ID PML_HUMAN Reviewed; 882 AA. AC P29590; E9PBR7; P29591; P29592; P29593; Q00755; Q15959; Q59FP9; Q8WUA0; AC Q96S41; Q9BPW2; Q9BWP7; Q9BZX6; Q9BZX7; Q9BZX8; Q9BZX9; Q9BZY0; Q9BZY2; AC Q9BZY3; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 3. DT 27-MAR-2024, entry version 261. DE RecName: Full=Protein PML; DE AltName: Full=E3 SUMO-protein ligase PML; DE EC=2.3.2.- {ECO:0000269|PubMed:20972456, ECO:0000269|PubMed:28250117}; DE AltName: Full=Promyelocytic leukemia protein; DE AltName: Full=RING finger protein 71; DE AltName: Full=RING-type E3 SUMO transferase PML {ECO:0000305}; DE AltName: Full=Tripartite motif-containing protein 19; DE Short=TRIM19; GN Name=PML; Synonyms=MYL, PP8675, RNF71, TRIM19; 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 PML-3), AND DISEASE. RX PubMed=1652369; DOI=10.1016/0092-8674(91)90113-d; RA de The H., Lavau C., Marchio A., Chomienne C., Degos L., Dejean A.; RT "The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in RT acute promyelocytic leukemia encodes a functionally altered RAR."; RL Cell 66:675-684(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PML-1; PML-5 AND PML-8), CHROMOSOMAL RP TRANSLOCATION WITH RARA, DISEASE, AND VARIANT LEU-645. RX PubMed=1720570; DOI=10.1126/science.1720570; RA Goddard A.D., Borrow J., Freemont P.S., Solomon E.; RT "Characterization of a zinc finger gene disrupted by the t(15;17) in acute RT promyelocytic leukemia."; RL Science 254:1371-1374(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PML-4). RX PubMed=1311253; DOI=10.1002/j.1460-2075.1992.tb05095.x; RA Kastner P., Perez A., Lutz Y., Rochette-Egly C., Gaub M.P., Durand B., RA Lanotte M., Berger R., Chambon P.; RT "Structure, localization and transcriptional properties of two classes of RT retinoic acid receptor alpha fusion proteins in acute promyelocytic RT leukemia (APL): structural similarities with a new family of RT oncoproteins."; RL EMBO J. 11:629-642(1992). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PML-6). RX PubMed=1652368; DOI=10.1016/0092-8674(91)90112-c; RA Kakizuka A., Miller W.H. Jr., Umenono K., Warrell R.P. Jr., Frankel S.R., RA Murty V.V., Dmitrovsky E., Evans R.M.; RT "Chromosomal translocation t(15;17) in human acute promyelocytic leukemia RT fuses RAR alpha with a novel putative transcription factor, PML."; RL Cell 66:663-674(1991). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS PML-1; PML-2; PML-4; PML-5; PML-6; RP PML-7; PML-8; PML-12 AND PML-14), AND VARIANT LEU-645. RX PubMed=11331580; DOI=10.1093/emboj/20.9.2140; RA Reymond A., Meroni G., Fantozzi A., Merla G., Cairo S., Luzi L., RA Riganelli D., Zanaria E., Messali S., Cainarca S., Guffanti A., Minucci S., RA Pelicci P.G., Ballabio A.; RT "The tripartite motif family identifies cell compartments."; RL EMBO J. 20:2140-2151(2001). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM PML-6). RA Goddard A.D., Solomon E.; RL Submitted (JAN-1992) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PML-13). 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 (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PML-11). RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RT "Homo sapiens protein coding cDNA."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM PML-13). RC TISSUE=Kidney; 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 [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 419-466, AND CHROMOSOMAL TRANSLOCATION RP WITH RARA. RX PubMed=1312695; RA Tong J.H., Dong S., Geng J.P., Huang W., Wang Z.Y., Sun G.L., Chen S.J., RA Chen Z., Larsen C.-J., Berger R.; RT "Molecular rearrangements of the MYL gene in acute promyelocytic leukemia RT (APL, M3) define a breakpoint cluster region as well as some molecular RT variants."; RL Oncogene 7:311-316(1992). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 454-503, AND CHROMOSOMAL TRANSLOCATION WITH RP RARA. RX PubMed=12691149; DOI=10.1080/1042819021000040305; RA Fujita K., Oba R., Harada H., Mori H., Niikura H., Isoyama K., Omine M.; RT "Cytogenetics, FISH and RT-PCR analysis of acute promyelocytic leukemia: RT structure of the fusion point in a case lacking classic t(15;17) RT translocation."; RL Leuk. Lymphoma 44:111-115(2003). RN [13] RP SUMOYLATION AT LYS-65; LYS-160 AND LYS-490, MUTAGENESIS OF LYS-65; LYS-133; RP LYS-150; LYS-160 AND LYS-490, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=9756909; DOI=10.1074/jbc.273.41.26675; RA Kamitani T., Kito K., Nguyen H.P., Wada H., Fukuda-Kamitani T., Yeh E.T.H.; RT "Identification of three major sentrinization sites in PML."; RL J. Biol. Chem. 273:26675-26682(1998). RN [14] RP INTERACTION WITH TRIM27. RX PubMed=9570750; DOI=10.1242/jcs.111.10.1319; RA Cao T., Duprez E., Borden K.L., Freemont P.S., Etkin L.D.; RT "Ret finger protein is a normal component of PML nuclear bodies and RT interacts directly with PML."; RL J. Cell Sci. 111:1319-1329(1998). RN [15] RP INTERACTION WITH LASSA VIRUS Z PROTEIN (MICROBIAL INFECTION). RX PubMed=9420283; DOI=10.1128/jvi.72.1.758-766.1998; RA Borden K.L., Campbell-Dwyer E.J., Salvato M.S.; RT "An arenavirus RING (zinc-binding) protein binds the oncoprotein RT promyelocyte leukemia protein (PML) and relocates PML nuclear bodies to the RT cytoplasm."; RL J. Virol. 72:758-766(1998). RN [16] RP INHIBITION OF SUMOYLATION BY HHV-5 (MICROBIAL INFECTION). RX PubMed=10233977; DOI=10.1128/jvi.73.6.5137-5143.1999; RA Mueller S., Dejean A.; RT "Viral immediate-early proteins abrogate the modification by SUMO-1 of PML RT and Sp100 proteins, correlating with nuclear body disruption."; RL J. Virol. 73:5137-5143(1999). RN [17] RP FUNCTION, AND INTERACTION WITH RARA; RXRA AND TRIM24. RX PubMed=10610177; DOI=10.1038/15463; RA Zhong S., Delva L., Rachez C., Cenciarelli C., Gandini D., Zhang H., RA Kalantry S., Freedman L.P., Pandolfi P.P.; RT "A RA-dependent, tumour-growth suppressive transcription complex is the RT target of the PML-RARalpha and T18 oncoproteins."; RL Nat. Genet. 23:287-295(1999). RN [18] RP SUMOYLATION AT LYS-65; LYS-160 AND LYS-490. RX PubMed=10779416; RA Zhong S., Muller S., Ronchetti S., Freemont P.S., Dejean A., Pandolfi P.P.; RT "Role of SUMO-1-modified PML in nuclear body formation."; RL Blood 95:2748-2752(2000). RN [19] RP FUNCTION, AND INTERACTION WITH DAXX. RX PubMed=10684855; DOI=10.1084/jem.191.4.631; RA Zhong S., Salomoni P., Ronchetti S., Guo A., Ruggero D., Pandolfi P.P.; RT "Promyelocytic leukemia protein (PML) and Daxx participate in a novel RT nuclear pathway for apoptosis."; RL J. Exp. Med. 191:631-640(2000). RN [20] RP INTERACTION WITH DAXX, AND SUBCELLULAR LOCATION. RX PubMed=10669754; DOI=10.1128/mcb.20.5.1784-1796.2000; RA Li H., Leo C., Zhu J., Wu X., O'Neil J., Park E.-J., Chen J.D.; RT "Sequestration and inhibition of Daxx-mediated transcriptional repression RT by PML."; RL Mol. Cell. Biol. 20:1784-1796(2000). RN [21] RP FUNCTION, INTERACTION WITH TP53, AND SUBCELLULAR LOCATION. RX PubMed=11025664; DOI=10.1038/35036365; RA Guo A., Salomoni P., Luo J., Shih A., Zhong S., Gu W., Pandolfi P.P.; RT "The function of PML in p53-dependent apoptosis."; RL Nat. Cell Biol. 2:730-736(2000). RN [22] RP FUNCTION IN HUMAN FOAMY VIRUS RESTRICTION, INTERACTION WITH HUMAN FOAMY RP VIRUS BEL1 AND BET (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION. RX PubMed=11432836; DOI=10.1093/emboj/20.13.3495; RA Regad T., Saib A., Lallemand-Breitenbach V., Pandolfi P.P., de The H., RA Chelbi-Alix M.K.; RT "PML mediates the interferon-induced antiviral state against a complex RT retrovirus via its association with the viral transactivator."; RL EMBO J. 20:3495-3505(2001). RN [23] RP FUNCTION, AND INTERACTION WITH EIF4E. RX PubMed=11500381; DOI=10.1093/emboj/20.16.4547; RA Cohen N., Sharma M., Kentsis A., Perez J.M., Strudwick S., Borden K.L.; RT "PML RING suppresses oncogenic transformation by reducing the affinity of RT eIF4E for mRNA."; RL EMBO J. 20:4547-4559(2001). RN [24] RP FUNCTION, AND INTERACTION WITH EIF4E. RX PubMed=11575918; DOI=10.1006/jmbi.2001.5003; RA Kentsis A., Dwyer E.C., Perez J.M., Sharma M., Chen A., Pan Z.Q., RA Borden K.L.; RT "The RING domains of the promyelocytic leukemia protein PML and the RT arenaviral protein Z repress translation by directly inhibiting translation RT initiation factor eIF4E."; RL J. Mol. Biol. 312:609-623(2001). RN [25] RP NOMENCLATURE OF ISOFORMS PML-1 THROUGH PML-7. RX PubMed=11704850; DOI=10.1038/sj.onc.1204765; RA Jensen K., Shiels C., Freemont P.S.; RT "PML protein isoforms and the RBCC/TRIM motif."; RL Oncogene 20:7223-7233(2001). RN [26] RP INTERACTION WITH SIRT1. RX PubMed=12006491; DOI=10.1093/emboj/21.10.2383; RA Langley E., Pearson M., Faretta M., Bauer U.-M., Frye R.A., Minucci S., RA Pelicci P.G., Kouzarides T.; RT "Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular RT senescence."; RL EMBO J. 21:2383-2396(2002). RN [27] RP SUMOYLATION, AND DESUMOYLATION BY SENP2. RX PubMed=12419228; DOI=10.1016/s1097-2765(02)00699-8; RA Best J.L., Ganiatsas S., Agarwal S., Changou A., Salomoni P., Shirihai O., RA Meluh P.B., Pandolfi P.P., Zon L.I.; RT "SUMO-1 protease-1 regulates gene transcription through PML."; RL Mol. Cell 10:843-855(2002). RN [28] RP FUNCTION IN DNA REPAIR, PHOSPHORYLATION AT SER-117 BY CHEK2, AND RP INTERACTION WITH CHEK2. RX PubMed=12402044; DOI=10.1038/ncb869; RA Yang S., Kuo C., Bisi J.E., Kim M.K.; RT "PML-dependent apoptosis after DNA damage is regulated by the checkpoint RT kinase hCds1/Chk2."; RL Nat. Cell Biol. 4:865-870(2002). RN [29] RP INTERACTION WITH RABIES VIRUS PHOSPHOPROTEINS, SUBCELLULAR LOCATION, AND RP FUNCTION. RX PubMed=12439746; DOI=10.1038/sj.onc.1205931; RA Blondel D., Regad T., Poisson N., Pavie B., Harper F., Pandolfi P.P., RA De The H., Chelbi-Alix M.K.; RT "Rabies virus P and small P products interact directly with PML and RT reorganize PML nuclear bodies."; RL Oncogene 21:7957-7970(2002). RN [30] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CHEK2 AND TP53. RX PubMed=12810724; DOI=10.1074/jbc.m301264200; RA Louria-Hayon I., Grossman T., Sionov R.V., Alsheich O., Pandolfi P.P., RA Haupt Y.; RT "The promyelocytic leukemia protein protects p53 from Mdm2-mediated RT inhibition and degradation."; RL J. Biol. Chem. 278:33134-33141(2003). RN [31] RP INTERACTION WITH TOPBP1. RX PubMed=12773567; DOI=10.1128/mcb.23.12.4247-4256.2003; RA Xu Z.-X., Timanova-Atanasova A., Zhao R.-X., Chang K.-S.; RT "PML colocalizes with and stabilizes the DNA damage response protein RT TopBP1."; RL Mol. Cell. Biol. 23:4247-4256(2003). RN [32] RP INTERACTION WITH SIAH1, AND DEGRADATION. RX PubMed=14645235; DOI=10.1074/jbc.m306407200; RA Fanelli M., Fantozzi A., De Luca P., Caprodossi S., Matsuzawa S., RA Lazar M.A., Pelicci P.G., Minucci S.; RT "The coiled-coil domain is the structural determinant for mammalian RT homologues of Drosophila Sina-mediated degradation of promyelocytic RT leukemia protein and other tripartite motif proteins by the proteasome."; RL J. Biol. Chem. 279:5374-5379(2004). RN [33] RP INHIBITION OF SUMOYLATION BY HHV-5 (MICROBIAL INFECTION), AND INTERACTION RP WITH HHV-5 IMMEDIATE EARLY PROTEIN IE1 (MICROBIAL INFECTION). RX PubMed=15163746; DOI=10.1128/jvi.78.12.6527-6542.2004; RA Lee H.R., Kim D.J., Lee J.M., Choi C.Y., Ahn B.Y., Hayward G.S., Ahn J.H.; RT "Ability of the human cytomegalovirus IE1 protein to modulate sumoylation RT of PML correlates with its functional activities in transcriptional RT regulation and infectivity in cultured fibroblast cells."; RL J. Virol. 78:6527-6542(2004). RN [34] RP FUNCTION, INTERACTION WITH ELF4, AND SUBCELLULAR LOCATION. RX PubMed=14976184; DOI=10.1074/jbc.m312439200; RA Suico M.A., Yoshida H., Seki Y., Uchikawa T., Lu Z., Shuto T., RA Matsuzaki K., Nakao M., Li J.-D., Kai H.; RT "Myeloid Elf-1-like factor, an ETS transcription factor, up-regulates RT lysozyme transcription in epithelial cells through interaction with RT promyelocytic leukemia protein."; RL J. Biol. Chem. 279:19091-19098(2004). RN [35] RP INTERACTION WITH ANKRD2. RX PubMed=15136035; DOI=10.1016/j.jmb.2004.03.071; RA Kojic S., Medeot E., Guccione E., Krmac H., Zara I., Martinelli V., RA Valle G., Faulkner G.; RT "The Ankrd2 protein, a link between the sarcomere and the nucleus in RT skeletal muscle."; RL J. Mol. Biol. 339:313-325(2004). RN [36] RP FUNCTION, INTERACTION WITH MDM2 AND RPL11, PHOSPHORYLATION BY ATR IN RP RESPONSE TO DNA DAMAGE, 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 [37] RP SUBCELLULAR LOCATION, AND INTERACTION WITH CHFR. RX PubMed=15467728; DOI=10.1038/nsmb837; RA Daniels M.J., Marson A., Venkitaraman A.R.; RT "PML bodies control the nuclear dynamics and function of the CHFR mitotic RT checkpoint protein."; RL Nat. Struct. Mol. Biol. 11:1114-1121(2004). RN [38] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH TGFBR1; TGFBR2; SMAD2; RP SMAD3 AND ZFYVE9/SARA. RX PubMed=15356634; DOI=10.1038/nature02783; RA Lin H.K., Bergmann S., Pandolfi P.P.; RT "Cytoplasmic PML function in TGF-beta signalling."; RL Nature 431:205-211(2004). RN [39] RP INTERACTION OF PML-RARALPHA ONCOPROTEIN WITH UBE2I, SUBCELLULAR LOCATION, RP SUMOYLATION, AND MUTAGENESIS OF CYS-88 AND PRO-89. RX PubMed=15809060; DOI=10.1016/j.bbrc.2005.03.052; RA Kim Y.E., Kim D.Y., Lee J.M., Kim S.T., Han T.H., Ahn J.H.; RT "Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for RT localization, sumoylation, and inhibition of monocyte differentiation."; RL Biochem. Biophys. Res. Commun. 330:746-754(2005). RN [40] RP SUBCELLULAR LOCATION. RX PubMed=16778193; DOI=10.1158/0008-5472.can-05-3792; RA Condemine W., Takahashi Y., Zhu J., Puvion-Dutilleul F., Guegan S., RA Janin A., de The H.; RT "Characterization of endogenous human promyelocytic leukemia isoforms."; RL Cancer Res. 66:6192-6198(2006). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-403; SER-518; SER-527 AND RP SER-530, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-565 (ISOFORM PML-5), RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-518; SER-527 AND SER-530 RP (ISOFORM PML-6), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [42] RP FUNCTION. RX PubMed=17030982; DOI=10.1083/jcb.200604009; RA Dellaire G., Ching R.W., Ahmed K., Jalali F., Tse K.C., Bristow R.G., RA Bazett-Jones D.P.; RT "Promyelocytic leukemia nuclear bodies behave as DNA damage sensors whose RT response to DNA double-strand breaks is regulated by NBS1 and the kinases RT ATM, Chk2, and ATR."; RL J. Cell Biol. 175:55-66(2006). RN [43] RP FUNCTION IN POLIOVIRUS RESTRICTION. RX PubMed=16912307; DOI=10.1128/jvi.00031-06; RA Pampin M., Simonin Y., Blondel B., Percherancier Y., Chelbi-Alix M.K.; RT "Cross talk between PML and p53 during poliovirus infection: implications RT for antiviral defense."; RL J. Virol. 80:8582-8592(2006). RN [44] RP SUBUNIT, SUMOYLATION, SUMO-BINDING MOTIF, MUTAGENESIS OF CYS-57 AND CYS-60, RP AND SUBCELLULAR LOCATION. RX PubMed=17081985; DOI=10.1016/j.molcel.2006.09.013; RA Shen T.H., Lin H.K., Scaglioni P.P., Yung T.M., Pandolfi P.P.; RT "The mechanisms of PML-nuclear body formation."; RL Mol. Cell 24:331-339(2006). RN [45] RP INTERACTION WITH PKM, FUNCTION, SUBCELLULAR LOCATION, DOMAIN, AND RP MUTAGENESIS OF LYS-487 AND LYS-490. RX PubMed=18298799; DOI=10.1111/j.1365-2443.2008.01165.x; RA Shimada N., Shinagawa T., Ishii S.; RT "Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML RT tumor suppressor protein."; RL Genes Cells 13:245-254(2008). RN [46] RP ACETYLATION AT LYS-487 AND LYS-515, AND MUTAGENESIS OF LYS-487 AND LYS-515. RX PubMed=18621739; DOI=10.1074/jbc.m802217200; RA Hayakawa F., Abe A., Kitabayashi I., Pandolfi P.P., Naoe T.; RT "Acetylation of PML is involved in histone deacetylase inhibitor-mediated RT apoptosis."; RL J. Biol. Chem. 283:24420-24425(2008). RN [47] RP FUNCTION IN HHV-5 RESTRICTION. RX PubMed=17942542; DOI=10.1128/jvi.01685-07; RA Tavalai N., Papior P., Rechter S., Stamminger T.; RT "Nuclear domain 10 components promyelocytic leukemia protein and hDaxx RT independently contribute to an intrinsic antiviral defense against human RT cytomegalovirus infection."; RL J. Virol. 82:126-137(2008). RN [48] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=18716620; DOI=10.1038/nature07290; RA Song M.S., Salmena L., Carracedo A., Egia A., Lo-Coco F., RA Teruya-Feldstein J., Pandolfi P.P.; RT "The deubiquitinylation and localization of PTEN are regulated by a HAUSP- RT PML network."; RL Nature 455:813-817(2008). RN [49] RP POLYUBIQUITINATION AT LYS-380; LYS-400; LYS-401 AND LYS-476 BY RNF4, RP PROTEASOMAL DEGRADATION, AND SUMOYLATION. RX PubMed=18408734; DOI=10.1038/ncb1716; RA Tatham M.H., Geoffroy M.C., Shen L., Plechanovova A., Hattersley N., RA Jaffray E.G., Palvimo J.J., Hay R.T.; RT "RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic- RT induced PML degradation."; RL Nat. Cell Biol. 10:538-546(2008). RN [50] RP FUNCTION, AND INTERACTION WITH SATB1. RX PubMed=17173041; DOI=10.1038/ncb1516; RA Kumar P.P., Bischof O., Purbey P.K., Notani D., Urlaub H., Dejean A., RA Galande S.; RT "Functional interaction between PML and SATB1 regulates chromatin-loop RT architecture and transcription of the MHC class I locus."; RL Nat. Cell Biol. 9:45-56(2007). RN [51] RP FUNCTION. RX PubMed=18391071; DOI=10.1083/jcb.200707018; RA Culjkovic B., Tan K., Orolicki S., Amri A., Meloche S., Borden K.L.; RT "The eIF4E RNA regulon promotes the Akt signaling pathway."; RL J. Cell Biol. 181:51-63(2008). RN [52] RP FUNCTION IN HHV-1 RESTRICTION, AND SUBCELLULAR LOCATION. RX PubMed=18509536; DOI=10.1371/journal.pone.0002277; RA McNally B.A., Trgovcich J., Maul G.G., Liu Y., Zheng P.; RT "A role for cytoplasmic PML in cellular resistance to viral infection."; RL PLoS ONE 3:E2277-E2277(2008). RN [53] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-403; SER-518; SER-527 AND RP SER-530, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [54] RP FUNCTION IN INFLUENZA A VIRUS RESTRICTION. RX PubMed=19703418; DOI=10.1016/j.bbrc.2009.08.091; RA Li W., Wang G., Zhang H., Zhang D., Zeng J., Chen X., Xu Y., Li K.; RT "Differential suppressive effect of promyelocytic leukemia protein on the RT replication of different subtypes/strains of influenza A virus."; RL Biochem. Biophys. Res. Commun. 389:84-89(2009). RN [55] RP FUNCTION, AND INTERACTION WITH TERT. RX PubMed=19567472; DOI=10.1242/jcs.048066; RA Oh W., Ghim J., Lee E.W., Yang M.R., Kim E.T., Ahn J.H., Song J.; RT "PML-IV functions as a negative regulator of telomerase by interacting with RT TERT."; RL J. Cell Sci. 122:2613-2622(2009). RN [56] RP PHOSPHORYLATION AT SER-8 AND SER-38 BY HIPK2, AND INTERACTION WITH HIPK2. RX PubMed=19015637; DOI=10.1038/onc.2008.420; RA Gresko E., Ritterhoff S., Sevilla-Perez J., Roscic A., Froebius K., RA Kotevic I., Vichalkovski A., Hess D., Hemmings B.A., Schmitz M.L.; RT "PML tumor suppressor is regulated by HIPK2-mediated phosphorylation in RT response to DNA damage."; RL Oncogene 28:698-708(2009). RN [57] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-530, 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 [58] RP INTERACTION WITH MORC3, AND SUBCELLULAR LOCATION. RX PubMed=20501696; DOI=10.1242/jcs.063586; RA Mimura Y., Takahashi K., Kawata K., Akazawa T., Inoue N.; RT "Two-step colocalization of MORC3 with PML nuclear bodies."; RL J. Cell Sci. 123:2014-2024(2010). RN [59] RP FUNCTION IN RABIES VIRUS RESTRICTION. RX PubMed=20702643; DOI=10.1128/jvi.01286-10; RA Blondel D., Kheddache S., Lahaye X., Dianoux L., Chelbi-Alix M.K.; RT "Resistance to rabies virus infection conferred by the PMLIV isoform."; RL J. Virol. 84:10719-10726(2010). RN [60] RP PHOSPHORYLATION BY CK2 (MICROBIAL INFECTION), AND SUBCELLULAR LOCATION. RX PubMed=20719947; DOI=10.1128/jvi.01183-10; RA Sivachandran N., Cao J.Y., Frappier L.; RT "Epstein-Barr virus nuclear antigen 1 Hijacks the host kinase CK2 to RT disrupt PML nuclear bodies."; RL J. Virol. 84:11113-11123(2010). RN [61] RP INTERACTION OF PML-4 AND PML-5 WITH HADV5 E1B-55K (MICROBIAL INFECTION). RX PubMed=20639899; DOI=10.1038/onc.2010.284; RA Wimmer P., Schreiner S., Everett R.D., Sirma H., Groitl P., Dobner T.; RT "SUMO modification of E1B-55K oncoprotein regulates isoform-specific RT binding to the tumour suppressor protein PML."; RL Oncogene 29:5511-5522(2010). RN [62] RP SUMOYLATION, AND UBIQUITINATION. RX PubMed=20943951; DOI=10.1091/mbc.e10-05-0449; RA Geoffroy M.C., Jaffray E.G., Walker K.J., Hay R.T.; RT "Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear RT bodies."; RL Mol. Biol. Cell 21:4227-4239(2010). RN [63] RP INTERACTION WITH CSNK2A1 AND CSNK2A3. RX PubMed=20625391; DOI=10.1371/journal.pone.0011418; RA Hung M.S., Lin Y.C., Mao J.H., Kim I.J., Xu Z., Yang C.T., Jablons D.M., RA You L.; RT "Functional polymorphism of the CK2alpha intronless gene plays oncogenic RT roles in lung cancer."; RL PLoS ONE 5:E11418-E11418(2010). RN [64] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-518 AND SER-527, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [65] RP INTERACTION WITH UBC9, SUBUNIT, UBIQUITINATION, SUMOYLATION, ARSENIC RP BINDING, DOMAIN, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=20378816; DOI=10.1126/science.1183424; RA Zhang X.W., Yan X.J., Zhou Z.R., Yang F.F., Wu Z.Y., Sun H.B., Liang W.X., RA Song A.X., Lallemand-Breitenbach V., Jeanne M., Zhang Q.Y., Yang H.Y., RA Huang Q.H., Zhou G.B., Tong J.H., Zhang Y., Wu J.H., Hu H.Y., de The H., RA Chen S.J., Chen Z.; RT "Arsenic trioxide controls the fate of the PML-RARalpha oncoprotein by RT directly binding PML."; RL Science 328:240-243(2010). RN [66] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [67] RP FUNCTION, AND INTERACTION WITH WRN. RX PubMed=21639834; DOI=10.1134/s000629791105004x; RA Liu J., Song Y., Qian J., Liu B., Dong Y., Tian B., Sun Z.; RT "Promyelocytic leukemia protein interacts with werner syndrome helicase and RT regulates double-strand break repair in gamma-irradiation-induced DNA RT damage responses."; RL Biochemistry (Mosc.) 76:550-554(2011). RN [68] RP UBIQUITINATION, PHOSPHORYLATION AT SER-518, AND MUTAGENESIS OF SER-518. RX PubMed=21840486; DOI=10.1016/j.ccr.2011.07.008; RA Yuan W.C., Lee Y.R., Huang S.F., Lin Y.M., Chen T.Y., Chung H.C., RA Tsai C.H., Chen H.Y., Chiang C.T., Lai C.K., Lu L.T., Chen C.H., Gu D.L., RA Pu Y.S., Jou Y.S., Lu K.P., Hsiao P.W., Shih H.M., Chen R.H.; RT "A Cullin3-KLHL20 Ubiquitin ligase-dependent pathway targets PML to RT potentiate HIF-1 signaling and prostate cancer progression."; RL Cancer Cell 20:214-228(2011). RN [69] RP REVIEW ON FUNCTION. RX PubMed=21475307; DOI=10.1038/cdd.2011.31; RA Pinton P., Giorgi C., Pandolfi P.P.; RT "The role of PML in the control of apoptotic cell fate: a new key player at RT ER-mitochondria sites."; RL Cell Death Differ. 18:1450-1456(2011). RN [70] RP REVIEW ON FUNCTION. RX PubMed=21501958; DOI=10.1016/j.ceb.2011.03.011; RA Carracedo A., Ito K., Pandolfi P.P.; RT "The nuclear bodies inside out: PML conquers the cytoplasm."; RL Curr. Opin. Cell Biol. 23:360-366(2011). RN [71] RP PHOSPHORYLATION AT SER-403; SER-505; SER-518 AND SER-527, AND INTERACTION RP WITH PIN1 AND MAPK1. RX PubMed=22033920; DOI=10.1074/jbc.m111.289512; RA Lim J.H., Liu Y., Reineke E., Kao H.Y.; RT "Mitogen-activated protein kinase extracellular signal-regulated kinase 2 RT phosphorylates and promotes Pin1 protein-dependent promyelocytic leukemia RT protein turnover."; RL J. Biol. Chem. 286:44403-44411(2011). RN [72] RP FUNCTION IN HSV-1 RESTRICTION. RX PubMed=21172801; DOI=10.1242/jcs.075390; RA Cuchet D., Sykes A., Nicolas A., Orr A., Murray J., Sirma H., Heeren J., RA Bartelt A., Everett R.D.; RT "PML isoforms I and II participate in PML-dependent restriction of HSV-1 RT replication."; RL J. Cell Sci. 124:280-291(2011). RN [73] RP REVIEW ON FUNCTION IN ANTIVIRAL DEFENSE. RX PubMed=21198351; DOI=10.1089/jir.2010.0111; RA Geoffroy M.C., Chelbi-Alix M.K.; RT "Role of promyelocytic leukemia protein in host antiviral defense."; RL J. Interferon Cytokine Res. 31:145-158(2011). RN [74] RP FUNCTION IN EMCV RESTRICTION, AND INTERACTION WITH EMCV P3D-POL (MICROBIAL RP INFECTION). RX PubMed=21994459; DOI=10.1128/jvi.05808-11; RA Maroui M.A., Pampin M., Chelbi-Alix M.K.; RT "Promyelocytic leukemia isoform IV confers resistance to RT encephalomyocarditis virus via the sequestration of 3D polymerase in RT nuclear bodies."; RL J. Virol. 85:13164-13173(2011). RN [75] RP SUMOYLATION, AND DESUMOYLATION BY SENP6. RX PubMed=21148299; DOI=10.1091/mbc.e10-06-0504; RA Hattersley N., Shen L., Jaffray E.G., Hay R.T.; RT "The SUMO protease SENP6 is a direct regulator of PML nuclear bodies."; RL Mol. Biol. Cell 22:78-90(2011). RN [76] RP REVIEW ON FUNCTION. RX PubMed=21161613; DOI=10.1007/s12035-010-8156-y; RA Salomoni P., Betts-Henderson J.; RT "The role of PML in the nervous system."; RL Mol. Neurobiol. 43:114-123(2011). RN [77] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=20972456; DOI=10.1038/onc.2010.462; RA Chu Y., Yang X.; RT "SUMO E3 ligase activity of TRIM proteins."; RL Oncogene 30:1108-1116(2011). RN [78] RP FUNCTION IN VARICELLA ZOSTER RESTRICTION, SUBCELLULAR LOCATION, AND RP INTERACTION WITH VZV VP26 (MICROBIAL INFECTION). RX PubMed=21304940; DOI=10.1371/journal.ppat.1001266; RA Reichelt M., Wang L., Sommer M., Perrino J., Nour A.M., Sen N., Baiker A., RA Zerboni L., Arvin A.M.; RT "Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral RT host defense against Varicella-Zoster virus."; RL PLoS Pathog. 7:E1001266-E1001266(2011). RN [79] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-518; SER-527 AND SER-530, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [80] RP SUMOYLATION AT LYS-65 AND LYS-160, PHOSPHORYLATION AT SER-565, SUBCELLULAR RP LOCATION, AND INTERACTION WITH PIAS1; PIAS2 AND CSNK2A1. RX PubMed=22406621; DOI=10.1158/0008-5472.can-11-3159; RA Rabellino A., Carter B., Konstantinidou G., Wu S.Y., Rimessi A., RA Byers L.A., Heymach J.V., Girard L., Chiang C.M., Teruya-Feldstein J., RA Scaglioni P.P.; RT "The SUMO E3-ligase PIAS1 regulates the tumor suppressor PML and its RT oncogenic counterpart PML-RARA."; RL Cancer Res. 72:2275-2284(2012). RN [81] RP SUBCELLULAR LOCATION, AND INTERACTION WITH MAGEA2. RX PubMed=22117195; DOI=10.1038/cdd.2011.173; RA Peche L.Y., Scolz M., Ladelfa M.F., Monte M., Schneider C.; RT "MageA2 restrains cellular senescence by targeting the function of RT PMLIV/p53 axis at the PML-NBs."; RL Cell Death Differ. 19:926-936(2012). RN [82] RP REVIEW ON FUNCTION. RX PubMed=22237204; DOI=10.1038/cddis.2011.122; RA Salomoni P., Dvorkina M., Michod D.; RT "Role of the promyelocytic leukaemia protein in cell death regulation."; RL Cell Death Dis. 3:E247-E247(2012). RN [83] RP FUNCTION, AND INTERACTION WITH TBX2; TBX3; E2F4 AND RBL2. RX PubMed=22002537; DOI=10.1038/emboj.2011.370; RA Martin N., Benhamed M., Nacerddine K., Demarque M.D., van Lohuizen M., RA Dejean A., Bischof O.; RT "Physical and functional interaction between PML and TBX2 in the RT establishment of cellular senescence."; RL EMBO J. 31:95-109(2012). RN [84] RP FUNCTION IN CIRCADIAN CLOCK, SUBCELLULAR LOCATION, INTERACTION WITH PER2, RP ACETYLATION AT LYS-487, AND DEACETYLATION BY SIRT1. RX PubMed=22274616; DOI=10.1038/emboj.2012.1; RA Miki T., Xu Z., Chen-Goodspeed M., Liu M., Van Oort-Jansen A., Rea M.A., RA Zhao Z., Lee C.C., Chang K.S.; RT "PML regulates PER2 nuclear localization and circadian function."; RL EMBO J. 31:1427-1439(2012). RN [85] RP REVIEW ON PTM. RX PubMed=23316480; DOI=10.3389/fonc.2012.00210; RA Cheng X., Kao H.Y.; RT "Post-translational modifications of PML: consequences and implications."; RL Front. Oncol. 2:210-210(2012). RN [86] RP FUNCTION, SUBCELLULAR LOCATION, SUMOYLATION AT LYS-490, AND INTERACTION RP WITH HDAC7; RANBP2 AND CTNNB1-TCF7L2 COMPLEX. RX PubMed=22155184; DOI=10.1053/j.gastro.2011.11.041; RA Satow R., Shitashige M., Jigami T., Fukami K., Honda K., Kitabayashi I., RA Yamada T.; RT "Beta-catenin inhibits promyelocytic leukemia protein tumor suppressor RT function in colorectal cancer cells."; RL Gastroenterology 142:572-581(2012). RN [87] RP INTERACTION WITH MOMLV IN AND RT (MICROBIAL INFECTION), AND SUBCELLULAR RP LOCATION. RX PubMed=22685230; DOI=10.1093/jb/mvs063; RA Okino Y., Inayoshi Y., Kojima Y., Kidani S., Kaneoka H., Honkawa A., RA Higuchi H., Nishijima K., Miyake K., Iijima S.; RT "Moloney murine leukemia virus integrase and reverse transcriptase interact RT with PML proteins."; RL J. Biochem. 152:161-169(2012). RN [88] RP FUNCTION. RX PubMed=22589541; DOI=10.1074/jbc.m112.340505; RA Cheng X., Liu Y., Chu H., Kao H.Y.; RT "Promyelocytic leukemia protein (PML) regulates endothelial cell network RT formation and migration in response to tumor necrosis factor alpha RT (TNFalpha) and interferon alpha (IFNalpha)."; RL J. Biol. Chem. 287:23356-23367(2012). RN [89] RP DOMAIN C-TERMINAL. RX PubMed=22773875; DOI=10.1074/jbc.m112.374769; RA Geng Y., Monajembashi S., Shao A., Cui D., He W., Chen Z., Hemmerich P., RA Tang J.; RT "Contribution of the C-terminal regions of promyelocytic leukemia protein RT (PML) isoforms II and V to PML nuclear body formation."; RL J. Biol. Chem. 287:30729-30742(2012). RN [90] RP REVIEW ON UBIQUITINATION. RX PubMed=22935031; DOI=10.1186/1423-0127-19-81; RA Chen R.H., Lee Y.R., Yuan W.C.; RT "The role of PML ubiquitination in human malignancies."; RL J. Biomed. Sci. 19:81-81(2012). RN [91] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CIITA. RX PubMed=23007646; DOI=10.1083/jcb.201112015; RA Ulbricht T., Alzrigat M., Horch A., Reuter N., von Mikecz A., Steimle V., RA Schmitt E., Kraemer O.H., Stamminger T., Hemmerich P.; RT "PML promotes MHC class II gene expression by stabilizing the class II RT transactivator."; RL J. Cell Biol. 199:49-63(2012). RN [92] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=22886304; DOI=10.1172/jci62129; RA Carracedo A., Weiss D., Leliaert A.K., Bhasin M., de Boer V.C., Laurent G., RA Adams A.C., Sundvall M., Song S.J., Ito K., Finley L.S., Egia A., RA Libermann T., Gerhart-Hines Z., Puigserver P., Haigis M.C., RA Maratos-Flier E., Richardson A.L., Schafer Z.T., Pandolfi P.P.; RT "A metabolic prosurvival role for PML in breast cancer."; RL J. Clin. Invest. 122:3088-3100(2012). RN [93] RP INTERACTION WITH HHV-1 ICP0 (MICROBIAL INFECTION). RX PubMed=22875967; DOI=10.1128/jvi.01145-12; RA Cuchet-Lourenco D., Vanni E., Glass M., Orr A., Everett R.D.; RT "Herpes simplex virus 1 ubiquitin ligase ICP0 interacts with PML isoform I RT and induces its SUMO-independent degradation."; RL J. Virol. 86:11209-11222(2012). RN [94] RP INTERACTION WITH TRIM16. RX PubMed=22629402; DOI=10.1371/journal.pone.0037470; RA Bell J.L., Malyukova A., Holien J.K., Koach J., Parker M.W., Kavallaris M., RA Marshall G.M., Cheung B.B.; RT "TRIM16 acts as an E3 ubiquitin ligase and can heterodimerize with other RT TRIM family members."; RL PLoS ONE 7:E37470-E37470(2012). RN [95] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36; SER-38; SER-48; SER-403; RP SER-505; SER-512; SER-518; SER-527; SER-530 AND THR-867, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and 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 [96] RP SUBCELLULAR LOCATION, AND INTERACTION WITH MDM2 AND MAPK7. 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 [97] RP UBIQUITINATION BY UHRF1. RX PubMed=22945642; DOI=10.1038/onc.2012.406; RA Guan D., Factor D., Liu Y., Wang Z., Kao H.Y.; RT "The epigenetic regulator UHRF1 promotes ubiquitination-mediated RT degradation of the tumor-suppressor protein promyelocytic leukemia RT protein."; RL Oncogene 32:3819-3828(2013). RN [98] RP SUMOYLATION, INTERACTION WITH RNF4, AND DOMAIN SIM. RX PubMed=23028697; DOI=10.1371/journal.pone.0044949; RA Maroui M.A., Kheddache-Atmane S., El Asmi F., Dianoux L., Aubry M., RA Chelbi-Alix M.K.; RT "Requirement of PML SUMO interacting motif for RNF4- or arsenic trioxide- RT induced degradation of nuclear PML isoforms."; RL PLoS ONE 7:E44949-E44949(2012). RN [99] RP FUNCTION. RX PubMed=23219818; DOI=10.1016/j.bbrc.2012.11.108; RA Kuroki M., Ariumi Y., Hijikata M., Ikeda M., Dansako H., Wakita T., RA Shimotohno K., Kato N.; RT "PML tumor suppressor protein is required for HCV production."; RL Biochem. Biophys. Res. Commun. 430:592-597(2013). RN [100] RP INTERACTION WITH NLRP3. RX PubMed=23430110; DOI=10.1182/blood-2012-05-432104; RA Lo Y.H., Huang Y.W., Wu Y.H., Tsai C.S., Lin Y.C., Mo S.T., Kuo W.C., RA Chuang Y.T., Jiang S.T., Shih H.M., Lai M.Z.; RT "Selective inhibition of the NLRP3 inflammasome by targeting to RT promyelocytic leukemia protein in mouse and human."; RL Blood 121:3185-3194(2013). RN [101] RP FUNCTION, AND INTERACTION WITH HUMAN ADENOVIRUS 2 E1A (MICROBIAL RP INFECTION). RX PubMed=23135708; DOI=10.1128/jvi.02023-12; RA Berscheminski J., Groitl P., Dobner T., Wimmer P., Schreiner S.; RT "The adenoviral oncogene E1A-13S interacts with a specific isoform of the RT tumor suppressor PML to enhance viral transcription."; RL J. Virol. 87:965-977(2013). RN [102] RP FUNCTION, AND INTERACTION WITH KAT6A. RX PubMed=23431171; DOI=10.1073/pnas.1300490110; RA Rokudai S., Laptenko O., Arnal S.M., Taya Y., Kitabayashi I., Prives C.; RT "MOZ increases p53 acetylation and premature senescence through its complex RT formation with PML."; RL Proc. Natl. Acad. Sci. U.S.A. 110:3895-3900(2013). RN [103] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-8; SER-36; SER-403; SER-518; RP SER-527 AND SER-530, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [104] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-65; LYS-380 AND LYS-490, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [105] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-65; LYS-160 AND LYS-490, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [106] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-65; LYS-160; LYS-380; LYS-394; RP LYS-478 AND LYS-490, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [107] RP INTERACTION OF PML-4 AND PML-5 WITH HADV5 E1B-55K (MICROBIAL INFECTION). RX PubMed=25772236; DOI=10.1038/onc.2015.63; RA Wimmer P., Berscheminski J., Blanchette P., Groitl P., Branton P.E., RA Hay R.T., Dobner T., Schreiner S.; RT "PML isoforms IV and V contribute to adenovirus-mediated oncogenic RT transformation by functionally inhibiting the tumor-suppressor p53."; RL Oncogene 35:69-82(2016). RN [108] RP SUMOYLATION AT LYS-160; LYS-380; LYS-400; LYS-490 AND LYS-497, MUTAGENESIS RP OF LYS-65; LYS-160; LYS-380; LYS-400; LYS-490 AND LYS-497, AND SUBCELLULAR RP LOCATION. RX PubMed=27211601; DOI=10.1038/srep26509; RA Liang Y.C., Lee C.C., Yao Y.L., Lai C.C., Schmitz M.L., Yang W.M.; RT "SUMO5, a novel poly-sumo isoform, regulates pml nuclear bodies."; RL Sci. Rep. 6:26509-26509(2016). RN [109] RP INTERACTION WITH PRDM1. RX PubMed=28842558; DOI=10.1038/s41467-017-00476-w; RA Wang W.F., Yan L., Liu Z., Liu L.X., Lin J., Liu Z.Y., Chen X.P., Zhang W., RA Xu Z.Z., Shi T., Li J.M., Zhao Y.L., Meng G., Xia Y., Li J.Y., Zhu J.; RT "HSP70-Hrd1 axis precludes the oncorepressor potential of N-terminal RT misfolded Blimp-1s in lymphoma cells."; RL Nat. Commun. 8:363-363(2017). RN [110] RP INHIBITION OF SUMOYLATION BY HHV-5 (MICROBIAL INFECTION), AND INTERACTION RP WITH HHV-5 IMMEDIATE EARLY PROTEIN IE1 (MICROBIAL INFECTION). RX PubMed=27903803; DOI=10.1128/jvi.02049-16; RA Schilling E.M., Scherer M., Reuter N., Schweininger J., Muller Y.A., RA Stamminger T.; RT "The Human Cytomegalovirus IE1 Protein Antagonizes PML Nuclear Body- RT Mediated Intrinsic Immunity via the Inhibition of PML De Novo RT SUMOylation."; RL J. Virol. 91:0-0(2017). RN [111] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-65; LYS-160; LYS-380; LYS-394; RP LYS-401; LYS-460; LYS-476; LYS-478; LYS-487; LYS-490 AND LYS-497, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [112] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND INTERACTION WITH HHV-5 IMMEDIATE RP EARLY PROTEIN IE1 (MICROBIAL INFECTION). RX PubMed=28250117; DOI=10.1128/jvi.02335-16; RA Reuter N., Schilling E.M., Scherer M., Mueller R., Stamminger T.; RT "The ND10 Component Promyelocytic Leukemia Protein Acts as an E3 Ligase for RT SUMOylation of the Major Immediate Early Protein IE1 of Human RT Cytomegalovirus."; RL J. Virol. 91:0-0(2017). RN [113] RP CLEAVAGE BY ENTEROVIRUS 71 PROTEASE 3C (MICROBIAL INFECTION), CLEAVAGE RP SITE, AND MUTAGENESIS OF GLN-430 AND GLN-444. RX PubMed=34930370; DOI=10.1186/s12985-021-01725-7; RA Li Z., Wu Y., Li H., Li W., Tan J., Qiao W.; RT "3C protease of enterovirus 71 cleaves promyelocytic leukemia protein and RT impairs PML-NBs production."; RL Virol. J. 18:255-255(2021). RN [114] RP SUBCELLULAR LOCATION. RX PubMed=36373674; DOI=10.7554/elife.79676; RA Oravcova M., Nie M., Zilio N., Maeda S., Jami-Alahmadi Y., RA Lazzerini-Denchi E., Wohlschlegel J.A., Ulrich H.D., Otomo T., Boddy M.N.; RT "The Nse5/6-like SIMC1-SLF2 complex localizes SMC5/6 to viral replication RT centers."; RL Elife 11:0-0(2022). RN [115] RP STRUCTURE BY NMR OF 49-104. RX PubMed=7729428; DOI=10.1002/j.1460-2075.1995.tb07139.x; RA Borden K.L.B., Boddy M.N., Lally J., O'Reilly N.J., Martin S., Howe K., RA Solomon E., Freemont P.S.; RT "The solution structure of the RING finger domain from the acute RT promyelocytic leukaemia proto-oncoprotein PML."; RL EMBO J. 14:1532-1541(1995). CC -!- FUNCTION: Functions via its association with PML-nuclear bodies (PML- CC NBs) in a wide range of important cellular processes, including tumor CC suppression, transcriptional regulation, apoptosis, senescence, DNA CC damage response, and viral defense mechanisms. Acts as the scaffold of CC PML-NBs allowing other proteins to shuttle in and out, a process which CC is regulated by SUMO-mediated modifications and interactions. Inhibits CC EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the CC 5' 7-methylguanosine (m7G) cap of target mRNAs (PubMed:11500381, CC PubMed:11575918, PubMed:18391071). Isoform PML-4 has a multifaceted CC role in the regulation of apoptosis and growth suppression: activates CC RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases CC respectively, negatively affects the PI3K pathway by inhibiting MTOR CC and activating PTEN, and positively regulates p53/TP53 by acting at CC different levels (by promoting its acetylation and phosphorylation and CC by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts CC as a transcriptional repressor of TBX2 during cellular senescence and CC the repression is dependent on a functional RBL2/E2F4 repressor CC complex, regulates double-strand break repair in gamma-irradiation- CC induced DNA damage responses via its interaction with WRN, acts as a CC negative regulator of telomerase by interacting with TERT, and CC regulates PER2 nuclear localization and circadian function. Isoform CC PML-6 inhibits specifically the activity of the tetrameric form of PKM. CC The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, CC isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in CC local chromatin-loop remodeling and gene expression regulation at the CC MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced CC MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is CC involved in the regulation of the TGF-beta signaling pathway. PML also CC regulates transcription activity of ELF4 and can act as an important CC mediator for TNF-alpha- and IFN-alpha-mediated inhibition of CC endothelial cell network formation and migration. CC {ECO:0000269|PubMed:11500381, ECO:0000269|PubMed:11575918, CC ECO:0000269|PubMed:18391071}. CC -!- FUNCTION: Exhibits antiviral activity against both DNA and RNA viruses. CC The antiviral activity can involve one or several isoform(s) and can be CC enhanced by the permanent PML-NB-associated protein DAXX or by the CC recruitment of p53/TP53 within these structures. Isoform PML-4 CC restricts varicella zoster virus (VZV) via sequestration of virion CC capsids in PML-NBs thereby preventing their nuclear egress and CC inhibiting formation of infectious virus particles. The sumoylated CC isoform PML-4 restricts rabies virus by inhibiting viral mRNA and CC protein synthesis. The cytoplasmic isoform PML-14 can restrict herpes CC simplex virus-1 (HHV-1) replication by sequestering the viral E3 CC ubiquitin-protein ligase ICP0 in the cytoplasm. Isoform PML-6 shows CC restriction activity towards human cytomegalovirus (HHV-5) and CC influenza A virus strains PR8(H1N1) and ST364(H3N2). Sumoylated isoform CC PML-4 and isoform PML-12 show antiviral activity against CC encephalomyocarditis virus (EMCV) by promoting nuclear sequestration of CC viral polymerase (P3D-POL) within PML NBs. Isoform PML-3 exhibits CC antiviral activity against poliovirus by inducing apoptosis in infected CC cells through the recruitment and the activation of p53/TP53 in the CC PML-NBs. Isoform PML-3 represses human foamy virus (HFV) transcription CC by complexing the HFV transactivator, bel1/tas, preventing its binding CC to viral DNA. PML may positively regulate infectious hepatitis C viral CC (HCV) production and isoform PML-2 may enhance adenovirus CC transcription. Functions as an E3 SUMO-protein ligase that sumoylates CC (HHV-5) immediate early protein IE1, thereby participating in the CC antiviral response (PubMed:20972456, PubMed:28250117). Isoforms PML-3 CC and PML-6 display the highest levels of sumoylation activity CC (PubMed:20972456, PubMed:28250117). {ECO:0000269|PubMed:20972456, CC ECO:0000269|PubMed:28250117}. CC -!- PATHWAY: Protein modification; protein sumoylation. CC {ECO:0000269|PubMed:20972456, ECO:0000269|PubMed:28250117}. CC -!- SUBUNIT: Key component of PML bodies. PML bodies are formed by the CC interaction of PML homodimers (via SUMO-binding motif) with sumoylated CC PML, leading to the assembly of higher oligomers. Several types of PML CC bodies have been observed. PML bodies can form hollow spheres that can CC sequester target proteins inside. Interacts (via SUMO-binding motif) CC with sumoylated proteins. Interacts (via C-terminus) with p53/TP53. CC Recruits p53/TP53 and CHEK2 into PML bodies, which promotes p53/TP53 CC phosphorylation at 'Ser-20' and prevents its proteasomal degradation. CC Interacts with MDM2, and sequesters MDM2 in the nucleolus, thereby CC preventing ubiquitination of p53/TP53. Interaction with PML-RARA CC oncoprotein and certain viral proteins causes disassembly of PML bodies CC and abolishes the normal PML function. Interacts with HIPK2, TERT, CC SIRT1, TOPBP1, TRIM27 and TRIM69. Interacts with ELF4 (via C-terminus). CC Interacts with ITPR3. Interacts (in the cytoplasm) with TGFBR1, TGFBR2 CC and PKM. Interacts (via the coiled-coil domain and when sumoylated) CC with SATB1. Interacts with UBE2I; the interaction is enhanced by CC arsenic binding. Interacts (PML-RARA oncoprotein, via the coiled-coil CC domain) with UBE2I; the interaction is enhanced by arsenic binding and CC is required for PML-RARA oncoprotein sumoylation and inhibition of RARA CC transactivational activity. Interacts with RB1, PPP1A, SMAD2, SMAD3, CC DAXX, RPL11 and MTOR. Interacts with PPARGC1A and KAT2A. Interacts with CC CSNK2A1 and CSNK2A3. Interacts with ANKRD2; the interaction is direct. CC Interacts (via SUMO-interacting motif) with sumoylated MORC3 CC (PubMed:20501696). Isoform PML-1, isoform PML-2, isoform PML-3, isoform CC PML-4, isoform PML-5 and isoform PML-6 interact with RNF4. Isoform PML- CC 1 interacts with NLRP3. Isoform PML-1, isoform PML-2, isoform PML-3, CC isoform PML-4 and isoform PML-5 interact with MAGEA2, RBL2, PER2 and CC E2F4. Isoform PML-2 interacts with CIITA. Isoform PML-2, isoform PML-3 CC and isoform PML-4 interact with TBX2. Isoform PML-4 interacts with CC RANBP2, HDAC7, KAT6A, WRN, PIN1, TBX3 and phosphorylated MAPK1/ERK2. CC Isoform PML-4 interacts with the CTNNB1 and TCF7L2/TCF4 complex. CC Isoform PML-4 preferentially interacts with MAPK7/BMK1 although other CC isoforms (isoform PML-1, isoform PML-2, isoform PML-3 and isoform PML- CC 6) also interact with it. Isoform PML-12 interacts with PIAS1, PIAS2 CC (isoform PIAS2-alpha) and CSNK2A1/CK2. Interacts with TRIM16. Interacts CC with PRDM1/Blimp-1 (PubMed:28842558). Interacts (via RING-type zinc CC finger) with EIF4E; the interaction results in conformational changes CC of both interacting proteins and reduces EIF4E affinity for the 5' m7G CC cap of mRNA, thus reducing EIF4E-mediated mRNA nuclear export CC (PubMed:11500381, PubMed:11575918). {ECO:0000269|PubMed:10610177, CC ECO:0000269|PubMed:10669754, ECO:0000269|PubMed:10684855, CC ECO:0000269|PubMed:11025664, ECO:0000269|PubMed:11500381, CC ECO:0000269|PubMed:11575918, ECO:0000269|PubMed:12006491, CC ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:12439746, CC ECO:0000269|PubMed:12773567, ECO:0000269|PubMed:12810724, CC ECO:0000269|PubMed:14645235, ECO:0000269|PubMed:14976184, CC ECO:0000269|PubMed:15136035, ECO:0000269|PubMed:15195100, CC ECO:0000269|PubMed:15356634, ECO:0000269|PubMed:15467728, CC ECO:0000269|PubMed:15809060, ECO:0000269|PubMed:17081985, CC ECO:0000269|PubMed:17173041, ECO:0000269|PubMed:18298799, CC ECO:0000269|PubMed:19015637, ECO:0000269|PubMed:19567472, CC ECO:0000269|PubMed:20378816, ECO:0000269|PubMed:20501696, CC ECO:0000269|PubMed:20625391, ECO:0000269|PubMed:21639834, CC ECO:0000269|PubMed:22002537, ECO:0000269|PubMed:22033920, CC ECO:0000269|PubMed:22117195, ECO:0000269|PubMed:22155184, CC ECO:0000269|PubMed:22274616, ECO:0000269|PubMed:22406621, CC ECO:0000269|PubMed:22629402, ECO:0000269|PubMed:22869143, CC ECO:0000269|PubMed:23007646, ECO:0000269|PubMed:23028697, CC ECO:0000269|PubMed:23430110, ECO:0000269|PubMed:23431171, CC ECO:0000269|PubMed:28842558, ECO:0000269|PubMed:9570750}. CC -!- SUBUNIT: (Microbial infection) Interacts with Lassa virus Z protein and CC rabies virus phosphoprotein. {ECO:0000269|PubMed:9420283}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-1 interacts with herpes CC simplex virus-1/HHV-1 ICP0. {ECO:0000269|PubMed:22875967}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-2 interacts with human CC adenovirus 2 E1A and this interaction stimulates E1A-dependent CC transcriptional activation. {ECO:0000269|PubMed:23135708}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-4 interacts with VZV capsid CC protein VP26/ORF23 capsid protein. {ECO:0000269|PubMed:21304940}. CC -!- SUBUNIT: (Microbial infection) The sumoylated isoform PML-4 interacts CC with encephalomyocarditis virus (EMCV) RNA-directed RNA polymerase 3D- CC POL (P3D-POL). {ECO:0000269|PubMed:21994459}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-6 interacts with moloney CC murine leukemia virus (MoMLV) integrase (IN) and reverse transcriptase CC (RT). {ECO:0000269|PubMed:22685230}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-4 and isoform PML-5 interact CC with human adenovirus 5 E1B-55K protein; these interactions promote CC efficient subnuclear targeting of E1B-55K to PML nuclear bodies. CC {ECO:0000269|PubMed:20639899, ECO:0000269|PubMed:23135708, CC ECO:0000269|PubMed:25772236}. CC -!- SUBUNIT: (Microbial infection) Isoform PML-3 interacts (via RING-type CC zinc finger) with human foamy virus bel1/tas and bet. CC {ECO:0000269|PubMed:11432836}. CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus CC (HHV-5) immediate early protein IE1; this interaction mediates PML CC desumoylation and PML-mediated sumoylation of IE1. CC {ECO:0000269|PubMed:27903803, ECO:0000269|PubMed:28250117, CC ECO:0000305|PubMed:15163746}. CC -!- INTERACTION: CC P29590; P68400: CSNK2A1; NbExp=2; IntAct=EBI-295890, EBI-347804; CC P29590; Q9UER7: DAXX; NbExp=6; IntAct=EBI-295890, EBI-77321; CC P29590; P25445: FAS; NbExp=4; IntAct=EBI-295890, EBI-494743; CC P29590; Q9Y2M5: KLHL20; NbExp=9; IntAct=EBI-295890, EBI-714379; CC P29590; Q13164: MAPK7; NbExp=6; IntAct=EBI-295890, EBI-1213983; CC P29590; Q00987: MDM2; NbExp=6; IntAct=EBI-295890, EBI-389668; CC P29590; O15055: PER2; NbExp=3; IntAct=EBI-295890, EBI-1054296; CC P29590; P25788: PSMA3; NbExp=2; IntAct=EBI-295890, EBI-348380; CC P29590; P63165: SUMO1; NbExp=6; IntAct=EBI-295890, EBI-80140; CC P29590; Q13207: TBX2; NbExp=2; IntAct=EBI-295890, EBI-2853051; CC P29590; Q6N021: TET2; NbExp=2; IntAct=EBI-295890, EBI-310727; CC P29590; Q15583: TGIF1; NbExp=3; IntAct=EBI-295890, EBI-714215; CC P29590; P04637: TP53; NbExp=4; IntAct=EBI-295890, EBI-366083; CC P29590; P62258: YWHAE; NbExp=2; IntAct=EBI-295890, EBI-356498; CC P29590; Q05516: ZBTB16; NbExp=7; IntAct=EBI-295890, EBI-711925; CC P29590; Q8UN00: gag-pro-pol; Xeno; NbExp=4; IntAct=EBI-295890, EBI-6692904; CC P29590; P03243-1; Xeno; NbExp=3; IntAct=EBI-295890, EBI-1927377; CC P29590; PRO_0000037566 [P27958]; Xeno; NbExp=6; IntAct=EBI-295890, EBI-6377335; CC P29590-2; P03243-1; Xeno; NbExp=3; IntAct=EBI-303996, EBI-1927377; CC P29590-3; P04489; Xeno; NbExp=4; IntAct=EBI-8099068, EBI-6398911; CC P29590-5; Q00987: MDM2; NbExp=6; IntAct=EBI-304008, EBI-389668; CC P29590-5; O14746: TERT; NbExp=7; IntAct=EBI-304008, EBI-1772203; CC P29590-5; Q05516: ZBTB16; NbExp=2; IntAct=EBI-304008, EBI-711925; CC P29590-5; P03243-1; Xeno; NbExp=3; IntAct=EBI-304008, EBI-1927377; CC P29590-5; PRO_0000039791 [P03304]; Xeno; NbExp=3; IntAct=EBI-304008, EBI-6726189; CC P29590-13; P29590-13: PML; NbExp=3; IntAct=EBI-12368281, EBI-12368281; CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleoplasm. Cytoplasm CC {ECO:0000269|PubMed:27211601}. Nucleus, PML body CC {ECO:0000269|PubMed:20501696, ECO:0000269|PubMed:20719947, CC ECO:0000269|PubMed:27211601, ECO:0000269|PubMed:36373674}. Nucleus, CC nucleolus. Endoplasmic reticulum membrane {ECO:0000250}; Peripheral CC membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Early CC endosome membrane; Peripheral membrane protein; Cytoplasmic side. CC Note=Isoform PML-1 can shuttle between the nucleus and cytoplasm. CC Isoform PML-2, isoform PML-3, isoform PML-4, isoform PML-5 and isoform CC PML-6 are nuclear isoforms whereas isoform PML-7 and isoform PML-14 CC lacking the nuclear localization signal are cytoplasmic isoforms. CC Detected in the nucleolus after DNA damage. Acetylation at Lys-487 is CC essential for its nuclear localization. Within the nucleus, most of PML CC is expressed in the diffuse nuclear fraction of the nucleoplasm and CC only a small fraction is found in the matrix-associated nuclear bodies CC (PML-NBs). The transfer of PML from the nucleoplasm to PML-NBs depends CC on its phosphorylation and sumoylation. The B1 box and the RING finger CC are also required for the localization in PML-NBs. Also found in CC specific membrane structures termed mitochondria-associated membranes CC (MAMs) which connect the endoplasmic reticulum (ER) and the CC mitochondria. Sequestered in the cytoplasm by interaction with rabies CC virus phosphoprotein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=12; CC Name=PML-1; Synonyms=PML-I, TRIM19alpha; CC IsoId=P29590-1; Sequence=Displayed; CC Name=PML-2; Synonyms=PML-II, TRIM19kappa; CC IsoId=P29590-8; Sequence=VSP_040595; CC Name=PML-3; Synonyms=PML-III; CC IsoId=P29590-9; Sequence=VSP_040596, VSP_040597; CC Name=PML-4; Synonyms=PML-IV, PML-X, TRIM19zeta; CC IsoId=P29590-5; Sequence=VSP_005744, VSP_005745; CC Name=PML-5; Synonyms=PML-2, PML-V, TRIM19beta; CC IsoId=P29590-2; Sequence=VSP_005739, VSP_005740; CC Name=PML-6; Synonyms=PML-3B, PML-VI, TRIM19epsilon; CC IsoId=P29590-4; Sequence=VSP_005742, VSP_005743; CC Name=PML-7; Synonyms=PML-VII, TRIM19theta; CC IsoId=P29590-10; Sequence=VSP_040591, VSP_040594; CC Name=PML-8; Synonyms=PML-2G, PML-IIG, TRIM19gamma; CC IsoId=P29590-3; Sequence=VSP_005741; CC Name=PML-11; Synonyms=PML-1A, PML-IA; CC IsoId=P29590-11; Sequence=VSP_040590; CC Name=PML-12; Synonyms=PML-4A, PML-IVA, TRIM19lambda; CC IsoId=P29590-12; Sequence=VSP_040590, VSP_005744, VSP_005745; CC Name=PML-13; Synonyms=PML-2A, PML-IIA; CC IsoId=P29590-13; Sequence=VSP_040590, VSP_040595; CC Name=PML-14; Synonyms=PML-6B, PML-VIB, TRIM19eta, TRIM19iota; CC IsoId=P29590-14; Sequence=VSP_040592, VSP_040593; CC -!- INDUCTION: By interferons alpha, beta and gamma. Up-regulated by IRF3 CC and p53/TP53. CC -!- DOMAIN: The coiled-coil domain mediates a strong homo/multidimerization CC activity essential for core assembly of PML-NBs. Interacts with PKM via CC its coiled-coil domain (PubMed:18298799). CC {ECO:0000269|PubMed:18298799}. CC -!- DOMAIN: The B box-type zinc binding domain and the coiled-coil domain CC mediate its interaction with PIAS1. {ECO:0000269|PubMed:22406621}. CC -!- DOMAIN: Binds arsenic via the RING-type zinc finger. CC {ECO:0000269|PubMed:20378816}. CC -!- DOMAIN: (Microbial infection) The RING-type zinc finger is necessary CC for the sumoylation of human cytomegalovirus (HHV-5) immediate early CC protein IE1. {ECO:0000269|PubMed:28250117}. CC -!- DOMAIN: The unique C-terminal domains of isoform PML-2 and isoform PML- CC 5 play an important role in regulating the localization, assembly CC dynamics, and functions of PML-NBs. {ECO:0000269|PubMed:22773875}. CC -!- DOMAIN: The Sumo interaction motif (SIM) is required for efficient CC ubiquitination, recruitment of proteasome components within PML-NBs and CC PML degradation in response to arsenic trioxide. CC {ECO:0000269|PubMed:23028697}. CC -!- PTM: Ubiquitinated; mediated by RNF4, RNF111, UHRF1, UBE3A/E6AP, CC BCR(KLHL20) E3 ubiquitin ligase complex E3 ligase complex, SIAH1 or CC SIAH2 and leading to subsequent proteasomal degradation CC (PubMed:18408734, PubMed:21840486, PubMed:22033920). Ubiquitination by CC BCR(KLHL20) E3 ubiquitin ligase complex E3 ligase complex requires CC CDK1/2-mediated phosphorylation at Ser-518 which in turn is recognized CC by prolyl-isopeptidase PIN1 and PIN1-catalyzed isomerization further CC potentiates PML interaction with KLHL20 (PubMed:21840486, CC PubMed:22033920). 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked CC polyubiquitination by RNF4 is polysumoylation-dependent CC (PubMed:18408734). Ubiquitination by RNF111 is polysumoylation- CC dependent (By similarity). {ECO:0000250|UniProtKB:Q60953, CC ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:21840486, CC ECO:0000269|PubMed:22033920}. CC -!- PTM: Sumoylation regulates PML's: stability in response to CC extracellular or intracellular stimuli, transcription directly and CC indirectly, through sequestration of or dissociation of the CC transcription factors from PML-NBs, ability to regulate apoptosis and CC its anti-viral activities. It is also essential for: maintaining proper CC PML nuclear bodies (PML-NBs) structure and normal function, recruitment CC of components of PML-NBs, the turnover and retention of PML in PML-NBs CC and the integrity of PML-NBs. Undergoes 'Lys-11'-linked sumoylation. CC Sumoylation on all three sites (Lys-65, Lys-160 and Lys-490) is CC required for nuclear body formation. Sumoylation on Lys-160 is a CC prerequisite for sumoylation on Lys-65. Lys-65 and Lys-160 are CC sumoylated by PISA1 and PIAS2. PIAS1-mediated sumoylation of PML CC promotes its interaction with CSNK2A1/CK2 and phosphorylation at Ser- CC 565 which in turn triggers its ubiquitin-mediated degradation. PIAS1- CC mediated sumoylation of PML-RARA promotes its ubiquitin-mediated CC degradation. The PML-RARA fusion protein requires the coiled-coil CC domain for sumoylation. Sumoylation at Lys-490 by RANBP2 is essential CC for the proper assembly of PML-NBs. SUMO1P1/SUMO5 conjugated PML at CC Lys-160, Lys-380, Lys-400, Lys-490 and Lys-497, but Lys-380, Lys-400 CC and Lys-497 are not key acceptor lysines. SUMO1P1/SUMO5 forms polymeric CC chain on Lys-160 of PML by successive conjugation at 'Lys-18'; CC facilitating recruitment of PML-NB components, which enlarges PML. CC SUMO1P1/SUMO5 conjugation of PML increases SUMO2/3 conjugation, which CC leads to the recruitment of RNF4 and ubiquitin-dependent disintegration CC of PML-NBs. SUMO1P1/SUMO5 monoconjugated Lys-490 (PubMed:27211601). DNA CC damage triggers its sumoylation while some but not all viral infections CC can abolish sumoylation. Desumoylated by SENP1, SENP2, SENP3, SENP5 and CC SENP6 (PubMed:27211601, PubMed:12419228, PubMed:21148299). Arsenic CC induces PML and PML-RARA polysumoylation and their subsequent RNF4- CC dependent ubiquitination and proteasomal degradation, and is used as CC treatment in acute promyelocytic leukemia (APL). The nuclear isoforms CC (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4, isoform CC PML-5 and isoform PML-6) show an increased sumoylation in response to CC arsenic trioxide. The cytoplasmic isoform PML-7 is not sumoylated. CC {ECO:0000269|PubMed:12419228, ECO:0000269|PubMed:18408734, CC ECO:0000269|PubMed:21148299, ECO:0000269|PubMed:22155184, CC ECO:0000269|PubMed:22406621, ECO:0000269|PubMed:27211601, CC ECO:0000269|PubMed:9756909}. CC -!- PTM: Phosphorylation is a major regulatory mechanism that controls PML CC protein abundance and the number and size of PML nuclear bodies (PML- CC NBs). Phosphorylated in response to DNA damage, probably by ATR CC (PubMed:15195100). HIPK2-mediated phosphorylation at Ser-8, Ser-36 and CC Ser-38 leads to increased accumulation of PML protein and its CC sumoylation and is required for the maximal pro-apoptotic activity of CC PML after DNA damage (PubMed:19015637). CHEK2-mediated phosphorylation CC at Ser-117 is important for PML-mediated apoptosis following DNA damage CC (PubMed:12402044). MAPK1-mediated phosphorylations at Ser-403, Ser-505, CC Ser-527 and Ser-530 and CDK1/2-mediated phosphorylation at Ser-518 CC promote PIN1-dependent PML degradation (PubMed:22033920, CC PubMed:21840486). CK2-mediated phosphorylation at Ser-565 primes PML CC ubiquitination via an unidentified ubiquitin ligase (PubMed:22406621, CC PubMed:20719947). {ECO:0000269|PubMed:12402044, CC ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:19015637, CC ECO:0000269|PubMed:20719947, ECO:0000269|PubMed:21840486, CC ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:22406621}. CC -!- PTM: (Microbial infection) Upon infection with Epstein-Barr virus, CC phosphorylated by CK2. Viral EBNA1 increases the association of CK2 CC with PML proteins, which increases PML phosphorylation by CK2, CC triggering the USP7-dependent polyubiquitylation and degradation of CC PML. {ECO:0000269|PubMed:20719947}. CC -!- PTM: Acetylation at Lys-487 is essential for its nuclear localization. CC Deacetylated at Lys-487 by SIRT1 and this deacetylation promotes PML CC control of PER2 nuclear localization. {ECO:0000269|PubMed:18621739, CC ECO:0000269|PubMed:22274616}. CC -!- PTM: (Microbial infection) Immediate early protein IE1 of human CC cytomegalovirus (HHV-5) interferes with the sumoylation of PML CC (PubMed:15163746, PubMed:10233977, PubMed:27903803). Immediate early CC protein IE1 inhibits PML de novo sumoylation (PubMed:27903803). CC {ECO:0000269|PubMed:10233977, ECO:0000269|PubMed:15163746, CC ECO:0000269|PubMed:27903803}. CC -!- PTM: (Microbial infection) Cleaved at two different sites by CC enterovirus 71 protease 3C, leading to impaired PML-Nuclear bodies CC formation. {ECO:0000269|PubMed:34930370}. CC -!- DISEASE: Note=A chromosomal aberration involving PML may be a cause of CC acute promyelocytic leukemia (APL). Translocation t(15;17)(q21;q21) CC with RARA. The PML breakpoints (type A and type B) lie on either side CC of an alternatively spliced exon. {ECO:0000269|PubMed:1652369, CC ECO:0000269|PubMed:1720570}. CC -!- MISCELLANEOUS: [Isoform PML-8]: Non-canonical splice sites. Might CC alternatively represent a polymorphic variation. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA60351.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA60352.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA60388.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=AAA60390.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB62809.1; Type=Miscellaneous discrepancy; Note=Chimeric cDNA.; Evidence={ECO:0000305}; CC Sequence=BAD92648.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/41/PML"; 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; S50913; AAB19601.2; -; mRNA. DR EMBL; M79462; AAA60388.1; ALT_INIT; mRNA. DR EMBL; M79463; AAA60351.1; ALT_INIT; mRNA. DR EMBL; M79464; AAA60390.1; ALT_INIT; mRNA. DR EMBL; X63131; CAA44841.1; -; mRNA. DR EMBL; M73778; AAA60125.1; -; mRNA. DR EMBL; M80185; AAA60352.1; ALT_INIT; mRNA. DR EMBL; AF230401; AAG50180.1; -; mRNA. DR EMBL; AF230402; AAG50181.1; -; mRNA. DR EMBL; AF230403; AAG50182.1; -; mRNA. DR EMBL; AF230405; AAG50184.1; -; mRNA. DR EMBL; AF230406; AAG50185.1; -; mRNA. DR EMBL; AF230407; AAG50186.1; -; mRNA. DR EMBL; AF230408; AAG50187.1; -; mRNA. DR EMBL; AF230409; AAG50188.1; -; mRNA. DR EMBL; AF230410; AAG50189.1; -; mRNA. DR EMBL; AF230411; AAG50190.1; -; mRNA. DR EMBL; BT009911; AAP88913.1; -; mRNA. DR EMBL; AB209411; BAD92648.1; ALT_INIT; mRNA. DR EMBL; AC013486; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC108137; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000080; AAH00080.2; -; mRNA. DR EMBL; BC020994; AAH20994.1; -; mRNA. DR EMBL; X64800; CAA46026.1; -; Genomic_DNA. DR EMBL; AB067754; BAB62809.1; ALT_SEQ; mRNA. DR CCDS; CCDS10255.1; -. [P29590-1] DR CCDS; CCDS10256.1; -. [P29590-10] DR CCDS; CCDS10257.1; -. [P29590-8] DR CCDS; CCDS10258.1; -. [P29590-13] DR CCDS; CCDS45297.1; -. [P29590-5] DR CCDS; CCDS45298.1; -. [P29590-2] DR CCDS; CCDS45299.1; -. [P29590-4] DR CCDS; CCDS45300.1; -. [P29590-14] DR CCDS; CCDS58386.1; -. [P29590-12] DR PIR; A40044; A40044. DR PIR; I38054; I38054. DR PIR; S19244; S19244. DR PIR; S42516; S42516. DR PIR; S44381; S44381. DR RefSeq; NP_002666.1; NM_002675.3. [P29590-5] DR RefSeq; NP_150241.2; NM_033238.2. [P29590-1] DR RefSeq; NP_150242.1; NM_033239.2. [P29590-8] DR RefSeq; NP_150243.2; NM_033240.2. [P29590-2] DR RefSeq; NP_150247.2; NM_033244.3. [P29590-4] DR RefSeq; NP_150249.1; NM_033246.2. [P29590-14] DR RefSeq; NP_150250.2; NM_033247.2. [P29590-10] DR RefSeq; NP_150252.1; NM_033249.2. [P29590-12] DR RefSeq; NP_150253.2; NM_033250.2. [P29590-13] DR PDB; 1BOR; NMR; -; A=49-104. DR PDB; 2MVW; NMR; -; A/B=120-168. DR PDB; 2MWX; NMR; -; A=49-104. DR PDB; 4WJN; X-ray; 1.50 A; B=547-573. DR PDB; 4WJO; X-ray; 1.46 A; B=547-573. DR PDB; 5YUF; X-ray; 1.60 A; A/B/C/D=49-99. DR PDB; 6IMQ; X-ray; 2.06 A; A/B/C/D=120-168. DR PDB; 6UYO; X-ray; 1.64 A; B/D=547-574. DR PDB; 6UYP; X-ray; 1.42 A; B=547-574. DR PDB; 6UYQ; X-ray; 1.50 A; B=547-574. DR PDB; 6UYR; X-ray; 1.30 A; B=547-574. DR PDB; 6UYS; X-ray; 1.59 A; B/D=547-574. DR PDB; 6UYT; X-ray; 1.66 A; B=547-574. DR PDB; 6UYU; X-ray; 1.66 A; B/D=547-574. DR PDB; 6UYV; X-ray; 1.40 A; B=547-574. DR PDB; 8DJH; X-ray; 1.77 A; B=546-573. DR PDB; 8DJI; X-ray; 1.97 A; B=547-574. DR PDB; 8J25; X-ray; 2.60 A; A=183-236. DR PDB; 8J2P; X-ray; 2.09 A; A/E=183-236. DR PDBsum; 1BOR; -. DR PDBsum; 2MVW; -. DR PDBsum; 2MWX; -. DR PDBsum; 4WJN; -. DR PDBsum; 4WJO; -. DR PDBsum; 5YUF; -. DR PDBsum; 6IMQ; -. DR PDBsum; 6UYO; -. DR PDBsum; 6UYP; -. DR PDBsum; 6UYQ; -. DR PDBsum; 6UYR; -. DR PDBsum; 6UYS; -. DR PDBsum; 6UYT; -. DR PDBsum; 6UYU; -. DR PDBsum; 6UYV; -. DR PDBsum; 8DJH; -. DR PDBsum; 8DJI; -. DR PDBsum; 8J25; -. DR PDBsum; 8J2P; -. DR AlphaFoldDB; P29590; -. DR BMRB; P29590; -. DR SMR; P29590; -. DR BioGRID; 111384; 729. DR CORUM; P29590; -. DR DIP; DIP-33053N; -. DR IntAct; P29590; 143. DR MINT; P29590; -. DR STRING; 9606.ENSP00000268058; -. DR DrugBank; DB01169; Arsenic trioxide. DR GlyGen; P29590; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P29590; -. DR PhosphoSitePlus; P29590; -. DR SwissPalm; P29590; -. DR BioMuta; PML; -. DR DMDM; 215274219; -. DR EPD; P29590; -. DR jPOST; P29590; -. DR MassIVE; P29590; -. DR MaxQB; P29590; -. DR PaxDb; 9606-ENSP00000268058; -. DR PeptideAtlas; P29590; -. DR ProteomicsDB; 19281; -. DR ProteomicsDB; 54589; -. [P29590-1] DR ProteomicsDB; 54590; -. [P29590-10] DR ProteomicsDB; 54591; -. [P29590-11] DR ProteomicsDB; 54592; -. [P29590-12] DR ProteomicsDB; 54593; -. [P29590-13] DR ProteomicsDB; 54594; -. [P29590-14] DR ProteomicsDB; 54595; -. [P29590-2] DR ProteomicsDB; 54596; -. [P29590-3] DR ProteomicsDB; 54597; -. [P29590-4] DR ProteomicsDB; 54598; -. [P29590-5] DR ProteomicsDB; 54599; -. [P29590-8] DR ProteomicsDB; 54600; -. [P29590-9] DR Pumba; P29590; -. DR Antibodypedia; 1737; 661 antibodies from 44 providers. DR DNASU; 5371; -. DR Ensembl; ENST00000268058.8; ENSP00000268058.3; ENSG00000140464.20. [P29590-1] DR Ensembl; ENST00000268059.10; ENSP00000268059.6; ENSG00000140464.20. [P29590-8] DR Ensembl; ENST00000354026.10; ENSP00000315434.8; ENSG00000140464.20. [P29590-13] DR Ensembl; ENST00000359928.8; ENSP00000353004.4; ENSG00000140464.20. [P29590-14] DR Ensembl; ENST00000395132.6; ENSP00000378564.2; ENSG00000140464.20. [P29590-10] DR Ensembl; ENST00000395135.7; ENSP00000378567.3; ENSG00000140464.20. [P29590-5] DR Ensembl; ENST00000435786.6; ENSP00000395576.2; ENSG00000140464.20. [P29590-2] DR Ensembl; ENST00000436891.7; ENSP00000394642.3; ENSG00000140464.20. [P29590-4] DR Ensembl; ENST00000564428.5; ENSP00000457023.1; ENSG00000140464.20. [P29590-12] DR Ensembl; ENST00000565898.5; ENSP00000455838.1; ENSG00000140464.20. [P29590-11] DR Ensembl; ENST00000567543.5; ENSP00000456277.1; ENSG00000140464.20. [P29590-14] DR Ensembl; ENST00000569477.5; ENSP00000455612.1; ENSG00000140464.20. [P29590-9] DR Ensembl; ENST00000569965.5; ENSP00000456486.1; ENSG00000140464.20. [P29590-4] DR GeneID; 5371; -. DR KEGG; hsa:5371; -. DR MANE-Select; ENST00000268058.8; ENSP00000268058.3; NM_033238.3; NP_150241.2. DR UCSC; uc002awk.4; human. [P29590-1] DR AGR; HGNC:9113; -. DR CTD; 5371; -. DR DisGeNET; 5371; -. DR GeneCards; PML; -. DR HGNC; HGNC:9113; PML. DR HPA; ENSG00000140464; Low tissue specificity. DR MalaCards; PML; -. DR MIM; 102578; gene. DR neXtProt; NX_P29590; -. DR OpenTargets; ENSG00000140464; -. DR Orphanet; 520; Acute promyelocytic leukemia. DR PharmGKB; PA33439; -. DR VEuPathDB; HostDB:ENSG00000140464; -. DR eggNOG; KOG2177; Eukaryota. DR GeneTree; ENSGT00510000048454; -. DR HOGENOM; CLU_009136_1_0_1; -. DR InParanoid; P29590; -. DR OrthoDB; 5352396at2759; -. DR PhylomeDB; P29590; -. DR TreeFam; TF336434; -. DR PathwayCommons; P29590; -. DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins. DR Reactome; R-HSA-3232142; SUMOylation of ubiquitinylation proteins. DR Reactome; R-HSA-6804758; Regulation of TP53 Activity through Acetylation. DR Reactome; R-HSA-877300; Interferon gamma signaling. DR Reactome; R-HSA-8934593; Regulation of RUNX1 Expression and Activity. DR Reactome; R-HSA-8948747; Regulation of PTEN localization. DR Reactome; R-HSA-9609690; HCMV Early Events. DR Reactome; R-HSA-9616222; Transcriptional regulation of granulopoiesis. [P29590-4] DR SignaLink; P29590; -. DR SIGNOR; P29590; -. DR UniPathway; UPA00886; -. DR BioGRID-ORCS; 5371; 21 hits in 1215 CRISPR screens. DR ChiTaRS; PML; human. DR EvolutionaryTrace; P29590; -. DR GeneWiki; Promyelocytic_leukemia_protein; -. DR GenomeRNAi; 5371; -. DR Pharos; P29590; Tbio. DR PRO; PR:P29590; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; P29590; Protein. DR Bgee; ENSG00000140464; Expressed in omental fat pad and 171 other cell types or tissues. DR ExpressionAtlas; P29590; baseline and differential. DR GO; GO:0000781; C:chromosome, telomeric region; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0000792; C:heterochromatin; IEA:Ensembl. DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IDA:UniProtKB. 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:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0050897; F:cobalt ion binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0060090; F:molecular adaptor activity; IDA:UniProt. DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL. DR GO; GO:0046332; F:SMAD binding; IEA:Ensembl. DR GO; GO:0032183; F:SUMO binding; IPI:UniProtKB. DR GO; GO:0019789; F:SUMO transferase activity; EXP:Reactome. DR GO; GO:0140037; F:sumo-dependent protein binding; IPI:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0061659; F:ubiquitin-like protein ligase activity; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB. DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IEA:Ensembl. DR GO; GO:0045165; P:cell fate commitment; IEA:Ensembl. DR GO; GO:0071353; P:cellular response to interleukin-4; IEA:Ensembl. DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl. DR GO; GO:0090398; P:cellular senescence; IDA:UniProtKB. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; ISS:UniProtKB. DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; ISS:UniProtKB. DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0010761; P:fibroblast migration; IEA:Ensembl. DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB. DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:UniProtKB. DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IEA:Ensembl. DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IEA:Ensembl. DR GO; GO:0051457; P:maintenance of protein location in nucleus; IDA:MGI. DR GO; GO:0030099; P:myeloid cell differentiation; IEA:Ensembl. DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB. DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IEA:Ensembl. DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; IDA:UniProtKB. DR GO; GO:0051974; P:negative regulation of telomerase activity; IMP:UniProtKB. DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; IMP:UniProtKB. DR GO; GO:0032938; P:negative regulation of translation in response to oxidative stress; IDA:UniProtKB. DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR GO; GO:0090402; P:oncogene-induced cell senescence; IEA:Ensembl. DR GO; GO:0030578; P:PML body organization; IDA:UniProtKB. DR GO; GO:0060058; P:positive regulation of apoptotic process involved in mammary gland involution; IDA:UniProtKB. DR GO; GO:0002230; P:positive regulation of defense response to virus by host; IMP:UniProtKB. DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:0031065; P:positive regulation of histone deacetylation; IDA:UniProtKB. DR GO; GO:2000758; P:positive regulation of peptidyl-lysine acetylation; IEA:Ensembl. DR GO; GO:1904816; P:positive regulation of protein localization to chromosome, telomeric region; IDA:BHF-UCL. DR GO; GO:1901798; P:positive regulation of signal transduction by p53 class mediator; IEA:Ensembl. DR GO; GO:0032206; P:positive regulation of telomere maintenance; IMP:BHF-UCL. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR GO; GO:0006606; P:protein import into nucleus; IEA:Ensembl. DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB. DR GO; GO:0016925; P:protein sumoylation; TAS:Reactome. DR GO; GO:0006605; P:protein targeting; IDA:UniProtKB. DR GO; GO:0065003; P:protein-containing complex assembly; IDA:UniProtKB. DR GO; GO:0031503; P:protein-containing complex localization; IEA:Ensembl. DR GO; GO:0010522; P:regulation of calcium ion transport into cytosol; ISS:UniProtKB. DR GO; GO:0030155; P:regulation of cell adhesion; IEA:Ensembl. DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB. DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IMP:UniProtKB. DR GO; GO:2000779; P:regulation of double-strand break repair; IMP:UniProtKB. DR GO; GO:0034097; P:response to cytokine; IDA:BHF-UCL. DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB. DR GO; GO:0009411; P:response to UV; IEA:Ensembl. DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IEA:Ensembl. DR GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl. DR GO; GO:0044790; P:suppression of viral release by host; IDA:UniProtKB. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IEA:Ensembl. DR CDD; cd19804; Bbox1_TRIM19_C-V; 1. DR CDD; cd19770; Bbox2_TRIM19_C-V; 1. DR CDD; cd16579; RING-HC_PML_C-V; 1. DR Gene3D; 3.30.160.60; Classic Zinc Finger; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR021978; PML-like_CC. DR InterPro; IPR047153; TRIM45/56/19. DR InterPro; IPR000315; Znf_B-box. DR InterPro; IPR018957; Znf_C3HC4_RING-type. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR25462; BONUS, ISOFORM C-RELATED; 1. DR PANTHER; PTHR25462:SF301; PROTEIN PML; 1. DR Pfam; PF12126; DUF3583; 1. DR Pfam; PF00643; zf-B_box; 1. DR Pfam; PF00097; zf-C3HC4; 1. DR SMART; SM00336; BBOX; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF57850; RING/U-box; 1. DR PROSITE; PS50119; ZF_BBOX; 2. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. DR Genevisible; P29590; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Antiviral defense; Apoptosis; Biological rhythms; KW Chromosomal rearrangement; Coiled coil; Cytoplasm; DNA-binding; KW Endoplasmic reticulum; Endosome; Host-virus interaction; Immunity; KW Innate immunity; Isopeptide bond; Membrane; Metal-binding; Nucleus; KW Phosphoprotein; Proto-oncogene; Reference proteome; Repeat; Transcription; KW Transcription regulation; Transferase; Tumor suppressor; Ubl conjugation; KW Zinc; Zinc-finger. FT CHAIN 1..882 FT /note="Protein PML" FT /id="PRO_0000056001" FT ZN_FING 57..92 FT /note="RING-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175" FT ZN_FING 124..166 FT /note="B box-type 1; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT ZN_FING 183..236 FT /note="B box-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT REGION 1..48 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 448..555 FT /note="Interaction with PER2" FT /evidence="ECO:0000269|PubMed:22274616" FT REGION 467..589 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 556..562 FT /note="Sumo interaction motif (SIM)" FT COILED 228..253 FT /evidence="ECO:0000255" FT MOTIF 476..490 FT /note="Nuclear localization signal" FT COMPBIAS 1..42 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 467..482 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 488..504 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 557..580 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 57 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 60 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 72 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 74 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 77 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 80 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT BINDING 88 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 91 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT BINDING 129 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 132 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 151 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 155 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 189 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 194 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 215 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT BINDING 222 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024" FT SITE 394..395 FT /note="Breakpoint for translocation to form PML-RARA FT oncogene in type A APL" FT SITE 430..431 FT /note="(Microbial infection) Cleavage by protease 3C of FT enterovirus 71" FT /evidence="ECO:0000269|PubMed:34930370" FT SITE 444..445 FT /note="(Microbial infection) Cleavage by protease 3C of FT enterovirus 71" FT /evidence="ECO:0000269|PubMed:34930370" FT SITE 552..553 FT /note="Breakpoint for translocation to form PML-RARA FT oncogene in type B APL" FT MOD_RES 8 FT /note="Phosphoserine; by HIPK2" FT /evidence="ECO:0000269|PubMed:19015637, FT ECO:0007744|PubMed:24275569" FT MOD_RES 36 FT /note="Phosphoserine; by HIPK2 and MAPK1" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 38 FT /note="Phosphoserine; by HIPK2 and MAPK1" FT /evidence="ECO:0000269|PubMed:19015637, FT ECO:0007744|PubMed:23186163" FT MOD_RES 48 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 117 FT /note="Phosphoserine; by CHEK2" FT /evidence="ECO:0000269|PubMed:12402044" FT MOD_RES 403 FT /note="Phosphoserine; by MAPK1 and MAPK7" FT /evidence="ECO:0000269|PubMed:22033920, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 487 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:18621739, FT ECO:0000269|PubMed:22274616" FT MOD_RES 493 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q60953" FT MOD_RES 504 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q60953" FT MOD_RES 505 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0000269|PubMed:22033920, FT ECO:0007744|PubMed:23186163" FT MOD_RES 512 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 515 FT /note="N6-acetyllysine" FT /evidence="ECO:0000305|PubMed:18621739" FT MOD_RES 518 FT /note="Phosphoserine; by CDK1 and CDK2" FT /evidence="ECO:0000269|PubMed:21840486, FT ECO:0000269|PubMed:22033920, ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 527 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0000269|PubMed:22033920, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 530 FT /note="Phosphoserine; by MAPK1" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 565 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000269|PubMed:22406621" FT MOD_RES 867 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT CROSSLNK 65 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000269|PubMed:10779416" FT CROSSLNK 65 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 160 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000269|PubMed:10779416" FT CROSSLNK 160 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1P1/SUMO5); alternate" FT /evidence="ECO:0000269|PubMed:27211601" FT CROSSLNK 160 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733" FT CROSSLNK 380 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in /SUMO5); alternate" FT /evidence="ECO:0000269|PubMed:27211601" FT CROSSLNK 380 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:28112733" FT CROSSLNK 380 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:18408734" FT CROSSLNK 394 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 400 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1P1/SUMO5); alternate" FT /evidence="ECO:0000269|PubMed:27211601" FT CROSSLNK 400 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:18408734" FT CROSSLNK 401 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 401 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:18408734" FT CROSSLNK 460 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 476 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 476 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin); alternate" FT /evidence="ECO:0000269|PubMed:18408734" FT CROSSLNK 478 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 487 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 490 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT /evidence="ECO:0000269|PubMed:10779416" FT CROSSLNK 490 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1P1/SUMO5); alternate" FT /evidence="ECO:0000269|PubMed:27211601" FT CROSSLNK 490 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:25218447, FT ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364, FT ECO:0007744|PubMed:28112733" FT CROSSLNK 497 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1); alternate" FT CROSSLNK 497 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1P1/SUMO5); alternate" FT /evidence="ECO:0000269|PubMed:27211601" FT CROSSLNK 497 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2); alternate" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 419..466 FT /note="Missing (in isoform PML-11, isoform PML-12 and FT isoform PML-13)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.7, FT ECO:0000303|Ref.8" FT /id="VSP_040590" FT VAR_SEQ 419..435 FT /note="PEEAERVKAQVQALGLA -> LPPPAHALTGPAQSSTH (in isoform FT PML-7)" FT /evidence="ECO:0000303|PubMed:11331580" FT /id="VSP_040591" FT VAR_SEQ 419..423 FT /note="PEEAE -> RNALW (in isoform PML-14)" FT /evidence="ECO:0000303|PubMed:11331580" FT /id="VSP_040592" FT VAR_SEQ 424..882 FT /note="Missing (in isoform PML-14)" FT /evidence="ECO:0000303|PubMed:11331580" FT /id="VSP_040593" FT VAR_SEQ 436..882 FT /note="Missing (in isoform PML-7)" FT /evidence="ECO:0000303|PubMed:11331580" FT /id="VSP_040594" FT VAR_SEQ 553..560 FT /note="EERVVVIS -> GRERNALW (in isoform PML-6)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1652368, ECO:0000303|Ref.6" FT /id="VSP_005742" FT VAR_SEQ 561..882 FT /note="Missing (in isoform PML-6)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1652368, ECO:0000303|Ref.6" FT /id="VSP_005743" FT VAR_SEQ 571..882 FT /note="SSRELDDSSSESSDLQLEGPSTLRVLDENLADPQAEDRPLVFFDLKIDNETQ FT KISQLAAVNRESKFRVVIQPEAFFSIYSKAVSLEVGLQHFLSFLSSMRRPILACYKLWG FT PGLPNFFRALEDINRLWEFQEAISGFLAALPLIRERVPGASSFKLKNLAQTYLARNMSE FT RSAMAAVLAMRDLCRLLEVSPGPQLAQHVYPFSSLQCFASLQPLVQAAVLPRAEARLLA FT LHNVSFMELLSAHRRDRQGGLKKYSRYLSLQTTTLPPAQPAFNLQALGTYFEGLLEGPA FT LARAEGVSTPLAGRGLAERASQQS -> CMEPMETAEPQSSPAHSSPAHSSPAHSSPVQ FT SLLRAQGASSLPCGTYHPPAWPPHQPAEQAATPDAEPHSEPPDHQERPAVHRGIRYLLY FT RAQRAIRLRHALRLHPQLHRAPIRTWSPHVVQASTPAITGPLNHPANAQEHPAQLQRGI FT SPPHRIRGAVRSRSRSLRGSSHLSQWLNNFFALPFSSMASQLDMSSVVGAGESRAQTLG FT AGVPPGDSVRGSMEASQVQVPLEASPITFPPPCAPERPPISPVPGARQAGL (in FT isoform PML-2 and isoform PML-13)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.7" FT /id="VSP_040595" FT VAR_SEQ 571..882 FT /note="SSRELDDSSSESSDLQLEGPSTLRVLDENLADPQAEDRPLVFFDLKIDNETQ FT KISQLAAVNRESKFRVVIQPEAFFSIYSKAVSLEVGLQHFLSFLSSMRRPILACYKLWG FT PGLPNFFRALEDINRLWEFQEAISGFLAALPLIRERVPGASSFKLKNLAQTYLARNMSE FT RSAMAAVLAMRDLCRLLEVSPGPQLAQHVYPFSSLQCFASLQPLVQAAVLPRAEARLLA FT LHNVSFMELLSAHRRDRQGGLKKYSRYLSLQTTTLPPAQPAFNLQALGTYFEGLLEGPA FT LARAEGVSTPLAGRGLAERASQQS -> CMEPMETAEPQSSPAHSSPAHSSPVQSLLRA FT QGASSLPCGTYHPPAWPPHQPAEQAATPDAEPHSEPPDHQERPAVHRGIRYLLYRAQRA FT IRLRHALRLHPQLHRAPIRTWSPHVVQASTPAITGPLNHPANAQEHPAQLQRGISPPHR FT IRGAVRSRSRSLRGSSHLSQWLNNFFALPFSSMASQLDMSSVVGAGESRAQTLGAGVPP FT GDSVRGSMEASQVQVPLEASPITFPPPCAPERPPISPVPGARQAGL (in isoform FT PML-8)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1720570" FT /id="VSP_005741" FT VAR_SEQ 571..641 FT /note="SSRELDDSSSESSDLQLEGPSTLRVLDENLADPQAEDRPLVFFDLKIDNETQ FT KISQLAAVNRESKFRVVIQ -> VSSSPQSEVLYWKVHGAHGDRRATVLASPLLASPLL FT ASPLLASPVSAESTRSLQPALWHIPPPSLASPPAR (in isoform PML-3)" FT /evidence="ECO:0000303|PubMed:1652369" FT /id="VSP_040596" FT VAR_SEQ 571..611 FT /note="SSRELDDSSSESSDLQLEGPSTLRVLDENLADPQAEDRPLV -> VSGPEVQ FT PRTPASPHFRSQGAQPQQVTLRLALRLGNFPVRH (in isoform PML-5)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1720570" FT /id="VSP_005739" FT VAR_SEQ 612..882 FT /note="Missing (in isoform PML-5)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1720570" FT /id="VSP_005740" FT VAR_SEQ 621..633 FT /note="TQKISQLAAVNRE -> SGFSWGYPHPFLI (in isoform PML-4 and FT isoform PML-12)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1311253" FT /id="VSP_005744" FT VAR_SEQ 634..882 FT /note="Missing (in isoform PML-4 and isoform PML-12)" FT /evidence="ECO:0000303|PubMed:11331580, FT ECO:0000303|PubMed:1311253" FT /id="VSP_005745" FT VAR_SEQ 642..882 FT /note="Missing (in isoform PML-3)" FT /evidence="ECO:0000303|PubMed:1652369" FT /id="VSP_040597" FT VARIANT 645 FT /note="F -> L (in dbSNP:rs5742915)" FT /evidence="ECO:0000269|PubMed:11331580, FT ECO:0000269|PubMed:1720570" FT /id="VAR_052090" FT MUTAGEN 57 FT /note="C->S: Strongly reduced sumoylation; when associated FT with S-60." FT /evidence="ECO:0000269|PubMed:17081985" FT MUTAGEN 60 FT /note="C->S: Strongly reduced sumoylation; when associated FT with S-57." FT /evidence="ECO:0000269|PubMed:17081985" FT MUTAGEN 65 FT /note="K->R: Loss of one sumoylation. No effect on nuclear FT body formation. Loss of 2 sumoylations; when associated FT with R-490 with or without R-133 or R-150. No effect on FT nuclear body formation; when associated with R-490. Loss FT the ability to be conjugated by SUMO1P1/SUMO5 but could be FT conjugated by SUMO1; when associated with R-160 and R-490." FT /evidence="ECO:0000269|PubMed:27211601, FT ECO:0000269|PubMed:9756909" FT MUTAGEN 65 FT /note="K->R: Loss of one sumoylation. No effect on nuclear FT body formation. Loss of 2 sumoylations; when associated FT with R-490 with or without R-133 or R-150. No effect on FT nuclear body formation; when associated with R-490. No FT sumoylation nor nuclear body formation; when associated FT with R-160 and R-490." FT /evidence="ECO:0000269|PubMed:9756909" FT MUTAGEN 68 FT /note="K->R: No effect on sumoylation levels." FT MUTAGEN 88 FT /note="C->S: No nuclear microspeckle location, no FT sumoylation and loss of intrinsic transcriptional repressor FT activity of PML-RARA oncoprotein; when associated with FT R-89." FT /evidence="ECO:0000269|PubMed:15809060" FT MUTAGEN 89 FT /note="P->R: No nuclear microspeckle location, no FT sumoylation and loss of intrinsic transcriptional repressor FT activity of PML-RARA oncoprotein; when associated with FT S-88." FT /evidence="ECO:0000269|PubMed:15809060" FT MUTAGEN 133 FT /note="K->R: Loss of 2 sumoylations; when associated with FT R-65 and R-490." FT /evidence="ECO:0000269|PubMed:9756909" FT MUTAGEN 150 FT /note="K->R: Loss of 2 sumoylations; when associated with FT R-65 and R-490." FT /evidence="ECO:0000269|PubMed:9756909" FT MUTAGEN 160 FT /note="K->R: Compromised the formation of high molecular FT weight species of SUMO1P1/SUMO5 conjugation on PML. Loss of FT 2 sumoylations; when associated with or without R-65. No FT sumoylation nor nuclear body formation; when associated FT with or without R-65 and R-490. Loss the ability to be FT conjugated by SUMO1P1/SUMO5 but could be conjugated by FT SUMO1; when associated with R-65 and R-490." FT /evidence="ECO:0000269|PubMed:27211601, FT ECO:0000269|PubMed:9756909" FT MUTAGEN 160 FT /note="K->R: Loss of 2 sumoylations; when associated with FT or without R-65. No sumoylation nor nuclear body formation; FT when associated with or without R-65 and R-490." FT /evidence="ECO:0000269|PubMed:9756909" FT MUTAGEN 380 FT /note="K->R: Does not affect SUMO1P1/SUMO5 conjugation." FT /evidence="ECO:0000269|PubMed:27211601" FT MUTAGEN 400 FT /note="K->R: Does not affect SUMO1P1/SUMO5 conjugation." FT /evidence="ECO:0000269|PubMed:27211601" FT MUTAGEN 430 FT /note="Q->A: Loss of cleavage by enterovirus 71 protease FT 3C." FT /evidence="ECO:0000269|PubMed:34930370" FT MUTAGEN 444 FT /note="Q->A: Loss of cleavage by enterovirus 71 protease FT 3C." FT /evidence="ECO:0000269|PubMed:34930370" FT MUTAGEN 487 FT /note="K->A: Loss of nuclear localization; when associated FT with A-490." FT /evidence="ECO:0000269|PubMed:18298799, FT ECO:0000269|PubMed:18621739" FT MUTAGEN 487 FT /note="K->R: Loss of nuclear localization. Reduced FT acetylation. Further decrease in acetylation; when FT associated with R-515." FT /evidence="ECO:0000269|PubMed:18298799, FT ECO:0000269|PubMed:18621739" FT MUTAGEN 490 FT /note="K->A: Loss of nuclear localization; when associated FT with A-487." FT /evidence="ECO:0000269|PubMed:18298799, FT ECO:0000269|PubMed:9756909" FT MUTAGEN 490 FT /note="K->R: Abolished conjugation of one SUMO1P1/SUMO5. FT Loss of 2 sumoylations; when associated with R-65 with or FT without R-133. No effect on nuclear body formation; when FT associated with R-65. No sumoylation nor nuclear body FT formation; when associated with R-65 and R-160. Loss the FT ability to be conjugated by SUMO1P1/SUMO5 but could be FT conjugated by SUMO1; when associated with R-65 and R-160." FT /evidence="ECO:0000269|PubMed:18298799, FT ECO:0000269|PubMed:27211601, ECO:0000269|PubMed:9756909" FT MUTAGEN 490 FT /note="K->R: Loss of 2 sumoylations; when associated with FT R-65 with or without R-133. No effect on nuclear body FT formation; when associated with R-65. No sumoylation nor FT nuclear body formation; when associated with R-65 and FT R-160." FT /evidence="ECO:0000269|PubMed:18298799, FT ECO:0000269|PubMed:9756909" FT MUTAGEN 497 FT /note="K->R: Does not affect SUMO1P1/SUMO5 conjugation." FT /evidence="ECO:0000269|PubMed:27211601" FT MUTAGEN 515 FT /note="K->R: Slightly reduced acetylation. Further decrease FT in acetylation; when associated with R-487." FT /evidence="ECO:0000269|PubMed:18621739" FT MUTAGEN 518 FT /note="S->A: Abolishes ubiquitination by the BCR(KLHL20) E3 FT ubiquitin ligase complex." FT /evidence="ECO:0000269|PubMed:21840486" FT MUTAGEN 556..559 FT /note="VVVI->AAAS: Abolishes SUMO1 binding." FT CONFLICT 224 FT /note="E -> D (in Ref. 7; AAP88913 and 10; FT AAH00080/AAH20994)" FT /evidence="ECO:0000305" FT CONFLICT 419 FT /note="P -> A (in Ref. 2; AAA60351/AAA60388/AAA60390, 4; FT AAA60352 and 5; AAG50182/AAG50184/AAG50185)" FT /evidence="ECO:0000305" FT STRAND 54..56 FT /evidence="ECO:0007829|PDB:5YUF" FT TURN 58..60 FT /evidence="ECO:0007829|PDB:5YUF" FT STRAND 62..66 FT /evidence="ECO:0007829|PDB:5YUF" FT HELIX 78..82 FT /evidence="ECO:0007829|PDB:5YUF" FT TURN 89..91 FT /evidence="ECO:0007829|PDB:5YUF" FT STRAND 93..96 FT /evidence="ECO:0007829|PDB:1BOR" FT STRAND 121..126 FT /evidence="ECO:0007829|PDB:6IMQ" FT TURN 130..132 FT /evidence="ECO:0007829|PDB:6IMQ" FT STRAND 138..140 FT /evidence="ECO:0007829|PDB:6IMQ" FT TURN 141..144 FT /evidence="ECO:0007829|PDB:6IMQ" FT STRAND 145..147 FT /evidence="ECO:0007829|PDB:6IMQ" FT HELIX 149..158 FT /evidence="ECO:0007829|PDB:6IMQ" FT STRAND 163..165 FT /evidence="ECO:0007829|PDB:6IMQ" FT STRAND 556..558 FT /evidence="ECO:0007829|PDB:6UYR" FT MOD_RES P29590-2:565 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT CONFLICT P29590-2:578 FT /note="P -> A (in Ref. 5; AAG50181)" FT /evidence="ECO:0000305" FT MOD_RES P29590-4:518 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES P29590-4:527 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT MOD_RES P29590-4:530 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983" FT CONFLICT P29590-10:419 FT /note="L -> V (in Ref. 5; AAG50187)" FT /evidence="ECO:0000305" SQ SEQUENCE 882 AA; 97551 MW; D50968A977E34287 CRC64; MEPAPARSPR PQQDPARPQE PTMPPPETPS EGRQPSPSPS PTERAPASEE EFQFLRCQQC QAEAKCPKLL PCLHTLCSGC LEASGMQCPI CQAPWPLGAD TPALDNVFFE SLQRRLSVYR QIVDAQAVCT RCKESADFWC FECEQLLCAK CFEAHQWFLK HEARPLAELR NQSVREFLDG TRKTNNIFCS NPNHRTPTLT SIYCRGCSKP LCCSCALLDS SHSELKCDIS AEIQQRQEEL DAMTQALQEQ DSAFGAVHAQ MHAAVGQLGR ARAETEELIR ERVRQVVAHV RAQERELLEA VDARYQRDYE EMASRLGRLD AVLQRIRTGS ALVQRMKCYA SDQEVLDMHG FLRQALCRLR QEEPQSLQAA VRTDGFDEFK VRLQDLSSCI TQGKDAAVSK KASPEAASTP RDPIDVDLPE EAERVKAQVQ ALGLAEAQPM AVVQSVPGAH PVPVYAFSIK GPSYGEDVSN TTTAQKRKCS QTQCPRKVIK MESEEGKEAR LARSSPEQPR PSTSKAVSPP HLDGPPSPRS PVIGSEVFLP NSNHVASGAG EAEERVVVIS SSEDSDAENS SSRELDDSSS ESSDLQLEGP STLRVLDENL ADPQAEDRPL VFFDLKIDNE TQKISQLAAV NRESKFRVVI QPEAFFSIYS KAVSLEVGLQ HFLSFLSSMR RPILACYKLW GPGLPNFFRA LEDINRLWEF QEAISGFLAA LPLIRERVPG ASSFKLKNLA QTYLARNMSE RSAMAAVLAM RDLCRLLEVS PGPQLAQHVY PFSSLQCFAS LQPLVQAAVL PRAEARLLAL HNVSFMELLS AHRRDRQGGL KKYSRYLSLQ TTTLPPAQPA FNLQALGTYF EGLLEGPALA RAEGVSTPLA GRGLAERASQ QS //