
  • regulation of macroautophagy Source: FlyBase
  • regulation of multicellular organism growth Source: FlyBase
  • regulation of organ growth Source: FlyBase
  • regulation of transcription, DNA-templated Source: UniProtKB
  • response to bacterium Source: FlyBase
  • response to oxidative stress Source: FlyBase
  • response to starvation Source: FlyBase
  • somatic muscle development Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Cell cycle, Differentiation, Growth regulation, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-DME-1181150. Signaling by NODAL.
R-DME-198693. AKT phosphorylates targets in the nucleus.
R-DME-211163. AKT-mediated inactivation of FOXO1A.
R-DME-5687128. MAPK6/MAPK4 signaling.
SignaLinkiQ95V55.

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein O1 Publication
Short name:
dFOXO1 Publication
Alternative name(s):
Protein FKHR
Gene namesi
Name:foxoImported
Synonyms:Afx
ORF Names:CG3143
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 3R

Organism-specific databases

FlyBaseiFBgn0038197. foxo.

Subcellular locationi

  • Cytoplasm 2 Publications
  • Nucleus PROSITE-ProRule annotation2 Publications

  • Note: When phosphorylated, translocated from nucleus to cytoplasm. Dephosphorylation triggers nuclear translocation.2 Publications

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mutant foxo lacking Akt1 phosphorylation sites no longer responds to insulin inhibition, remains in the nucleus, and is constitutively active, inducing cell arrest.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi44 – 441T → A: Abolishes phosphorylation; when associated with A-190 and A-259. 1 Publication
Mutagenesisi190 – 1901S → A: Abolishes phosphorylation; when associated with A-44 and A-259. 1 Publication
Mutagenesisi259 – 2591S → A: Abolishes phosphorylation; when associated with A-44 and A-190. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 613613Forkhead box protein OPRO_0000371436Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei44 – 441Phosphothreonine; by PKB/AKT11 Publication
Modified residuei75 – 751Phosphoserine1 Publication
Modified residuei190 – 1901Phosphoserine; by PKB/AKT11 Publication
Modified residuei259 – 2591Phosphoserine; by PKB/AKT11 Publication
Modified residuei262 – 2621Phosphoserine1 Publication
Modified residuei263 – 2631Phosphoserine1 Publication
Modified residuei268 – 2681Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ95V55.
PRIDEiQ95V55.

PTM databases

iPTMnetiQ95V55.

Expressioni

Gene expression databases

BgeeiFBgn0038197.
GenevisibleiQ95V55. DM.

Interactioni

Subunit structurei

Interacts with melt.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
HDAC4Q8I9J63EBI-500849,EBI-4288282

Protein-protein interaction databases

BioGridi66786. 4 interactions.
IntActiQ95V55. 4 interactions.
MINTiMINT-831229.
STRINGi7227.FBpp0293589.

Structurei

3D structure databases

ProteinModelPortaliQ95V55.
SMRiQ95V55. Positions 90-203.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi314 – 569256Gln-richSequence analysisAdd
BLAST

Sequence similaritiesi

Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00790000123003.
HOGENOMiHOG000229954.
InParanoidiQ95V55.
KOiK09408.
OrthoDBiEOG091G06K3.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform B1 Publication (identifier: Q95V55-1) [UniParc]FASTAAdd to basket
Also known as: C1 Publication

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MMDGYAQEWP RLTHTDNGLA MDQLGGDLPL DVGFEPQTRA RSNTWPCPRP
60 70 80 90 100
ENFVEPTDEL DSTKASNQQL APGDSQQAIQ NANAAKKNSS RRNAWGNLSY
110 120 130 140 150
ADLITHAIGS ATDKRLTLSQ IYEWMVQNVP YFKDKGDSNS SAGWKNSIRH
160 170 180 190 200
NLSLHNRFMR VQNEGTGKSS WWMLNPEAKP GKSVRRRAAS METSRYEKRR
210 220 230 240 250
GRAKKRVEAL RQAGVVGLND ATPSPSSSVS EGLDHFPESP LHSGGGFQLS
260 270 280 290 300
PDFRQRASSN ASSCGRLSPI RAQDLEPDWG FPVDYQNTTM TQAHAQALEE
310 320 330 340 350
LTGTMADELT LCNQQQQGFS AASGLPSQPP PPPYQPPQHQ QAQQQQQQQS
360 370 380 390 400
PYALNGPASG YNTLQPQSQC LLHRSLNCSC MHNARDGLSP NSVTTTMSPA
410 420 430 440 450
YPNSEPSSDS LNTYSNVVLD GPADTAALMV QQQQQQQQQQ QLSASLEGQC
460 470 480 490 500
LEVLNNEAQP IDEFNLENFP VGNLECNVEE LLQQEMSYGG LLDINIPLAT
510 520 530 540 550
VNTNLVNSSS GPLSISNISN LSNISSNSGS SLSLNQLQAQ LQQQQQQQQA
560 570 580 590 600
QQQQQAQQQQ QQHQQHQQQL LLNNNNNSSS SLELATQTAT TNLNARVQYS
610
QPSVVTSPPS WVH
Length:613
Mass (Da):67,413
Last modified:December 1, 2001 - v1
Checksum:iB472822ACA169BF9
GO
Isoform A1 Publication (identifier: Q95V55-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     146-243: NSIRHNLSLH...DHFPESPLHS → SFAINALLSS...APQVTINCDD

Note: No experimental confirmation available.Curated
Show »
Length:798
Mass (Da):87,696
Checksum:iD2FC95047EC055DD
GO
Isoform D1 Publication (identifier: Q95V55-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     146-304: NSIRHNLSLH...AQALEELTGT → DLQILQFFYI...CQFLRTPEPH
     305-613: Missing.

Note: No experimental confirmation available.Curated
Show »
Length:304
Mass (Da):33,832
Checksum:i677D0D71F2B8EC54
GO
Isoform E1 Publication (identifier: Q95V55-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     146-447: NSIRHNLSLH...QQQQLSASLE → SFAINALLSS...CQFLRTPEPH
     448-613: Missing.

Show »
Length:448
Mass (Da):49,960
Checksum:i1642D86999B6C997
GO

Sequence cautioni

The sequence AAL13947 differs from that shown. Reason: Erroneous initiation. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei146 – 447302NSIRH…SASLE → SFAINALLSSDRFSFCLHRS IPPLAVIKDQRLLKNSLRWL RRNRRRLFHLIPETLFFADS ALPANFSFFLRRLVVVRWFR GLADRWFGGSVARVFIIENS SSQSGDLAIEPVPKFYELST NQSECKWQSGMAVDKTWIIG GDPVSATCRDSVSPISRSNG PMKYAYLIRDDSVSWGSNEL HTSQSVAAQPLYEGPKRGHR QVILVDAQPGGQARQVCAPP CRFHGDVPVREAARQGQEAG GGTASGGRGGPQRCHALAQQ QRQRGAGSLSRESAPQWRWL PIIARFPATRLIQCQFLRTP EPH in isoform E. 1 PublicationVSP_053039Add
BLAST
Alternative sequencei146 – 304159NSIRH…ELTGT → DLQILQFFYIQYISVFAKYI YLYVHICFSLVLVTELHTSQ SVAAQPLYEGPKRGHRQVIL VDAQPGGQARQVCAPPCRFH GDVPVREAARQGQEAGGGTA SGGRGGPQRCHALAQQQRQR GAGSLSRESAPQWRWLPIIA RFPATRLIQCQFLRTPEPH in isoform D. 1 PublicationVSP_053040Add
BLAST
Alternative sequencei146 – 24398NSIRH…SPLHS → SFAINALLSSDRFSFCLHRS IPPLAVIKDQRLLKNSLRWL RRNRRRLFHLIPETLFFADS ALPANFSFFLRRLVVVRWFR GLADRWFGGSVARVFIIENS SSQSGDLAIEPVPKFYELST NQSECKWQSGMAVDKTWIIG GDPVSATCRDSVSPISRSNG PMKYAYLIRDDSVSWGSNEL HTSQSVAAQPLYEGPKRGHR QVILVDAQPGGQARQVCAPP CRFHGDVPVREAARQGQEAG GGTASGGRGGPQRCHALAQQ QRQRGAGSLSRESAPQVTIN CDD in isoform A. 1 PublicationVSP_053041Add
BLAST
Alternative sequencei305 – 613309Missing in isoform D. 1 PublicationVSP_053042Add
BLAST
Alternative sequencei448 – 613166Missing in isoform E. 1 PublicationVSP_053043Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF426831 mRNA. Translation: AAL28078.1.
AF416728 mRNA. Translation: AAL09043.1.
AE014297 Genomic DNA. Translation: AAF55012.2.
AE014297 Genomic DNA. Translation: AAS65147.1.
AE014297 Genomic DNA. Translation: AAS65148.1.
AE014297 Genomic DNA. Translation: ACL83512.1.
AY058718 mRNA. Translation: AAL13947.1. Different initiation.
AY089542 mRNA. Translation: AAL90280.1.
RefSeqiNP_001262557.1. NM_001275628.1.
NP_650330.3. NM_142073.5.
NP_996204.1. NM_206482.3. [Q95V55-1]
NP_996205.1. NM_206483.3. [Q95V55-1]
UniGeneiDm.3957.

Genome annotation databases

EnsemblMetazoaiFBtr0082886; FBpp0089343; FBgn0038197. [Q95V55-1]
FBtr0082887; FBpp0089344; FBgn0038197. [Q95V55-1]
GeneIDi41709.
KEGGidme:Dmel_CG3143.
UCSCiCG3143-RB. d. melanogaster. [Q95V55-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF426831 mRNA. Translation: AAL28078.1.
AF416728 mRNA. Translation: AAL09043.1.
AE014297 Genomic DNA. Translation: AAF55012.2.
AE014297 Genomic DNA. Translation: AAS65147.1.
AE014297 Genomic DNA. Translation: AAS65148.1.
AE014297 Genomic DNA. Translation: ACL83512.1.
AY058718 mRNA. Translation: AAL13947.1. Different initiation.
AY089542 mRNA. Translation: AAL90280.1.
RefSeqiNP_001262557.1. NM_001275628.1.
NP_650330.3. NM_142073.5.
NP_996204.1. NM_206482.3. [Q95V55-1]
NP_996205.1. NM_206483.3. [Q95V55-1]
UniGeneiDm.3957.

3D structure databases

ProteinModelPortaliQ95V55.
SMRiQ95V55. Positions 90-203.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi66786. 4 interactions.
IntActiQ95V55. 4 interactions.
MINTiMINT-831229.
STRINGi7227.FBpp0293589.

PTM databases

iPTMnetiQ95V55.

Proteomic databases

PaxDbiQ95V55.
PRIDEiQ95V55.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0082886; FBpp0089343; FBgn0038197. [Q95V55-1]
FBtr0082887; FBpp0089344; FBgn0038197. [Q95V55-1]
GeneIDi41709.
KEGGidme:Dmel_CG3143.
UCSCiCG3143-RB. d. melanogaster. [Q95V55-1]

Organism-specific databases

CTDi41709.
FlyBaseiFBgn0038197. foxo.

Phylogenomic databases

eggNOGiKOG2294. Eukaryota.
COG5025. LUCA.
GeneTreeiENSGT00790000123003.
HOGENOMiHOG000229954.
InParanoidiQ95V55.
KOiK09408.
OrthoDBiEOG091G06K3.

Enzyme and pathway databases

ReactomeiR-DME-1181150. Signaling by NODAL.
R-DME-198693. AKT phosphorylates targets in the nucleus.
R-DME-211163. AKT-mediated inactivation of FOXO1A.
R-DME-5687128. MAPK6/MAPK4 signaling.
SignaLinkiQ95V55.

Miscellaneous databases

ChiTaRSifoxo. fly.
GenomeRNAii41709.
PROiQ95V55.

Gene expression databases

BgeeiFBgn0038197.
GenevisibleiQ95V55. DM.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
InterProiIPR001766. Fork_head_dom.
IPR030456. TF_fork_head_CS_2.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00250. Forkhead. 1 hit.
[Graphical view]
PRINTSiPR00053. FORKHEAD.
SMARTiSM00339. FH. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
PROSITEiPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiFOXO_DROME
AccessioniPrimary (citable) accession number: Q95V55
Secondary accession number(s): Q7KF42, Q95TK1, Q9VFN8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 16, 2009
Last sequence update: December 1, 2001
Last modified: September 7, 2016
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.