The following text describes a protein:
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 (By similarity). Also acts as a ubiquitin ligase E3 toward itself, ARRB1 and ARBB2. Permits the nuclear export of p53/TP53 (By similarity). Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein (By similarity). Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation (By similarity). Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53 (By similarity). Also a component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways (By similarity). Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus (By similarity). Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation (By similarity). Ubiquitinates DCX, leading to DCX degradation and reduction of the dendritic spine density of olfactory bulb granule cells. Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis. Negatively regulates NDUFS1, leading to decreased mitochondrial respiration, marked oxidative stress, and commitment to the mitochondrial pathway of apoptosis. 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.
Miscellaneous:
MISCELLANEOUS: [Isoform Mdm2-p76]: Does not bind to p53. Can be produced by alternative initiation at Met-50 of isoform Mdm2-p90, but is produced more efficiently by alternative splicing.
Subcellular Localization:
Nucleus, nucleoplasm. Cytoplasm. Nucleus, nucleolus. Nucleus. Note=Colocalizes with RASSF1 isoform A in the nucleus (By similarity). 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.
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.
Sequence:
MCNTNMSVSTEGAASTSQIPASEQETLVRPKPLLLKLLKSVGAQNDTYTMKEIIFYIGQYIMTKRLYDEKQQHIVYCSNDLLGDVFGVPSFSVKEHRKIYAMIYRNLVAVSQQDSGTSLSESRRQPEGGSDLKDPLQAPPEEKPSSSDLISRLSTSSRRRSISETEENTDELPGERHRKRRRSLSFDPSLGLCELREMCSGGSSSSSSSSSESTETPSHQDLDDGVSEHSGDCLDQDSVSDQFSVEFEVESLDSEDYSLSDEGHELSDEDDEVYRVTVYQTGESDTDSFEGDPEISLADYWKCTSCNEMNPPLPSHCKRCWTLRENWLPDDKGKDKVEISEKAKLENSAQAEEGLDVPDGKKLTENDAKEPCAEEDSEEKAEQTPLSQESDDYSQPSTSSSIVYSSQESVKELKEETQDKDESVESSFSLNAIEPCVICQGRPKNGCIVHGKTGHLMSCFTCAKKLKKRNKPCPVCRQPIQMIVLTYFN