MDM4

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{{STRUCTURE_3jzo| PDB=3jzo | SIZE=400| SCENE= |right|CAPTION=Human MDM4 p53-binding domain (grey) complex peptide inhibitor (green) and K+ ion, [[3jzo]] }}
{{STRUCTURE_3jzo| PDB=3jzo | SIZE=400| SCENE= |right|CAPTION=Human MDM4 p53-binding domain (grey) complex peptide inhibitor (green) and K+ ion, [[3jzo]] }}
== Function ==
== Function ==
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'''MDM4''' is a 490 amino acid protein containing a RING finger domain and a nuclear localization signal. MDM4 interacts with protein MDM2<ref>PMID:12101245</ref>. Both of these proteins show structure similarity and contain a p53-binding domain in their N terminal.
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'''MDM4''' is a 490 amino acid protein containing a RING finger domain (residues 300-339) and a nuclear localization signal. MDM4 interacts with protein MDM2<ref>PMID:12101245</ref>. Both of these proteins show structure similarity and contain a p53-binding domain (or SWIB domain) in their N terminal (residues 23-111).
== Relevance ==
== Relevance ==
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[[3dab]], [[2mwy]] – hMDM4 SWIB domain + p53 transactivation domain<br />
[[3dab]], [[2mwy]] – hMDM4 SWIB domain + p53 transactivation domain<br />
[[2n06]], [[2n0u]], [[2n0w]], [[2n14]] – hMDM4 SWIB domain + p53 transactivation domain – NMR<br />
[[2n06]], [[2n0u]], [[2n0w]], [[2n14]] – hMDM4 SWIB domain + p53 transactivation domain – NMR<br />
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[[3fdo]], [[3jzo]], [[3jzp]], [[3jzq]], [[3jzr]], [[3jzs]] – hMDM4 p53-binding domain + peptide<br />
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[[3fdo]], [[3jzo]], [[3jzp]], [[3jzq]], [[3jzr]], [[3jzs]] – hMDM4 SWIB domain + peptide<br />
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[[3lbj]] - hMDM4 p53-binding domain + inhibitor<br />
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[[3fe7]], [[3fea]], [[3eqy]] - hMDM4 SWIB domain (mutant) + peptide<br />
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[[3u15]] - hMDM4 p53-binding domain + indolyl hydantoin<br />
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[[3lbj]], [[3u15]] - hMDM4 SWIB domain + inhibitor<br />
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[[3dac]] – hMDM4 (mutant) + p53 transactivation domain<br />
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[[3dac]] – hMDM4 SWIB domain (mutant) + p53 transactivation domain<br />
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[[2vyr]] – hMDM4 N terminal + antibody<br />
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[[2vyr]] – hMDM4 SWIB domain + antibody<br />
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[[3fe7]], [[3fea]], [[3eqy]] - hMDM4 N terminal (mutant) + peptide<br />
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[[2vje]], [[2vjf]] – hMDM2 residues 383-446 + hMDM4 residues 428-490<br />
[[2vje]], [[2vjf]] – hMDM2 residues 383-446 + hMDM4 residues 428-490<br />
[[2z5s]] - zMDM4 SWIB domain + p53 transactivation domain – zebrafish<br />
[[2z5s]] - zMDM4 SWIB domain + p53 transactivation domain – zebrafish<br />

Revision as of 07:55, 20 April 2016

Template:STRUCTURE 3jzo

Contents

Function

MDM4 is a 490 amino acid protein containing a RING finger domain (residues 300-339) and a nuclear localization signal. MDM4 interacts with protein MDM2[1]. Both of these proteins show structure similarity and contain a p53-binding domain (or SWIB domain) in their N terminal (residues 23-111).

Relevance

MDM4 which is a negative regulator of p53 is upregulated in human melanomas and thus is a key therapeutic target[2].

3D Structures of MDM4

Updated on 20-April-2016

2cr8 – hMDM4 ZF-RNBP domain – NMR
3dab, 2mwy – hMDM4 SWIB domain + p53 transactivation domain
2n06, 2n0u, 2n0w, 2n14 – hMDM4 SWIB domain + p53 transactivation domain – NMR
3fdo, 3jzo, 3jzp, 3jzq, 3jzr, 3jzs – hMDM4 SWIB domain + peptide
3fe7, 3fea, 3eqy - hMDM4 SWIB domain (mutant) + peptide
3lbj, 3u15 - hMDM4 SWIB domain + inhibitor
3dac – hMDM4 SWIB domain (mutant) + p53 transactivation domain
2vyr – hMDM4 SWIB domain + antibody
2vje, 2vjf – hMDM2 residues 383-446 + hMDM4 residues 428-490
2z5s - zMDM4 SWIB domain + p53 transactivation domain – zebrafish
2z5t - zMDM4 SWIB domain (mutant) + p53 transactivation domain
4n5t - zMDM4 SWIB domain (mutant) + stapled peptide

References

  1. ↑ Migliorini D, Lazzerini Denchi E, Danovi D, Jochemsen A, Capillo M, Gobbi A, Helin K, Pelicci PG, Marine JC. Mdm4 (Mdmx) regulates p53-induced growth arrest and neuronal cell death during early embryonic mouse development. Mol Cell Biol. 2002 Aug;22(15):5527-38. PMID:12101245
  2. ↑ Gembarska A, Luciani F, Fedele C, Russell EA, Dewaele M, Villar S, Zwolinska A, Haupt S, de Lange J, Yip D, Goydos J, Haigh JJ, Haupt Y, Larue L, Jochemsen A, Shi H, Moriceau G, Lo RS, Ghanem G, Shackleton M, Bernal F, Marine JC. MDM4 is a key therapeutic target in cutaneous melanoma. Nat Med. 2012 Aug;18(8):1239-47. doi: 10.1038/nm.2863. Epub 2012 Jul 22. PMID:22820643 doi:http://dx.doi.org/10.1038/nm.2863

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Michal Harel, Joel L. Sussman, Alexander Berchansky

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