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: 283.8   (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: 283.8   (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

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (401)

Explore Interacting Targets

1 – 10 of 401

• See Interactions on String-DB

TUBA3C

Tchem

Novelty:  0.0187396

p_int:  0.999994601

p_ni:  0.000005399

Data Source:  BioPlex

GOPC

Tbio

Novelty:  0.01110168

p_int:  0.999988706

p_ni:  0.000011294

Data Source:  BioPlex

ACOT8

Tbio

Family:  Enzyme

Novelty:  0.02218214

p_int:  0.999972054

p_ni:  0.000027946

Score:  0.519

Data Source:  BioPlex,STRINGDB

TNNC2

Tbio

Novelty:  0.07759506

p_int:  0.999894145

p_ni:  0.000105855

Data Source:  BioPlex

TULP3

Tbio

Family:  TF

Novelty:  0.06911636

p_int:  0.998683501

p_ni:  0.001316499

Data Source:  BioPlex

SNX11

Tdark

Novelty:  0.21586113

p_int:  0.998194592

p_ni:  0.001805408

Score:  0.193

Data Source:  BioPlex,STRINGDB

TMED7

Tdark

Novelty:  0.31193294

p_int:  0.99608934

p_ni:  0.00391066

Data Source:  BioPlex

KLHL40

Tbio

Novelty:  0.0432945

p_int:  0.995079652

p_ni:  0.004920348

Data Source:  BioPlex

NDUFS1

Tclin

Family:  Enzyme

Novelty:  0.0215624

p_int:  0.989181776

p_ni:  0.010818224

Score:  0.176

Data Source:  BioPlex,STRINGDB

TRIML2

Tdark

Family:  Enzyme

Novelty:  0.38455379

p_int:  0.982996873

p_ni:  0.017003127

Score:  0.365

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (3)

Explore Nearest Tclin Targets

Downstream (3)

1 – 3 of 3

CSF1R

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  3

1: Acute myeloid leukemia

2: Transcriptional misregulation in cancer

3: Pathways in cancer

CSF3R

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  1

1: Pathways in cancer

CSF2RA

Tclin

Family:  Other

KEGG Distance:  2

Common Pathways:  1

1: Pathways in cancer

Pathways (48)

Reactome (25)

KEGG (7)

PathwayCommons (9)

WikiPathways (7)

Cytokine Signaling in Immune system (R-HSA-1280215)

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5

1 – 5 of 25

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Generic Transcription Pathway	1195 targets	R-HSA-212436
Reactome	Immune System	2246 targets	R-HSA-168256

Name	Explore in Pharos	Explore in Source
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Developmental Biology	1055 targets	R-HSA-1266738
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436
Immune System	2246 targets	R-HSA-168256

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (84)

Functions (10)

Components (12)

Processes (62)

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1 – 10 of 10

GO Term	Evidence	Assigned by
SUMO transferase activity	Inferred from Experiment (EXP)	Reactome
cobalt ion binding	Inferred from Direct Assay (IDA)	UniProtKB
protein heterodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
transcription coactivator activity	Inferred from Direct Assay (IDA)	UniProtKB
zinc ion binding	Inferred from Direct Assay (IDA)	UniProtKB
protein homodimerization activity	Inferred from Physical Interaction (IPI)	BHF-UCL
SUMO binding	Inferred from Physical Interaction (IPI)	UniProtKB
ubiquitin protein ligase binding	Inferred from Physical Interaction (IPI)	UniProtKB
SMAD binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
DNA binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations (null)

No disease associations found

GWAS Traits (24)

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1 – 5 of 24

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
exfoliation syndrome	EFO_0004235	4	4	0	15	98.7
body height	EFO_0004339	4	3	4		92.5
appendicular lean mass	EFO_0004980	4	2	4		91.7
BMI-adjusted waist circumference	EFO_0007789	7	8	23		89
BMI-adjusted hip circumference	EFO_0008039	2	9	11		85.6

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
exfoliation syndrome	EFO_0004235	0	15	98.7
body height	EFO_0004339	4		92.5
appendicular lean mass	EFO_0004980	4		91.7
BMI-adjusted waist circumference	EFO_0007789	23		89
BMI-adjusted hip circumference	EFO_0008039	11		85.6

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UniProt Keyword Find Similar Targets

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3D-structure
Acetylation
Activator
Alternative splicing
Antiviral defense
Apoptosis
Biological rhythms
Chromosomal rearrangement
Coiled coil
Complete proteome

GWAS Trait Find Similar Targets

No Header	No Header
anthropometric measurement
appendicular lean mass
birth weight
BMI-adjusted hip circumference
BMI-adjusted waist circumference
BMI-adjusted waist-hip ratio
body fat distribution
body height
body mass index
coronary artery disease

MGI Phenotype Find Similar Targets

No Header	No Header
cellular phenotype
endocrine/exocrine gland phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging
neoplasm

IDG Resources

No IDG generated resources found

Orthologs (9)

1 – 5 of 9

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	promyelocytic leukemia		453736
Macaque	promyelocytic leukemia		700379
Mouse	promyelocytic leukemia	MGI:104662	18854
Rat	promyelocytic leukemia	RGD:1562602	315713
Dog	promyelocytic leukemia		487641

Species	Name	OMA	EggNOG	Inparanoid
Chimp	promyelocytic leukemia
Macaque	promyelocytic leukemia
Mouse	promyelocytic leukemia
Rat	promyelocytic leukemia
Dog	promyelocytic leukemia

Publication Statistics

PubMed Score 283.80

PubMed score by year

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PubTator Score 1594.29

PubTator score by year

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Related Publications

Text Mined References (440)

GeneRif Annotations (330)

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PMID	Year	Title