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    MDM2 MDM2 proto-oncogene, E3 ubiquitin protein ligase [ Homo sapiens (human) ]

    Gene ID: 4193, updated on 24-Aug-2015
    Official Symbol
    MDM2provided by HGNC
    Official Full Name
    MDM2 proto-oncogene, E3 ubiquitin protein ligaseprovided by HGNC
    Primary source
    HGNC:HGNC:6973
    See related
    Ensembl:ENSG00000135679; HPRD:01272; 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; 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]
    Orthologs
    See MDM2 in Epigenomics, MapViewer
    Location:
    12q14.3-q15
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    107 current GRCh38.p2 (GCF_000001405.28) 12 NC_000012.12 (68808168..68845544)
    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

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Accelerated tumor formation, susceptibility to
    MedGen: C3280690 OMIM: 614401 GeneReviews: Not available
    Compare labs

    NHGRI GWAS Catalog

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

    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 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

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      TP53 network, organism-specific biosystemP53 is not a lonely genome guardian, it operates with the assistance of p73 and p63 within a complex network including distinct but complementary pathways. This protein family presents a high le...
    • Thyroid hormone signaling pathway, organism-specific biosystem (from KEGG)
      Thyroid hormone signaling pathway, organism-specific biosystemThe thyroid hormones (THs) are important regulators of growth, development and metabolism. The action of TH is mainly mediated by T3 (3,5,3'-triiodo-L-thyronine). Thyroid hormones, L-thyroxine (T4) a...
    • Trafficking of AMPA receptors, organism-specific biosystem (from REACTOME)
      Trafficking of AMPA receptors, organism-specific biosystemRepetitive presynaptic activity causes long lasting changes in the postsynaptic transmission by changing the type and the number of AMPA receptors. These changes are brought about by trafficking mec...
    • Transcriptional misregulation in cancer, organism-specific biosystem (from KEGG)
      Transcriptional misregulation in cancer, organism-specific biosystem
      Transcriptional misregulation in cancer
    • Transcriptional misregulation in cancer, conserved biosystem (from KEGG)
      Transcriptional misregulation in cancer, conserved biosystem
      Transcriptional misregulation in cancer
    • Transmission across Chemical Synapses, organism-specific biosystem (from REACTOME)
      Transmission across Chemical Synapses, organism-specific biosystemChemical synapses are specialized junctions that are used for communication between neurons, neurons and muscle or gland cells. The synapse involves a pre-synaptic neuron and a post-synaptic neuron,...
    • Tryptophan metabolism, organism-specific biosystem (from WikiPathways)
      Tryptophan metabolism, organism-specific biosystem
      Tryptophan metabolism
    • Ubiquitin mediated proteolysis, organism-specific biosystem (from KEGG)
      Ubiquitin mediated proteolysis, organism-specific biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
    • Ubiquitin mediated proteolysis, conserved biosystem (from KEGG)
      Ubiquitin mediated proteolysis, conserved biosystemProtein ubiquitination plays an important role in eukaryotic cellular processes. It mainly functions as a signal for 26S proteasome dependent protein degradation. The addition of ubiquitin to protein...
    • Viral carcinogenesis, organism-specific biosystem (from KEGG)
      Viral carcinogenesis, organism-specific biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
    • Viral carcinogenesis, conserved biosystem (from KEGG)
      Viral carcinogenesis, conserved biosystemThere is a strong association between viruses and the development of human malignancies. We now know that at least six human viruses, Epstein-Barr virus (EBV), hepatitis B virus (HBV), hepatitis C vi...
    • p53 pathway, organism-specific biosystem (from Pathway Interaction Database)
      p53 pathway, organism-specific biosystem
      p53 pathway
    • p53 signaling pathway, organism-specific biosystem (from KEGG)
      p53 signaling pathway, organism-specific biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
    • p53 signaling pathway, conserved biosystem (from KEGG)
      p53 signaling pathway, conserved biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
    • p53-Dependent G1 DNA Damage Response, organism-specific biosystem (from REACTOME)
      p53-Dependent G1 DNA Damage Response, organism-specific biosystemMost of the damage-induced modifications of p53 are dependent on the ATM kinase. The first link between ATM and p53 was predicted based on the earlier studies that showed that AT cells exhibit a redu...
    • p53-Dependent G1/S DNA damage checkpoint, organism-specific biosystem (from REACTOME)
      p53-Dependent G1/S DNA damage checkpoint, organism-specific biosystemThe arrest at G1/S checkpoint is mediated by the action of a widely known tumor suppressor protein, p53. Loss of p53 functions, as a result of mutations in cancer prevent the G1/S checkpoint (Kuerbi...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • MGC5370, MGC71221

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    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 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    scaffold protein binding IEA
    Inferred from Electronic Annotation
    more info
     
    ubiquitin protein ligase activity IMP
    Inferred from Mutant Phenotype
    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
     
    Fc-epsilon receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    cellular response to hypoxia IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    epidermal growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    establishment of protein localization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    fibroblast growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    innate immune response TAS
    Traceable Author Statement
    more info
     
    negative regulation of DNA damage response, signal transduction by p53 class mediator IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of apoptotic process IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of cell cycle arrest IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of signal transduction by p53 class mediator IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of transcription from RNA polymerase II promoter IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    neurotrophin TRK receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    peptidyl-lysine modification IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    phosphatidylinositol-mediated signaling TAS
    Traceable Author Statement
    more info
     
    positive regulation of cell proliferation TAS
    Traceable Author Statement
    more info
    PubMed 
    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 
    protein complex assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein destabilization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein localization to nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein ubiquitination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein ubiquitination involved in ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein ubiquitination involved in ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of protein catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to antibiotic IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    synaptic transmission TAS
    Traceable Author Statement
    more info
     
    traversing start control point of mitotic cell cycle 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 
    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 complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Preferred Names
    E3 ubiquitin-protein ligase Mdm2
    Names
    MDM2 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_002383.2

    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_001145337.2NP_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
      UniProtKB/TrEMBL
      A7UKX8
      UniProtKB/TrEMBL
      A7UKX9
      Conserved Domains (3) summary
      cd00162
      Location:391435
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam00641
      Location:252280
      zf-RanBP; Zn-finger in Ran binding protein and others
      pfam02201
      Location:40100
      SWIB; SWIB/MDM2 domain
    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
      G3XA89
      UniProtKB/Swiss-Prot
      Q00987
      Conserved Domains (3) summary
      cd00162
      Location:389433
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam00641
      Location:250278
      zf-RanBP; Zn-finger in Ran binding protein and others
      pfam02201
      Location:46106
      SWIB; SWIB/MDM2 domain
    3. NM_001145340.2NP_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
      UniProtKB/TrEMBL
      Q96DS0
      Conserved Domains (2) summary
      cd00162
      Location:242286
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam00641
      Location:104131
      zf-RanBP; Zn-finger in Ran binding protein and others
    4. NM_001278462.1NP_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
      A7UKX9
      UniProtKB/Swiss-Prot
      Q00987
      UniProtKB/TrEMBL
      Q96DS0
      Related
      ENSP00000348637, ENST00000356290
      Conserved Domains (2) summary
      cd00162
      Location:268312
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam00641
      Location:129157
      zf-RanBP; Zn-finger in Ran binding protein and others
    5. 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
      ENSP00000417281, ENST00000462284
      Conserved Domains (3) summary
      cd00162
      Location:444488
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam00641
      Location:305333
      zf-RanBP; Zn-finger in Ran binding protein and others
      pfam02201
      Location:46106
      SWIB; SWIB/MDM2 domain

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

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

    Reference GRCh38.p2 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p2 Primary Assembly

      Range
      68808168..68845544
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006719400.2XP_006719463.1  

      See identical proteins and their annotated locations for XP_006719463.1

      Conserved Domains (2) summary
      cd00162
      Location:337381
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam00641
      Location:198226
      zf-RanBP; Zn-finger in Ran binding protein and others
    2. XM_005268872.3XP_005268929.1  

      See identical proteins and their annotated locations for XP_005268929.1

      UniProtKB/Swiss-Prot
      Q00987
      Conserved Domains (3) summary
      cd00162
      Location:438482
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam00641
      Location:299327
      zf-RanBP; Zn-finger in Ran binding protein and others
      pfam02201
      Location:40100
      SWIB; SWIB/MDM2 domain
    3. XM_006719399.2XP_006719462.1  

      UniProtKB/Swiss-Prot
      Q00987
      Conserved Domains (3) summary
      cd00162
      Location:377421
      RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...
      pfam00641
      Location:238266
      zf-RanBP; Zn-finger in Ran binding protein and others
      cl02489
      Location:139
      SWIB; SWIB/MDM2 domain

    Alternate CHM1_1.1

    Genomic

    1. NC_018923.2 Alternate CHM1_1.1

      Range
      69170604..69207918
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    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.