MDM2_DANRE
ID MDM2_DANRE Reviewed; 445 AA.
AC O42354;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=E3 ubiquitin-protein ligase Mdm2;
DE EC=2.3.2.27;
DE AltName: Full=Double minute 2 protein;
DE AltName: Full=RING-type E3 ubiquitin transferase Mdm2 {ECO:0000305};
DE AltName: Full=p53-binding protein Mdm2;
GN Name=mdm2;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Neel H., Piette J.;
RT "Partial cDNA nucleotide sequence of the zebrafish homolog of Mdm2.";
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Lin Y.T., Chou C.M., Leu J.H., Tsai S.C., Huang C.J.;
RT "A gene encoding MDM2-like protein from zebrafish.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
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 -!- SIMILARITY: Belongs to the MDM2/MDM4 family. {ECO:0000305}.
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DR EMBL; AF010255; AAB64176.1; -; mRNA.
DR EMBL; AF356346; AAM00198.1; -; mRNA.
DR PDB; 7AH2; X-ray; 2.87 A; AAA/BBB=377-445.
DR PDBsum; 7AH2; -.
DR AlphaFoldDB; O42354; -.
DR SMR; O42354; -.
DR STRING; 7955.ENSDARP00000108555; -.
DR ZFIN; ZDB-GENE-990415-153; mdm2.
DR eggNOG; ENOG502QQNV; Eukaryota.
DR InParanoid; O42354; -.
DR Reactome; R-DRE-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-DRE-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-DRE-2559585; Oncogene Induced Senescence.
DR Reactome; R-DRE-3232142; SUMOylation of ubiquitinylation proteins.
DR Reactome; R-DRE-5689880; Ub-specific processing proteases.
DR Reactome; R-DRE-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-DRE-6804757; Regulation of TP53 Degradation.
DR Reactome; R-DRE-69541; Stabilization of p53.
DR Reactome; R-DRE-8941858; Regulation of RUNX3 expression and activity.
DR PRO; PR:O42354; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
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:0002039; F:p53 binding; IBA:GO_Central.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ZFIN.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IMP:ZFIN.
DR GO; GO:1902254; P:negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator; IGI:ZFIN.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:InterPro.
DR GO; GO:0035775; P:pronephric glomerulus morphogenesis; IMP:ZFIN.
DR GO; GO:0051726; P:regulation of cell cycle; IEA:InterPro.
DR GO; GO:0031647; P:regulation of protein stability; IGI:ZFIN.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0010165; P:response to X-ray; IGI:ZFIN.
DR CDD; cd16783; mRING-HC-C2H2C4_MDM2; 1.
DR Gene3D; 1.10.245.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
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 PIRSF; PIRSF500700; MDM2; 1.
DR PIRSF; PIRSF006748; p53_MDM_2/4; 1.
DR SUPFAM; SSF47592; SSF47592; 1.
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..445
FT /note="E3 ubiquitin-protein ligase Mdm2"
FT /id="PRO_0000157335"
FT DOMAIN 19..102
FT /note="SWIB/MDM2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01273"
FT ZN_FING 274..303
FT /note="RanBP2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT ZN_FING 392..433
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 106..168
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 188..224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 190..279
FT /note="ARF-binding"
FT REGION 222..306
FT /note="Region II"
FT REGION 313..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 160..166
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 171..183
FT /note="Nuclear export signal"
FT MOTIF 420..427
FT /note="Nucleolar localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 136..168
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 313..341
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 445 AA; 49950 MW; 6FA8175A8A8E6261 CRC64;
MATESCLSSS QISKVDNEKL VRPKVQLKSL LEDAGADKDV FTMKEVMFYL GKYIMSKELY
DKQQQHIVHC GEDPLGAVLG VKSFSVKEPR ALFALINRNL VTVKNPESQS TFSEPRSQSE
PDRGPGDTDS DSRSSTSQQQ RRRRRSSDPE SSSAEDESRE RRKRHKSDSF SLTFDDSLSW
CVIGGLHRER GNSESSDANS NSDVGISRSE GSEESEDSDS DSDNFSVEFE VESINSDAYS
ENDVDSVPGE NEIYEVTIFA EDEDSFDEDT EITEADYWKC PKCDQFNPPL PRHCKSCWTV
RADWLPETHS NWENLSRNTR TNPEDTSVTT TPNTTFEKKL SKPSSPLPET DDGVDVPTPP
LLRRGSSQEE TPELERFNSL EACLPATCLE PCVICQSRPK NGCIVHGRTG HLMACYTCAK
KLKNRNKLCP VCREPIQSVV LTYMS
