CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011904
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
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
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
245MLNPEGGKSGKSPRRacetylation[1]
248PEGGKSGKSPRRRAAacetylation[1]
262ASMDNNSKFAKSRSRacetylation[2]
265DNNSKFAKSRSRAAKacetylation[1, 2]
274RSRAAKKKASLQSGQacetylation[2]
Reference
 [1] Proteome-wide prediction of acetylation substrates.
 Basu A, Rose KL, Zhang J, Beavis RC, Ueberheide B, Garcia BA, Chait B, Zhao Y, Hunt DF, Segal E, Allis CD, Hake SB.
 Proc Natl Acad Sci U S A. 2009 Aug 18;106(33):13785-90. [PMID: 19666589]
 [2] Characterization and prediction of lysine (K)-acetyl-transferase specific acetylation sites.
 Li T, Du Y, Wang L, Huang L, Li W, Lu M, Zhang X, Zhu WG.
 Mol Cell Proteomics. 2012 Jan;11(1):M111.011080. [PMID: 21964354] 
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 159 235 Fork-head.
 REGION 211 218 DNA-binding.
 REGION 234 237 DNA-binding.
 REGION 283 563 Sufficient for interaction with NLK (By
 REGION 363 459 Required for interaction with RUNX2 (By
 MOTIF 251 253 Nuclear localization signal.
 MOTIF 462 466 Required for interaction with SIRT1 (By
 MOD_RES 24 24 Phosphothreonine; by PKB/AKT1 or PKB/AKT2
 MOD_RES 212 212 Phosphoserine; by STK4/MST1.
 MOD_RES 245 245 N6-acetyllysine (By similarity).
 MOD_RES 248 248 N6-acetyllysine (By similarity).
 MOD_RES 249 249 Phosphoserine; by CDK1.
 MOD_RES 251 251 Omega-N-methylarginine; by PRMT1 (By
 MOD_RES 253 253 Omega-N-methylarginine; by PRMT1 (By
 MOD_RES 256 256 Phosphoserine; by PKB/AKT1 and SGK1.
 MOD_RES 265 265 N6-acetyllysine (By similarity).
 MOD_RES 287 287 Phosphoserine.
 MOD_RES 319 319 Phosphoserine; by PKB/AKT1.
 MOD_RES 322 322 Phosphoserine; by CK1 and SGK1.
 MOD_RES 325 325 Phosphoserine; by CK1.
 MOD_RES 329 329 Phosphoserine; by DYRK1A.
 MOD_RES 467 467 Phosphothreonine (By similarity).
 MOD_RES 468 468 Phosphoserine (By similarity).  
Keyword
 3D-structure; Acetylation; Activator; Apoptosis; Chromosomal rearrangement; Complete proteome; Cytoplasm; DNA-binding; Methylation; Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; Transcription; Transcription regulation; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 655 AA 
Protein Sequence
MAEAPQVVEI DPDFEPLPRP RSCTWPLPRP EFSQSNSATS SPAPSGSAAA NPDAAAGLPS 60
ASAAAVSADF MSNLSLLEES EDFPQAPGSV AAAVAAAAAA AATGGLCGDF QGPEAGCLHP 120
APPQPPPPGP LSQHPPVPPA AAGPLAGQPR KSSSSRRNAW GNLSYADLIT KAIESSAEKR 180
LTLSQIYEWM VKSVPYFKDK GDSNSSAGWK NSIRHNLSLH SKFIRVQNEG TGKSSWWMLN 240
PEGGKSGKSP RRRAASMDNN SKFAKSRSRA AKKKASLQSG QEGAGDSPGS QFSKWPASPG 300
SHSNDDFDNW STFRPRTSSN ASTISGRLSP IMTEQDDLGE GDVHSMVYPP SAAKMASTLP 360
SLSEISNPEN MENLLDNLNL LSSPTSLTVS TQSSPGTMMQ QTPCYSFAPP NTSLNSPSPN 420
YQKYTYGQSS MSPLPQMPIQ TLQDNKSSYG GMSQYNCAPG LLKELLTSDS PPHNDIMTPV 480
DPGVAQPNSR VLGQNVMMGP NSVMSTYGSQ ASHNKMMNPS SHTHPGHAQQ TSAVNGRPLP 540
HTVSTMPHTS GMNRLTQVKT PVQVPLPHPM QMSALGGYSS VSSCNGYGRM GLLHQEKLPS 600
DLDGMFIERL DCDMESIIRN DLMDGDTLDF NFDNVLPNQS FPHSVKTTTH SWVSG 655 
Gene Ontology
 GO:0005829; C:cytosol; ISS:UniProtKB.
 GO:0005739; C:mitochondrion; ISS:UniProtKB.
 GO:0005667; C:transcription factor complex; IBA:RefGenome.
 GO:0003682; F:chromatin binding; ISS:UniProtKB.
 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; ISS:UniProtKB.
 GO:0001078; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription; IEA:Compara.
 GO:0003705; F:RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity; IBA:RefGenome.
 GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
 GO:0008134; F:transcription factor binding; IBA:RefGenome.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0001568; P:blood vessel development; IBA:RefGenome.
 GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
 GO:0070417; P:cellular response to cold; ISS:UniProtKB.
 GO:0071732; P:cellular response to nitric oxide; ISS:UniProtKB.
 GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
 GO:0009790; P:embryo development; IBA:RefGenome.
 GO:0031018; P:endocrine pancreas development; TAS:Reactome.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0045444; P:fat cell differentiation; ISS:UniProtKB.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0008286; P:insulin receptor signaling pathway; ISS:UniProtKB.
 GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
 GO:0045599; P:negative regulation of fat cell differentiation; ISS:UniProtKB.
 GO:0032873; P:negative regulation of stress-activated MAPK cascade; IDA:BHF-UCL.
 GO:0045892; P:negative regulation of transcription, DNA-dependent; ISS:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0007389; P:pattern specification process; IBA:RefGenome.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0045722; P:positive regulation of gluconeogenesis; IEA:Compara.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0006473; P:protein acetylation; ISS:UniProtKB.
 GO:0042127; P:regulation of cell proliferation; IBA:RefGenome.
 GO:2000505; P:regulation of energy homeostasis; ISS:UniProtKB.
 GO:0051090; P:regulation of sequence-specific DNA binding transcription factor activity; IBA:RefGenome.
 GO:0006974; P:response to DNA damage stimulus; ISS:UniProtKB.
 GO:0001659; P:temperature homeostasis; ISS: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.