MDM4
Summary: This gene encodes a nuclear protein that contains a p53 binding domain at the N-terminus and a RING finger domain at the C-terminus, and shows structural similarity to p53-binding protein MDM2. Both proteins bind the p53 tumor suppressor protein and inhibit its activity, and have been shown to be overexpressed in a variety of human cancers. However, unlike MDM2 which degrades p53, this protein inhibits p53 by binding its transcriptional activation domain. This protein also interacts with MDM2 protein via the RING finger domain, and inhibits the latter's degradation. So this protein can reverse MDM2-targeted degradation of p53, while maintaining suppression of p53 transactivation and apoptotic functions. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Feb 2011].
| Name | OMIM ID | Ensembl ID | HGNC ID | PHARMGKB ID | Map Location |
|---|---|---|---|---|---|
| MDM4, p53 regulator | MIM:602704 | Ensembl:ENSG00000198625 | HGNC:HGNC:6974 | PA30719 | 1q32.1 |
GO terms in MDM4
| Term Type | Evidence Type | GO Term ID | GO Des. |
|---|---|---|---|
| MF | IPI | GO:0005515 | protein binding |
| MF | TAS | GO:0008270 | zinc ion binding |
| MF | IPI | GO:0019899 | enzyme binding |
| MF | TAS | GO:0061630 | ubiquitin protein ligase activity |
| CC | IDA | GO:0005634 | nucleus |
| CC | NAS | GO:0005634 | nucleus |
| CC | TAS | GO:0005654 | nucleoplasm |
| BP | IDA | GO:0000122 | negative regulation of transcription by RNA polymerase II |
| BP | TAS | GO:0006977 | DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest |
| BP | IEP | GO:0008283 | cell proliferation |
| BP | TAS | GO:0008285 | negative regulation of cell proliferation |
| BP | IEA | GO:0016567 | protein ubiquitination |
| BP | TAS | GO:0016579 | protein deubiquitination |
| BP | IEP | GO:0030330 | DNA damage response, signal transduction by p53 class mediator |
| BP | IMP | GO:0042177 | negative regulation of protein catabolic process |
| BP | IEA | GO:0043066 | negative regulation of apoptotic process |
| BP | IEP | GO:0045023 | G0 to G1 transition |
| BP | IEP | GO:0050821 | protein stabilization |
| BP | IDA | GO:0065003 | protein-containing complex assembly |
| BP | IEA | GO:0071157 | negative regulation of cell cycle arrest |
| BP | IEP | GO:0071456 | cellular response to hypoxia |
| BP | TAS | GO:1901796 | regulation of signal transduction by p53 class mediator |
Gene expression in normal tissue: MDM4
Gene-model tissue-cancer distribution: Bubble Plot
Gene-drug pathway distribution
Pathways in MDM4
| Database | Pathway ID | Pathway Des. |
|---|---|---|
| pid | p53regulationpathway | p53 pathway |
| kegg | hsa04115 | p53 signaling pathway - Homo sapiens (human) |
| kegg | hsa05206 | MicroRNAs in cancer - Homo sapiens (human) |
| wikipathways | WP2261 | Signaling Pathways in Glioblastoma |
| reactome | R-HSA-1640170 | Cell Cycle |
| reactome | R-HSA-212436 | Generic Transcription Pathway |
| reactome | R-HSA-2262752 | Cellular responses to stress |
| reactome | R-HSA-2559580 | Oxidative Stress Induced Senescence |
| reactome | R-HSA-2559583 | Cellular Senescence |
| reactome | R-HSA-2559585 | Oncogene Induced Senescence |
| reactome | R-HSA-3700989 | Transcriptional Regulation by TP53 |
| reactome | R-HSA-392499 | Metabolism of proteins |
| reactome | R-HSA-5633007 | Regulation of TP53 Activity |
| reactome | R-HSA-5688426 | Deubiquitination |
| reactome | R-HSA-5689880 | Ub-specific processing proteases |
| reactome | R-HSA-597592 | Post-translational protein modification |
| reactome | R-HSA-6804756 | Regulation of TP53 Activity through Phosphorylation |
| reactome | R-HSA-6804757 | Regulation of TP53 Degradation |
| reactome | R-HSA-6804760 | Regulation of TP53 Activity through Methylation |
| reactome | R-HSA-6806003 | Regulation of TP53 Expression and Degradation |
| reactome | R-HSA-69541 | Stabilization of p53 |
| reactome | R-HSA-69563 | p53-Dependent G1 DNA Damage Response |
| reactome | R-HSA-69580 | p53-Dependent G1/S DNA damage checkpoint |
| reactome | R-HSA-69615 | G1/S DNA Damage Checkpoints |
| reactome | R-HSA-69620 | Cell Cycle Checkpoints |
| reactome | R-HSA-73857 | RNA Polymerase II Transcription |
| reactome | R-HSA-74160 | Gene expression (Transcription) |
| reactome | R-HSA-8953897 | Cellular responses to external stimuli |
Gene-Drug: Aster Plot
| Drug ID | Drug Name | Model Num. |
|---|---|---|
| iGMDRD705 | Nakiterpiosin | 3 |
| iGMDRD6 | AM-580 | 2 |
| iGMDRD77 | Itraconazole | 3 |
| iGMDRD318 | PAC-1 | 3 |
| iGMDRD138 | PX 12 | 2 |
| iGMDRD137 | Indisulam | 4 |
| iGMDRD255 | SB225002 | 2 |
| iGMDRD64 | Parbendazole | 3 |
| iGMDRD399 | Selumetinib | 2 |
| iGMDRD286 | Nsc 632839 | 1 |
| iGMDRD188 | Piperlongumine | 2 |
| iGMDRD871 | BRD6368 | 2 |
| iGMDRD398 | Sepantronium | 2 |
| iGMDRD506 | Fedratinib | 3 |
| iGMDRD329 | Merck60 | 3 |
| iGMDRD781 | Sirolimus | 3 |
| iGMDRD405 | PIK-75 | 2 |
| iGMDRD307 | Manumycin A | 1 |
| iGMDRD433 | Lexibulin | 2 |
| iGMDRD940 | MDM2/MDMX inhibitor | 2 |
| iGMDRD512 | nutlin 3 | 1 |
| iGMDRD123 | Isoevodiamine | 3 |
| iGMDRD901 | ELCPK | 3 |
| iGMDRD341 | Triacsin c | 3 |
| iGMDRD446 | LY 2183240 | 4 |
| iGMDRD193 | Fqi1 | 3 |
| iGMDRD61 | Kinetin riboside | 4 |
| iGMDRD237 | ABT-751 | 5 |
| iGMDRD351 | GW843682X | 2 |
Gene in drug-gene network: Network Plot
Gene-drug targets distribution
Gene Structure: PDB
Models in MDM4
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