UniProt Accession

 FOXO1_MOUSE; Q9R1E0; Q9JJW4 

Genbank Protein ID

 AF126056; AJ252157; AK137629; AK154041; CH466530 

Genbank Nucleotide ID

 AAD40636.1; CAB86873.1; BAE23437.1; BAE32333.1; EDL35224.1 

Protein Name

 Forkhead box protein O1 

Protein Synonyms/Alias

 Forkhead box protein O1A; Forkhead in rhabdomyosarcoma 

Gene Name

 Foxo1 

Gene Synonyms/Alias

 Fkhr; Foxo1a 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
242	MLNPEGGKSGKSPRR	acetylation	[1]
245	PEGGKSGKSPRRRAA	acetylation	[1]
262	DNNSKFAKSRGRAAK	acetylation	[1]

Reference

 [1] Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity.
 Daitoku H, Hatta M, Matsuzaki H, Aratani S, Ohshima T, Miyagishi M, Nakajima T, Fukamizu A.
 Proc Natl Acad Sci U S A. 2004 Jul 6;101(27):10042-7. [PMID: 15220471] 

Functional Description

 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. 

Sequence Annotation

 DNA_BIND 156 232 Fork-head.
 REGION 208 215 DNA-binding (By similarity).
 REGION 231 234 DNA-binding (By similarity).
 REGION 280 562 Sufficient for interaction with NLK.
 REGION 360 456 Required for interaction with RUNX2.
 MOTIF 248 250 Nuclear localization signal (By
 MOTIF 459 463 Required for interaction with SIRT1.
 MOD_RES 24 24 Phosphothreonine; by PKB/AKT1 or PKB/AKT2
 MOD_RES 209 209 Phosphoserine; by STK4/MST1 (By
 MOD_RES 242 242 N6-acetyllysine.
 MOD_RES 245 245 N6-acetyllysine.
 MOD_RES 246 246 Phosphoserine; by CDK1 (By similarity).
 MOD_RES 248 248 Omega-N-methylarginine; by PRMT1.
 MOD_RES 250 250 Omega-N-methylarginine; by PRMT1.
 MOD_RES 253 253 Phosphoserine; by PKB/AKT1 and SGK1.
 MOD_RES 262 262 N6-acetyllysine.
 MOD_RES 284 284 Phosphoserine (By similarity).
 MOD_RES 316 316 Phosphoserine; by PKB/AKT1 or PKB/AKT2.
 MOD_RES 319 319 Phosphoserine; by CK1 and SGK1.
 MOD_RES 322 322 Phosphoserine; by CK1 (By similarity).
 MOD_RES 326 326 Phosphoserine; by DYRK1A (By similarity).
 MOD_RES 464 464 Phosphothreonine.
 MOD_RES 465 465 Phosphoserine.  

Keyword

 Acetylation; Activator; Apoptosis; Complete proteome; Cytoplasm; DNA-binding; Methylation; Nucleus; Phosphoprotein; Reference proteome; Transcription; Transcription regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 652 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; IBA:RefGenome.
 GO:0005667; C:transcription factor complex; IBA:RefGenome.
 GO:0008301; F:DNA binding, bending; IBA:RefGenome.
 GO:0003690; F:double-stranded DNA binding; IBA:RefGenome.
 GO:0019901; F:protein kinase binding; IBA:RefGenome.
 GO:0051721; F:protein phosphatase 2A binding; IDA:UniProtKB.
 GO:0001078; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription; IDA:MGI.
 GO:0003705; F:RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; IBA:RefGenome.
 GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
 GO:0008134; F:transcription factor binding; IBA:RefGenome.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0001568; P:blood vessel development; IMP:MGI.
 GO:0071732; P:cellular response to nitric oxide; IDA:UniProtKB.
 GO:0009790; P:embryo development; IBA:RefGenome.
 GO:0031018; P:endocrine pancreas development; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; IMP:MGI.
 GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
 GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB.
 GO:0032873; P:negative regulation of stress-activated MAPK cascade; IBA:RefGenome.
 GO:0007389; P:pattern specification process; IBA:RefGenome.
 GO:0045722; P:positive regulation of gluconeogenesis; IMP:MGI.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
 GO:0042127; P:regulation of cell proliferation; IMP:MGI.
 GO:0035947; P:regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter; IMP:MGI.
 GO:0051090; P:regulation of sequence-specific DNA binding transcription factor activity; IBA:RefGenome.
 GO:0006974; P:response to DNA damage stimulus; IDA:UniProtKB.
 GO:0009888; P:tissue development; IBA:RefGenome. 

Interpro

 IPR001766; TF_fork_head.
 IPR018122; TF_fork_head_CS.
 IPR011991; WHTH_DNA-bd_dom. 

Pfam

 PF00250; Fork_head 

SMART

 SM00339; FH 

PROSITE

 PS00657; FORK_HEAD_1
 PS00658; FORK_HEAD_2
 PS50039; FORK_HEAD_3 

PRINTS

 PR00053; FORKHEAD.