InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Pml

Summary

InnateDB Protein

IDBP-252401.6

Last Modified

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

Gene Symbol

Pml

Protein Name

promyelocytic leukemia

Synonyms

1200009E24Rik; AI661194; Trim19;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000109771

InnateDB Gene

IDBG-171712 (Pml)

Protein Structure

UniProt Annotation

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. Positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2- dependent degradation). Regulates phosphorylation of ITPR3 and plays a role in the regulation of calcium homeostasis at the endoplasmic reticulum. Regulates RB1 phosphorylation and activity. Acts as both a negative regulator of PPARGC1A acetylation and a potent activator of PPAR signaling and fatty acid oxidation. Regulates translation of HIF1A by sequestering MTOR, and thereby plays a role in neoangiogenesis and tumor vascularization. Regulates PER2 nuclear localization and circadian function. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. Required for normal development of the brain cortex during embryogenesis. Plays a role in granulopoiesis or monopoiesis of myeloid progenitor cells. May play a role regulating stem and progenitor cell fate in tissues as diverse as blood, brain and breast. Shows antiviral activity towards lymphocytic choriomeningitis virus (LCMV) and the vesicular stomatitis virus (VSV). {ECO:0000269PubMed:10637504, ECO:0000269PubMed:11907221, ECO:0000269PubMed:12439746, ECO:0000269PubMed:14976551, ECO:0000269PubMed:15195100, ECO:0000269PubMed:15356634, ECO:0000269PubMed:16915281, ECO:0000269PubMed:19136970, ECO:0000269PubMed:21030605, ECO:0000269PubMed:21427174, ECO:0000269PubMed:21779477, ECO:0000269PubMed:22274616, ECO:0000269PubMed:22886304, ECO:0000269PubMed:23279884, ECO:0000269PubMed:9488655, ECO:0000269PubMed:9806545}.

Subcellular Localization

Nucleus {ECO:0000250}. Nucleus, nucleoplasm. Cytoplasm. Nucleus, PML body. Nucleus, nucleolus {ECO:0000250}. Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Early endosome membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Note=Detected in the nucleolus after DNA damage. Acetylation at Lys-497 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 (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 35 experimentally validated interaction(s) in this database.
They are also associated with 155 interaction(s) predicted by orthology.

Experimentally validated
Total	35 [view]
Protein-Protein	34 [view]
Protein-DNA	0
Protein-RNA	1 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	155 [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: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: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: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: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: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