Foxo3
entrez
56484
canonical
uniprot
Q9WVH4
canonical
ensembl
ENSMUSG00000048756
resolver
ensp
ENSMUSP00000050683
resolver
ensp
ENSMUSP00000101141
resolver
ensp
ENSMUSP00000135380
resolver
enst
ENSMUST00000056974
resolver
enst
ENSMUST00000105502
resolver
enst
ENSMUST00000175881
resolver
genesymbol
Foxo3
resolver
genesymbol_syn
Fkhr2
resolver
genesymbol_syn
Foxo3a
resolver
uniprot
D3Z6Y6
resolver
uniprot
Q05CZ4
resolver
uniprot_entry
FOXO3_MOUSE
resolver
uniprot_sec
D3Z6Y6
resolver
uniprot_sec
Q05CZ4
resolver
amino_acid_sequence
MAEAPASPVPLSPLEVELDPEFEPQSRPRSCTWPLQRPELQASPAKPSGETAADSMIPEEDDDEDDEDGGGRASSAMVIGGGVSSTLGSGLLLEDSAMLLAPGGQDLGSGPASAAGALSGGTPTQLQPQQPLPQPQPGAAGGSGQPRKCSSRRNAWGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWIINPDGGKSGKAPRRRAVSMDNSNKYTKSRGRAAKKKAALQAAPESADDSPSQLSKWPGSPTSRSSDELDAWTDFRSRTNSNASTVSGRLSPILASTELDDVQDDDGPLSPMLYSSSASLSPSVSKPCTVELPRLTDMAGTMNLNDGLAENLMDDLLDNIALPPSQPSPPGGLMQRGSSFPYTAKSSGLGSPTGSFNSTVFGPSSLNSLRQSPMQTIQENRPATFSSVSHYGNQTLQDLLASDSLSHSDVMMTQSDPLMSQASTAVSAQNARRNVMLRNDPMMSFAAQPTQGSLVNQNLLHHQHQTQGALGGSRALSNSVSNMGLSDSSSLGSAKHQQQSPASQSMQTLSDSLSGSSLYSASANLPVMGHDKFPSDLDLDMFNGSLECDMESIIRSELMDADGLDFNFDSLISTQNVVGLNVGNFTGAKQASSQSWVPG
uniprot
proteins
function
FUNCTION: Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:18054315, PubMed:18054316, PubMed:23805378). Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins (PubMed:18054315, PubMed:18054316, PubMed:25402684). Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (By similarity). Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation (By similarity). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription (PubMed:23283301). Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (PubMed:32103177). Also acts as a key regulator of regulatory T-cells (Treg) differentiation by activating expression of FOXP3 (By similarity). {ECO:0000250|UniProtKB:O43524, ECO:0000269|PubMed:18054315, ECO:0000269|PubMed:18054316, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:25402684, ECO:0000269|PubMed:32103177}.
uniprot
proteins
mass_dalton
71064
uniprot
proteins
mutagenesis
MUTAGEN 298; /note="S->A: Abolishes phosphorylation by CAMK2A. Loss of transcriptional activity."; /evidence="ECO:0000269|PubMed:23805378
uniprot
proteins
post_translational_modification
PTM: Deacetylation by SIRT1 or SIRT2 stimulates interaction of FOXO3 with SKP2 and facilitates SCF(SKP2)-mediated FOXO3 ubiquitination and proteasomal degradation (By similarity). Deacetylation by SIRT2 stimulates FOXO3-mediated transcriptional activity in response to oxidative stress (PubMed:17521387). Deacetylated by SIRT3 (By similarity). Deacetylation by SIRT3 stimulates FOXO3-mediated mtDNA transcriptional activity in response to metabolic stress (By similarity). {ECO:0000250|UniProtKB:O43524, ECO:0000269|PubMed:17521387}.; PTM: In the presence of survival factors such as IGF1, phosphorylated on Thr-32 and Ser-252 by AKT1/PKB (Probable). This phosphorylated form then interacts with 14-3-3 proteins and is retained in the cytoplasm (Probable). Survival factor withdrawal induces dephosphorylation and promotes translocation to the nucleus where the dephosphorylated protein induces transcription of target genes and triggers apoptosis (By similarity). Although AKT1/PKB doesn't appear to phosphorylate Ser-314 directly, it may activate other kinases that trigger phosphorylation at this residue (By similarity). Phosphorylated by STK4/MST1 on Ser-208 upon oxidative stress, which leads to dissociation from YWHAB/14-3-3-beta and nuclear translocation (By similarity). Phosphorylated by PIM1 (By similarity). Phosphorylation by AMPK leads to the activation of transcriptional activity without affecting subcellular localization (By similarity). Phosphorylated by AMPK on Ser-30 in response to metabolic stress which mediates FOXO3 mitochondrial translocation (By similarity). Phosphorylation by MAPKAPK5 promotes nuclear localization and DNA-binding, leading to induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation (By similarity). Phosphorylated by CHUK/IKKA and IKBKB/IKKB (By similarity). TNF-induced inactivation of FOXO3 requires its phosphorylation at Ser-643 by IKBKB/IKKB which promotes FOXO3 retention in the cytoplasm, polyubiquitination and ubiquitin-mediated proteasomal degradation (By similarity). May be dephosphorylated by calcineurin A on Ser-298 which abolishes FOXO3 transcriptional activity (PubMed:23805378). Phosphorylation at Ser-252 promotes its degradation by the proteasome (By similarity). Dephosphorylation at Ser-252 by protein phosphatase 2A (PPP2CA) promotes its stabilization; interaction with PPP2CA is enhanced by AMBRA1 (By similarity). Dephosphorylated by CTDSPL2 (PubMed:28851713). {ECO:0000250|UniProtKB:O43524, ECO:0000269|PubMed:23805378, ECO:0000269|PubMed:28851713, ECO:0000305|PubMed:18054315}.; PTM: Heavily methylated by SET9 which decreases stability, while moderately increasing transcriptional activity. The main methylation site is Lys-270. Methylation doesn't affect subcellular location. {ECO:0000250|UniProtKB:O43524}.; PTM: Polyubiquitinated. Ubiquitinated by a SCF complex containing SKP2, leading to proteasomal degradation. {ECO:0000250|UniProtKB:O43524}.; PTM: The N-terminus is cleaved following import into the mitochondrion. {ECO:0000269|PubMed:29445193}.
uniprot
proteins
pubmed
11353388
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17521387
uniprot
proteins
pubmed
18054315
uniprot
proteins
pubmed
18054316
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22510882
uniprot
proteins
pubmed
23283301
uniprot
proteins
pubmed
23805378
uniprot
proteins
pubmed
23806337
uniprot
proteins
pubmed
25402684
uniprot
proteins
pubmed
28851713
uniprot
proteins
pubmed
29445193
uniprot
proteins
pubmed
32103177
uniprot
proteins
pubmed
38886174
uniprot
proteins
sequence_length
672
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:18054315, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:32103177}. Nucleus {ECO:0000269|PubMed:18054315, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:28851713, ECO:0000269|PubMed:32103177}. Mitochondrion matrix {ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:29445193}. Mitochondrion outer membrane {ECO:0000269|PubMed:29445193}; Peripheral membrane protein {ECO:0000269|PubMed:29445193}; Cytoplasmic side {ECO:0000269|PubMed:29445193}. Note=Retention in the cytoplasm contributes to its inactivation (By similarity). Translocates to the nucleus upon oxidative stress and in the absence of survival factors (By similarity). Translocates from the cytosol to the nucleus following dephosphorylation in response to autophagy-inducing stimuli (PubMed:18054315). Translocates in a AMPK-dependent manner into the mitochondrion in response to metabolic stress (PubMed:23283301, PubMed:29445193). Serum deprivation increases localization to the nucleus, leading to activate expression of SOX9 and subsequent chondrogenesis (PubMed:32103177). {ECO:0000250|UniProtKB:O43524, ECO:0000269|PubMed:18054315, ECO:0000269|PubMed:23283301, ECO:0000269|PubMed:29445193, ECO:0000269|PubMed:32103177}.
uniprot
proteins