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

Gene ID: 4193, updated on 5-Jan-2025

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; AllianceGenome:HGNC:6973
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
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Genomic context

See MDM2 in Genome Data Viewer
Location:
12q15
Exon count:
12
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (68808172..68850686)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (68784018..68830265)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (69201952..69244466)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene solute carrier family 35 member E3 Neighboring gene MAPK activated protein kinase 2 pseudogene Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:69181025-69181579 Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:69181580-69182133 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4648 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:69202246-69203445 Neighboring gene SZRD1 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6647 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:69225023-69225696 Neighboring gene carboxypeptidase M Neighboring gene RNA, U7 small nuclear 4 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4649 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4650 Neighboring gene PRELI domain containing 2 pseudogene 1

Genomic regions, transcripts, and products

Expression

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 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: C5231460 OMIM: 618681 GeneReviews: Not available
Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies susceptibility loci of silica related pneumoconiosis in Han Chinese.
EBI GWAS 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

General gene information

Clone Names

  • MGC5370, MGC71221

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 5S rRNA binding PubMed 
enables NEDD8 ligase activity PubMed 
enables SUMO transferase activity PubMed 
enables disordered domain specific binding PubMed 
enables enzyme binding PubMed 
enables identical protein binding PubMed 
enables ligase activity PubMed 
enables p53 binding PubMed 
enables peroxisome proliferator activated receptor binding  
enables protein binding PubMed 
enables protein domain specific binding PubMed 
enables receptor serine/threonine kinase binding  
enables ribonucleoprotein complex binding PubMed 
enables ubiquitin binding PubMed 
enables ubiquitin protein ligase activity  
enables ubiquitin protein ligase activity PubMed 
enables ubiquitin protein ligase activity PubMed 
enables ubiquitin protein ligase activity PubMed 
enables ubiquitin protein ligase binding PubMed 
enables ubiquitin-protein transferase activity PubMed 
enables ubiquitin-protein transferase activity PubMed 
enables zinc ion binding PubMed 
Items 1 - 25 of 73
Process Evidence Code Pubs
involved_in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest PubMed 
involved_in amyloid fibril formation PubMed 
involved_in apoptotic process PubMed 
involved_in atrial septum development  
involved_in atrioventricular valve morphogenesis  
involved_in blood vessel development  
involved_in blood vessel remodeling  
involved_in cardiac septum morphogenesis  
involved_in cellular response to UV-C  
involved_in cellular response to actinomycin D PubMed 
involved_in cellular response to alkaloid  
involved_in cellular response to estrogen stimulus  
involved_in cellular response to gamma radiation PubMed 
involved_in cellular response to growth factor stimulus  
involved_in cellular response to hydrogen peroxide  
involved_in cellular response to hypoxia PubMed 
involved_in cellular response to peptide hormone stimulus  
involved_in cellular response to vitamin B1  
involved_in endocardial cushion morphogenesis  
involved_in establishment of protein localization PubMed 
involved_in fibroblast activation  
involved_in negative regulation of DNA damage response, signal transduction by p53 class mediator PubMed 
involved_in negative regulation of DNA-templated transcription PubMed 
involved_in negative regulation of DNA-templated transcription PubMed 
involved_in negative regulation of apoptotic process  
involved_in negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator PubMed 
involved_in negative regulation of neuron projection development  
involved_in negative regulation of protein processing  
involved_in negative regulation of signal transduction by p53 class mediator PubMed 
involved_in negative regulation of signal transduction by p53 class mediator PubMed 
involved_in negative regulation of transcription by RNA polymerase II PubMed 
involved_in positive regulation of cell population proliferation PubMed 
involved_in positive regulation of gene expression  
involved_in positive regulation of mitotic cell cycle  
involved_in positive regulation of mitotic cell cycle PubMed 
involved_in positive regulation of muscle cell differentiation  
involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process PubMed 
involved_in positive regulation of protein export from nucleus  
involved_in positive regulation of vascular associated smooth muscle cell migration  
involved_in positive regulation of vascular associated smooth muscle cell proliferation  
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process PubMed 
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process PubMed 
involved_in protein autoubiquitination PubMed 
involved_in protein destabilization PubMed 
involved_in protein destabilization PubMed 
involved_in protein localization to nucleus PubMed 
involved_in protein polyubiquitination PubMed 
involved_in protein sumoylation  
involved_in protein ubiquitination PubMed 
involved_in protein-containing complex assembly PubMed 
involved_in proteolysis involved in protein catabolic process PubMed 
acts_upstream_of regulation of cell cycle PubMed 
involved_in regulation of heart rate  
involved_in regulation of postsynaptic neurotransmitter receptor internalization  
involved_in regulation of protein catabolic process PubMed 
involved_in regulation of protein catabolic process at postsynapse, modulating synaptic transmission  
involved_in response to antibiotic PubMed 
involved_in response to cocaine  
involved_in response to ether  
involved_in response to formaldehyde  
involved_in response to iron ion  
involved_in response to magnesium ion  
involved_in response to steroid hormone  
involved_in response to toxic substance  
involved_in response to water-immersion restraint stress  
involved_in response to xenobiotic stimulus  
involved_in traversing start control point of mitotic cell cycle  
involved_in ubiquitin-dependent protein catabolic process  
involved_in ubiquitin-dependent protein catabolic process PubMed 
involved_in ubiquitin-dependent protein catabolic process PubMed 
acts_upstream_of_or_within ubiquitin-dependent protein catabolic process PubMed 
involved_in ubiquitin-dependent protein catabolic process PubMed 
involved_in ventricular septum development  
Items 1 - 25 of 73
Component Evidence Code Pubs
is_active_in cytoplasm  
located_in cytoplasm PubMed 
located_in cytoplasm PubMed 
located_in cytosol  
located_in endocytic vesicle membrane  
located_in glutamatergic synapse  
colocalizes_with nuclear body PubMed 
is_active_in nucleolus  
located_in nucleolus PubMed 
located_in nucleolus PubMed 
located_in nucleoplasm PubMed 
located_in nucleoplasm  
located_in nucleus PubMed 
located_in nucleus PubMed 
located_in plasma membrane  
located_in postsynaptic density  
part_of protein-containing complex PubMed 
part_of protein-containing complex PubMed 
part_of transcription repressor complex PubMed 

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_047284809.1
XP_054228034.1
XP_054228035.1

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

  1. NG_016708.2 RefSeqGene

    Range
    5007..42374
    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
    A0A0A8KB70, A0A0A8KB75
    Conserved Domains (3) summary
    cd17672
    Location:25107
    MDM2; p53-binding domain found in E3 ubiquitin-protein ligase MDM2 and similar proteins
    pfam00641
    Location:252281
    zf-RanBP; Zn-finger in Ran binding protein and others
    cd16783
    Location:388444
    mRING-HC-C2H2C4_MDM2; Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2 and similar proteins
  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/TrEMBL
    A8WFP2, 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
    A0A0C4DFR5
    Related
    ENSP00000335096.4, ENST00000348801.7
    Conserved Domains (3) summary
    COG5271
    Location:41231
    MDN1; Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis]
    pfam00641
    Location:104132
    zf-RanBP; Zn-finger in Ran binding protein and others
    cd16783
    Location:239295
    mRING-HC-C2H2C4_MDM2; Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2 and similar proteins
  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/TrEMBL
    A0A0C4DFR5
    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
    Consensus CDS
    CCDS91724.1
    UniProtKB/Swiss-Prot
    A6NL51, A8K2S6, Q00987, Q13226, Q13297, Q13298, Q13299, Q13300, Q13301, Q53XW0, Q71TW9, Q8WYJ1, Q8WYJ2, Q9UGI3, Q9UMT8
    UniProtKB/TrEMBL
    A8WFP2
    Related
    ENSP00000444430.2, ENST00000539479.6
  6. NM_002392.6NP_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
    Consensus CDS
    CCDS8986.2
    UniProtKB/TrEMBL
    A8WFP2
    Related
    ENSP00000258149.6, ENST00000258149.11
    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: 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

  1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

    Range
    68808172..68850686
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047428853.1XP_047284809.1  E3 ubiquitin-protein ligase Mdm2 isoform X1

    UniProtKB/TrEMBL
    J3KN53

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    68784018..68830265
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054372059.1XP_054228034.1  E3 ubiquitin-protein ligase Mdm2 isoform X2

    UniProtKB/TrEMBL
    A8WFP2
  2. XM_054372060.1XP_054228035.1  E3 ubiquitin-protein ligase Mdm2 isoform X1

    UniProtKB/TrEMBL
    J3KN53

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