Gene: MDM2

Basic information

Tag Content
Uniprot ID Q00987; A6NL51; A8K2S6; Q13226; Q13297; Q13298; Q13299; Q13300; Q13301; Q53XW0; Q71TW9; Q8WYJ1; Q8WYJ2; Q9UGI3; Q9UMT8;
Entrez ID 4193
Genbank protein ID AAA75516.1; AAA75514.1; BAF83030.1; AAL40179.1; AAF42995.1; AAM78554.1; AAA82061.1; AAA82237.1; AAA60568.1; AAL40180.1; AAA75518.1; AAP35922.1; CAB64448.1; CAA78055.1; AAA75517.1; AAA75515.1;
Genbank nucleotide ID XM_006719399.3; NM_001278462.1; XM_005268872.4; NM_001145339.2; NM_002392.5;
Ensembl protein ID ENSP00000353611; ENSP00000258149; ENSP00000444430; ENSP00000377065; ENSP00000299252;
Ensembl nucleotide ID ENSG00000135679
Gene name E3 ubiquitin-protein ligase Mdm2
Gene symbol MDM2
Organism Homo sapiens
NCBI taxa ID 9606
Cleft type
Developmental stage
Data sources Homology search
Reference
Functional description E3 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). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (By similarity).
Sequence
MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM KEVLFYLGQY 60
IMTKRLYDEK QQHIVYCSND LLGDLFGVPS FSVKEHRKIY TMIYRNLVVV NQQESSDSGT 120
SVSENRCHLE GGSDQKDLVQ ELQEEKPSSS HLVSRPSTSS RRRAISETEE NSDELSGERQ 180
RKRHKSDSIS LSFDESLALC VIREICCERS SSSESTGTPS NPDLDAGVSE HSGDWLDQDS 240
VSDQFSVEFE VESLDSEDYS LSEEGQELSD EDDEVYQVTV YQAGESDTDS FEEDPEISLA 300
DYWKCTSCNE MNPPLPSHCN RCWALRENWL PEDKGKDKGE ISEKAKLENS TQAEEGFDVP 360
DCKKTIVNDS RESCVEENDD KITQASQSQE SEDYSQPSTS SSIIYSSQED VKEFEREETQ 420
DKEESVESSL PLNAIEPCVI CQGRPKNGCI VHGKTGHLMA CFTCAKKLKK RNKPCPVCRQ 480
PIQMIVLTYF P 491

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression in different tissues (GTEx V7)

  

Gene expression in different tissues (ENCODE)

  

Protein structural annotations

3D structure in PDB database

Protein disorder information

Orthologous information

Relation Gene symbol Entrez ID UniProt ID Cleft type Developmental stage Species Evidence Details
1:1 orthologMDM2540378F1MYE6Bos taurusPredictionMore>>
1:1 orthologMDM2102173163A0A452FBR9Capra hircusPredictionMore>>
1:1 orthologMDM24193Q00987Homo sapiensPredictionMore>>
1:1 orthologMdm217246P23804CPOMus musculusPublicationMore>>
1:1 orthologMDM2742141A0A2I3TD93Pan troglodytesPredictionMore>>
1:1 orthologMdm2314856A0A0G2JVC1Rattus norvegicusPredictionMore>>
1:1 orthologmdm2B0R0S9Danio rerioPredictionMore>>

Other genetic variants/mutations

loading...

Disease or phenotype associated information

loading...

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID GO Term Evidence
GO:0002039 p53 bindingIPI
GO:0004842 ubiquitin-protein transferase activityIMP
GO:0004842 ubiquitin-protein transferase activityIDA
GO:0005515 protein bindingIPI
GO:0008097 5S rRNA bindingIDA
GO:0008270 zinc ion bindingIDA
GO:0016874 ligase activityIDA
GO:0019789 SUMO transferase activityEXP
GO:0019899 enzyme bindingIPI
GO:0019904 protein domain specific bindingIPI
GO:0031625 ubiquitin protein ligase bindingIPI
GO:0033612 receptor serine/threonine kinase bindingIEA
GO:0042802 identical protein bindingIPI
GO:0042975 peroxisome proliferator activated receptor bindingIEA
GO:0043021 ribonucleoprotein complex bindingIDA
GO:0043130 ubiquitin bindingIDA
GO:0047485 protein N-terminus bindingIPI
GO:0061630 ubiquitin protein ligase activityIDA
GO:0061630 ubiquitin protein ligase activityIMP
GO:0061630 ubiquitin protein ligase activityTAS
GO:0061663 NEDD8 ligase activityIMP
GO:0097110 scaffold protein bindingIEA
GO:0097718 disordered domain specific bindingIPI

GO:Biological Process

GO ID GO Term Evidence
GO:0000122 negative regulation of transcription by RNA polymerase IIIDA
GO:0000209 protein polyubiquitinationTAS
GO:0001568 blood vessel developmentIEA
GO:0001974 blood vessel remodelingIEA
GO:0002027 regulation of heart rateIEA
GO:0003181 atrioventricular valve morphogenesisIEA
GO:0003203 endocardial cushion morphogenesisIEA
GO:0003281 ventricular septum developmentIEA
GO:0003283 atrial septum developmentIEA
GO:0006511 ubiquitin-dependent protein catabolic processIDA
GO:0006511 ubiquitin-dependent protein catabolic processIMP
GO:0006511 ubiquitin-dependent protein catabolic processIGI
GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrestIMP
GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrestTAS
GO:0007089 traversing start control point of mitotic cell cycleIEA
GO:0008284 positive regulation of cell population proliferationTAS
GO:0010039 response to iron ionIEA
GO:0010628 positive regulation of gene expressionIEA
GO:0010955 negative regulation of protein processingIEA
GO:0010977 negative regulation of neuron projection developmentIEA
GO:0016032 viral processIEA
GO:0016567 protein ubiquitinationIDA
GO:0016579 protein deubiquitinationTAS
GO:0016925 protein sumoylationIEA
GO:0018205 peptidyl-lysine modificationIMP
GO:0031648 protein destabilizationIDA
GO:0031648 protein destabilizationIMP
GO:0032026 response to magnesium ionIEA
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic processIDA
GO:0034504 protein localization to nucleusIDA
GO:0036369 transcription factor catabolic processTAS
GO:0042176 regulation of protein catabolic processIDA
GO:0042220 response to cocaineIEA
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic processIEA
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic processTAS
GO:0043278 response to morphineIEA
GO:0043518 negative regulation of DNA damage response, signal transduction by p53 class mediatorIDA
GO:0045184 establishment of protein localizationIDA
GO:0045472 response to etherIEA
GO:0045892 negative regulation of transcription, DNA-templatedIMP
GO:0045892 negative regulation of transcription, DNA-templatedIDA
GO:0045931 positive regulation of mitotic cell cycleIMP
GO:0046677 response to antibioticIEP
GO:0046827 positive regulation of protein export from nucleusIEA
GO:0048545 response to steroid hormoneIEA
GO:0051149 positive regulation of muscle cell differentiationIEA
GO:0051603 proteolysis involved in cellular protein catabolic processIMP
GO:0051865 protein autoubiquitinationIMP
GO:0060411 cardiac septum morphogenesisIEA
GO:0065003 protein-containing complex assemblyIDA
GO:0070301 cellular response to hydrogen peroxideIEA
GO:0071157 negative regulation of cell cycle arrestIDA
GO:0071301 cellular response to vitamin B1IEA
GO:0071312 cellular response to alkaloidIEA
GO:0071363 cellular response to growth factor stimulusIEA
GO:0071375 cellular response to peptide hormone stimulusIEA
GO:0071391 cellular response to estrogen stimulusIEA
GO:0071456 cellular response to hypoxiaIEP
GO:0071480 cellular response to gamma radiationIDA
GO:0071494 cellular response to UV-CIEA
GO:0072717 cellular response to actinomycin DIDA
GO:1901796 regulation of signal transduction by p53 class mediatorTAS
GO:1901797 negative regulation of signal transduction by p53 class mediatorIDA
GO:1901797 negative regulation of signal transduction by p53 class mediatorTAS
GO:1902254 negative regulation of intrinsic apoptotic signaling pathway by p53 class mediatorIMP
GO:1904404 response to formaldehydeIEA
GO:1904707 positive regulation of vascular smooth muscle cell proliferationIEA
GO:1904754 positive regulation of vascular associated smooth muscle cell migrationIEA
GO:1990000 amyloid fibril formationIMP
GO:1990785 response to water-immersion restraint stressIEA

GO:Cellular Component

GO ID GO Term Evidence
GO:0005634 nucleusIDA
GO:0005634 nucleusIMP
GO:0005654 nucleoplasmIDA
GO:0005654 nucleoplasmTAS
GO:0005730 nucleolusIDA
GO:0005730 nucleolusIMP
GO:0005737 cytoplasmIMP
GO:0005829 cytosolTAS
GO:0005886 plasma membraneTAS
GO:0030666 endocytic vesicle membraneTAS
GO:0032991 protein-containing complexIMP
GO:0032991 protein-containing complexIDA
GO:0045202 synapseIEA
GO:0016604 nuclear bodyIDA

Reactome Pathway

Reactome ID Reactome Term Evidence
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmissionTAS
R-HSA-112315 Transmission across Chemical SynapsesTAS
R-HSA-112316 Neuronal SystemTAS
R-HSA-1257604 PIP3 activates AKT signalingTAS
R-HSA-162582 Signal TransductionTAS
R-HSA-1640170 Cell CycleTAS
R-HSA-1643685 DiseaseTAS
R-HSA-198323 AKT phosphorylates targets in the cytosolTAS
R-HSA-212436 Generic Transcription PathwayTAS
R-HSA-2219528 PI3K/AKT Signaling in CancerTAS
R-HSA-2262752 Cellular responses to stressTAS
R-HSA-2559580 Oxidative Stress Induced SenescenceTAS
R-HSA-2559583 Cellular SenescenceTAS
R-HSA-2559585 Oncogene Induced SenescenceTAS
R-HSA-2990846 SUMOylationTAS
R-HSA-3108232 SUMO E3 ligases SUMOylate target proteinsTAS
R-HSA-3232118 SUMOylation of transcription factorsTAS
R-HSA-3232142 SUMOylation of ubiquitinylation proteinsTAS
R-HSA-3700989 Transcriptional Regulation by TP53TAS
R-HSA-392499 Metabolism of proteinsTAS
R-HSA-399719 Trafficking of AMPA receptorsTAS
R-HSA-399721 Glutamate binding, activation of AMPA receptors and synaptic plasticityTAS
R-HSA-5633007 Regulation of TP53 ActivityTAS
R-HSA-5663202 Diseases of signal transductionTAS
R-HSA-5674400 Constitutive Signaling by AKT1 E17K in CancerTAS
R-HSA-5688426 DeubiquitinationTAS
R-HSA-5689880 Ub-specific processing proteasesTAS
R-HSA-597592 Post-translational protein modificationTAS
R-HSA-6804756 Regulation of TP53 Activity through PhosphorylationTAS
R-HSA-6804757 Regulation of TP53 DegradationTAS
R-HSA-6804760 Regulation of TP53 Activity through MethylationTAS
R-HSA-6806003 Regulation of TP53 Expression and DegradationTAS
R-HSA-69541 Stabilization of p53TAS
R-HSA-69563 p53-Dependent G1 DNA Damage ResponseTAS
R-HSA-69580 p53-Dependent G1/S DNA damage checkpointTAS
R-HSA-69615 G1/S DNA Damage CheckpointsTAS
R-HSA-69620 Cell Cycle CheckpointsTAS
R-HSA-73857 RNA Polymerase II TranscriptionTAS
R-HSA-74160 Gene expression (Transcription)TAS
R-HSA-8878159 Transcriptional regulation by RUNX3TAS
R-HSA-8941858 Regulation of RUNX3 expression and activityTAS
R-HSA-8953897 Cellular responses to external stimuliTAS
R-HSA-9006925 Intracellular signaling by second messengersTAS

Drugs and compounds information

loading...

Functional annotations

Keywords

Keyword ID Keyword Term
KW-0002 3D-structure
KW-0025 Alternative splicing
KW-0963 Cytoplasm
KW-0945 Host-virus interaction
KW-0479 Metal-binding
KW-0539 Nucleus
KW-0597 Phosphoprotein
KW-0656 Proto-oncogene
KW-1185 Reference proteome
KW-0808 Transferase
KW-0832 Ubl conjugation
KW-0833 Ubl conjugation pathway
KW-0862 Zinc
KW-0863 Zinc-finger

Interpro

InterPro ID InterPro Term
IPR028340 Mdm2
IPR015459 MDM2_E3_ligase
IPR016495 p53_neg-reg_MDM_2/4
IPR036885 SWIB_MDM2_dom_sf
IPR003121 SWIB_MDM2_domain
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD

PROSITE

PROSITE ID PROSITE Term
PS01358 ZF_RANBP2_1
PS50199 ZF_RANBP2_2
PS50089 ZF_RING_2

Pfam

Pfam ID Pfam Term
PF02201 SWIB
PF00641 zf-RanBP

Protein-protein interaction

Protein-miRNA interaction