Q12778

※ Protein Information

Tag	Content
UniProt Accession	FOXO1_HUMAN; Q12778;
Entrez ID	2308
GenBank Protein ID
GenBank Nucleotide ID
Protein Name	Forkhead box protein O1 (Forkhead box protein O1A) (Forkhead in rhabdomyosarcoma)
Gene Name	FOXO1; FKHR; FOXO1A
Organism	Homo sapiens
NCBI Taxa ID	9606
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 synergistically with ATF4 to s(view all) 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 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 SKT4/MST1. Promotes neural cell death. Mediates insulin action on adipose tissue. 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. Mediates the function of MLIP in cardiomyocytes hypertrophy and cardiac remodeling (By similarity).
Sequence (Fasta)	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 656 Fasta Sequence >Q12778\|FOXO1; FKHR; FOXO1A\|Homo sapiens (Human) MAEAPQVVEIDPDFEPLPRPRSCTWPLPRPEFSQSNSATSSPAPSGSAAANPDAAAGLPSASAAAVSADFMSNLSLLEESEDFPQAPGSVAAAVAAAAAAAATGGLCGDFQGPEAGCLHPAPPQPPPPGPLSQHPPVPPAAAGPLAGQPRKSSSSRRNAWGNLSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIRVQNEGTGKSSWWMLNPEGGKSGKSPRRRAASMDNNSKFAKSRSRAAKKKASLQSGQEGAGDSPGSQFSKWPASPGSHSNDDFDNWSTFRPRTSSNASTISGRLSPIMTEQDDLGEGDVHSMVYPPSAAKMASTLPSLSEISNPENMENLLDNLNLLSSPTSLTVSTQSSPGTMMQQTPCYSFAPPNTSLNSPSPNYQKYTYGQSSMSPLPQMPIQTLQDNKSSYGGMSQYNCAPGLLKELLTSDSPPHNDIMTPVDPGVAQPNSRVLGQNVMMGPNSVMSTYGSQASHNKMMNPSSHTHPGHAQQTSAVNGRPLPHTVSTMPHTSGMNRLTQVKTPVQVPLPHPMQMSALGGYSSVSSCNGYGRMGLLHQEKLPSDLDGMFIERLDCDMESIIRNDLMDGDTLDFNFDNVLPNQSFPHSVKTTTHSWVSG

※ PTM-Disease Association

Num	PTM	Disease	Type	PTM Site	PMID
1	Serine Phosphorylation	Prostate cancer/carcinoma/adenocarcinoma	P	S249	21969818
1	[Reference]: Inhibition of cyclin-dependent kinase phosphorylation of FOXO1 and prostate cancer cell growth by a peptide derived from FOXO1
2	Serine Phosphorylation	Hepatitis	D	S256	18316359
2	[Reference]: FOXO1 upregulation was confirmed at protein levels in steatohepatitis and, in the presence of oxidative stress, was associated with decreased Ser(256) phosphorylation, decreased Akt1, and increased Jun NH(2)-terminal kinase-1 activity.
3	Serine Phosphorylation	Astrocytoma/Astrocytoma glioblastoma	U	S256	23874926
3	[Reference]: Astrocytoma samples expressed higher cytoplasmic FOXO1 and pFOXO1 than normal brain samples

※ Disease Cross-ref Annotation

Database	Annotation
Cancer Gene Census	alveolar rhabdomyosarcoma
CTD (Curated) (count: 4)	MESH:D006976 ; Hypertension, Pulmonary MESH:D007640 ; Keratoconus MESH:D015470 ; Leukemia, Myeloid, Acute MESH:D018232 ; Rhabdomyosarcoma, Alveolar
DisGeNet (Curated) (count: 4)	C0022578; Keratoconus C0023467; Leukemia, Myelocytic, Acute C0206655; Alveolar rhabdomyosarcoma C4020899; Autosomal recessive predisposition
GWASdb (count: 9) (view all)	rs2701858; Atrial fibrillation; familial atrial fibrillation rs2701859; Myopia (pathological); myopia rs9549236; Multiple complex diseases; Null rs2951787; Urinary metabolites; kidney disease rs4943794; Longevity and age-related phenotypes; Null rs7986407; Myopia (pathological); myopia rs10507486; Longevity and age-related phenotypes; Null rs9549244; Rheumatoid arthritis; rheumatoid arthritis rs9549244; Myopia (pathological); myopia

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 39) (view all)	212 SSAGWKNSIRHNLSL dbPAF 218 NSIRHNLSLHSKFIR dbPAF 234 QNEGTGKSSWWMLNP dbPAF 235 NEGTGKSSWWMLNPE dbPAF 24 LPRPRSCTWPLPRPE dbPAF 249 EGGKSGKSPRRRAAS dbPAF 256 SPRRRAASMDNNSKF dbPAF 287 GQEGAGDSPGSQFSK dbPAF 290 GAGDSPGSQFSKWPA dbPAF 293 DSPGSQFSKWPASPG dbPAF 298 QFSKWPASPGSHSND dbPAF 301 KWPASPGSHSNDDFD dbPAF 303 PASPGSHSNDDFDNW dbPAF 317 WSTFRPRTSSNASTI dbPAF 318 STFRPRTSSNASTIS dbPAF 319 TFRPRTSSNASTISG dbPAF 322 PRTSSNASTISGRLS dbPAF 323 RTSSNASTISGRLSP dbPAF 325 SSNASTISGRLSPIM dbPAF 329 STISGRLSPIMTEQD dbPAF 333 GRLSPIMTEQDDLGE dbPAF 383 DNLNLLSSPTSLTVS dbPAF 394 LTVSTQSSPGTMMQQ dbPAF 402 PGTMMQQTPCYSFAP dbPAF 416 PPNTSLNSPSPNYQK dbPAF 418 NTSLNSPSPNYQKYT dbPAF 429 QKYTYGQSSMSPLPQ dbPAF 430 KYTYGQSSMSPLPQM dbPAF 432 TYGQSSMSPLPQMPI dbPAF 467 GLLKELLTSDSPPHN dbPAF 468 LLKELLTSDSPPHND dbPAF 470 KELLTSDSPPHNDIM dbPAF 478 PPHNDIMTPVDPGVA dbPAF 505 MGPNSVMSTYGSQAS dbPAF 509 SVMSTYGSQASHNKM dbPAF 648 FPHSVKTTTHSWVSG dbPAF 649 PHSVKTTTHSWVSG* dbPAF 651 SVKTTTHSWVSG* dbPAF 654 TTTHSWVSG**** dbPAF
Acetylation (count: 5)	245 MLNPEGGKSGKSPRR PLMD 248 PEGGKSGKSPRRRAA PLMD 262 ASMDNNSKFAKSRSR PLMD 265 DNNSKFAKSRSRAAK PLMD 274 RSRAAKKKASLQSGQ PLMD

PTM

Modification Sites

Phosphorylation
(count: 39)
(view all)

212       SSAGWKNSIRHNLSL     dbPAF
218       NSIRHNLSLHSKFIR     dbPAF
234       QNEGTGKSSWWMLNP     dbPAF
235       NEGTGKSSWWMLNPE     dbPAF
24        LPRPRSCTWPLPRPE     dbPAF
249       EGGKSGKSPRRRAAS     dbPAF

Acetylation
(count: 5)

245       MLNPEGGKSGKSPRR     PLMD
248       PEGGKSGKSPRRRAA     PLMD
262       ASMDNNSKFAKSRSR     PLMD
265       DNNSKFAKSRSRAAK     PLMD
274       RSRAAKKKASLQSGQ     PLMD

※ Protein-Protein Interaction

Network

Interaction

Source

P03372	Q12778	HPRD; IntAct
P06493	Q12778	IntAct
P10275	Q12778	HPRD; IntAct
P10276	Q12778	HPRD
P10828	Q12778	HPRD
P12931	Q12778	HPRD
P14635	Q12778	IntAct
P17676	Q12778	HPRD
P20719	Q12778	HPRD
P31260	Q12778	HPRD
P31749	Q12778	HPRD; DIP
P31750	Q12778	MINT
P35222	Q12778	HPRD
P35575	Q12778	HPRD
P37231	Q12778	HPRD
P41235	Q12778	HPRD
P49715	Q12778	MINT
P49841	Q12778	HPRD
P55316	Q12778	HPRD
P61981	Q12778	HPRD
P63104	Q12778	HPRD
P84022	Q12778	HPRD
Q12778	Q13043	DIP
Q12778	Q13153	HPRD
Q12778	Q13485	HPRD
Q12778	Q13627	HPRD
Q12778	Q14192	HPRD; IntAct
Q12778	Q4LE28	HPRD
Q12778	Q92793	IntAct
Q12778	Q96EB6	HPRD; IntAct
Q12778	Q9HCP0	HPRD

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction