InnateDB Protein
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IDBP-143372.6
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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Foxo1
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Protein Name
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forkhead box O1
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Synonyms
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Afxh; AI876417; FKHR; Fkhr1; Foxo1a;
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Species
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Mus musculus
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Ensembl Protein
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ENSMUSP00000055308
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InnateDB Gene
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IDBG-143370 (Foxo1)
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Protein Structure
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Function |
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. {ECO:0000269PubMed:12754525, ECO:0000269PubMed:15184386, ECO:0000269PubMed:15220471, ECO:0000269PubMed:16917544, ECO:0000269PubMed:17681146, ECO:0000269PubMed:20519497, ECO:0000269PubMed:20668652, ECO:0000269PubMed:21196578, ECO:0000269PubMed:21335550, ECO:0000269PubMed:21471200, ECO:0000269PubMed:22298775, ECO:0000269PubMed:22417654, ECO:0000269PubMed:22510882}.
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Subcellular Localization |
Cytoplasm. Nucleus. Note=Shuttles between the cytoplasm and nucleus. Largely nuclear in unstimulated cells. In osteoblasts, colocalizes with ATF4 and RUNX2 in the nucleus (By similarity). 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-proteosomal pathway. Phosphorylation at Ser-249 by CDK1 disrupts binding of 14-3-3 proteins and promotes nuclear accumulation. Phosphorylation by NLK results in nuclear export. Translocates to the nucleus upon oxidative stress-induced phosphorylation at Ser-212 by STK4/MST1. SGK1-mediated phosphorylation also results in nuclear translocation. Retained in the nucleus under stress stimuli including oxidative stress, nutrient deprivation or nitric oxide. Methylated form is nuclear. {ECO:0000250}.
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Disease Associations |
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Tissue Specificity |
Expressed in white and brown adipose tissues (at protein level). {ECO:0000269PubMed:22510882}.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 38 experimentally validated interaction(s) in this database.
They are also associated with 38 interaction(s) predicted by orthology.
Experimentally validated |
Total |
38
[view]
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Protein-Protein |
26
[view]
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Protein-DNA |
11
[view]
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
1
[view]
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DNA-RNA |
0
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Predicted by orthology |
Total |
38 [view]
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Molecular Function |
Accession |
GO Term |
GO:0000989
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transcription factor binding transcription factor activity
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GO:0001078
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RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription
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GO:0003677
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DNA binding
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GO:0003700
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sequence-specific DNA binding transcription factor activity
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GO:0005515
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protein binding
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GO:0008301
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DNA binding, bending
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GO:0031625
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ubiquitin protein ligase binding
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GO:0043565
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sequence-specific DNA binding
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GO:0051721
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protein phosphatase 2A binding
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Biological Process |
GO:0000122
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negative regulation of transcription from RNA polymerase II promoter
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GO:0001568
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blood vessel development
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GO:0006351
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transcription, DNA-templated
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GO:0006355
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regulation of transcription, DNA-templated
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GO:0006357
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regulation of transcription from RNA polymerase II promoter
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GO:0006915
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apoptotic process
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GO:0006974
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cellular response to DNA damage stimulus
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GO:0007389
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pattern specification process
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GO:0008286
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insulin receptor signaling pathway
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GO:0009267
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cellular response to starvation
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GO:0009888
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tissue development
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GO:0010508
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positive regulation of autophagy
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GO:0031018
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endocrine pancreas development
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GO:0032869
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cellular response to insulin stimulus
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GO:0032873
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negative regulation of stress-activated MAPK cascade
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GO:0034599
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cellular response to oxidative stress
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GO:0035947
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regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter
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GO:0042127
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regulation of cell proliferation
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GO:0042593
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glucose homeostasis
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GO:0043065
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positive regulation of apoptotic process
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GO:0043066
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negative regulation of apoptotic process
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GO:0045599
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negative regulation of fat cell differentiation
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GO:0045722
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positive regulation of gluconeogenesis
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GO:0045732
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positive regulation of protein catabolic process
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GO:0045893
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positive regulation of transcription, DNA-templated
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GO:0045944
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positive regulation of transcription from RNA polymerase II promoter
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GO:0071455
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cellular response to hyperoxia
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GO:0071732
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cellular response to nitric oxide
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Cellular Component |
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PDB ID |
MGI:1890077
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InterPro |
IPR001766
Transcription factor, fork head
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PFAM |
PF00250
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PRINTS |
PR00053
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PIRSF |
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SMART |
SM00339
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TIGRFAMs |
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Modification |
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SwissProt |
Q9R1E0
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PhosphoSite |
PhosphoSite-Q9R1E0
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TrEMBL |
Q8CA93
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UniProt Splice Variant |
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Entrez Gene |
56458
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UniGene |
Mm.408547
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RefSeq |
NP_062713
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MGI ID |
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MGI Symbol |
Foxo1
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OMIM |
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CCDS |
CCDS17343
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HPRD |
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IMGT |
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EMBL |
AF126056
AJ252157
AK039265
AK043583
AK137629
AK154041
CH466530
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GenPept |
AAD40636
BAC30298
BAC31588
BAE23437
BAE32333
CAB86873
EDL35224
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