Pml
entrez
18854
canonical
uniprot
Q60953
canonical
ensembl
ENSMUSG00000036986
resolver
ensp
ENSMUSP00000082816
resolver
ensp
ENSMUSP00000109771
resolver
ensp
ENSMUSP00000116787
resolver
ensp
ENSMUSP00000122854
resolver
ensp
ENSMUSP00000197693
resolver
ensp
ENSMUSP00000357713
resolver
enst
ENSMUST00000135310
resolver
genesymbol
Pml
resolver
uniprot
A0A068EW80
resolver
uniprot
D3Z3A6
resolver
uniprot
Q8BSJ6
resolver
uniprot
Q8CEJ1
resolver
uniprot
Q8VCC4
resolver
uniprot_entry
A0A068EW80_MOUSE
resolver
uniprot_entry
D3Z3A6_MOUSE
resolver
uniprot_entry
PML_MOUSE
resolver
uniprot_entry
Q8BSJ6_MOUSE
resolver
uniprot_sec
Q8CEJ1
resolver
uniprot_sec
Q8VCC4
resolver
amino_acid_sequence
METEPVSVQKVPAPPGSPCRQQDSALTPTPTMPPPEEPSEDYEHSQSPAEQAIQEEFQFLRCPSCQAQAKCPKLLPCLHTLCSGCLEAPGLQCPICKAPGQADANGEALDNVFFESLQRRLAVFRQIVDAQAACTRCKGLADFWCFECEQLICSKCFEAHQWYLKHEARPLADLRDNSVSSFLDSTRKSNIFCSNTNHRNPALTDIYCRGCAKPLCCTCALLDRNHSHLHCDIGEEIQQWHEELGTMTQTLEEQGRTFDSAHAQMCSAIGQLDHARADIEKQIRARVRQVVDYVQAQERELLEAVNDRYQRDYQEIAGQLSCLEAVLQRIRTSGALVKRMKLYASDQEVLDMHSFLRKALCSLRQEEPQNQKVQLLTRGFEEFKLCLQDFISCITQRINAAVASPEAASNQPEAASTHPVTTSTPEDLEQPKEVQSVQAQALELSKTQPVAMVKTVPGAHPVPVYAFSMQGPTYREEASQTVGSMKRKCSHEDCSRKIIKMESTEENEDRLATSSPEQSWPSTFKATSPPHLDGTSNPESTVPEKKILLPNNNHVTSDTGETEERVVVISSSEDSDTENLSSHELDDSSSESSSLQLEGPNSLKALDESLAEPHLEDRTLVFFDLKIDNETQKISQLAAVNRESKFRVLIQPEAFSVYSKAVSLEAGLRHFLSFLTTMHRPILACSRLWGPGLPIFFQTLSDINKLWEFQDTISGFLAVLPLIRERIPGASSFKLGNLAKTYLARNMSERSALASVLAMRDLCCLLEISPGLPLAQHIYSFSSLQCFASLQPLIQASVLPQSEARLLALHNVSFVELLNAYRTNRQEGLKKYVHYLSLQTTPLSSSASTQVAQFLQALSTHMEGLLEGHAPAGAEGKAESKGCLA
uniprot
proteins
function
FUNCTION: 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. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs (By similarity). 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). {ECO:0000250|UniProtKB:P29590, ECO:0000269|PubMed:10637504, ECO:0000269|PubMed:11907221, ECO:0000269|PubMed:12439746, ECO:0000269|PubMed:14976551, ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15356634, ECO:0000269|PubMed:16915281, ECO:0000269|PubMed:19136970, ECO:0000269|PubMed:21030605, ECO:0000269|PubMed:21427174, ECO:0000269|PubMed:21779477, ECO:0000269|PubMed:22274616, ECO:0000269|PubMed:22886304, ECO:0000269|PubMed:23279884, ECO:0000269|PubMed:9488655, ECO:0000269|PubMed:9806545}.
uniprot
proteins
mass_dalton
98242
uniprot
proteins
post_translational_modification
PTM: Ubiquitinated; mediated by RNF4, RNF111, UHRF1, UBE3A/E6AP, BCR(KLHL20) E3 ubiquitin ligase complex, SIAH1 or SIAH2 and leading to subsequent proteasomal degradation. 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent (By similarity). Ubiquitination by RNF111 is polysumoylation-dependent (PubMed:23530056). 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). {ECO:0000250|UniProtKB:P29590, ECO:0000269|PubMed:23530056}.; PTM: Sumoylation regulates PML's: stability in response to extracellular or intracellular stimuli, transcription directly and indirectly, through sequestration of or dissociation of the transcription factors from PML-NBs, ability to regulate apoptosis and its anti-viral activities. It is also essential for: maintaining proper PML nuclear bodies (PML-NBs) structure and normal function, recruitment of components of PML-NBs, the turnover and retention of PML in PML-NBs and the integrity of PML-NBs. Undergoes 'Lys-11'-linked sumoylation. Sumoylation on all three sites (Lys-70, Lys-165 and Lys-500) is required for nuclear body formation. Sumoylation on Lys-165 is a prerequisite for sumoylation on Lys-70. Lys-70 and Lys-165 are sumoylated by PISA1 and PIAS2. PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 and phosphorylation at Ser-575 which in turn triggers its ubiquitin-mediated degradation. Sumoylation at Lys-500 by RANBP2 is essential for the proper assembly of PML-NBs. Desumoylated by SENP1, SENP2, SENP3, SENP5 and SENP6 (By similarity). {ECO:0000250|UniProtKB:P29590}.; PTM: Phosphorylation is a major regulatory mechanism that controls PML protein abundance and the number and size of PML nuclear bodies (PML-NBs). Phosphorylated in response to DNA damage, probably by ATR. 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. MAPK1- mediated phosphorylations at Ser-404, Ser-515 and Ser-540 and CDK1/2-mediated phosphorylation at Ser-528 promote PIN1-dependent PML degradation. CK2-mediated phosphorylation at Ser-575 primes PML ubiquitination via an unidentified ubiquitin ligase (By similarity). {ECO:0000250|UniProtKB:P29590}.; PTM: Acetylation at Lys-497 is essential for its nuclear localization. Deacetylated at Lys-497 by SIRT1 and this deacetylation promotes PML control of PER2 nuclear localization (By similarity). {ECO:0000250|UniProtKB:P29590}.
uniprot
proteins
pubmed
10637504
uniprot
proteins
pubmed
10779416
uniprot
proteins
pubmed
11500381
uniprot
proteins
pubmed
11575918
uniprot
proteins
pubmed
11907221
uniprot
proteins
pubmed
12439746
uniprot
proteins
pubmed
12837286
uniprot
proteins
pubmed
14645235
uniprot
proteins
pubmed
14976551
uniprot
proteins
pubmed
15195100
uniprot
proteins
pubmed
15356634
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16915281
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
18630941
uniprot
proteins
pubmed
19131326
uniprot
proteins
pubmed
19136970
uniprot
proteins
pubmed
19652541
uniprot
proteins
pubmed
21030605
uniprot
proteins
pubmed
21161613
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21427174
uniprot
proteins
pubmed
21779477
uniprot
proteins
pubmed
22274616
uniprot
proteins
pubmed
22886304
uniprot
proteins
pubmed
23279884
uniprot
proteins
pubmed
23530056
uniprot
proteins
pubmed
8563172
uniprot
proteins
pubmed
9488655
uniprot
proteins
pubmed
9806545
uniprot
proteins
sequence_length
885
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Nucleus, nucleoplasm. Cytoplasm. Nucleus, PML body. Nucleus, nucleolus {ECO:0000250}. Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Early endosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Note=Detected in the nucleolus after DNA damage. Acetylation at Lys-497 is essential for its nuclear localization. Within the nucleus, most of PML is expressed in the diffuse nuclear fraction of the nucleoplasm and only a small fraction is found in the matrix-associated nuclear bodies (PML-NBs). The transfer of PML from the nucleoplasm to PML-NBs depends on its phosphorylation and sumoylation. The B1 box and the RING finger are also required for the localization in PML-NBs. Also found in specific membrane structures termed mitochondria-associated membranes (MAMs) which connect the endoplasmic reticulum (ER) and the mitochondria (By similarity). {ECO:0000250}.
uniprot
proteins