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

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: mouse all
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Genomic context

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_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Long-Read MDM4 Sequencing Reveals Aberrant Isoform Landscape in Metastatic Melanomas.
Title: Long-Read MDM4 Sequencing Reveals Aberrant Isoform Landscape in Metastatic Melanomas.
miR-34c-5p inhibited fibroblast proliferation, differentiation and epithelial-mesenchymal transition in benign airway stenosis via MDMX/p53 pathway.
Title: miR-34c-5p inhibited fibroblast proliferation, differentiation and epithelial-mesenchymal transition in benign airway stenosis via MDMX/p53 pathway.
MDM4 was associated with poor prognosis and tumor-immune infiltration of cancers.
Title: MDM4 was associated with poor prognosis and tumor-immune infiltration of cancers.
LINC01094 accelerates the metastasis of hepatocellular carcinoma via the miR-26b-3p/MDM4 axis.
Title: LINC01094 accelerates the metastasis of hepatocellular carcinoma via the miR-26b-3p/MDM4 axis.
Reduced murine double minute 2 and 4 protein, but not messenger RNA, expression is associated with more severe disease in myelodysplastic syndromes and acute myeloblastic leukaemia.
Title: Reduced murine double minute 2 and 4 protein, but not messenger RNA, expression is associated with more severe disease in myelodysplastic syndromes and acute myeloblastic leukaemia.
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.
MicroRNA miR-34a-5p inhibition restrains oxidative stress injury of macrophages by targeting MDM4.
Title: MicroRNA miR-34a-5p inhibition restrains oxidative stress injury of macrophages by targeting MDM4.
MDM4 polymorphisms associated with the risk but not the prognosis of esophageal cancer in Cixian high-incidence region from northern China.
Title: MDM4 polymorphisms associated with the risk but not the prognosis of esophageal cancer in Cixian high-incidence region from northern China.
(1)H, (15)N and (13)C backbone resonance assignments of the acidic domain of the human MDMX protein.
Title: (1)H, (15)N and (13)C backbone resonance assignments of the acidic domain of the human MDMX protein.
CPSF4 promotes triple negative breast cancer metastasis by upregulating MDM4.
Title: CPSF4 promotes triple negative breast cancer metastasis by upregulating MDM4.

Submit: New GeneRIF Correction See all GeneRIFs (215)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-76197 (e-PCR)
- UniSTS:43281

D11S2560 (e-PCR)
- UniSTS:37928

PMC156606P1 (e-PCR)
- UniSTS:271408

D8S2279 (e-PCR)
- UniSTS:473907

D13S116 (e-PCR)
- UniSTS:147007

SHGC-76181 (e-PCR)
- UniSTS:13135

NoName (e-PCR)
- UniSTS:485483

RH79802 (e-PCR)
- UniSTS:88688

D15S1477 (e-PCR)
- UniSTS:474482

D1S1423 (e-PCR)
- UniSTS:149619

D1S1425 (e-PCR)
- UniSTS:149621

D1S2250 (e-PCR)
- UniSTS:74361

SHGC-67307 (e-PCR)
- UniSTS:89991

D1S3601 (e-PCR)
- UniSTS:3244

L18441 (e-PCR)
- UniSTS:71348

RH80388 (e-PCR)
- UniSTS:89563

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

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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)

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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.

Genomic

NG_029367.1 RefSeqGene

Range

5028..46742

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001204171.2 → NP_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:250 → 279

zf-RanBP; Zn-finger in Ran binding protein and others

pfam13920
Location:385 → 432

zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
NM_001204172.2 → NP_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:109 → 156

zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
NM_001278516.2 → NP_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:51 → 76

SWIB; SWIB/MDM2 domain
NM_001278517.2 → NP_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:202 → 231

zf-RanBP; Zn-finger in Ran binding protein and others

pfam13920
Location:337 → 384

zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
NM_001278518.2 → NP_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:26 → 76

SWIB; SWIB/MDM2 domain
NM_001278519.2 → NP_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:77 → 106

zf-RanBP; Zn-finger in Ran binding protein and others

pfam13920
Location:212 → 259

zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
NM_002393.5 → NP_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:300 → 329

zf-RanBP; Zn-finger in Ran binding protein and others

cd16784
Location:432 → 490

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

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

204516406..204558120

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_024447114.2 → XP_024302882.1 protein Mdm4 isoform X3

UniProtKB/Swiss-Prot

O15151, Q2M2Y2, Q32SL2, Q6GS18, Q8IV83

Conserved Domains (2) summary

pfam00641
Location:300 → 329

zf-RanBP; Zn-finger in Ran binding protein and others

cd16784
Location:432 → 490

mRING-HC-C2H2C4_MDM4; Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins
XM_047420951.1 → XP_047276907.1 protein Mdm4 isoform X5
XM_024447115.2 → XP_024302883.1 protein Mdm4 isoform X3

UniProtKB/Swiss-Prot

O15151, Q2M2Y2, Q32SL2, Q6GS18, Q8IV83

Conserved Domains (2) summary

pfam00641
Location:300 → 329

zf-RanBP; Zn-finger in Ran binding protein and others

cd16784
Location:432 → 490

mRING-HC-C2H2C4_MDM4; Modified RING finger, HC subclass (C2H2C4-type), found in protein MDM4 and similar proteins
XM_017001311.2 → XP_016856800.1 protein Mdm4 isoform X1
XM_017001312.2 → XP_016856801.1 protein Mdm4 isoform X2
XM_017001313.2 → XP_016856802.1 protein Mdm4 isoform X4
XM_047420955.1 → XP_047276911.1 protein Mdm4 isoform X7

UniProtKB/TrEMBL

Q6MZR7
XM_047420961.1 → XP_047276917.1 protein Mdm4 isoform X8

UniProtKB/TrEMBL

Q58HK1
XM_047420952.1 → XP_047276908.1 protein Mdm4 isoform X6