InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: PML

Summary

InnateDB Gene

IDBG-21462.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PML

Gene Name

promyelocytic leukemia

Synonyms

MYL; PP8675; RNF71; TRIM19

Species

Homo sapiens

Ensembl Gene

ENSG00000140464

Encoded Proteins

IDBP-21464

promyelocytic leukemia

IDBP-21466

promyelocytic leukemia

IDBP-21468

promyelocytic leukemia

IDBP-21470

promyelocytic leukemia

IDBP-240140

promyelocytic leukemia

IDBP-240142

promyelocytic leukemia

IDBP-377356

promyelocytic leukemia

IDBP-377370

promyelocytic leukemia

IDBP-746718

IDBP-746331

IDBP-747347

IDBP-746600

IDBP-747048

IDBP-744480

IDBP-745766

IDBP-746532

IDBP-747608

IDBP-746438

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 21131187

PML, a member of the TRIM protein family, is upregulated by Type I and Type II interferons and have been found to restrict viral replication by modulating the RIG-I pathway.

PMID 21779477

Pml(-/-) mice are resistant to LPS-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-kB pathway. Pml(-/-) mice also exhibit impaired function of macrophages and are thus unable to clear pathogenic microorganisms. (Demonstrated in murine model)

InnateDB Annotation from Orthologs

Summary

PMID 21131187

[Mus musculus] Pml, a member of the Trim protein family, is upregulated by Type I and Type II interferons and have been found to restrict viral replication by modulating the RIG-I pathway.

PMID 21779477

[Mus musculus] Pml(-/-) mice are resistant to LPS-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-kB pathway. Pml(-/-) mice also exhibit impaired function of macrophages and are thus unable to clear pathogenic microorganisms.

Entrez Gene

Summary

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]
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]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 15:73994673-74047812

Strand

Forward strand

Band

q24.1

Transcripts

ENST00000268058	ENSP00000268058
ENST00000359928	ENSP00000353004
ENST00000268059	ENSP00000268059
ENST00000354026	ENSP00000315434
ENST00000395135	ENSP00000378567
ENST00000395132	ENSP00000378564
ENST00000436891	ENSP00000394642
ENST00000435786	ENSP00000395576
ENST00000565898	ENSP00000455838
ENST00000564428	ENSP00000457023
ENST00000566068	ENSP00000458061
ENST00000564725
ENST00000569161
ENST00000570213
ENST00000565317
ENST00000567543	ENSP00000456277
ENST00000567606	ENSP00000457669
ENST00000563500	ENSP00000457032
ENST00000569965	ENSP00000456486
ENST00000562086	ENSP00000456329
ENST00000569477	ENSP00000455612
ENST00000565239	ENSP00000456989

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 277 experimentally validated interaction(s) in this database.
They are also associated with 22 interaction(s) predicted by orthology.

Experimentally validated
Total	277 [view]
Protein-Protein	275 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	22 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003713	transcription coactivator activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0031625	ubiquitin protein ligase binding
GO:0032183	SUMO binding
GO:0042803	protein homodimerization activity
GO:0046332	SMAD binding
GO:0046982	protein heterodimerization activity
GO:0050897	cobalt ion binding

Biological Process

GO:0001666	response to hypoxia
GO:0001932	regulation of protein phosphorylation
GO:0002230	positive regulation of defense response to virus by host
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006461	protein complex assembly
GO:0006605	protein targeting
GO:0006915	apoptotic process
GO:0006919	activation of cysteine-type endopeptidase activity involved in apoptotic process
GO:0006977	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0007050	cell cycle arrest
GO:0007179	transforming growth factor beta receptor signaling pathway
GO:0007182	common-partner SMAD protein phosphorylation
GO:0007184	SMAD protein import into nucleus
GO:0007569	cell aging
GO:0008285	negative regulation of cell proliferation
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage
GO:0008631	intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0009411	response to UV
GO:0010332	response to gamma radiation
GO:0010522	regulation of calcium ion transport into cytosol
GO:0016032	viral process
GO:0016525	negative regulation of angiogenesis
GO:0019221	cytokine-mediated signaling pathway
GO:0030099	myeloid cell differentiation
GO:0030308	negative regulation of cell growth
GO:0030578	PML body organization
GO:0031065	positive regulation of histone deacetylation
GO:0032211	negative regulation of telomere maintenance via telomerase
GO:0032469	endoplasmic reticulum calcium ion homeostasis
GO:0032922	circadian regulation of gene expression
GO:0032938	negative regulation of translation in response to oxidative stress
GO:0034097	response to cytokine
GO:0042752	regulation of circadian rhythm
GO:0042771	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0043153	entrainment of circadian clock by photoperiod
GO:0043161	proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0045087	innate immune response (InnateDB)
GO:0045165	cell fate commitment
GO:0045343	regulation of MHC class I biosynthetic process
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045930	negative regulation of mitotic cell cycle
GO:0048384	retinoic acid receptor signaling pathway
GO:0050821	protein stabilization
GO:0051457	maintenance of protein location in nucleus
GO:0051607	defense response to virus
GO:0051974	negative regulation of telomerase activity
GO:0060058	positive regulation of apoptotic process involved in mammary gland involution
GO:0060333	interferon-gamma-mediated signaling pathway
GO:0060444	branching involved in mammary gland duct morphogenesis
GO:0070059	intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress
GO:0071353	cellular response to interleukin-4
GO:0072332	intrinsic apoptotic signaling pathway by p53 class mediator
GO:0090398	cellular senescence
GO:0097191	extrinsic apoptotic signaling pathway
GO:1902187	negative regulation of viral release from host cell
GO:2000059	negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000779	regulation of double-strand break repair
GO:2001235	positive regulation of apoptotic signaling pathway
GO:2001238	positive regulation of extrinsic apoptotic signaling pathway

Cellular Component

GO:0005622	intracellular
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0016363	nuclear matrix
GO:0016605	PML body
GO:0031901	early endosome membrane
GO:0031965	nuclear membrane
GO:0042406	extrinsic component of endoplasmic reticulum membrane