PML_MOUSE
ID PML_MOUSE Reviewed; 885 AA.
AC Q60953; Q8CEJ1; Q8VCC4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 29-MAY-2007, sequence version 3.
DT 03-AUG-2022, entry version 204.
DE RecName: Full=Protein PML;
GN Name=Pml;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Salivary gland;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-839 (ISOFORM 2).
RX PubMed=8563172; DOI=10.1007/bf00354296;
RA Goddard A.D., Yuan J.Q., Fairbairn L., Dexter M., Borrow J., Kozak C.,
RA Solomon E.;
RT "Cloning of the murine homolog of the leukemia-associated PML gene.";
RL Mamm. Genome 6:732-737(1995).
RN [4]
RP SEQUENCE REVISION TO 130; 212; 284; 638; 731; 750; 770-772; 820 AND 839.
RA Goddard A.D., Howe K., Solomon E.;
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9806545; DOI=10.1038/3073;
RA Wang Z.G., Ruggero D., Ronchetti S., Zhong S., Gaboli M., Rivi R.,
RA Pandolfi P.P.;
RT "PML is essential for multiple apoptotic pathways.";
RL Nat. Genet. 20:266-272(1998).
RN [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=9488655; DOI=10.1126/science.279.5356.1547;
RA Wang Z.G., Delva L., Gaboli M., Rivi R., Giorgio M., Cordon-Cardo C.,
RA Grosveld F., Pandolfi P.P.;
RT "Role of PML in cell growth and the retinoic acid pathway.";
RL Science 279:1547-1551(1998).
RN [7]
RP FUNCTION.
RX PubMed=10637504; DOI=10.1038/sj.onc.1203367;
RA Zhong S., Hu P., Ye T.Z., Stan R., Ellis N.A., Pandolfi P.P.;
RT "A role for PML and the nuclear body in genomic stability.";
RL Oncogene 18:7941-7947(1999).
RN [8]
RP SUMOYLATION, SUBCELLULAR LOCATION, AND SUBUNIT.
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 [9]
RP FUNCTION IN LCMV AND VSV RESTRICTION.
RX PubMed=11907221; DOI=10.1128/jvi.76.8.3810-3818.2002;
RA Bonilla W.V., Pinschewer D.D., Klenerman P., Rousson V., Gaboli M.,
RA Pandolfi P.P., Zinkernagel R.M., Salvato M.S., Hengartner H.;
RT "Effects of promyelocytic leukemia protein on virus-host balance.";
RL J. Virol. 76:3810-3818(2002).
RN [10]
RP DISRUPTION PHENOTYPE, AND 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 [11]
RP INTERACTION WITH TRIM69.
RX PubMed=12837286; DOI=10.1016/s0014-4827(03)00110-1;
RA Shyu H.-W., Hsu S.-H., Hsieh-Li H.-M., Li H.;
RT "Forced expression of RNF36 induces cell apoptosis.";
RL Exp. Cell Res. 287:301-313(2003).
RN [12]
RP FUNCTION.
RX PubMed=14976551; DOI=10.1038/sj.emboj.7600109;
RA Insinga A., Monestiroli S., Ronzoni S., Carbone R., Pearson M., Pruneri G.,
RA Viale G., Appella E., Pelicci P., Minucci S.;
RT "Impairment of p53 acetylation, stability and function by an oncogenic
RT transcription factor.";
RL EMBO J. 23:1144-1154(2004).
RN [13]
RP INTERACTION WITH SIAH2, 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 [14]
RP FUNCTION, INTERACTION WITH MDM2 AND RPL11, AND SUBCELLULAR LOCATION.
RX PubMed=15195100; DOI=10.1038/ncb1147;
RA Bernardi R., Scaglioni P.P., Bergmann S., Horn H.F., Vousden K.H.,
RA Pandolfi P.P.;
RT "PML regulates p53 stability by sequestering Mdm2 to the nucleolus.";
RL Nat. Cell Biol. 6:665-672(2004).
RN [15]
RP FUNCTION.
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 [16]
RP DISRUPTION PHENOTYPE, FUNCTION, AND INTERACTION WITH MTOR.
RX PubMed=16915281; DOI=10.1038/nature05029;
RA Bernardi R., Guernah I., Jin D., Grisendi S., Alimonti A.,
RA Teruya-Feldstein J., Cordon-Cardo C., Simon M.C., Rafii S., Pandolfi P.P.;
RT "PML inhibits HIF-1alpha translation and neoangiogenesis through repression
RT of mTOR.";
RL Nature 442:779-785(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17; SER-514 AND SER-515, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [19]
RP REVIEW ON FUNCTION.
RX PubMed=19652541; DOI=10.4161/cc.8.17.9462;
RA Li W., Rich T., Watson C.J.;
RT "PML: a tumor suppressor that regulates cell fate in mammary gland.";
RL Cell Cycle 8:2711-2717(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-528, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [21]
RP DISRUPTION PHENOTYPE, INTERACTION WITH RB1, AND FUNCTION.
RX PubMed=19136970; DOI=10.1038/nn.2251;
RA Regad T., Bellodi C., Nicotera P., Salomoni P.;
RT "The tumor suppressor Pml regulates cell fate in the developing
RT neocortex.";
RL Nat. Neurosci. 12:132-140(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-17; SER-404; SER-503;
RP SER-514; SER-515; SER-528; THR-535; SER-536 AND SER-609, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [23]
RP FUNCTION, INTERACTION WITH ITPR3, AND SUBCELLULAR LOCATION.
RX PubMed=21030605; DOI=10.1126/science.1189157;
RA Giorgi C., Ito K., Lin H.K., Santangelo C., Wieckowski M.R.,
RA Lebiedzinska M., Bononi A., Bonora M., Duszynski J., Bernardi R.,
RA Rizzuto R., Tacchetti C., Pinton P., Pandolfi P.P.;
RT "PML regulates apoptosis at endoplasmic reticulum by modulating calcium
RT release.";
RL Science 330:1247-1251(2010).
RN [24]
RP FUNCTION.
RX PubMed=21779477; DOI=10.1177/1947601911402682;
RA Lunardi A., Gaboli M., Giorgio M., Rivi R., Bygrave A., Antoniou M.,
RA Drabek D., Dzierzak E., Fagioli M., Salmena L., Botto M., Cordon-Cardo C.,
RA Luzzatto L., Pelicci P.G., Grosveld F., Pandolfi P.P.;
RT "A role for PML in innate immunity.";
RL Genes Cancer 2:10-19(2011).
RN [25]
RP FUNCTION.
RX PubMed=21427174; DOI=10.1093/intimm/dxr004;
RA Khalfin-Rabinovich Y., Weinstein A., Levi B.Z.;
RT "PML is a key component for the differentiation of myeloid progenitor cells
RT to macrophages.";
RL Int. Immunol. 23:287-296(2011).
RN [26]
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 [27]
RP FUNCTION IN CIRCADIAN CLOCK, SUBCELLULAR LOCATION, INTERACTION WITH PML,
RP AND DISRUPTION PHENOTYPE.
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 [28]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PPARGC1A AND KAT2A.
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 [29]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23279884; DOI=10.1111/gbb.12014;
RA Butler K., Martinez L.A., Tejada-Simon M.V.;
RT "Impaired cognitive function and reduced anxiety-related behavior in a
RT promyelocytic leukemia (PML) tumor suppressor protein-deficient mouse.";
RL Genes Brain Behav. 12:189-202(2013).
RN [30]
RP UBIQUITINATION.
RX PubMed=23530056; DOI=10.1128/mcb.01019-12;
RA Erker Y., Neyret-Kahn H., Seeler J.S., Dejean A., Atfi A., Levy L.;
RT "Arkadia, a novel SUMO-targeted ubiquitin ligase involved in PML
RT degradation.";
RL Mol. Cell. Biol. 33:2163-2177(2013).
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.
CC Positively regulates p53/TP53 by acting at different levels (by
CC promoting its acetylation and phosphorylation and by inhibiting its
CC MDM2-dependent degradation). Regulates phosphorylation of ITPR3 and
CC plays a role in the regulation of calcium homeostasis at the
CC endoplasmic reticulum. Regulates RB1 phosphorylation and activity. Acts
CC as both a negative regulator of PPARGC1A acetylation and a potent
CC activator of PPAR signaling and fatty acid oxidation. Regulates
CC translation of HIF1A by sequestering MTOR, and thereby plays a role in
CC neoangiogenesis and tumor vascularization. Regulates PER2 nuclear
CC localization and circadian function. Cytoplasmic PML is involved in the
CC regulation of the TGF-beta signaling pathway. Required for normal
CC development of the brain cortex during embryogenesis. Plays a role in
CC granulopoiesis or monopoiesis of myeloid progenitor cells. May play a
CC role regulating stem and progenitor cell fate in tissues as diverse as
CC blood, brain and breast. Shows antiviral activity towards lymphocytic
CC choriomeningitis virus (LCMV) and the vesicular stomatitis virus (VSV).
CC {ECO:0000269|PubMed:10637504, ECO:0000269|PubMed:11907221,
CC ECO:0000269|PubMed:12439746, ECO:0000269|PubMed:14976551,
CC ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15356634,
CC ECO:0000269|PubMed:16915281, ECO:0000269|PubMed:19136970,
CC ECO:0000269|PubMed:21030605, ECO:0000269|PubMed:21427174,
CC ECO:0000269|PubMed:21779477, ECO:0000269|PubMed:22274616,
CC ECO:0000269|PubMed:22886304, ECO:0000269|PubMed:23279884,
CC ECO:0000269|PubMed:9488655, ECO:0000269|PubMed:9806545}.
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 TERT, SIRT1,
CC TOPBP1, TRIM27 and TRIM69. Interacts with ELF4 (via C-terminus).
CC Interacts with Lassa virus Z protein and rabies virus phosphoprotein.
CC Interacts (in the cytoplasm) with TGFBR1, TGFBR2 and PKM. Interacts
CC (via the coiled-coil domain and when sumoylated) with SATB1. Interacts
CC with UBE2I; the interaction is enhanced by arsenic binding. Interacts
CC with SMAD2, SMAD3, DAXX, RPL11, HIPK2 and MTOR. Interacts with ITPR3,
CC PPP1A and RB1. Interacts with RNF4, NLRP3, MAGEA2, RBL2, PER2, E2F4 and
CC MAPK7/BMK1. Interacts with CSNK2A1 and CSNK2A3. Interacts with ANKRD2;
CC the interaction is direct. Interacts with PPARGC1A AND KAT2A. Interacts
CC (via SUMO-interacting motif) with sumoylated MORC3 (By similarity).
CC Interacts with TRIM16. Interacts with PRDM1 (By similarity).
CC {ECO:0000250|UniProtKB:P29590, ECO:0000269|PubMed:10779416,
CC ECO:0000269|PubMed:12837286, ECO:0000269|PubMed:14645235,
CC ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:16915281,
CC ECO:0000269|PubMed:19136970, ECO:0000269|PubMed:21030605,
CC ECO:0000269|PubMed:22274616, ECO:0000269|PubMed:22886304}.
CC -!- INTERACTION:
CC Q60953; P25446: Fas; NbExp=6; IntAct=EBI-3895605, EBI-296206;
CC Q60953; Q505F1: Nr2c1; NbExp=2; IntAct=EBI-3895605, EBI-15617004;
CC Q60953; O54943: Per2; NbExp=4; IntAct=EBI-3895605, EBI-1266779;
CC Q60953; Q60979: Skil; NbExp=5; IntAct=EBI-3895605, EBI-7213804;
CC Q60953; Q8UN00: gag-pro-pol; Xeno; NbExp=4; IntAct=EBI-3895605, EBI-6692904;
CC Q60953; Q16236: NFE2L2; Xeno; NbExp=2; IntAct=EBI-3895605, EBI-2007911;
CC Q60953-2; Q14DJ8: Axin1; NbExp=4; IntAct=EBI-4406901, EBI-4312125;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Nucleus, nucleoplasm.
CC Cytoplasm. Nucleus, PML body. Nucleus, nucleolus {ECO:0000250}.
CC Endoplasmic reticulum membrane; Peripheral membrane protein;
CC Cytoplasmic side. Early endosome membrane {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}.
CC Note=Detected in the nucleolus after DNA damage. Acetylation at Lys-497
CC is essential for its nuclear localization. Within the nucleus, most of
CC PML 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 (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q60953-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q60953-2; Sequence=VSP_026028;
CC -!- DOMAIN: The coiled-coil domain mediates a strong homo/multidimerization
CC activity essential for core assembly of PML-NBs. {ECO:0000250}.
CC -!- DOMAIN: Binds arsenic via the RING-type zinc finger. {ECO:0000250}.
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. {ECO:0000250}.
CC -!- PTM: Ubiquitinated; mediated by RNF4, RNF111, UHRF1, UBE3A/E6AP,
CC BCR(KLHL20) E3 ubiquitin ligase complex, SIAH1 or SIAH2 and leading to
CC subsequent proteasomal degradation. 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and
CC 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent
CC (By similarity). Ubiquitination by RNF111 is polysumoylation-dependent
CC (PubMed:23530056). Ubiquitination by BCR(KLHL20) E3 ubiquitin ligase
CC complex requires CDK1/2-mediated phosphorylation at Ser-528 which in
CC turn is recognized by prolyl-isopeptidase PIN1 and PIN1-catalyzed
CC isomerization further potentiates PML interaction with KLHL20 (By
CC similarity). {ECO:0000250|UniProtKB:P29590,
CC ECO:0000269|PubMed:23530056}.
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-70, Lys-165 and Lys-500) is
CC required for nuclear body formation. Sumoylation on Lys-165 is a
CC prerequisite for sumoylation on Lys-70. Lys-70 and Lys-165 are
CC sumoylated by PISA1 and PIAS2. PIAS1-mediated sumoylation of PML
CC promotes its interaction with CSNK2A1/CK2 and phosphorylation at Ser-
CC 575 which in turn triggers its ubiquitin-mediated degradation.
CC Sumoylation at Lys-500 by RANBP2 is essential for the proper assembly
CC of PML-NBs. Desumoylated by SENP1, SENP2, SENP3, SENP5 and SENP6 (By
CC similarity). {ECO:0000250|UniProtKB:P29590}.
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-17, Ser-45 and Ser-47 leads to
CC increased accumulation of PML protein and its sumoylation and is
CC required for the maximal pro-apoptotic activity of PML after DNA
CC damage. MAPK1- mediated phosphorylations at Ser-404, Ser-515 and Ser-
CC 540 and CDK1/2-mediated phosphorylation at Ser-528 promote PIN1-
CC dependent PML degradation. CK2-mediated phosphorylation at Ser-575
CC primes PML ubiquitination via an unidentified ubiquitin ligase (By
CC similarity). {ECO:0000250|UniProtKB:P29590}.
CC -!- PTM: Acetylation at Lys-497 is essential for its nuclear localization.
CC Deacetylated at Lys-497 by SIRT1 and this deacetylation promotes PML
CC control of PER2 nuclear localization (By similarity).
CC {ECO:0000250|UniProtKB:P29590}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate and
CC are fertile. They show leukopenia with reduced levels of circulating
CC granulocytes and myeloid cells. They are highly susceptible to
CC infections, causing a reduced life span. Mice do not exhibit normal
CC apoptosis of hematopoietic stem cells after DNA damage due to
CC irradiation. They do not exhibit normal apoptosis in response to FAS,
CC TNF, TGFB1, interferons and ceramide, and show impaired activation of
CC caspases in response to pro-apoptotic stimuli. Mice are highly
CC susceptible to chemical carcinogens. Mice display accelerated
CC revascularization after ischemia. Newborns have smaller brains with a
CC reduced size of the brain cortex. Mice display aberrant learning and
CC memory, lower levels of anxiety-like behavior and specific deficits in
CC long-term plasticity. Mice display a compromised endogenous circadian
CC clock with reduced precision and stability of the period length.
CC {ECO:0000269|PubMed:12439746, ECO:0000269|PubMed:16915281,
CC ECO:0000269|PubMed:19136970, ECO:0000269|PubMed:22274616,
CC ECO:0000269|PubMed:23279884, ECO:0000269|PubMed:9488655,
CC ECO:0000269|PubMed:9806545}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA97601.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AK028044; BAC25716.1; -; mRNA.
DR EMBL; BC020990; AAH20990.2; -; mRNA.
DR EMBL; U33626; AAA97601.2; ALT_INIT; mRNA.
DR CCDS; CCDS23239.1; -. [Q60953-1]
DR CCDS; CCDS23240.2; -. [Q60953-2]
DR RefSeq; NP_001298017.1; NM_001311088.1.
DR RefSeq; NP_032910.3; NM_008884.5. [Q60953-2]
DR RefSeq; NP_835188.2; NM_178087.4. [Q60953-1]
DR AlphaFoldDB; Q60953; -.
DR BioGRID; 202265; 28.
DR DIP; DIP-29279N; -.
DR IntAct; Q60953; 23.
DR MINT; Q60953; -.
DR STRING; 10090.ENSMUSP00000082816; -.
DR iPTMnet; Q60953; -.
DR PhosphoSitePlus; Q60953; -.
DR EPD; Q60953; -.
DR jPOST; Q60953; -.
DR MaxQB; Q60953; -.
DR PaxDb; Q60953; -.
DR PeptideAtlas; Q60953; -.
DR PRIDE; Q60953; -.
DR ProteomicsDB; 289459; -. [Q60953-1]
DR ProteomicsDB; 289460; -. [Q60953-2]
DR Antibodypedia; 1737; 594 antibodies from 44 providers.
DR DNASU; 18854; -.
DR Ensembl; ENSMUST00000085673; ENSMUSP00000082816; ENSMUSG00000036986. [Q60953-1]
DR Ensembl; ENSMUST00000114136; ENSMUSP00000109771; ENSMUSG00000036986. [Q60953-2]
DR GeneID; 18854; -.
DR KEGG; mmu:18854; -.
DR UCSC; uc009pwp.2; mouse. [Q60953-1]
DR UCSC; uc009pwq.2; mouse. [Q60953-2]
DR CTD; 5371; -.
DR MGI; MGI:104662; Pml.
DR VEuPathDB; HostDB:ENSMUSG00000036986; -.
DR eggNOG; KOG2177; Eukaryota.
DR GeneTree; ENSGT00510000048454; -.
DR HOGENOM; CLU_009136_1_0_1; -.
DR InParanoid; Q60953; -.
DR OMA; QRIRMGG; -.
DR OrthoDB; 421875at2759; -.
DR PhylomeDB; Q60953; -.
DR TreeFam; TF336434; -.
DR Reactome; R-MMU-3108214; SUMOylation of DNA damage response and repair proteins.
DR Reactome; R-MMU-3232142; SUMOylation of ubiquitinylation proteins.
DR Reactome; R-MMU-6804758; Regulation of TP53 Activity through Acetylation.
DR Reactome; R-MMU-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-MMU-8948747; Regulation of PTEN localization.
DR BioGRID-ORCS; 18854; 2 hits in 113 CRISPR screens.
DR ChiTaRS; Pml; mouse.
DR PRO; PR:Q60953; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q60953; protein.
DR Bgee; ENSMUSG00000036986; Expressed in embryonic post-anal tail and 231 other tissues.
DR ExpressionAtlas; Q60953; baseline and differential.
DR Genevisible; Q60953; MM.
DR GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042406; C:extrinsic component of endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IDA:MGI.
DR GO; GO:0031965; C:nuclear membrane; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IDA:MGI.
DR GO; GO:0050897; F:cobalt ion binding; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0046332; F:SMAD binding; IDA:MGI.
DR GO; GO:0032183; F:SUMO binding; ISO:MGI.
DR GO; GO:0019789; F:SUMO transferase activity; ISO:MGI.
DR GO; GO:0140037; F:sumo-dependent protein binding; ISO:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:MGI.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IMP:MGI.
DR GO; GO:0045165; P:cell fate commitment; IMP:MGI.
DR GO; GO:0071353; P:cellular response to interleukin-4; IDA:MGI.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0090398; P:cellular senescence; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0007182; P:common-partner SMAD protein phosphorylation; IMP:MGI.
DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IMP:UniProtKB.
DR GO; GO:0032469; P:endoplasmic reticulum calcium ion homeostasis; IMP:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IDA:UniProtKB.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0010761; P:fibroblast migration; IMP:CACAO.
DR GO; GO:0045087; P:innate immune response; IDA:UniProtKB.
DR GO; GO:0072332; P:intrinsic apoptotic signaling pathway by p53 class mediator; IMP:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IMP:MGI.
DR GO; GO:0008631; P:intrinsic apoptotic signaling pathway in response to oxidative stress; IMP:MGI.
DR GO; GO:0051457; P:maintenance of protein location in nucleus; ISO:MGI.
DR GO; GO:0030099; P:myeloid cell differentiation; IMP:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:AgBase.
DR GO; GO:0032692; P:negative regulation of interleukin-1 production; IMP:AgBase.
DR GO; GO:0045930; P:negative regulation of mitotic cell cycle; ISO:MGI.
DR GO; GO:0051974; P:negative regulation of telomerase activity; ISO:MGI.
DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0032938; P:negative regulation of translation in response to oxidative stress; ISO:MGI.
DR GO; GO:2000059; P:negative regulation of ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0090402; P:oncogene-induced cell senescence; IMP:UniProtKB.
DR GO; GO:0030578; P:PML body organization; IDA:MGI.
DR GO; GO:0060058; P:positive regulation of apoptotic process involved in mammary gland involution; ISO:MGI.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISO:MGI.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:CACAO.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; ISS:UniProtKB.
DR GO; GO:2000758; P:positive regulation of peptidyl-lysine acetylation; IMP:UniProtKB.
DR GO; GO:1904816; P:positive regulation of protein localization to chromosome, telomeric region; ISO:MGI.
DR GO; GO:1901798; P:positive regulation of signal transduction by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0006606; P:protein import into nucleus; IMP:MGI.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:0006605; P:protein targeting; ISS:UniProtKB.
DR GO; GO:0065003; P:protein-containing complex assembly; ISS:UniProtKB.
DR GO; GO:0031503; P:protein-containing complex localization; IMP:MGI.
DR GO; GO:0010522; P:regulation of calcium ion transport into cytosol; IMP:UniProtKB.
DR GO; GO:0030155; P:regulation of cell adhesion; IMP:CACAO.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:MGI.
DR GO; GO:0042752; P:regulation of circadian rhythm; IDA:UniProtKB.
DR GO; GO:2000779; P:regulation of double-strand break repair; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0034097; P:response to cytokine; ISO:MGI.
DR GO; GO:0010332; P:response to gamma radiation; IMP:MGI.
DR GO; GO:0001666; P:response to hypoxia; IMP:MGI.
DR GO; GO:0009411; P:response to UV; IMP:MGI.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IMP:MGI.
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; IMP:MGI.
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 Acetylation; Activator; Alternative splicing; Antiviral defense; Apoptosis;
KW Biological rhythms; Coiled coil; Cytoplasm; DNA-binding;
KW Endoplasmic reticulum; Endosome; Host-virus interaction; Immunity;
KW Innate immunity; Isopeptide bond; Membrane; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Tumor suppressor; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..885
FT /note="Protein PML"
FT /id="PRO_0000056002"
FT ZN_FING 62..97
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 129..171
FT /note="B box-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT ZN_FING 188..239
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 404..434
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 458..565
FT /note="Interaction with PER2"
FT /evidence="ECO:0000250"
FT REGION 500..599
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 566..572
FT /note="Sumo interaction motif (SIM)"
FT /evidence="ECO:0000250"
FT COILED 295..331
FT /evidence="ECO:0000255"
FT MOTIF 486..500
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 513..557
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 567..585
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 62
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 65
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 77
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 79
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 85
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 96
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 134
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 137
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 156
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 193
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 198
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 219
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT BINDING 226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00024"
FT MOD_RES 17
FT /note="Phosphoserine; by HIPK2"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 45
FT /note="Phosphoserine; by HIPK2 and MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT MOD_RES 47
FT /note="Phosphoserine; by HIPK2 and MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT MOD_RES 404
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 497
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT MOD_RES 503
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 514
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 515
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 522
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT MOD_RES 525
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT MOD_RES 528
FT /note="Phosphoserine; by CDK1 and CDK2"
FT /evidence="ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 535
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 536
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 540
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT MOD_RES 575
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT MOD_RES 609
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CROSSLNK 70
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 70
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT CROSSLNK 165
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 165
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT CROSSLNK 384
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT CROSSLNK 384
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT CROSSLNK 486
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT CROSSLNK 486
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT CROSSLNK 488
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT CROSSLNK 497
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT CROSSLNK 500
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250"
FT CROSSLNK 500
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P29590"
FT VAR_SEQ 431..476
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:8563172"
FT /id="VSP_026028"
FT CONFLICT 210
FT /note="G -> V (in Ref. 1; BAC25716)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="A -> V (in Ref. 1; BAC25716)"
FT /evidence="ECO:0000305"
FT CONFLICT 424
FT /note="T -> S (in Ref. 1; BAC25716)"
FT /evidence="ECO:0000305"
FT CONFLICT 429
FT /note="E -> V (in Ref. 2; AAH20990)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 885 AA; 98242 MW; 6A2F93F4CD482FDD CRC64;
METEPVSVQK VPAPPGSPCR QQDSALTPTP TMPPPEEPSE DYEHSQSPAE QAIQEEFQFL
RCPSCQAQAK CPKLLPCLHT LCSGCLEAPG LQCPICKAPG QADANGEALD NVFFESLQRR
LAVFRQIVDA QAACTRCKGL ADFWCFECEQ LICSKCFEAH QWYLKHEARP LADLRDNSVS
SFLDSTRKSN IFCSNTNHRN PALTDIYCRG CAKPLCCTCA LLDRNHSHLH CDIGEEIQQW
HEELGTMTQT LEEQGRTFDS AHAQMCSAIG QLDHARADIE KQIRARVRQV VDYVQAQERE
LLEAVNDRYQ RDYQEIAGQL SCLEAVLQRI RTSGALVKRM KLYASDQEVL DMHSFLRKAL
CSLRQEEPQN QKVQLLTRGF EEFKLCLQDF ISCITQRINA AVASPEAASN QPEAASTHPV
TTSTPEDLEQ PKEVQSVQAQ ALELSKTQPV AMVKTVPGAH PVPVYAFSMQ GPTYREEASQ
TVGSMKRKCS HEDCSRKIIK MESTEENEDR LATSSPEQSW PSTFKATSPP HLDGTSNPES
TVPEKKILLP NNNHVTSDTG ETEERVVVIS SSEDSDTENL SSHELDDSSS ESSSLQLEGP
NSLKALDESL AEPHLEDRTL VFFDLKIDNE TQKISQLAAV NRESKFRVLI QPEAFSVYSK
AVSLEAGLRH FLSFLTTMHR PILACSRLWG PGLPIFFQTL SDINKLWEFQ DTISGFLAVL
PLIRERIPGA SSFKLGNLAK TYLARNMSER SALASVLAMR DLCCLLEISP GLPLAQHIYS
FSSLQCFASL QPLIQASVLP QSEARLLALH NVSFVELLNA YRTNRQEGLK KYVHYLSLQT
TPLSSSASTQ VAQFLQALST HMEGLLEGHA PAGAEGKAES KGCLA
