DegronMD - Q00987(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). Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention rather than mitochondrial localization resulting in decreased supercomplex assembly (interactions between complex I and complex III), decreased complex I activity, ROS production, and apoptosis (PubMed:30879903). {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, ECO:0000269|PubMed:30879903}. View more >>

GO - Biological processes (BP): amyloid fibril formation [GO:1990000]; apoptotic process [GO:0006915]; 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 actinomycin D [GO:0072717]; cellular response to gamma radiation [GO:0071480]; cellular response to hypoxia [GO:0071456]; 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 DNA damage response, signal transduction by p53 class mediator [GO:0043518]; negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator [GO:1902254]; negative regulation of signal transduction by p53 class mediator [GO:1901797]; negative regulation of transcription, DNA-templated [GO:0045892]; negative regulation of transcription by RNA polymerase II [GO:0000122]; positive regulation of cell population proliferation [GO:0008284]; positive regulation of mitotic cell cycle [GO:0045931]; positive regulation of muscle cell differentiation [GO:0051149]; positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436]; proteasome-mediated ubiquitin-dependent protein catabolic process [GO:0043161]; protein autoubiquitination [GO:0051865]; protein-containing complex assembly [GO:0065003]; protein destabilization [GO:0031648]; protein localization to nucleus [GO:0034504]; protein polyubiquitination [GO:0000209]; protein ubiquitination [GO:0016567]; proteolysis involved in cellular protein catabolic process [GO:0051603]; regulation of cell cycle [GO:0051726]; regulation of heart rate [GO:0002027]; regulation of protein catabolic process [GO:0042176]; regulation of transcription by RNA polymerase II [GO:0006357]; response to antibiotic [GO:0046677]; transcription factor catabolic process [GO:0036369]; traversing start control point of mitotic cell cycle [GO:0007089]; ubiquitin-dependent protein catabolic process [GO:0006511]; ventricular septum development [GO:0003281] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S127F	TCGA-06-5416	GBM	TCGA	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.2222
p.Q146P	TCGA-22-5492	LUSC	TCGA	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation blocking ubiquitination signal	0.5
p.P153H	TCGA-69-8255	LUAD	TCGA	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation rewiring degron network	0.25
p.R169I	TCGA-A5-A0G2	UCEC	TCGA	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation rewiring degron network	0.0833
p.E151D	TCGA-BS-A0UV	UCEC	TCGA	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation rewiring degron network	0.1944
p.D399E	TCGA-RD-A8NB	STAD	TCGA	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation altering degron motif	0.6758
p.H126Y	DO48386	BLCA	ICGC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.25
p.E411G	DO218347	BRCA	ICGC	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation rewiring degron network	0.0556
p.R130T	DO222692	ESCA	ICGC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.1389
p.L405F	DO229036	LICA	ICGC	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation blocking phosphorylation signal	0.6667
p.R130I	DO229037	LICA	ICGC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.1389
p.S400C	DO44794	LICA	ICGC	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation altering degron motif	0.7541
p.R158H	DO23308	LINC	ICGC	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation altering degron motif	0.8244
p.R158H	ACH-000608	Ovarian Cancer	CCLE	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation altering degron motif	0.8244
p.R158H	ACH-000999	Colon/Colorectal Cancer	CCLE	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation altering degron motif	0.8244
p.R158H	SNU-1040	large intestine	COSMIC	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation altering degron motif	0.8244
p.P122H	DO25360	LUAD	ICGC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation altering degron motif	0.7694
p.E390Q	DO23762	LUAD	ICGC	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation rewiring degron network	0.1389
p.Q115P	DO27208	LUSC	ICGC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.2778
p.R158C	DO52402	UCEC	ICGC	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation altering degron motif	0.8301
p.A409V	DO41871	UCEC	ICGC	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation rewiring degron network	0.1111
p.E120D	DO42793	UCEC	ICGC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation altering degron motif	0.6758
p.I410S	SIDM00193	Colorectal Carcinoma	GDSC	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation rewiring degron network	0.0833
p.I410S	SNU-81	large intestine	COSMIC	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation rewiring degron network	0.0833
p.Y411C	SIDM01387	Small Cell Lung Carcinoma	GDSC	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation rewiring degron network	0.0556
p.S400N	ACH-000410	Bone Cancer	CCLE	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation altering degron motif	0.7069
p.S400N	Saos-2	bone	COSMIC	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation altering degron motif	0.7069
p.I164T	ACH-000649	Kidney Cancer	CCLE	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation rewiring degron network	0.2222
p.L150V	ACH-000880	Gastric Cancer	CCLE	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation rewiring degron network	0.1667
p.L150V	AGS	stomach	COSMIC	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation rewiring degron network	0.1667
p.H128D	DSH1	urinary tract	COSMIC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.1944
p.L120F	RVH-421	skin	COSMIC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation altering degron motif	0.6981
p.L120F	COLO-741	large intestine	COSMIC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation altering degron motif	0.6981
p.S152N	Saos-2	bone	COSMIC	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation rewiring degron network	0.2222
p.L126V	AGS	stomach	COSMIC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.25
p.I404S	SNU-81	large intestine	COSMIC	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation rewiring degron network	0.25
p.D132V	MOLT-4	haematopoietic and lymphoid tissue	COSMIC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.0833
p.M410I	ML-2	haematopoietic and lymphoid tissue	COSMIC	PSTSS	DEG_SPOP_SBC_1	397:401	Mutation rewiring degron network	0.0833
p.E155G	MOLT-13	haematopoietic and lymphoid tissue	COSMIC	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation rewiring degron network	0.3056
p.D154V	MOLT-4	haematopoietic and lymphoid tissue	COSMIC	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation rewiring degron network	0.2778
p.S128P	REH	haematopoietic and lymphoid tissue	COSMIC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.1944
p.E162K	HCC1569	breast	COSMIC	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation rewiring degron network	0.2778
p.K108N	HT-115	large intestine	COSMIC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.0833
p.I156S	SNU-81	large intestine	COSMIC	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation altering degron motif	0.7341
p.C113Y	CW-2	large intestine	COSMIC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.2222
p.D107V	MOLT-4	haematopoietic and lymphoid tissue	COSMIC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.0556
p.E157D	SJSA-1	bone	COSMIC	PSTSS	DEG_SPOP_SBC_1	156:160	Mutation altering degron motif	0.6758
p.I131S	SNU-81	large intestine	COSMIC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.1111
p.E132D	SJSA-1	bone	COSMIC	DSGTSVS	DEG_SCF_TRCP1_1	117:123	Mutation rewiring degron network	0.0833

Kaplan plot for MDM2 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

MDM2

UniProt ID: Q00987

Entrez ID: 4193

Protein name: E3 ubiquitin-protein ligase Mdm2 (EC 2.3.2.27) (Double minute 2 protein) (Hdm2) (Oncoprotein Mdm2) (RING-type E3 ubiquitin transferase Mdm2) (p53-binding protein Mdm2)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for MDM2 in