Tbio PML Protein PML

Protein Summary

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. 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 (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. The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This phosphoprotein localizes to nuclear bodies where it functions as a transcription factor and tumor suppressor. Its expression is cell-cycle related and it regulates the p53 response to oncogenic signals. The gene is often involved in the translocation with the retinoic acid receptor alpha gene associated with acute promyelocytic leukemia (APL). Extensive alternative splicing of this gene results in several variations of the protein's central and C-terminal regions; all variants encode the same N-terminus. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P29590
• E9PBR7
• P29591
• P29592
• P29593
• Q00755
• Q15959
• Q59FP9
• Q8WUA0
• Q96S41
• Q9BPW2
• Q9BWP7
• Q9BZX6
• Q9BZX7
• Q9BZX8
• Q9BZX9
• Q9BZY0
• Q9BZY2
• Q9BZY3

Gene Name

• PML

Ensembl ID

• ENST00000268058
• ENSP00000268058
• ENSG00000140464
• ENST00000268059
• ENSP00000268059
• ENST00000354026
• ENSP00000315434
• ENST00000359928
• ENSP00000353004
• ENST00000395132
• ENSP00000378564
• ENST00000395135
• ENSP00000378567
• ENST00000435786
• ENSP00000395576
• ENST00000436891
• ENSP00000394642
• ENST00000564428
• ENSP00000457023
• ENST00000565898
• ENSP00000455838
• ENST00000567543
• ENSP00000456277
• ENST00000569477
• ENSP00000455612
• ENST00000569965
• ENSP00000456486

Symbol

• MYL
• PP8675
• RNF71
• TRIM19
• MYL
• RNF71
• PP8675
• TRIM19

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
virus perturbation	1
transcription factor perturbation	0.96
drug perturbation	0.87

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 321.3   (req: < 5)

Gene RIFs: 330   (req: <= 3)

Antibodies: 545   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 321.3   (req: >= 5)

Gene RIFs: 330   (req: > 3)

Antibodies: 545   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 72

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0