PML - Protein PML - human protein (Function)
 
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PML »  Protein PML
 
Protein also known as:  Tripartite motif-containing protein 19.
Gene name:  PML
Entry whose protein(s) existence is based on evidence at protein level
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1 356 12
GENE REF ISO

Function

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Overview 
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.  
  • UniProtKB
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.  
  • UniProtKB
Isoforms  PML-5 and 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.  
1
  • UniProtKB
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.  
1
  • UniProtKB
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).  
  • UniProtKB
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.  
  • UniProtKB
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.  
  • UniProtKB
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.  
  • UniProtKB
Isoform  PML-6   Shows restriction activity towards human cytomegalovirus (HCMV) 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.  
  • UniProtKB
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.  
  • UniProtKB
GO molecular function 
Isoform  PML-6   Cobalt ion bindingdefinition[GO:0050897]  
1
  • UniProtKB
DNA bindingdefinition[GO:0003677]  
1
  • UniProtKB KW
Protein bindingdefinition[GO:0005515]  
53
  • IntAct
  • UniProtKB
  • ParkinsonsUK-UCL
  • BHF-UCL
Isoform  PML-8   Protein heterodimerization activitydefinition[GO:0046982]  
1
  • UniProtKB
Protein homodimerization activitydefinition[GO:0042803]  
1
  • BHF-UCL
SMAD bindingdefinition[GO:0046332] silver  
1
  • Ortholog Compara
SUMO bindingdefinition[GO:0032183]  
1
  • UniProtKB
Isoform  PML-4   Transcription coactivator activitydefinition[GO:0003713]  
2
  • UniProtKB
Ubiquitin protein ligase bindingdefinition[GO:0031625]  
1
  • UniProtKB
Zinc ion bindingdefinition[GO:0008270]  
2
  • UniProtKB
  • InterPro 2 GO
GO biological process 
Activation of cysteine-type endopeptidase activity involved in apoptotic processdefinition[GO:0006919] silver  
1
  • Ortholog Compara
Isoform  PML-8   Apoptotic processdefinition[GO:0006915]  
1
  • UniProtKB
Branching involved in mammary gland duct morphogenesisdefinition[GO:0060444] silver  
1
  • Ortholog Compara
Cell cycle arrestdefinition[GO:0007050]  
3
  • UniProtKB
  • Ortholog Compara
Cell fate commitmentdefinition[GO:0045165] silver  
1
  • Ortholog Compara
Cellular response to interleukin-4definition[GO:0071353] silver  
1
  • Ortholog Compara
Cellular senescencedefinition[GO:0090398]  
3
  • UniProtKB
Circadian regulation of gene expressiondefinition[GO:0032922]  
1
  • Ortholog Curator
Common-partner SMAD protein phosphorylationdefinition[GO:0007182] silver  
1
  • Ortholog Compara
Defense response to virusdefinition[GO:0051607]  
1
  • UniProtKB KW
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrestdefinition[GO:0006977]  
1
  • Ortholog Curator
Endoplasmic reticulum calcium ion homeostasisdefinition[GO:0032469]  
1
  • Ortholog Curator
Entrainment of circadian clock by photoperioddefinition[GO:0043153]  
1
  • Ortholog Curator
Extrinsic apoptotic signaling pathwaydefinition[GO:0097191] silver  
1
  • Ortholog Compara
Innate immune responsedefinition[GO:0045087]  
1
  • UniProtKB
Isoform  PML-4   Intrinsic apoptotic signaling pathway in response to DNA damagedefinition[GO:0008630]  
1
  • UniProtKB
Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediatordefinition[GO:0042771]  
1
  • Ortholog Curator
Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stressdefinition[GO:0070059] silver  
1
  • Ortholog Compara
Intrinsic apoptotic signaling pathway in response to oxidative stressdefinition[GO:0008631] silver  
1
  • Ortholog Compara
Maintenance of protein location in nucleusdefinition[GO:0051457]  
1
  • MGI
Myeloid cell differentiationdefinition[GO:0030099] silver  
1
  • Ortholog Compara
Negative regulation of angiogenesisdefinition[GO:0016525]  
1
  • UniProtKB
Isoforms  PML-8 and PML-4   Negative regulation of cell growthdefinition[GO:0030308]  
4
  • UniProtKB
Negative regulation of cell proliferationdefinition[GO:0008285]  
1
  • BHF-UCL
Isoform  PML-8   Negative regulation of mitotic cell cycledefinition[GO:0045930]  
1
  • UniProtKB
Negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic processdefinition[GO:2000059]  
1
  • UniProtKB
Negative regulation of telomerase activitydefinition[GO:0051974]  
1
  • UniProtKB
Negative regulation of telomere maintenance via telomerasedefinition[GO:0032211]  
1
  • UniProtKB
Isoforms  PML-8 , PML-6 and PML-4   Negative regulation of transcription, DNA-templateddefinition[GO:0045892]  
4
  • UniProtKB
Isoform  PML-4   Negative regulation of translation in response to oxidative stressdefinition[GO:0032938]  
1
  • UniProtKB
Negative regulation of viral release from host celldefinition[GO:1902187]  
1
  • UniProtKB
PML body organizationdefinition[GO:0030578]  
3
  • UniProtKB
Isoform  PML-4   Positive regulation of apoptotic process involved in mammary gland involutiondefinition[GO:0060058]  
1
  • UniProtKB
Isoforms  PML-5 and PML-6   Positive regulation of defense response to virus by hostdefinition[GO:0002230]  
2
  • UniProtKB
Positive regulation of extrinsic apoptotic signaling pathwaydefinition[GO:2001238]  
1
  • UniProtKB
Isoform  PML-4   Positive regulation of histone deacetylationdefinition[GO:0031065]  
1
  • UniProtKB
Proteasome-mediated ubiquitin-dependent protein catabolic processdefinition[GO:0043161]  
1
  • UniProtKB
Protein complex assemblydefinition[GO:0006461]  
1
  • UniProtKB
Isoform  PML-4   Protein stabilizationdefinition[GO:0050821]  
1
  • UniProtKB
Isoform  PML-4   Protein targetingdefinition[GO:0006605]  
2
  • UniProtKB
Regulation of calcium ion transport into cytosoldefinition[GO:0010522]  
1
  • Ortholog Curator
Regulation of circadian rhythmdefinition[GO:0042752]  
1
  • Ortholog Curator
Regulation of double-strand break repairdefinition[GO:2000779]  
1
  • UniProtKB
Regulation of MHC class I biosynthetic processdefinition[GO:0045343] silver  
1
  • Ortholog Compara
Regulation of protein phosphorylationdefinition[GO:0001932]  
1
  • Ortholog Curator
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
1
  • UniProtKB
Response to cytokinedefinition[GO:0034097]  
1
  • BHF-UCL
Response to gamma radiationdefinition[GO:0010332] silver  
1
  • Ortholog Compara
Response to hypoxiadefinition[GO:0001666]  
1
  • UniProtKB
Response to UVdefinition[GO:0009411] silver  
1
  • Ortholog Compara
Retinoic acid receptor signaling pathwaydefinition[GO:0048384] silver  
1
  • Ortholog Compara
SMAD protein import into nucleusdefinition[GO:0007184] silver  
1
  • Ortholog Compara
Transcription, DNA-templateddefinition[GO:0006351]  
1
  • UniProtKB KW
Transforming growth factor beta receptor signaling pathwaydefinition[GO:0007179] silver  
1
  • Ortholog Compara
Viral processdefinition[GO:0016032]  
1
  • UniProtKB KW
Pathways 
According to KEGG, this protein belongs to the following pathways:
Acute myeloid leukemia  hsa05221+5371  
Endocytosis  hsa04144+5371  
Herpes simplex infection  hsa05168+5371  
Influenza A  hsa05164+5371  
Pathways in cancer  hsa05200+5371  
Ubiquitin mediated proteolysis  hsa04120+5371  
According to Reactome, this protein belongs to the following pathway:
Interferon gamma signaling  REACT_25078  
 

Keywords

Biological process 
Antiviral defense  definition   [KW-0051]
Apoptosis  definition   [KW-0053]
Biological rhythms  definition   [KW-0090]
Host-virus interaction  definition   [KW-0945]
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Activator  definition   [KW-0010]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links