E3 ubiquitin-protein ligase Mdm2

An E3 ubiquitin-protein ligase Mdm2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q00987]

Synonyms

EC 2.3.2.27;
Double minute 2 protein;
Hdm2;
Oncoprotein Mdm2;
RING-type E3 ubiquitin transferase Mdm2;
p53-binding protein Mdm2

Research

Bioassay Publications (70)

Timeframe	Studies on this Protein(%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	8 (11.43)	29.6817
2010's	53 (75.71)	24.3611
2020's	9 (12.86)	2.80

Compounds (19)

Drugs with Potency Measurements

Drug	Taxonomy	Measurement	Average (mM)	Bioassay(s)	Publication(s)
nutlin 2	Homo sapiens (human)	Potency	0.3000	1	1
nutlin-3a	Homo sapiens (human)	Potency	0.3000	1	1

Drugs with Inhibition Measurements

Drug	Taxonomy	Measurement	Average (mM)	Bioassay(s)	Publication(s)
catechol	Homo sapiens (human)	IC50	100.0000	1	1
gossypol	Homo sapiens (human)	Ki	25.0000	1	1
quinone	Homo sapiens (human)	IC50	13.9000	1	1
vorinostat	Homo sapiens (human)	Ki	20.0000	1	1
apomorphine	Homo sapiens (human)	IC50	10.1367	3	3
cytarabine	Homo sapiens (human)	IC50	0.0200	1	1
nutlin 3	Homo sapiens (human)	IC50	0.2948	3	3
nutlin 3	Homo sapiens (human)	Ki	0.0955	4	4
nutlin 2	Homo sapiens (human)	IC50	0.1400	4	4
nutlin 1	Homo sapiens (human)	IC50	1.7133	3	3
nutlin 1	Homo sapiens (human)	Ki	1.2400	1	1
nutlin-3a	Homo sapiens (human)	IC50	1.4548	34	34
nutlin-3a	Homo sapiens (human)	Ki	0.0860	15	15
MI-63	Homo sapiens (human)	IC50	3.6677	5	5
MI-63	Homo sapiens (human)	Ki	0.0027	4	4
nutlin-3b	Homo sapiens (human)	IC50	6.8540	2	2
nutlin-3b	Homo sapiens (human)	Ki	0.1984	1	1
pb 12	Homo sapiens (human)	Ki	0.9176	5	5
spautin-1	Homo sapiens (human)	IC50	0.6000	1	1
nvp-cgm097	Homo sapiens (human)	IC50	2.5568	4	4
nvp-cgm097	Homo sapiens (human)	Ki	0.0013	1	1
rg7388	Homo sapiens (human)	IC50	0.0078	4	4
sar405838	Homo sapiens (human)	IC50	0.1000	1	1
sar405838	Homo sapiens (human)	Ki	0.0020	8	8
rg7112	Homo sapiens (human)	IC50	0.0180	4	4
amg 232	Homo sapiens (human)	IC50	0.0006	4	4

Drugs with Activation Measurements

Drug	Taxonomy	Measurement	Average (mM)	Bioassay(s)	Publication(s)
nutlin 3	Homo sapiens (human)	Kd	0.2400	1	1
nutlin-3a	Homo sapiens (human)	Kd	0.6050	7	7
nutlin-3b	Homo sapiens (human)	Kd	0.1500	1	1
nvp-cgm097	Homo sapiens (human)	Kd	0.0023	1	1
rg7388	Homo sapiens (human)	Kd	0.0050	2	2
sar405838	Homo sapiens (human)	Kd	0.0027	1	1
rg7112	Homo sapiens (human)	Kd	0.0068	2	2
amg 232	Homo sapiens (human)	Kd	0.0000	3	3

Enables

This protein enables 18 target(s):

Target	Category	Definition
p53 binding	molecular function	Binding to one of the p53 family of proteins. [GOC:hjd]
ubiquitin-protein transferase activity	molecular function	Catalysis of the transfer of ubiquitin from one protein to another via the reaction X-Ub + Y = Y-Ub + X, where both X-Ub and Y-Ub are covalent linkages. [GOC:BioGRID, GOC:jh2, PMID:9635407]
protein binding	molecular function	Binding to a protein. [GOC:go_curators]
5S rRNA binding	molecular function	Binding to a 5S ribosomal RNA, the smallest RNA constituent of a ribosome. [GOC:jl, ISBN:0321000382]
zinc ion binding	molecular function	Binding to a zinc ion (Zn). [GOC:ai]
ligase activity	molecular function	Catalysis of the joining of two molecules, or two groups within a single molecule, using the energy from the hydrolysis of ATP, a similar triphosphate, or a pH gradient. [GOC:mah]
SUMO transferase activity	molecular function	Catalysis of the transfer of SUMO from one protein to another via the reaction X-SUMO + Y = Y-SUMO + X, where both X-SUMO and Y-SUMO are covalent linkages. [GOC:rn, PMID:11031248, PMID:11265250]
enzyme binding	molecular function	Binding to an enzyme, a protein with catalytic activity. [GOC:jl]
protein domain specific binding	molecular function	Binding to a specific domain of a protein. [GOC:go_curators]
ubiquitin protein ligase binding	molecular function	Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins. [GOC:vp]
receptor serine/threonine kinase binding	molecular function	Binding to a receptor that possesses protein serine/threonine kinase activity. [GOC:mah]
identical protein binding	molecular function	Binding to an identical protein or proteins. [GOC:jl]
peroxisome proliferator activated receptor binding	molecular function	Binding to a peroxisome proliferator activated receptor, alpha, beta or gamma. [GOC:jl, PMID:12769781]
ribonucleoprotein complex binding	molecular function	Binding to a complex of RNA and protein. [GOC:bf, GOC:go_curators, GOC:vk]
ubiquitin binding	molecular function	Binding to ubiquitin, a protein that when covalently bound to other cellular proteins marks them for proteolytic degradation. [GOC:ecd]
ubiquitin protein ligase activity	molecular function	Catalysis of the transfer of ubiquitin to a substrate protein via the reaction X-ubiquitin + S = X + S-ubiquitin, where X is either an E2 or E3 enzyme, the X-ubiquitin linkage is a thioester bond, and the S-ubiquitin linkage is an amide bond: an isopeptide bond between the C-terminal glycine of ubiquitin and the epsilon-amino group of lysine residues in the substrate or, in the linear extension of ubiquitin chains, a peptide bond the between the C-terminal glycine and N-terminal methionine of ubiquitin residues. [GOC:BioGRID, GOC:dph, GOC:mah, GOC:tb, PMID:22863777]
NEDD8 ligase activity	molecular function	Catalysis of the transfer of NEDD8 to a substrate protein via the reaction X-NEDD8 + S = X + S-NEDD8, where X is either an E2 or E3 enzyme, the X-NEDD8 linkage is a thioester bond, and the S-NEDD8 linkage is an isopeptide bond between the C-terminal amino acid of NEDD8 and the epsilon-amino group of lysine residues in the substrate. [GOC:dph]
disordered domain specific binding	molecular function	Binding to a disordered domain of a protein. [GOC:gg, PMID:11746698]

Located In

This protein is located in 7 target(s):

Target	Category	Definition
nucleus	cellular component	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. [GOC:go_curators]
nucleoplasm	cellular component	That part of the nuclear content other than the chromosomes or the nucleolus. [GOC:ma, ISBN:0124325653]
nucleolus	cellular component	A small, dense body one or more of which are present in the nucleus of eukaryotic cells. It is rich in RNA and protein, is not bounded by a limiting membrane, and is not seen during mitosis. Its prime function is the transcription of the nucleolar DNA into 45S ribosomal-precursor RNA, the processing of this RNA into 5.8S, 18S, and 28S components of ribosomal RNA, and the association of these components with 5S RNA and proteins synthesized outside the nucleolus. This association results in the formation of ribonucleoprotein precursors; these pass into the cytoplasm and mature into the 40S and 60S subunits of the ribosome. [ISBN:0198506732]
cytoplasm	cellular component	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. [ISBN:0198547684]
cytosol	cellular component	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. [GOC:hjd, GOC:jl]
plasma membrane	cellular component	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. [ISBN:0716731363]
endocytic vesicle membrane	cellular component	The lipid bilayer surrounding an endocytic vesicle. [GOC:mah]

Part Of

This protein is part of 2 target(s):

Target	Category	Definition
transcription repressor complex	cellular component	A protein complex that possesses activity that prevents or downregulates transcription. [GOC:mah]
protein-containing complex	cellular component	A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together. [GOC:dos, GOC:mah]

Involved In

This protein is involved in 63 target(s):

Target	Category	Definition
negative regulation of transcription by RNA polymerase II	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. [GOC:go_curators, GOC:txnOH]
protein polyubiquitination	biological process	Addition of multiple ubiquitin groups to a protein, forming a ubiquitin chain. [ISBN:0815316194]
blood vessel development	biological process	The process whose specific outcome is the progression of a blood vessel over time, from its formation to the mature structure. The blood vessel is the vasculature carrying blood. [GOC:hjd, UBERON:0001981]
blood vessel remodeling	biological process	The reorganization or renovation of existing blood vessels. [GOC:hjd]
regulation of heart rate	biological process	Any process that modulates the frequency or rate of heart contraction. [GOC:dph, GOC:tb, PMID:10358008]
atrioventricular valve morphogenesis	biological process	The process in which the structure of the atrioventricular valve is generated and organized. [GOC:mtg_heart]
endocardial cushion morphogenesis	biological process	The process in which the anatomical structure of the endocardial cushion is generated and organized. The endocardial cushion is a specialized region of mesenchymal cells that will give rise to the heart septa and valves. [GOC:mtg_heart]
ventricular septum development	biological process	The progression of the ventricular septum over time from its formation to the mature structure. [GOC:mtg_heart]
atrial septum development	biological process	The progression of the atrial septum over time, from its initial formation to the mature structure. [GOC:mtg_heart]
ubiquitin-dependent protein catabolic process	biological process	The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of a ubiquitin group, or multiple ubiquitin groups, to the protein. [GOC:go_curators]
apoptotic process	biological process	A programmed cell death process which begins when a cell receives an internal (e.g. DNA damage) or external signal (e.g. an extracellular death ligand), and proceeds through a series of biochemical events (signaling pathway phase) which trigger an execution phase. The execution phase is the last step of an apoptotic process, and is typically characterized by rounding-up of the cell, retraction of pseudopodes, reduction of cellular volume (pyknosis), chromatin condensation, nuclear fragmentation (karyorrhexis), plasma membrane blebbing and fragmentation of the cell into apoptotic bodies. When the execution phase is completed, the cell has died. [GOC:cjm, GOC:dhl, GOC:ecd, GOC:go_curators, GOC:mtg_apoptosis, GOC:tb, ISBN:0198506732, PMID:18846107, PMID:21494263]
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	biological process	A cascade of processes induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage and resulting in the stopping or reduction in rate of the cell cycle. [GOC:go_curators]
traversing start control point of mitotic cell cycle	biological process	A cell cycle process by which a cell commits to entering S phase via a positive feedback mechanism between the regulation of transcription and G1 CDK activity. [GOC:mtg_cell_cycle]
positive regulation of cell population proliferation	biological process	Any process that activates or increases the rate or extent of cell proliferation. [GOC:go_curators]
response to xenobiotic stimulus	biological process	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical. [GOC:jl, GOC:krc]
response to toxic substance	biological process	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a toxic stimulus. [GOC:lr]
response to iron ion	biological process	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an iron ion stimulus. [GOC:sm]
positive regulation of gene expression	biological process	Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). [GOC:txnOH-2018]
negative regulation of protein processing	biological process	Any process that decreases the rate, frequency or extent of protein maturation by peptide bond cleavage. [GOC:dph, GOC:mah, GOC:tb]
negative regulation of neuron projection development	biological process	Any process that decreases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites). [GOC:dph, GOC:tb]
protein ubiquitination	biological process	The process in which one or more ubiquitin groups are added to a protein. [GOC:ai]
protein sumoylation	biological process	The process in which a SUMO protein (small ubiquitin-related modifier) is conjugated to a target protein via an isopeptide bond between the carboxy-terminus of SUMO with an epsilon-amino group of a lysine residue of the target protein. [GOC:jl, PMID:11265250]
protein destabilization	biological process	Any process that decreases the stability of a protein, making it more vulnerable to degradative processes or aggregation. [GOC:mah]
response to magnesium ion	biological process	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a magnesium ion stimulus. [GOC:mah]
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	biological process	Any process that activates or increases the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome. [GOC:mah]
protein localization to nucleus	biological process	A process in which a protein transports or maintains the localization of another protein to the nucleus. [GOC:ecd]
regulation of protein catabolic process	biological process	Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the breakdown of a protein by the destruction of the native, active configuration, with or without the hydrolysis of peptide bonds. [GOC:go_curators, GOC:jl]
response to cocaine	biological process	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cocaine stimulus. Cocaine is a crystalline alkaloid obtained from the leaves of the coca plant. [GOC:ef, GOC:jl]
proteasome-mediated ubiquitin-dependent protein catabolic process	biological process	The chemical reactions and pathways resulting in the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome. [GOC:go_curators]
negative regulation of DNA damage response, signal transduction by p53 class mediator	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of the cascade of processes induced by the cell cycle regulator phosphoprotein p53, or an equivalent protein, in response to the detection of DNA damage. [GOC:jl]
establishment of protein localization	biological process	The directed movement of a protein to a specific location. [GOC:bf]
response to ether	biological process	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a ether stimulus. [GOC:go_curators]
negative regulation of DNA-templated transcription	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription. [GOC:go_curators, GOC:txnOH]
positive regulation of mitotic cell cycle	biological process	Any process that activates or increases the rate or extent of progression through the mitotic cell cycle. [GOC:dph, GOC:go_curators, GOC:tb]
response to antibiotic	biological process	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an antibiotic stimulus. An antibiotic is a chemical substance produced by a microorganism which has the capacity to inhibit the growth of or to kill other microorganisms. [GOC:ai, GOC:ef]
positive regulation of protein export from nucleus	biological process	Any process that activates or increases the frequency, rate or extent of directed movement of proteins from the nucleus into the cytoplasm. [GOC:bf]
response to steroid hormone	biological process	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a steroid hormone stimulus. [GOC:go_curators]
positive regulation of muscle cell differentiation	biological process	Any process that activates or increases the frequency, rate or extent of muscle cell differentiation. [CL:0000187, GOC:ai]
proteolysis involved in protein catabolic process	biological process	The hydrolysis of a peptide bond or bonds within a protein as part of the chemical reactions and pathways resulting in the breakdown of a protein by individual cells. [GOC:ai, GOC:dph, GOC:tb]
protein autoubiquitination	biological process	The ubiquitination by a protein of one or more of its own amino acid residues, or residues on an identical protein. Ubiquitination occurs on the lysine residue by formation of an isopeptide crosslink. [GOC:ai]
cardiac septum morphogenesis	biological process	The process in which the anatomical structure of a cardiac septum is generated and organized. A cardiac septum is a partition that separates parts of the heart. [GOC:dph, GOC:mtg_heart]
protein-containing complex assembly	biological process	The aggregation, arrangement and bonding together of a set of macromolecules to form a protein-containing complex. [GOC:jl]
cellular response to hydrogen peroxide	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrogen peroxide (H2O2) stimulus. [CHEBI:16240, GOC:mah]
cellular response to vitamin B1	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a vitamin B1 stimulus. [GOC:mah]
cellular response to alkaloid	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an alkaloid stimulus. Alkaloids are a large group of nitrogenous substances found in naturally in plants, many of which have extracts that are pharmacologically active. [GOC:mah]
cellular response to growth factor stimulus	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a growth factor stimulus. [GOC:mah]
cellular response to peptide hormone stimulus	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a peptide hormone stimulus. A peptide hormone is any of a class of peptides that are secreted into the blood stream and have endocrine functions in living animals. [GOC:mah]
cellular response to estrogen stimulus	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of stimulus by an estrogen, C18 steroid hormones that can stimulate the development of female sexual characteristics. [GOC:mah]
cellular response to hypoxia	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level. [GOC:mah]
cellular response to gamma radiation	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a gamma radiation stimulus. Gamma radiation is a form of electromagnetic radiation (EMR) or light emission of a specific frequency produced from sub-atomic particle interaction, such as electron-positron annihilation and radioactive decay. Gamma rays are generally characterized as EMR having the highest frequency and energy, and also the shortest wavelength, within the electromagnetic radiation spectrum. [GOC:mah]
cellular response to UV-C	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a UV-C radiation stimulus. UV-C radiation (UV-C light) spans the wavelengths 100 to 280 nm. [GOC:mah]
fibroblast activation	biological process	A change in the morphology or behavior of a fibroblast resulting from exposure to an activating factor such as a cellular or soluble ligand. [CL:0000057, GOC:BHF, GOC:mah]
cellular response to actinomycin D	biological process	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an actinomycin D stimulus. [GOC:mah]
negative regulation of signal transduction by p53 class mediator	biological process	Any process that stops, prevents or reduces the frequency, rate or extent of signal transduction by p53 class mediator. [GOC:TermGenie]
negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator	biological process	Any process that stops, prevents or reduces the frequency, rate or extent of intrinsic apoptotic signaling pathway by p53 class mediator. [GOC:BHF, GOC:mtg_apoptosis, GOC:rl, GOC:TermGenie, PMID:15705871]
response to formaldehyde	biological process	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a formaldehyde stimulus. [GO_REF:0000071, GOC:TermGenie, PMID:9149109]
positive regulation of vascular associated smooth muscle cell proliferation	biological process	Any process that activates or increases the frequency, rate or extent of vascular smooth muscle cell proliferation. [GO_REF:0000058, GOC:TermGenie, PMID:23246467]
positive regulation of vascular associated smooth muscle cell migration	biological process	Any process that activates or increases the frequency, rate or extent of vascular associated smooth muscle cell migration. [GO_REF:0000058, GOC:BHF, GOC:BHF_miRNA, GOC:rph, GOC:TermGenie, PMID:20693317]
amyloid fibril formation	biological process	The generation of amyloid fibrils, insoluble fibrous protein aggregates exhibiting beta sheet structure, from proteins. [GOC:cvs, GOC:jj, GOC:ppm, GOC:sj, PMID:21148556, PMID:22817896, PMID:28937655, PMID:29654159]
response to water-immersion restraint stress	biological process	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of water immersion while being held immobile. [PMID:10882227]
negative regulation of apoptotic process	biological process	Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. [GOC:jl, GOC:mtg_apoptosis]
cell cycle	biological process	The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division. [GOC:go_curators, GOC:mtg_cell_cycle]
regulation of gene expression	biological process	Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). [GOC:txnOH-2018]