Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0006375
UniProt IDP29590
Primary gene name(s)PML
Synonym gene name(s)MYL, PP8675, RNF71, TRIM19
Protein nameProtein PML
Protein functionFunctions 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.; FUNCTION: 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, 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. 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.
Subcellular locationNucleus. Nucleus, nucleoplasm. Cytoplasm. Nucleus, PML body {ECO:0000269|PubMed:20501696}. Nucleus, nucleolus. Endoplasmic reticulum membrane {ECO:0000250};
Peripheral membrane protein {ECO:0000250};
Cytoplasmic side {ECO:0000250}. Early endosome membrane;
Peripheral membrane protein;
Cytoplasmic side. Note=Isoform PML-1 can shuttle between the nucleus and cytoplasm. Isoform PML-2, isoform PML-3, isoform PML-4, isoform PML-5 and isoform PML-6 are nuclear isoforms whereas isoform PML-7 and isoform PML-14 lacking the nuclear localization signal are cytoplasmic isoforms. Detected in the nucleolus after DNA damage. Acetylation at Lys-487 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. Sequestered in the cytoplasm by interaction with rabies virus phosphoprotein.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P29590
Gene Ontology
(Biological Process)
Complete annatation
activation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0006919];
apoptotic process [GO:0006915];
branching involved in mammary gland duct morphogenesis [GO:0060444];
cell cycle arrest [GO:0007050];
cell fate commitment [GO:0045165];
cellular response to interleukin-4 [GO:0071353];
cellular senescence [GO:0090398];
circadian regulation of gene expression [GO:0032922];
common-partner SMAD protein phosphorylation [GO:0007182];
defense response to virus [GO:0051607];
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977];
endoplasmic reticulum calcium ion homeostasis [GO:0032469];
entrainment of circadian clock by photoperiod [GO:0043153];
extrinsic apoptotic signaling pathway [GO:0097191];
fibroblast migration [GO:0010761];
innate immune response [GO:0045087];
interferon-gamma-mediated signaling pathway [GO:0060333];
intrinsic apoptotic signaling pathway in response to DNA damage [GO:0008630];
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator [GO:0042771];
intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress [GO:0070059];
intrinsic apoptotic signaling pathway in response to oxidative stress [GO:0008631];
maintenance of protein location in nucleus [GO:0051457];
myeloid cell differentiation [GO:0030099];
negative regulation of angiogenesis [GO:0016525];
negative regulation of cell growth [GO:0030308];
negative regulation of cell proliferation [GO:0008285];
negative regulation of interleukin-1 beta secretion [GO:0050713];
negative regulation of mitotic cell cycle [GO:0045930];
negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:2000059];
negative regulation of telomerase activity [GO:0051974];
negative regulation of telomere maintenance via telomerase [GO:0032211];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of translation in response to oxidative stress [GO:0032938];
negative regulation of viral release from host cell [GO:1902187];
PML body organization [GO:0030578];
positive regulation of apoptotic process involved in mammary gland involution [GO:0060058];
positive regulation of defense response to virus by host [GO:0002230];
positive regulation of extrinsic apoptotic signaling pathway [GO:2001238];
positive regulation of fibroblast proliferation [GO:0048146];
positive regulation of histone deacetylation [GO:0031065];
positive regulation of MHC class I biosynthetic process [GO:0045345];
positive regulation of protein localization to chromosome, telomeric region [GO:1904816];
positive regulation of telomere maintenance [GO:0032206];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161];
protein complex assembly [GO:0006461];
protein stabilization [GO:0050821];
protein sumoylation [GO:0016925];
protein targeting [GO:0006605];
regulation of calcium ion transport into cytosol [GO:0010522];
regulation of cell adhesion [GO:0030155];
regulation of circadian rhythm [GO:0042752];
regulation of double-strand break repair [GO:2000779];
regulation of protein phosphorylation [GO:0001932];
regulation of signal transduction by p53 class mediator [GO:1901796];
regulation of transcription, DNA-templated [GO:0006355];
response to cytokine [GO:0034097];
response to gamma radiation [GO:0010332];
response to hypoxia [GO:0001666];
response to UV [GO:0009411];
retinoic acid receptor signaling pathway [GO:0048384];
SMAD protein import into nucleus [GO:0007184];
transcription, DNA-templated [GO:0006351];
transforming growth factor beta receptor signaling pathway [GO:0007179]
Gene Ontology
(Molecular Function)
Complete annatation
cobalt ion binding [GO:0050897];
DNA binding [GO:0003677];
protein heterodimerization activity [GO:0046982];
protein homodimerization activity [GO:0042803];
SUMO binding [GO:0032183];
transcription coactivator activity [GO:0003713];
ubiquitin protein ligase binding [GO:0031625];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
early endosome membrane [GO:0031901];
extrinsic component of endoplasmic reticulum membrane [GO:0042406];
nuclear chromosome, telomeric region [GO:0000784];
nuclear matrix [GO:0016363];
nuclear membrane [GO:0031965];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
PML body [GO:0016605]
Protein-protein interaction111384
Phylogenetic treeP29590
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: numerous RNA and DNA viruses
      Viral life cycle: various
      Mechanism related to antiviral activity: organize multiprotein nuclear bodies
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-0.4974378028682690.130049414519460.217073930620142
AZA vs. DISU0.2157093289717520.3956969885089620.902586488791209
AZA vs. IL70.00145480777982890.9940016798893150.999311006273513
AZA vs. SAHA0.365915026191290.1361928687536520.469109316180418
DISU vs. CD30.7011187985477570.05502434657184220.116659949987665
DISU vs. IL7-0.2240014790810920.3748106102014960.74699491211658
DISU vs. SAHA0.1529469407104480.603779023943030.874985752839509
DMSO vs. AZA-0.01673527054718720.9209950808568251
DMSO vs. CD30.4703259271214990.1428442194320490.228153121534899
DMSO vs. DISU-0.233926130270770.3390568769256590.83759035206982
DMSO vs. IL70.02551862299394340.8877140138857760.975883512837617
DMSO vs. SAHA0.377426526502930.1125111432610530.398508916589267
HIV vs. Mock in Activation0.3964659011546920.5252970796747350.999983755607037
HIV vs. Mock in Latency0.1017028836561050.5396613128792430.999834320637052
IL7 vs. CD30.5036700741991280.1189191510519330.216531307340471
SAHA vs. CD30.8403358982819630.01843939054981150.0430357155932568
SAHA vs. IL70.3623651565693070.1413196949726430.354510414714198
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.337353 0.0144598
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.965 0.898 0.895 0.957 0.842
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1BOR NMR - A=49-104.
2MVW NMR - A/B=120-168.
2MWX NMR - A=49-104.
4WJN X-ray 1.5Å B=547-573.
4WJO X-ray 1.4Å B=547-573.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
integrase interacts with 11430827
19750561
Envelope surface glycoprotein gp160; precursor interacts with 19023333
19023333
19177012
Tat regulated by 12727882
Envelope surface glycoprotein gp160; precursor cooperates with 19164952
19177012

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa05164 Influenza A - Homo sapiens (human)
hsa05168 Herpes simplex infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05221 Acute myeloid leukemia - Homo sapiens (human)
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