Human Gene MDM4 (ENST00000367183.7) from GENCODE V44
Description: Homo sapiens MDM4 regulator of p53 (MDM4), transcript variant 3, mRNA. (from RefSeq NM_001204172) RefSeq Summary (NM_001204172): 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]. Gencode Transcript: ENST00000367183.7 Gencode Gene: ENSG00000198625.14 Transcript (Including UTRs) Position: hg38 chr1:204,516,379-204,558,119 Size: 41,741 Total Exon Count: 3 Strand: + Coding Region Position: hg38 chr1:204,525,519-204,549,682 Size: 24,164 Coding Exon Count: 2
ID:MDM4_HUMAN DESCRIPTION: RecName: Full=Protein Mdm4; AltName: Full=Double minute 4 protein; AltName: Full=Mdm2-like p53-binding protein; AltName: Full=Protein Mdmx; AltName: Full=p53-binding protein Mdm4; FUNCTION: Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions. SUBUNIT: Interacts with MDM2, TP53, TP73 and USP2. Found in a trimeric complex with UPB2, MDM2 and MDM4. Interacts (phosphorylated) with YWHAG; negatively regulates MDM4 activity toward TP53. INTERACTION: Q00987:MDM2; NbExp=6; IntAct=EBI-398437, EBI-389668; Q13064:MKRN3; NbExp=2; IntAct=EBI-398437, EBI-2340269; P04637:TP53; NbExp=4; IntAct=EBI-398437, EBI-366083; P62837:UBE2D2; NbExp=2; IntAct=EBI-398437, EBI-347677; SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Expressed in all tissues tested with high levels in thymus. INDUCTION: Down-regulated by cisplatin (at protein level). DOMAIN: Region I is sufficient for binding TP53 and inhibiting its G1 arrest and apoptosis functions. It also binds TP73. Region II contains most of a central acidic region and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc mediates the heterooligomerization with MDM2. PTM: Phosphorylated. Phosphorylation at Ser-367 promotes interaction with YWHAG and subsequent ubiquitination and degradation. Phosphorylation at Ser-342 also induces ubiquitination and degradation but to a lower extent. PTM: Ubiquitinated and degraded by MDM2. Deubiquitination by USP2 on the other hand stabilizes the MDM4 protein. MASS SPECTROMETRY: Mass=54863.3; Method=MALDI; Range=1-490; Source=PubMed:11840567; SIMILARITY: Belongs to the MDM2/MDM4 family. SIMILARITY: Contains 1 RanBP2-type zinc finger. SIMILARITY: Contains 1 RING-type zinc finger. SIMILARITY: Contains 1 SWIB domain. WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mdm4/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O15151
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest GO:0008283 cell proliferation GO:0008285 negative regulation of cell proliferation GO:0016567 protein ubiquitination GO:0016579 protein deubiquitination GO:0030330 DNA damage response, signal transduction by p53 class mediator GO:0042177 negative regulation of protein catabolic process GO:0043066 negative regulation of apoptotic process GO:0045023 G0 to G1 transition GO:0050821 protein stabilization GO:0065003 macromolecular complex assembly GO:0071157 negative regulation of cell cycle arrest GO:0071456 cellular response to hypoxia GO:1901796 regulation of signal transduction by p53 class mediator
US Server
