Foxo1
entrez
56458
canonical
uniprot
Q9R1E0
canonical
ensembl
ENSMUSG00000044167
resolver
ensp
ENSMUSP00000055308
resolver
enst
ENSMUST00000053764
resolver
genesymbol
Foxo1
resolver
genesymbol_syn
Fkhr
resolver
genesymbol_syn
Foxo1a
resolver
uniprot
Q9JJW4
resolver
uniprot_entry
FOXO1_MOUSE
resolver
uniprot_sec
Q9JJW4
resolver
amino_acid_sequence
MAEAPQVVETDPDFEPLPRQRSCTWPLPRPEFNQSNSTTSSPAPSGGAAANPDAAASLASASAVSTDFMSNLSLLEESEDFARAPGCVAVAAAAAASRGLCGDFQGPEAGCVHPAPPQPPPTGPLSQPPPVPPSAAAAAGPLAGQPRKTSSSRRNAWGNLSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIRVQNEGTGKSSWWMLNPEGGKSGKSPRRRAASMDNNSKFAKSRGRAAKKKASLQSGQEGPGDSPGSQFSKWPASPGSHSNDDFDNWSTFRPRTSSNASTISGRLSPIMTEQDDLGDGDVHSLVYPPSAAKMASTLPSLSEISNPENMENLLDNLNLLSSPTSLTVSTQSSPGSMMQQTPCYSFAPPNTSLNSPSPNYSKYTYGQSSMSPLPQMPMQTLQDSKSSYGGLNQYNCAPGLLKELLTSDSPPHNDIMSPVDPGVAQPNSRVLGQNVMMGPNSVMPAYGSQASHNKMMNPSSHTHPGHAQQTASVNGRTLPHVVNTMPHTSAMNRLTPVKTPLQVPLSHPMQMSALGSYSSVSSCNGYGRMGVLHQEKLPSDLDGMFIERLDCDMESIIRNDLMDGDTLDFNFDNVLPNQSFPHSVKTTTHSWVSG
uniprot
proteins
function
FUNCTION: Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress (PubMed:12219087, PubMed:12754525, PubMed:15184386, PubMed:15220471, PubMed:16917544, PubMed:17090532, PubMed:17627282, PubMed:17681146, PubMed:20519497, PubMed:20668652, PubMed:21196578, PubMed:21335550, PubMed:21471200, PubMed:22298775, PubMed:22417654, PubMed:22510882, PubMed:27457971, PubMed:34914893). Binds to the insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3' (PubMed:17090532, PubMed:21335550). Activity suppressed by insulin (PubMed:12754525, PubMed:17627282). Main regulator of redox balance and osteoblast numbers and controls bone mass (PubMed:21471200, PubMed:22298775). Orchestrates the endocrine function of the skeleton in regulating glucose metabolism (PubMed:21471200, PubMed:22298775). 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). Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity (PubMed:22298775). Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP (PubMed:21471200). Acts as an inhibitor of glucose sensing in pancreatic beta cells by acting as a transcription repressor and suppressing expression of PDX1 (PubMed:12219087, PubMed:27457971). In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC1 and PCK1 (PubMed:12754525, PubMed:25009184). Also promotes gluconeogenesis by directly promoting expression of PPARGC1A and G6PC1 (By similarity). Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1 (By similarity). Promotes neural cell death (By similarity). Mediates insulin action on adipose tissue (By similarity). Regulates the expression of adipogenic genes such as PPARG during preadipocyte differentiation and, adipocyte size and adipose tissue-specific gene expression in response to excessive calorie intake (By similarity). Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells (PubMed:21196578). Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner (By similarity). Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity). Positive regulator of apoptosis in cardiac smooth muscle cells as a result of its transcriptional activation of pro-apoptotic genes (By similarity). Regulates endothelial cell (EC) viability and apoptosis in a PPIA/CYPA-dependent manner via transcription of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (By similarity). {ECO:0000250|UniProtKB:A4L7N3, ECO:0000250|UniProtKB:G3V7R4, ECO:0000250|UniProtKB:Q12778, ECO:0000269|PubMed:12219087, ECO:0000269|PubMed:12754525, ECO:0000269|PubMed:15184386, ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:16917544, ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:17627282, ECO:0000269|PubMed:17681146, ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:20668652, ECO:0000269|PubMed:21196578, ECO:0000269|PubMed:21335550, ECO:0000269|PubMed:21471200, ECO:0000269|PubMed:22298775, ECO:0000269|PubMed:22417654, ECO:0000269|PubMed:22510882, ECO:0000269|PubMed:25009184, ECO:0000269|PubMed:27457971, ECO:0000269|PubMed:32103177, ECO:0000269|PubMed:34914893}.
uniprot
proteins
mass_dalton
69518
uniprot
proteins
mutagenesis
MUTAGEN 24; /note="T->A: Decreases insulin-induced phosphorylation by approximately 30%. Nuclear location but transcriptional activity decreased by about 50%. Abolishes the SIRT1 deacetylase binding and increases acetylation; when associated with A-253; A-316; A-462 and A-463. Increased insulin-induced phosphorylation at Ser-253 and binding of 14-3-3 proteins; when associated with Q-219; Q-242; Q-245; Q-259; Q-262; Q-271 and Q-291. Increased binding of 14-3-3 proteins even with decreased insulin-induced phosphorylation at Ser-253; when associated with R-219; R-242; R-245; R-259; R-262; R-271 and R-291."; /evidence="ECO:0000269|PubMed:10347145, ECO:0000269|PubMed:16917544, ECO:0000269|PubMed:20519497"; MUTAGEN 29; /note="R->K: Little change in levels of methylation; when associated with K-147; K-154; K-311 and K-313."; /evidence="ECO:0000269|PubMed:18951090"; MUTAGEN 147; /note="R->K: Little change in levels of methylation; when associated with K-29; K-154; K-311 and K-313."; /evidence="ECO:0000269|PubMed:18951090"; MUTAGEN 154; /note="R->K: Little change in levels of methylation; when associated with K-29; K-147; K-311 and K-313."; /evidence="ECO:0000269|PubMed:18951090"; MUTAGEN 206; /note="W->G: Loss of interaction with CEBPA."; /evidence="ECO:0000269|PubMed:17627282"; MUTAGEN 212; /note="H->P: Loss of interaction with CEBPA."; /evidence="ECO:0000269|PubMed:17627282"; MUTAGEN 219; /note="K->Q: Mimics acetylation. Cytoplasmic location in absence or presence of insulin, no change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with Q-242; Q-245; Q-259; Q-262; Q-271 and Q-291. Increased insulin-induced phosphorylation at Ser-253 and binding of 14-3-3 proteins; when associated with A-24; Q-242; Q-245; Q-259; Q-262; Q-271 and Q-291."; /evidence="ECO:0000269|PubMed:20519497"; MUTAGEN 219; /note="K->R: Translocates to the cytoplasm after insulin-stimulation. No change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with R-242; R-245; R-259; R-262; R-271 and R-291. Increased binding of 14-3-3 proteins even with decreased insulin-induced phosphorylation at Ser-253; when associated with A-24; R-242; R-245; R-259; R-262; R-271 and R-291."; /evidence="ECO:0000269|PubMed:20519497"; MUTAGEN 242; /note="K->Q,A: Mimics acetylation. Cytoplasmic location in absence or presence of insulin. Decreased DNA-binding by about half. Enhanced phosphorylation by PKB/AKT1, no effect on interaction with CEBPA; when associated with either A-245 or Q-245 and either A-262 or Q-262. either A-262 or Q-262. Cytoplasmic location in absence or presence of insulin, no change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with Q-219; Q-245; Q-259; Q-262; Q-271 and Q-291. Increased insulin-induced phosphorylation at Ser-253 and binding of 14-3-3 proteins; when associated with A-24; Q-219; Q-245; Q-259; Q-262; Q-271 and Q-291."; /evidence="ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 242; /note="K->R: Reduced acetylation and transcriptional activity increased by about 1.5 fold. Completely abolishes acetylation, increases interaction with CEBPA and transcriptional activity increased by about 3-fold; when associated with R-245 and R-262. Transcriptional activity not inhibited by FCOR; when associated with R-245; R-259; R-262; R-271 and R-291. Predominantly nuclear and translocates to the cytoplasm on insulin-stimulation. No change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with R-219; R-245; R-259; R-262; R-271 and R-291. Increased binding of 14-3-3 proteins even with decreased insulin-induced phosphorylation at Ser-253; when associated with A-24; R-219; R-245; R-259; R-262; R-271 and R-291."; /evidence="ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 245; /note="K->Q,A: Mimics acetylation. Decreased DNA-binding by about half. Enhanced phosphorylation by PKB/AKT1, no effect on interaction with CEBPA; when associated with either A-242 or Q-242 and either A-262 or Q-262. Cytoplasmic location in absence or presence of insulin, no change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with Q-219; Q-242; Q-259; Q-262; Q-271 and Q-291. Increased insulin-induced phosphorylation at Ser-253 and binding of 14-3-3 proteins; when associated with A-24; Q-219; Q-242; Q-259; Q-262; Q-271 and Q-291."; /evidence="ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 245; /note="K->R: Reduced acetylation and transcriptional activity increased by about 1.5-fold. Completely abolishes acetylation, increases interaction with CEBPA and transcriptional activity increased by about 3-fold; when associated with R-242 and R-262. Transcriptional activity not inhibited by FCOR; when associated with R-242; R-259; R-262; R-271 and R-291. Predominantly nuclear and translocates to the cytoplasm on insulin-stimulation. No change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with R-219; R-242; R-259; R-262; R-271 and R-291. Increased binding of 14-3-3 proteins even with decreased insulin-induced phosphorylation at Ser-253; when associated with A-24; R-219; R-242; R-259; R-262; R-271 and R-291."; /evidence="ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 248; /note="R->K: Some decrease in levels of methylation. Greatly decreased methylation levels; when associated with K-250."; /evidence="ECO:0000269|PubMed:18951090"; MUTAGEN 249; /note="R->K: No change in methylation levels."; /evidence="ECO:0000269|PubMed:18951090"; MUTAGEN 250; /note="R->K: Some decrease in levels of methylation. Greatly decreased methylation levels; when associated with K-248."; /evidence="ECO:0000269|PubMed:18951090"; MUTAGEN 253; /note="S->A: Abolishes insulin-induced phosphorylation when associated with A-463. Nuclear location but transcriptional activity decreased by about 50%. Abolishes the SIRT1 deacetylase binding and increases acetylation; when associated with A-24; A-316; A-462 and A-463."; /evidence="ECO:0000269|PubMed:10347145, ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:16917544, ECO:0000269|PubMed:20519497"; MUTAGEN 259; /note="K->Q: Mimics acetylation. Cytoplasmic location in absence or presence of insulin, no change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with Q-219; Q-242; Q-245; Q-262; Q-271 and Q-291. Increased insulin-induced phosphorylation at Ser-253 and binding of 14-3-3 proteins; when associated with A-24; Q-219; Q-242; Q-245; Q-262; Q-271 and Q-291."; /evidence="ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 259; /note="K->R: Transcriptional activity not inhibited by FCOR; when associated with R-242; R-245; R-262; R-271 and R-291. Predominantly nuclear and translocates to the cytoplasm on insulin-stimulation. No change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with R-219; R-242; R-245; R-262; R-271 and R-291. Increased binding of 14-3-3 proteins even with decreased insulin-induced phosphorylation at Ser-253; when associated with A-24; R-219; R-242; R-245; R-262; R-271 and R-291."; /evidence="ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 262; /note="K->Q,A: Mimics acetylation. Decreased DNA-binding by about half and enhanced phosphorylation by PKB/AKT1, no effect on interaction with CEBPA; when associated with either A-242 or Q-242 and either A-245 or Q-245. Cytoplasmic location in absence or presence of insulin, no change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with Q-219; Q-242; Q-245; Q-259; Q-271 and Q-291. Increased insulin-induced phosphorylation at Ser-253 and binding of 14-3-3 proteins; when associated with A-24; Q-219; Q-242; Q-245; Q-259; Q-271 and Q-291."; /evidence="ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 262; /note="K->R: Significant reduction in acetylation and transcriptional activity increased by about 2.0 fold. Completely abolishes acetylation, increases interaction with CEBPA and transcriptional activity increased by about 3-fold; when associated with R-242 and R-245. Transcriptional activity not inhibited by FCOR; when associated with R-242; R-245; R-259; R-271 and R-291. Predominantly nuclear and translocates to the cytoplasm on insulin-stimulation. No change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with R-219; R-242; R-245; R-259; R-271 and R-291. Increased binding of 14-3-3 proteins even with decreased insulin-induced phosphorylation at Ser-253; when associated with A-24; R-219; R-242; R-245; R-259; R-271 and R-291."; /evidence="ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 271; /note="K->Q: Mimics acetylation. Cytoplasmic location in absence or presence of insulin, no change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with Q-219; Q-242; Q-245; Q-259; Q-262 and Q-291. Increased insulin-induced phosphorylation at Ser-253 and binding of 14-3-3 proteins; when associated with A-24; Q-219; Q-242; Q-245; Q-259; Q-262 and Q-291."; /evidence="ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 271; /note="K->R: Transcriptional activity not inhibited by FCOR; when associated with R-242; R-245; R-259; R-262 and R-291. Predominantly nuclear and translocates to the cytoplasm on insulin-stimulation. No inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with R-219; R-242; R-245; R-259; R-262 and R-291. Increased binding of 14-3-3 proteins even with decreased insulin-induced phosphorylation at Ser-253; when associated with A-24; R-219; R-242; R-245; R-259; R-262 and R-291."; /evidence="ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 284; /note="S->A: Decreases phosphorylation by NLK; when associated with A-295; A-326; A-380; A-391; A-399; A-413 and A-415."; /evidence="ECO:0000269|PubMed:20061393"; MUTAGEN 291; /note="K->Q: Mimics acetylation. Cytoplasmic location in absence or presence of insulin, no change on the inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with Q-219; Q-242; Q-245; Q-259; Q-262 and Q-271. Increased insulin-induced phosphorylation at Ser-253 and binding of 14-3-3 proteins; when associated with A-24: Q-219; Q-242; Q-245; Q-259; Q-262 and Q-271."; /evidence="ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 291; /note="K->R: Transcriptional activity not inhibited by FCOR; when associated with R-242; R-245; R-259; R-262 and R-271. Predominantly nuclear and translocates to the cytoplasm on insulin-stimulation. No inhibitory effect of oxidative stress on insulin-induced phosphorylations, but no inhibition of these phosphorylations by resveratrol; when associated with R-219; R-242; R-245; R-259; R-262 and R-271. Increased binding of 14-3-3 proteins even with decreased insulin-induced phosphorylation at Ser-253; when associated with A-24; R-219; R-242; R-245; R-259; R-262 and R-271."; /evidence="ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"; MUTAGEN 295; /note="S->A: Decreases phosphorylation by NLK; when associated with A-284; A-326; A-380; A-391; A-399; A-413 and A-415."; /evidence="ECO:0000269|PubMed:20061393"; MUTAGEN 311; /note="R->K: Little change in levels of methylation; when associated with K-29; K-147; K-154 and K-313."; /evidence="ECO:0000269|PubMed:18951090"; MUTAGEN 313; /note="R->K: Little change in levels of methylation; when associated with K-29; K-147; K-154 and K-311."; /evidence="ECO:0000269|PubMed:18951090"; MUTAGEN 316; /note="S->A: Decreases insulin-induced phosphorylation by approximately 30%. Abolishes the SIRT1 deacetylase binding and increases acetylation; when associated with A-24; A-253; A-462 and A-463."; /evidence="ECO:0000269|PubMed:10347145, ECO:0000269|PubMed:16917544"; MUTAGEN 326; /note="S->A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-380; A-391; A-399; A-413 and A-415."; /evidence="ECO:0000269|PubMed:20061393"; MUTAGEN 380; /note="S->A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-326; A-391; A-399; A-413 and A-415."; /evidence="ECO:0000269|PubMed:20061393"; MUTAGEN 391; /note="S->A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-326; A-380; A-399; A-413 and A-415."; /evidence="ECO:0000269|PubMed:20061393"; MUTAGEN 399; /note="T->A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-326; A-380; A-391; A-413 and A-415."; /evidence="ECO:0000269|PubMed:20061393"; MUTAGEN 413; /note="S->A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-326; A-380; A-391; A-399 and A-415."; /evidence="ECO:0000269|PubMed:20061393"; MUTAGEN 415; /note="S->A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-326; A-380; A-391; A-399 and A-413."; /evidence="ECO:0000269|PubMed:20061393"; MUTAGEN 462; /note="L->A: Decreased transcriptional activity by about 2-fold in the absence of serum; when associated with A-463. Nuclear location but transcriptional activity decreased by about 50%. Abolishes the SIRT1 deacetylase binding and increases acetylation; when associated with A-24; A-253; A-316 and A-463."; /evidence="ECO:0000269|PubMed:16917544"; MUTAGEN 463; /note="L->A: Decreased transcriptional activity by about 2-fold in the absence of serum; when associated with A-463. Nuclear location but transcriptional activity decreased by about 50%. Abolishes the SIRT1 deacetylase binding and increases acetylation; when associated with A-24; A-253; A-316 and A-462."; /evidence="ECO:0000269|PubMed:16917544
uniprot
proteins
post_translational_modification
PTM: Phosphorylation by NLK promotes nuclear export and inhibits the transcriptional activity. In response to growth factors, phosphorylation on Thr-24, Ser-253 and Ser-319 by PKB/AKT1 promotes nuclear export and inactivation of transactivational activity. Phosphorylation on Thr-24 is required for binding 14-3-3 proteins. Phosphorylation of Ser-253 decreases DNA-binding activity and promotes the phosphorylation of Thr-24 and Ser-316, permitting phosphorylation of Ser-319 and Ser-322, probably by CDK1, leading to nuclear exclusion and loss of function. Stress signals, such as response to oxygen or nitric oxide, attenuate the PKB/AKT1-mediated phosphorylation leading to nuclear retention. Phosphorylation of Ser-326 is independent of IGF1 and leads to reduced function. Dephosphorylated on Thr-24 and Ser-253 by PP2A in beta-cells under oxidative stress leading to nuclear retention (By similarity). Phosphorylation of Ser-246 by CDK1 disrupts binding of 14-3-3 proteins leading to nuclear accumulation and has no effect on DNA-binding nor transcriptional activity. Phosphorylation by STK4/MST1 on Ser-209, upon oxidative stress, inhibits binding to 14-3-3 proteins and nuclear export (By similarity). PPIA/CYPA promotes its dephosphorylation on Ser-253 (By similarity). Dephosphorylated by CTDSPL2 (PubMed:28851713). {ECO:0000250|UniProtKB:Q12778, ECO:0000269|PubMed:10347145, ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:19965929, ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:28851713}.; PTM: Ubiquitinated by SKP2 (By similarity). Ubiquitinated, leading to proteasomal degradation (PubMed:28790135). Ubiquitinated by STUB1/CHIP; when Ser-253 is phosphorylated (By similarity). {ECO:0000250|UniProtKB:Q12778, ECO:0000269|PubMed:28790135}.; PTM: Methylation inhibits PKB/AKT1-mediated phosphorylation at Ser-253, promoting nuclear retention and increasing the transcriptional activity and cell death. Methylation increased by oxidative stress. {ECO:0000269|PubMed:10347145, ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:18951090, ECO:0000269|PubMed:19965929, ECO:0000269|PubMed:20519497}.; PTM: Acetylation at Lys-259 and Lys-271 are necessary for autophagic cell death induction (By similarity). Deacetylated by SIRT2 in response to oxidative stress or serum deprivation, thereby negatively regulating FOXO1-mediated autophagic cell death (By similarity). Once in the nucleus, acetylated by CREBBP/EP300 (By similarity). Acetylation diminishes the interaction with target DNA and attenuates the transcriptional activity. It increases the phosphorylation at Ser-253, and is required for the transcriptional inhibition by FCOR (By similarity). Deacetylation by SIRT1 results in reactivation of the transcriptional activity (PubMed:15220471, PubMed:16076959, PubMed:17090532). Acetylation of FOXO1 diminishes its binding to PPARG in adipocytes. Deacetylated by SIRT2; deacetylation of FOXO1 directly increases its repressive binding to PPARG and inhibits adipocyte differentiation (PubMed:17681146, PubMed:19037106, PubMed:20519497, PubMed:21196578). Oxidative stress by hydrogen peroxide treatment appears to promote deacetylation and uncoupling of insulin-induced phosphorylation (By similarity). By contrast, resveratrol acts independently of acetylation (By similarity). Acetylated at Lys-420, promoting its localization to the nucleus and transcription factor activity (PubMed:25009184). Deacetylation at Lys-420 by SIRT6, promotes its translocation into the cytoplasm, preventing its transcription factor activity (PubMed:25009184, PubMed:27457971). Deacetylation and subsequent inhibition by SIRT6 has different effects depending on cell types: it inhibits gluconeogenesis in hepatocytes, promotes glucose sensing in pancreatic beta-cells and regulates lipid catabolism in brown adipocytes (PubMed:25009184, PubMed:27457971, PubMed:31442424). {ECO:0000250|UniProtKB:Q12778, ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:17681146, ECO:0000269|PubMed:19037106, ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:21196578, ECO:0000269|PubMed:25009184, ECO:0000269|PubMed:27457971, ECO:0000269|PubMed:31442424}.
uniprot
proteins
pubmed
10347145
uniprot
proteins
pubmed
12219087
uniprot
proteins
pubmed
12754525
uniprot
proteins
pubmed
15184386
uniprot
proteins
pubmed
15220471
uniprot
proteins
pubmed
16076959
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16917544
uniprot
proteins
pubmed
17050673
uniprot
proteins
pubmed
17090532
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
17627282
uniprot
proteins
pubmed
17681146
uniprot
proteins
pubmed
18388859
uniprot
proteins
pubmed
18951090
uniprot
proteins
pubmed
19037106
uniprot
proteins
pubmed
19965929
uniprot
proteins
pubmed
20061393
uniprot
proteins
pubmed
20519497
uniprot
proteins
pubmed
20668652
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21196578
uniprot
proteins
pubmed
21317886
uniprot
proteins
pubmed
21335550
uniprot
proteins
pubmed
21471200
uniprot
proteins
pubmed
22298775
uniprot
proteins
pubmed
22417654
uniprot
proteins
pubmed
22510882
uniprot
proteins
pubmed
25009184
uniprot
proteins
pubmed
27457971
uniprot
proteins
pubmed
27827363
uniprot
proteins
pubmed
28790135
uniprot
proteins
pubmed
28851713
uniprot
proteins
pubmed
31442424
uniprot
proteins
pubmed
32103177
uniprot
proteins
pubmed
34914893
uniprot
proteins
sequence_length
652
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18388859, ECO:0000269|PubMed:21317886, ECO:0000269|PubMed:27457971, ECO:0000269|PubMed:32103177}. Nucleus {ECO:0000269|PubMed:17627282, ECO:0000269|PubMed:18388859, ECO:0000269|PubMed:19965929, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:21196578, ECO:0000269|PubMed:21317886, ECO:0000269|PubMed:22298775, ECO:0000269|PubMed:27457971, ECO:0000269|PubMed:28790135, ECO:0000269|PubMed:28851713, ECO:0000269|PubMed:32103177}. Note=Shuttles between the cytoplasm and nucleus (PubMed:32103177). Largely nuclear in unstimulated cells (By similarity). In osteoblasts, colocalizes with ATF4 and RUNX2 in the nucleus (PubMed:22298775). Serum deprivation increases localization to the nucleus, leading to activate expression of SOX9 and subsequent chondrogenesis (PubMed:32103177). Insulin-induced phosphorylation at Ser-253 by PKB/AKT1 leads, via stimulation of Thr-24 phosphorylation, to binding of 14-3-3 proteins and nuclear export to the cytoplasm where it is degraded by the ubiquitin-proteasomal pathway (By similarity). Phosphorylation at Ser-249 by CDK1 disrupts binding of 14-3-3 proteins and promotes nuclear accumulation (By similarity). Phosphorylation by NLK results in nuclear export (PubMed:20061393). Translocates to the nucleus upon oxidative stress-induced phosphorylation at Ser-212 by STK4/MST1 (By similarity). SGK1-mediated phosphorylation also results in nuclear translocation (PubMed:19965929). Retained in the nucleus under stress stimuli including oxidative stress, nutrient deprivation or nitric oxide (PubMed:21196578). Methylated form is nuclear (PubMed:18951090). PPIA/CYPA stimulates its nuclear accumulation (By similarity). Deacetylation by SIRT6, promotes its translocation into the cytoplasm (PubMed:27457971). {ECO:0000250|UniProtKB:Q12778, ECO:0000269|PubMed:18951090, ECO:0000269|PubMed:19965929, ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:21196578, ECO:0000269|PubMed:22298775, ECO:0000269|PubMed:27457971, ECO:0000269|PubMed:32103177}.
uniprot
proteins