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Mdm4 transformed mouse 3T3 cell double minute 4 [ Mus musculus (house mouse) ]

Gene ID: 17248, updated on 5-Mar-2024

Summary

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Official Symbol
Mdm4provided by MGI
Official Full Name
transformed mouse 3T3 cell double minute 4provided by MGI
Primary source
MGI:MGI:107934
See related
Ensembl:ENSMUSG00000054387 AllianceGenome:MGI:107934
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Mus musculus
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as
Mdmx; 4933417N07Rik
Summary
This gene encodes a protein that has been shown to negatively regulate the activity of the tumor suppressor protein p53. Homozygous knockout mice exhibit embryonic lethality as a result of p53-dependent apoptosis and cell cycle arrest. Amplification of this gene or overexpression of the encoded protein has been linked to a range of human cancers. A pseudogene has been identified on the X chromosome. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Nov 2014]
Expression
Ubiquitous expression in limb E14.5 (RPKM 31.1), CNS E14 (RPKM 26.8) and 26 other tissues See more
Orthologs
human all
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Genomic context

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See Mdm4 in Genome Data Viewer
Location:
1 E4; 1 57.75 cM
Exon count:
14
Annotation release Status Assembly Chr Location
RS_2024_02 current GRCm39 (GCF_000001635.27) 1 NC_000067.7 (132913843..132958325, complement)
108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 1 NC_000067.6 (132986105..133030587, complement)

Chromosome 1 - NC_000067.7Genomic Context describing neighboring genes Neighboring gene leucine rich repeat protein 2, neuronal Neighboring gene STARR-seq mESC enhancer starr_02265 Neighboring gene predicted gene, 31159 Neighboring gene predicted gene, 38687 Neighboring gene STARR-seq mESC enhancer starr_02266 Neighboring gene STARR-seq mESC enhancer starr_02269 Neighboring gene STARR-seq mESC enhancer starr_02270 Neighboring gene STARR-positive B cell enhancer ABC_E1560 Neighboring gene STARR-positive B cell enhancer ABC_E4346 Neighboring gene CapStarr-seq enhancer MGSCv37_chr1:134930319-134930502 Neighboring gene predicted gene 29257 Neighboring gene predicted gene, 41953 Neighboring gene nuclear encoded tRNA lysine 26 (anticodon TTT) Neighboring gene nuclear encoded tRNA lysine 25 (anticodon TTT)

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: Mouse ENCODE transcriptome data
  • Description: RNA profiling data sets generated by the Mouse ENCODE project.
  • BioProject: PRJNA66167
  • Publication: PMID 25409824
  • Analysis date: n/a

Bibliography

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Related articles in PubMed

  1. Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice. Qu J, et al. J Exp Med, 2021 May 3. PMID 33688918, Free PMC Article
  2. Recombinant Butelase-Mediated Cyclization of the p53-Binding Domain of the Oncoprotein MdmX-Stabilized Protein Conformation as a Promising Model for Structural Investigation. Pi N, et al. Biochemistry, 2019 Jul 9. PMID 31187974
  3. Caspase-dependent degradation of MDMx/MDM4 cell cycle regulatory protein in amyloid β-induced neuronal damage. Colacurcio DJ, et al. Neurosci Lett, 2015 Nov 16. PMID 26477779, Free PMC Article
  4. Dissecting the p53-Mdm2 feedback loop in vivo: uncoupling the role in p53 stability and activity. Pant V, et al. Oncotarget, 2014 Mar 15. PMID 24658419, Free PMC Article
  5. Mouse models of Mdm2 and Mdm4 and their clinical implications. Xiong S. Chin J Cancer, 2013 Jul. PMID 23327795, Free PMC Article

See all (140) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Murine double minute X plays a central role in leukemic transformation and may be a promising target for leukemia prevention strategies.
    Title: Murine double minute X plays a central role in leukemic transformation and may be a promising target for leukemia prevention strategies.
  2. MDMX is essential for the regulation of p53 protein levels in the absence of a functional MDM2 C-terminal tail.
    Title: MDMX is essential for the regulation of p53 protein levels in the absence of a functional MDM2 C-terminal tail.
  3. The ion channel TRPM7 regulates zinc-depletion-induced MDMX degradation.
    Title: The ion channel TRPM7 regulates zinc-depletion-induced MDMX degradation.
  4. MDMX acts as a pervasive preleukemic-to-acute myeloid leukemia transition mechanism.
    Title: MDMX acts as a pervasive preleukemic-to-acute myeloid leukemia transition mechanism.
  5. Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice.
    Title: Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice.
  6. MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment.
    Title: MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment.
  7. Mdm4 controls ureteric bud branching via regulation of p53 activity.
    Title: Mdm4 controls ureteric bud branching via regulation of p53 activity.
  8. CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells.
    Title: CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells.
  9. Effects of MDM4 Gene Regulation by miR-34a on LOVO Cell Proliferation.
    Title: Effects of MDM4 Gene Regulation by miR-34a on LOVO Cell Proliferation.
  10. MDMX inhibits casein kinase 1alpha activity and stimulates Wnt signaling.
    Title: MDMX inhibits casein kinase 1α activity and stimulates Wnt signaling.
Submit: New GeneRIF Correction See all GeneRIFs (60)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics  (MGI)
  • Gene trapped (1)  1 citation
  • Targeted (10)  1 citation
  • Chemically induced (ENU) (2) 
  • Endonuclease-mediated (3) 

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by MGI

Function Evidence Code Pubs
enables enzyme binding ISO
Inferred from Sequence Orthology
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin-protein transferase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
acts_upstream_of_or_within atrial septum development IGI
Inferred from Genetic Interaction
more info
 PubMed 
acts_upstream_of_or_within atrioventricular valve morphogenesis IGI
Inferred from Genetic Interaction
more info
 PubMed 
acts_upstream_of_or_within endocardial cushion morphogenesis IGI
Inferred from Genetic Interaction
more info
 PubMed 
acts_upstream_of_or_within heart valve development IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in negative regulation of DNA-templated transcription ISO
Inferred from Sequence Orthology
more info
  
involved_in negative regulation of apoptotic process IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of protein catabolic process ISO
Inferred from Sequence Orthology
more info
  
involved_in negative regulation of transcription by RNA polymerase II ISO
Inferred from Sequence Orthology
more info
  
acts_upstream_of_or_within positive regulation of cell population proliferation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein ubiquitination IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein-containing complex assembly ISO
Inferred from Sequence Orthology
more info
  
involved_in regulation of cell cycle IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within regulation of heart rate IGI
Inferred from Genetic Interaction
more info
 PubMed 
acts_upstream_of_or_within ventricular septum development IGI
Inferred from Genetic Interaction
more info
 PubMed 
Component Evidence Code Pubs
located_in nucleoplasm ISO
Inferred from Sequence Orthology
more info
  
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  
part_of transcription repressor complex ISO
Inferred from Sequence Orthology
more info
  

General protein information

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Preferred Names
protein Mdm4
Names
double minute 4 protein
mdm2-like p53-binding protein
p53-binding protein Mdm4
protein Mdmx

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001302801.1 → NP_001289730.1  protein Mdm4 isoform 1

    See identical proteins and their annotated locations for NP_001289730.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1). Both variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    AK017719, AK043359, AK046448, AK049576, AK083349, BC058680, CJ101093
    Consensus CDS
    CCDS78683.1
    UniProtKB/TrEMBL
    Q3UTC9, Q99L86
    Related
    ENSMUSP00000068661.7, ENSMUST00000067398.13
    Conserved Domains (3) summary
    cd16784
    Location:432 → 490
    mRING-HC-C2H2C4_MDM4; Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins
    cd17673
    Location:30 → 108
    MDM4; p53-binding domain found in MDM4 and similar proteins
    pfam00641
    Location:301 → 329
    zf-RanBP; Zn-finger in Ran binding protein and others

  2. NM_001302802.1 → NP_001289731.1  protein Mdm4 isoform 1

    See identical proteins and their annotated locations for NP_001289731.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same isoform (1).
    Source sequence(s)
    AC137948, AK043359, AK046448, AK083349, AK139529, BC058680
    Consensus CDS
    CCDS78683.1
    UniProtKB/TrEMBL
    Q3UTC9, Q99L86
    Conserved Domains (3) summary
    cd16784
    Location:432 → 490
    mRING-HC-C2H2C4_MDM4; Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins
    cd17673
    Location:30 → 108
    MDM4; p53-binding domain found in MDM4 and similar proteins
    pfam00641
    Location:301 → 329
    zf-RanBP; Zn-finger in Ran binding protein and others

  3. NM_001302803.1 → NP_001289732.1  protein Mdm4 isoform 2

    See identical proteins and their annotated locations for NP_001289732.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. The resulting isoform (2) is shorter compared to isoform 1. Both variants 3 and 4 encode the same isoform (2).
    Source sequence(s)
    AK017719, AK043359, AK046448, AK083349, BC058680, CJ101093
    Consensus CDS
    CCDS15290.1
    UniProtKB/Swiss-Prot
    O35618, Q9CYG1
    UniProtKB/TrEMBL
    Q99L86
    Related
    ENSMUSP00000140609.2, ENSMUST00000188090.7
    Conserved Domains (3) summary
    pfam00641
    Location:299 → 328
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:434 → 481
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
    cl02489
    Location:26 → 76
    SWIB; SWIB/MDM2 domain

  4. NM_001302804.1 → NP_001289733.1  protein Mdm4 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses an alternate splice site in an internal exon, compared to variant 1. This variant represents translation initiation at a downstream AUG compared to variant 1; the 5'-most initiation codon, as used in variant 1, is associated with a truncated ORF that would render the transcript a candidate for nonsense-mediated decay (NMD). Leaky scanning may allow translation initiation at the downstream AUG to encode an isoform (3) that has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AK043359, AK046448, AK049576, AK083349, BC058680, CJ101093
    UniProtKB/Swiss-Prot
    O35618
    Conserved Domains (2) summary
    pfam00641
    Location:172 → 201
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:307 → 354
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)

  5. NM_008575.4 → NP_032601.2  protein Mdm4 isoform 2

    See identical proteins and their annotated locations for NP_032601.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate exon in the 5' UTR and uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. The resulting isoform (2) is shorter compared to isoform 1. Both variants 3 and 4 encode the same isoform (2).
    Source sequence(s)
    AK043359, AK046448, AK083349, BC058680, CJ101093
    Consensus CDS
    CCDS15290.1
    UniProtKB/Swiss-Prot
    O35618, Q9CYG1
    UniProtKB/TrEMBL
    Q99L86
    Related
    ENSMUSP00000070411.4, ENSMUST00000067429.10
    Conserved Domains (3) summary
    pfam00641
    Location:299 → 328
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:434 → 481
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
    cl02489
    Location:26 → 76
    SWIB; SWIB/MDM2 domain

RNA

  1. NR_126506.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (S) lacks an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD). There is contradictory data on whether this variant produces a functional protein (PMIDs 10075736, 21541195, 24013503).
    Source sequence(s)
    AK043359, AK046448, AK049690, BC058680, CJ101093

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

  1. NC_000067.7 Reference GRCm39 C57BL/6J

    Range
    132913843..132958325 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006529233.4 → XP_006529296.1  protein Mdm4 isoform X1

    See identical proteins and their annotated locations for XP_006529296.1

    UniProtKB/TrEMBL
    Q3UTC9, Q99L86
    Conserved Domains (3) summary
    cd16784
    Location:432 → 490
    mRING-HC-C2H2C4_MDM4; Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins
    cd17673
    Location:30 → 108
    MDM4; p53-binding domain found in MDM4 and similar proteins
    pfam00641
    Location:301 → 329
    zf-RanBP; Zn-finger in Ran binding protein and others

RNA

  1. XR_003953685.1 RNA Sequence

  2. XR_003953686.2 RNA Sequence

  3. XR_387151.5 RNA Sequence

Nucleotide Protein Strain
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
O35618.2 GenPept UniProtKB/Swiss-Prot:O35618

Gene LinkOut

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