Summary of MDM2
This gene codes for a nuclear-localized E3 ubiquitin ligase. The protein can promote tumor formation. Overexpression may cause cancer. There is a pseudogene on chromosome 2 [R]
The Function of MDM2
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.
Protein names
Recommended name:
E3 ubiquitin-protein ligase Mdm2Alternative name(s):
Double minute 2 proteinHdm2
Oncoprotein Mdm2
p53-binding protein Mdm2
- RS2279744 (MDM2) ??
- RS3730536 (MDM2) ??
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Top Gene-Substance Interactions
MDM2 Interacts with These Diseases
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Substances That Increase MDM2
| Substances | Interaction | Organism | Category |
Substances That Decrease MDM2
| Substances | Interaction | Organism | Category |
Advanced Summary
From NCBI Gene: Accelerated tumor formation, susceptibility toFrom UniProt: 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.
From NCBI Gene: 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] From UniProt: 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.
Conditions with Increased Gene Activity
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Conditions with Decreased Gene Activity
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Technical
The following transcription factors affect gene expression:
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.
Gene Pathways:
Induction:
By DNA damage.
Caution:
A report observed N-glycosylation at Asn-349 (PubMed:19139490). However, as the protein is not extracellular, additional evidences are required to confirm this result.
Molecular Function:
- P53 Binding
- Ubiquitin-Protein Transferase Activity
- Zinc Ion Binding
- Ligase Activity
- Sumo Transferase Activity
- Enzyme Binding
- Ubiquitin Protein Ligase Binding
- Identical Protein Binding
- Ubiquitin Protein Ligase Activity
Biological Processes:
- Negative Regulation Of Transcription From Rna Polymerase Ii Promoter
- Blood Vessel Development
- Blood Vessel Remodeling
- Regulation Of Heart Rate
- Atrioventricular Valve Morphogenesis
- Endocardial Cushion Morphogenesis
- Ventricular Septum Development
- Atrial Septum Development
- Protein Complex Assembly
- Dna Damage Response, Signal Transduction By P53 Class Mediator Resulting In Cell Cycle Arrest
- Traversing Start Control Point Of Mitotic Cell Cycle
- Positive Regulation Of Cell Proliferation
- Response To Toxic Substance
- Response To Carbohydrate
- Response To Iron Ion
- Positive Regulation Of Gene Expression
- Negative Regulation Of Protein Processing
- Negative Regulation Of Neuron Projection Development
- Viral Process
- Protein Ubiquitination
- Protein Sumoylation
- Peptidyl-Lysine Modification
- Protein Destabilization
- Response To Magnesium Ion
- Positive Regulation Of Proteasomal Ubiquitin-Dependent Protein Catabolic Process
- Protein Localization To Nucleus
- Transcription Factor Catabolic Process
- Regulation Of Protein Catabolic Process
- Response To Cocaine
- Protein Ubiquitination Involved In Ubiquitin-Dependent Protein Catabolic Process
- Negative Regulation Of Cysteine-Type Endopeptidase Activity Involved In Apoptotic Process
- Response To Morphine
- Negative Regulation Of Dna Damage Response, Signal Transduction By P53 Class Mediator
- Establishment Of Protein Localization
- Response To Ether
- Negative Regulation Of Transcription, Dna-Templated
- Positive Regulation Of Mitotic Cell Cycle
- Response To Antibiotic
- Positive Regulation Of Protein Export From Nucleus
- Response To Steroid Hormone
- Protein Autoubiquitination
- Cardiac Septum Morphogenesis
- Cellular Response To Hydrogen Peroxide
- Negative Regulation Of Cell Cycle Arrest
- Cellular Response To Antibiotic
- Cellular Response To Vitamin B1
- Cellular Response To Alkaloid
- Cellular Response To Growth Factor Stimulus
- Cellular Response To Peptide Hormone Stimulus
- Cellular Response To Estrogen Stimulus
- Cellular Response To Hypoxia
- Cellular Response To Uv-C
- Regulation Of Signal Transduction By P53 Class Mediator
- Negative Regulation Of Signal Transduction By P53 Class Mediator
- Positive Regulation Of Vascular Smooth Muscle Cell Proliferation
- Positive Regulation Of Vascular Associated Smooth Muscle Cell Migration
- Response To Water-Immersion Restraint Stress