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