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IID00464
UniprotQ12778
ProteinForkhead box protein O1
GeneFOXO1
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
xml
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
655
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 143-270 Hetero dimer :
 Evidence X-RAY 4lg0 A Reference
       Region 4lg0 A 143-155 disorder
       Region 4lg0 A 156-244 order
       Region 4lg0 A 245-270 disorder
Seq 151-259 Homo dimer :
 Evidence X-RAY 5dui B Reference
       Region 5dui B 151-160 disorder
       Region 5dui B 161-245 order
       Region 5dui B 246-259 disorder
 Evidence X-RAY 5dui A Reference
       Region 5dui A 151-159 disorder
       Region 5dui A 160-245 order
       Region 5dui A 246-259 disorder
Seq 151-266 Monomer :
 Evidence X-RAY 3coa F Reference
       Region 3coa F 151-154 disorder
       Region 3coa F 155-241 order
       Region 3coa F 242-266 disorder
 Evidence X-RAY 3coa C Reference
       Region 3coa C 151-155 disorder
       Region 3coa C 156-241 order
       Region 3coa C 242-266 disorder
 Evidence X-RAY 3co7 F Reference
       Region 3co7 F 151-154 disorder
       Region 3co7 F 155-241 order
       Region 3co7 F 242-266 disorder
 Evidence X-RAY 3co7 C Reference
       Region 3co7 C 151-154 disorder
       Region 3co7 C 155-241 order
       Region 3co7 C 242-266 disorder
 Evidence X-RAY 3co6 C Reference
       Region 3co6 C 151-153 disorder
       Region 3co6 C 154-244 order
       Region 3co6 C 245-249 disorder
Seqphosphorylation
    235-235 Phosphoserine; by STK4/MST1
    234-234 Phosphoserine; by STK4/MST1
    218-218 Phosphoserine; by STK4/MST1
    212-212 Phosphoserine; by STK4/MST1
    24-24 Phosphothreonine; by PKB/AKT1 or PKB/AKT2 and SGK1
    322-322 Phosphoserine; by CK1 and SGK1
    249-249 Phosphoserine; by CDK1
    256-256 Phosphoserine; by PKB/AKT1 and SGK1
    287-287 Phosphoserine
    298-298 Phosphoserine
    319-319 Phosphoserine; by PKB/AKT1
    325-325 Phosphoserine; by CK1
    329-329 Phosphoserine; by DYRK1A
    333-333 Phosphothreonine
Seqacetylation
    248-248 N6-acetyllysine
    262-262 N6-acetyllysine
    265-265 N6-acetyllysine
    274-274 N6-acetyllysine
    245-245 N6-acetyllysine
    423-423 N6-acetyllysine
 
Prediction
NeProc
Disorder 1-161,201-206,246-628,635-655
Order 162-200,207-245,629-634
ProS 6-33,157-161,246-262,271-275,296-299,304-313,374-381,595-628,650-655
AlphaFold
Disorder 1-10,12-124,126-156,204-205,243-253,255-613,620-655
Order 11-11,125-125,157-203,206-242,254-254,614-619
Pfam Hmmer
PF00250 124-269 9.1e-23
SEG 33-68 ,90-102 ,120-149 ,261-276 ,373-394 ,409-420
Function
Function in SwissProt
Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress (PubMed:10358076, PubMed:12228231, PubMed:15220471, PubMed:15890677, PubMed:18356527, PubMed:19221179, PubMed:20543840, PubMed:21245099). 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:10358076). Activity suppressed by insulin (PubMed:10358076). Main regulator of redox balance and osteoblast numbers and controls bone mass (By similarity). Orchestrates the endocrine function of the skeleton in regulating glucose metabolism (By similarity). 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 (By similarity). Acts synergistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity (By similarity). Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP (By similarity). In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1, G6PC1 and PCK1 (By similarity). Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and STK4/MST1 (PubMed:18356527, PubMed:19221179). Promotes neural cell death (PubMed:18356527). 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 (By similarity). Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner (PubMed:20543840). Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (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 (PubMed:31063815).
Biological Process
Diagram with PDB data
FOXO1/SFN14-3-3 sigma in complex with FOXO1 pT24 peptide