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

Gene ID: 4194, updated on 7-Jun-2020

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
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

Genomic context

See MDM4 in Genome Data Viewer
Location:
1q32.1
Exon count:
13
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 1 NC_000001.11 (204516377..204558120)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (204485507..204596131)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene tRNA-Lys (anticodon TTT) 3-1 Neighboring gene tRNA-Lys (anticodon TTT) 3-2 Neighboring gene penta-EF-hand domain containing 1 pseudogene Neighboring gene uncharacterized LOC105371692 Neighboring gene RNA, 5S ribosomal pseudogene 74 Neighboring gene leucine rich repeat neuronal 2

Genomic regions, transcripts, and products

Expression

  • Project title: 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: CN280850 OMIM: 618849 GeneReviews: Not available
not available

NHGRI GWAS Catalog

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC132766, DKFZp781B1423

Gene Ontology Provided by GOA

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

General protein information

Preferred Names
protein Mdm4
Names
MDM4 protein variant G
MDM4 protein variant Y
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)

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_001204171.1NP_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_001204172.1NP_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_001278516.1NP_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, BP247507, BX108199
    Consensus CDS
    CCDS60396.1
    UniProtKB/Swiss-Prot
    O15151
    UniProtKB/TrEMBL
    Q68DC0
    Related
    ENSP00000375811.2, ENST00000391947.6
    Conserved Domains (1) summary
    cl02489
    Location:5176
    SWIB; SWIB/MDM2 domain
  4. NM_001278517.1NP_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, BP247507, BX108199
    Consensus CDS
    CCDS73009.1
    UniProtKB/Swiss-Prot
    O15151
    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_001278518.1NP_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, BP247507, BX108199
    Consensus CDS
    CCDS73007.1
    UniProtKB/Swiss-Prot
    O15151
    UniProtKB/TrEMBL
    A0A087WUE3
    Related
    ENSP00000478581.1, ENST00000616250.4
    Conserved Domains (1) summary
    cl02489
    Location:2676
    SWIB; SWIB/MDM2 domain
  6. NM_001278519.1NP_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, BP247507, BX108199
    Consensus CDS
    CCDS73008.1
    UniProtKB/Swiss-Prot
    O15151
    UniProtKB/TrEMBL
    A0A087WTR9
    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
    UniProtKB/TrEMBL
    A0A024R990, Q59FS6
    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: Homo sapiens Updated Annotation Release 109.

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p13 Primary Assembly

    Range
    204516377..204558120
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    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_024447115.1XP_024302883.1  protein Mdm4 isoform X3

    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
  3. XM_017001311.1XP_016856800.1  protein Mdm4 isoform X1

  4. XM_017001312.1XP_016856801.1  protein Mdm4 isoform X2

  5. XM_017001313.1XP_016856802.1  protein Mdm4 isoform X4

RNA

  1. XR_001737183.1 RNA Sequence

  2. XR_001737179.1 RNA Sequence

  3. XR_001737181.1 RNA Sequence

  4. XR_001737180.2 RNA Sequence

  5. XR_002956626.1 RNA Sequence

  6. XR_001737182.1 RNA Sequence

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