FOXO1 - Forkhead box protein O1 - human protein (Function)
 
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FOXO1 »  Forkhead box protein O1
 
Protein also known as:  Forkhead in rhabdomyosarcoma.
Gene name:  FOXO1
Entry whose protein(s) existence is based on evidence at protein level
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1 349 1
GENE REF ISO

Function

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Overview 
Transcription factor that is the main target of insulin signaling and regulates metabolic homeostasis in response to oxidative stress. 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'. Activity suppressed by insulin. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Acts syngernistically with ATF4 to suppress osteocalcin/BGLAP activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity. Also suppresses the transcriptional activity of RUNX2, an upstream activator of osteocalcin/BGLAP. In hepatocytes, promotes gluconeogenesis by acting together with PPARGC1A to activate the expression of genes such as IGFBP1, G6PC and PPCK1. Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and SKT4/MST1. Promotes neural cell death. Mediates insulin action on adipose. 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. Regulates the transcriptional activity of GADD45A and repair of nitric oxide-damaged DNA in beta-cells. Required for the autophagic cell death induction in response to starvation or oxidative stress in a transcription-independent manner.  
9
  • UniProtKB
GO molecular function 
Chromatin bindingdefinition[GO:0003682]  
1
  • UniProtKB
Protein bindingdefinition[GO:0005515]  
10
  • IntAct
  • UniProtKB
  • HGNC
Protein phosphatase 2A bindingdefinition[GO:0051721]  
1
  • Ortholog Curator
RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcriptiondefinition[GO:0001078] silver  
1
  • Ortholog Compara
Sequence-specific DNA bindingdefinition[GO:0043565]  
1
  • UniProtKB
Sequence-specific DNA binding RNA polymerase II transcription factor activitydefinition[GO:0000981]  
1
  • RefGenome
Transcription factor binding transcription factor activitydefinition[GO:0000989] silver  
1
  • Ortholog Compara
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • UniProtKB
GO biological process 
Apoptotic processdefinition[GO:0006915]  
1
  • UniProtKB KW
Autophagydefinition[GO:0006914]  
1
  • UniProtKB KW
Blood vessel developmentdefinition[GO:0001568] silver  
1
  • Ortholog Compara
Cellular glucose homeostasisdefinition[GO:0001678]  
1
  • UniProtKB
Cellular response to colddefinition[GO:0070417]  
1
  • UniProtKB
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
1
  • Ortholog Curator
Cellular response to hyperoxiadefinition[GO:0071455]  
1
  • UniProtKB
Cellular response to insulin stimulusdefinition[GO:0032869]  
1
  • Ortholog Curator
Cellular response to nitric oxidedefinition[GO:0071732]  
1
  • Ortholog Curator
Cellular response to oxidative stressdefinition[GO:0034599]  
1
  • Ortholog Curator
Cellular response to starvationdefinition[GO:0009267]  
2
  • UniProtKB
Fat cell differentiationdefinition[GO:0045444]  
1
  • UniProtKB
Insulin receptor signaling pathwaydefinition[GO:0008286]  
1
  • Ortholog Curator
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • UniProtKB
Negative regulation of fat cell differentiationdefinition[GO:0045599]  
1
  • Ortholog Curator
Negative regulation of stress-activated MAPK cascadedefinition[GO:0032873]  
1
  • BHF-UCL
Negative regulation of transcription from RNA polymerase II promoterdefinition[GO:0000122] silver  
1
  • Ortholog Compara
Negative regulation of transcription, DNA-templateddefinition[GO:0045892]  
1
  • UniProtKB
Positive regulation of apoptotic processdefinition[GO:0043065]  
1
  • UniProtKB
Positive regulation of autophagydefinition[GO:0010508]  
1
  • UniProtKB
Positive regulation of gluconeogenesisdefinition[GO:0045722] silver  
1
  • Ortholog Compara
Positive regulation of protein catabolic processdefinition[GO:0045732]  
1
  • UniProtKB
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
2
  • UniProtKB
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
3
  • UniProtKB
Protein acetylationdefinition[GO:0006473]  
1
  • UniProtKB
Regulation of cell proliferationdefinition[GO:0042127] silver  
1
  • Ortholog Compara
Regulation of energy homeostasisdefinition[GO:2000505]  
1
  • UniProtKB
Regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoterdefinition[GO:0035947] silver  
1
  • Ortholog Compara
Temperature homeostasisdefinition[GO:0001659]  
1
  • UniProtKB
Transcription from RNA polymerase II promoterdefinition[GO:0006366]  
1
  • RefGenome
Pathways 
According to KEGG, this protein belongs to the following pathways:
Insulin signaling pathway  hsa04910+2308  
Pathways in cancer  hsa05200+2308  
Prostate cancer  hsa05215+2308  
According to Reactome, this protein belongs to the following pathways:
AKT phosphorylates targets in the nucleus  REACT_12442  
AKT-mediated inactivation of FOXO1A  REACT_13655  
Constitutive PI3K/AKT Signaling in Cancer  REACT_147727  
Regulation of gene expression in beta cells  REACT_13819  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Autophagy  definition   [KW-0072]
Differentiation  definition   [KW-0221]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: FOXO1
GenomeRNAi: 2308
PRO: PR:Q12778