MDM2: Polycystic Ovarian Syndrome Database

Gene Information

Gene Symbol

MDM2

Aliases

ACTFS, HDMX, LSKB, hdm2

Entrez Gene ID

4193

Gene Name

MDM2 proto-oncogene

Chromosomal Location

12q15

HGNC ID

HGNC:6973

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]

RefSeq DNA

NG_016708.1

RefSeq mRNA

NM_002392.5, NM_001145337.3, NM_001145339.2, NM_001145340.3, NM_001278462.2, NM_001367990.1

e!Ensembl

Gene	ENSG00000135679
Transcript	ENST00000258149, ENST00000311420, ENST00000393417, ENST00000258148, ENST00000539479, ENST00000393415, ENST00000523991, ENST00000543323, ENST00000393416, ENST00000481186, ENST00000393410, ENST00000496959, ENST00000299252, ENST00000360430, ENST00000517852, ENST00000546048, ENST00000540352, ENST00000542502, ENST00000537182, ENST00000536089, ENST00000393413, ENST00000350057, ENST00000545204, ENST00000544561, ENST00000665020, ENST00000666617, ENST00000671567, ENST00000348801, ENST00000478070, ENST00000393412, ENST00000428863
Protein	ENSP00000258149, ENSP00000310742, ENSP00000429021, ENSP00000258148, ENSP00000444430, ENSP00000377067, ENSP00000427828, ENSP00000439238, ENSP00000377068, ENSP00000431110, ENSP00000377062, ENSP00000429692, ENSP00000299252, ENSP00000353611, ENSP00000430257, ENSP00000445222, ENSP00000445030, ENSP00000444566, ENSP00000443450, ENSP00000444028, ENSP00000377065, ENSP00000266624, ENSP00000444597, ENSP00000441841, ENSP00000499718, ENSP00000499763, ENSP00000499407, ENSP00000335096, ENSP00000430906, ENSP00000377064, ENSP00000410694

SNPs

SNP Id	Upstream Sequence	SNP	Downstream Sequence	Functional Significance	References
rs2279744					26440054

Gene Ontology (GO)

Show/Hide all(58 )

GO ID	Ontology	Function	Evidence	Reference
GO:0000122	Biological process	Negative regulation of transcription by RNA polymerase II	IDA	9271120, 17310983
GO:0006511	Biological process	Ubiquitin-dependent protein catabolic process	IDA	11278372, 15314173, 16173922, 17310983
GO:0006511	Biological process	Ubiquitin-dependent protein catabolic process	IGI	17237821
GO:0006511	Biological process	Ubiquitin-dependent protein catabolic process	IMP	16479015, 18560357, 24506068
GO:0006977	Biological process	DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	IMP	21726810
GO:0008284	Biological process	Positive regulation of cell proliferation	TAS	7791904
GO:0016567	Biological process	Protein ubiquitination	IDA	9450543, 15878855, 19656744, 20153724
GO:0018205	Biological process	Peptidyl-lysine modification	IMP	19372219
GO:0031648	Biological process	Protein destabilization	IDA	9529249, 10360174, 15314173
GO:0031648	Biological process	Protein destabilization	IMP	16479015, 18560357
GO:0032436	Biological process	Positive regulation of proteasomal ubiquitin-dependent protein catabolic process	IDA	11278372
GO:0034504	Biological process	Protein localization to nucleus	IDA	10360174
GO:0036369	Biological process	Transcription factor catabolic process	TAS	20181722
GO:0042176	Biological process	Regulation of protein catabolic process	IDA	9153395
GO:0043518	Biological process	Negative regulation of DNA damage response, signal transduction by p53 class mediator	IDA	9529249, 10360174
GO:0045184	Biological process	Establishment of protein localization	IDA	10360174
GO:0045892	Biological process	Negative regulation of transcription, DNA-templated	IDA	9271120
GO:0045892	Biological process	Negative regulation of transcription, DNA-templated	IMP	16479015, 25417702
GO:0045931	Biological process	Positive regulation of mitotic cell cycle	IMP	17290220
GO:0046677	Biological process	Response to antibiotic	IEP	20810912
GO:0051603	Biological process	Proteolysis involved in cellular protein catabolic process	IMP	25417702
GO:0051865	Biological process	Protein autoubiquitination	IMP	16479015, 17237821
GO:0065003	Biological process	Protein-containing complex assembly	IDA	10608892, 12915590
GO:0071157	Biological process	Negative regulation of cell cycle arrest	IDA	9529249
GO:0071456	Biological process	Cellular response to hypoxia	IEP	20810912
GO:0071480	Biological process	Cellular response to gamma radiation	IDA	16213212
GO:0072717	Biological process	Cellular response to actinomycin D	IDA	15314173
GO:1901797	Biological process	Negative regulation of signal transduction by p53 class mediator	IDA	16173922
GO:1902254	Biological process	Negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	IMP	17310983
GO:1990000	Biological process	Amyloid fibril formation	IMP	12630860
GO:0005634	Cellular component	Nucleus	IDA	10360174, 29295817
GO:0005634	Cellular component	Nucleus	IMP	15314173, 21726810
GO:0005654	Cellular component	Nucleoplasm	IDA	10707090, 12915590
GO:0005730	Cellular component	Nucleolus	IDA	10707090, 22869143
GO:0005730	Cellular component	Nucleolus	IMP	11718560
GO:0005737	Cellular component	Cytoplasm	IMP	15314173, 21726810
GO:0016604	Cellular component	Nuclear body	IDA	10360174
GO:0032991	Cellular component	Protein-containing complex	IDA	9529249, 17310983
GO:0032991	Cellular component	Protein-containing complex	IMP	11718560, 15314173, 16479015
GO:0002039	Molecular function	P53 binding	IPI	9529249, 15053879, 20173098, 25417702
GO:0004842	Molecular function	Ubiquitin-protein transferase activity	IDA	9450543
GO:0004842	Molecular function	Ubiquitin-protein transferase activity	IMP	20173098
GO:0005515	Molecular function	Protein binding	IPI	7791904, 8875929, 9271120, 9529249, 10196247, 10608892, 11178989, 12740913, 12915590, 15144954, 15195100, 15313915, 15314173, 15364927, 15604276, 15878855, 15916963, 16023600, 16173922, 16374512, 16402859, 16432196, 16474402, 16845383, 17006543, 17080083, 17110929, 17139261, 1715990
GO:0008097	Molecular function	5S rRNA binding	IDA	24120868
GO:0008270	Molecular function	Zinc ion binding	IDA	10722742
GO:0016874	Molecular function	Ligase activity	IDA	17142452
GO:0019789	Molecular function	SUMO transferase activity	EXP	21900752
GO:0019899	Molecular function	Enzyme binding	IPI	15577914, 17290220, 18566590, 20173098
GO:0019904	Molecular function	Protein domain specific binding	IPI	16479015
GO:0031625	Molecular function	Ubiquitin protein ligase binding	IPI	18382127, 29295817
GO:0042802	Molecular function	Identical protein binding	IPI	17159902, 17936559, 22493164
GO:0043021	Molecular function	Ribonucleoprotein complex binding	IDA	24120868
GO:0043130	Molecular function	Ubiquitin binding	IDA	29295817
GO:0047485	Molecular function	Protein N-terminus binding	IPI	11718560
GO:0061630	Molecular function	Ubiquitin protein ligase activity	IDA	15314173, 17310983
GO:0061630	Molecular function	Ubiquitin protein ligase activity	IMP	16479015, 18560357, 19372219
GO:0061663	Molecular function	NEDD8 ligase activity	IMP	18560357
GO:0097718	Molecular function	Disordered domain specific binding	IPI	12630860

Protein Information

Protein Name

E3 ubiquitin-protein ligase Mdm2, 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

Function

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).

Refseq Proteins

NP_002383.2, NP_001138809.1, NP_001138811.1, NP_001138812.1, NP_001265391.1, NP_001354919.1

UniProt

Q00987

PDB

1RV1, 1T4E, 1T4F, 1YCR, 1Z1M, 2AXI, 2C6A, 2C6B, 2F1Y, 2FOP, 2GV2, 2HDP, 2LZG, 2M86, 2MPS, 2RUH, 2VJE, 2VJF, 3EQS, 3G03, 3IUX, 3IWY, 3JZK, 3JZR, 3JZS, 3LBK, 3LBL, 3LNJ, 3LNZ, 3MQS, 3TJ2, 3TPX, 3TU1, 3V3B, 3VBG, 3VZV, 3W69, 4DIJ, 4ERE, 4ERF, 4HBM, 4HFZ, 4HG7, 4JV7, 4JV9, 4JVE, 4JVR, 4JWR, 4MDN, 4MDQ, 4OAS,