PML_HUMAN
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 03-AUG-2022, entry version 252.
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 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 [24]
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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
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 [35]
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 [36]
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 [37]
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 [38]
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 [39]
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 [40]
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 [41]
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 [42]
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 [43]
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 [44]
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 [45]
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 [46]
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 [47]
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 [48]
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 [49]
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 [50]
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 [51]
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 [52]
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 [53]
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 [54]
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 [55]
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 [56]
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 [57]
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 [58]
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 [59]
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 [60]
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 [61]
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 [62]
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 [63]
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 [64]
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 [65]
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 [66]
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 [67]
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 [68]
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 [69]
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 [70]
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 [71]
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 [72]
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 [73]
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 [74]
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 [75]
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 [76]
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 [77]
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 [78]
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 [79]
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 [80]
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 [81]
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 [82]
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 [83]
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 [84]
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 [85]
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 [86]
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 [87]
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 [88]
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 [89]
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 [90]
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 [91]
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 [92]
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 [93]
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 [94]
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 [95]
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 [96]
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 [97]
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 [98]
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 [99]
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 [100]
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 [101]
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 [102]
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 [103]
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 [104]
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 [105]
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 [106]
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 [107]
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 [108]
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 [109]
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 [110]
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. Isoform
CC PML-4 has a multifaceted role in the regulation of apoptosis and growth
CC suppression: activates RB1 and inhibits AKT1 via interactions with PP1
CC and PP2A phosphatases respectively, negatively affects the PI3K pathway
CC by inhibiting MTOR and activating PTEN, and positively regulates
CC p53/TP53 by acting at different levels (by promoting its acetylation
CC and phosphorylation and by inhibiting its MDM2-dependent degradation).
CC Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during
CC cellular senescence and the repression is dependent on a functional
CC RBL2/E2F4 repressor complex, regulates double-strand break repair in
CC gamma-irradiation-induced DNA damage responses via its interaction with
CC WRN, acts as a negative regulator of telomerase by interacting with
CC TERT, and regulates PER2 nuclear localization and circadian function.
CC Isoform PML-6 inhibits specifically the activity of the tetrameric form
CC of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform
CC PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are
CC involved in local chromatin-loop remodeling and gene expression
CC regulation at the MHC-I locus. Isoform PML-2 is required for efficient
CC IFN-gamma induced MHC II gene transcription via regulation of CIITA.
CC Cytoplasmic PML is involved in the regulation of the TGF-beta signaling
CC pathway. PML also regulates transcription activity of ELF4 and can act
CC as an important mediator for TNF-alpha- and IFN-alpha-mediated
CC inhibition of endothelial cell network formation and migration.
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). {ECO:0000269|PubMed:10610177,
CC ECO:0000269|PubMed:10669754, ECO:0000269|PubMed:10684855,
CC ECO:0000269|PubMed:11025664, 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; 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:27211601}. 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. HIPK2-
CC mediated phosphorylation at Ser-8, Ser-36 and Ser-38 leads to increased
CC accumulation of PML protein and its sumoylation and is required for the
CC maximal pro-apoptotic activity of PML after DNA damage. CHEK2-mediated
CC phosphorylation at Ser-117 is important for PML-mediated apoptosis
CC following DNA damage. MAPK1-mediated phosphorylations at Ser-403, Ser-
CC 505, Ser-527 and Ser-530 and CDK1/2-mediated phosphorylation at Ser-518
CC promote PIN1-dependent PML degradation. CK2-mediated phosphorylation at
CC Ser-565 primes PML ubiquitination via an unidentified ubiquitin ligase.
CC {ECO:0000269|PubMed:12402044, ECO:0000269|PubMed:15195100,
CC ECO:0000269|PubMed:18408734, ECO:0000269|PubMed:19015637,
CC ECO:0000269|PubMed:21840486, ECO:0000269|PubMed:22033920,
CC ECO:0000269|PubMed:22406621}.
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="http://atlasgeneticsoncology.org/Genes/PMLID41.html";
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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 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 AlphaFoldDB; P29590; -.
DR BMRB; P29590; -.
DR SMR; P29590; -.
DR BioGRID; 111384; 343.
DR CORUM; P29590; -.
DR DIP; DIP-33053N; -.
DR IntAct; P29590; 140.
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 BioMuta; PML; -.
DR DMDM; 215274219; -.
DR EPD; P29590; -.
DR jPOST; P29590; -.
DR MassIVE; P29590; -.
DR MaxQB; P29590; -.
DR PaxDb; P29590; -.
DR PeptideAtlas; P29590; -.
DR PRIDE; 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 Antibodypedia; 1737; 594 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 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; 421875at2759; -.
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 1136 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 169 other tissues.
DR ExpressionAtlas; P29590; baseline and differential.
DR Genevisible; P29590; HS.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
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:0042406; C:extrinsic component of endoplasmic reticulum membrane; ISS:UniProtKB.
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: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:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IEA:Ensembl.
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:0007182; P:common-partner SMAD protein phosphorylation; IEA:Ensembl.
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: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:0045892; P:negative regulation of transcription, DNA-templated; IDA: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:0045893; P:positive regulation of transcription, DNA-templated; IBA:GO_Central.
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: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:2000779; P:regulation of double-strand break repair; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; 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: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 Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR021978; DUF3583.
DR InterPro; IPR000315; Znf_B-box.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR Pfam; PF12126; DUF3583; 1.
DR Pfam; PF00643; zf-B_box; 1.
DR SMART; SM00336; BBOX; 1.
DR SMART; SM00184; RING; 1.
DR PROSITE; PS50119; ZF_BBOX; 2.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
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 R-
FT 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 S-
FT 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 R-
FT 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; AAH00080/
FT 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
