CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-010811
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 E3 ubiquitin-protein ligase Mdm2 
Protein Synonyms/Alias
 Double minute 2 protein; Hdm2; Oncoprotein Mdm2; p53-binding protein Mdm2 
Gene Name
 MDM2 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
446VICQGRPKNGCIVHGsumoylation[1]
466MACFTCAKKLKKRNKacetylation[2]
467ACFTCAKKLKKRNKPacetylation[2]
469FTCAKKLKKRNKPCPacetylation[2]
470TCAKKLKKRNKPCPVacetylation[2]
Reference
 [1] SUMO-1 modification of Mdm2 prevents its self-ubiquitination and increases Mdm2 ability to ubiquitinate p53.
 Buschmann T, Fuchs SY, Lee CG, Pan ZQ, Ronai Z.
 Cell. 2000 Jun 23;101(7):753-62. [PMID: 10892746]
 [2] Inhibition of p53 degradation by Mdm2 acetylation.
 Wang X, Taplick J, Geva N, Oren M.
 FEBS Lett. 2004 Mar 12;561(1-3):195-201. [PMID: 15013777] 
Functional Description
 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 SNAI1 and promotes them to proteasomal degradation. 
Sequence Annotation
 DOMAIN 27 107 SWIB.
 ZN_FING 299 328 RanBP2-type.
 ZN_FING 438 479 RING-type.
 REGION 1 110 Necessary for interaction with USP2.
 REGION 150 230 Interaction with PYHIN1.
 REGION 170 306 Interaction with MTBP (By similarity).
 REGION 210 304 ARF-binding.
 REGION 223 232 Interaction with USP7.
 REGION 242 331 Region II.
 REGION 276 491 Necessary for interaction with USP2.
 MOTIF 179 185 Nuclear localization signal (Potential).
 MOTIF 190 202 Nuclear export signal.
 MOTIF 466 473 Nucleolar localization signal
 MOD_RES 166 166 Phosphoserine; by SGK1.
 MOD_RES 240 240 Phosphoserine.
 MOD_RES 242 242 Phosphoserine.
 MOD_RES 246 246 Phosphoserine.
 MOD_RES 260 260 Phosphoserine.
 MOD_RES 262 262 Phosphoserine.
 MOD_RES 386 386 Phosphoserine; by ATM.
 MOD_RES 395 395 Phosphoserine; by ATM.
 MOD_RES 407 407 Phosphoserine; by ATM.
 MOD_RES 419 419 Phosphothreonine; by ATM.
 MOD_RES 425 425 Phosphoserine; by ATM.
 MOD_RES 429 429 Phosphoserine; by ATM.  
Keyword
 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; Host-virus interaction; Ligase; Metal-binding; Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome; Ubl conjugation; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 491 AA 
Protein Sequence
MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM KEVLFYLGQY 60
IMTKRLYDEK QQHIVYCSND LLGDLFGVPS FSVKEHRKIY TMIYRNLVVV NQQESSDSGT 120
SVSENRCHLE GGSDQKDLVQ ELQEEKPSSS HLVSRPSTSS RRRAISETEE NSDELSGERQ 180
RKRHKSDSIS LSFDESLALC VIREICCERS SSSESTGTPS NPDLDAGVSE HSGDWLDQDS 240
VSDQFSVEFE VESLDSEDYS LSEEGQELSD EDDEVYQVTV YQAGESDTDS FEEDPEISLA 300
DYWKCTSCNE MNPPLPSHCN RCWALRENWL PEDKGKDKGE ISEKAKLENS TQAEEGFDVP 360
DCKKTIVNDS RESCVEENDD KITQASQSQE SEDYSQPSTS SSIIYSSQED VKEFEREETQ 420
DKEESVESSL PLNAIEPCVI CQGRPKNGCI VHGKTGHLMA CFTCAKKLKK RNKPCPVCRQ 480
PIQMIVLTYF P 491 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; IDA:UniProtKB.
 GO:0005886; C:plasma membrane; TAS:Reactome.
 GO:0043234; C:protein complex; IDA:BHF-UCL.
 GO:0045202; C:synapse; IEA:Compara.
 GO:0004842; F:ubiquitin-protein ligase activity; IDA:UniProtKB.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0071229; P:cellular response to acid; IEA:Compara.
 GO:0071312; P:cellular response to alkaloid; IEA:Compara.
 GO:0071236; P:cellular response to antibiotic; IEA:Compara.
 GO:0071391; P:cellular response to estrogen stimulus; IEA:Compara.
 GO:0070301; P:cellular response to hydrogen peroxide; IEA:Compara.
 GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB.
 GO:0071375; P:cellular response to peptide hormone stimulus; IEA:Compara.
 GO:0071494; P:cellular response to UV-C; IEA:Compara.
 GO:0071301; P:cellular response to vitamin B1; IEA:Compara.
 GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IMP:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0045184; P:establishment of protein localization; IDA:BHF-UCL.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
 GO:0071157; P:negative regulation of cell cycle arrest; IDA:BHF-UCL.
 GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Compara.
 GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL.
 GO:0010955; P:negative regulation of protein processing; IEA:Compara.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0018205; P:peptidyl-lysine modification; IMP:BHF-UCL.
 GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome.
 GO:0008284; P:positive regulation of cell proliferation; TAS:BHF-UCL.
 GO:0010628; P:positive regulation of gene expression; IEA:Compara.
 GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
 GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
 GO:0046827; P:positive regulation of protein export from nucleus; IEA:Compara.
 GO:0006461; P:protein complex assembly; IDA:UniProtKB.
 GO:0031648; P:protein destabilization; IDA:BHF-UCL.
 GO:0034504; P:protein localization to nucleus; IDA:BHF-UCL.
 GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
 GO:0046677; P:response to antibiotic; IEP:UniProtKB.
 GO:0009743; P:response to carbohydrate stimulus; IEA:Compara.
 GO:0042220; P:response to cocaine; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0045472; P:response to ether; IEA:Compara.
 GO:0010039; P:response to iron ion; IEA:Compara.
 GO:0032026; P:response to magnesium ion; IEA:Compara.
 GO:0043278; P:response to morphine; IEA:Compara.
 GO:0007268; P:synaptic transmission; TAS:Reactome.
 GO:0007089; P:traversing start control point of mitotic cell cycle; IEA:Compara.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR015459; MDM2_E3_ligase.
 IPR016495; p53_neg-reg_MDM_2/4.
 IPR003121; SWIB_MDM2_domain.
 IPR001876; Znf_RanBP2.
 IPR001841; Znf_RING.
 IPR013083; Znf_RING/FYVE/PHD. 
Pfam
 PF02201; SWIB
 PF00641; zf-RanBP 
SMART
 SM00184; RING 
PROSITE
 PS01358; ZF_RANBP2_1
 PS50199; ZF_RANBP2_2
 PS00518; ZF_RING_1
 PS50089; ZF_RING_2 
PRINTS