PML_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PML_MOUSE
• UniProt AC: Q60953
• Protein Name: Protein PML
• Gene Name: Pml
• Organism: Mus musculus (Mouse).
• Sequence Length: 885
• Subcellular Localization: Nucleus. Nucleus, nucleoplasm. Cytoplasm. Nucleus, PML body. Nucleus, nucleolus. Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Detected in the nu
• Protein Description: Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Regulates phosphorylation of ITPR3 and plays a role in the regulation of calcium homeostasis at the endoplasmic reticulum. Regulates RB1 phosphorylation and activity. Acts as both a negative regulator of PPARGC1A acetylation and a potent activator of PPAR signaling and fatty acid oxidation. Regulates translation of HIF1A by sequestering MTOR, and thereby plays a role in neoangiogenesis and tumor vascularization. Regulates PER2 nuclear localization and circadian function. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. Required for normal development of the brain cortex during embryogenesis. Plays a role in granulopoiesis or monopoiesis of myeloid progenitor cells. May play a role regulating stem and progenitor cell fate in tissues as diverse as blood, brain and breast. Shows antiviral activity towards lymphocytic choriomeningitis virus (LCMV) and the vesicular stomatitis virus (VSV)..
• Protein Sequence: METEPVSVQKVPAPPGSPCRQQDSALTPTPTMPPPEEPSEDYEHSQSPAEQAIQEEFQFLRCPSCQAQAKCPKLLPCLHTLCSGCLEAPGLQCPICKAPGQADANGEALDNVFFESLQRRLAVFRQIVDAQAACTRCKGLADFWCFECEQLICSKCFEAHQWYLKHEARPLADLRDNSVSSFLDSTRKSNIFCSNTNHRNPALTDIYCRGCAKPLCCTCALLDRNHSHLHCDIGEEIQQWHEELGTMTQTLEEQGRTFDSAHAQMCSAIGQLDHARADIEKQIRARVRQVVDYVQAQERELLEAVNDRYQRDYQEIAGQLSCLEAVLQRIRTSGALVKRMKLYASDQEVLDMHSFLRKALCSLRQEEPQNQKVQLLTRGFEEFKLCLQDFISCITQRINAAVASPEAASNQPEAASTHPVTTSTPEDLEQPKEVQSVQAQALELSKTQPVAMVKTVPGAHPVPVYAFSMQGPTYREEASQTVGSMKRKCSHEDCSRKIIKMESTEENEDRLATSSPEQSWPSTFKATSPPHLDGTSNPESTVPEKKILLPNNNHVTSDTGETEERVVVISSSEDSDTENLSSHELDDSSSESSSLQLEGPNSLKALDESLAEPHLEDRTLVFFDLKIDNETQKISQLAAVNRESKFRVLIQPEAFSVYSKAVSLEAGLRHFLSFLTTMHRPILACSRLWGPGLPIFFQTLSDINKLWEFQDTISGFLAVLPLIRERIPGASSFKLGNLAKTYLARNMSERSALASVLAMRDLCCLLEISPGLPLAQHIYSFSSLQCFASLQPLIQASVLPQSEARLLALHNVSFVELLNAYRTNRQEGLKKYVHYLSLQTTPLSSSASTQVAQFLQALSTHMEGLLEGHAPAGAEGKAESKGCLA

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
17	Phosphorylation	KVPAPPGSPCRQQDS CCCCCCCCCCCCCCC	26.97	27087446
24	Phosphorylation	SPCRQQDSALTPTPT CCCCCCCCCCCCCCC	22.35	23649490
27	Phosphorylation	RQQDSALTPTPTMPP CCCCCCCCCCCCCCC	25.49	23649490
29	Phosphorylation	QDSALTPTPTMPPPE CCCCCCCCCCCCCCC	26.59	23649490
39	Phosphorylation	MPPPEEPSEDYEHSQ CCCCCCCCCCCCCCC	46.51	26026062
42	Phosphorylation	PEEPSEDYEHSQSPA CCCCCCCCCCCCCHH	16.10	21183079
45	Phosphorylation	PSEDYEHSQSPAEQA CCCCCCCCCCHHHHH	22.03	26026062
47	Phosphorylation	EDYEHSQSPAEQAIQ CCCCCCCCHHHHHHH	29.14	19060867
178	Phosphorylation	LADLRDNSVSSFLDS HHHCCCCCHHHHHHH	27.89	26370283
322	Glutathionylation	EIAGQLSCLEAVLQR HHHHHHHHHHHHHHH	5.60	24333276
372	Ubiquitination	QEEPQNQKVQLLTRG CCCCCHHHHHHHHHC	39.23	22790023
404 (in isoform 2)	Phosphorylation	-	19.37	26160508
404	Phosphorylation	RINAAVASPEAASNQ HHHHHHCCHHHHHCC	19.37	27087446
409 (in isoform 2)	Phosphorylation	-	42.94	24704852
409	Phosphorylation	VASPEAASNQPEAAS HCCHHHHHCCCCHHH	42.94	26239621
416 (in isoform 2)	Phosphorylation	-	34.01	26160508
416	Phosphorylation	SNQPEAASTHPVTTS HCCCCHHHCCCCCCC	34.01	26239621
417 (in isoform 2)	Phosphorylation	-	26.02	24704852
417	Phosphorylation	NQPEAASTHPVTTST CCCCHHHCCCCCCCC	26.02	26239621
421 (in isoform 2)	Phosphorylation	-	21.34	26160508
421	Phosphorylation	AASTHPVTTSTPEDL HHHCCCCCCCCHHHH	21.34	26239621
422 (in isoform 2)	Phosphorylation	-	30.73	26160508
422	Phosphorylation	ASTHPVTTSTPEDLE HHCCCCCCCCHHHHC	30.73	26239621
423 (in isoform 2)	Phosphorylation	-	32.38	26160508
423	Phosphorylation	STHPVTTSTPEDLEQ HCCCCCCCCHHHHCC	32.38	26239621
424	Phosphorylation	THPVTTSTPEDLEQP CCCCCCCCHHHHCCC	28.71	26239621
424 (in isoform 2)	Phosphorylation	-	28.71	24704852
433 (in isoform 2)	Phosphorylation	-	53.09	29472430
438 (in isoform 2)	Phosphorylation	-	32.76	21189417
444 (in isoform 2)	Phosphorylation	-	7.09	25266776
454	Ubiquitination	TQPVAMVKTVPGAHP CCCEEEEEECCCCCC	30.62	22790023
481	Phosphorylation	YREEASQTVGSMKRK HHHHHHHHHHHHHHH	25.08	27149854
484	Phosphorylation	EASQTVGSMKRKCSH HHHHHHHHHHHHCCH	19.45	27149854
486	Ubiquitination	SQTVGSMKRKCSHED HHHHHHHHHHCCHHH	50.86	-
490	Phosphorylation	GSMKRKCSHEDCSRK HHHHHHCCHHHHHHH	32.71	24899341
495	Phosphorylation	KCSHEDCSRKIIKME HCCHHHHHHHEEECC	49.26	25266776
497	Acetylation	SHEDCSRKIIKMEST CHHHHHHHEEECCCC	32.27	-
503	Phosphorylation	RKIIKMESTEENEDR HHEEECCCCCCCHHH	37.31	25521595
504	Phosphorylation	KIIKMESTEENEDRL HEEECCCCCCCHHHC	33.73	27742792
513	Phosphorylation	ENEDRLATSSPEQSW CCHHHCCCCCCHHCC	34.04	22942356
514	Phosphorylation	NEDRLATSSPEQSWP CHHHCCCCCCHHCCC	37.98	27087446
515	Phosphorylation	EDRLATSSPEQSWPS HHHCCCCCCHHCCCC	28.27	27087446
519	Phosphorylation	ATSSPEQSWPSTFKA CCCCCHHCCCCCCCC	39.01	21082442
522	Phosphorylation	SPEQSWPSTFKATSP CCHHCCCCCCCCCCC	39.97	25619855
523	Phosphorylation	PEQSWPSTFKATSPP CHHCCCCCCCCCCCC	25.69	25619855
525	Acetylation	QSWPSTFKATSPPHL HCCCCCCCCCCCCCC	51.33	-
527	Phosphorylation	WPSTFKATSPPHLDG CCCCCCCCCCCCCCC	42.21	27742792
528	Phosphorylation	PSTFKATSPPHLDGT CCCCCCCCCCCCCCC	41.09	27087446
535	Phosphorylation	SPPHLDGTSNPESTV CCCCCCCCCCCCCCC	25.62	27742792
536	Phosphorylation	PPHLDGTSNPESTVP CCCCCCCCCCCCCCC	56.78	27087446
540	Phosphorylation	DGTSNPESTVPEKKI CCCCCCCCCCCCCEE	35.64	21082442
541	Phosphorylation	GTSNPESTVPEKKIL CCCCCCCCCCCCEEE	38.12	20469934
545	Acetylation	PESTVPEKKILLPNN CCCCCCCCEEECCCC	38.76	23806337
546	Ubiquitination	ESTVPEKKILLPNNN CCCCCCCEEECCCCC	36.60	-
556	Phosphorylation	LPNNNHVTSDTGETE CCCCCCCCCCCCCCE	17.21	24723360
557	Phosphorylation	PNNNHVTSDTGETEE CCCCCCCCCCCCCEE	31.89	26824392
559	Phosphorylation	NNHVTSDTGETEERV CCCCCCCCCCCEEEE	36.36	21082442
562	Phosphorylation	VTSDTGETEERVVVI CCCCCCCCEEEEEEE	44.48	26643407
575	Phosphorylation	VISSSEDSDTENLSS EEECCCCCCCCCCCC	42.24	-
609	Phosphorylation	SLKALDESLAEPHLE HHHHHHHHHCCCCCC	32.33	26824392
633	Ubiquitination	KIDNETQKISQLAAV EECCCHHHHHHHHCC	52.31	22790023
658	Phosphorylation	QPEAFSVYSKAVSLE CHHHHHHHHHHHHHH	11.85	26026062
734	Ubiquitination	IPGASSFKLGNLAKT CCCCCCCHHHHHHHH	58.39	22790023
740	Ubiquitination	FKLGNLAKTYLARNM CHHHHHHHHHHHCCC	40.65	-

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
17	S	Phosphorylation	Kinase	HIPK2	Q9QZR5	Uniprot
45	S	Phosphorylation	Kinase	HIPK2	Q9QZR5	Uniprot
45	S	Phosphorylation	Kinase	MAPK1	P63085	Uniprot
47	S	Phosphorylation	Kinase	HIPK2	Q9QZR5	Uniprot
47	S	Phosphorylation	Kinase	MAPK1	P63085	Uniprot
515	S	Phosphorylation	Kinase	MAPK1	P63085	Uniprot
528	S	Phosphorylation	Kinase	CDK1	P11440	Uniprot
528	S	Phosphorylation	Kinase	CDK2	P97377	Uniprot
540	S	Phosphorylation	Kinase	MAPK1	P63085	Uniprot
575	S	Phosphorylation	Kinase	CK2	-	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Siah1a	P61092	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Siah2	Q06986	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
6	K	ubiquitylation	'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent (By similarity).	23530056
6	K	Sumoylation	'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent (By similarity).	23530056
11	K	ubiquitylation	'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent (By similarity).	23530056
11	K	Sumoylation	'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent (By similarity).	23530056
17	S	Phosphorylation	HIPK2-mediated phosphorylation at Ser-17, Ser-45 and Ser-47 leads to increased accumulation of PML protein and its sumoylation and is required for the maximal pro-apoptotic activity of PML after DNA damage.	17242355
17	S	Sumoylation	HIPK2-mediated phosphorylation at Ser-17, Ser-45 and Ser-47 leads to increased accumulation of PML protein and its sumoylation and is required for the maximal pro-apoptotic activity of PML after DNA damage.	17242355
45	S	Sumoylation	HIPK2-mediated phosphorylation at Ser-17, Ser-45 and Ser-47 leads to increased accumulation of PML protein and its sumoylation and is required for the maximal pro-apoptotic activity of PML after DNA damage.	-
45	S	Phosphorylation	HIPK2-mediated phosphorylation at Ser-17, Ser-45 and Ser-47 leads to increased accumulation of PML protein and its sumoylation and is required for the maximal pro-apoptotic activity of PML after DNA damage.	-
47	S	Sumoylation	HIPK2-mediated phosphorylation at Ser-17, Ser-45 and Ser-47 leads to increased accumulation of PML protein and its sumoylation and is required for the maximal pro-apoptotic activity of PML after DNA damage.	-
47	S	Phosphorylation	HIPK2-mediated phosphorylation at Ser-17, Ser-45 and Ser-47 leads to increased accumulation of PML protein and its sumoylation and is required for the maximal pro-apoptotic activity of PML after DNA damage.	-
48	K	ubiquitylation	'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent (By similarity).	23530056
48	K	Sumoylation	'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent (By similarity).	23530056
70	K	Sumoylation	Lys-70 and Lys-165 are sumoylated by PISA1 and PIAS2.	-
70	K	Sumoylation	Sumoylation on Lys-165 is a prerequisite for sumoylation on Lys-70.	-
70	K	Sumoylation	Sumoylation on all three sites (Lys-70, Lys-165 and Lys-500) is required for nuclear body formation.	-
165	K	Sumoylation	Sumoylation on all three sites (Lys-70, Lys-165 and Lys-500) is required for nuclear body formation.	-
165	K	Sumoylation	Sumoylation on Lys-165 is a prerequisite for sumoylation on Lys-70.	-
165	K	Sumoylation	Lys-70 and Lys-165 are sumoylated by PISA1 and PIAS2.	-
404	S	Phosphorylation	MAPK1- mediated phosphorylations at Ser-404, Ser-515 and Ser-540 and CDK1/2-mediated phosphorylation at Ser-528 promote PIN1-dependent PML degradation.	21183079
497	K	Acetylation	Acetylation at Lys-497 is essential for its nuclear localization.	-
497	K	Acetylation	Deacetylated at Lys-497 by SIRT1 and this deacetylation promotes PML control of PER2 nuclear localization (By similarity).	-
500	K	Sumoylation	Sumoylation on all three sites (Lys-70, Lys-165 and Lys-500) is required for nuclear body formation.	-
500	K	Sumoylation	Sumoylation at Lys-500 by RANBP2 is essential for the proper assembly of PML-NBs.	-
515	S	Phosphorylation	MAPK1- mediated phosphorylations at Ser-404, Ser-515 and Ser-540 and CDK1/2-mediated phosphorylation at Ser-528 promote PIN1-dependent PML degradation.	17242355
528	S	Phosphorylation	MAPK1- mediated phosphorylations at Ser-404, Ser-515 and Ser-540 and CDK1/2-mediated phosphorylation at Ser-528 promote PIN1-dependent PML degradation.	19131326
528	S	Phosphorylation	Ubiquitination by BCR(KLHL20) E3 ubiquitin ligase complex requires CDK1/2-mediated phosphorylation at Ser-528 which in turn is recognized by prolyl-isopeptidase PIN1 and PIN1-catalyzed isomerization further potentiates PML interaction with KLHL20 (By similarity).	19131326
528	S	ubiquitylation	Ubiquitination by BCR(KLHL20) E3 ubiquitin ligase complex requires CDK1/2-mediated phosphorylation at Ser-528 which in turn is recognized by prolyl-isopeptidase PIN1 and PIN1-catalyzed isomerization further potentiates PML interaction with KLHL20 (By similarity).	19131326
540	S	Phosphorylation	MAPK1- mediated phosphorylations at Ser-404, Ser-515 and Ser-540 and CDK1/2-mediated phosphorylation at Ser-528 promote PIN1-dependent PML degradation.	-
575	S	Phosphorylation	CK2-mediated phosphorylation at Ser-575 primes PML ubiquitination via an unidentified ubiquitin ligase (By similarity).	-
575	S	Phosphorylation	PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 and phosphorylation at Ser-575 which in turn triggers its ubiquitin-mediated degradation.	-
575	S	Sumoylation	PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 and phosphorylation at Ser-575 which in turn triggers its ubiquitin-mediated degradation.	-
575	S	ubiquitylation	CK2-mediated phosphorylation at Ser-575 primes PML ubiquitination via an unidentified ubiquitin ligase (By similarity).	-
575	S	ubiquitylation	PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 and phosphorylation at Ser-575 which in turn triggers its ubiquitin-mediated degradation.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of PML_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
MTOR_MOUSE	Mtor	physical	16915281
PML_MOUSE	Pml	physical	20211142
ZSC21_MOUSE	Zscan21	physical	20211142
RPAB1_MOUSE	Polr2e	physical	20211142
T2EB_MOUSE	Gtf2e2	physical	20211142
T2EA_MOUSE	Gtf2e1	physical	20211142
MED16_MOUSE	Med16	physical	20211142
MED17_MOUSE	Med17	physical	20211142
AXIN1_HUMAN	AXIN1	physical	21057547
P53_HUMAN	TP53	physical	21057547
HIPK2_HUMAN	HIPK2	physical	21057547
SPI1_MOUSE	Spi1	physical	17562868
SKIL_MOUSE	Skil	physical	19745809
PIN1_MOUSE	Pin1	physical	28143738

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Large scale localization of protein phosphorylation by use ofelectron capture dissociation mass spectrometry.";
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
Mol. Cell. Proteomics 8:904-912(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-528, AND MASSSPECTROMETRY.
PubMed: 19131326

"Solid tumor proteome and phosphoproteome analysis by high resolutionmass spectrometry.";
Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J.,Faessler R., Mann M.;
J. Proteome Res. 7:5314-5326(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-609, AND MASSSPECTROMETRY.
PubMed: 19367708

"Specific phosphopeptide enrichment with immobilized titanium ionaffinity chromatography adsorbent for phosphoproteome analysis.";
Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
J. Proteome Res. 7:3957-3967(2008).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17, AND MASSSPECTROMETRY.
PubMed: 18630941

"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 SER-514; SER-515; THR-527;SER-528 AND THR-556, AND MASS SPECTROMETRY.
PubMed: 17242355