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Aliases for MDM4 Gene

Aliases for MDM4 Gene

  • MDM4, P53 Regulator 2 3 5
  • Mdm2-Like P53-Binding Protein 3 4
  • Protein Mdmx 3 4
  • MDMX 3 4
  • Mdm4, Transformed 3T3 Cell Double Minute 4, P53 Binding Protein (Mouse) 2
  • Mouse Double Minute 4, Human Homolog Of; P53-Binding Protein 2
  • Double Minute 4, Human Homolog Of; P53-Binding Protein 3
  • Mdm4 P53 Binding Protein Homolog (Mouse) 2
  • Mdm4 P53 Binding Protein Homolog 3
  • P53-Binding Protein Mdm4 4
  • Double Minute 4 Protein 4
  • MDM4 Protein Variant G 3
  • MDM4 Protein Variant Y 3
  • MDM4-Related Protein 1 3
  • Protein Mdm4 3
  • HDMX 3
  • MRP1 3

External Ids for MDM4 Gene

Previous GeneCards Identifiers for MDM4 Gene

  • GC01P202211
  • GC01P199946
  • GC01P200846
  • GC01P201662
  • GC01P201629
  • GC01P201217
  • GC01P202752
  • GC01P204486
  • GC01P175650

Summaries for MDM4 Gene

Entrez Gene Summary for MDM4 Gene

  • 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]

CIViC summary for MDM4 Gene

GeneCards Summary for MDM4 Gene

MDM4 (MDM4, P53 Regulator) is a Protein Coding gene. Diseases associated with MDM4 include Intraocular Retinoblastoma and Familial Retinoblastoma. Among its related pathways are Gene Expression and Cell Cycle, Mitotic. Gene Ontology (GO) annotations related to this gene include enzyme binding. An important paralog of this gene is MDM2.

UniProtKB/Swiss-Prot for MDM4 Gene

  • 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.

Gene Wiki entry for MDM4 Gene

Additional gene information for MDM4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for MDM4 Gene

Genomics for MDM4 Gene

GeneHancer (GH) Regulatory Elements for MDM4 Gene

Promoters and enhancers for MDM4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH01J204511 Promoter/Enhancer 2.8 EPDnew FANTOM5 Ensembl ENCODE dbSUPER 775.7 +0.7 701 11.9 CLOCK ZFP64 FEZF1 DMAP1 YBX1 YY1 SLC30A9 ZNF213 E2F8 ZNF416 MDM4 ZC3H11A SNRPE ZBED6 PPP1R15B PIK3C2B LOC101929459 ENSG00000236108 NFASC SOX13
GH01J205210 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE 117 +695.1 695094 2.8 ZFP64 DMAP1 YY1 SLC30A9 ZNF213 E2F8 ZNF143 ZNF263 SP3 NFYC DSTYK MDM4 ELK4 PPP1R15B RBBP5 NFASC TMCC2 CNTN2 RPL13AP11 LOC100420878
GH01J205120 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE 93.8 +605.4 605418 2.9 CLOCK ZFP64 FEZF1 DMAP1 IRF4 YY1 ZNF213 E2F8 ZNF143 SP3 RBBP5 MDM4 ELK4 PPP1R15B TMCC2 DSTYK NFASC LOC100420878 RPL13AP11 LOC101929459
GH01J203860 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE 80.8 -654.8 -654824 2.9 CLOCK ZFP64 DMAP1 IRF4 YY1 SLC30A9 ZNF213 E2F8 ZNF143 ZNF548 SNRPE GC01P203865 GC01P203862 ZC3H11A MDM4 HNRNPA1P59 PPP1R15B ZBED6 LOC100506747 PRELP
GH01J204193 Promoter/Enhancer 1.6 EPDnew Ensembl ENCODE 76.1 -319.6 -319594 6.6 PKNOX1 NEUROD1 SIN3A YBX1 TCF12 FOS MCM5 ZNF488 ZNF658 NBN KISS1 ZC3H11A MDM4 ZBED6 PPP1R15B SNRPE ETNK2 ERLNC1 ENSG00000231691 PLEKHA6
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around MDM4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the MDM4 gene promoter:
  • PPAR-alpha
  • MZF-1
  • NRF-2
  • c-Ets-1
  • TBP
  • Elk-1
  • HEN1

Genomic Locations for MDM4 Gene

Genomic Locations for MDM4 Gene
chr1:204,516,379-204,581,681
(GRCh38/hg38)
Size:
65,303 bases
Orientation:
Plus strand
chr1:204,485,507-204,542,871
(GRCh37/hg19)
Size:
57,365 bases
Orientation:
Plus strand

Genomic View for MDM4 Gene

Genes around MDM4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
MDM4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for MDM4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for MDM4 Gene

Proteins for MDM4 Gene

  • Protein details for MDM4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O15151-MDM4_HUMAN
    Recommended name:
    Protein Mdm4
    Protein Accession:
    O15151
    Secondary Accessions:
    • Q2M2Y2
    • Q32SL2
    • Q6GS18
    • Q8IV83

    Protein attributes for MDM4 Gene

    Size:
    490 amino acids
    Molecular mass:
    54864 Da
    Quaternary structure:
    • Interacts with MDM2, TP53, TP73 and USP2. Found in a trimeric complex with USP2, MDM2 and MDM4. Interacts (phosphorylated) with YWHAG; negatively regulates MDM4 activity toward TP53.

    Three dimensional structures from OCA and Proteopedia for MDM4 Gene

    Alternative splice isoforms for MDM4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for MDM4 Gene

Post-translational modifications for MDM4 Gene

  • 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.
  • Ubiquitinated and degraded by MDM2. Deubiquitination by USP2 on the other hand stabilizes the MDM4 protein.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for MDM4 Gene

Domains & Families for MDM4 Gene

Gene Families for MDM4 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Predicted intracellular proteins

Graphical View of Domain Structure for InterPro Entry

O15151

UniProtKB/Swiss-Prot:

MDM4_HUMAN :
  • 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.
  • Belongs to the MDM2/MDM4 family.
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.
Family:
  • Belongs to the MDM2/MDM4 family.
genes like me logo Genes that share domains with MDM4: view

Function for MDM4 Gene

Molecular function for MDM4 Gene

UniProtKB/Swiss-Prot 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.
UniProtKB/Swiss-Prot Induction:
Down-regulated by cisplatin (at protein level).
GENATLAS Biochemistry:
murine p53 binding protein Mdmx homolog,also homolog to murine Mdm2,ubiquitously expressed with high levels in thymus

Phenotypes From GWAS Catalog for MDM4 Gene

Gene Ontology (GO) - Molecular Function for MDM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI,IEA 10469568
GO:0008270 zinc ion binding TAS 10608892
GO:0019899 enzyme binding IPI 19838211
GO:0046872 metal ion binding IEA --
GO:0061630 ubiquitin protein ligase activity TAS --
genes like me logo Genes that share ontologies with MDM4: view
genes like me logo Genes that share phenotypes with MDM4: view

Animal Models for MDM4 Gene

MGI Knock Outs for MDM4:

Animal Model Products

miRNA for MDM4 Gene

miRTarBase miRNAs that target MDM4

Clone Products

  • Addgene plasmids for MDM4

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for MDM4 Gene

Localization for MDM4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for MDM4 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for MDM4 gene
Compartment Confidence
nucleus 5
cytosol 2
mitochondrion 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for MDM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,NAS 9226370
GO:0005654 nucleoplasm TAS --
genes like me logo Genes that share ontologies with MDM4: view

Pathways & Interactions for MDM4 Gene

genes like me logo Genes that share pathways with MDM4: view

Pathways by source for MDM4 Gene

2 KEGG pathways for MDM4 Gene
1 Qiagen pathway for MDM4 Gene

SIGNOR curated interactions for MDM4 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for MDM4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 9226370
GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest TAS --
GO:0008283 cell proliferation IEP 12101245
GO:0008285 negative regulation of cell proliferation TAS 9226370
GO:0016567 protein ubiquitination IEA --
genes like me logo Genes that share ontologies with MDM4: view

Drugs & Compounds for MDM4 Gene

(5) Drugs for MDM4 Gene - From: PharmGKB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Docetaxel Approved, Investigational Pharma Microtubulin disassembly inhibitor, Tubulin and VEGF inhibitor, Taxanes 2040
Epirubicin Approved Pharma 426
NSC 207895 (XI-006) Pharma MDMX inhibitor,anti-cancer agent 0
SJ 172550 Pharma MDMX inhibitor 0
genes like me logo Genes that share compounds with MDM4: view

Transcripts for MDM4 Gene

Unigene Clusters for MDM4 Gene

Mdm4 p53 binding protein homolog (mouse):
Representative Sequences:

Clone Products

  • Addgene plasmids for MDM4

Alternative Splicing Database (ASD) splice patterns (SP) for MDM4 Gene

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12a · 12b ^ 13a · 13b · 13c ·
SP1: - - - - - -
SP2: - - - - - - -
SP3: - - - - - -
SP4: - - -
SP5: - -
SP6: - - -
SP7: - - - - - - - - - - - - - - -
SP8:
SP9:

ExUns: 13d · 13e · 13f
SP1:
SP2:
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:

Relevant External Links for MDM4 Gene

GeneLoc Exon Structure for
MDM4
ECgene alternative splicing isoforms for
MDM4

Expression for MDM4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for MDM4 Gene

Protein differential expression in normal tissues from HIPED for MDM4 Gene

This gene is overexpressed in Blymphocyte (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for MDM4 Gene



Protein tissue co-expression partners for MDM4 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of MDM4 Gene:

MDM4

SOURCE GeneReport for Unigene cluster for MDM4 Gene:

Hs.497492

mRNA Expression by UniProt/SwissProt for MDM4 Gene:

O15151-MDM4_HUMAN
Tissue specificity: Expressed in all tissues tested with high levels in thymus.

Evidence on tissue expression from TISSUES for MDM4 Gene

  • Nervous system(4.6)
  • Stomach(4.2)
genes like me logo Genes that share expression patterns with MDM4: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for MDM4 Gene

Orthologs for MDM4 Gene

This gene was present in the common ancestor of chordates.

Orthologs for MDM4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia MDM4 34 33
  • 99.52 (n)
OneToOne
dog
(Canis familiaris)
Mammalia MDM4 34 33
  • 92.59 (n)
OneToOne
cow
(Bos Taurus)
Mammalia MDM4 34 33
  • 91.36 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Mdm4 33
  • 86.07 (n)
mouse
(Mus musculus)
Mammalia Mdm4 16 34 33
  • 85.52 (n)
oppossum
(Monodelphis domestica)
Mammalia MDM4 34
  • 75 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia MDM4 34
  • 72 (a)
OneToOne
chicken
(Gallus gallus)
Aves MDM4 34 33
  • 67.02 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 34
  • 68 (a)
OneToMany
-- 34
  • 57 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia mdm4 33
  • 57.33 (n)
Str.9227 33
African clawed frog
(Xenopus laevis)
Amphibia MGC52974 33
zebrafish
(Danio rerio)
Actinopterygii mdm4 34 33
  • 57.46 (n)
OneToOne
wufa09h09 33
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 24 (a)
OneToMany
Species where no ortholog for MDM4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for MDM4 Gene

ENSEMBL:
Gene Tree for MDM4 (if available)
TreeFam:
Gene Tree for MDM4 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for MDM4: view image

Paralogs for MDM4 Gene

Paralogs for MDM4 Gene

(7) SIMAP similar genes for MDM4 Gene using alignment to 6 proteins:

  • MDM4_HUMAN
  • B4E122_HUMAN
  • M9UVU3_HUMAN
  • Q5T0Y2_HUMAN
  • Q5T0Y3_HUMAN
  • Q5T0Y4_HUMAN

Pseudogenes.org Pseudogenes for MDM4 Gene

genes like me logo Genes that share paralogs with MDM4: view

Variants for MDM4 Gene

Sequence variations from dbSNP and Humsavar for MDM4 Gene

SNP ID Clin Chr 01 pos Variation AA Info Type
rs41299595 uncertain-significance, not provided 204,549,329(+) A/C 3_prime_UTR_variant, coding_sequence_variant, genic_downstream_transcript_variant, missense_variant, non_coding_transcript_variant
rs1000021179 -- 204,557,354(+) T/A 3_prime_UTR_variant, genic_downstream_transcript_variant
rs1000067274 -- 204,557,102(+) A/C 3_prime_UTR_variant, genic_downstream_transcript_variant
rs1000086224 -- 204,521,149(+) T/C genic_upstream_transcript_variant, intron_variant
rs1000095008 -- 204,517,256(+) AAAAAA/AAAAAAA genic_upstream_transcript_variant, intron_variant

Structural Variations from Database of Genomic Variants (DGV) for MDM4 Gene

Variant ID Type Subtype PubMed ID
nsv4154 CNV insertion 18451855
nsv826431 CNV loss 20364138

Variation tolerance for MDM4 Gene

Residual Variation Intolerance Score: 28.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 2.71; 46.36% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for MDM4 Gene

Human Gene Mutation Database (HGMD)
MDM4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
MDM4

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for MDM4 Gene

Disorders for MDM4 Gene

MalaCards: The human disease database

(2) MalaCards diseases for MDM4 Gene - From: HGMD and DISEASES

Disorder Aliases PubMed IDs
intraocular retinoblastoma
  • pediatric intraocular retinoblastoma
familial retinoblastoma
  • retinoblastoma
- elite association - COSMIC cancer census association via MalaCards
Search MDM4 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for MDM4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with MDM4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for MDM4 Gene

Publications for MDM4 Gene

  1. Isolation and identification of the human homolog of a new p53-binding protein, Mdmx. (PMID: 9226370) Shvarts A … Jochemsen AG (Genomics 1997) 2 3 4 22 58
  2. MdmX is a substrate for the deubiquitinating enzyme USP2a. (PMID: 19838211) Allende-Vega N … Saville MK (Oncogene 2010) 3 4 22 58
  3. 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. (PMID: 16511572) Jin Y … Lu H (The EMBO journal 2006) 3 4 22 58
  4. ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage. (PMID: 16163388) Chen L … Chen J (The EMBO journal 2005) 3 4 22 58
  5. The p53-Mdm2 interaction and the E3 ligase activity of Mdm2/Mdm4 are conserved from lampreys to humans. (PMID: 26798135) Coffill CR … Lane DP (Genes & development 2016) 2 3 58

Products for MDM4 Gene