MDM2_HUMAN
ID MDM2_HUMAN Reviewed; 491 AA.
AC Q00987; A6NL51; A8K2S6; Q13226; Q13297; Q13298; Q13299; Q13300; Q13301;
AC Q53XW0; Q71TW9; Q8WYJ1; Q8WYJ2; Q9UGI3; Q9UMT8;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 263.
DE RecName: Full=E3 ubiquitin-protein ligase Mdm2;
DE EC=2.3.2.27 {ECO:0000269|PubMed:12821780};
DE AltName: Full=Double minute 2 protein;
DE Short=Hdm2;
DE AltName: Full=Oncoprotein Mdm2;
DE AltName: Full=RING-type E3 ubiquitin transferase Mdm2 {ECO:0000305};
DE AltName: Full=p53-binding protein Mdm2;
GN Name=MDM2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MDM2).
RC TISSUE=Colon;
RX PubMed=1614537; DOI=10.1038/358080a0;
RA Oliner J.D., Kinzler K.W., Meltzer P.S., George D.L., Vogelstein B.;
RT "Amplification of a gene encoding a p53-associated protein in human
RT sarcomas.";
RL Nature 358:80-83(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MDM2-A; MDM2-B; MDM2-C; MDM2-D AND
RP MDM2-E).
RC TISSUE=Ovarian carcinoma;
RX PubMed=8705862; DOI=10.1038/nm0896-912;
RA Sigalas I., Calvert A.H., Anderson J.J., Neal D.E., Lunec J.;
RT "Alternatively spliced mdm2 transcripts with loss of p53 binding domain
RT sequences: transforming ability and frequent detection in human cancer.";
RL Nat. Med. 2:912-917(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MDM2-ALPHA).
RX PubMed=10597303; DOI=10.1038/sj.onc.1203182;
RA Veldhoen N., Metcalfe S., Milner J.;
RT "A novel exon within the mdm2 gene modulates translation initiation in
RT vitro and disrupts the p53-binding domain of mdm2 protein.";
RL Oncogene 18:7026-7033(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MDM2-F AND MDM2-G), AND INTERACTION
RP WITH TP53.
RX PubMed=11351297; DOI=10.1002/ijc.1271;
RA Tamborini E., Della Torre G., Lavarino C., Azzarelli A., Carpinelli P.,
RA Pierotti M.A., Pilotti S.;
RT "Analysis of the molecular species generated by MDM2 gene amplification in
RT liposarcomas.";
RL Int. J. Cancer 92:790-796(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MDM2).
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MDM2).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 11).
RC TISSUE=Rhabdomyosarcoma;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
RX PubMed=7651818; DOI=10.1093/nar/23.14.2584;
RA Zauberman A., Flusberg D., Haupt Y., Barak Y., Oren M.;
RT "A functional p53-responsive intronic promoter is contained within the
RT human mdm2 gene.";
RL Nucleic Acids Res. 23:2584-2592(1995).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
RX PubMed=9270029;
RA Landers J.E., Cassel S.L., George D.L.;
RT "Translational enhancement of mdm2 oncogene expression in human tumor cells
RT containing a stabilized wild-type p53 protein.";
RL Cancer Res. 57:3562-3568(1997).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-491 (ISOFORM MDM2-A1).
RX PubMed=15315825; DOI=10.1016/j.gene.2004.05.015;
RA Liang H., Atkins H., Abdel-Fattah R., Jones S.N., Lunec J.;
RT "Genomic organisation of the human MDM2 oncogene and relationship to its
RT alternatively spliced mRNAs.";
RL Gene 338:217-223(2004).
RN [13]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 301-481.
RX PubMed=11087894; DOI=10.1016/s0027-5107(00)00112-3;
RA Taubert H., Kappler M., Meye A., Bartel F., Schlott T., Lautenschlaeger C.,
RA Bache M., Schmidt H., Wuerl P.;
RT "A MboII polymorphism in exon 11 of the human MDM2 gene occurring in normal
RT blood donors and in soft tissue sarcoma patients: an indication for an
RT increased cancer susceptibility?";
RL Mutat. Res. 456:39-44(2000).
RN [14]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH TP53.
RX PubMed=7689721;
RA Olson D.C., Marechal V., Momand J., Chen J., Romocki C., Levine A.J.;
RT "Identification and characterization of multiple mdm-2 proteins and mdm-2-
RT p53 protein complexes.";
RL Oncogene 8:2353-2360(1993).
RN [15]
RP MUTAGENESIS OF CYS-464.
RX PubMed=9450543; DOI=10.1016/s0014-5793(97)01480-4;
RA Honda R., Tanaka H., Yasuda H.;
RT "Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53.";
RL FEBS Lett. 420:25-27(1997).
RN [16]
RP MUTAGENESIS OF CYS-441 AND CYS-478.
RX PubMed=10608892; DOI=10.1074/jbc.274.53.38189;
RA Sharp D.A., Kratowicz S.A., Sank M.J., George D.L.;
RT "Stabilization of the MDM2 oncoprotein by interaction with the structurally
RT related MDMX protein.";
RL J. Biol. Chem. 274:38189-38196(1999).
RN [17]
RP PHOSPHORYLATION BY ATM.
RX PubMed=10611322; DOI=10.1073/pnas.96.26.14973;
RA Khosravi R., Maya R., Gottlieb T., Oren M., Shiloh Y., Shkedy D.;
RT "Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation in
RT response to DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:14973-14977(1999).
RN [18]
RP MUTAGENESIS.
RX PubMed=10722742; DOI=10.1074/jbc.275.12.8945;
RA Fang S., Jensen J.P., Ludwig R.L., Vousden K.H., Weissman A.M.;
RT "Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and
RT p53.";
RL J. Biol. Chem. 275:8945-8951(2000).
RN [19]
RP NUCLEOLAR LOCALIZATION SIGNAL.
RX PubMed=10707090; DOI=10.1038/35004057;
RA Lohrum M.A.E., Ashcroft M., Kubbutat M.H.G., Vousden K.H.;
RT "Identification of a cryptic nucleolar-localization signal in MDM2.";
RL Nat. Cell Biol. 2:179-181(2000).
RN [20]
RP MUTAGENESIS OF CYS-449.
RX PubMed=10723139; DOI=10.1038/sj.onc.1203464;
RA Honda R., Yasuda H.;
RT "Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on
RT the RING finger domain of the ligase.";
RL Oncogene 19:1473-1476(2000).
RN [21]
RP PHOSPHORYLATION AT SER-240; SER-242; SER-246; SER-260 AND SER-262.
RX PubMed=12167711; DOI=10.1128/mcb.22.17.6170-6182.2002;
RA Blattner C., Hay T., Meek D.W., Lane D.P.;
RT "Hypophosphorylation of Mdm2 augments p53 stability.";
RL Mol. Cell. Biol. 22:6170-6182(2002).
RN [22]
RP INTERACTION WITH HIV-1 TAT (MICROBIAL INFECTION).
RX PubMed=12883554; DOI=10.1038/ncb1023;
RA Bres V., Kiernan R.E., Linares L.K., Chable-Bessia C., Plechakova O.,
RA Treand C., Emiliani S., Peloponese J.-M., Jeang K.-T., Coux O.,
RA Scheffner M., Benkirane M.;
RT "A non-proteolytic role for ubiquitin in Tat-mediated transactivation of
RT the HIV-1 promoter.";
RL Nat. Cell Biol. 5:754-761(2003).
RN [23]
RP FUNCTION IN UBIQUITINATION OF IGF1R, CATALYTIC ACTIVITY, AND INTERACTION
RP WITH IGF1R.
RX PubMed=12821780; DOI=10.1073/pnas.1431613100;
RA Girnita L., Girnita A., Larsson O.;
RT "Mdm2-dependent ubiquitination and degradation of the insulin-like growth
RT factor 1 receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:8247-8252(2003).
RN [24]
RP INTERACTION WITH FHIT.
RX PubMed=15313915; DOI=10.1158/0008-5472.can-04-0195;
RA Nishizaki M., Sasaki J., Fang B., Atkinson E.N., Minna J.D., Roth J.A.,
RA Ji L.;
RT "Synergistic tumor suppression by coexpression of FHIT and p53 coincides
RT with FHIT-mediated MDM2 inactivation and p53 stabilization in human non-
RT small cell lung cancer cells.";
RL Cancer Res. 64:5745-5752(2004).
RN [25]
RP INVOLVEMENT IN SUSCEPTIBILITY TO ACCELERATED TUMOR FORMATION.
RX PubMed=15550242; DOI=10.1016/j.cell.2004.11.022;
RA Bond G.L., Hu W., Bond E.E., Robins H., Lutzker S.G., Arva N.C.,
RA Bargonetti J., Bartel F., Taubert H., Wuerl P., Onel K., Yip L.,
RA Hwang S.J., Strong L.C., Lozano G., Levine A.J.;
RT "A single nucleotide polymorphism in the MDM2 promoter attenuates the p53
RT tumor suppressor pathway and accelerates tumor formation in humans.";
RL Cell 119:591-602(2004).
RN [26]
RP INTERACTION WITH DAXX.
RX PubMed=15364927; DOI=10.1074/jbc.m406743200;
RA Zhao L.Y., Liu J., Sidhu G.S., Niu Y., Liu Y., Wang R., Liao D.;
RT "Negative regulation of p53 functions by Daxx and the involvement of
RT MDM2.";
RL J. Biol. Chem. 279:50566-50579(2004).
RN [27]
RP FUNCTION, INTERACTION WITH USP7, AND DEUBIQUITINATION BY USP7.
RX PubMed=15053880; DOI=10.1016/s1097-2765(04)00157-1;
RA Li M., Brooks C.L., Kon N., Gu W.;
RT "A dynamic role of HAUSP in the p53-Mdm2 pathway.";
RL Mol. Cell 13:879-886(2004).
RN [28]
RP FUNCTION, INTERACTION WITH PML AND RPL11, AND SUBCELLULAR LOCATION.
RX PubMed=15195100; DOI=10.1038/ncb1147;
RA Bernardi R., Scaglioni P.P., Bergmann S., Horn H.F., Vousden K.H.,
RA Pandolfi P.P.;
RT "PML regulates p53 stability by sequestering Mdm2 to the nucleolus.";
RL Nat. Cell Biol. 6:665-672(2004).
RN [29]
RP INTERACTION WITH ARRB1 AND ARRB2.
RX PubMed=15878855; DOI=10.1074/jbc.m501129200;
RA Girnita L., Shenoy S.K., Sehat B., Vasilcanu R., Girnita A.,
RA Lefkowitz R.J., Larsson O.;
RT "{beta}-Arrestin is crucial for ubiquitination and down-regulation of the
RT insulin-like growth factor-1 receptor by acting as adaptor for the MDM2 E3
RT ligase.";
RL J. Biol. Chem. 280:24412-24419(2005).
RN [30]
RP INTERACTION WITH WWOX AND TP53.
RX PubMed=16219768; DOI=10.1074/jbc.m505590200;
RA Chang N.-S., Doherty J., Ensign A., Schultz L., Hsu L.-J., Hong Q.;
RT "WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-,
RT and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds
RT and stabilizes serine 46-phosphorylated p53.";
RL J. Biol. Chem. 280:43100-43108(2005).
RN [31]
RP FUNCTION, AND INTERACTION WITH PSMA3.
RX PubMed=16337594; DOI=10.1016/j.molcel.2005.10.017;
RA Sdek P., Ying H., Chang D.L., Qiu W., Zheng H., Touitou R., Allday M.J.,
RA Xiao Z.X.;
RT "MDM2 promotes proteasome-dependent ubiquitin-independent degradation of
RT retinoblastoma protein.";
RL Mol. Cell 20:699-708(2005).
RN [32]
RP FUNCTION, INTERACTION WITH MTBP, AND MUTAGENESIS OF CYS-464.
RX PubMed=15632057; DOI=10.1128/mcb.25.2.545-553.2005;
RA Brady M., Vlatkovic N., Boyd M.T.;
RT "Regulation of p53 and MDM2 activity by MTBP.";
RL Mol. Cell. Biol. 25:545-553(2005).
RN [33]
RP INTERACTION WITH CDK5RAP3 AND CDKN2A/ARF.
RX PubMed=16173922; DOI=10.1042/bj20050960;
RA Wang J., He X., Luo Y., Yarbrough W.G.;
RT "A novel ARF-binding protein (LZAP) alters ARF regulation of HDM2.";
RL Biochem. J. 393:489-501(2006).
RN [34]
RP UBIQUITINATION, INTERACTION WITH PYHIN1, AND MUTAGENESIS OF CYS-464.
RX PubMed=16479015; DOI=10.1128/mcb.26.5.1979-1996.2006;
RA Ding Y., Lee J.-F., Lu H., Lee M.-H., Yan D.-H.;
RT "Interferon-inducible protein IFIXalpha1 functions as a negative regulator
RT of HDM2.";
RL Mol. Cell. Biol. 26:1979-1996(2006).
RN [35]
RP IDENTIFICATION IN A COMPLEX WITH DAXX AND USP7, INTERACTION WITH DAXX, AND
RP SUBCELLULAR LOCATION.
RX PubMed=16845383; DOI=10.1038/ncb1442;
RA Tang J., Qu L.K., Zhang J., Wang W., Michaelson J.S., Degenhardt Y.Y.,
RA El-Deiry W.S., Yang X.;
RT "Critical role for Daxx in regulating Mdm2.";
RL Nat. Cell Biol. 8:855-862(2006).
RN [36]
RP INTERACTION WITH CDKN2AIP.
RX PubMed=17460193; DOI=10.1196/annals.1395.033;
RA Kamrul H.M., Wadhwa R., Kaul S.C.;
RT "CARF binds to three members (ARF, p53, and HDM2) of the p53 tumor-
RT suppressor pathway.";
RL Ann. N. Y. Acad. Sci. 1100:312-315(2007).
RN [37]
RP FUNCTION, INTERACTION WITH USP2, UBIQUITINATION, AND DEUBIQUITINATION BY
RP USP2.
RX PubMed=17290220; DOI=10.1038/sj.emboj.7601567;
RA Stevenson L.F., Sparks A., Allende-Vega N., Xirodimas D.P., Lane D.P.,
RA Saville M.K.;
RT "The deubiquitinating enzyme USP2a regulates the p53 pathway by targeting
RT Mdm2.";
RL EMBO J. 26:976-986(2007).
RN [38]
RP INVOLVEMENT IN SUSCEPTIBILITY TO ACCELERATED TUMOR FORMATION AND
RP LI-FRAUMENI SYNDROME.
RX PubMed=17003841; DOI=10.1038/sj.ejhg.5201715;
RA Ruijs M.W., Schmidt M.K., Nevanlinna H., Tommiska J., Aittomaki K.,
RA Pruntel R., Verhoef S., Van't Veer L.J.;
RT "The single-nucleotide polymorphism 309 in the MDM2 gene contributes to the
RT Li-Fraumeni syndrome and related phenotypes.";
RL Eur. J. Hum. Genet. 15:110-114(2007).
RN [39]
RP INTERACTION WITH TBRG1.
RX PubMed=17110379; DOI=10.1074/jbc.m609612200;
RA Tompkins V.S., Hagen J., Frazier A.A., Lushnikova T., Fitzgerald M.P.,
RA di Tommaso A.D., Ladeveze V., Domann F.E., Eischen C.M., Quelle D.E.;
RT "A novel nuclear interactor of ARF and MDM2 (NIAM) that maintains
RT chromosomal stability.";
RL J. Biol. Chem. 282:1322-1333(2007).
RN [40]
RP INTERACTION WITH RBBP6.
RX PubMed=17470788; DOI=10.1073/pnas.0701916104;
RA Li L., Deng B., Xing G., Teng Y., Tian C., Cheng X., Yin X., Yang J.,
RA Gao X., Zhu Y., Sun Q., Zhang L., Yang X., He F.;
RT "PACT is a negative regulator of p53 and essential for cell growth and
RT embryonic development.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:7951-7956(2007).
RN [41]
RP INTERACTION WITH RFFL AND RNF34, AND AUTOUBIQUITINATION.
RX PubMed=18382127; DOI=10.4161/cc.7.5.5701;
RA Yang W., Dicker D.T., Chen J., El-Deiry W.S.;
RT "CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing
RT MDM2.";
RL Cell Cycle 7:670-682(2008).
RN [42]
RP IDENTIFICATION IN A COMPLEX WITH DAXX; RASSF1 AND USP7, INTERACTION WITH
RP RASSF1; USP7 AND DAXX, AND SUBCELLULAR LOCATION.
RX PubMed=18566590; DOI=10.1038/emboj.2008.115;
RA Song M.S., Song S.J., Kim S.Y., Oh H.J., Lim D.S.;
RT "The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by
RT disrupting the MDM2-DAXX-HAUSP complex.";
RL EMBO J. 27:1863-1874(2008).
RN [43]
RP RETRACTION NOTICE OF PUBMED:18566590, AND CAUTION.
RX PubMed=18768758; DOI=10.1091/mbc.e08-01-0067;
RA Zweitzig D.R., Shcherbik N., Haines D.S.;
RT "AAA ATPase p97 and adaptor UBXD1 suppress MDM2 ubiquitination and
RT degradation and promote constitutive p53 turnover.";
RL Mol. Biol. Cell 19:5029-5029(2008).
RN [44]
RP PHOSPHORYLATION AT SER-386; SER-395; SER-407; THR-419; SER-425 AND SER-429.
RX PubMed=19816404; DOI=10.1038/emboj.2009.294;
RA Cheng Q., Chen L., Li Z., Lane W.S., Chen J.;
RT "ATM activates p53 by regulating MDM2 oligomerization and E3
RT processivity.";
RL EMBO J. 28:3857-3867(2009).
RN [45]
RP FUNCTION, INTERACTION WITH RYBP, AND IDENTIFICATION IN A COMPLEX WITH RYBP
RP AND TP53.
RX PubMed=19098711; DOI=10.1038/embor.2008.231;
RA Chen D., Zhang J., Li M., Rayburn E.R., Wang H., Zhang R.;
RT "RYBP stabilizes p53 by modulating MDM2.";
RL EMBO Rep. 10:166-172(2009).
RN [46]
RP FUNCTION, AND INTERACTION WITH MTA1.
RX PubMed=19837670; DOI=10.1074/jbc.m109.056499;
RA Li D.Q., Divijendra Natha Reddy S., Pakala S.B., Wu X., Zhang Y.,
RA Rayala S.K., Kumar R.;
RT "MTA1 coregulator regulates p53 stability and function.";
RL J. Biol. Chem. 284:34545-34552(2009).
RN [47]
RP PHOSPHORYLATION AT SER-166 BY SGK1.
RX PubMed=19756449; DOI=10.1007/s00109-009-0525-5;
RA Amato R., D'Antona L., Porciatti G., Agosti V., Menniti M., Rinaldo C.,
RA Costa N., Bellacchio E., Mattarocci S., Fuiano G., Soddu S., Paggi M.G.,
RA Lang F., Perrotti N.;
RT "Sgk1 activates MDM2-dependent p53 degradation and affects cell
RT proliferation, survival, and differentiation.";
RL J. Mol. Med. 87:1221-1239(2009).
RN [48]
RP INTERACTION WITH HHV-8 PROTEIN VIRF4 (MICROBIAL INFECTION).
RX PubMed=19369353; DOI=10.1128/jvi.02353-08;
RA Lee H.R., Toth Z., Shin Y.C., Lee J.S., Chang H., Gu W., Oh T.K., Kim M.H.,
RA Jung J.U.;
RT "Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor
RT 4 targets MDM2 to deregulate the p53 tumor suppressor pathway.";
RL J. Virol. 83:6739-6747(2009).
RN [49]
RP FUNCTION, INTERACTION WITH APEX1, AND MUTAGENESIS OF CYS-464.
RX PubMed=19219073; DOI=10.1038/onc.2009.5;
RA Busso C.S., Iwakuma T., Izumi T.;
RT "Ubiquitination of mammalian AP endonuclease (APE1) regulated by the p53-
RT MDM2 signaling pathway.";
RL Oncogene 28:1616-1625(2009).
RN [50]
RP IDENTIFICATION.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [51]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [52]
RP FUNCTION, AND INTERACTION WITH SNAI1.
RX PubMed=20385133; DOI=10.1016/j.febslet.2010.04.006;
RA Lim S.O., Kim H., Jung G.;
RT "p53 inhibits tumor cell invasion via the degradation of snail protein in
RT hepatocellular carcinoma.";
RL FEBS Lett. 584:2231-2236(2010).
RN [53]
RP FUNCTION IN DYRK2 UBIQUITINATION, AND INTERACTION WITH DYRK2.
RX PubMed=19965871; DOI=10.1074/jbc.m109.042341;
RA Taira N., Yamamoto H., Yamaguchi T., Miki Y., Yoshida K.;
RT "ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the
RT apoptotic response to DNA damage.";
RL J. Biol. Chem. 285:4909-4919(2010).
RN [54]
RP INTERACTION WITH TRIM28 IN THE TRIM28/KAP1-ERBB4-MDM2 COMPLEX AND WITH TP53
RP IN THE TRIM28/KAP1-MDM2-P53/TP53 COMPLEX, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=20858735; DOI=10.1158/1541-7786.mcr-10-0042;
RA Gilmore-Hebert M., Ramabhadran R., Stern D.F.;
RT "Interactions of ErbB4 and Kap1 connect the growth factor and DNA damage
RT response pathways.";
RL Mol. Cancer Res. 8:1388-1398(2010).
RN [55]
RP FUNCTION, INTERACTION WITH TP53 AND RFWD3, AND MUTAGENESIS OF CYS-464.
RX PubMed=20173098; DOI=10.1073/pnas.0912094107;
RA Fu X., Yucer N., Liu S., Li M., Yi P., Mu J.J., Yang T., Chu J., Jung S.Y.,
RA O'Malley B.W., Gu W., Qin J., Wang Y.;
RT "RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53 stability in
RT response to DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:4579-4584(2010).
RN [56]
RP INTERACTION WITH USP2 AND MDM4.
RX PubMed=19838211; DOI=10.1038/onc.2009.330;
RA Allende-Vega N., Sparks A., Lane D.P., Saville M.K.;
RT "MdmX is a substrate for the deubiquitinating enzyme USP2a.";
RL Oncogene 29:432-441(2010).
RN [57]
RP FUNCTION, AND INTERACTION WITH SNAI1 AND NOTCH1.
RX PubMed=22128911; DOI=10.1186/1741-7007-9-83;
RA Lim S.O., Kim H.S., Quan X., Ahn S.M., Kim H., Hsieh D., Seong J.K.,
RA Jung G.;
RT "Notch1 binds and induces degradation of Snail in hepatocellular
RT carcinoma.";
RL BMC Biol. 9:83-83(2011).
RN [58]
RP INTERACTION WITH TRIM13, AND UBIQUITINATION.
RX PubMed=21333377; DOI=10.1016/j.ejcb.2010.12.001;
RA Joo H.M., Kim J.Y., Jeong J.B., Seong K.M., Nam S.Y., Yang K.H., Kim C.S.,
RA Kim H.S., Jeong M., An S., Jin Y.W.;
RT "Ret finger protein 2 enhances ionizing radiation-induced apoptosis via
RT degradation of AKT and MDM2.";
RL Eur. J. Cell Biol. 90:420-431(2011).
RN [59]
RP SUBUNIT.
RX PubMed=24120868; DOI=10.1016/j.celrep.2013.08.049;
RA Sloan K.E., Bohnsack M.T., Watkins N.J.;
RT "The 5S RNP couples p53 homeostasis to ribosome biogenesis and nucleolar
RT stress.";
RL Cell Rep. 5:237-247(2013).
RN [60]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [61]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH PML.
RX PubMed=22869143; DOI=10.1038/onc.2012.332;
RA Yang Q., Liao L., Deng X., Chen R., Gray N.S., Yates J.R. III, Lee J.D.;
RT "BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2
RT interaction.";
RL Oncogene 32:3156-3164(2013).
RN [62]
RP INTERACTION WITH RPL23A.
RX PubMed=26203195; DOI=10.1074/jbc.m115.637280;
RA Datta D., Anbarasu K., Rajabather S., Priya R.S., Desai P., Mahalingam S.;
RT "Nucleolar GTP-binding protein-1 (NGP-1) promotes G1 to S phase transition
RT by activating cyclin-dependent kinase inhibitor p21 Cip1/Waf1.";
RL J. Biol. Chem. 290:21536-21552(2015).
RN [63]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NDUFS1, MUTAGENESIS OF
RP GLY-58 AND CYS-464, AUTOUBIQUITINATION, AND REGION.
RX PubMed=30879903; DOI=10.1016/j.molcel.2019.02.012;
RA Elkholi R., Abraham-Enachescu I., Trotta A.P., Rubio-Patino C.,
RA Mohammed J.N., Luna-Vargas M.P.A., Gelles J.D., Kaminetsky J.R.,
RA Serasinghe M.N., Zou C., Ali S., McStay G.P., Pfleger C.M., Chipuk J.E.;
RT "MDM2 Integrates Cellular Respiration and Apoptotic Signaling through
RT NDUFS1 and the Mitochondrial Network.";
RL Mol. Cell 74:452-465(2019).
RN [64]
RP INVOLVEMENT IN LSKB.
RX PubMed=28846075; DOI=10.1172/jci92171;
RA Lessel D., Wu D., Trujillo C., Ramezani T., Lessel I., Alwasiyah M.K.,
RA Saha B., Hisama F.M., Rading K., Goebel I., Schuetz P., Speit G.,
RA Hoegel J., Thiele H., Nuernberg G., Nuernberg P., Hammerschmidt M., Zhu Y.,
RA Tong D.R., Katz C., Martin G.M., Oshima J., Prives C., Kubisch C.;
RT "Dysfunction of the MDM2/p53 axis is linked to premature aging.";
RL J. Clin. Invest. 127:3598-3608(2017).
RN [65]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 25-109 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).
RN [66]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 224-232 IN COMPLEX WITH USP7, AND
RP INTERACTION WITH USP7.
RX PubMed=16402859; DOI=10.1371/journal.pbio.0040027;
RA Hu M., Gu L., Li M., Jeffrey P.D., Gu W., Shi Y.;
RT "Structural basis of competitive recognition of p53 and MDM2 by HAUSP/USP7:
RT implications for the regulation of the p53-MDM2 pathway.";
RL PLoS Biol. 4:228-239(2006).
RN [67]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 145-150 IN COMPLEX WITH USP7, AND
RP INTERACTION WITH USP7.
RX PubMed=16474402; DOI=10.1038/nsmb1067;
RA Sheng Y., Saridakis V., Sarkari F., Duan S., Wu T., Arrowsmith C.H.,
RA Frappier L.;
RT "Molecular recognition of p53 and MDM2 by USP7/HAUSP.";
RL Nat. Struct. Mol. Biol. 13:285-291(2006).
CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination of
CC p53/TP53, leading to its degradation by the proteasome. Inhibits
CC p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by
CC binding its transcriptional activation domain. Also acts as a ubiquitin
CC ligase E3 toward itself and ARRB1. Permits the nuclear export of
CC p53/TP53. Promotes proteasome-dependent ubiquitin-independent
CC degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated
CC apoptosis by inducing its ubiquitination and degradation. Component of
CC the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53.
CC Also a component of the TRIM28/KAP1-ERBB4-MDM2 complex which links
CC growth factor and DNA damage response pathways. Mediates ubiquitination
CC and subsequent proteasome degradation of DYRK2 in nucleus.
CC Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal
CC degradation (PubMed:12821780, PubMed:15053880, PubMed:15195100,
CC PubMed:15632057, PubMed:16337594, PubMed:17290220, PubMed:19098711,
CC PubMed:19219073, PubMed:19837670, PubMed:19965871, PubMed:20173098,
CC PubMed:20385133, PubMed:20858735, PubMed:22128911). Ubiquitinates DCX,
CC leading to DCX degradation and reduction of the dendritic spine density
CC of olfactory bulb granule cells (By similarity). Ubiquitinates DLG4,
CC leading to proteasomal degradation of DLG4 which is required for AMPA
CC receptor endocytosis (By similarity). Negatively regulates NDUFS1,
CC leading to decreased mitochondrial respiration, marked oxidative
CC stress, and commitment to the mitochondrial pathway of apoptosis
CC (PubMed:30879903). Binds NDUFS1 leading to its cytosolic retention
CC rather than mitochondrial localization resulting in decreased
CC supercomplex assembly (interactions between complex I and complex III),
CC decreased complex I activity, ROS production, and apoptosis
CC (PubMed:30879903). {ECO:0000250|UniProtKB:P23804,
CC ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880,
CC ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15632057,
CC ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:17290220,
CC ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073,
CC ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19965871,
CC ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133,
CC ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:22128911,
CC ECO:0000269|PubMed:30879903}.
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:0000269|PubMed:12821780};
CC -!- SUBUNIT: Interacts with p53/TP53, TP73/p73, RBL5 and RP11. Binds
CC specifically to RNA. Can interact with RB1, E1A-associated protein
CC EP300 and the E2F1 transcription factor. Forms a ternary complex with
CC p53/TP53 and WWOX. Interacts with CDKN2AIP, RFWD3, USP7, PYHIN1, and
CC RBBP6. Interacts with ARRB1 and ARRB2. Interacts with PSMA3. Found in a
CC trimeric complex with MDM2, MDM4 and USP2. Interacts with USP2 (via N-
CC terminus and C-terminus). Interacts with MDM4. Part of a complex with
CC MDM2, DAXX, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and
CC USP7. Interacts directly with DAXX and USP7. Interacts (via C-terminus)
CC with RASSF1 isoform A (via N-terminus); the interaction is independent
CC of TP53. Interacts with APEX1; leading to its ubiquitination and
CC degradation. Interacts with RYBP; this inhibits ubiquitination of TP53.
CC Identified in a complex with RYBP and p53/TP53. Also a component of the
CC TRIM28/KAP1-MDM2-p53/TP53 complex involved in regulating p53/TP53
CC stabilization and activity. Binds directly both p53/TP53 and TRIM28.
CC Component of the TRIM28/KAP1-ERBB4-MDM2 complex involved in connecting
CC growth factor responses with DNA damage. Interacts directly with both
CC TRIM28 and ERBB4 in the complex. Interacts with DYRK2. Interacts with
CC IGF1R. Interacts with TRIM13; the interaction ubiquitinates MDM2
CC leading to its proteasomal degradation. Interacts with SNAI1; this
CC interaction promotes SNAI1 ubiquitination. Interacts with NOTCH1 (via
CC intracellular domain). Interacts with FHIT. Interacts with RFFL and
CC RNF34; the interaction stabilizes MDM2. Interacts with CDK5RAP3 and
CC CDKN2A/ARF; form a ternary complex involved in regulation of p53/TP53
CC (PubMed:16173922). Interacts with MTA1. Interacts with AARB2. Interacts
CC with MTBP. Interacts with PML. Interacts with TBRG1. Interacts with the
CC 5S RNP which is composed of the 5S RNA, RPL5 and RPL11; the interaction
CC is direct, occurs in the nucleoplasm and negatively regulates MDM2-
CC mediated TP53 ubiquitination and degradation (PubMed:15195100,
CC PubMed:24120868). Interacts with ADGRB1; the interaction results in
CC inhibition of MDM2-mediated ubiquitination and degradation of
CC DLG4/PSD95, promoting DLG4 stability and regulating synaptic plasticity
CC (By similarity). Interacts with RPL23A; this interaction may promote
CC p53/TP53 polyubiquitination (PubMed:26203195). Interacts with NDUFS1
CC (PubMed:30879903). {ECO:0000250|UniProtKB:P23804,
CC ECO:0000269|PubMed:11351297, ECO:0000269|PubMed:12821780,
CC ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15195100,
CC ECO:0000269|PubMed:15313915, ECO:0000269|PubMed:15364927,
CC ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:15878855,
CC ECO:0000269|PubMed:16173922, ECO:0000269|PubMed:16219768,
CC ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:16402859,
CC ECO:0000269|PubMed:16474402, ECO:0000269|PubMed:16479015,
CC ECO:0000269|PubMed:16845383, ECO:0000269|PubMed:17110379,
CC ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:17460193,
CC ECO:0000269|PubMed:17470788, ECO:0000269|PubMed:18382127,
CC ECO:0000269|PubMed:18566590, ECO:0000269|PubMed:19098711,
CC ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19837670,
CC ECO:0000269|PubMed:19838211, ECO:0000269|PubMed:19965871,
CC ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133,
CC ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:21333377,
CC ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:22869143,
CC ECO:0000269|PubMed:24120868, ECO:0000269|PubMed:26203195,
CC ECO:0000269|PubMed:30879903, ECO:0000269|PubMed:7689721,
CC ECO:0000269|PubMed:8875929}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes virus 8 protein v-
CC IRF4. {ECO:0000269|PubMed:19369353}.
CC -!- SUBUNIT: (Microbial infection) Interacts with and ubiquitinates HIV-1
CC Tat. {ECO:0000269|PubMed:12883554}.
CC -!- INTERACTION:
CC Q00987; P31749: AKT1; NbExp=4; IntAct=EBI-389668, EBI-296087;
CC Q00987; P10275: AR; NbExp=2; IntAct=EBI-389668, EBI-608057;
CC Q00987; P49407: ARRB1; NbExp=3; IntAct=EBI-389668, EBI-743313;
CC Q00987; Q9Y297: BTRC; NbExp=9; IntAct=EBI-389668, EBI-307461;
CC Q00987; P42574: CASP3; NbExp=2; IntAct=EBI-389668, EBI-524064;
CC Q00987; Q8N726: CDKN2A; NbExp=5; IntAct=EBI-389668, EBI-625922;
CC Q00987; P48729: CSNK1A1; NbExp=3; IntAct=EBI-389668, EBI-1383726;
CC Q00987; P48729-2: CSNK1A1; NbExp=3; IntAct=EBI-389668, EBI-2040168;
CC Q00987; P48730: CSNK1D; NbExp=6; IntAct=EBI-389668, EBI-751621;
CC Q00987; P49674: CSNK1E; NbExp=3; IntAct=EBI-389668, EBI-749343;
CC Q00987; Q13616: CUL1; NbExp=3; IntAct=EBI-389668, EBI-359390;
CC Q00987; Q9UER7: DAXX; NbExp=18; IntAct=EBI-389668, EBI-77321;
CC Q00987; P78352: DLG4; NbExp=3; IntAct=EBI-389668, EBI-80389;
CC Q00987; P68104: EEF1A1; NbExp=9; IntAct=EBI-389668, EBI-352162;
CC Q00987; P03372: ESR1; NbExp=2; IntAct=EBI-389668, EBI-78473;
CC Q00987; P15311: EZR; NbExp=3; IntAct=EBI-389668, EBI-1056902;
CC Q00987; Q9UKB1: FBXW11; NbExp=4; IntAct=EBI-389668, EBI-355189;
CC Q00987; Q00688: FKBP3; NbExp=2; IntAct=EBI-389668, EBI-1044081;
CC Q00987; Q9BVP2: GNL3; NbExp=3; IntAct=EBI-389668, EBI-641642;
CC Q00987; Q9NVN8: GNL3L; NbExp=8; IntAct=EBI-389668, EBI-746682;
CC Q00987; Q5T7V8: GORAB; NbExp=6; IntAct=EBI-389668, EBI-3917143;
CC Q00987; P25098: GRK2; NbExp=4; IntAct=EBI-389668, EBI-3904795;
CC Q00987; P61978: HNRNPK; NbExp=2; IntAct=EBI-389668, EBI-304185;
CC Q00987; Q8N9B5: JMY; NbExp=2; IntAct=EBI-389668, EBI-866435;
CC Q00987; P05412: JUN; NbExp=3; IntAct=EBI-389668, EBI-852823;
CC Q00987; P17535: JUND; NbExp=3; IntAct=EBI-389668, EBI-2682803;
CC Q00987; Q9BY89: KIAA1671; NbExp=3; IntAct=EBI-389668, EBI-8796741;
CC Q00987; Q00987: MDM2; NbExp=4; IntAct=EBI-389668, EBI-389668;
CC Q00987; O15151: MDM4; NbExp=10; IntAct=EBI-389668, EBI-398437;
CC Q00987; P19338: NCL; NbExp=8; IntAct=EBI-389668, EBI-346967;
CC Q00987; P06748: NPM1; NbExp=5; IntAct=EBI-389668, EBI-78579;
CC Q00987; Q15466: NR0B2; NbExp=4; IntAct=EBI-389668, EBI-3910729;
CC Q00987; P49757: NUMB; NbExp=9; IntAct=EBI-389668, EBI-915016;
CC Q00987; Q96FW1: OTUB1; NbExp=5; IntAct=EBI-389668, EBI-1058491;
CC Q00987; P53350: PLK1; NbExp=7; IntAct=EBI-389668, EBI-476768;
CC Q00987; P29590: PML; NbExp=6; IntAct=EBI-389668, EBI-295890;
CC Q00987; P29590-5: PML; NbExp=6; IntAct=EBI-389668, EBI-304008;
CC Q00987; O15297: PPM1D; NbExp=4; IntAct=EBI-389668, EBI-1551512;
CC Q00987; Q13362: PPP2R5C; NbExp=5; IntAct=EBI-389668, EBI-1266156;
CC Q00987; P25788: PSMA3; NbExp=2; IntAct=EBI-389668, EBI-348380;
CC Q00987; P61289: PSME3; NbExp=8; IntAct=EBI-389668, EBI-355546;
CC Q00987; Q9NS23: RASSF1; NbExp=5; IntAct=EBI-389668, EBI-367363;
CC Q00987; P06400: RB1; NbExp=5; IntAct=EBI-389668, EBI-491274;
CC Q00987; Q6PCD5: RFWD3; NbExp=2; IntAct=EBI-389668, EBI-2129159;
CC Q00987; Q9Y4L5: RNF115; NbExp=3; IntAct=EBI-389668, EBI-2129242;
CC Q00987; P62913: RPL11; NbExp=11; IntAct=EBI-389668, EBI-354380;
CC Q00987; P62829: RPL23; NbExp=3; IntAct=EBI-389668, EBI-353303;
CC Q00987; P46777: RPL5; NbExp=5; IntAct=EBI-389668, EBI-358018;
CC Q00987; P42677: RPS27; NbExp=5; IntAct=EBI-389668, EBI-356336;
CC Q00987; Q71UM5: RPS27L; NbExp=6; IntAct=EBI-389668, EBI-355126;
CC Q00987; P23396: RPS3; NbExp=8; IntAct=EBI-389668, EBI-351193;
CC Q00987; P62081: RPS7; NbExp=15; IntAct=EBI-389668, EBI-354360;
CC Q00987; Q7LG56: RRM2B; NbExp=2; IntAct=EBI-389668, EBI-9009083;
CC Q00987; Q7LG56-1: RRM2B; NbExp=2; IntAct=EBI-389668, EBI-15741413;
CC Q00987; Q8N488: RYBP; NbExp=11; IntAct=EBI-389668, EBI-752324;
CC Q00987; Q92736: RYR2; NbExp=2; IntAct=EBI-389668, EBI-1170425;
CC Q00987; P23297: S100A1; NbExp=2; IntAct=EBI-389668, EBI-743686;
CC Q00987; P29034: S100A2; NbExp=2; IntAct=EBI-389668, EBI-752230;
CC Q00987; P26447: S100A4; NbExp=3; IntAct=EBI-389668, EBI-717058;
CC Q00987; P06703: S100A6; NbExp=2; IntAct=EBI-389668, EBI-352877;
CC Q00987; P04271: S100B; NbExp=2; IntAct=EBI-389668, EBI-458391;
CC Q00987; Q01105: SET; NbExp=2; IntAct=EBI-389668, EBI-1053182;
CC Q00987; P04637: TP53; NbExp=97; IntAct=EBI-389668, EBI-366083;
CC Q00987; O15350: TP73; NbExp=4; IntAct=EBI-389668, EBI-389606;
CC Q00987; P0CG48: UBC; NbExp=6; IntAct=EBI-389668, EBI-3390054;
CC Q00987; O75604: USP2; NbExp=4; IntAct=EBI-389668, EBI-743272;
CC Q00987; Q93009: USP7; NbExp=35; IntAct=EBI-389668, EBI-302474;
CC Q00987; P29067: Arrb2; Xeno; NbExp=4; IntAct=EBI-389668, EBI-1636616;
CC Q00987; Q06486: Csnk1d; Xeno; NbExp=2; IntAct=EBI-389668, EBI-2910316;
CC Q00987; Q62446: Fkbp3; Xeno; NbExp=4; IntAct=EBI-389668, EBI-8313562;
CC Q00987; Q61937: Npm1; Xeno; NbExp=2; IntAct=EBI-389668, EBI-626362;
CC Q00987; PRO_0000283876 [P0C6X5]: rep; Xeno; NbExp=3; IntAct=EBI-389668, EBI-25622115;
CC Q00987; Q2HR73: vIRF-4; Xeno; NbExp=2; IntAct=EBI-389668, EBI-9001898;
CC Q00987; Q6P5F9: Xpo1; Xeno; NbExp=4; IntAct=EBI-389668, EBI-2550236;
CC Q00987-11; Q6PCD5: RFWD3; NbExp=5; IntAct=EBI-5279149, EBI-2129159;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Cytoplasm
CC {ECO:0000269|PubMed:30879903}. Nucleus, nucleolus. Nucleus
CC {ECO:0000269|PubMed:30879903}. Note=Expressed predominantly in the
CC nucleoplasm. Interaction with ARF(P14) results in the localization of
CC both proteins to the nucleolus. The nucleolar localization signals in
CC both ARF(P14) and MDM2 may be necessary to allow efficient nucleolar
CC localization of both proteins. Colocalizes with RASSF1 isoform A in the
CC nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=11;
CC Name=Mdm2;
CC IsoId=Q00987-1; Sequence=Displayed;
CC Name=Mdm2-A;
CC IsoId=Q00987-2; Sequence=VSP_003208;
CC Name=Mdm2-A1;
CC IsoId=Q00987-3; Sequence=VSP_003208, VSP_003214;
CC Name=Mdm2-B;
CC IsoId=Q00987-4; Sequence=VSP_003209;
CC Name=Mdm2-C;
CC IsoId=Q00987-5; Sequence=VSP_003211;
CC Name=Mdm2-D;
CC IsoId=Q00987-6; Sequence=VSP_003210;
CC Name=Mdm2-E;
CC IsoId=Q00987-7; Sequence=VSP_003212, VSP_003213;
CC Name=Mdm2-alpha;
CC IsoId=Q00987-8; Sequence=VSP_003207;
CC Name=Mdm2-F;
CC IsoId=Q00987-9; Sequence=VSP_022578;
CC Name=Mdm2-G;
CC IsoId=Q00987-10; Sequence=VSP_022579;
CC Name=11;
CC IsoId=Q00987-11; Sequence=VSP_037997;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Isoform Mdm2-A, isoform Mdm2-B, isoform
CC Mdm2-C, isoform Mdm2-D, isoform Mdm2-E, isoform Mdm2-F and isoform
CC Mdm2-G are observed in a range of cancers but absent in normal tissues.
CC -!- INDUCTION: By DNA damage.
CC -!- DOMAIN: Region I is sufficient for binding p53 and inhibiting its G1
CC arrest and apoptosis functions. It also binds p73 and E2F1. Region II
CC contains most of a central acidic region required for interaction with
CC ribosomal protein L5 and a putative C4-type zinc finger. The RING
CC finger domain which coordinates two molecules of zinc interacts
CC specifically with RNA whether or not zinc is present and mediates the
CC heterooligomerization with MDM4. It is also essential for its ubiquitin
CC ligase E3 activity toward p53 and itself.
CC -!- PTM: Phosphorylation on Ser-166 by SGK1 activates ubiquitination of
CC p53/TP53. Phosphorylated at multiple sites near the RING domain by ATM
CC upon DNA damage; this prevents oligomerization and E3 ligase
CC processivity and impedes constitutive p53/TP53 degradation.
CC {ECO:0000269|PubMed:10611322, ECO:0000269|PubMed:12167711,
CC ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:19756449,
CC ECO:0000269|PubMed:19816404}.
CC -!- PTM: Autoubiquitination leads to proteasomal degradation; resulting in
CC p53/TP53 activation it may be regulated by SFN. Also ubiquitinated by
CC TRIM13. Deubiquitinated by USP2 leads to its accumulation and increases
CC deubiquitination and degradation of p53/TP53. Deubiquitinated by USP7
CC leading to its stabilization. {ECO:0000269|PubMed:18382127,
CC ECO:0000269|PubMed:30879903}.
CC -!- POLYMORPHISM: A polymorphism in the MDM2 promoter is associated with
CC susceptibility to accelerated tumor formation in both hereditary and
CC sporadic cancers [MIM:614401]. It also contributes to susceptibility to
CC Li-Fraumeni syndrome, in patients carrying a TP53 germline mutation.
CC -!- DISEASE: Note=Seems to be amplified in certain tumors (including soft
CC tissue sarcomas, osteosarcomas and gliomas). A higher frequency of
CC splice variants lacking p53 binding domain sequences was found in late-
CC stage and high-grade ovarian and bladder carcinomas. Four of the splice
CC variants show loss of p53 binding.
CC -!- DISEASE: Lessel-Kubisch syndrome (LSKB) [MIM:618681]: An autosomal
CC recessive progeroid syndrome characterized by short stature, pinched
CC facial features, prematurely gray hair, scleroderma-like skin changes,
CC small kidneys and consecutive kidney failure, followed by severe
CC arterial hypertension. {ECO:0000269|PubMed:28846075}. Note=The disease
CC may be caused by variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: MDM2 RING finger mutations that failed to ubiquitinate
CC p53 in vitro did not target p53 for degradation when expressed in
CC cells.
CC -!- MISCELLANEOUS: [Isoform Mdm2-F]: Does not interact with p53/TP53.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the MDM2/MDM4 family. {ECO:0000305}.
CC -!- CAUTION: Was reported to interact with UBXN6 but the corresponding
CC article has been retracted (PubMed:18768758).
CC -!- CAUTION: A report observed N-glycosylation at Asn-349
CC (PubMed:19139490). However, as the protein is not extracellular,
CC additional evidence is required to confirm this result.
CC {ECO:0000305|PubMed:19139490}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MDM2ID115ch12q15.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mdm2/";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Mdm2 entry;
CC URL="https://en.wikipedia.org/wiki/Mdm2";
CC ---------------------------------------------------------------------------
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DR EMBL; M92424; AAA60568.1; -; mRNA.
DR EMBL; Z12020; CAA78055.1; -; mRNA.
DR EMBL; U33199; AAA75514.1; -; mRNA.
DR EMBL; U33200; AAA75515.1; -; mRNA.
DR EMBL; U33201; AAA75516.1; -; mRNA.
DR EMBL; U33202; AAA75517.1; -; mRNA.
DR EMBL; U33203; AAA75518.1; -; mRNA.
DR EMBL; AF092844; AAL40179.1; -; mRNA.
DR EMBL; AF092845; AAL40180.1; -; mRNA.
DR EMBL; AK290341; BAF83030.1; -; mRNA.
DR EMBL; BT007258; AAP35922.1; -; mRNA.
DR EMBL; AF527840; AAM78554.1; -; Genomic_DNA.
DR EMBL; AC025423; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009893; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; U28935; AAA82237.1; -; Genomic_DNA.
DR EMBL; U39736; AAA82061.1; -; Genomic_DNA.
DR EMBL; AF201370; AAF42995.1; -; mRNA.
DR EMBL; AJ251943; CAB64448.1; -; Genomic_DNA.
DR CCDS; CCDS61189.1; -. [Q00987-5]
DR CCDS; CCDS8986.2; -. [Q00987-11]
DR PIR; S24354; S24354.
DR RefSeq; NP_001138811.1; NM_001145339.2.
DR RefSeq; NP_001265391.1; NM_001278462.1. [Q00987-5]
DR RefSeq; NP_002383.2; NM_002392.5. [Q00987-11]
DR RefSeq; XP_005268929.1; XM_005268872.4.
DR RefSeq; XP_006719462.1; XM_006719399.3. [Q00987-8]
DR PDB; 1RV1; X-ray; 2.30 A; A/B/C=25-109.
DR PDB; 1T4E; X-ray; 2.60 A; A/B=17-111.
DR PDB; 1T4F; X-ray; 1.90 A; M=17-125.
DR PDB; 1YCR; X-ray; 2.60 A; A=17-125.
DR PDB; 1Z1M; NMR; -; A=1-118.
DR PDB; 2AXI; X-ray; 1.40 A; A=17-125.
DR PDB; 2C6A; NMR; -; A=290-335.
DR PDB; 2C6B; NMR; -; A=290-335.
DR PDB; 2F1Y; X-ray; 1.70 A; A=224-232.
DR PDB; 2FOP; X-ray; 2.10 A; B=145-150.
DR PDB; 2GV2; X-ray; 1.80 A; A=17-125.
DR PDB; 2HDP; NMR; -; A/B=429-491.
DR PDB; 2LZG; NMR; -; A=1-125.
DR PDB; 2M86; NMR; -; B=17-125.
DR PDB; 2MPS; NMR; -; A=3-109.
DR PDB; 2RUH; NMR; -; A=6-102.
DR PDB; 2VJE; X-ray; 2.20 A; A/C=428-491.
DR PDB; 2VJF; X-ray; 2.30 A; A/C=428-491.
DR PDB; 3EQS; X-ray; 1.65 A; A=25-109.
DR PDB; 3G03; X-ray; 1.80 A; A/C=18-125.
DR PDB; 3IUX; X-ray; 1.65 A; A/C=25-109.
DR PDB; 3IWY; X-ray; 1.93 A; A/C=25-109.
DR PDB; 3JZK; X-ray; 2.10 A; A=17-111.
DR PDB; 3JZR; X-ray; 2.10 A; A=17-125.
DR PDB; 3JZS; X-ray; 1.78 A; A=24-109.
DR PDB; 3LBK; X-ray; 2.30 A; A=18-111.
DR PDB; 3LBL; X-ray; 1.60 A; A/C/E=18-111.
DR PDB; 3LNJ; X-ray; 2.40 A; A/C/E=25-109.
DR PDB; 3LNZ; X-ray; 1.95 A; A/C/E/G/I/K/M/O=25-109.
DR PDB; 3MQS; X-ray; 2.40 A; D=394-403.
DR PDB; 3TJ2; X-ray; 2.10 A; A/C=18-111.
DR PDB; 3TPX; X-ray; 1.80 A; A/C/E=25-109.
DR PDB; 3TU1; X-ray; 1.60 A; A=18-125.
DR PDB; 3V3B; X-ray; 2.00 A; A/B=24-110.
DR PDB; 3VBG; X-ray; 2.80 A; A/B/C/D=25-109.
DR PDB; 3VZV; X-ray; 2.80 A; A/B=25-109.
DR PDB; 3W69; X-ray; 1.90 A; A/B=25-109.
DR PDB; 4DIJ; X-ray; 1.90 A; A/B=17-111.
DR PDB; 4ERE; X-ray; 1.80 A; A/B=17-111.
DR PDB; 4ERF; X-ray; 2.00 A; A/C/E=17-111.
DR PDB; 4HBM; X-ray; 1.90 A; A/B/C/D/E/F/G/H=6-125.
DR PDB; 4HFZ; X-ray; 2.69 A; A/C=17-125.
DR PDB; 4HG7; X-ray; 1.60 A; A=17-108.
DR PDB; 4JV7; X-ray; 2.20 A; A=18-111.
DR PDB; 4JV9; X-ray; 2.50 A; A=18-111.
DR PDB; 4JVE; X-ray; 2.30 A; A=18-111.
DR PDB; 4JVR; X-ray; 1.70 A; A/C/E=18-111.
DR PDB; 4JWR; X-ray; 2.35 A; A/B/C=17-111.
DR PDB; 4MDN; X-ray; 1.90 A; A=18-110.
DR PDB; 4MDQ; X-ray; 2.12 A; A=25-110.
DR PDB; 4OAS; X-ray; 1.70 A; A/C/E=17-111.
DR PDB; 4OBA; X-ray; 1.60 A; A/B/C=17-111.
DR PDB; 4OCC; X-ray; 1.80 A; A/C/E=17-111.
DR PDB; 4ODE; X-ray; 1.80 A; A=6-110.
DR PDB; 4ODF; X-ray; 2.20 A; A=6-110.
DR PDB; 4OGN; X-ray; 1.38 A; A=6-110.
DR PDB; 4OGT; X-ray; 1.54 A; A=6-110.
DR PDB; 4OGV; X-ray; 2.20 A; A/B/C=17-111.
DR PDB; 4OQ3; X-ray; 2.30 A; A/B/C/D=17-111.
DR PDB; 4QO4; X-ray; 1.70 A; A=17-111.
DR PDB; 4QOC; X-ray; 1.70 A; A/C/E/G/I/K=17-111.
DR PDB; 4UD7; X-ray; 1.60 A; A/B/C/D=17-125.
DR PDB; 4UE1; X-ray; 1.45 A; A/B/C/D=17-125.
DR PDB; 4UMN; X-ray; 1.99 A; A/B=6-125.
DR PDB; 4WT2; X-ray; 1.42 A; A=6-110.
DR PDB; 4XXB; X-ray; 2.40 A; B=290-437.
DR PDB; 4ZFI; X-ray; 2.00 A; A/B/C/D=18-113.
DR PDB; 4ZGK; X-ray; 2.00 A; A/B=18-114.
DR PDB; 4ZYC; X-ray; 1.95 A; A/B/C=17-111.
DR PDB; 4ZYF; X-ray; 1.80 A; A=17-111.
DR PDB; 4ZYI; X-ray; 1.67 A; A=17-111.
DR PDB; 5AFG; X-ray; 1.90 A; A=17-108.
DR PDB; 5C5A; X-ray; 1.15 A; A/B=20-111.
DR PDB; 5HMH; X-ray; 1.79 A; A/B=21-116.
DR PDB; 5HMI; X-ray; 1.74 A; A/B=18-116.
DR PDB; 5HMK; X-ray; 2.17 A; A/B=17-125.
DR PDB; 5J7F; X-ray; 2.00 A; A/B/C/D=1-125.
DR PDB; 5J7G; X-ray; 1.85 A; A/B/C/D=18-125.
DR PDB; 5LAV; X-ray; 1.73 A; A=19-111.
DR PDB; 5LAW; X-ray; 1.64 A; A=18-111.
DR PDB; 5LAY; X-ray; 2.71 A; A/B/C/D/E/F=17-111.
DR PDB; 5LAZ; X-ray; 1.66 A; A=18-111.
DR PDB; 5LN2; X-ray; 1.58 A; A=17-111.
DR PDB; 5MNJ; X-ray; 2.16 A; C/G=428-491.
DR PDB; 5OAI; X-ray; 2.00 A; A=18-113.
DR PDB; 5OC8; X-ray; 1.56 A; A=17-111.
DR PDB; 5SWK; X-ray; 1.92 A; A/B=1-150.
DR PDB; 5TRF; X-ray; 2.10 A; A/B/C/D/E=10-118.
DR PDB; 5UMM; X-ray; 1.65 A; A/C=25-109.
DR PDB; 5VK0; X-ray; 1.80 A; A/C/E/G/I/K/M/O/Q/S/U/W=25-109.
DR PDB; 5WTS; X-ray; 3.00 A; B=6-125.
DR PDB; 5XXK; X-ray; 1.66 A; A/B=6-125.
DR PDB; 5Z02; X-ray; 1.35 A; A=24-112.
DR PDB; 5ZXF; X-ray; 1.25 A; A=24-110.
DR PDB; 6AAW; X-ray; 2.00 A; A=6-125.
DR PDB; 6GGN; X-ray; 2.00 A; A=17-111.
DR PDB; 6H22; X-ray; 2.01 A; A/B=17-108.
DR PDB; 6HFA; X-ray; 1.79 A; A/B=17-111.
DR PDB; 6I29; X-ray; 2.10 A; A=17-111.
DR PDB; 6I3S; X-ray; 1.77 A; A=18-111.
DR PDB; 6IM9; X-ray; 3.30 A; B=6-125.
DR PDB; 6KZU; X-ray; 1.79 A; A=6-125.
DR PDB; 6Q96; X-ray; 1.80 A; A/B=17-111.
DR PDB; 6Q9H; X-ray; 2.00 A; A=17-111.
DR PDB; 6Q9L; X-ray; 1.13 A; A/B=17-111.
DR PDB; 6Q9O; X-ray; 1.21 A; A/B=17-111.
DR PDB; 6SQO; X-ray; 1.41 A; A/D=430-491.
DR PDB; 6T2D; X-ray; 1.80 A; A=24-109.
DR PDB; 6T2E; X-ray; 2.40 A; A=24-109.
DR PDB; 6T2F; X-ray; 2.09 A; A=24-109.
DR PDB; 6Y4Q; X-ray; 1.63 A; A/B=17-108.
DR PDB; 7AD0; X-ray; 2.07 A; A/B/C/D/E/F=24-113.
DR PDB; 7AI0; X-ray; 1.56 A; AAA/DDD=419-491.
DR PDB; 7AI1; X-ray; 2.07 A; AAA/DDD=419-491.
DR PDB; 7AYE; X-ray; 2.95 A; A=17-125.
DR PDB; 7BIR; X-ray; 2.02 A; A=17-109.
DR PDB; 7BIT; X-ray; 2.13 A; A=17-125.
DR PDB; 7BIV; X-ray; 1.64 A; A=17-109.
DR PDB; 7BJ0; X-ray; 2.00 A; A/B=17-125.
DR PDB; 7BJ6; X-ray; 1.59 A; A=17-109.
DR PDB; 7BMG; X-ray; 1.83 A; A=17-109.
DR PDB; 7KJM; X-ray; 1.40 A; A/C=25-109.
DR PDB; 7NA1; X-ray; 2.30 A; A/B=17-125.
DR PDB; 7NA2; X-ray; 1.86 A; A/B=17-125.
DR PDB; 7NA3; X-ray; 2.21 A; A=17-125.
DR PDB; 7NA4; X-ray; 1.84 A; A=17-125.
DR PDB; 7NUS; X-ray; 1.45 A; A/B/C=17-111.
DR PDBsum; 1RV1; -.
DR PDBsum; 1T4E; -.
DR PDBsum; 1T4F; -.
DR PDBsum; 1YCR; -.
DR PDBsum; 1Z1M; -.
DR PDBsum; 2AXI; -.
DR PDBsum; 2C6A; -.
DR PDBsum; 2C6B; -.
DR PDBsum; 2F1Y; -.
DR PDBsum; 2FOP; -.
DR PDBsum; 2GV2; -.
DR PDBsum; 2HDP; -.
DR PDBsum; 2LZG; -.
DR PDBsum; 2M86; -.
DR PDBsum; 2MPS; -.
DR PDBsum; 2RUH; -.
DR PDBsum; 2VJE; -.
DR PDBsum; 2VJF; -.
DR PDBsum; 3EQS; -.
DR PDBsum; 3G03; -.
DR PDBsum; 3IUX; -.
DR PDBsum; 3IWY; -.
DR PDBsum; 3JZK; -.
DR PDBsum; 3JZR; -.
DR PDBsum; 3JZS; -.
DR PDBsum; 3LBK; -.
DR PDBsum; 3LBL; -.
DR PDBsum; 3LNJ; -.
DR PDBsum; 3LNZ; -.
DR PDBsum; 3MQS; -.
DR PDBsum; 3TJ2; -.
DR PDBsum; 3TPX; -.
DR PDBsum; 3TU1; -.
DR PDBsum; 3V3B; -.
DR PDBsum; 3VBG; -.
DR PDBsum; 3VZV; -.
DR PDBsum; 3W69; -.
DR PDBsum; 4DIJ; -.
DR PDBsum; 4ERE; -.
DR PDBsum; 4ERF; -.
DR PDBsum; 4HBM; -.
DR PDBsum; 4HFZ; -.
DR PDBsum; 4HG7; -.
DR PDBsum; 4JV7; -.
DR PDBsum; 4JV9; -.
DR PDBsum; 4JVE; -.
DR PDBsum; 4JVR; -.
DR PDBsum; 4JWR; -.
DR PDBsum; 4MDN; -.
DR PDBsum; 4MDQ; -.
DR PDBsum; 4OAS; -.
DR PDBsum; 4OBA; -.
DR PDBsum; 4OCC; -.
DR PDBsum; 4ODE; -.
DR PDBsum; 4ODF; -.
DR PDBsum; 4OGN; -.
DR PDBsum; 4OGT; -.
DR PDBsum; 4OGV; -.
DR PDBsum; 4OQ3; -.
DR PDBsum; 4QO4; -.
DR PDBsum; 4QOC; -.
DR PDBsum; 4UD7; -.
DR PDBsum; 4UE1; -.
DR PDBsum; 4UMN; -.
DR PDBsum; 4WT2; -.
DR PDBsum; 4XXB; -.
DR PDBsum; 4ZFI; -.
DR PDBsum; 4ZGK; -.
DR PDBsum; 4ZYC; -.
DR PDBsum; 4ZYF; -.
DR PDBsum; 4ZYI; -.
DR PDBsum; 5AFG; -.
DR PDBsum; 5C5A; -.
DR PDBsum; 5HMH; -.
DR PDBsum; 5HMI; -.
DR PDBsum; 5HMK; -.
DR PDBsum; 5J7F; -.
DR PDBsum; 5J7G; -.
DR PDBsum; 5LAV; -.
DR PDBsum; 5LAW; -.
DR PDBsum; 5LAY; -.
DR PDBsum; 5LAZ; -.
DR PDBsum; 5LN2; -.
DR PDBsum; 5MNJ; -.
DR PDBsum; 5OAI; -.
DR PDBsum; 5OC8; -.
DR PDBsum; 5SWK; -.
DR PDBsum; 5TRF; -.
DR PDBsum; 5UMM; -.
DR PDBsum; 5VK0; -.
DR PDBsum; 5WTS; -.
DR PDBsum; 5XXK; -.
DR PDBsum; 5Z02; -.
DR PDBsum; 5ZXF; -.
DR PDBsum; 6AAW; -.
DR PDBsum; 6GGN; -.
DR PDBsum; 6H22; -.
DR PDBsum; 6HFA; -.
DR PDBsum; 6I29; -.
DR PDBsum; 6I3S; -.
DR PDBsum; 6IM9; -.
DR PDBsum; 6KZU; -.
DR PDBsum; 6Q96; -.
DR PDBsum; 6Q9H; -.
DR PDBsum; 6Q9L; -.
DR PDBsum; 6Q9O; -.
DR PDBsum; 6SQO; -.
DR PDBsum; 6T2D; -.
DR PDBsum; 6T2E; -.
DR PDBsum; 6T2F; -.
DR PDBsum; 6Y4Q; -.
DR PDBsum; 7AD0; -.
DR PDBsum; 7AI0; -.
DR PDBsum; 7AI1; -.
DR PDBsum; 7AYE; -.
DR PDBsum; 7BIR; -.
DR PDBsum; 7BIT; -.
DR PDBsum; 7BIV; -.
DR PDBsum; 7BJ0; -.
DR PDBsum; 7BJ6; -.
DR PDBsum; 7BMG; -.
DR PDBsum; 7KJM; -.
DR PDBsum; 7NA1; -.
DR PDBsum; 7NA2; -.
DR PDBsum; 7NA3; -.
DR PDBsum; 7NA4; -.
DR PDBsum; 7NUS; -.
DR AlphaFoldDB; Q00987; -.
DR BMRB; Q00987; -.
DR SMR; Q00987; -.
DR BioGRID; 110358; 637.
DR ComplexPortal; CPX-6093; p53-MDM2-MDM4 transcriptional regulation complex.
DR ComplexPortal; CPX-759; p53-MDM2 transcriptional regulation complex.
DR CORUM; Q00987; -.
DR DIP; DIP-392N; -.
DR ELM; Q00987; -.
DR IntAct; Q00987; 225.
DR MINT; Q00987; -.
DR STRING; 9606.ENSP00000258149; -.
DR BindingDB; Q00987; -.
DR ChEMBL; CHEMBL5023; -.
DR DrugBank; DB02872; Cis-[4,5-Bis-(4-Bromophenyl)-2-(2-Ethoxy-4-Methoxyphenyl)-4,5-Dihydroimidazol-1-Yl]-[4-(2-Hydroxyethyl)Piperazin-1-Yl]Methanone.
DR DrugBank; DB04144; Cis-[4,5-Bis-(4-Chlorophenyl)-2-(2-Isopropoxy-4-Methoxyphenyl)-4,5-Dihyd Roimidazol-1-Yl]-Piperazin-1-Yl-Methanone.
DR DrugBank; DB01593; Zinc.
DR DrugBank; DB14487; Zinc acetate.
DR DrugBank; DB14533; Zinc chloride.
DR DrugBank; DB14548; Zinc sulfate, unspecified form.
DR GuidetoPHARMACOLOGY; 3136; -.
DR MoonDB; Q00987; Predicted.
DR GlyConnect; 2034; 1 N-Linked glycan (1 site).
DR GlyGen; Q00987; 1 site, 2 N-linked glycans (1 site).
DR iPTMnet; Q00987; -.
DR PhosphoSitePlus; Q00987; -.
DR BioMuta; MDM2; -.
DR DMDM; 266516; -.
DR EPD; Q00987; -.
DR MassIVE; Q00987; -.
DR MaxQB; Q00987; -.
DR PaxDb; Q00987; -.
DR PeptideAtlas; Q00987; -.
DR PRIDE; Q00987; -.
DR ProteomicsDB; 57889; -. [Q00987-1]
DR ProteomicsDB; 57890; -. [Q00987-10]
DR ProteomicsDB; 57891; -. [Q00987-11]
DR ProteomicsDB; 57892; -. [Q00987-2]
DR ProteomicsDB; 57893; -. [Q00987-3]
DR ProteomicsDB; 57894; -. [Q00987-4]
DR ProteomicsDB; 57895; -. [Q00987-5]
DR ProteomicsDB; 57898; -. [Q00987-8]
DR ProteomicsDB; 57899; -. [Q00987-9]
DR Antibodypedia; 3664; 1834 antibodies from 47 providers.
DR CPTC; Q00987; 1 antibody.
DR DNASU; 4193; -.
DR Ensembl; ENST00000258149.11; ENSP00000258149.6; ENSG00000135679.27. [Q00987-11]
DR Ensembl; ENST00000299252.8; ENSP00000299252.4; ENSG00000135679.27. [Q00987-5]
DR Ensembl; ENST00000360430.6; ENSP00000353611.2; ENSG00000135679.27. [Q00987-2]
DR Ensembl; ENST00000393413.7; ENSP00000377065.3; ENSG00000135679.27. [Q00987-4]
DR Ensembl; ENST00000539479.6; ENSP00000444430.2; ENSG00000135679.27. [Q00987-1]
DR GeneID; 4193; -.
DR KEGG; hsa:4193; -.
DR MANE-Select; ENST00000258149.11; ENSP00000258149.6; NM_002392.6; NP_002383.2. [Q00987-11]
DR UCSC; uc001sui.6; human. [Q00987-1]
DR CTD; 4193; -.
DR DisGeNET; 4193; -.
DR GeneCards; MDM2; -.
DR HGNC; HGNC:6973; MDM2.
DR HPA; ENSG00000135679; Low tissue specificity.
DR MalaCards; MDM2; -.
DR MIM; 164785; gene.
DR MIM; 614401; phenotype.
DR MIM; 618681; phenotype.
DR neXtProt; NX_Q00987; -.
DR OpenTargets; ENSG00000135679; -.
DR Orphanet; 99970; Dedifferentiated liposarcoma.
DR Orphanet; 524; Li-Fraumeni syndrome.
DR Orphanet; 99971; Well-differentiated liposarcoma.
DR PharmGKB; PA30718; -.
DR VEuPathDB; HostDB:ENSG00000135679; -.
DR eggNOG; ENOG502QQNV; Eukaryota.
DR GeneTree; ENSGT00530000063539; -.
DR HOGENOM; CLU_043544_1_0_1; -.
DR InParanoid; Q00987; -.
DR OMA; LGELPCK; -.
DR OrthoDB; 1329283at2759; -.
DR PhylomeDB; Q00987; -.
DR TreeFam; TF105306; -.
DR BRENDA; 2.3.2.27; 2681.
DR PathwayCommons; Q00987; -.
DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-2559585; Oncogene Induced Senescence.
DR Reactome; R-HSA-3232118; SUMOylation of transcription factors.
DR Reactome; R-HSA-3232142; SUMOylation of ubiquitinylation proteins.
DR Reactome; R-HSA-399719; Trafficking of AMPA receptors.
DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-6804757; Regulation of TP53 Degradation.
DR Reactome; R-HSA-6804760; Regulation of TP53 Activity through Methylation.
DR Reactome; R-HSA-69541; Stabilization of p53.
DR Reactome; R-HSA-8941858; Regulation of RUNX3 expression and activity.
DR SignaLink; Q00987; -.
DR SIGNOR; Q00987; -.
DR BioGRID-ORCS; 4193; 210 hits in 1135 CRISPR screens.
DR ChiTaRS; MDM2; human.
DR EvolutionaryTrace; Q00987; -.
DR GeneWiki; Mdm2; -.
DR GenomeRNAi; 4193; -.
DR Pharos; Q00987; Tchem.
DR PRO; PR:Q00987; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q00987; protein.
DR Bgee; ENSG00000135679; Expressed in calcaneal tendon and 177 other tissues.
DR ExpressionAtlas; Q00987; baseline and differential.
DR Genevisible; Q00987; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0032991; C:protein-containing complex; IDA:CAFA.
DR GO; GO:0017053; C:transcription repressor complex; IPI:ComplexPortal.
DR GO; GO:0008097; F:5S rRNA binding; IDA:UniProtKB.
DR GO; GO:0097718; F:disordered domain specific binding; IPI:CAFA.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016874; F:ligase activity; IDA:UniProtKB.
DR GO; GO:0061663; F:NEDD8 ligase activity; IMP:CAFA.
DR GO; GO:0002039; F:p53 binding; IPI:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:CAFA.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; IDA:UniProtKB.
DR GO; GO:0019789; F:SUMO transferase activity; EXP:Reactome.
DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IDA:CAFA.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:1990000; P:amyloid fibril formation; IMP:CAFA.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:0003283; P:atrial septum development; IEA:Ensembl.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; IEA:Ensembl.
DR GO; GO:0001568; P:blood vessel development; IEA:Ensembl.
DR GO; GO:0001974; P:blood vessel remodeling; IEA:Ensembl.
DR GO; GO:0060411; P:cardiac septum morphogenesis; IEA:Ensembl.
DR GO; GO:0072717; P:cellular response to actinomycin D; IDA:CAFA.
DR GO; GO:0071480; P:cellular response to gamma radiation; IDA:CAFA.
DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IMP:UniProtKB.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; IEA:Ensembl.
DR GO; GO:0045184; P:establishment of protein localization; IDA:BHF-UCL.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL.
DR GO; GO:1902254; P:negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator; IMP:CAFA.
DR GO; GO:1901797; P:negative regulation of signal transduction by p53 class mediator; IDA:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; TAS:BHF-UCL.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:BHF-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; TAS:ARUK-UCL.
DR GO; GO:0051865; P:protein autoubiquitination; IMP:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IDA:BHF-UCL.
DR GO; GO:0034504; P:protein localization to nucleus; IDA:BHF-UCL.
DR GO; GO:0000209; P:protein polyubiquitination; TAS:ARUK-UCL.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB.
DR GO; GO:0051603; P:proteolysis involved in protein catabolic process; IMP:CAFA.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:BHF-UCL.
DR GO; GO:0002027; P:regulation of heart rate; IEA:Ensembl.
DR GO; GO:0042176; P:regulation of protein catabolic process; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0046677; P:response to antibiotic; IEP:UniProtKB.
DR GO; GO:0036369; P:transcription factor catabolic process; TAS:ParkinsonsUK-UCL.
DR GO; GO:0007089; P:traversing start control point of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0003281; P:ventricular septum development; IEA:Ensembl.
DR CDD; cd16783; mRING-HC-C2H2C4_MDM2; 1.
DR DisProt; DP00334; -.
DR DisProt; DP01133; -. [Q00987-11]
DR Gene3D; 1.10.245.10; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR IDEAL; IID00163; -.
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; Alternative splicing; Apoptosis; Cytoplasm;
KW Host-virus interaction; Metal-binding; Nucleus; Phosphoprotein;
KW Proto-oncogene; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..491
FT /note="E3 ubiquitin-protein ligase Mdm2"
FT /id="PRO_0000157332"
FT DOMAIN 26..109
FT /note="SWIB/MDM2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01273"
FT ZN_FING 299..328
FT /note="RanBP2-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00322"
FT ZN_FING 438..479
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT REGION 1..110
FT /note="Necessary for interaction with USP2"
FT REGION 1..101
FT /note="Sufficient to promote the mitochondrial pathway of
FT apoptosis"
FT /evidence="ECO:0000269|PubMed:30879903"
FT REGION 141..187
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 150..230
FT /note="Interaction with PYHIN1 and necessary for
FT interaction with RFFL and RNF34"
FT /evidence="ECO:0000269|PubMed:16479015,
FT ECO:0000269|PubMed:18382127"
FT REGION 170..306
FT /note="Interaction with MTBP"
FT /evidence="ECO:0000250"
FT REGION 210..304
FT /note="ARF-binding"
FT REGION 211..237
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 223..232
FT /note="Interaction with USP7"
FT REGION 242..331
FT /note="Region II"
FT REGION 253..274
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 276..491
FT /note="Necessary for interaction with USP2"
FT REGION 371..427
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 179..185
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 190..202
FT /note="Nuclear export signal"
FT MOTIF 466..473
FT /note="Nucleolar localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 145..161
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 162..187
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 211..225
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 380..408
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 409..425
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 166
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000269|PubMed:19756449,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 190
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23804"
FT MOD_RES 240
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12167711"
FT MOD_RES 242
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12167711"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12167711"
FT MOD_RES 260
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12167711"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12167711"
FT MOD_RES 386
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:19816404"
FT MOD_RES 395
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:19816404"
FT MOD_RES 407
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:19816404"
FT MOD_RES 419
FT /note="Phosphothreonine; by ATM"
FT /evidence="ECO:0000269|PubMed:19816404"
FT MOD_RES 425
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:19816404"
FT MOD_RES 429
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:19816404"
FT VAR_SEQ 1..61
FT /note="Missing (in isoform Mdm2-alpha)"
FT /evidence="ECO:0000303|PubMed:10597303"
FT /id="VSP_003207"
FT VAR_SEQ 1
FT /note="M -> MVRSRQM (in isoform 11)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037997"
FT VAR_SEQ 28..300
FT /note="Missing (in isoform Mdm2-B)"
FT /evidence="ECO:0000303|PubMed:8705862"
FT /id="VSP_003209"
FT VAR_SEQ 28..222
FT /note="Missing (in isoform Mdm2-A and isoform Mdm2-A1)"
FT /evidence="ECO:0000303|PubMed:15315825,
FT ECO:0000303|PubMed:8705862"
FT /id="VSP_003208"
FT VAR_SEQ 30..388
FT /note="Missing (in isoform Mdm2-D)"
FT /evidence="ECO:0000303|PubMed:8705862"
FT /id="VSP_003210"
FT VAR_SEQ 53..222
FT /note="Missing (in isoform Mdm2-C)"
FT /evidence="ECO:0000303|PubMed:8705862"
FT /id="VSP_003211"
FT VAR_SEQ 53..97
FT /note="Missing (in isoform Mdm2-F)"
FT /evidence="ECO:0000303|PubMed:11351297"
FT /id="VSP_022578"
FT VAR_SEQ 76..102
FT /note="YCSNDLLGDLFGVPSFSVKEHRKIYTM -> NDCANLFPLVDLSIRELYISN
FT YITLGI (in isoform Mdm2-E)"
FT /evidence="ECO:0000303|PubMed:8705862"
FT /id="VSP_003212"
FT VAR_SEQ 103..491
FT /note="Missing (in isoform Mdm2-E)"
FT /evidence="ECO:0000303|PubMed:8705862"
FT /id="VSP_003213"
FT VAR_SEQ 115..169
FT /note="Missing (in isoform Mdm2-G)"
FT /evidence="ECO:0000303|PubMed:11351297"
FT /id="VSP_022579"
FT VAR_SEQ 275..300
FT /note="Missing (in isoform Mdm2-A1)"
FT /evidence="ECO:0000303|PubMed:15315825"
FT /id="VSP_003214"
FT MUTAGEN 58
FT /note="G->A: No effect on its ability to induce apoptosis."
FT /evidence="ECO:0000269|PubMed:30879903"
FT MUTAGEN 305
FT /note="C->S: No loss of ubiquitin ligase E3 activity."
FT /evidence="ECO:0000269|PubMed:10722742"
FT MUTAGEN 374
FT /note="C->T: No loss of ubiquitin ligase E3 activity."
FT /evidence="ECO:0000269|PubMed:10722742"
FT MUTAGEN 438
FT /note="C->L: No loss of ubiquitin ligase E3 activity."
FT /evidence="ECO:0000269|PubMed:10722742"
FT MUTAGEN 441
FT /note="C->G: Fails to interact with MDM4."
FT /evidence="ECO:0000269|PubMed:10608892"
FT MUTAGEN 449
FT /note="C->A: Loss of ubiquitin ligase E3 activity."
FT /evidence="ECO:0000269|PubMed:10723139"
FT MUTAGEN 449
FT /note="C->S: No substantial decrease of ubiquitin ligase E3
FT activity."
FT /evidence="ECO:0000269|PubMed:10723139"
FT MUTAGEN 452
FT /note="H->A: Loss of ubiquitin ligase E3 activity."
FT /evidence="ECO:0000269|PubMed:10722742"
FT MUTAGEN 455
FT /note="T->A: Significant decrease of ubiquitin ligase E3
FT activity."
FT /evidence="ECO:0000269|PubMed:10722742"
FT MUTAGEN 457
FT /note="H->S: Loss of ubiquitin ligase E3 activity."
FT /evidence="ECO:0000269|PubMed:10722742"
FT MUTAGEN 461
FT /note="C->S: Loss of ubiquitin ligase E3 activity."
FT /evidence="ECO:0000269|PubMed:10722742"
FT MUTAGEN 464
FT /note="C->A: Loss of ubiquitin ligase E3 activity, enhances
FT protein stability. Does not inhibit interaction with APEX1,
FT but inhibits its ubiquitin ligase E3 activity on APEX1. No
FT effect on its ability to induce apoptosis."
FT /evidence="ECO:0000269|PubMed:15632057,
FT ECO:0000269|PubMed:16479015, ECO:0000269|PubMed:19219073,
FT ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:30879903,
FT ECO:0000269|PubMed:9450543"
FT MUTAGEN 475
FT /note="C->G: Loss of ubiquitin ligase E3 activity."
FT /evidence="ECO:0000269|PubMed:10722742"
FT MUTAGEN 478
FT /note="C->R: Fails to interact with MDM4."
FT /evidence="ECO:0000269|PubMed:10608892"
FT MUTAGEN 478
FT /note="C->S: Loss of ubiquitin ligase E3 activity."
FT /evidence="ECO:0000269|PubMed:10608892"
FT CONFLICT 17
FT /note="S -> P (in Ref. 10; AAA82237)"
FT /evidence="ECO:0000305"
FT STRAND 7..10
FT /evidence="ECO:0007829|PDB:4WT2"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:4WT2"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:2LZG"
FT HELIX 21..24
FT /evidence="ECO:0007829|PDB:6Q9L"
FT STRAND 27..30
FT /evidence="ECO:0007829|PDB:6Q9L"
FT HELIX 32..39
FT /evidence="ECO:0007829|PDB:6Q9L"
FT TURN 40..42
FT /evidence="ECO:0007829|PDB:6Q9L"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:6Q9L"
FT HELIX 50..63
FT /evidence="ECO:0007829|PDB:6Q9L"
FT TURN 64..67
FT /evidence="ECO:0007829|PDB:4ODF"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:6Q9L"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:6Q9L"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:3LBK"
FT HELIX 81..86
FT /evidence="ECO:0007829|PDB:6Q9L"
FT STRAND 89..92
FT /evidence="ECO:0007829|PDB:6Q9L"
FT HELIX 96..104
FT /evidence="ECO:0007829|PDB:6Q9L"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:6Q9L"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:2C6A"
FT HELIX 299..301
FT /evidence="ECO:0007829|PDB:4XXB"
FT TURN 306..308
FT /evidence="ECO:0007829|PDB:4XXB"
FT STRAND 314..318
FT /evidence="ECO:0007829|PDB:4XXB"
FT TURN 320..322
FT /evidence="ECO:0007829|PDB:4XXB"
FT HELIX 432..435
FT /evidence="ECO:0007829|PDB:6SQO"
FT TURN 439..441
FT /evidence="ECO:0007829|PDB:6SQO"
FT STRAND 442..444
FT /evidence="ECO:0007829|PDB:6SQO"
FT STRAND 448..452
FT /evidence="ECO:0007829|PDB:6SQO"
FT STRAND 455..460
FT /evidence="ECO:0007829|PDB:6SQO"
FT HELIX 462..470
FT /evidence="ECO:0007829|PDB:6SQO"
FT TURN 476..478
FT /evidence="ECO:0007829|PDB:6SQO"
FT STRAND 484..489
FT /evidence="ECO:0007829|PDB:6SQO"
SQ SEQUENCE 491 AA; 55233 MW; F37CE163876BC983 CRC64;
MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM KEVLFYLGQY
IMTKRLYDEK QQHIVYCSND LLGDLFGVPS FSVKEHRKIY TMIYRNLVVV NQQESSDSGT
SVSENRCHLE GGSDQKDLVQ ELQEEKPSSS HLVSRPSTSS RRRAISETEE NSDELSGERQ
RKRHKSDSIS LSFDESLALC VIREICCERS SSSESTGTPS NPDLDAGVSE HSGDWLDQDS
VSDQFSVEFE VESLDSEDYS LSEEGQELSD EDDEVYQVTV YQAGESDTDS FEEDPEISLA
DYWKCTSCNE MNPPLPSHCN RCWALRENWL PEDKGKDKGE ISEKAKLENS TQAEEGFDVP
DCKKTIVNDS RESCVEENDD KITQASQSQE SEDYSQPSTS SSIIYSSQED VKEFEREETQ
DKEESVESSL PLNAIEPCVI CQGRPKNGCI VHGKTGHLMA CFTCAKKLKK RNKPCPVCRQ
PIQMIVLTYF P
