InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: MDM2

Summary

InnateDB Protein

IDBP-46441.7

Last Modified

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

Gene Symbol

MDM2

Protein Name

Mdm2 p53 binding protein homolog (mouse)

Synonyms

ACTFS; hdm2; HDMX;

Species

Homo sapiens

Ensembl Protein

ENSP00000348637

InnateDB Gene

IDBG-46431 (MDM2)

Protein Structure

UniProt Annotation

Function

E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation. {ECO:0000269PubMed:12821780, ECO:0000269PubMed:15053880, ECO:0000269PubMed:15195100, ECO:0000269PubMed:15632057, ECO:0000269PubMed:16337594, ECO:0000269PubMed:17290220, ECO:0000269PubMed:19098711, ECO:0000269PubMed:19219073, ECO:0000269PubMed:19837670, ECO:0000269PubMed:19965871, ECO:0000269PubMed:20173098, ECO:0000269PubMed:20385133, ECO:0000269PubMed:20858735, ECO:0000269PubMed:22128911}.

Subcellular Localization

Nucleus, nucleoplasm. Cytoplasm. Nucleus, nucleolus. Note=Expressed predominantly in the nucleoplasm. Interaction with ARF(P14) results in the localization of both proteins to the nucleolus. The nucleolar localization signals in both ARF(P14) and MDM2 may be necessary to allow efficient nucleolar localization of both proteins. Colocalizes with RASSF1 isoform A in the nucleus.

Disease Associations

Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding.

Tissue Specificity

Ubiquitous. Isoform Mdm2-A, isoform Mdm2-B, isoform Mdm2-C, isoform Mdm2-D, isoform Mdm2-E, isoform Mdm2-F and isoform Mdm2-G are observed in a range of cancers but absent in normal tissues.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 932 experimentally validated interaction(s) in this database.
They are also associated with 39 interaction(s) predicted by orthology.

Experimentally validated
Total	932 [view]
Protein-Protein	915 [view]
Protein-DNA	10 [view]
Protein-RNA	1 [view]
DNA-DNA	6 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	39 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002039	p53 binding
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0016874	ligase activity
GO:0019899	enzyme binding
GO:0031625	ubiquitin protein ligase binding
GO:0042802	identical protein binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0006461	protein complex assembly
GO:0006977	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007268	synaptic transmission
GO:0008284	positive regulation of cell proliferation
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0016032	viral process
GO:0016567	protein ubiquitination
GO:0018205	peptidyl-lysine modification
GO:0031648	protein destabilization
GO:0032436	positive regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0034504	protein localization to nucleus
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0042176	regulation of protein catabolic process
GO:0042787	protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0043066	negative regulation of apoptotic process
GO:0043518	negative regulation of DNA damage response, signal transduction by p53 class mediator
GO:0045087	innate immune response
GO:0045184	establishment of protein localization
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045931	positive regulation of mitotic cell cycle
GO:0046677	response to antibiotic
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048015	phosphatidylinositol-mediated signaling
GO:0071157	negative regulation of cell cycle arrest
GO:0071456	cellular response to hypoxia

Cellular Component

GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005730	nucleolus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0016604	nuclear body
GO:0030666	endocytic vesicle membrane
GO:0043234	protein complex