MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v02/MSV000084773/primary200OK0000Anne-Claude Gingrashttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=fa9a390227c24bb3b676d460e7c9abeegingras@lunenfeld.caMassIVE21UNIMOD:4 - "Iodoacetamide derivative."UNIMOD:259 - "13C(6) 15N(2) Silac label."UNIMOD:366 - "Deamidation in presence of O18."UNIMOD:35 - "Oxidation or Hydroxylation."UNIMOD:267 - "13C(6) 15N(4) Silac label."UNIMOD:329 - "Monomethylated arginine."ProteomicsOrbitrap Fusion LumosHomo Sapiens (ncbitaxon:9606)LTRIProtein arginine methyltransferases (PRMTs) regulate diverse biological processes and are increasingly being recognized for their potential as drug targets. Here we report the discovery of a potent, selective, and cell-active chemical probe for PRMT7. SGC3027 is a cell permeable prodrug, which in cells is converted to SGC8158, a potent, SAM-competitive PRMT7 inhibitor. Inhibition or knockout of cellular PRMT7 results in drastically reduced levels of arginine monomethylated HSP70 family stress-associated proteins. Structural and biochemical analyses reveal that PRMT7-driven in vitro methylation of HSP70 at R469 requires an ATP-bound, open conformation of HSP70. In cells, SGC3027 inhibits methylation of both constitutive and inducible forms of HSP70, and leads to decreased tolerance for perturbations of proteostasis including heat shock and proteasome inhibitors. These results demonstrate a role for PRMT7 and arginine methylation in stress response.Pharmacological inhibition of PRMT7 links arginine monomethylation to the cellular stress response.Szewczyk Magdalena M MM, Ishikawa Yoshinori Y, Organ Shawna S, Sakai Nozomu N, Li Fengling F, Halabelian Levon L, Ackloo Suzanne S, Couzens Amber L AL, Eram Mohammad M, Dilworth David D, Fukushi Hideto H, Harding Rachel R, Dela Seña Carlo C CC, Sugo Tsukasa T, Hayashi Kozo K, McLeod David D, Zepeda Carlos C, Aman Ahmed A, Sánchez-Osuna Maria M, Bonneil Eric E, Takagi Shinji S, Al-Awar Rima R, Tyers Mike M, Richard Stephane S, Takizawa Masayuki M, Gingras Anne-Claude AC, Arrowsmith Cheryl H CH, Vedadi Masoud M, Brown Peter J PJ, Nara Hiroshi H, Barsyte-Lovejoy Dalia DhUMP1, Menage a trois, dSOH1, DmelCG1057, Lipocortin II, hur, LPC2D, PN-1, PAP-IV, HEL-S-270, Annexin-2, Cyclin-G1-interacting protein, 3110004A18Rik, dTRAP18, SKmel28, Umph-1, Calpactin-1 heavy chain, 2610206B05Rik, SKMEL-28, PN-I, mPH2, melg, 1600024P05Rik, Annexin II, RING finger protein MAT1, P-36, 3.1.3.5, D130050K19Rik, RING finger protein 66, CAL1H, Cytosolic 5'-nucleotidase III, SKMel28, E130115E11Rik, CG1057, ANX2L4, P36, SK-MEL 28, AU-Mel, Pyrimidine 5'-nucleotidase 1, UMPH, LIP2, SK MEL 28, PSN1, lupin, POMP, SKMel-28, SK.MEL.28, NT5C3, Cytosolic 5'-nucleotidase 3, AA415044, P5'N-1, p36, MAT1, SKMEL28 cell, p35, Nt5c3a, elav1, Uridine 5'-monophosphate hydrolase 1, ANX2, SK-MEL28, elrA, SKML-28, SKMEL28, Early development regulatory protein 2, AI842776, Edr2, Elavl1, Umph1, Placental anticoagulant protein IV, Protein I, Xel-1, Trap18., Med31, Calpactin I heavy chain, Mph2, A3galt2, P5N-1, SK-Mel28, Nt5y, SK Mel 28, LPC2, BcDNA:GM28912, UMPH1, Chromobindin-8, hua, D4Ertd810e, cN-III, CDK7|cyclin-H assembly factorData Set., Co-Immunoprecipitations, Bru, Pfeiffer's disease (disorder), Papers, Data Set, Raw, determination, DL-Arginine Acetate, Arginine Hydrochloride, 2-Amino-5-guanidinovaleric acid, L Isomer, Goal, arginine, FBN, Monohydrate, Mononucleosis, 2-amino-5-guanidinopentanoic acid, Arginin, L-Isomer, DL Arginine Acetate, not genetically inherited, L-(+)-arginine, Co Immunoprecipitation, ACMICD, RGD1304869, Mono, (2S)-2-amino-5-(carbamimidamido)pentanoic acid, Publication, L-Isomer Arginine, ECTOL1, Harg, chemical analysis, 4933402B05Rik, Hydrochloride, Immune Precipitations, Kissing disease, MFS1, Del(8)44H, L Arginine, Arg, Immune Precipitation, WMS, WMS2, Gammaherpesviral mononucleosis (disorder), L-Arginine, Svc, (S)-2-amino-5-guanidinopentanoic acid, Col4a-1, Co-Immunoprecipitation, (2S)-2-amino-5-guanidinopentanoic acid, (S)-2-Amino-5-guanidinovaleric acid, R, Precipitation, Arginine, Glandular Fever, mononucleosis, Monohydrate DL-Arginine Acetate, MASS, infectious mononucleosis, OCTD, reaction, Table, Immune, glandular fever, Infectious Mononucleosis, Pfeiffer's disease, Monocytic angina, SSKS, Manuscripts, Filatov's disease, L-Arg, monocytic angina, BC006705, Glandular fever, Gammaherpesviral mononucleosis, assay, Precipitations, GPHYSD2, 2-amino-5-(carbamimidamido)pentanoic acid, SGS, L-ArgininL-Arginine, (S)-2-amino-5-guanidinopentanoic acid, L-Arginin., DL-Arginine Acetate, (2S)-2-amino-5-guanidinopentanoic acid, (S)-2-Amino-5-guanidinovaleric acid, Arginine Hydrochloride, 2-Amino-5-guanidinovaleric acid, R, L Isomer, arginine, Monohydrate, Arginine, Monohydrate DL-Arginine Acetate, 2-amino-5-guanidinopentanoic acid, Arginin, L-Isomer, DL Arginine Acetate, RGD1304869, L-(+)-arginine, (2S)-2-amino-5-(carbamimidamido)pentanoic acid, L-Isomer Arginine, Harg, 4933402B05Rik, Hydrochloride, L-Arg, BC006705, L Arginine, Arg, 2-amino-5-(carbamimidamido)pentanoic acidForms, ATHSP70, Striadyne, Heat Shock Stress, Kinship, Proteasome Inhibitor, Product, l(3)L3929, Hsc-4, scd, Progress Reports, RGD1304869, dmTAF[[II]]230, protein polypeptide chains, Biological Phenomenon, Biological, Summary Report, DmelCG1915, Life Cycle, irp94, DmelCG6489, DmelCG18743, hsp70 Ba, (S)-2-amino-5-guanidinopentanoic acid, Kinship Network, TFIID TAF250, Progress Report, cel, R, HSPH2, Arginine, HS24/P52, proteins, Monohydrate DL-Arginine Acetate, S-(5'-deoxyadenosin-5'-yl)-L-methionine, Hsp70Bc, Hsp70Bb, hsp70 Aa, Hsp70Bd, Field Reports, medicine, CrATP, Cr(H2O)4 ATP, Role Concepts, hsc70, Hsp70b, ATPsyn-&bgr, dTAF[[II]]230, Hsp70a, Heat Shock Response, ATPsyn-b, titin, TAF200, arginine, Test, HS24|P52, Heat Stresses, HSP70Bbb, SAMe, Hsp70B, Hsp70A, Role Concept, Dm-hsp70, Role, Magnesium Salt, ARABIDOPSIS HEAT SHOCK PROTEIN 70, DmelCG4264, Field, 5-dideoxy-beta-D-ribofuranos-5-yl][(3S)-3-amino-3-carboxypropyl](methyl)sulfonium, hsp-70, Report, Taf250, Hsp70A7d, dhsp70, CG18242, HSC70-4, CG31449, TAF230, CG18245, CG5834, l(3)j7A4, Magnesium Adenosine Triphosphate, In Vitro as Topic, conformation, Processes, 2-Amino-5-guanidinovaleric acid, ATP-MgCl2, hs70, IB, protein-containing complex, SLS, Sls, bs17d06.y1, Adenylpyrophosphate, 87A, In Vitro Testing, Harg, hsp70RY, AdoMet, DMHSP7A2, Gene Products, Titin, Technique, hsp70Bb-prime, In Vitro Tests, Heat Stress Response, Pro Drug, In, Methyltransferase, dTAF[[II]]250, Pro-Drugs, DMHSP7D1, cell, BAP74, Hsp 70, beta-ATPase, CG31359, Hsc70, CG31354, Proteostases, dTAF250, l(3)dre8, drugs, ATPasebeta, HSC70, MnATP, ATPase beta, KZ, L-Arg, Hsp-70Aa, Investigative Reports, Hsc4p, MCP, Methylations, ATPB, Biologic, CG31366, Pharmaceuticals, inhibitors, Products, Family Research, Precursor, Proteins, BG:DS00004.13, (3S)-5'-[(3-amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine, L-Isomer, Cell, Hsp70ab, dTAF230, Concept, Family Members, ATP-syn-B, hsp70A, hsp70B, E(csp)1545, In Vitro Test, native protein, L-Isomer Arginine, hsc70-4, Research Reports, 4933402B05Rik, TAF[[II]]250/230, Vitro Testing, Taf[[II]]250, hsp70a, dhsp70Aa, hsp70b, l(3)03550, Homeostasis, Pharmaceutic Preparations, underdeveloped, i190, (2S)-2-amino-5-guanidinopentanoic acid, D-Titin, Gene Proteins, DmHSP70AA, Heat-Stress Responses, Reports, Families, In Vitro Technique, Stress, DmelCG31449, Hsp70Bbc, Pharmaceutical Products, Relatives, Heat-Stress Response, HSP70Bc, Hsp70aB, Calcium Salt, Networks, Heat-Shock Reaction, l(3)Ca, Adenosine Triphosphate, DL-Arginine Acetate, Hsp70, Monohydrate, d-titin, protein, heat shock protein 70, HSP70, Biological Processes, APG-2, Techniques, Roles, Pharmaceutical Product, Hsp110, Concepts, Heat, Inhibitors, Arg, Drug Precursors, protein aggregate, Phenomenon, Summary Reports, Ket, Family Life Cycle, Shock, Chromium Adenosine Triphosphate, RY, Heat-Stress Reaction, DmelCG5834, S-adenosylmethionine, hsc4, (S)-2-Amino-5-guanidinovaleric acid, hypoplasia, xhsp70, Homeostases, DmelCG31359, ket, Progress, Prodrugs, ATPsyn b, GRP78, Pharmaceutical, DmelCG31366, CG4264, Family Life Cycles, ATP, inner salt, Chromium Ammonium Salt, L-Arginin, Process, dHsp70, Arginine Hydrochloride, Heat-Shock Responses, 0020/01, TAFII-250, Arginin, TAF250/230, TAFII250, Investigative Report, Heat Shock Stresses, Manganese Salt, Pharmaceutic, Biological Process, Filiation, HSC4, Hsc4, CG11154, L-Arginine, Biologic Phenomena, Methylations., In Vitro, Hsp70-BC, Hsp70-Ab, Tests, Heat-Stress Reactions, CG17603, TAF[[II]], Life Cycles, CaATP, CG1915, SR3-5, MgATP, BC006705, CG6489, Inhibitor, d230, Family Member, Testings, Proteasome Endopeptidase Complex Inhibitors, L Isomer, Gene, Protein Homeostasis, dTAFII250, hsp70(87A), hsp70Ab, hsp70Aa, HEL-S-5a, Network, [1-(adenin-9-yl)-1, EfW1, L-(+)-arginine, Hsp70-1, Investigative, polypeptide chain, (2S)-2-amino-5-(carbamimidamido)pentanoic acid, reduced, dmTAF1, Taf230, ATP-synbeta, hsp70Ba, tiny, hsp70Bc, hsp70Bb, anon-CREST, Hsp-c4, l(3)j1D7, dhsc70, TAF250, Drugs, Taf200, DmelCG11154, Research, ATP MgCl2, inhibiteur, Taf1p, CG18857, hsp70 87A, hsp70 87C, inhibidor, Chromium Salt, Pro Drugs, Prodrug, Heat Shock Reaction, S-Adenosylmethionine, anon-WO0118547.237, l(3)rL182, Preparation, Kinship Networks, TAF, Family, relational structural quality, 2-amino-5-(carbamimidamido)pentanoic acid, Drug Precursor, small, TAF[[II]]250, protein complex, drug, Protein Homeostases, Magnesium Chloride, l(3)84Ab, inhibitor, Precursors, l(3)62Ca, 2-amino-5-guanidinopentanoic acid, Adenosine 5'-(tetrahydrogen triphosphate), DL Arginine Acetate, Testing, Proteasome, kettin, HSC-70, Atriphos, ML-1, Heat Stress, hsp68, natural protein, p230, Protein, Phenomena, Hydrochloride, In Vitro Testings, hsp70, TFIID, Heat Stress Reaction, L Arginine, methylation, Hsp70(87C), CG18743, SAM, D-titin, Hsp70.1, Manganese Adenosine Triphosphate, TAF[[II]]230, Acylcarnitine, Heat-Shock Reactions, E(nd)195, TAF[II]250, Heat Shock, Heat Shocks, sam, sal, Protein Gene Products, Drug, Preparations, DmelCG17603, CT41299, Pro-Drug, hsp 70, ATPIB, l(3)S002001, Summary, Field Report, Pharmaceutical Preparation, TAF10falseSzewczyk_InhibitionOfPRMT7_P36_2020This dataset consists of 16 raw MS files, acquired on Orbitrap Fusion Lumos Tribrid mass spectrometer operated in Data Dependent Acquisition (DDA) mode for the 8 input files and DDA with simultaneous parallel reaction monitoring (targeted masses; 599.33, 604.33, 608.23, 606.33, 407.89, 403.22, 651.35, 657.29, 656.02, 652.62, and 611.34) for the 8 mono-methyl arginine immunoprecipitation files. Samples were generated by Magdalena M Szewczyk and mass spectrometric acquisition was performed by Amber L Couzens. Analysis was performed by Amber L Couzens, Suzanne Ackloo, and David Dilworth The files are associated with a manuscript submitted for publication by Magdalena M Szewczyk et al. The main goal of this paper was to enable further discovery of PRMT7 biology and to explore its potential as a therapeutic target. Dalia Barsyte-Lovejoy (d.barsyte@utoronto.ca) and Hiroshi Nara (nara@pharm.or.jp) are the corresponding authors of the manuscript; Anne-Claude Gingras should be contacted for questions on this dataset (gingras@lunenfeld.ca). This submission is associated with 1 Supplementary Files (in addition to this README file) MassIVE_Table 1 describes the composition of this dataset Wed Jan 08 08:53:00 GMT 2020MSV00008477332409666