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

    Gene ID: 17248, updated on 2-Nov-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 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. Mouse models of Mdm2 and Mdm4 and their clinical implications. Xiong S. Chin J Cancer, 2013 Jul. PMID 23327795, Free PMC Article
    2. Mdm4 loss in the intestinal epithelium leads to compartmentalized cell death but no tissue abnormalities. Valentin-Vega YA, et al. Differentiation, 2009 Jun. PMID 19371999, Free PMC Article
    3. 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
    4. 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
    5. Regulation of MDM4. Markey MP. Front Biosci (Landmark Ed), 2011 Jan 1. PMID 21196223

    See all (143) 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)
    • Chemically induced (ENU) (2) 
    • Endonuclease-mediated (3) 
    • Gene trapped (1)  1 citation
    • Targeted (10)  1 citation

    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
    involved_in DNA damage response, signal transduction by p53 class mediator ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    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 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 protein catabolic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in negative regulation of transcription by RNA polymerase II ISS
    Inferred from Sequence or Structural Similarity
    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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