FOXO1 (forkhead box O1)

Gene

• Entrez ID: 2308
• Gene name: Forkhead box O1
• Gene symbol: FOXO1
• Synonyms: FKH1, FKHR, FOXO1A
• Chromosome: 13
• Chromosome location: 13q14.11
• Summary: This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. The specific function of this gene has not yet been determined; however, it may play a role in myogenic growth and differentiation. Translocation of this gene with PAX3 has been associated with alveolar rhabdomyosarcoma. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT001086	hsa-miR-182-5p	qRT-PCR, Luciferase reporter assay, Western blot	19574223
MIRT001086	hsa-miR-182-5p	Immunohistochemistry, Microarray, qRT-PCR	24865442
MIRT001086	hsa-miR-182-5p	PAR-CLIP	22012620
MIRT001087	hsa-miR-96-5p	qRT-PCR, Luciferase reporter assay, Western blot	19574223
MIRT001087	hsa-miR-96-5p	Immunohistochemistry, Northern blot, qRT-PCR, Western blot	20028871
MIRT001087	hsa-miR-96-5p	Microarray	23807165
MIRT001087	hsa-miR-96-5p	PAR-CLIP	22012620
MIRT001087	hsa-miR-96-5p	Luciferase reporter assay, qRT-PCR, Western blot	26617698
MIRT001087	hsa-miR-96-5p	Luciferase reporter assay, qRT-PCR, Western blot	25369914
MIRT001088	hsa-miR-27a-3p	qRT-PCR, Luciferase reporter assay, Western blot	19574223
MIRT001088	hsa-miR-27a-3p	Immunohistochemistry, Northern blot, qRT-PCR, Western blot	20028871
MIRT001088	hsa-miR-27a-3p	Immunohistochemistry, qRT-PCR, Western blot	22213032
MIRT001088	hsa-miR-27a-3p	Immunohistochemistry, In situ hybridization, Microarray, qRT-PCR	24746199
MIRT003297	hsa-miR-186-5p	Immunohistochemistry, Northern blot, qRT-PCR, Western blot	20028871
MIRT003298	hsa-miR-183-5p	Immunohistochemistry, Northern blot, qRT-PCR, Western blot	20028871
MIRT003298	hsa-miR-183-5p	PAR-CLIP	22012620
MIRT003298	hsa-miR-183-5p	Luciferase reporter assay, qRT-PCR, Western blot	24368418
MIRT003299	hsa-miR-153-3p	Immunohistochemistry, Northern blot, qRT-PCR, Western blot	20028871
MIRT003300	hsa-miR-9-5p	Immunohistochemistry, Northern blot, qRT-PCR, Western blot	20028871
MIRT003300	hsa-miR-9-5p	Luciferase reporter assay	23509296
MIRT003300	hsa-miR-9-5p	Luciferase reporter assay, qRT-PCR, Western blot	26593208
MIRT006733	hsa-miR-223-3p	Flow, Immunocytochemistry, Luciferase reporter assay, qRT-PCR, Western blot	22569260
MIRT006733	hsa-miR-223-3p	Luciferase reporter assay	24324762
MIRT016933	hsa-miR-335-5p	Microarray	18185580
MIRT027447	hsa-miR-98-5p	Microarray	19088304
MIRT038575	hsa-miR-106b-3p	CLASH	23622248
MIRT045840	hsa-miR-132-3p	CLASH	23622248
MIRT045840	hsa-miR-132-3p	Luciferase reporter assay, qRT-PCR, Western blot	26298723
MIRT045840	hsa-miR-132-3p	Luciferase reporter assay, Western blot	27556448
MIRT048219	hsa-miR-196a-5p	CLASH	23622248
MIRT048219	hsa-miR-196a-5p	Luciferase reporter assay, qRT-PCR, Western blot	24423924
MIRT048219	hsa-miR-196a-5p	Luciferase reporter assay, Western blot	27108614
MIRT048219	hsa-miR-196a-5p	Immunoblot, Luciferase reporter assay	27880728
MIRT051345	hsa-miR-15a-5p	CLASH	23622248
MIRT051345	hsa-miR-15a-5p	Luciferase reporter assay, qRT-PCR, Western blot	24862853
MIRT052909	hsa-miR-15b-5p	Luciferase reporter assay, qRT-PCR, Western blot	24862853
MIRT053058	hsa-miR-370-3p	Luciferase reporter assay, qRT-PCR, Western blot	23721824
MIRT053058	hsa-miR-370-3p	Flow, Luciferase reporter assay, qRT-PCR, Western blot	23029264
MIRT053590	hsa-miR-107	Luciferase reporter assay, qRT-PCR, Western blot	24374340
MIRT054366	hsa-miR-132-5p	In situ hybridization, Luciferase reporter assay, Next Generation Sequencing (NGS), Western blot	24014289
MIRT068628	hsa-let-7c-3p	PAR-CLIP	21572407
MIRT068628	hsa-let-7c-3p	PAR-CLIP	20371350
MIRT438508	hsa-miR-27b-3p	Immunohistochemistry, In situ hybridization, Microarray, qRT-PCR	24746199
MIRT438508	hsa-miR-27b-3p	qRT-PCR, Western blot	26452502
MIRT440614	hsa-miR-376a-3p	HITS-CLIP	24374217
MIRT445364	hsa-miR-526a	PAR-CLIP	22100165
MIRT445365	hsa-miR-523-5p	PAR-CLIP	22100165
MIRT445366	hsa-miR-522-5p	PAR-CLIP	22100165
MIRT445367	hsa-miR-520c-5p	PAR-CLIP	22100165
MIRT445368	hsa-miR-519c-5p	PAR-CLIP	22100165
MIRT445369	hsa-miR-519b-5p	PAR-CLIP	22100165
MIRT445370	hsa-miR-519a-5p	PAR-CLIP	22100165
MIRT445371	hsa-miR-518f-5p	PAR-CLIP	22100165
MIRT445372	hsa-miR-518e-5p	PAR-CLIP	22100165
MIRT445373	hsa-miR-518d-5p	PAR-CLIP	22100165
MIRT445374	hsa-miR-1253	PAR-CLIP	22100165
MIRT445375	hsa-miR-1251-5p	PAR-CLIP	22100165
MIRT445376	hsa-miR-517-5p	PAR-CLIP	22100165
MIRT445377	hsa-miR-520g-5p	PAR-CLIP	22100165
MIRT445378	hsa-miR-3123	PAR-CLIP	22100165
MIRT445379	hsa-miR-8087	PAR-CLIP	22100165
MIRT445380	hsa-miR-3925-5p	PAR-CLIP	22100165
MIRT537315	hsa-miR-1271-5p	PAR-CLIP	22012620
MIRT537316	hsa-miR-593-5p	PAR-CLIP	22012620
MIRT537317	hsa-miR-935	PAR-CLIP	22012620
MIRT537318	hsa-miR-5000-5p	PAR-CLIP	22012620
MIRT537320	hsa-miR-941	PAR-CLIP	22012620
MIRT557807	hsa-miR-3177-5p	PAR-CLIP	21572407
MIRT557807	hsa-miR-3177-5p	PAR-CLIP	20371350
MIRT557808	hsa-miR-324-5p	PAR-CLIP	21572407
MIRT557808	hsa-miR-324-5p	PAR-CLIP	20371350
MIRT557809	hsa-miR-186-3p	PAR-CLIP	21572407
MIRT557809	hsa-miR-186-3p	PAR-CLIP	20371350
MIRT557810	hsa-miR-520h	PAR-CLIP	21572407
MIRT557810	hsa-miR-520h	PAR-CLIP	20371350
MIRT557811	hsa-miR-520g-3p	PAR-CLIP	21572407
MIRT557811	hsa-miR-520g-3p	PAR-CLIP	20371350
MIRT557812	hsa-miR-6715a-3p	PAR-CLIP	21572407
MIRT557813	hsa-miR-4733-5p	PAR-CLIP	21572407
MIRT557813	hsa-miR-4733-5p	PAR-CLIP	20371350
MIRT557814	hsa-miR-34c-3p	PAR-CLIP	21572407
MIRT557815	hsa-miR-499b-3p	PAR-CLIP	21572407
MIRT557816	hsa-miR-499a-3p	PAR-CLIP	21572407
MIRT557817	hsa-miR-562	PAR-CLIP	21572407
MIRT557817	hsa-miR-562	PAR-CLIP	20371350
MIRT658091	hsa-miR-6809-3p	HITS-CLIP	23824327
MIRT658092	hsa-miR-4753-3p	HITS-CLIP	23824327
MIRT658093	hsa-miR-942-5p	HITS-CLIP	23824327
MIRT658094	hsa-miR-130b-5p	HITS-CLIP	23824327
MIRT658095	hsa-miR-4282	HITS-CLIP	23824327
MIRT731353	hsa-miR-9-3p	Luciferase reporter assay, Western blot	28397066
MIRT732296	hsa-miR-135b-5p	Flow, Luciferase reporter assay, Western blot	26617737
MIRT732954	hsa-miR-200c-3p	Luciferase reporter assay, qRT-PCR, Western blot	27917915
MIRT733356	hsa-miR-135a-5p	Luciferase reporter assay, qRT-PCR, Western blot	25888950
MIRT733356	hsa-miR-135a-5p	Luciferase reporter assay	26261511
MIRT733356	hsa-miR-135a-5p	Luciferase reporter assay, qRT-PCR, Western blot	27486383
MIRT733620	hsa-miR-222-3p	qRT-PCR, Western blot	27746366
MIRT733783	hsa-miR-339-3p	Western blot	25695055
MIRT734323	hsa-miR-215-3p	Luciferase reporter assay, qRT-PCR, Western blot	28485164
MIRT734356	hsa-miR-486-5p	Luciferase reporter assay, Western blot	25515961
MIRT735215	hsa-miR-21-5p	Luciferase reporter assay, qRT-PCR, Western blot	25909227

Transcription factors

Transcription factor	Regulation	Reference
FOXC1	Unknown	17993506;21837767
KLF5	Unknown	21487104
PARP1	Repression	19281796
TSC22D3	Repression	20018851

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA	21873635
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001223	Function	Transcription coactivator binding	IEA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	ISS
GO:0001659	Process	Temperature homeostasis	ISS	22510882
GO:0001678	Process	Cellular glucose homeostasis	ISS	22510882
GO:0003682	Function	Chromatin binding	ISS	22510882
GO:0003700	Function	DNA-binding transcription factor activity	IMP	31063815
GO:0005515	Function	Protein binding	IPI	11237865, 11353774, 15220471, 15692560, 15890677, 17030088, 18235501, 18408765, 18786403, 20543840, 24419615, 24983498, 25241761, 25609649, 28514442, 31063815
GO:0005634	Component	Nucleus	IBA	21873635
GO:0005634	Component	Nucleus	IDA	11311120, 12228231, 18680538, 20543840, 31063815
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IDA	11237865, 11311120, 12228231, 20543840, 31063815
GO:0005739	Component	Mitochondrion	ISS	22510882
GO:0005829	Component	Cytosol	ISS	22510882
GO:0005829	Component	Cytosol	TAS
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA	21873635
GO:0006473	Process	Protein acetylation	ISS	22510882
GO:0006914	Process	Autophagy	IEA
GO:0006915	Process	Apoptotic process	IMP	31063815
GO:0006974	Process	Cellular response to DNA damage stimulus	ISS
GO:0008013	Function	Beta-catenin binding	IDA	15905404
GO:0008286	Process	Insulin receptor signaling pathway	IBA	21873635
GO:0008286	Process	Insulin receptor signaling pathway	ISS
GO:0009267	Process	Cellular response to starvation	IDA	20543840
GO:0009267	Process	Cellular response to starvation	ISS	22510882
GO:0010508	Process	Positive regulation of autophagy	IMP	20543840
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS
GO:0031018	Process	Endocrine pancreas development	TAS
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	20543840
GO:0032869	Process	Cellular response to insulin stimulus	ISS
GO:0032873	Process	Negative regulation of stress-activated MAPK cascade	IDA	19696738
GO:0034599	Process	Cellular response to oxidative stress	ISS
GO:0043065	Process	Positive regulation of apoptotic process	IMP	20543840
GO:0043066	Process	Negative regulation of apoptotic process	IDA	10871843
GO:0043565	Function	Sequence-specific DNA binding	IDA	12228231
GO:0045444	Process	Fat cell differentiation	ISS	22510882
GO:0045599	Process	Negative regulation of fat cell differentiation	ISS
GO:0045732	Process	Positive regulation of protein catabolic process	IMP	20543840
GO:0045892	Process	Negative regulation of transcription, DNA-templated	ISS	22510882
GO:0045893	Process	Positive regulation of transcription, DNA-templated	IDA	7862145, 10871843, 12228231
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	10871843, 12228231
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	27577745
GO:0051721	Function	Protein phosphatase 2A binding	ISS
GO:0070166	Process	Enamel mineralization	IEA
GO:0070301	Process	Cellular response to hydrogen peroxide	IEA
GO:0070417	Process	Cellular response to cold	ISS	22510882
GO:0070542	Process	Response to fatty acid	ISS
GO:0071455	Process	Cellular response to hyperoxia	IDA	20543840
GO:0071549	Process	Cellular response to dexamethasone stimulus	IEA
GO:0071732	Process	Cellular response to nitric oxide	ISS
GO:0097009	Process	Energy homeostasis	ISS	22510882
GO:1902617	Process	Response to fluoride	IEA
GO:1903243	Process	Negative regulation of cardiac muscle hypertrophy in response to stress	ISS

Other IDs

• MIM: 136533
• HGNC: 3819
• e!Ensembl: ENSG00000150907

Protein

• UniProt ID: Q12778
• Protein name: Forkhead box protein O1 (Forkhead box protein O1A) (Forkhead in rhabdomyosarcoma)
• Protein function: 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).
• PDB: 3CO6, 3CO7, 3COA, 4LG0, 5DUI, 6LBI, 6QVW, 6QZR, 6QZS
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00250	Forkhead	160 → 247	Forkhead domain	Domain
  PF16675	FOXO_KIX_bdg	423 → 504	KIX-binding domain of forkhead box O, CR2	Family
  PF16676	FOXO-TAD	595 → 635	Transactivation domain of FOXO protein family	Domain

• Sequence:

  MAEAPQVVEIDPDFEPLPRPRSCTWPLPRPEFSQSNSATSSPAPSGSAAANPDAAAGLPS
  ASAAAVSADFMSNLSLLEESEDFPQAPGSVAAAVAAAAAAAATGGLCGDFQGPEAGCLHP
  APPQPPPPGPLSQHPPVPPAAAGPLAGQPRKSSSSRRNAWGNLSYADLITKAIESSAEKR
  LTLSQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIRVQNEGTGKSSWWMLN
  PEGGKSGKSPRRRAASMDNNSKFAKSRSRAAKKKASLQSGQEGAGDSPGSQFSKWPASPG
  SHSNDDFDNWSTFRPRTSSNASTISGRLSPIMTEQDDLGEGDVHSMVYPPSAAKMASTLP
  SLSEISNPENMENLLDNLNLLSSPTSLTVSTQSSPGTMMQQTPCYSFAPPNTSLNSPSPN
  YQKYTYGQSSMSPLPQMPIQTLQDNKSSYGGMSQYNCAPGLLKELLTSDSPPHNDIMTPV
  DPGVAQPNSRVLGQNVMMGPNSVMSTYGSQASHNKMMNPSSHTHPGHAQQTSAVNGRPLP
  HTVSTMPHTSGMNRLTQVKTPVQVPLPHPMQMSALGGYSSVSSCNGYGRMGLLHQEKLPS
  DLDGMFIERLDCDMESIIRNDLMDGDTLDFNFDNVLPNQSFPHSVKTTTHSWVSG

• Sequence length: 655