E3 ubiquitin-protein ligase Mdm2

Details

Name
E3 ubiquitin-protein ligase Mdm2
Synonyms
  • 2.3.2.27
  • Double minute 2 protein
  • Oncoprotein Mdm2
  • p53-binding protein Mdm2
  • RING-type E3 ubiquitin transferase Mdm2
Gene Name
Mdm2
Organism
Mouse
Amino acid sequence
>lcl|BSEQ0052719|E3 ubiquitin-protein ligase Mdm2
MCNTNMSVSTEGAASTSQIPASEQETLVRPKPLLLKLLKSVGAQNDTYTMKEIIFYIGQY
IMTKRLYDEKQQHIVYCSNDLLGDVFGVPSFSVKEHRKIYAMIYRNLVAVSQQDSGTSLS
ESRRQPEGGSDLKDPLQAPPEEKPSSSDLISRLSTSSRRRSISETEENTDELPGERHRKR
RRSLSFDPSLGLCELREMCSGGSSSSSSSSSESTETPSHQDLDDGVSEHSGDCLDQDSVS
DQFSVEFEVESLDSEDYSLSDEGHELSDEDDEVYRVTVYQTGESDTDSFEGDPEISLADY
WKCTSCNEMNPPLPSHCKRCWTLRENWLPDDKGKDKVEISEKAKLENSAQAEEGLDVPDG
KKLTENDAKEPCAEEDSEEKAEQTPLSQESDDYSQPSTSSSIVYSSQESVKELKEETQDK
DESVESSFSLNAIEPCVICQGRPKNGCIVHGKTGHLMSCFTCAKKLKKRNKPCPVCRQPI
QMIVLTYFN
Number of residues
489
Molecular Weight
54557.48
Theoretical pI
Not Available
GO Classification
Functions
5S rRNA binding / disordered domain specific binding / enzyme binding / identical protein binding / ligase activity / NEDD8 ligase activity / p53 binding / peroxisome proliferator activated receptor binding / protein domain specific binding / protein N-terminus binding / receptor serine/threonine kinase binding / ribonucleoprotein complex binding / SUMO transferase activity / ubiquitin binding / ubiquitin protein ligase activity / ubiquitin protein ligase binding / ubiquitin-protein transferase activity / zinc ion binding
Processes
amyloid fibril formation / apoptotic process / atrial septum development / atrioventricular valve morphogenesis / blood vessel development / blood vessel remodeling / cardiac septum morphogenesis / cellular response to actinomycin D / cellular response to alkaloid / cellular response to estrogen stimulus / cellular response to gamma radiation / cellular response to growth factor stimulus / cellular response to hydrogen peroxide / cellular response to hypoxia / cellular response to peptide hormone stimulus / cellular response to UV-C / cellular response to vitamin B1 / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / endocardial cushion morphogenesis / establishment of protein localization / heart development / heart valve development / negative regulation of apoptotic process / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / negative regulation of DNA damage response, signal transduction by p53 class mediator / negative regulation of gene expression / negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of neuron projection development / negative regulation of protein processing / negative regulation of signal transduction by p53 class mediator / negative regulation of transcription by RNA polymerase II / negative regulation of transcription, DNA-templated / positive regulation of cell cycle / positive regulation of gene expression / positive regulation of mitotic cell cycle / positive regulation of muscle cell differentiation / positive regulation of proteasomal ubiquitin-dependent protein catabolic process / positive regulation of protein export from nucleus / positive regulation of transcription by RNA polymerase II / positive regulation of vascular associated smooth muscle cell migration / positive regulation of vascular associated smooth muscle cell proliferation / protein autoubiquitination / protein destabilization / protein localization to nucleus / protein ubiquitination / protein-containing complex assembly / proteolysis involved in cellular protein catabolic process / regulation of cell cycle / regulation of gene expression / regulation of heart rate / regulation of protein catabolic process / regulation of transcription by RNA polymerase II / response to cocaine / response to drug / response to ether / response to formaldehyde / response to iron ion / response to magnesium ion / response to morphine / response to steroid hormone / response to toxic substance / response to water-immersion restraint stress / traversing start control point of mitotic cell cycle / ubiquitin-dependent protein catabolic process / ventricular septum development
Components
cytoplasm / cytosol / nuclear body / nucleolus / nucleoplasm / nucleus / plasma membrane / protein-containing complex / synapse
General Function
E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome (PubMed:15195100, PubMed:21804542). 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 (PubMed:11588219). 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 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 (PubMed:25088421). Ubiquitinates DLG4, leading to proteasomal degradation of DLG4 which is required for AMPA receptor endocytosis (PubMed:14642282). 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).
Specific Function
5s rrna binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0052720|E3 ubiquitin-protein ligase Mdm2 (Mdm2)
ATGTGCAATACCAACATGTCTGTGTCTACCGAGGGTGCTGCAAGCACCTCACAGATTCCA
GCTTCGGAACAAGAGACTCTGGTTAGACCAAAACCATTGCTTTTGAAGTTGTTAAAGTCC
GTTGGAGCGCAAAACGACACTTACACTATGAAAGAGATTATATTTTATATTGGCCAGTAT
ATTATGACTAAGAGGTTATATGACGAGAAGCAGCAGCACATTGTGTATTGTTCAAATGAT
CTCCTAGGAGATGTGTTTGGAGTCCCGAGTTTCTCTGTGAAGGAGCACAGGAAAATATAT
GCAATGATCTACAGAAATTTAGTGGCTGTAAGTCAGCAAGACTCTGGCACATCGCTGAGT
GAGAGCAGACGTCAGCCTGAAGGTGGGAGTGATCTGAAGGATCCTTTGCAAGCGCCACCA
GAAGAGAAACCTTCATCTTCTGATTTAATTTCTAGACTGTCTACCTCATCTAGAAGGAGA
TCCATTAGTGAGACAGAAGAGAACACAGATGAGCTACCTGGGGAGCGGCACCGGAAGCGC
CGCAGGTCCCTGTCCTTTGATCCGAGCCTGGGTCTGTGTGAGCTGAGGGAGATGTGCAGC
GGCGGCAGCAGCAGCAGTAGCAGCAGCAGCAGCGAGTCCACAGAGACGCCCTCGCATCAG
GATCTTGACGATGGCGTAAGTGAGCATTCTGGTGATTGCCTGGATCAGGATTCAGTTTCT
GATCAGTTTAGCGTGGAATTTGAAGTTGAGTCTCTGGACTCGGAAGATTACAGCCTGAGT
GACGAAGGGCACGAGCTCTCAGATGAGGATGATGAGGTCTATCGGGTCACAGTCTATCAG
ACAGGAGAAAGCGATACAGACTCTTTTGAAGGAGATCCTGAGATTTCCTTAGCTGACTAT
TGGAAGTGTACCTCATGCAATGAAATGAATCCTCCCCTTCCATCACACTGCAAAAGATGC
TGGACCCTTCGTGAGAACTGGCTTCCAGACGATAAGGGGAAAGATAAAGTGGAAATCTCT
GAAAAAGCCAAACTGGAAAACTCAGCTCAGGCAGAAGAAGGCTTGGATGTGCCTGATGGC
AAAAAGCTGACAGAGAATGATGCTAAAGAGCCATGTGCTGAGGAGGACAGCGAGGAGAAG
GCCGAACAGACGCCCCTGTCCCAGGAGAGTGACGACTATTCCCAACCATCGACTTCCAGC
AGCATTGTTTATAGCAGCCAAGAAAGCGTGAAAGAGTTGAAGGAGGAAACGCAGGACAAA
GACGAGAGTGTGGAATCTAGCTTCTCCCTGAATGCCATCGAACCATGTGTGATCTGCCAG
GGGCGGCCTAAAAATGGCTGCATTGTTCACGGCAAGACTGGACACCTCATGTCATGTTTC
ACGTGTGCAAAGAAGCTAAAAAAAAGAAACAAGCCCTGCCCAGTGTGCAGACAGCCAATC
CAAATGATTGTGCTAACTTACTTCAACTAG
Chromosome Location
10
Locus
10 66.32 cM
External Identifiers
ResourceLink
UniProtKB IDP23804
UniProtKB Entry NameMDM2_MOUSE
General References
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails