DegronMD - P29590(PML)

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.; 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 (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). {ECO:0000269|PubMed:20972456, ECO:0000269|PubMed:28250117}. View more >>

GO - Biological processes (BP): 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 fate commitment [GO:0045165]; cellular response to interleukin-4 [GO:0071353]; cellular response to leukemia inhibitory factor [GO:1990830]; cellular senescence [GO:0090398]; circadian regulation of gene expression [GO:0032922]; common-partner SMAD protein phosphorylation [GO:0007182]; 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]; 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 population proliferation [GO:0008285]; negative regulation of interleukin-1 beta production [GO:0032691]; negative regulation of mitotic cell cycle [GO:0045930]; 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 ubiquitin-dependent protein catabolic process [GO:2000059]; oncogene-induced cell senescence [GO:0090402]; 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 peptidyl-lysine acetylation [GO:2000758]; positive regulation of protein localization to chromosome, telomeric region [GO:1904816]; positive regulation of signal transduction by p53 class mediator [GO:1901798]; positive regulation of telomere maintenance [GO:0032206]; positive regulation of transcription, DNA-templated [GO:0045893]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]; protein-containing complex assembly [GO:0065003]; protein import into nucleus [GO:0006606]; protein stabilization [GO:0050821]; protein targeting [GO:0006605]; regulation of calcium ion transport into cytosol [GO:0010522]; regulation of cell adhesion [GO:0030155]; regulation of cell cycle [GO:0051726]; regulation of circadian rhythm [GO:0042752]; regulation of double-strand break repair [GO:2000779]; regulation of protein phosphorylation [GO:0001932]; 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]; suppression of viral release by host [GO:0044790]; transforming growth factor beta receptor signaling pathway [GO:0007179] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.V556I	TCGA-B5-A0JX	UCEC	TCGA	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.2778
p.V556I	DO43322	UCEC	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.2778
p.E568K	TCGA-D1-A103	UCEC	TCGA	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.1667
p.E568K	TCGA-EA-A97N	CESC	TCGA	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.1667
p.E568K	DO49935	CESC	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.1667
p.E568K	DO42312	UCEC	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.1667
p.G550W	TCGA-FY-A3BL	THCA	TCGA	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.1111
p.G550W	DO40190	THCA	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.1111
p.S561N	TCGA-VQ-A924	STAD	TCGA	VISSS	DEG_SPOP_SBC_1	558:562	Mutation altering degron motif	0.818
p.S561N	DO51795	STAD	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation altering degron motif	0.818
p.A558V	DO7780	COAD	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation altering degron motif	0.6936
p.A558V	DO233088	GACA	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation altering degron motif	0.6936
p.A558V	DO43186	UCEC	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation altering degron motif	0.6936
p.A549V	DO230312	COCA	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.0833
p.G550R	DO233115	GACA	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.1111
p.R555C	DO233731	GACA	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.25
p.R555C	DO219774	UCEC	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.25
p.P564Q	DO228969	LICA	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.2778
p.V556F	DO229025	LICA	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.2778
p.G549W	DO23108	LINC	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.0833
p.G549W	DO45041	LINC	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.0833
p.S571F	DO220902	MELA	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.0833
p.R555H	DO36386	READ	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.25
p.P564S	DO218863	SKCA	ICGC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.2778
p.A567V	SIDM01314	Colorectal Carcinoma	GDSC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.1944
p.A549T	SIDM01265	Plasma Cell Myeloma	GDSC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.0833
p.A549T	SIDM01072	Squamous Cell Lung Carcinoma	GDSC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.0833
p.M572V	SIDM01183	Other Solid Cancers	GDSC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.0556
p.M572V	UMC-11	lung	COSMIC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.0556
p.V558L	SIDM00537	Colorectal Carcinoma	GDSC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation altering degron motif	0.6765
p.V558L	ACH-001345	Colon/Colorectal Cancer	CCLE	VISSS	DEG_SPOP_SBC_1	558:562	Mutation altering degron motif	0.6765
p.V558L	GP5d	large intestine	COSMIC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation altering degron motif	0.6765
p.N569Y	ACH-001385	Head and Neck Cancer	CCLE	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.1389
p.S563N	MZ7-mel	skin	COSMIC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation rewiring degron network	0.3056
p.W560C	GP5d	large intestine	COSMIC	VISSS	DEG_SPOP_SBC_1	558:562	Mutation altering degron motif	0.7

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PML

UniProt ID: P29590

Entrez ID: 5371

Protein name: Protein PML (E3 SUMO-protein ligase PML) (EC 2.3.2.-) (Promyelocytic leukemia protein) (RING finger protein 71) (RING-type E3 SUMO transferase PML) (Tripartite motif-containing protein 19) (TRIM19)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PML in