MDM4 [The Human Chemical-Genetic Interaction Map Project]

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======= MDM4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: MDM4
  * **<color #00a2e8>Official Name</color>**: MDM4 regulator of p53
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4194|4194]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O15151|O15151]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=MDM4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MDM4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/602704|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:16511572}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|zf-RanBP|
|SWIB|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|G0 to G1 transition|
|atrial septum development|
|negative regulation of cell cycle arrest|
|atrioventricular valve morphogenesis|
|atrioventricular valve development|
|endocardial cushion morphogenesis|
|cardiac atrium development|
|endocardial cushion development|
|mesenchyme morphogenesis|
|heart valve morphogenesis|
|DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest|
|intracellular signal transduction involved in G1 DNA damage checkpoint|
|signal transduction involved in mitotic DNA damage checkpoint|
|signal transduction involved in mitotic G1 DNA damage checkpoint|
|signal transduction involved in mitotic cell cycle checkpoint|
|signal transduction involved in mitotic DNA integrity checkpoint|
|heart valve development|
|mitotic G1 DNA damage checkpoint|
|mitotic G1/S transition checkpoint|
|G1 DNA damage checkpoint|
|signal transduction involved in DNA integrity checkpoint|
|signal transduction involved in DNA damage checkpoint|
|ventricular septum development|
|signal transduction involved in cell cycle checkpoint|
|DNA damage response, signal transduction by p53 class mediator|
|positive regulation of cell cycle arrest|
|mitotic DNA damage checkpoint|
|negative regulation of G1/S transition of mitotic cell cycle|
|mitotic DNA integrity checkpoint|
|signal transduction in response to DNA damage|
|negative regulation of cell cycle G1/S phase transition|
|regulation of cell cycle arrest|
|cardiac septum development|
|signal transduction by p53 class mediator|
|cardiac ventricle development|
|DNA damage checkpoint|
|negative regulation of protein catabolic process|
|DNA integrity checkpoint|
|regulation of G1/S transition of mitotic cell cycle|
|mitotic cell cycle checkpoint|
|regulation of cell cycle G1/S phase transition|
|cardiac chamber development|
|protein stabilization|
|regulation of signal transduction by p53 class mediator|
|cellular response to hypoxia|
|cell cycle checkpoint|
|cellular response to decreased oxygen levels|
|negative regulation of mitotic cell cycle phase transition|
|cellular response to oxygen levels|
|mesenchyme development|
|negative regulation of cell cycle phase transition|
|heart morphogenesis|
|protein deubiquitination|
|positive regulation of cell cycle process|
|regulation of protein stability|
|protein modification by small protein removal|
|negative regulation of mitotic cell cycle|
|negative regulation of catabolic process|
|negative regulation of cell cycle process|
|response to hypoxia|
|enzyme binding|
|response to decreased oxygen levels|
|positive regulation of cell cycle|
|response to oxygen levels|
|regulation of protein catabolic process|
|regulation of mitotic cell cycle phase transition|
|regulation of cell cycle phase transition|
|heart development|
|cell population proliferation|
|tissue morphogenesis|
|negative regulation of cell cycle|
|mitotic cell cycle process|
|regulation of mitotic cell cycle|
|negative regulation of cell population proliferation|
|mitotic cell cycle|
|regulation of cell cycle process|
|cellular response to DNA damage stimulus|
|zinc ion binding|
|negative regulation of transcription by RNA polymerase II|
|circulatory system development|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|animal organ morphogenesis|
|protein modification by small protein conjugation or removal|
|regulation of catabolic process|
|negative regulation of cell death|
|cell cycle process|
|negative regulation of protein metabolic process|
|response to abiotic stimulus|
|regulation of cell cycle|
|negative regulation of transcription, DNA-templated|
|negative regulation of nucleic acid-templated transcription|
|negative regulation of RNA biosynthetic process|
|proteolysis|
|negative regulation of RNA metabolic process|
|cell cycle|
|negative regulation of cellular macromolecule biosynthetic process|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|protein-containing complex assembly|
|regulation of programmed cell death|
|regulation of cell population proliferation|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|negative regulation of gene expression|
|tissue development|
|regulation of intracellular signal transduction|
|protein-containing complex subunit organization|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp294|Nutlin-3A 1.6μM R06 exp294]]|-2.75|
|[[:results:exp518|RK-33 8μM R08 exp518]]|-2.01|
|[[:results:exp346|CoCl2 18μM R07 exp346]]|-1.79|
|[[:results:exp485|GSK626616 14μM R08 exp485]]|-1.78|
|[[:results:exp460|BML-284 0.09μM R08 exp460]]|-1.75|
|[[:results:exp217|Mdivi-1 15μM R05 exp217]]|-1.75|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 1/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|1/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 2323
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 8.32 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='MDM4 Expression in NALM6 Cells: 8.32'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>