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Parameter | Value |
---|---|
Gene | PML |
Protein Name | PML_HUMAN |
Organism | Homo sapiens (Human) |
Alternative name(s) | Protein PML (Promyelocytic leukemia protein) (RING finger protein 71) (Tripartite motif-containing protein 19) |
Protein Family | N/A |
NCBI Gene ID | 5371 |
UniProt ID | P29590 |
Enzyme Class | - |
Molecular Weight | 97551 |
Protein Length | 882 |
Protein Domain | InterPro | Pfam |
3D Structure |
PDBe |
PDBj |
RCSB PDB |
DrugPort
ModBase | SwissModel |
Gene Expression | Gene Expression Atlas |
Function and Disease | OMIM |
Protein-protein Interaction Database | STRING | IntAct | MINT |
Kinase Database | Phospho.ELM | PhosphoSite | NetworKIN |
Catalytic Activity (UniProt annotation) | - |
Localization | Nucleus. Nucleus, nucleoplasm. Cytoplasm 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. |
Function (UniProt annotation) | 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. |
Gene Ontology | GO:0000784; GO:0000792; GO:0001666; GO:0001932; GO:0002230; GO:0003677; GO:0003713; GO:0005634; GO:0005654; GO:0005730; GO:0005737; GO:0005829; GO:0006355; GO:0006605; GO:0006606; GO:0006915; GO:0006919; GO:0006977; GO:0007050; GO:0007179; GO:0007182; GO:0008270; GO:0008285; GO:0008630; GO:0008631; GO:0009411; GO:0010332; GO:0010522; GO:0010761; GO:0016032; GO:0016363; GO:0016525; GO:0016605; GO:0019789; GO:0030099; GO:0030155; GO:0030308; GO:0030578; GO:0031065; GO:0031625; GO:0031901; GO:0031965; GO:0032183; GO:0032206; GO:0032211; GO:0032469; GO:0032922; GO:0032938; GO:0034097; GO:0042406; GO:0042752; GO:0042771; GO:0042803; GO:0043153; GO:0043161; GO:0045087; GO:0045165; GO:0045892; GO:0045930; GO:0046332; GO:0046982; GO:0048146; GO:0048384; GO:0050713; GO:0050821; GO:0050897; GO:0051457; GO:0051607; GO:0051974; GO:0060058; GO:0060333; GO:0060444; GO:0065003; GO:0070059; GO:0071353; GO:0090398; GO:0097191; GO:1901796; GO:1902187; GO:1904816; GO:1990830; GO:2000059; GO:2000779; GO:2001238 |
Gene Name | Organism | P-Site | Sequence(+/-7) | Conservation | Disorder | Curator Assessment | Reliability | Evidence Class | Evidence Logic | PubMed | Phospho-ELM | PhosphoSite-Plus |
---|---|---|---|---|---|---|---|---|---|---|---|---|
CHEK2 (O96017) | Homo sapiens | S117 | ESLQRRLSVYRQIVD | 0.681 | 0.1424 | - | - | - | - | - | - |
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Reactome Pathways
KEGG Pathways
Pathway ID | Pathway Name |
---|---|
hsa04120 | Ubiquitin mediated proteolysis |
hsa04144 | Endocytosis |
hsa05164 | Influenza A |
hsa05200 | Pathways in cancer |
hsa05221 | Acute myeloid leukemia |
NCI Nature PID Pathways
Pathway ID | Pathway Name |
---|---|
tgfbrpathway | TGF-beta receptor signaling |