ID MDM2_XENLA Reviewed; 473 AA. AC P56273; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2000, sequence version 2. DT 27-MAR-2024, entry version 139. DE RecName: Full=E3 ubiquitin-protein ligase Mdm2; DE EC=2.3.2.27; DE AltName: Full=Double minute 2 protein; DE Short=Xdm2; DE AltName: Full=RING-type E3 ubiquitin transferase Mdm2 {ECO:0000305}; DE AltName: Full=p53-binding protein Mdm2; GN Name=mdm2; OS Xenopus laevis (African clawed frog). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia; OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus. OX NCBI_TaxID=8355; RN [1] RP NUCLEOTIDE SEQUENCE. RX PubMed=9136986; DOI=10.1038/sj.onc.1200967; RA Marechal V., Elenbaas B., Taneyhill L., Piette J., Mechali M., RA Nicolas J.-C., Levine A.J., Moreau J.; RT "Conservation of structural domains and biochemical activities of the MDM2 RT protein from Xenopus laevis."; RL Oncogene 14:1427-1433(1997). RN [2] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 13-119 IN COMPLEX WITH P53. RX PubMed=8875929; DOI=10.1126/science.274.5289.948; RA Kussie P.H., Gorina S., Marechal V., Elenbaas B., Moreau J., Levine A.J., RA Pavletich N.P.; RT "Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor RT transactivation domain."; RL Science 274:948-953(1996). CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of CC p53/TP53, leading to its degradation by the proteasome. CC {ECO:0000250|UniProtKB:Q00987}. CC -!- CATALYTIC ACTIVITY: CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; CC EC=2.3.2.27; Evidence={ECO:0000250|UniProtKB:Q00987}; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm CC {ECO:0000250|UniProtKB:P23804}. Cytoplasm CC {ECO:0000250|UniProtKB:P23804}. Nucleus, nucleolus CC {ECO:0000250|UniProtKB:P23804}. Nucleus {ECO:0000250|UniProtKB:Q00987}. CC -!- DEVELOPMENTAL STAGE: Expression increases from oocyte stage I/II to CC reach its maximum in oocyte stage v/vi in unfertilized eggs, and then CC progressively decreases to become undetectable at the gastrula stage. CC -!- SIMILARITY: Belongs to the MDM2/MDM4 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR PDB; 1TTV; NMR; -; A=13-119. DR PDB; 1YCQ; X-ray; 2.30 A; A=13-119. DR PDB; 4IPF; X-ray; 1.70 A; A=21-105. DR PDB; 4J3E; X-ray; 1.91 A; A=21-105. DR PDB; 4J74; X-ray; 1.20 A; A=21-105. DR PDB; 4J7D; X-ray; 1.25 A; A=21-105. DR PDB; 4J7E; X-ray; 1.63 A; A=21-105. DR PDB; 4JRG; X-ray; 1.90 A; A/B=21-105. DR PDB; 4JSC; X-ray; 2.50 A; A/B=21-105. DR PDB; 4LWT; X-ray; 1.60 A; A=21-105. DR PDB; 4LWU; X-ray; 1.14 A; A=21-105. DR PDB; 4LWV; X-ray; 2.32 A; A/B/C=21-105. DR PDBsum; 1TTV; -. DR PDBsum; 1YCQ; -. DR PDBsum; 4IPF; -. DR PDBsum; 4J3E; -. DR PDBsum; 4J74; -. DR PDBsum; 4J7D; -. DR PDBsum; 4J7E; -. DR PDBsum; 4JRG; -. DR PDBsum; 4JSC; -. DR PDBsum; 4LWT; -. DR PDBsum; 4LWU; -. DR PDBsum; 4LWV; -. DR AlphaFoldDB; P56273; -. DR BMRB; P56273; -. DR SMR; P56273; -. DR IntAct; P56273; 1. DR EvolutionaryTrace; P56273; -. DR Proteomes; UP000186698; Genome assembly. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IEA:InterPro. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro. DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:InterPro. DR GO; GO:0065008; P:regulation of biological quality; IEA:UniProt. DR GO; GO:0051726; P:regulation of cell cycle; IEA:InterPro. DR CDD; cd17672; MDM2; 1. DR CDD; cd16783; mRING-HC-C2H2C4_MDM2; 1. DR Gene3D; 1.10.245.10; SWIB/MDM2 domain; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR Gene3D; 2.30.30.380; Zn-finger domain of Sec23/24; 1. DR IDEAL; IID50077; -. DR InterPro; IPR028340; Mdm2. DR InterPro; IPR044080; MDM2_mRING-HC-C2H2C4. DR InterPro; IPR016495; p53_neg-reg_MDM_2/4. DR InterPro; IPR036885; SWIB_MDM2_dom_sf. DR InterPro; IPR003121; SWIB_MDM2_domain. DR InterPro; IPR001876; Znf_RanBP2. DR InterPro; IPR036443; Znf_RanBP2_sf. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR46858:SF13; E3 UBIQUITIN-PROTEIN LIGASE MDM2; 1. DR PANTHER; PTHR46858; OS05G0521000 PROTEIN; 1. DR Pfam; PF02201; SWIB; 1. DR Pfam; PF13920; zf-C3HC4_3; 1. DR Pfam; PF00641; zf-RanBP; 1. DR PIRSF; PIRSF500700; MDM2; 1. DR PIRSF; PIRSF006748; p53_MDM_2/4; 1. DR SUPFAM; SSF90209; Ran binding protein zinc finger-like; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR SUPFAM; SSF47592; SWIB/MDM2 domain; 2. DR PROSITE; PS51925; SWIB_MDM2; 1. DR PROSITE; PS01358; ZF_RANBP2_1; 1. DR PROSITE; PS50199; ZF_RANBP2_2; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Metal-binding; Nucleus; Reference proteome; KW Transferase; Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1..473 FT /note="E3 ubiquitin-protein ligase Mdm2" FT /id="PRO_0000157334" FT DOMAIN 22..105 FT /note="SWIB/MDM2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01273" FT ZN_FING 290..319 FT /note="RanBP2-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322" FT ZN_FING 420..461 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT REGION 140..181 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 205..285 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 230..322 FT /note="Region II" FT REGION 348..411 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 173..179 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 161..181 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 205..219 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 220..235 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 358..373 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 375..398 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT STRAND 24..26 FT /evidence="ECO:0007829|PDB:4JRG" FT HELIX 28..36 FT /evidence="ECO:0007829|PDB:4LWU" FT HELIX 46..59 FT /evidence="ECO:0007829|PDB:4LWU" FT STRAND 65..67 FT /evidence="ECO:0007829|PDB:4J74" FT STRAND 70..72 FT /evidence="ECO:0007829|PDB:4LWU" FT HELIX 77..82 FT /evidence="ECO:0007829|PDB:4LWU" FT STRAND 85..88 FT /evidence="ECO:0007829|PDB:4LWU" FT HELIX 92..100 FT /evidence="ECO:0007829|PDB:4LWU" FT STRAND 103..106 FT /evidence="ECO:0007829|PDB:1YCQ" SQ SEQUENCE 473 AA; 53464 MW; 7DA668DE8B3BEE01 CRC64; MNLTSTTNCL ENNHISTSDQ EKLVQPTPLL LSLLKSAGAQ KETFTMKEVI YHLGQYIMAK QLYDEKQQHI VHCSNDPLGE LFGVQEFSVK EPRRLYAMIS RNLVSANVKE SSEDIFGNVC CFPDKQSSQK EKLQELPDKL IAPASDSKPC NLSQRKSSNE TEEISSVDHP AEQQRKRHKS DSFSLTFDES LSWWVISGLR CDRNSSESTD SSSNSDPERH STNDNSEHDS DQFSVEFEVE SVCSDDYSPS GDEHGVSEEE EINDEVYQVT IYETEESETD SFDVDTEISE ADYWKCPECG EVNPPLPSYC PRCWTVRKDW LPEQRRKEPP PSKRKLLEIE EDEGFDVPDC KKSKLTSSQD TNVDKKEAEN IQNSESQETE DCSQPSTSGS IASCSQEVTK EDSSKESMES SLPLTSIDPC VICQTRPKNG CIVHGRTGHL MACYTCAKKL KKRNKPCPVC REPIQMIVLT YFS //