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Details on Person UniProt:O15151 MDM4
| Class:Id | ReferenceGeneProduct:59111 |
|---|---|
| _chainChangeLog | chain:1-490 added on Sat February 7 2015 |
| _displayName | UniProt:O15151 MDM4 |
| _timestamp | 2026-02-20 22:12:23 |
| chain | chain:1-490 |
| checksum | 415E6FA5A0C69857 |
| comment | FUNCTION Contributes to p53/TP53 regulation (PubMed:32300648). Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding their transcriptional activation domains. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions.SUBUNIT Component of a ternary complex composed of FAM193A, MDM4 and MDM2; interaction of FAM193A with MDM4 is mediated by the MDM4 RING-type zinc finger and results in MDM4 destabilization, leading to enhanced p53/TP53 transcriptional activity (PubMed:36897777). Although FAM193A interacts with MDM4 and MDM2, it does not affect formation of the p53-MDM2-MDM4 transcriptional repressor complex (PubMed:36897777). Interacts with MDM2; enhances the ubiquitin ligase activity of MDM2 on TP53 (PubMed:16163388, PubMed:19838211, PubMed:32300648, PubMed:25384516). Interacts with TP53. Interacts with TP73 and USP2. Found in a trimeric complex with USP2, MDM2 and MDM4. Interacts (phosphorylated) with YWHAG; negatively regulates MDM4 activity toward TP53 (PubMed:16511572). Interacts with RAD54B; RAD54B enhances the ubiquitin ligase activity of MDM2 on TP53 by promoting MDM2-MDM4 heterodimerization.INTERACTION Additional isoforms seem to exist.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 The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Cancer-specific isoform, may counteract MDM2/MDM4-mediated p53 degradation.SIMILARITY Belongs to the MDM2/MDM4 family. |
| description | recommendedName: Protein Mdm4 alternativeName: Double minute 4 protein alternativeName: Mdm2-like p53-binding protein alternativeName: Protein Mdmx alternativeName: p53-binding protein Mdm4 |
| geneName | MDM4 MDMX |
| identifier | O15151 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Cytoplasm Disease variant Metal-binding Nucleus Phosphoprotein Proteomics identification Reference proteome Ubl conjugation Zinc Zinc-finger |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | MDM4 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8997267] ENSEMBL:ENSG00000198625 MDM4 [Homo sapiens] |
| secondaryIdentifier | MDM4_HUMAN Q2M2Y2 Q32SL2 Q6GS18 Q8IV83 |
| sequenceLength | 490 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:385512] UniProt:O15151-2 MDM4 [Homo sapiens] [ReferenceIsoform:385513] UniProt:O15151-3 MDM4 [Homo sapiens] [ReferenceIsoform:401310] UniProt:O15151-1 MDM4 [Homo sapiens] [ReferenceIsoform:8971063] UniProt:O15151-4 MDM4 [Homo sapiens] [ReferenceIsoform:8971064] UniProt:O15151-5 MDM4 [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:349430] MDM4 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:349441] p-S346,S367,S403-MDM4 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:349461] p-S403-MDM4 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:6782502] PolyUb-MDM4 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:6804725] Ub,p-S346,S367,S403-MDM4 [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:6804938] PolyUb,p-S342,S367,S403-MDM4 [nucleoplasm] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:349431] O-phospho-L-serine at 342 [ModifiedResidue:349469] O-phospho-L-serine at 403 [ModifiedResidue:349477] O-phospho-L-serine at 367 [ModifiedResidue:349487] phosphorylated residue at unknown position [GroupModifiedResidue:6782506] ubiquitinylated lysine (PolyUb [nucleoplasm]) at unknown position [ModifiedResidue:6804722] ubiquitinylated lysine at unknown position |
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No pathways have been reviewed or authored by UniProt:O15151 MDM4 (59111)
