MDM2_XENLA
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 03-AUG-2022, entry version 135.
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 PRIDE; P56273; -.
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:0000122; P:negative regulation of transcription by RNA polymerase II; 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; cd16783; mRING-HC-C2H2C4_MDM2; 1.
DR Gene3D; 1.10.245.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR IDEAL; IID50077; -.
DR InterPro; IPR028340; Mdm2.
DR InterPro; IPR015459; MDM2_E3_ligase.
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; PTHR13844:SF15; PTHR13844:SF15; 1.
DR Pfam; PF02201; SWIB; 1.
DR Pfam; PF00641; zf-RanBP; 1.
DR PIRSF; PIRSF500700; MDM2; 1.
DR PIRSF; PIRSF006748; p53_MDM_2/4; 1.
DR SUPFAM; SSF47592; SSF47592; 2.
DR SUPFAM; SSF90209; SSF90209; 1.
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
