dbPTM

FOXO1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	FOXO1_MOUSE
UniProt AC	Q9R1E0
Protein Name	Forkhead box protein O1
Gene Name	Foxo1
Organism	Mus musculus (Mouse).
Sequence Length	652
Subcellular Localization	Cytoplasm . Nucleus . 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-253 by PKB/AKT1 leads, via
Protein 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 STK4/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)..
Protein Sequence	MAEAPQVVETDPDFEPLPRQRSCTWPLPRPEFNQSNSTTSSPAPSGGAAANPDAAASLASASAVSTDFMSNLSLLEESEDFARAPGCVAVAAAAAASRGLCGDFQGPEAGCVHPAPPQPPPTGPLSQPPPVPPSAAAAAGPLAGQPRKTSSSRRNAWGNLSYADLITKAIESSAEKRLTLSQIYEWMVKSVPYFKDKGDSNSSAGWKNSIRHNLSLHSKFIRVQNEGTGKSSWWMLNPEGGKSGKSPRRRAASMDNNSKFAKSRGRAAKKKASLQSGQEGPGDSPGSQFSKWPASPGSHSNDDFDNWSTFRPRTSSNASTISGRLSPIMTEQDDLGDGDVHSLVYPPSAAKMASTLPSLSEISNPENMENLLDNLNLLSSPTSLTVSTQSSPGSMMQQTPCYSFAPPNTSLNSPSPNYSKYTYGQSSMSPLPQMPMQTLQDSKSSYGGLNQYNCAPGLLKELLTSDSPPHNDIMSPVDPGVAQPNSRVLGQNVMMGPNSVMPAYGSQASHNKMMNPSSHTHPGHAQQTASVNGRTLPHVVNTMPHTSAMNRLTPVKTPLQVPLSHPMQMSALGSYSSVSSCNGYGRMGVLHQEKLPSDLDGMFIERLDCDMESIIRNDLMDGDTLDFNFDNVLPNQSFPHSVKTTTHSWVSG

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
24	Phosphorylation	LPRQRSCTWPLPRPE CCCCCCCCCCCCCCC	31.22	10377430
209	Phosphorylation	SSAGWKNSIRHNLSL CCHHHHHHHHHHHEE	19.78	-
215	Phosphorylation	NSIRHNLSLHSKFIR HHHHHHHEEECEEEE	29.38	30352176
231	Phosphorylation	QNEGTGKSSWWMLNP EECCCCCCCEEEECC	32.32	-
232	Phosphorylation	NEGTGKSSWWMLNPE ECCCCCCCEEEECCC	28.39	-
242	Acetylation	MLNPEGGKSGKSPRR EECCCCCCCCCCHHH	67.88	17090532
245	Acetylation	PEGGKSGKSPRRRAA CCCCCCCCCHHHHHH	65.46	17090532
246	Phosphorylation	EGGKSGKSPRRRAAS CCCCCCCCHHHHHHH	27.45	18356527
248	Methylation	GKSGKSPRRRAASMD CCCCCCHHHHHHHCC	48.05	18951090
250	Methylation	SGKSPRRRAASMDNN CCCCHHHHHHHCCCC	35.47	18951090
253	Phosphorylation	SPRRRAASMDNNSKF CHHHHHHHCCCCHHH	26.19	27087446
258	Phosphorylation	AASMDNNSKFAKSRG HHHCCCCHHHHHHHH	35.09	22324799
259	Acetylation	ASMDNNSKFAKSRGR HHCCCCHHHHHHHHH	52.01	-
262	Acetylation	DNNSKFAKSRGRAAK CCCHHHHHHHHHHHH	43.76	17090532
271	Acetylation	RGRAAKKKASLQSGQ HHHHHHHHHHHCCCC	42.36	-
273	Phosphorylation	RAAKKKASLQSGQEG HHHHHHHHHCCCCCC	35.50	25619855
276	Phosphorylation	KKKASLQSGQEGPGD HHHHHHCCCCCCCCC	47.97	25619855
284	Phosphorylation	GQEGPGDSPGSQFSK CCCCCCCCCCCCCCC	36.76	25521595
287	Phosphorylation	GPGDSPGSQFSKWPA CCCCCCCCCCCCCCC	31.28	25619855
290	Phosphorylation	DSPGSQFSKWPASPG CCCCCCCCCCCCCCC	26.61	25619855
295	Phosphorylation	QFSKWPASPGSHSND CCCCCCCCCCCCCCC	26.22	23684622
298	Phosphorylation	KWPASPGSHSNDDFD CCCCCCCCCCCCCCC	27.42	26643407
300	Phosphorylation	PASPGSHSNDDFDNW CCCCCCCCCCCCCCC	43.59	26643407
314	Phosphorylation	WSTFRPRTSSNASTI CCCCCCCCCCCCCEE	38.91	27087446
315	Phosphorylation	STFRPRTSSNASTIS CCCCCCCCCCCCEEC	23.91	19060867
316	Phosphorylation	TFRPRTSSNASTISG CCCCCCCCCCCEECC	35.48	27087446
319	Phosphorylation	PRTSSNASTISGRLS CCCCCCCCEECCCCC	30.44	25521595
320	Phosphorylation	RTSSNASTISGRLSP CCCCCCCEECCCCCC	19.42	29472430
322	Phosphorylation	SSNASTISGRLSPIM CCCCCEECCCCCCCC	20.25	29472430
326	Phosphorylation	STISGRLSPIMTEQD CEECCCCCCCCCCCC	15.83	25521595
330	Phosphorylation	GRLSPIMTEQDDLGD CCCCCCCCCCCCCCC	31.08	27087446
342	Phosphorylation	LGDGDVHSLVYPPSA CCCCCCCCEECCHHH	21.27	29899451
380	Phosphorylation	DNLNLLSSPTSLTVS HHHHHCCCCCEEEEE	31.97	22817900
391	Phosphorylation	LTVSTQSSPGSMMQQ EEEECCCCCCCCCCC	24.38	22817900
399	Phosphorylation	PGSMMQQTPCYSFAP CCCCCCCCCCCCCCC	9.83	22817900
413	Phosphorylation	PPNTSLNSPSPNYSK CCCCCCCCCCCCCCC	31.86	17113751
415	Phosphorylation	NTSLNSPSPNYSKYT CCCCCCCCCCCCCCC	26.12	17113751
421	Phosphorylation	PSPNYSKYTYGQSSM CCCCCCCCCCCCCCC	10.15	28833060
422	Phosphorylation	SPNYSKYTYGQSSMS CCCCCCCCCCCCCCC	25.55	28833060
423	Phosphorylation	PNYSKYTYGQSSMSP CCCCCCCCCCCCCCC	15.30	28833060
426	Phosphorylation	SKYTYGQSSMSPLPQ CCCCCCCCCCCCCCC	24.52	28833060
427	Phosphorylation	KYTYGQSSMSPLPQM CCCCCCCCCCCCCCC	18.52	28833060
429	Phosphorylation	TYGQSSMSPLPQMPM CCCCCCCCCCCCCCC	25.82	28833060
438	Phosphorylation	LPQMPMQTLQDSKSS CCCCCCCHHCCCHHC	21.82	28833060
464	Phosphorylation	GLLKELLTSDSPPHN HHHHHHHCCCCCCCC	43.01	27742792
465	Phosphorylation	LLKELLTSDSPPHND HHHHHHCCCCCCCCC	35.74	27742792
467	Phosphorylation	KELLTSDSPPHNDIM HHHHCCCCCCCCCCC	39.85	25521595
475	Phosphorylation	PPHNDIMSPVDPGVA CCCCCCCCCCCCCCC	23.31	27742792
499	Phosphorylation	NVMMGPNSVMPAYGS CCCCCCCCCCCCCCC	23.95	12724332
553	Phosphorylation	TSAMNRLTPVKTPLQ CCCCCCCCCCCCCCC	23.85	22503562
557	Phosphorylation	NRLTPVKTPLQVPLS CCCCCCCCCCCCCCC	29.48	17113751
646	O-linked_Glycosylation	PHSVKTTTHSWVSG- CCCCCCCCCCCCCC-	21.10	28528544

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
24	T	Phosphorylation	Kinase	AKT1	P31750	Uniprot
24	T	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
24	T	Phosphorylation	Kinase	AKT2	Q60823	Uniprot
24	T	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
24	T	Phosphorylation	Kinase	SGK1	Q9WVC6	Uniprot
150	S	Phosphorylation	Kinase	PKACA	P17612	PSP
209	S	Phosphorylation	Kinase	MST1	P26928	Uniprot
246	S	Phosphorylation	Kinase	CDK1	P06493	PSP
246	S	Phosphorylation	Kinase	CDK1	P11440	Uniprot
246	S	Phosphorylation	Kinase	CDK2	P24941	PSP
246	S	Phosphorylation	Kinase	CDK5	Q00535	PSP
246	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
253	S	Phosphorylation	Kinase	AKT1	P31750	Uniprot
253	S	Phosphorylation	Kinase	PKB_GROUP	-	PhosphoELM
253	S	Phosphorylation	Kinase	AKT-FAMILY	-	GPS
253	S	Phosphorylation	Kinase	SGK1	Q9WVC6	Uniprot
273	S	Phosphorylation	Kinase	PKACA	P17612	PSP
284	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
284	S	Phosphorylation	Kinase	MAPK14	P47811	GPS
295	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
295	S	Phosphorylation	Kinase	MAPK14	P47811	GPS
316	S	Phosphorylation	Kinase	AKT1	P31750	Uniprot
316	S	Phosphorylation	Kinase	AKT2	Q60823	Uniprot
319	S	Phosphorylation	Kinase	CK1	-	Uniprot
319	S	Phosphorylation	Kinase	CK1-FAMILY	-	GPS
319	S	Phosphorylation	Kinase	SGK1	Q9WVC6	Uniprot
322	S	Phosphorylation	Kinase	CK1	-	Uniprot
326	S	Phosphorylation	Kinase	MAPK14	P47811	GPS
326	S	Phosphorylation	Kinase	MAPK3	Q63844	GPS
326	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
413	S	Phosphorylation	Kinase	MAPK14	P47811	GPS
413	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
415	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
429	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
429	S	Phosphorylation	Kinase	MAPK14	P47811	GPS
467	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
467	S	Phosphorylation	Kinase	MAPK14	P47811	GPS
475	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
475	S	Phosphorylation	Kinase	MAPK14	P47811	GPS
557	T	Phosphorylation	Kinase	MAPK14	P47811	GPS
557	T	Phosphorylation	Kinase	MAPK1	P63085	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	Fbxo32	Q9CPU7	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Skp2	Q9Z0Z3	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Itch	Q8C863	PMID:24859451

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
24	T	Phosphorylation	10347145
Phosphorylation on Thr-24 is required for binding 14-3-3 proteins.
24	T	Phosphorylation	10347145
Phosphorylation of Ser-253 decreases DNA-binding activity and promotes the phosphorylation of Thr-24 and Ser-316, permitting phosphorylation of Ser-319 and Ser-322, probably by CDK1, leading to nuclear exclusion and loss of function.
24	T	Phosphorylation	10347145
In response to growth factors, phosphorylation on Thr-24, Ser-253 and Ser-319 by PKB/AKT1 promotes nuclear export and inactivation of transactivational activity.
24	T	Phosphorylation	10347145
Dephosphorylated on Thr-24 and Ser-253 by PP2A in beta-cells under oxidative stress leading to nuclear retention (By similarity).
24	T	Oxidation	10347145
Dephosphorylated on Thr-24 and Ser-253 by PP2A in beta-cells under oxidative stress leading to nuclear retention (By similarity).
209	S	Oxidation	10347145
Phosphorylation by STK4/MST1 on Ser-209, upon oxidative stress, inhibits binding to 14-3-3 proteins and nuclear export (By similarity).
209	S	Phosphorylation	10347145
Phosphorylation by STK4/MST1 on Ser-209, upon oxidative stress, inhibits binding to 14-3-3 proteins and nuclear export (By similarity).
246	S	Phosphorylation	10347145
Phosphorylation of Ser-246 by CDK1 disrupts binding of 14-3-3 proteins leading to nuclear accumulation and has no effect on DNA-binding nor transcriptional activity.
253	S	Phosphorylation	10347145
PPIA/CYPA promotes its dephosphorylation on Ser-253 (By similarity).
253	S	Phosphorylation	10347145
Phosphorylation of Ser-253 decreases DNA-binding activity and promotes the phosphorylation of Thr-24 and Ser-316, permitting phosphorylation of Ser-319 and Ser-322, probably by CDK1, leading to nuclear exclusion and loss of function.
253	S	Phosphorylation	10347145
Methylation inhibits PKB/AKT1-mediated phosphorylation at Ser-253, promoting nuclear retention and increasing the transcriptional activity and cell death.
253	S	Phosphorylation	10347145
It increases the phosphorylation at Ser-253, and is required for the transcriptional inhibition by FCOR.
253	S	Phosphorylation	10347145
In response to growth factors, phosphorylation on Thr-24, Ser-253 and Ser-319 by PKB/AKT1 promotes nuclear export and inactivation of transactivational activity.
253	S	Phosphorylation	10347145
Dephosphorylated on Thr-24 and Ser-253 by PP2A in beta-cells under oxidative stress leading to nuclear retention (By similarity).
253	S	Oxidation	10347145
Dephosphorylated on Thr-24 and Ser-253 by PP2A in beta-cells under oxidative stress leading to nuclear retention (By similarity).
253	S	Methylation	10347145
Methylation inhibits PKB/AKT1-mediated phosphorylation at Ser-253, promoting nuclear retention and increasing the transcriptional activity and cell death.
259	K	Acetylation	20519497
Acetylation at Lys-259 and Lys-271 are necessary for autophagic cell death induction.
271	K	Acetylation	20519497
Acetylation at Lys-259 and Lys-271 are necessary for autophagic cell death induction.
316	S	Phosphorylation	10347145
Phosphorylation of Ser-253 decreases DNA-binding activity and promotes the phosphorylation of Thr-24 and Ser-316, permitting phosphorylation of Ser-319 and Ser-322, probably by CDK1, leading to nuclear exclusion and loss of function.
319	S	Phosphorylation	19965929
In response to growth factors, phosphorylation on Thr-24, Ser-253 and Ser-319 by PKB/AKT1 promotes nuclear export and inactivation of transactivational activity.
319	S	Phosphorylation	19965929
Phosphorylation of Ser-253 decreases DNA-binding activity and promotes the phosphorylation of Thr-24 and Ser-316, permitting phosphorylation of Ser-319 and Ser-322, probably by CDK1, leading to nuclear exclusion and loss of function.
322	S	Phosphorylation	10347145
Phosphorylation of Ser-253 decreases DNA-binding activity and promotes the phosphorylation of Thr-24 and Ser-316, permitting phosphorylation of Ser-319 and Ser-322, probably by CDK1, leading to nuclear exclusion and loss of function.
326	S	Phosphorylation	21183079
Phosphorylation of Ser-326 is independent of IGF1 and leads to reduced function.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of FOXO1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NR0B2_MOUSE	Nr0b2	physical	21081708
BSH_MOUSE	Bsx	physical	17550780
WDFY2_MOUSE	Wdfy2	physical	18388859
PPARG_HUMAN	PPARG	physical	12966085
SIR1_MOUSE	Sirt1	physical	22514318
NECD_MOUSE	Ndn	physical	22514318

Drug and Disease Associations

Kegg Drug
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of FOXO1_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Serum- and glucocorticoid-inducible kinase 1 (SGK1) regulatesadipocyte differentiation via forkhead box O1."; Di Pietro N., Panel V., Hayes S., Bagattin A., Meruvu S., Pandolfi A.,Hugendubler L., Fejes-Toth G., Naray-Fejes-Toth A., Mueller E.; Mol. Endocrinol. 24:370-380(2010). Cited for: PHOSPHORYLATION AT THR-24; SER-253 AND SER-319 BY SGK1, ANDSUBCELLULAR LOCATION.	19965929 [Abstract]
"Large-scale phosphorylation analysis of mouse liver."; Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-464 AND SER-465, ANDMASS SPECTROMETRY.	17242355 [Abstract]
"Insulin stimulates phosphorylation of the forkhead transcriptionfactor FKHR on serine 253 through a Wortmannin-sensitive pathway."; Nakae J., Park B.C., Accili D.; J. Biol. Chem. 274:15982-15985(1999). Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT THR-24; SER-253 ANDSER-316, AND MUTAGENESIS OF THR-24; SER-253 AND SER-316.	10347145 [Abstract]

show

show

show

show

show

show

show

show

show

show

show

show

show

show

show

show

show

show

show

show

show

show

show