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 27-MAR-2024, entry version 272. 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 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 [44] 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 [45] 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 [46] 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 [47] 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 [48] 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 [49] 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 [50] 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 [51] 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 [52] 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 [53] 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 [54] 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 [55] 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 [56] 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 [57] 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 [58] 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 [59] 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 [60] 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 [61] 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 [62] RP FUNCTION, AND INTERACTION WITH MORN3. RX PubMed=29681526; DOI=10.1016/j.chembiol.2018.03.010; RA Liang L., Wang H., Shi H., Li Z., Yao H., Bu Z., Song N., Li C., Xiang D., RA Zhang Y., Wang J., Hu Y., Xu Q., Ma Y., Cheng Z., Wang Y., Zhao S., RA Qian J., Chen Y., Fang J.Y., Xu J.; RT "A Designed Peptide Targets Two Types of Modifications of p53 with Anti- RT cancer Activity."; RL Cell Chem. Biol. 25:761-774.e5(2018). 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 CC (PubMed:29681526). Inhibits p53/TP53- and p73/TP73-mediated cell cycle CC arrest and apoptosis by binding its transcriptional activation domain. CC Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the CC nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin- CC independent degradation of retinoblastoma RB1 protein. Inhibits DAXX- CC mediated apoptosis by inducing its ubiquitination and degradation. CC Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in CC stabilizing p53/TP53. Also a component of the TRIM28/KAP1-ERBB4-MDM2 CC complex which links growth factor and DNA damage response pathways. CC Mediates ubiquitination and subsequent proteasome degradation of DYRK2 CC in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to CC proteasomal degradation (PubMed:12821780, PubMed:15053880, CC PubMed:15195100, PubMed:15632057, PubMed:16337594, PubMed:17290220, CC PubMed:19098711, PubMed:19219073, PubMed:19837670, PubMed:19965871, CC PubMed:20173098, PubMed:20385133, PubMed:20858735, PubMed:22128911). CC Ubiquitinates DCX, leading to DCX degradation and reduction of the CC dendritic spine density of olfactory bulb granule cells (By CC similarity). Ubiquitinates DLG4, leading to proteasomal degradation of CC DLG4 which is required for AMPA receptor endocytosis (By similarity). CC Negatively regulates NDUFS1, leading to decreased mitochondrial CC respiration, marked oxidative stress, and commitment to the CC mitochondrial pathway of apoptosis (PubMed:30879903). Binds NDUFS1 CC leading to its cytosolic retention rather than mitochondrial CC localization resulting in decreased supercomplex assembly (interactions CC between complex I and complex III), decreased complex I activity, ROS CC production, and apoptosis (PubMed:30879903). CC {ECO:0000250|UniProtKB:P23804, ECO:0000269|PubMed:12821780, CC ECO:0000269|PubMed:15053880, ECO:0000269|PubMed:15195100, CC ECO:0000269|PubMed:15632057, ECO:0000269|PubMed:16337594, CC ECO:0000269|PubMed:17290220, ECO:0000269|PubMed:19098711, CC ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19837670, CC ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, CC ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, CC ECO:0000269|PubMed:22128911, ECO:0000269|PubMed:29681526, 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). Interacts with MORN3; the interaction enhances the CC ubiquitination of p53/TP53 (PubMed:29681526). CC {ECO:0000250|UniProtKB:P23804, ECO:0000269|PubMed:11351297, CC ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880, CC ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15313915, CC ECO:0000269|PubMed:15364927, ECO:0000269|PubMed:15632057, CC ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16173922, CC ECO:0000269|PubMed:16219768, ECO:0000269|PubMed:16337594, CC ECO:0000269|PubMed:16402859, ECO:0000269|PubMed:16474402, CC ECO:0000269|PubMed:16479015, ECO:0000269|PubMed:16845383, CC ECO:0000269|PubMed:17110379, ECO:0000269|PubMed:17290220, CC ECO:0000269|PubMed:17460193, ECO:0000269|PubMed:17470788, CC ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:18566590, CC ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073, CC ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19838211, CC ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, CC ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, CC ECO:0000269|PubMed:21333377, ECO:0000269|PubMed:22128911, CC ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:24120868, CC ECO:0000269|PubMed:26203195, ECO:0000269|PubMed:29681526, 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=2; 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=7; 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=2; 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=110; 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=34; 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: 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="https://atlasgeneticsoncology.org/gene/115/MDM2"; 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 --------------------------------------------------------------------------- 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 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 CCDS; CCDS91724.1; -. [Q00987-1] 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. 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; 6YR6; X-ray; 1.75 A; B/D/F/H=180-192. 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 PDB; 7QDQ; X-ray; 1.26 A; A=20-111. DR PDB; 8AEU; X-ray; 2.00 A; A=18-113. DR PDB; 8BGU; EM; 4.10 A; F=1-491. DR PDB; 8EI9; X-ray; 3.90 A; B=17-111. DR PDB; 8EIA; X-ray; 3.60 A; B=17-111. DR PDB; 8EIB; X-ray; 3.76 A; B=17-111. DR PDB; 8EIC; X-ray; 2.62 A; B=17-111. DR PDB; 8F0Z; X-ray; 1.61 A; A=17-111. DR PDB; 8F10; X-ray; 1.28 A; A=17-111. DR PDB; 8F12; X-ray; 1.86 A; A=17-111. DR PDB; 8F13; X-ray; 1.40 A; A=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; 6YR6; -. 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 PDBsum; 7QDQ; -. DR PDBsum; 8AEU; -. DR PDBsum; 8BGU; -. DR PDBsum; 8EI9; -. DR PDBsum; 8EIA; -. DR PDBsum; 8EIB; -. DR PDBsum; 8EIC; -. DR PDBsum; 8F0Z; -. DR PDBsum; 8F10; -. DR PDBsum; 8F12; -. DR PDBsum; 8F13; -. DR AlphaFoldDB; Q00987; -. DR BMRB; Q00987; -. DR EMDB; EMD-16036; -. DR SMR; Q00987; -. DR BioGRID; 110358; 662. 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; 217. 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 GlyCosmos; Q00987; 1 site, 2 glycans. DR GlyGen; Q00987; 1 site, 2 N-linked glycans (1 site). DR iPTMnet; Q00987; -. DR PhosphoSitePlus; Q00987; -. DR BioMuta; MDM2; -. DR DMDM; 266516; -. DR CPTAC; CPTAC-5913; -. DR EPD; Q00987; -. DR MassIVE; Q00987; -. DR MaxQB; Q00987; -. DR PaxDb; 9606-ENSP00000258149; -. DR PeptideAtlas; 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; 2147 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 AGR; HGNC:6973; -. 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; DYWRCSK; -. DR OrthoDB; 2916169at2759; -. 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 Reactome; R-HSA-9768919; NPAS4 regulates expression of target genes. DR SignaLink; Q00987; -. DR SIGNOR; Q00987; -. DR BioGRID-ORCS; 4193; 213 hits in 1219 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 179 other cell types or tissues. DR ExpressionAtlas; Q00987; baseline and differential. 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:0042975; F:peroxisome proliferator activated receptor binding; IEA:Ensembl. DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB. DR GO; GO:0033612; F:receptor serine/threonine kinase binding; IEA:Ensembl. 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:0071312; P:cellular response to alkaloid; IEA:Ensembl. DR GO; GO:0071391; P:cellular response to estrogen stimulus; IEA:Ensembl. DR GO; GO:0071480; P:cellular response to gamma radiation; IDA:CAFA. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB. DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IEA:Ensembl. DR GO; GO:0071494; P:cellular response to UV-C; IEA:Ensembl. DR GO; GO:0071301; P:cellular response to vitamin B1; IEA:Ensembl. 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:0072537; P:fibroblast activation; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IBA:GO_Central. DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:1902254; P:negative regulation of intrinsic apoptotic signaling pathway by p53 class mediator; IMP:CAFA. DR GO; GO:0010977; P:negative regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0010955; P:negative regulation of protein processing; IEA:Ensembl. 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:0008284; P:positive regulation of cell population proliferation; TAS:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl. 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:0046827; P:positive regulation of protein export from nucleus; IEA:Ensembl. DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IEA:Ensembl. DR GO; GO:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IEA:Ensembl. 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:0016925; P:protein sumoylation; TAS:Reactome. 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:0010468; P:regulation of gene expression; IBA:GO_Central. 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:0046677; P:response to antibiotic; IEP:UniProtKB. DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl. DR GO; GO:0045472; P:response to ether; IEA:Ensembl. DR GO; GO:1904404; P:response to formaldehyde; IEA:Ensembl. DR GO; GO:0010039; P:response to iron ion; IEA:Ensembl. DR GO; GO:0032026; P:response to magnesium ion; IEA:Ensembl. DR GO; GO:0048545; P:response to steroid hormone; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:1990785; P:response to water-immersion restraint stress; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. 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; cd17672; MDM2; 1. DR CDD; cd16783; mRING-HC-C2H2C4_MDM2; 1. DR DisProt; DP00334; -. DR DisProt; DP01133; -. [Q00987-11] 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; IID00163; -. 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. DR Genevisible; Q00987; HS. 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 //