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    MDM4 MDM4 regulator of p53 [ Homo sapiens (human) ]

    Gene ID: 4194, updated on 28-Oct-2024

    Summary

    Official Symbol
    MDM4provided by HGNC
    Official Full Name
    MDM4 regulator of p53provided by HGNC
    Primary source
    HGNC:HGNC:6974
    See related
    Ensembl:ENSG00000198625 MIM:602704; AllianceGenome:HGNC:6974
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HDMX; MDMX; MRP1; BMFS6
    Summary
    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]
    Expression
    Ubiquitous expression in bone marrow (RPKM 9.7), skin (RPKM 6.5) and 24 other tissues See more
    Orthologs
    NEW
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    Try the new Transcript table

    Genomic context

    See MDM4 in Genome Data Viewer
    Location:
    1q32.1
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (204516406..204558120)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (203780802..203822528)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (204485534..204527248)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr1:204475600-204476516 Neighboring gene Sharpr-MPRA regulatory region 2072 Neighboring gene tRNA-Lys (anticodon TTT) 3-1 Neighboring gene tRNA-Lys (anticodon TTT) 3-2 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:204484788-204485987 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr1:204493521-204494720 Neighboring gene penta-EF-hand domain containing 1 pseudogene Neighboring gene uncharacterized LOC105371692 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 1729 Neighboring gene RNA, 5S ribosomal pseudogene 74 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:204541896-204542596 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:204547373-204547904 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:204568422-204568952 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:204568953-204569483 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:204587827-204588686 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:204588687-204589545 Neighboring gene leucine rich repeat neuronal 2

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Bone marrow failure syndrome 6
    MedGen: C5394274 OMIM: 618849 GeneReviews: Not available
    Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide study of common SNPs and CNVs in cognitive performance in the CANTAB.
    EBI GWAS Catalog
    Common genetic variants associated with cognitive performance identified using the proxy-phenotype method.
    EBI GWAS Catalog
    Genome-wide association studies identify four ER negative-specific breast cancer risk loci.
    EBI GWAS Catalog
    Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer.
    EBI GWAS Catalog
    Genome-wide association study in BRCA1 mutation carriers identifies novel loci associated with breast and ovarian cancer risk.
    EBI GWAS Catalog
    GWAS of 126,559 individuals identifies genetic variants associated with educational attainment.
    EBI GWAS Catalog
    Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC132766, DKFZp781B1423

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    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
     
    enables zinc ion binding TAS
    Traceable Author Statement
    more info
    PubMed 
    Process Evidence Code Pubs
    involved_in DNA damage response, signal transduction by p53 class mediator IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    acts_upstream_of_or_within atrial septum development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    acts_upstream_of_or_within atrioventricular valve morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to hypoxia IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    acts_upstream_of_or_within endocardial cushion morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    acts_upstream_of_or_within heart valve development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of DNA-templated transcription IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of DNA-templated transcription NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in negative regulation of cell population proliferation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein stabilization IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in protein ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in protein-containing complex assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of cell cycle IEA
    Inferred from Electronic Annotation
    more info
     
    acts_upstream_of_or_within ventricular septum development ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Component Evidence Code Pubs
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    located_in nucleus NAS
    Non-traceable Author Statement
    more info
    PubMed 
    part_of transcription repressor complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 

    General protein information

    Preferred Names
    protein Mdm4
    Names
    MDM4, p53 regulator
    MDM4-related protein 1
    Mdm4 p53 binding protein homolog
    double minute 4, human homolog of; p53-binding protein
    mdm2-like p53-binding protein
    protein Mdmx

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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.

    Genomic

    1. NG_029367.1 RefSeqGene

      Range
      5028..46742
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001204171.2NP_001191100.1  protein Mdm4 isoform 2

      See identical proteins and their annotated locations for NP_001191100.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2, also known as MDM4-A or HDMX-A) lacks an in-frame coding exon compared to variant 1, resulting in a shorter isoform (2) missing an internal protein segment in the 3' coding region compared to isoform 1.
      Source sequence(s)
      AB209383, AK097188, AL512306, BC105106, BP247507, BP334671, BX108199
      Consensus CDS
      CCDS55674.1
      UniProtKB/Swiss-Prot
      O15151
      UniProtKB/TrEMBL
      Q59FS6
      Related
      ENSP00000396840.2, ENST00000454264.6
      Conserved Domains (2) summary
      pfam00641
      Location:250279
      zf-RanBP; Zn-finger in Ran binding protein and others
      pfam13920
      Location:385432
      zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
    2. NM_001204172.2NP_001191101.1  protein Mdm4 isoform 3

      See identical proteins and their annotated locations for NP_001191101.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3, also known as MDM4-211 or HDMX211) is missing 8 consecutive coding exons, and uses an alternate acceptor splice site at the 3' terminal exon compared to variant 1. However, it maintains the reading frame, and encodes a very short isoform (3) that lacks the N-terminal p53 binding domain, but retains the ring finger domain at the C-terminus. This isoform has been shown to bind and stabilize oncoprotein HDM2, and also indirectly stabilize p53 protein by counteracting its degradation by HDM2. Screening of lung cancer biopsies shows the presence of this isoform in samples that overexpress HDM2 protein, supporting a pathologic role for this protein (PMID:16266988).
      Source sequence(s)
      AB209383, AK097188, AL512306, AY923176, BP247507, BP334671, BX108199
      Consensus CDS
      CCDS55675.1
      UniProtKB/Swiss-Prot
      O15151
      UniProtKB/TrEMBL
      Q59FS6
      Related
      ENSP00000356151.3, ENST00000367183.7
      Conserved Domains (1) summary
      pfam13920
      Location:109156
      zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
    3. NM_001278516.2NP_001265445.1  protein Mdm4 isoform 4

      See identical proteins and their annotated locations for NP_001265445.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4, also known as MDM4-S, HDMX-S, or HDMX-E) lacks an internal coding exon compared to variant 1. The resulting isoform (4) has a much shorter and alternate C-terminus compared to isoform 1. Annotation of this protein causes this transcript to be a candidate for nonsense-mediated mRNA decay (NMD); however, this protein was shown in PMID: 10075736 to be biologically valid.
      Source sequence(s)
      AK310903, AL512306, BC067299, BX108199
      Consensus CDS
      CCDS60396.1
      UniProtKB/TrEMBL
      Q58HK1, Q68DC0
      Related
      ENSP00000375811.2, ENST00000391947.6
      Conserved Domains (1) summary
      cl02489
      Location:5176
      SWIB; SWIB/MDM2 domain
    4. NM_001278517.2NP_001265446.1  protein Mdm4 isoform 5

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5, also known as MDM4-G or HDMX-G) lacks three consecutive exons and part of the fourth compared to variant 1. The resulting isoform (5) has the same N- and C-termini but lacks a large internal segment compared to isoform 1.
      Source sequence(s)
      AL512306, BC067299, BX108199
      Consensus CDS
      CCDS73009.1
      UniProtKB/TrEMBL
      A0A087WZ58
      Related
      ENSP00000482388.1, ENST00000614459.4
      Conserved Domains (2) summary
      pfam00641
      Location:202231
      zf-RanBP; Zn-finger in Ran binding protein and others
      pfam13920
      Location:337384
      zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
    5. NM_001278518.2NP_001265447.1  protein Mdm4 isoform 6

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6, also known as MDM4-ALT1, XALT1, or HDMX-ALT1) lacks four consecutive exons compared to variant 1. The resulting isoform (6) has a shorter and distinct C-terminus compared to isoform 1. Annotation of this protein causes this transcript to be a candidate for nonsense-mediated mRNA decay (NMD); however, since transcript variant 4 escapes NMD, it is likely that isoform 6 is also biologically valid.
      Source sequence(s)
      AL512306, BC067299, BX108199
      Consensus CDS
      CCDS73007.1
      UniProtKB/TrEMBL
      A0A087WUE3, B4E122
      Related
      ENSP00000478581.1, ENST00000616250.4
      Conserved Domains (1) summary
      cl02489
      Location:2676
      SWIB; SWIB/MDM2 domain
    6. NM_001278519.2NP_001265448.1  protein Mdm4 isoform 7

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7, also known as MDM4-ALT2, XALT2, or HDMX-ALT2) lacks six consecutive exons compared to variant 1. The resulting isoform (7) has the same N- and C-termini but lacks a large internal segment compared to isoform 1.
      Source sequence(s)
      AL512306, BC067299, BX108199
      Consensus CDS
      CCDS73008.1
      UniProtKB/TrEMBL
      A0A087WTR9, Q59FS6
      Related
      ENSP00000478080.1, ENST00000612738.4
      Conserved Domains (2) summary
      pfam00641
      Location:77106
      zf-RanBP; Zn-finger in Ran binding protein and others
      pfam13920
      Location:212259
      zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
    7. NM_002393.5NP_002384.2  protein Mdm4 isoform 1

      See identical proteins and their annotated locations for NP_002384.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1, also known as MDM4-FL or HDMX) represents the predominant transcript, and encodes the longest isoform (1).
      Source sequence(s)
      AB209383, AK097188, AL512306, BC067299, BP247507, BP334671, BX108199
      Consensus CDS
      CCDS1447.1
      UniProtKB/Swiss-Prot
      O15151, Q2M2Y2, Q32SL2, Q6GS18, Q8IV83
      Related
      ENSP00000356150.3, ENST00000367182.8
      Conserved Domains (2) summary
      pfam00641
      Location:300329
      zf-RanBP; Zn-finger in Ran binding protein and others
      cd16784
      Location:432490
      mRING-HC-C2H2C4_MDM4; Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      204516406..204558120
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024447114.2XP_024302882.1  protein Mdm4 isoform X3

      UniProtKB/Swiss-Prot
      O15151, Q2M2Y2, Q32SL2, Q6GS18, Q8IV83
      Conserved Domains (2) summary
      pfam00641
      Location:300329
      zf-RanBP; Zn-finger in Ran binding protein and others
      cd16784
      Location:432490
      mRING-HC-C2H2C4_MDM4; Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins
    2. XM_047420951.1XP_047276907.1  protein Mdm4 isoform X5

    3. XM_024447115.2XP_024302883.1  protein Mdm4 isoform X3

      UniProtKB/Swiss-Prot
      O15151, Q2M2Y2, Q32SL2, Q6GS18, Q8IV83
      Conserved Domains (2) summary
      pfam00641
      Location:300329
      zf-RanBP; Zn-finger in Ran binding protein and others
      cd16784
      Location:432490
      mRING-HC-C2H2C4_MDM4; Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins
    4. XM_017001311.2XP_016856800.1  protein Mdm4 isoform X1

    5. XM_017001312.2XP_016856801.1  protein Mdm4 isoform X2

    6. XM_017001313.2XP_016856802.1  protein Mdm4 isoform X4

    7. XM_047420955.1XP_047276911.1  protein Mdm4 isoform X7

    8. XM_047420961.1XP_047276917.1  protein Mdm4 isoform X8

    9. XM_047420952.1XP_047276908.1  protein Mdm4 isoform X6

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      203780802..203822528
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054336650.1XP_054192625.1  protein Mdm4 isoform X7

    2. XM_054336651.1XP_054192626.1  protein Mdm4 isoform X8