| Gene Symbol | FOXO1 |
|---|---|
| Entrez Gene | 2308 |
| Alt Symbol | FKH1, FKHR, FOXO1A |
| Species | Human |
| Gene Type | protein-coding |
| Description | forkhead box O1 |
| Other Description | forkhead box protein O1|forkhead box protein O1A|forkhead, Drosophila, homolog of, in rhabdomyosarcoma |
| Swissprots | Q6NSK6 Q5VYC7 O43523 Q12778 |
| Accessions | AAC50342 AAC50343 EAX08627 Q12778 AF032885 AAC39591 AK310511 BC021981 AAH21981 BC070065 AAH70065 BT007455 AAP36123 BX648278 U02310 AAA03629 U36922 XM_011535008 XP_011533310 XM_011535009 XP_011533311 XM_011535010 XP_011533312 XR_941536 NM_002015 NP_002006 |
| 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 synergistically 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 and CEBPA to activate the expression of genes such as IGFBP1, G6PC and PCK1. Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and S |
| Subcellular Location | Cytoplasm {ECO:0000250|UniProtKB:Q9R1E0}. Nucleus {ECO:0000250|UniProtKB:Q9R1E0}. 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-256 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. Retained in the nucleus on methylation. {ECO:0000250}. |
| Tissue Specificity | Ubiquitous. {ECO:0000269|PubMed:9479491}. |
| Top Pathways | Insulin signaling pathway, Prostate cancer, AMPK signaling pathway, Glucagon signaling pathway, Transcriptional misregulation in cancer |