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

Summary

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

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_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
The ion channel TRPM7 regulates zinc-depletion-induced MDMX degradation.
Title: The ion channel TRPM7 regulates zinc-depletion-induced MDMX degradation.
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.
Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice.
Title: Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice.
MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment.
Title: MDMX phosphorylation-dependent p53 downregulation contributes to an immunosuppressive tumor microenvironment.
Mdm4 controls ureteric bud branching via regulation of p53 activity.
Title: Mdm4 controls ureteric bud branching via regulation of p53 activity.
CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells.
Title: CDK9 activity is critical for maintaining MDM4 overexpression in tumor cells.
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.
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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH124266 (e-PCR)
- UniSTS:161088

RH136260 (e-PCR)
- UniSTS:210253

PMC133932P1 (e-PCR)
- UniSTS:270692

AU021806 (e-PCR)
- UniSTS:207208

Mdm4 (e-PCR), detects polymorphism
- UniSTS:226177

RH127234 (e-PCR)
- UniSTS:209802

RH125448 (e-PCR)
- UniSTS:162267

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)

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
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
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
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)
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

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

NC_000067.7 Reference GRCm39 C57BL/6J

Range

132913843..132958325 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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