U.S. flag

An official website of the United States government

Links from GEO Profiles

    • Showing Current items.

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

    Gene ID: 4193, updated on 10-Dec-2024

    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    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

    BioGRID CRISPR Screen Phenotypes (218 hits/1333 screens)

    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)

    NEW Try the new Transcript table

    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_001145337.3 → NP_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:25 → 107
      MDM2; p53-binding domain found in E3 ubiquitin-protein ligase MDM2 and similar proteins
      pfam00641
      Location:252 → 281
      zf-RanBP; Zn-finger in Ran binding protein and others
      cd16783
      Location:388 → 444
      mRING-HC-C2H2C4_MDM2; Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2 and similar proteins
    2. NM_001145339.2 → NP_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:250 → 279
      zf-RanBP; Zn-finger in Ran binding protein and others
      pfam02201
      Location:51 → 98
      SWIB; SWIB/MDM2 domain
      pfam13920
      Location:387 → 434
      zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
    3. NM_001145340.3 → NP_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:41 → 231
      MDN1; Midasin, AAA ATPase with vWA domain, involved in ribosome maturation [Translation, ribosomal structure and biogenesis]
      pfam00641
      Location:104 → 132
      zf-RanBP; Zn-finger in Ran binding protein and others
      cd16783
      Location:239 → 295
      mRING-HC-C2H2C4_MDM2; Modified RING finger, HC subclass (C2H2C4-type), found in E3 ubiquitin-protein ligase MDM2 and similar proteins
    4. NM_001278462.2 → NP_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:129 → 158
      zf-RanBP; Zn-finger in Ran binding protein and others
      pfam13920
      Location:266 → 313
      zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
    5. NM_001367990.1 → NP_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_002392.6 → NP_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:305 → 334
      zf-RanBP; Zn-finger in Ran binding protein and others
      pfam02201
      Location:51 → 98
      SWIB; SWIB/MDM2 domain
      pfam13920
      Location:442 → 489
      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_047428853.1 → XP_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_054372059.1 → XP_054228034.1  E3 ubiquitin-protein ligase Mdm2 isoform X2

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

      UniProtKB/TrEMBL
      J3KN53

    External link. Please review our privacy policy.