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Identification
HMDB Protein ID HMDBP14480
Secondary Accession Numbers None
Name Protein PML
Synonyms
  1. E3 SUMO-protein ligase PML
  2. Promyelocytic leukemia protein
  3. RING finger protein 71
  4. RING-type E3 SUMO transferase PML
  5. Tripartite motif-containing protein 19
  6. TRIM19
Gene Name PML
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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. Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important mediator for TNF-alpha- and IFN-alpha-mediated inhibition of endothelial cell network formation and migration.Exhibits antiviral activity against both DNA and RNA viruses. The antiviral activity can involve one or several isoform(s) and can be enhanced by the permanent PML-NB-associated protein DAXX or by the recruitment of p53/TP53 within these structures. Isoform PML-4 restricts varicella zoster virus (VZV) via sequestration of virion capsids in PML-NBs thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The sumoylated isoform PML-4 restricts rabies virus by inhibiting viral mRNA and protein synthesis. The cytoplasmic isoform PML-14 can restrict herpes simplex virus-1 (HHV-1) replication by sequestering the viral E3 ubiquitin-protein ligase ICP0 in the cytoplasm. Isoform PML-6 shows restriction activity towards human cytomegalovirus (HHV-5) and influenza A virus strains PR8(H1N1) and ST364(H3N2). Sumoylated isoform PML-4 and isoform PML-12 show antiviral activity against encephalomyocarditis virus (EMCV) by promoting nuclear sequestration of viral polymerase (P3D-POL) within PML NBs. Isoform PML-3 exhibits antiviral activity against poliovirus by inducing apoptosis in infected cells through the recruitment and the activation of p53/TP53 in the PML-NBs. Isoform PML-3 represses human foamy virus (HFV) transcription by complexing the HFV transactivator, bel1/tas, preventing its binding to viral DNA. PML may positively regulate infectious hepatitis C viral (HCV) production and isoform PML-2 may enhance adenovirus transcription. Functions as an E3 SUMO-protein ligase that sumoylates (HHV-5) immediate early protein IE1, thereby participating in the antiviral response (PubMed:20972456, PubMed:28250117). Isoforms PML-3 and PML-6 display the highest levels of sumoylation activity (PubMed:20972456, PubMed:28250117).
Pathways
  • Acute myeloid leukemia
  • Endocytosis
  • Herpes simplex virus 1 infection
  • Influenza A
  • protein sumoylation
  • Transcriptional misregulation in cancer
  • Ubiquitin mediated proteolysis
Reactions Not Available
GO Classification
Biological Process
cellular response to leukemia inhibitory factor
intrinsic apoptotic signaling pathway in response to oxidative stress
branching involved in mammary gland duct morphogenesis
entrainment of circadian clock by photoperiod
endoplasmic reticulum calcium ion homeostasis
maintenance of protein location in nucleus
negative regulation of telomere maintenance via telomerase
activation of cysteine-type endopeptidase activity involved in apoptotic process
negative regulation of translation in response to oxidative stress
negative regulation of ubiquitin-dependent protein catabolic process
negative regulation of viral release from host cell
PML body organization
positive regulation of protein localization to chromosome, telomeric region
cell cycle arrest
positive regulation of telomere maintenance
apoptotic process
regulation of calcium ion transport into cytosol
regulation of double-strand break repair
positive regulation of fibroblast proliferation
viral life cycle
positive regulation of apoptotic process involved in mammary gland involution
response to gamma radiation
positive regulation of extrinsic apoptotic signaling pathway
negative regulation of interleukin-1 beta production
protein stabilization
cellular senescence
negative regulation of telomerase activity
granulocyte differentiation
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
interferon-gamma-mediated signaling pathway
positive regulation of histone deacetylation
negative regulation of mitotic cell cycle
response to UV
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
defense response to virus
innate immune response
negative regulation of transcription, DNA-dependent
positive regulation of transcription, DNA-dependent
positive regulation of defense response to virus by host
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
cell fate commitment
negative regulation of angiogenesis
negative regulation of cell growth
regulation of protein phosphorylation
fibroblast migration
transforming growth factor beta receptor signaling pathway
negative regulation of cell proliferation
regulation of circadian rhythm
regulation of cell adhesion
cellular response to interleukin-4
response to cytokine stimulus
regulation of transcription, DNA-dependent
proteasomal ubiquitin-dependent protein catabolic process
retinoic acid receptor signaling pathway
protein targeting
intrinsic apoptotic signaling pathway in response to DNA damage
protein import into nucleus
response to hypoxia
circadian regulation of gene expression
common-partner SMAD protein phosphorylation
extrinsic apoptotic signaling pathway
regulation of signal transduction by p53 class mediator
protein-containing complex assembly
Cellular Component
cytosol
heterochromatin
cytoplasm
nucleolus
nucleus
early endosome membrane
nucleoplasm
extrinsic component of endoplasmic reticulum membrane
nuclear matrix
PML body
chromatin
nuclear membrane
chromosome, telomeric region
Molecular Function
cobalt ion binding
SUMO binding
sumo-dependent protein binding
ubiquitin-protein ligase activity
ubiquitin protein ligase binding
zinc ion binding
transcription coactivator activity
protein homodimerization activity
identical protein binding
DNA binding
SMAD binding
protein heterodimerization activity
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 882
Molecular Weight 97549.475
Theoretical pI 6.218
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P29590
UniProtKB/Swiss-Prot Entry Name PML_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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