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IID00433
UniprotO43524
ProteinForkhead box protein O3
GeneFOXO3
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
673
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 151-253 Monomer :
 Evidence NMR 2k86 A Reference
       Region 2k86 A 151-251 order
       Region 2k86 A 151-151 high_rmsd
       Region 2k86 A 228-229 high_rmsd
       Region 2k86 A 247-251 high_rmsd
 Evidence X-RAY 2uzk C Reference
       Region 2uzk C 158-247 order
       Region 2uzk C 248-253 disorder
 Evidence X-RAY 2uzk A Reference
       Region 2uzk A 158-253 order
Seq 461-483,618-635 Hetero dimer : IID50008Complex
 Evidence NMR 2lqi B This region is the chimera protein. Reference
       Region 2lqi B 461-483 order
       Region 2lqi B 461-464 high_rmsd
       Region 2lqi B 482-483 high_rmsd
       Region 2lqi B 618-635 order
 Evidence NMR 2lqh B This region is the chimera protein. Reference
       Region 2lqh B 461-483 order
       Region 2lqh B 461-464 high_rmsd
       Region 2lqh B 483-483 high_rmsd
       Region 2lqh B 618-635 order
Seqdisorder 461-483,618-635
 Evidence CD Reference
       Region 461-483 disorder
       Region 618-635 disorder
SeqProS verified 466-481,623-634 Hetero dimer : IID50008Complex
       Region 2lqh B 461-483 order
       Region 2lqi B 461-483 order
       Region 2lqh B 618-635 order
       Region 2lqi B 618-635 order
       Region 461-483 disorder
       Region 618-635 disorder
Seqphosphorylation
    294-294 Phosphoserine
    284-284 Phosphoserine
    280-280 Phosphoserine
    253-253 Phosphoserine; by PKB/AKT1 and MAPKAPK5
    215-215 Phosphoserine; by MAPKAPK5
    209-209 Phosphoserine; by STK4/MST1
    179-179 Phosphothreonine; by AMPK
    299-299 Phosphoserine; by CaMK2A
    32-32 Phosphothreonine; by PKB/AKT1
    30-30 Phosphoserine; by AMPK
    644-644 Phosphoserine; by IKKB
    626-626 Phosphoserine; by AMPK
    588-588 Phosphoserine; by AMPK
    555-555 Phosphoserine; by AMPK and MAPKAPK5
    551-551 Phosphoserine; by MAPKAPK5
    421-421 Phosphoserine
    413-413 Phosphoserine; by AMPK
    399-399 Phosphoserine; by AMPK
    315-315 Phosphoserine; by SGK1
    311-311 Phosphoserine
Seqacetylation
    242-242 N6-acetyllysine
 
Prediction
NeProc
Disorder 1-159,199-203,242-611,624-630,647-673
Order 160-198,204-241,612-623,631-646
ProS 13-40,154-159,242-246,270-273,305-310,356-359,469-472,604-611,624-630,668-673
AlphaFold
Disorder 1-133,135-153,201-202,228-228,240-248,256-622,630-673
Order 134-134,154-200,203-227,229-239,249-255,623-629
Pfam Hmmer
PF00250 134-249 1e-20
SEG 2-15 ,59-94 ,121-147 ,267-273 ,342-359 ,468-483 ,530-539 ,583-599
Function
Function in SwissProt
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:10102273, PubMed:16751106, PubMed:21329882). 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 (By similarity). Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (PubMed:10102273, PubMed:16751106). 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 (PubMed:21329882). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription (PubMed:23283301). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription. 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).
Biological Process
Diagram with PDB data
FOXO3/YWHAECrystal Structure of 14-3-3 epsilon with FOXO3a peptide