Linked Life Data

Q00987

Source:http://identifiers.org/uniprot/Q00987

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
biopax3:comment
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 an 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 promotes it to proteasomal degradation. SUBUNIT: Binds p53/TP53, TP73/p73, ARF/P14, PML, RBL5 and RP11, and specifically to RNA. Can interact with RB1, E1A-associated protein EP300 and the E2F1 transcription factor. Forms a ternary complex with p53/TP53 and WWOX. Interacts with CDKN2AIP, MTBP, RFWD3, TBRG1, USP7, PYHIN1, UBXN6, and RBBP6. Isoform Mdm2-F does not interact with p53/TP53. Interacts with and ubiquitinates HIV-1 Tat. Interacts with ARRB1 and ARRB2. Interacts (isoform 2) with PSMA3. Found in a trimeric complex with MDM2, MDM4 and UPB2. Interacts with USP2 (via N-terminus and C-terminus). Interacts with MDM4. Part of a complex with MDM2, DAXX, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts directly with DAXX and USP7. Interacts (via C-terminus) with RASSF1 isoform A (via N-terminus); the interaction is independent of TP53. Interacts with APEX1; leading to its ubiquitination and degradation. Interacts with RYBP; this inhibits ubiquitination of TP53. Identified in a complex with RYBP and p53/TP53. Also component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in regulating p53/TP53 stabilization and activity. Binds directly both p53/TP53 and TRIM28. Component of the TRIM28/KAP1-ERBB4-MDM2 complex involved in connecting growth factor responses with DNA damage. Interacts directly with both TRIM28 and ERBB4 in the complex. Interacts with DYRK2. Interacts with IGF1R. Interacts with TRIM13; the interaction ubiquitinates MDM2 leading to its proteasomal degradation. SUBCELLULAR LOCATION: 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. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=11; Name=Mdm2; IsoId=Q00987-1; Sequence=Displayed; Name=Mdm2-A; IsoId=Q00987-2; Sequence=VSP_003208; Name=Mdm2-A1; IsoId=Q00987-3; Sequence=VSP_003208, VSP_003214; Name=Mdm2-B; IsoId=Q00987-4; Sequence=VSP_003209; Name=Mdm2-C; IsoId=Q00987-5; Sequence=VSP_003211; Name=Mdm2-D; IsoId=Q00987-6; Sequence=VSP_003210; Name=Mdm2-E; IsoId=Q00987-7; Sequence=VSP_003212, VSP_003213; Name=Mdm2-alpha; IsoId=Q00987-8; Sequence=VSP_003207; Name=Mdm2-F; IsoId=Q00987-9; Sequence=VSP_022578; Name=Mdm2-G; IsoId=Q00987-10; Sequence=VSP_022579; Name=11; IsoId=Q00987-11; Sequence=VSP_037997; TISSUE SPECIFICITY: Ubiquitous. Isoform Mdm2-A, isoform Mdm2-B, isoform Mdm2-C, isoform Mdm2-D, isoform Mdm2-E, isoform Mdm2-F and isoform Mdm2-G are observed in a range of cancers but absent in normal tissues. INDUCTION: By DNA damage. DOMAIN: Region I is sufficient for binding p53 and inhibiting its G1 arrest and apoptosis functions. It also binds p73 and E2F1. Region II contains most of a central acidic region required for interaction with ribosomal protein L5 and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc interacts specifically with RNA whether or not zinc is present and mediates the heterooligomerization with MDM4. It is also essential for its ubiquitin ligase E3 activity toward p53 and itself. PTM: Phosphorylated in response to ionizing radiation in an ATM- dependent manner. Phosphorylation on Ser-166 by SGK1 activates ubiquitination of p53/TP53. PTM: Auto-ubiquitinated; which leads to proteasomal degradation. Also ubiquitinated by TRIM13. Deubiquitinated by USP2 leads to its accumulation and increases deubiquitination and degradation of p53/TP53. Deubiquitinated by USP7 leading to its stabilization. POLYMORPHISM: A polymorphism in the MDM2 promoter is associated with susceptibility to accelerated tumor formation in both hereditary and sporadic cancers [MIM:614401]. It also contributes to susceptibility to Li-Fraumeni syndrome, in patients carrying a TP53 germline mutation. DISEASE: Note=Seems to be amplified in certain tumors (including soft tissue sarcomas, osteosarcomas and gliomas). A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding. MISCELLANEOUS: MDM2 RING finger mutations that failed to ubiquitinate p53 in vitro did not target p53 for degradation when expressed in cells. SIMILARITY: Belongs to the MDM2/MDM4 family. SIMILARITY: Contains 1 RanBP2-type zinc finger. SIMILARITY: Contains 1 RING-type zinc finger. SIMILARITY: Contains 1 SWIB domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MDM2ID115ch12q15.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mdm2/"; WEB RESOURCE: Name=Wikipedia; Note=Mdm2 entry; URL="http://en.wikipedia.org/wiki/Mdm2"; GENE SYNONYMS:MDM2. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 491 AA; 55233 MW; F37CE163876BC983 CRC64;
biopax3:xref
biopax3:displayName
MDM2_HUMAN
biopax3:name
6.3.2.-, Double minute 2 protein, Hdm2, MDM2, Oncoprotein Mdm2, p53-binding protein Mdm2
biopax3:entityFeature
biopax3:organism
biopax3:sequence
MCNTNMSVPTDGAVTTSQIPASEQETLVRPKPLLLKLLKSVGAQKDTYTMKEVLFYLGQYIMTKRLYDEKQQHIVYCSNDLLGDLFGVPSFSVKEHRKIYTMIYRNLVVVNQQESSDSGTSVSENRCHLEGGSDQKDLVQELQEEKPSSSHLVSRPSTSSRRRAISETEENSDELSGERQRKRHKSDSISLSFDESLALCVIREICCERSSSSESTGTPSNPDLDAGVSEHSGDWLDQDSVSDQFSVEFEVESLDSEDYSLSEEGQELSDEDDEVYQVTVYQAGESDTDSFEEDPEISLADYWKCTSCNEMNPPLPSHCNRCWALRENWLPEDKGKDKGEISEKAKLENSTQAEEGFDVPDCKKTIVNDSRESCVEENDDKITQASQSQESEDYSQPSTSSSIIYSSQEDVKEFEREETQDKEESVESSLPLNAIEPCVICQGRPKNGCIVHGKTGHLMACFTCAKKLKKRNKPCPVCRQPIQMIVLTYFP
biopax3:standardName
E3 ubiquitin-protein ligase Mdm2