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MDM2 MDM2 proto-oncogene [ Homo sapiens (human) ]

Gene ID: 4193, updated on 16-Feb-2020

Summary

Official Symbol
MDM2provided by HGNC
Official Full Name
MDM2 proto-oncogeneprovided by HGNC
Primary source
HGNC:HGNC:6973
See related
Ensembl:ENSG00000135679 MIM:164785
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; LSKB; hdm2; ACTFS
Summary
This gene encodes a nuclear-localized E3 ubiquitin ligase. The encoded protein can promote tumor formation by targeting tumor suppressor proteins, such as p53, for proteasomal degradation. This gene is itself transcriptionally-regulated by p53. Overexpression or amplification of this locus is detected in a variety of different cancers. There is a pseudogene for this gene on chromosome 2. Alternative splicing results in a multitude of transcript variants, many of which may be expressed only in tumor cells. [provided by RefSeq, Jun 2013]
Expression
Ubiquitous expression in colon (RPKM 13.6), bone marrow (RPKM 9.8) and 25 other tissues See more
Orthologs

Genomic context

See MDM2 in Genome Data Viewer
Location:
12q15
Exon count:
13
Annotation release Status Assembly Chr Location
109.20191205 current GRCh38.p13 (GCF_000001405.39) 12 NC_000012.12 (68808149..68850686)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (69201952..69239324)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369820 Neighboring gene SUZ RNA binding domain containing 1 pseudogene Neighboring gene carboxypeptidase M Neighboring gene RNA, U7 small nuclear 4 pseudogene Neighboring gene PRELI domain containing 2 pseudogene 1

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
Accelerated tumor formation, susceptibility to
MedGen: C3280690 OMIM: 614401 GeneReviews: Not available
Compare labs
LESSEL-KUBISCH SYNDROME
MedGen: CN262921 OMIM: 618681 GeneReviews: Not available
not available

NHGRI GWAS Catalog

Description
A genome-wide association study identifies susceptibility loci of silica related pneumoconiosis in Han Chinese.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Tat tat Ubiquitination of HIV-1 Tat by Hdm2 is required for efficient replication of HIV-1, indicating Hdm2 regulates Tat function and is a Tat co-activator PubMed
tat Hdm2 interacts directly with HIV-1 Tat and ubiquitinates Tat on amino acid residue Lys71 PubMed
Vif vif HIV-1 Vif interacts with MDM2, which can be inhibited through mutating amino acids E88, W89, L64, or I66 in MDM2, R93 in Vif, or by increasing CBF-B expression PubMed
vif MDM2 reduces cellular Vif levels and reversely increases A3G levels, because the interaction between MDM2 and Vif prevents A3G from binding to Vif PubMed
vif MDM2 inhibits HIV-1 replication in non-permissive target cells through Vif degradation PubMed
vif The N-terminal region (residues 1-50) of HIV-1 Vif is important for binding to MDM2. The interaction domain of MDM2 with Vif to amino-acids 168-320, which are located in its central acidic and zinc-finger domains PubMed
vif HIV-1 Vif stabilizes TP53 by blocking MDM2-induced ubiquitination and inhibits MDM2-mediated nuclear export of TP53, leading to support viral replication through inducing G2 cell cycle arrest PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC5370, MGC71221

Gene Ontology Provided by GOA

Function Evidence Code Pubs
5S rRNA binding IDA
Inferred from Direct Assay
more info
PubMed 
NEDD8 ligase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
SUMO transferase activity EXP
Inferred from Experiment
more info
PubMed 
disordered domain specific binding IPI
Inferred from Physical Interaction
more info
PubMed 
enzyme binding IPI
Inferred from Physical Interaction
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
ligase activity IDA
Inferred from Direct Assay
more info
PubMed 
p53 binding IPI
Inferred from Physical Interaction
more info
PubMed 
peroxisome proliferator activated receptor binding IEA
Inferred from Electronic Annotation
more info
 
protein N-terminus binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein domain specific binding IPI
Inferred from Physical Interaction
more info
PubMed 
receptor serine/threonine kinase binding IEA
Inferred from Electronic Annotation
more info
 
ribonucleoprotein complex binding IDA
Inferred from Direct Assay
more info
PubMed 
scaffold protein binding IEA
Inferred from Electronic Annotation
more info
 
ubiquitin binding IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin protein ligase activity IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin protein ligase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
ubiquitin protein ligase activity TAS
Traceable Author Statement
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin-protein transferase activity IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin-protein transferase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
zinc ion binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest IMP
Inferred from Mutant Phenotype
more info
PubMed 
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest TAS
Traceable Author Statement
more info
 
amyloid fibril formation IMP
Inferred from Mutant Phenotype
more info
PubMed 
atrial septum development IEA
Inferred from Electronic Annotation
more info
 
atrioventricular valve morphogenesis IEA
Inferred from Electronic Annotation
more info
 
blood vessel development IEA
Inferred from Electronic Annotation
more info
 
blood vessel remodeling IEA
Inferred from Electronic Annotation
more info
 
cardiac septum morphogenesis IEA
Inferred from Electronic Annotation
more info
 
cellular response to UV-C IEA
Inferred from Electronic Annotation
more info
 
cellular response to actinomycin D IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to alkaloid IEA
Inferred from Electronic Annotation
more info
 
cellular response to estrogen stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to gamma radiation IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to hydrogen peroxide IEA
Inferred from Electronic Annotation
more info
 
cellular response to hypoxia IEP
Inferred from Expression Pattern
more info
PubMed 
cellular response to peptide hormone stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to vitamin B1 IEA
Inferred from Electronic Annotation
more info
 
endocardial cushion morphogenesis IEA
Inferred from Electronic Annotation
more info
 
establishment of protein localization IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of DNA damage response, signal transduction by p53 class mediator IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell cycle arrest IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process IEA
Inferred from Electronic Annotation
more info
 
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of neuron projection development IEA
Inferred from Electronic Annotation
more info
 
negative regulation of protein processing IEA
Inferred from Electronic Annotation
more info
 
negative regulation of signal transduction by p53 class mediator IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of signal transduction by p53 class mediator TAS
Traceable Author Statement
more info
PubMed 
negative regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transcription, DNA-templated IMP
Inferred from Mutant Phenotype
more info
PubMed 
peptidyl-lysine modification IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of cell proliferation TAS
Traceable Author Statement
more info
PubMed 
positive regulation of gene expression IEA
Inferred from Electronic Annotation
more info
 
positive regulation of mitotic cell cycle IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of proteasomal ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of protein export from nucleus IEA
Inferred from Electronic Annotation
more info
 
positive regulation of vascular associated smooth muscle cell migration IEA
Inferred from Electronic Annotation
more info
 
positive regulation of vascular smooth muscle cell proliferation IEA
Inferred from Electronic Annotation
more info
 
proteasome-mediated ubiquitin-dependent protein catabolic process TAS
Traceable Author Statement
more info
PubMed 
protein autoubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein destabilization IDA
Inferred from Direct Assay
more info
PubMed 
protein destabilization IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein deubiquitination TAS
Traceable Author Statement
more info
 
protein localization to nucleus IDA
Inferred from Direct Assay
more info
PubMed 
protein polyubiquitination TAS
Traceable Author Statement
more info
PubMed 
protein sumoylation IEA
Inferred from Electronic Annotation
more info
 
protein ubiquitination IDA
Inferred from Direct Assay
more info
PubMed 
protein-containing complex assembly IDA
Inferred from Direct Assay
more info
PubMed 
proteolysis involved in cellular protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of heart rate IEA
Inferred from Electronic Annotation
more info
 
regulation of protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
regulation of signal transduction by p53 class mediator TAS
Traceable Author Statement
more info
 
response to antibiotic IEP
Inferred from Expression Pattern
more info
PubMed 
response to cocaine IEA
Inferred from Electronic Annotation
more info
 
response to ether IEA
Inferred from Electronic Annotation
more info
 
response to formaldehyde IEA
Inferred from Electronic Annotation
more info
 
response to iron ion IEA
Inferred from Electronic Annotation
more info
 
response to magnesium ion IEA
Inferred from Electronic Annotation
more info
 
response to morphine IEA
Inferred from Electronic Annotation
more info
 
response to steroid hormone IEA
Inferred from Electronic Annotation
more info
 
response to water-immersion restraint stress IEA
Inferred from Electronic Annotation
more info
 
transcription factor catabolic process TAS
Traceable Author Statement
more info
PubMed 
traversing start control point of mitotic cell cycle IEA
Inferred from Electronic Annotation
more info
 
ubiquitin-dependent protein catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
ubiquitin-dependent protein catabolic process IGI
Inferred from Genetic Interaction
more info
PubMed 
ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
ventricular septum development IEA
Inferred from Electronic Annotation
more info
 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cytoplasm IMP
Inferred from Mutant Phenotype
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
endocytic vesicle membrane TAS
Traceable Author Statement
more info
 
colocalizes_with nuclear body IDA
Inferred from Direct Assay
more info
PubMed 
nucleolus IDA
Inferred from Direct Assay
more info
PubMed 
nucleolus IMP
Inferred from Mutant Phenotype
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
nucleus IMP
Inferred from Mutant Phenotype
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 
protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 
protein-containing complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
synapse IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
E3 ubiquitin-protein ligase Mdm2
Names
MDM2 oncogene, E3 ubiquitin protein ligase
MDM2 proto-oncogene, E3 ubiquitin protein ligase
Mdm2, p53 E3 ubiquitin protein ligase homolog
Mdm2, transformed 3T3 cell double minute 2, p53 binding protein
double minute 2, human homolog of; p53-binding protein
oncoprotein Mdm2
NP_001138809.1
NP_001138811.1
NP_001138812.1
NP_001265391.1
NP_001354919.1
NP_002383.2
XP_006719462.1
XP_006719463.1

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_016708.1 RefSeqGene

    Range
    4982..42354
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001145337.3NP_001138809.1  E3 ubiquitin-protein ligase Mdm2 isoform g

    See identical proteins and their annotated locations for NP_001138809.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3, also known as P2-MDM2-10) contains multiple differences in the 5' UTR and coding region, compared to variant 1. It uses an alternate promoter and initiates translation at a downstream in-frame start codon. The encoded isoform (g) has a shorter N-terminus and is shorter than isoform a.
    Source sequence(s)
    AC025423, BE930512, EU076747, EU076748
    UniProtKB/TrEMBL
    A0A0A8KB75, A7UKX8, A7UKX9
    Conserved Domains (3) summary
    pfam00641
    Location:252281
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam02201
    Location:4592
    SWIB; SWIB/MDM2 domain
    pfam13920
    Location:389436
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
  2. NM_001145339.2NP_001138811.1  E3 ubiquitin-protein ligase Mdm2 isoform h

    See identical proteins and their annotated locations for NP_001138811.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2, also known as MDM2g) lacks two coding exons, but maintains the reading frame, compared to variant 1. The encoded isoform (h) is shorter than isoform a.
    Source sequence(s)
    AC025423, AF092844, BE930512, HY174841
    UniProtKB/Swiss-Prot
    Q00987
    UniProtKB/TrEMBL
    G3XA89
    Related
    ENSP00000258148.7, ENST00000258148.11
    Conserved Domains (3) summary
    pfam00641
    Location:250279
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam02201
    Location:5198
    SWIB; SWIB/MDM2 domain
    pfam13920
    Location:387434
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
  3. NM_001145340.3NP_001138812.1  E3 ubiquitin-protein ligase Mdm2 isoform i

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4, also known as P2-MDM2-C1) contains multiple differences in the 5' UTR and coding region, compared to variant 1. It uses an alternate promoter and initiates translation at a downstream in-frame start codon. The encoded isoform (i) has a shorter N-terminus and is shorter than isoform a.
    Source sequence(s)
    AC025423, AF385327, BE930512, EU076746
    UniProtKB/TrEMBL
    A7UKX7, Q96DS0
    Related
    ENSP00000335096.4, ENST00000348801.7
    Conserved Domains (2) summary
    pfam00641
    Location:104132
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:240287
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
  4. NM_001278462.2NP_001265391.1  E3 ubiquitin-protein ligase Mdm2 isoform l

    See identical proteins and their annotated locations for NP_001265391.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5, also known as P2-MDM2-C) contains multiple differences in the 5' UTR and coding region, compared to variant 1. It uses an alternate promoter and initiates translation at a downstream in-frame start codon. The encoded isoform (l) has a shorter N-terminus and is shorter than isoform a.
    Source sequence(s)
    AC025423, AF385327, AK290341, BE930512, EU076748
    Consensus CDS
    CCDS61189.1
    UniProtKB/Swiss-Prot
    Q00987
    UniProtKB/TrEMBL
    A7UKX9, Q96DS0
    Related
    ENSP00000299252.4, ENST00000299252.8
    Conserved Domains (2) summary
    pfam00641
    Location:129158
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:266313
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
  5. NM_001367990.1NP_001354919.1  E3 ubiquitin-protein ligase Mdm2 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC025423
    Related
    ENSP00000444430.2, ENST00000539479.6
  6. NM_002392.5NP_002383.2  E3 ubiquitin-protein ligase Mdm2 isoform a

    See identical proteins and their annotated locations for NP_002383.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a).
    Source sequence(s)
    AC025423, AK290341, BE930512, HY174841
    Consensus CDS
    CCDS8986.2
    UniProtKB/Swiss-Prot
    Q00987
    Related
    ENSP00000258149.6, ENST00000258149.10
    Conserved Domains (3) summary
    pfam00641
    Location:305334
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam02201
    Location:5198
    SWIB; SWIB/MDM2 domain
    pfam13920
    Location:442489
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p13 Primary Assembly

    Range
    68808149..68850686
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006719400.4XP_006719463.1  E3 ubiquitin-protein ligase Mdm2 isoform X3

    See identical proteins and their annotated locations for XP_006719463.1

    Conserved Domains (2) summary
    pfam00641
    Location:198227
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:335382
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
  2. XM_006719399.4XP_006719462.1  E3 ubiquitin-protein ligase Mdm2 isoform X2

    UniProtKB/Swiss-Prot
    Q00987
    Conserved Domains (2) summary
    pfam00641
    Location:238267
    zf-RanBP; Zn-finger in Ran binding protein and others
    pfam13920
    Location:375422
    zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_001145336.1: Suppressed sequence

    Description
    NM_001145336.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
  2. NM_006878.3: Suppressed sequence

    Description
    NM_006878.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript, which lacks consecutive internal exons and contains non-consensus splice sites, compared to the reported wild-type transcript.
  3. NM_006879.3: Suppressed sequence

    Description
    NM_006879.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript, which lacks consecutive internal exons and contains non-consensus splice sites, compared to the reported wild-type transcript.
  4. NM_006880.2: Suppressed sequence

    Description
    NM_006880.2: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
  5. NM_006881.3: Suppressed sequence

    Description
    NM_006881.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript, which lacks consecutive internal exons and contains non-consensus splice sites, compared to the reported wild-type transcript.
  6. NM_006882.3: Suppressed sequence

    Description
    NM_006882.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript, which lacks consecutive internal exons and contains non-consensus splice sites, compared to the reported wild-type transcript.
  7. NM_032739.1: Suppressed sequence

    Description
    NM_032739.1: This RefSeq was permanently suppressed because it is primarily UTR sequence.
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