Tchem MDM2 E3 ubiquitin-protein ligase Mdm2

Protein Summary

Description

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 (PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity). This gene encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. This gene is itself transcriptionally-regulated by p53. Overexpression or amplification of this locus is detected in a variety of different cancers. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in a multitude of transcript variants, many of which may be expressed only in tumor cells. [provided by RefSeq, Jun 2013]

Uniprot Accession IDs

• Q00987
• A6NL51
• A8K2S6
• Q13226
• Q13297
• Q13298
• Q13299
• Q13300
• Q13301
• Q53XW0
• Q71TW9
• Q8WYJ1
• Q8WYJ2
• Q9UGI3
• Q9UMT8

Gene Name

• MDM2

Ensembl ID

• ENST00000258149
• ENSP00000258149
• ENSG00000135679
• ENST00000299252
• ENSP00000299252
• ENST00000360430
• ENSP00000353611
• ENST00000393413
• ENSP00000377065
• ENST00000539479
• ENSP00000444430

Symbol

• HDMX
• hdm2
• ACTFS

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
co-expressed gene	1
hub protein	1
kinase	1

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Chromatin/chromatin-binding Protein / E3 Ubiquitin-protein Ligase Mdm2

DTO Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Chromatin/chromatin-binding Protein / E3 Ubiquitin-protein Ligase Mdm2

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: 3735.32   (req: < 5)

Gene RIFs: 1393   (req: <= 3)

Antibodies: 1567   (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: 3735.32   (req: >= 5)

Gene RIFs: 1393   (req: > 3)

Antibodies: 1567   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 79

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 1834

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 3