dbPTM

FOXO3_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	FOXO3_MOUSE
UniProt AC	Q9WVH4
Protein Name	Forkhead box protein O3 {ECO:0000305}
Gene Name	Foxo3 {ECO:0000312\|MGI:MGI:1890081}
Organism	Mus musculus (Mouse).
Sequence Length	672
Subcellular Localization	Cytoplasm, cytosol . Nucleus . Mitochondrion matrix . Mitochondrion outer membrane Peripheral membrane protein Cytoplasmic side . Retention in the cytoplasm contributes to its inactivation (By similarity). Translocates to the nucleus upon oxidati
Protein Description	Transcriptional activator. [PubMed: 23805378 Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (By similarity Recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' (By similarity Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation (By similarity In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription]
Protein Sequence	MAEAPASPVPLSPLEVELDPEFEPQSRPRSCTWPLQRPELQASPAKPSGETAADSMIPEEDDDEDDEDGGGRASSAMVIGGGVSSTLGSGLLLEDSAMLLAPGGQDLGSGPASAAGALSGGTPTQLQPQQPLPQPQPGAAGGSGQPRKCSSRRNAWGNLSYADLITRAIESSPDKRLTLSQIYEWMVRCVPYFKDKGDSNSSAGWKNSIRHNLSLHSRFMRVQNEGTGKSSWWIINPDGGKSGKAPRRRAVSMDNSNKYTKSRGRAAKKKAALQAAPESADDSPSQLSKWPGSPTSRSSDELDAWTDFRSRTNSNASTVSGRLSPILASTELDDVQDDDGPLSPMLYSSSASLSPSVSKPCTVELPRLTDMAGTMNLNDGLAENLMDDLLDNIALPPSQPSPPGGLMQRGSSFPYTAKSSGLGSPTGSFNSTVFGPSSLNSLRQSPMQTIQENRPATFSSVSHYGNQTLQDLLASDSLSHSDVMMTQSDPLMSQASTAVSAQNARRNVMLRNDPMMSFAAQPTQGSLVNQNLLHHQHQTQGALGGSRALSNSVSNMGLSDSSSLGSAKHQQQSPASQSMQTLSDSLSGSSLYSASANLPVMGHDKFPSDLDLDMFNGSLECDMESIIRSELMDADGLDFNFDSLISTQNVVGLNVGNFTGAKQASSQSWVPG

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
7	Phosphorylation	-MAEAPASPVPLSPL -CCCCCCCCCCCCCC	25.93	26824392
12	Phosphorylation	PASPVPLSPLEVELD CCCCCCCCCCEEECC	22.74	26824392
30	Phosphorylation	EPQSRPRSCTWPLQR CCCCCCCCCCCCCCC	20.69	26643407
32	Phosphorylation	QSRPRSCTWPLQRPE CCCCCCCCCCCCCHH	31.22	11896584
43	Phosphorylation	QRPELQASPAKPSGE CCHHHCCCCCCCCCC	16.66	22817900
46	Methylation	ELQASPAKPSGETAA HHCCCCCCCCCCCCH	43.00	-
48	Phosphorylation	QASPAKPSGETAADS CCCCCCCCCCCCHHH	48.86	22817900
51	Phosphorylation	PAKPSGETAADSMIP CCCCCCCCCHHHCCC	30.58	25338131
55	Phosphorylation	SGETAADSMIPEEDD CCCCCHHHCCCCCCC	17.55	21183079
89	Phosphorylation	GVSSTLGSGLLLEDS CHHHCCCCCCCCCCC	29.40	14976264
148	Methylation	GGSGQPRKCSSRRNA CCCCCCCCCCCCCCC	45.19	-
178	Phosphorylation	SSPDKRLTLSQIYEW CCCCCCEEHHHHHHH	28.53	-
208	Phosphorylation	SSAGWKNSIRHNLSL CCHHHHHHHHHHHHH	19.78	-
214	Phosphorylation	NSIRHNLSLHSRFMR HHHHHHHHHHHEEEE	29.38	-
217	Phosphorylation	RHNLSLHSRFMRVQN HHHHHHHHEEEEEEE	32.29	25619855
229	Methylation	VQNEGTGKSSWWIIN EEECCCCCCCEEEEC	40.95	-
241	Acetylation	IINPDGGKSGKAPRR EECCCCCCCCCCCCC	62.66	23806337
252	Phosphorylation	APRRRAVSMDNSNKY CCCCCEECCCCCCHH	21.31	25521595
256	Phosphorylation	RAVSMDNSNKYTKSR CEECCCCCCHHHHHH	30.36	23737553
258	Acetylation	VSMDNSNKYTKSRGR ECCCCCCHHHHHHHH	54.86	66049
260	Phosphorylation	MDNSNKYTKSRGRAA CCCCCHHHHHHHHHH	24.93	25266776
261	Methylation	DNSNKYTKSRGRAAK CCCCHHHHHHHHHHH	34.76	-
270	Acetylation	RGRAAKKKAALQAAP HHHHHHHHHHHHHCC	37.88	66053
270	Methylation	RGRAAKKKAALQAAP HHHHHHHHHHHHHCC	37.88	-
279	Phosphorylation	ALQAAPESADDSPSQ HHHHCCCCCCCCHHH	35.62	21082442
283	Phosphorylation	APESADDSPSQLSKW CCCCCCCCHHHHHCC	27.31	25521595
285	Phosphorylation	ESADDSPSQLSKWPG CCCCCCHHHHHCCCC	47.94	21082442
288	Phosphorylation	DDSPSQLSKWPGSPT CCCHHHHHCCCCCCC	25.66	25619855
289	Acetylation	DSPSQLSKWPGSPTS CCHHHHHCCCCCCCC	67.03	66057
289	Methylation	DSPSQLSKWPGSPTS CCHHHHHCCCCCCCC	67.03	-
293	Phosphorylation	QLSKWPGSPTSRSSD HHHCCCCCCCCCCHH	22.41	23684622
295	Phosphorylation	SKWPGSPTSRSSDEL HCCCCCCCCCCHHHH	38.17	26643407
296	Phosphorylation	KWPGSPTSRSSDELD CCCCCCCCCCHHHHH	33.28	25266776
298	Phosphorylation	PGSPTSRSSDELDAW CCCCCCCCHHHHHHH	41.74	21082442
299	Phosphorylation	GSPTSRSSDELDAWT CCCCCCCHHHHHHHH	33.71	26643407
310	Phosphorylation	DAWTDFRSRTNSNAS HHHHCHHHHCCCCCC	43.37	26370283
314	Phosphorylation	DFRSRTNSNASTVSG CHHHHCCCCCCCCCC	32.91	12857750
317	Phosphorylation	SRTNSNASTVSGRLS HHCCCCCCCCCCCCC	33.32	12857750
320	Phosphorylation	NSNASTVSGRLSPIL CCCCCCCCCCCCCCC	20.48	12857750
398	Phosphorylation	DNIALPPSQPSPPGG HHCCCCCCCCCCCCC	53.43	-
401	Phosphorylation	ALPPSQPSPPGGLMQ CCCCCCCCCCCCCCC	35.77	23649490
412	Phosphorylation	GLMQRGSSFPYTAKS CCCCCCCCCCCCCCC	32.82	14976264
418	Methylation	SSFPYTAKSSGLGSP CCCCCCCCCCCCCCC	37.04	-
419	Phosphorylation	SFPYTAKSSGLGSPT CCCCCCCCCCCCCCC	27.46	26745281
420	Phosphorylation	FPYTAKSSGLGSPTG CCCCCCCCCCCCCCC	37.01	26745281
424	Phosphorylation	AKSSGLGSPTGSFNS CCCCCCCCCCCCCCC	25.08	22942356
426	Phosphorylation	SSGLGSPTGSFNSTV CCCCCCCCCCCCCCC	47.34	26745281
428	Phosphorylation	GLGSPTGSFNSTVFG CCCCCCCCCCCCCCC	24.59	23737553
431	Phosphorylation	SPTGSFNSTVFGPSS CCCCCCCCCCCCHHH	24.76	23737553
432	Phosphorylation	PTGSFNSTVFGPSSL CCCCCCCCCCCHHHH	22.43	23737553
437	Phosphorylation	NSTVFGPSSLNSLRQ CCCCCCHHHHHHHHC	48.08	25777480
438	Phosphorylation	STVFGPSSLNSLRQS CCCCCHHHHHHHHCC	34.40	25777480
441	Phosphorylation	FGPSSLNSLRQSPMQ CCHHHHHHHHCCCCC	30.17	25777480
550	Phosphorylation	LGGSRALSNSVSNMG CCHHHHHHHHHHCCC	26.52	22345495
552	Phosphorylation	GSRALSNSVSNMGLS HHHHHHHHHHCCCCC	24.44	22807455
554	Phosphorylation	RALSNSVSNMGLSDS HHHHHHHHCCCCCCC	22.41	22345495
559	Phosphorylation	SVSNMGLSDSSSLGS HHHCCCCCCCCCHHH	29.71	22807455
562	Phosphorylation	NMGLSDSSSLGSAKH CCCCCCCCCHHHHHH	34.27	22807455
568	Acetylation	SSSLGSAKHQQQSPA CCCHHHHHHHHCCCC	43.58	66061
573	Phosphorylation	SAKHQQQSPASQSMQ HHHHHHCCCCHHHHH	20.35	14976264
587	Phosphorylation	QTLSDSLSGSSLYSA HHHHHHHCCCCCCCC	40.35	-
625	Phosphorylation	SLECDMESIIRSELM CEECCHHHHHHHHHC	19.37	-
643	Phosphorylation	GLDFNFDSLISTQNV CCCCCHHHHEECCCE	24.38	-

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
32	T	Phosphorylation	Kinase	AKT1	P31749	PSP
32	T	Phosphorylation	Kinase	AKT1	P31750	PSP
32	T	Phosphorylation	Kinase	SGK1	O00141	PSP
293	S	Phosphorylation	Kinase	MAPK1	P63085	GPS
293	S	Phosphorylation	Kinase	MAPK3	Q63844	GPS
298	S	Phosphorylation	Kinase	CAMK2A	P11798	Uniprot
314	S	Phosphorylation	Kinase	SGK1	Q9WVC6	Uniprot
398	S	Phosphorylation	Kinase	AMPK	-	Uniprot
412	S	Phosphorylation	Kinase	PRKAA1	Q13131	GPS
412	S	Phosphorylation	Kinase	AMPK	-	Uniprot
550	S	Phosphorylation	Kinase	MAPKAPK5	O54992	Uniprot
554	S	Phosphorylation	Kinase	MAPKAPK5	O54992	Uniprot
554	S	Phosphorylation	Kinase	AMPK	-	Uniprot
587	S	Phosphorylation	Kinase	AMPK	-	Uniprot
625	S	Phosphorylation	Kinase	AMPK	-	Uniprot
643	S	Phosphorylation	Kinase	IKKB	O88351	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
30	S	Phosphorylation	23805378
Phosphorylated by AMPK on Ser-30 in response to metabolic stress which mediates FOXO3 mitochondrial translocation (By similarity).
32	T	Phosphorylation	23805378
In the presence of survival factors such as IGF-1, phosphorylated on Thr-32 and Ser-252 by AKT1/PKB (Probable).
208	S	Oxidation	23805378
Phosphorylated by STK4/MST1 on Ser-208 upon oxidative stress, which leads to dissociation from YWHAB/14-3-3-beta and nuclear translocation (By similarity).
208	S	Phosphorylation	23805378
Phosphorylated by STK4/MST1 on Ser-208 upon oxidative stress, which leads to dissociation from YWHAB/14-3-3-beta and nuclear translocation (By similarity).
252	S	Phosphorylation	23805378
In the presence of survival factors such as IGF-1, phosphorylated on Thr-32 and Ser-252 by AKT1/PKB (Probable).
270	K	Methylation	-
The main methylation site is Lys-270.
298	S	Phosphorylation	23805378
May be dephosphorylated by calcineurin A on Ser-298 which abolishes FOXO3 transcriptional activity.
314	S	Phosphorylation	23805378
Although AKT1/PKB doesn't appear to phosphorylate Ser-314 directly, it may activate other kinases that trigger phosphorylation at this residue (By similarity).
643	S	Phosphorylation	23805378
TNF-induced inactivation of FOXO3 requires its phosphorylation at Ser-643 by IKBKB/IKKB which promotes FOXO3 retention in the cytoplasm, polyubiquitination and ubiquitin-mediated proteasomal degradation (By similarity).
643	S	ubiquitylation	23805378
TNF-induced inactivation of FOXO3 requires its phosphorylation at Ser-643 by IKBKB/IKKB which promotes FOXO3 retention in the cytoplasm, polyubiquitination and ubiquitin-mediated proteasomal degradation (By similarity).

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 FOXO3_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MDM2_MOUSE	Mdm2	physical	22094330
EP300_MOUSE	Ep300	physical	22094330
HIF1A_MOUSE	Hif1a	physical	18268343

Drug and Disease Associations

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

Regulatory Network of FOXO3_MOUSE

Related Literatures of Post-Translational Modification

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