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

Gene ID: 4194, updated on 12-Apr-2014
Official Symbol
MDM4provided by HGNC
Official Full Name
MDM4, p53 regulatorprovided by HGNC
Primary source
HGNC:6974
Locus tag
RP11-430C7.1
See related
Ensembl:ENSG00000198625; HPRD:04082; MIM:602704; Vega:OTTHUMG00000035877
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
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]
Location :
1q32
Sequence :
Chromosome: 1; NC_000001.11 (204516379..204627003)
See MDM4 in Epigenomics, MapViewer

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene penta-EF-hand domain containing 1 pseudogene Neighboring gene transfer RNA lysine 16 (anticodon UUU) Neighboring gene transfer RNA lysine 34 (anticodon UUU) Neighboring gene RNA, 5S ribosomal pseudogene 74 Neighboring gene leucine rich repeat neuronal 2 Neighboring gene RNA, 5S ribosomal pseudogene 75 Neighboring gene neurofascin Neighboring gene ribosomal protein L13a pseudogene 11

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

Description
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NHGRI GWA Catalog
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NHGRI GWA Catalog
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
NHGRI GWA Catalog
  • MicroRNAs in cancer, organism-specific biosystem (from KEGG)
    MicroRNAs in cancer, organism-specific biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...
  • MicroRNAs in cancer, conserved biosystem (from KEGG)
    MicroRNAs in cancer, conserved biosystemMicroRNA (miRNA) is a cluster of small non-encoding RNA molecules of 21 - 23 nucleotides in length, which controls gene expression post-transcriptionally either via the degradation of target mRNAs or...
  • Signaling Pathways in Glioblastoma, organism-specific biosystem (from WikiPathways)
    Signaling Pathways in Glioblastoma, organism-specific biosystemThe most frequently altered genes in glioblastoma. This pathway originally accompanied the 2008 Nature publication on the comprehensive genomic characterization of human glioblastoma genes and core p...
  • p53 pathway, organism-specific biosystem (from Pathway Interaction Database)
    p53 pathway, organism-specific biosystem
    p53 pathway
  • p53 signaling pathway, organism-specific biosystem (from KEGG)
    p53 signaling pathway, organism-specific biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
  • p53 signaling pathway, conserved biosystem (from KEGG)
    p53 signaling pathway, conserved biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

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 
G0 to G1 transition IEP
Inferred from Expression Pattern
more info
PubMed 
cell proliferation IEP
Inferred from Expression Pattern
more info
PubMed 
cellular response to hypoxia IEP
Inferred from Expression Pattern
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 from RNA polymerase II promoter IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of cell proliferation IEA
Inferred from Electronic Annotation
more info
 
protein complex assembly IDA
Inferred from Direct Assay
more info
PubMed 
protein stabilization IEP
Inferred from Expression Pattern
more info
PubMed 
Component Evidence Code Pubs
nucleus NAS
Non-traceable Author Statement
more info
PubMed 
Preferred Names
protein Mdm4
Names
protein Mdm4
protein Mdmx
MDM4 protein variant G
MDM4 protein variant Y
MDM4-related protein 1
mdm2-like p53-binding protein
Mdm4 p53 binding protein homolog
double minute 4, human homolog of; p53-binding protein

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
    5001..46742
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    See proteins identical to 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
    Conserved Domains (3) summary
    pfam00641
    Location:250278
    Blast Score: 107
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:385432
    Blast Score: 99
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
    cl02489
    Location:2676
    Blast Score: 141
    SWIB; SWIB/MDM2 domain
  2. NM_001204172.1NP_001191101.1  protein Mdm4 isoform 3

    See proteins identical to 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
    Conserved Domains (1) summary
    pfam13920
    Location:109156
    Blast Score: 85
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
  3. NM_001278516.1NP_001265445.1  protein Mdm4 isoform 4

    See proteins identical to 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
    Conserved Domains (1) summary
    cl02489
    Location:2676
    Blast Score: 138
    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
    UniProtKB/Swiss-Prot
    O15151
    Conserved Domains (2) summary
    pfam00641
    Location:202230
    Blast Score: 105
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:337384
    Blast Score: 100
    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
    UniProtKB/Swiss-Prot
    O15151
    Conserved Domains (1) summary
    cl02489
    Location:2676
    Blast Score: 140
    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
    UniProtKB/Swiss-Prot
    O15151
    Conserved Domains (2) summary
    pfam00641
    Location:77105
    Blast Score: 100
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:212259
    Blast Score: 89
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
  7. NM_002393.4NP_002384.2  protein Mdm4 isoform 1

    See proteins identical to 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
    Q59FS6
    Related
    ENSP00000356150, OTTHUMP00000034072, ENST00000367182, OTTHUMT00000087415
    Conserved Domains (3) summary
    pfam00641
    Location:300328
    Blast Score: 109
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:435482
    Blast Score: 102
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
    cl02489
    Location:2676
    Blast Score: 142
    SWIB; SWIB/MDM2 domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000001.11

    Range
    204516379..204627003
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006711329.1XP_006711392.1  

    Conserved Domains (1) summary
    cl02489
    Location:2676
    Blast Score: 142
    SWIB; SWIB/MDM2 domain
  2. XM_006711328.1XP_006711391.1  

    Conserved Domains (3) summary
    pfam00641
    Location:295323
    Blast Score: 109
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:430477
    Blast Score: 102
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
    cl02489
    Location:2676
    Blast Score: 143
    SWIB; SWIB/MDM2 domain

RNA

  1. XR_241079.1 RNA Sequence

  2. XR_426774.1 RNA Sequence

  3. XR_426775.1 RNA Sequence

Alternate HuRef

Genomic

  1. AC_000133.1 Alternate HuRef

    Range
    175650570..175692491
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.1

Genomic

  1. NC_018912.2 Alternate CHM1_1.1

    Range
    205908863..205950615
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

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