Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0008762
UniProt IDQ00987
Primary gene name(s)MDM2
Synonym gene name(s)unknown
Protein nameE3 ubiquitin-protein ligase Mdm2
Protein functionE3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation, PubMed:12821780, PubMed:15053880, PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911. Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells, By similarity. {ECO:0000250|UniProtKB:P23804, ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:22128911}.
Subcellular locationNucleus, nucleoplasm. Cytoplasm. Nucleus, nucleolus. Note=Expressed predominantly in the nucleoplasm. Interaction with ARF(P14 results in the localization of both proteins to the nucleolus. The nucleolar localization signals in both ARF(P14 and MDM2 may be necessary to allow efficient nucleolar localization of both proteins. Colocalizes with RASSF1 isoform A in the nucleus.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q00987
Gene Ontology
(Biological Process)
Complete annatation
atrial septum development [GO:0003283];
atrioventricular valve morphogenesis [GO:0003181];
blood vessel development [GO:0001568];
blood vessel remodeling [GO:0001974];
cardiac septum morphogenesis [GO:0060411];
cellular response to alkaloid [GO:0071312];
cellular response to antibiotic [GO:0071236];
cellular response to estrogen stimulus [GO:0071391];
cellular response to growth factor stimulus [GO:0071363];
cellular response to hydrogen peroxide [GO:0070301];
cellular response to hypoxia [GO:0071456];
cellular response to peptide hormone stimulus [GO:0071375];
cellular response to UV-C [GO:0071494];
cellular response to vitamin B1 [GO:0071301];
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest [GO:0006977];
endocardial cushion morphogenesis [GO:0003203];
establishment of protein localization [GO:0045184];
negative regulation of cell cycle arrest [GO:0071157];
negative regulation of cysteine-type endopeptidase activity involved in apoptotic process [GO:0043154];
negative regulation of DNA damage response, signal transduction by p53 class mediator [GO:0043518];
negative regulation of neuron projection development [GO:0010977];
negative regulation of protein processing [GO:0010955];
negative regulation of signal transduction by p53 class mediator [GO:1901797];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
peptidyl-lysine modification [GO:0018205];
positive regulation of cell proliferation [GO:0008284];
positive regulation of gene expression [GO:0010628];
positive regulation of mitotic cell cycle [GO:0045931];
positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436];
positive regulation of protein export from nucleus [GO:0046827];
positive regulation of vascular associated smooth muscle cell migration [GO:1904754];
positive regulation of vascular smooth muscle cell proliferation [GO:1904707];
protein autoubiquitination [GO:0051865];
protein complex assembly [GO:0006461];
protein destabilization [GO:0031648];
protein localization to nucleus [GO:0034504];
protein sumoylation [GO:0016925];
protein ubiquitination [GO:0016567];
protein ubiquitination involved in ubiquitin-dependent protein catabolic process [GO:0042787];
regulation of heart rate [GO:0002027];
regulation of protein catabolic process [GO:0042176];
regulation of signal transduction by p53 class mediator [GO:1901796];
response to antibiotic [GO:0046677];
response to carbohydrate [GO:0009743];
response to cocaine [GO:0042220];
response to drug [GO:0042493];
response to ether [GO:0045472];
response to iron ion [GO:0010039];
response to magnesium ion [GO:0032026];
response to morphine [GO:0043278];
response to steroid hormone [GO:0048545];
response to toxic substance [GO:0009636];
response to water-immersion restraint stress [GO:1990785];
transcription factor catabolic process [GO:0036369];
traversing start control point of mitotic cell cycle [GO:0007089];
ventricular septum development [GO:0003281];
viral process [GO:0016032]
Gene Ontology
(Molecular Function)
Complete annatation
enzyme binding [GO:0019899];
identical protein binding [GO:0042802];
ligase activity [GO:0016874];
p53 binding [GO:0002039];
SUMO transferase activity [GO:0019789];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin protein ligase binding [GO:0031625];
ubiquitin-protein transferase activity [GO:0004842];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endocytic vesicle membrane [GO:0030666];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
protein complex [GO:0043234];
synapse [GO:0045202]
Protein-protein interaction110358
Phylogenetic treeQ00987
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.8499693460563180.01046466369638550.0270769804689996
AZA vs. DISU0.2632162259577820.2991301369072490.86128089010194
AZA vs. IL70.1762996238490210.3606153969656350.999311006273513
AZA vs. SAHA-0.7765458562831840.001565640187083160.0279958009253755
DISU vs. CD3-0.5996453171265490.09915203993480170.185206672859628
DISU vs. IL7-0.09582608371296530.7033072738081330.923741138299926
DISU vs. SAHA-1.038706241796160.0004175524517738840.0109442313055377
DMSO vs. AZA-0.3657985408880050.0292497967831461
DMSO vs. CD3-1.225119000161930.0001777841690786540.000749389621480113
DMSO vs. DISU-0.6301256783938980.01026892370208350.218886393480055
DMSO vs. IL70.5488658140154060.002431616101901460.095799956198368
DMSO vs. SAHA-0.4182847281898430.07695605778850960.324031866752002
HIV vs. Mock in Activation-0.01413362976865090.9818652419292150.999983755607037
HIV vs. Mock in Latency0.1241584798041590.4528936069824890.999834320637052
IL7 vs. CD3-0.6655292720576020.03896423397261590.0896325093072755
SAHA vs. CD3-1.651350773980585.47701154718361e-063.69630828553771e-05
SAHA vs. IL7-0.9560560371153070.0001008813494424170.00197491618375972
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.980951 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB02872 Cis-[4,5-Bis-(4-Bromophenyl)-2-(2-Ethoxy-4-Methoxyphenyl)-4,5-Dihydroimidazol-1-Yl]-[4-(2-Hydroxyethyl)Piperazin-1-Yl]Methanone experimental unknown unknown
DB04144 Cis-[4,5-Bis-(4-Chlorophenyl)-2-(2-Isopropoxy-4-Methoxyphenyl)-4,5-Dihyd Roimidazol-1-Yl]-Piperazin-1-Yl-Methanone experimental unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1RV1 X-ray 2.3Å A/B/C=25-109.
1T4E X-ray 2.6Å A/B=17-111.
1T4F X-ray 1.9Å M=17-125.
1YCR X-ray 2.6Å A=17-125.
1Z1M NMR - A=1-118.
2AXI X-ray 1.4Å A=17-125.
2C6A NMR - A=290-335.
2C6B NMR - A=290-335.
2F1Y X-ray 1.7Å A=224-232.
2FOP X-ray 2.1Å B=145-150.
2GV2 X-ray 1.8Å A=17-125.
2HDP NMR - A/B=429-491.
2LZG NMR - A=1-125.
2M86 NMR - B=17-125.
2MPS NMR - A=3-109.
2RUH NMR - A=6-102.
2VJE X-ray 2.2Å A/C=428-491.
2VJF X-ray 2.3Å A/C=428-491.
3EQS X-ray 1.6Å A=25-109.
3G03 X-ray 1.8Å A/C=18-125.
3IUX X-ray 1.6Å A/C=25-109.
3IWY X-ray 1.9Å A/C=25-109.
3JZK X-ray 2.1Å A=17-111.
3JZR X-ray 2.1Å A=17-125.
3JZS X-ray 1.7Å A=24-109.
3LBK X-ray 2.3Å A=18-111.
3LBL X-ray 1.6Å A/C/E=18-111.
3LNJ X-ray 2.4Å A/C/E=25-109.
3LNZ X-ray 1.9Å A/C/E/G/I/K/M/O=25-109.
3MQS X-ray 2.4Å D=394-403.
3TJ2 X-ray 2.1Å A/C=18-111.
3TPX X-ray 1.8Å A/C/E=25-109.
3TU1 X-ray 1.6Å A=18-125.
3V3B X-ray 2.0Å A/B=24-110.
3VBG X-ray 2.8Å A/B/C/D=25-109.
3VZV X-ray 2.8Å A/B=25-109.
3W69 X-ray 1.9Å A/B=25-109.
4DIJ X-ray 1.9Å A/B=17-111.
4ERE X-ray 1.8Å A/B=17-111.
4ERF X-ray 2.0Å A/C/E=17-111.
4HBM X-ray 1.9Å A/B/C/D/E/F/G/H=6-125.
4HFZ X-ray 2.6Å A/C=17-125.
4HG7 X-ray 1.6Å A=17-108.
4JV7 X-ray 2.2Å A=18-111.
4JV9 X-ray 2.5Å A=18-111.
4JVE X-ray 2.3Å A=18-111.
4JVR X-ray 1.7Å A/C/E=18-111.
4JWR X-ray 2.3Å A/B/C=17-111.
4MDN X-ray 1.9Å A=18-110.
4MDQ X-ray 2.1Å A=25-110.
4OAS X-ray 1.7Å A/C/E=17-111.
4OBA X-ray 1.6Å A/B/C=17-111.
4OCC X-ray 1.8Å A/C/E=17-111.
4ODE X-ray 1.8Å A=6-110.
4ODF X-ray 2.2Å A=6-110.
4OGN X-ray 1.3Å A=6-110.
4OGT X-ray 1.5Å A=6-110.
4OGV X-ray 2.2Å A/B/C=17-111.
4OQ3 X-ray 2.3Å A/B/C/D=17-111.
4QO4 X-ray 1.7Å A=17-111.
4QOC X-ray 1.7Å A/C/E/G/I/K=17-111.
4UD7 X-ray 1.6Å A/B/C/D=17-125.
4UE1 X-ray 1.4Å A/B/C/D=17-125.
4UMN X-ray 1.9Å A/B=6-125.
4WT2 X-ray 1.4Å A=6-110.
4XXB X-ray 2.4Å B=290-437.
4ZFI X-ray 2.0Å A/B/C/D=18-113.
4ZGK X-ray 2.0Å A/B=18-114.
4ZYC X-ray 1.9Å A/B/C=17-111.
4ZYF X-ray 1.8Å A=17-111.
4ZYI X-ray 1.6Å A=17-111.
5AFG X-ray 1.9Å A=17-108.
5C5A X-ray 1.1Å A/B=20-111.
5HMH X-ray 1.7Å A/B=21-116.
5HMI X-ray 1.7Å A/B=18-116.
5HMK X-ray 2.1Å A/B=17-125.
5LN2 X-ray 1.5Å A=17-111.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Vif binds 19128510
Vif inhibits 21071676
Vif interacts with 19128510
Tat ubiquitinated by 12883554
Vif degraded by 19128510
Tat regulated by 12883554

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa01522 Endocrine resistance - Homo sapiens (human)
hsa01524 Platinum drug resistance - Homo sapiens (human)
hsa04068 FoxO signaling pathway - Homo sapiens (human)
hsa04110 Cell cycle - Homo sapiens (human)
hsa04115 p53 signaling pathway - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04151 PI3K-Akt signaling pathway - Homo sapiens (human)
hsa04919 Thyroid hormone signaling pathway - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05200 Pathways in cancer - Homo sapiens (human)
hsa05202 Transcriptional misregulation in cancer - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05205 Proteoglycans in cancer - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)
hsa05214 Glioma - Homo sapiens (human)
hsa05215 Prostate cancer - Homo sapiens (human)
hsa05218 Melanoma - Homo sapiens (human)
hsa05219 Bladder cancer - Homo sapiens (human)
hsa05220 Chronic myeloid leukemia - Homo sapiens (human)