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Parameter | Value |
---|---|
Gene | MDM2 |
Protein Name | MDM2_HUMAN |
Organism | Homo sapiens (Human) |
Alternative name(s) | 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) |
Protein Family | MDM2/MDM4 family |
NCBI Gene ID | 4193 |
UniProt ID | Q00987 |
Enzyme Class | 2.3.2.27 |
Molecular Weight | 55233 |
Protein Length | 491 |
Protein Domain | InterPro | Pfam |
3D Structure |
PDBe |
PDBj |
RCSB PDB |
DrugPort
ModBase | SwissModel |
Gene Expression | Gene Expression Atlas |
Function and Disease | OMIM |
Protein-protein Interaction Database | STRING | IntAct | MINT |
Kinase Database | Phospho.ELM | PhosphoSite | NetworKIN |
Catalytic Activity (UniProt annotation) | S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. |
Localization | Nucleus, 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. |
Function (UniProt annotation) | 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). |
Gene Ontology | GO:0000122; GO:0001568; GO:0001974; GO:0002027; GO:0002039; GO:0003181; GO:0003203; GO:0003281; GO:0003283; GO:0004842; GO:0005634; GO:0005654; GO:0005730; GO:0005737; GO:0005829; GO:0005886; GO:0006511; GO:0006977; GO:0007089; GO:0008097; GO:0008270; GO:0008284; GO:0010039; GO:0010628; GO:0010955; GO:0010977; GO:0016032; GO:0016567; GO:0016579; GO:0016874; GO:0018205; GO:0019789; GO:0019899; GO:0019904; GO:0030666; GO:0031625; GO:0031648; GO:0032026; GO:0032436; GO:0032991; GO:0033612; GO:0034504; GO:0036369; GO:0042176; GO:0042220; GO:0042802; GO:0042975; GO:0043021; GO:0043130; GO:0043154; GO:0043278; GO:0043518; GO:0045184; GO:0045202; GO:0045472; GO:0045892; GO:0045931; GO:0046677; GO:0046827; GO:0047485; GO:0048545; GO:0051603; GO:0051865; GO:0060411; GO:0061630; GO:0061663; GO:0065003; GO:0070301; GO:0071157; GO:0071301; GO:0071312; GO:0071363; GO:0071375; GO:0071391; GO:0071456; GO:0071480; GO:0071494; GO:0072717; GO:0097110; GO:0097718; GO:1901796; GO:1901797; GO:1902254; GO:1904404; GO:1904707; GO:1904754; GO:1990000; GO:1990785 |
Gene Name | Organism | P-Site | Sequence(+/-7) | Conservation | Disorder | Curator Assessment | Reliability | Evidence Class | Evidence Logic | PubMed | Phospho-ELM | PhosphoSite-Plus |
---|---|---|---|---|---|---|---|---|---|---|---|---|
MAPKAPK2 (P49137) | Homo sapiens | S157 | SHLVSRPSTSSRRRA | 0.615 | 0.6482 | TP | certain | experimental | 72 | 73 | 55 | 9 | 273 | | 15688025 | - |
|
MAPKAPK2 (P49137) | Homo sapiens | S166 | SSRRRAISETEENSD | 0.815 | 0.7799 | TP | certain | experimental | 72 | 73 | 55 | 9 | 273 | | 15688025 | - |
|
PIM1 (P11309) | Homo sapiens | S166 | SSRRRAISETEENSD | 0.815 | 0.7799 | TP | certain | experimental | 72 | 73 | 8 | 55 | 107 | 23 | | 18467333 | - |
|
PIM1* (P11309) | Homo sapiens | S186 | RQRKRHKSDSISLSF | 0.958 | 0.6136 | TP | likely | experimental | 73 | 8 | 55 | 107 | 72 | 23 | | 18467333 | - |
|
DAPK1 (P53355) | Homo sapiens | S166 | SSRRRAISETEENSD | 0.815 | 0.7799 | TP | certain | - | 161 | 131 | 9 | 73 | | 15001356 | - |
|
DAPK1 (P53355) | Homo sapiens | S186 | RQRKRHKSDSISLSF | 0.958 | 0.6136 | TP | certain | - | 161 | 131 | 9 | 73 | | 15001356 | - |
|
DAPK3 (O43293) | Homo sapiens | S186 | RQRKRHKSDSISLSF | 0.958 | 0.6136 | - | - | - | - | - | - |
|
RPS6KA1 (Q15418) | Homo sapiens | S166 | SSRRRAISETEENSD | 0.815 | 0.7799 | - | - | - | - | - | - |
|
RPS6KA1 (Q15418) | Homo sapiens | S186 | RQRKRHKSDSISLSF | 0.958 | 0.6136 | - | - | - | - | - | - |
|
PIM2 (Q9P1W9) | Homo sapiens | S166 | SSRRRAISETEENSD | 0.815 | 0.7799 | - | - | - | - | - | - |
|
PIM2 (Q9P1W9) | Homo sapiens | S186 | RQRKRHKSDSISLSF | 0.958 | 0.6136 | - | - | - | - | - | - |
|
Reactome Pathways
KEGG Pathways
NCI Nature PID Pathways