Prideapplication/xmlftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/Fletcher-EtheringtonetalPeptides.xlsxftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/Fletcher-EtheringtonetalProteins.xlsxftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A3_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_J1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_singleshot_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A6_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_B1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A5_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_H1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_B1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_F1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A2_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A8_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A11_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_K1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_D1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A4_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A12_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_I1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A10_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A7_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_A1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL2_A9_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_G1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_L1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_C1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/WCL1_E1_run1.rawftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/07/PXD017279/PRIDEsubmission-Detailsofsamples.docxprimaryOK200mpw1001@cam.ac.ukMichael WeekesMass SpectrometryShotgun proteomicsNot availablehost-pathogen interactionproteasomemlklcell deathHuman cytomegalovirus; cell death; necroptosis; host-pathogen interaction; quantitative proteomics; protein degradation; proteasome; mlklprotein degradationquantitative proteomicsnecroptosisHuman cytomegalovirushttp://www.ebi.ac.uk/pride/archive/projects/PXD017279Cell CultureFibroblastAt 48 hpi, cells were washed twice with PBS, and lysed (6M Guanidine/50 mM HEPES pH 8.5). From this point on, lysates from the 12h degradation screen from Nightingale et al. were treated identically to lysates from the second repeat of the 48h degradation screen (Experiment 2). Dithiothreitol (DTT) was added to half of the sample to a final concentration of 5 mM and incubated at room temperature for 20 mins. Cysteines were alkylated with 15 mM iodoacetamide and incubated for 20 min at room temperature in the dark. Excess iodoacetamide was quenched with DTT for 15 mins. Samples were diluted with 200 mM HEPES pH 8.5 to 1.5 M Guanidine followed by digestion at room temperature for 3 h with LysC protease at a 1:100 protease-to-protein ratio. Samples were further diluted with 200mM HEPES pH8.5 to 0.5 M Guanidine. Trypsin was then added at a 1:100 protease-to-protein ratio followed by overnight incubation at 37°C. The reaction was quenched with 5% formic acid and centrifuged at 21,000 g for 10 min to remove undigested protein. Peptides were subjected to C18 solid-phase extraction (SPE, Sep-Pak, Waters) and vacuum-centrifuged to near-dryness. Peptide Labelling with Tandem Mass Tags In preparation for TMT labelling, desalted peptides were dissolved in 200mM HEPES pH8.5. Peptide concentration was measured by microBCA (Pierce), and 25 g of peptide labelled with TMT reagent as previously described, and detailed in the attached Word file. An unfractionated single-shot was analysed initially to ensure similar peptide loading across each TMT channel, thus avoiding the need for excessive electronic normalization. In Experiment 1, as all normalisation factors were >0.5 and <2, data for the single-shot experiment was analysed with data for the corresponding fractions to increase the overall number of peptides quantified. In Experiment 2, data from 13 fractions was used in the analysis. Normalisation is discussed in ‘Data Analysis’ and high pH reversed-phase (HpRP) fractionation is discussed below. Offline HpRP Fractionation TMT-labelled tryptic peptides were subjected to HpRP fractionation using an Ultimate 3000 RSLC UHPLC system (Thermo Fisher Scientific) equipped with a 2.1 mm internal diameter (ID) x 25 cm long, 1.7 µm particle Kinetix Evo C18 column (Phenomenex) as previously described (Nightingale et al Cell Host and Microbe 2018). LC-MS3 For Experiment 1, mass spectrometry data was acquired using an Orbitrap Fusion mass spectrometer (Thermo Fisher Scientific, San Jose, CA). Peptides were separated using a Proxeon EASY-nLC 1000 LC pump equipped with a 75 μm inner diameter microcapillary column packed with 0.5 cm of Magic C4 resin (5 μm, 100 Å, Michrom Bioresources) followed by ∼20 cm of GP118 resin (1.8 μm, 120 Å, Sepax Technologies). Peptides were separated using a 3 hr gradient of 6 to 30% acetonitrile in 0.125% formic acid at a flow rate of 300 nL/min. Each analysis used a MultiNotch MS3-based TMT method (8, 9). The following settings were used: MS1: 400-1400 Th, Quadrupole isolation, 120,000 Resolution, 2x105 AGC target, 100 ms maximum injection time, ions injected for all parallisable time. MS2: Quadrupole isolation at an isolation width of m/z 0.5, CID fragmentation (NCE 35) with ion trap scanning out in rapid mode from m/z 350, 4000 AGC target, 150 ms maximum injection time, in centroid mode. MS3: In Synchronous Precursor Selection mode, the top 10 MS2 ions were selected for HCD fragmentation (NCE 55) and scanned in the Orbitrap at 60,000 resolution with an AGC target of 5x104 and a maximum accumulation time of 150 ms, ions were not accumulated for all parallelisable time. The entire MS/MS/MS cycle had a target time of 3 s. Dynamic exclusion was set to +/- 7 ppm for 90 s. MS2 fragmentation was trigged on precursors 5x103 counts and above. For Experiment 2, mass spectrometry data was similarly acquired using an Orbitrap Lumos (Thermo Fisher Scientific, San Jose, CA).PrideTMTiodoacetamide derivatized residueTMT6plex-126 reporter+balance reagent acylated residuemonohydroxylated residueMass spectra were processed using a Sequest-based software pipeline for quantitative proteomics, ‘‘MassPike’’, through a collaborative arrangement with Professor Steven Gygi’s laboratory at Harvard Medical School. MS spectra were converted to mzXML using an extractor built upon Thermo Fisher’s RAW File Reader library (version 4.0.26). This software is a component of the MassPike software platform and is licensed by Harvard Medical School. A combined database was constructed from (a) the human Uniprot database (26th January, 2017), (b) the HCMV strain Merlin Uniprot database, (c) all additional non-canonical human cytomegalovirus ORFs described by Stern-Ginossar et al. (11), (d) a six-frame translation of HCMV strain Merlin filtered to include all potential ORFs of ≥8 amino acids (delimited by stop-stop rather than requiring ATG-stop) and (e) common contaminants such as porcine trypsin and endoproteinase LysC. ORFs from the six-frame translation (6FT-ORFs) were named as follows: 6FT_Frame_ORFnumber_length, where Frame is numbered 1-6, and length is the length in amino acids. The combined database was concatenated with a reverse database composed of all protein sequences in reversed order. Searches were performed using a 20 ppm precursor ion tolerance. Fragment ion tolerance was set to 1.0 Th. TMT tags on lysine residues and peptide N termini (Experiment 1: 229.162932 Da; Experiment 2: 304.2071) and carbamidomethylation of cysteine residues (57.02146 Da) were set as static modifications, while oxidation of methionine residues (15.99492 Da) was set as a variable modification. To control the fraction of erroneous protein identifications, a target-decoy strategy was employed (12). Peptide spectral matches (PSMs) were filtered to an initial peptide-level false discovery rate (FDR) of 1% with subsequent filtering to attain a final protein-level FDR of 1%. PSM filtering was performed using a linear discriminant analysis, as described previously (12). The following parameters were considered: XCorr, DCn, missed cleavages, peptide length, charge state, and precursor mass accuracy. Protein assembly was guided by principles of parsimony to produce the smallest set of proteins necessary to account for all observed peptides (algorithm described in (12)). Proteins were quantified by summing TMT reporter ion counts across all matching peptide-spectral matches using ’’MassPike’’, as described previously (8). Briefly, a 0.003 Th window around the theoretical m/z of each reporter ion was scanned for ions and the maximum intensity nearest to the theoretical m/z was used. The primary determinant of quantitation quality is the number of TMT reporter ions detected in each MS3 spectrum, which is directly proportional to the signal-to-noise (S:N) ratio observed for each ion. Conservatively, every individual peptide used for quantitation was required to contribute sufficient TMT reporter ions so that each on its own could be expected to provide a representative picture of relative protein abundance (8). An isolation specificity filter with a cut-off of 50% was additionally employed to minimise peptide co-isolation (8). Peptide-spectral matches with poor quality MS3 spectra (a combined S:N ratio of less than 120 (experiment 1) or 240 (experiment 2) across all TMT reporter ions) or no MS3 spectra at all were excluded from quantitation. Peptides meeting the stated criteria for reliable quantitation were then summed by parent protein, in effect weighting the contributions of individual peptides to the total protein signal based on their individual TMT reporter ion yields. Protein quantitation values were exported for further analysis in Excel. For protein quantitation, reverse and contaminant proteins were removed, then each reporter ion channel was summed across all quantified proteins and normalised assuming equal protein loading across all channels. For further analysis and display in Figures, fractional TMT signals were used (i.e. reporting the fraction of maximal signal observed for each protein in each TMT channel, rather than the absolute normalized signal intensity). This effectively corrected for differences in the numbers of peptides observed per protein.ProteomicsMichael WeekesOrbitrap Fusion LumosOrbitrap FusionPARTIALCambridge Institute for Medical Research, University of Cambridge, Hills Road, Cambridge, CB2 0XY, UKCytomegalovirusHomo Sapiens (human)Not availablempw1001@cam.ac.ukUniversity of CambridgeUnited Kingdomsodium salt, l(2)k04204, l(4)17, single-organism catabolic process, type 1, l(4)13, ammonium formate, Gli, 13C-labeled, cadmium salt, MeCN, PLXN5, ion, PNT-P1, Cid[Mel], Ci[D], fond, EY3-1, magnesium formate, CycEI, Apaf-1, zinc salt, CENP-A, Long Term, SeP, CENP-C, 5730420M11Rik, dmTAF[[II]]230, Polypeptides, solid, protein polypeptide chains, CEH, cobalt(II) formate dihydrate, type I, CH3-C#N, B1, 1, 2, NEPII, Analysis, D-ets-2, 3520, SEH, WMS, Sep, SEP, HPI, (R*, SET, 2810441M03Rik, Divorced, BcDNA:RE21270, sarcoma of breast, hac-1, TFIID TAF250, Analyses, cel, catabolism, phosphatase 2A inhibitor I2PP2A, Salt, Su(Mir)1, proteins, Divorces, number of, T6G21.3, sEP, AI047805, DmelCG4299, isolation and purification, set, CI, hydroperoxide isomerase activity, column, Magics, sample, D1, s, Prx3, DmAAF34715, nickel salt, SGS, accumulated, CiD, Ce, dTAF[[II]]230, Stars, Ci, BZRP, cobalt (+2) salt, anon-53Fa, TAF200, Longterm Effect, l(2)SH0173, Guanidine Monohydroiodine, breast sarcoma, Cyc E, proline oxidase deficiency, Spectrum Analysis, not genetically inherited, collisionally activated dissociation, CID, ciD, Cid, PBS, ACMICD, PBR, sodium (4:1:1) salt, BG:DS07108.3, Dm1, magnesium salt, span., ci-D, l(2)05206, CG6829, dark/hac-1/dapaf-1, pntP2, breakdown, Pointed-P1, HLA-DR-associated protein II, Grv, CENP-A/Cid, CENP-A/CID, DI-2, CENPA, I-2Dm, Ets94F, formate, Spectrometry, pooled, Guanidine Phosphate, cromium (+3), inhibitor of granzyme A-activated DNase, beta Trypsin, I-2PP1, Painful bladder syndrome, TAF-IBETA, Taf250, grv, 4-hydroxyphenyllactate:NAD+ oxidoreductase activity, ammonium (4:1) salt, 2018, TAF-Ibeta, methyl cyanide, lead (+2) salt, STARS, TMT, 42/4, Ci-155, TAF230, BPBS, Cleland Reagent, 0998/12, OG12X, nickel formate dihydrate, cycline, lead formate, sarcoma of the breast, Effects, DmcyclinE, aluminum salt, number, Pierce, 4-dimercapto-, precursor, R*)-, NAT13P, protein-containing complex, thomson, body system, combined T and B cell immunodeficiency, CG7826, mass-to-charge ratio, l(2)k05821, cdi7, period, CenpA, DMPOINT1A, Guanidium, cyclinE, l(2)k15606, isolation, IT, CG7835, Cdi7, CDI7, CG42273, system, nat13, Siah, Monohydroiodine, anatomical systems, dTAF[[II]]250, pointed-RC, thallium (+1) salt, Longterm, cell, Monosodium Salt, beta-Trypsin, rubidium salt, 2pp2a, pk18, Long-Term, methanoic acid, DmcycE, ions, MBR, EK3-2, CG10574, CD156, Injectable, l(3)07825, dTAF250, Monohydrobromide, Guanidinium Chloride, HPRP, 2PP2A, (9Z, 13-hydro-lyase activity, HYRPRO1, dSET, dSet, PTBR, CG2125, CG17077, peptidos, 14Z)-(13S)-hydroperoxyoctadeca-9, 4-(2-hydroxyethyl)-, PTHB1, dark/dapaf-1/hac-1, Guanidine Monohydrate, Ets, Guanidine Nitrate, 1-(14)C-labeled, degradation, dApaf-1, mak3, CG18076, Clelands Reagent, Mell1, potassium formate, BG:DS00004.13, copper (+2) salt, backward, acetonitrile, Cell, dTAF230, polypeptide, APAF1, Experiment, l(2)k02514, Temperatures, native protein, DmCycE, Hac-1, ci[D], I-2PP2A, C18, cupric formate, chemical analysis, Long Term Effects, Dm I-2, TAF[[II]]250/230, Nitrate, MFS1, attached, aluminum formate, pnt-P1, pnt-P2, Mass Spectrum Analyses, Cleland's, Guanidine Monohydrobromide, AU020952, Taf[[II]]250, hydroperoxide dehydratase activity, Guanidine, lithium formate, DmelCG2125, l(2)k02602, Guanidine Sulfate, ci155, CenH3, hyperprolinemia caused by mutation in PRODH, Separations, Striated muscle activator of Rho-dependent signaling, Chloride, Dark/Dapaf-1/HAC1, kak, ethanenitrile, hyperprolinemia type 1, mDRC, CD156a, OG12, Longterm Effects, ME-IV, 11-dienoate-forming], plan specification, Cleland's Reagent, linoleic acid hydroperoxide isomerase, D-CycE, 13-hydro-lyase [(9Z)-(13S)-12, Og12x, Mak3, CenpA/CID, Sulfate, POINT, NEP2, reversed, CG8705, MAK3, multicellular organismal catabolic process, Hac-1/Dark, host organism, IPP2A2, NCMe, determination, affixed to, selection process, DmelCG6829, DmelCG17077, zinc formate, Nl1, Monohydrate, atado, Guanidine Sulfate (2:1), HEPES Monosodium Salt, lead salt, Pnt, protein, 6330543G17Rik, combined T cell and B cell immunodeficiency, 11, peptide, 11E, ammonium tetraformate, png, peptido, ClvPrd, Ccne, NL1, Min, Apaf1, NL2, protein aggregate, ARK, Injectables, Effect, DmelCG42273, Pnt-P1, Mass Spectrum Analysis, CG13329, HEPES Monosodium, peptides, dermoid cyst with malignant transformation, TAF-I, long, E430039A18Rik, min, arc, mAPC, IBP, Phosphate, purification, CG12352, copper, ark, T1, hNAT5, reaction, IGAAD, lithium salt, hSAN, 1-Piperazineethanesulfonic acid, Sputolysin, DmelCG10574, ppm, Cenp-A, l(2)CA4, Guanidine Sulfate (1:1), dApaf1, Bladder pain syndrome, GPHYSD2, ammonium (2:1) salt, Long-Term Effects, Mak3p, phapii, Monohydrochloride, D-Apaf-1, NAT13, Dmel_CG7826, StF-IT-1, D-Ets-2, Th, ets94F, 0123/09, extra or missing physical or functional parts, TAFII-250, TAF250/230, br37, Nat13, shortstop/kakapo, Spectroscopy, S-adenosyl-L-methionine:thiol S-methyltransferase activity, TAFII250, HCD, Cleland, Ionen, MMEL2, DmelCG18076, nickel (+2) salt, Dmel_CG7835, cenpA, Mnb, MNB, parent ion, ammonium salt, Painful Bladder Syndrome, Ci/Gli, Ci/GLI, CenH3/CID, MS/MS, Xylella fastidiosa str. Temecula1, cobaltous formate, Guanidine Monohydrochloride, 3-Butanediol, hac1, MASS, CG4299, AW124434, CG17603, TAF[[II]], SHOT, organ system, congenital combined immunodeficiency, ptd, dapaf-1S, PntP2, apaf-1, dapaf-1L, l35Dd, precursor ion, Acetamide, SR3-5, PntP1, E(E2F)3D, copper salt, hyperprolinemia, PNTP2, Eph2, Polypeptide, HEPES, i2pp2a, PNTP1, 2600005K24Rik, time, Bladder Pain Syndrome, d230, nat5, Dapaf-1/HAC-1, Reagent, ETS2, Ets2, cesium salt, Z-350, FBN, PLEXIN-B1, dTAFII250, NAT5P, cycE, Spectrum Analyses, EfW1, l(2)br37, PHAPII, CYCLE, formic acid, 4-(3-(4-(1-(4-methylphenyl)-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)benzoyl)indole-1-yl)butyric acid, Dark/Hac-1/dApaf1, l(4)102ABc, method, pntegfr, Hac1, potassium salt, 0608/07, Dark/Hac-1/dApaf-1, polypeptide chain, template-activating factor I, dmTAF1, Ms1, ECTOL1, Taf230, Injection, 14C-labeled, method used in an experiment, Mass, Separated, Shot, Mass Spectroscopy, TAF250, CenH3[Cid], CenH3[CID], Guanidium Chloride, CG2916, Taf200, l(2)k10821, CYCE, MS1, MS3, iones, MS2, DmelCG3938, CyclE, ipp2a2, dapaf-1, DmelCG13329, 3938, Taf1p, dapaf, labeling, dark, calcium formate, PRODH hyperprolinemia, OCTD, Xylella fastidiosa (strain Temecula1 / ATCC 700964), X-linked combined immunodeficiency, l(2)k05007, 13-epoxyoctadeca-9, dm-cycE, 10^[-6], DARK, Electronic, taf-ibeta, male sterility 1, DmelCG12352, has or lacks parts of type, SELP, Nat5, NAT5, N-2-Hydroxyethylpiperazine-N'-2'-ethanesulfonic Acid, cromium (+3) salt, Long-Term Effect, dArk, TAF, Dapaf-1, Guanidine Hydrochloride, l(3)j1B7, 2-iodo-, sodium formate, thiol methyltransferase activity, span, combined immunodeficiency, DYRK1, data, TAF[[II]]250, nickel formate, DBI, 3H-labeled, protein complex, kop, igaad, strontium formate, l(3)84Ab, cenH3, apaf1, CG18637, strontium salt, Guanidinium, Peptide, mereological quality, sep5, AW112078, CAD, PKBS, natural protein, Ci155, p230, Protein, I2PP2A, Hydrochloride, Guanidine Sulfite (1:1), TFIID, linoleate hydroperoxide isomerase, Dyrk1, Dark, Vacuums, CyeE, connected anatomical system, Dark/Apaf-I, ACETONITRILE, l(3)s118306, tandem MS, WMS2, cyanomethane, teratoma with malignant transformation, San, SAN, 14-trienoate 12, Mass Spectrum, l(2)k05434, Separation, TAF[[II]]230, MALE STERILITY 1 PROTEIN, l(2)k03010, CC1, DmelCG2916, l(2)35Dd, Tripcellim, N 2 Hydroxyethylpiperazine N' 2' ethanesulfonic Acid, TAF[II]250, dApaf-1/DARK/HAC-1, sample population, chromic formate, san, Trypure, dSET/TAF-Ibeta, Ets58AB, 2610030F17Rik, DmelCG17603, Ion, concentration, SSKS, cardinality, calcium salt, Peptid, assay, AA407739, CG3938, dAPAF-1, TAF1, CID/CENP-ASalivary Gland Viruses, human being, Viruses, accidental cell death., Salivary Gland, protein complex, proteins, protein, protein-containing complex, man, Human Herpesvirus 5, human, Cell, Human, protein polypeptide chains, Cytomegaloviruses, native protein, natural protein, polypeptide chain, Herpesvirus 5 (beta), Protein, Herpesvirus 5, Virus, HHV 5, necrosis, protein aggregate, Salivary Gland Virus, DeathSH2-Bb, protein translation, Bru, IPP2A2, Raw, ion, Lysine Hydrochloride, determination, Laboratory, Aminosaeure, mDcn, Irip, Amino acid, protein, composed of, NAALAdase, Inclusion Diseases, 5730420M11Rik, peptide, Polypeptides, NAALADase I, Cut, protein polypeptide chains, L-Isomer Methionine, FOLH, unspecified, STOP, Lysine Acetate, Drug Tolerance, Methionine, ClvPrd, peptido, SALIVARY GLAND VIRUS DIS, l(1)7Ba, l(1)7Bb, Virus, 2, C530001K22Rik, Software Engineering, 3.4.17.21, Analysis, protein aggregate, WMS, Computer Program, Cytomegaloviral infection, L Lysine, CYTOMEGALOVIRUS INFECT, Svc, SH2-B, somitogenic mesoderm, SET, F, amino acids, dermoid cyst with malignant transformation, peptides, reference sample, Membrane glutamate carboxypeptidase, Analyses, TAF-I, K, Cytomegalic, M, Open, phosphatase 2A inhibitor I2PP2A, Computer Programs and Programming, epsilon-diaminocaproic acid, PGS2, composition, proteins, purification, NAALAD1, number of, Cytomegalic Inclusion Diseases, ecotype, Folylpoly-gamma-glutamate carboxypeptidase, CG11387, DmelCG4299, isolation and purification, set, IGAAD, Cytomegaloviruses, LYS, DmelCG10574, ppm, Lysin, CT, Half Cystine, GPHYSD2, Salivary Gland Virus, Racemethionine, z, Disease due to Cytomegalovirus, drug tolerance, SGS, ratio, DC, phapii, protein anabolism, Noise, protein biosynthetic process, Zinc Cysteinate, unsegmented mesenchyme, immune system tolerance, Aminokarbonsaeure, T5E21.12, CYTOMEGALIC INCLUSION DIS, 2-Amino-4-(methylthio)butyric acid, Ct, Pollution, CMV infection, StF-IT-1, Th, PG40, extra or missing physical or functional parts, SH2-B PH domain-containing signaling mediator 1, Source Softwares, alpha-amino carboxylic acids, Software Tools, ACMICD, Programs, Program, Computer Applications, S-adenosyl-L-methionine:thiol S-methyltransferase activity, CMV - Cytomegalovirus infection, Ionen, Cytomegalovirus infectious disease, PSM, Psm, Algorithm, Computer Applications Software, Diseases, Computer Applications Softwares, protein formation, lysine, Immunologic Tolerance, NOS, Mtap6, Methionin, cultivar, laboratory, methionine, Softwares, Hmet, presumptive somite mesoderm, Prostate-specific membrane antigen, BcDNA:GH10590, T5E21_12, parent ion, Amino Acid, Acid, Pteroylpoly-gamma-glutamate carboxypeptidase, figures, Software Applications, HLA-DR-associated protein II, Amino acids, DI-2, Source Software, content, I-2Dm, FGCP, CSCD, proportionality, School, common, rate, L-Cysteine, MASS, CG4299, alpha, inhibitor of granzyme A-activated DNase, [X]Cytomegaloviral disease, beta Trypsin, human, I-2PP1, Pro-rich, Applications, Self Tolerance, TAF-IBETA, precursor ion, Tolerance, protein synthesis, PSMA, Acids, TAF-Ibeta, Polypeptide, Noise Pollution, Cytomegalovirus infection (disorder), i2pp2a, TMT, Liquimeth, Computer Software Applications, SH2 domain-containing protein 1B, human being, Cysteine Hydrochloride, 2-amino-4-(methylsulfanyl)butanoic acid, l(1)VE614, Peptidomics, False, Salivary Gland, Cytomegalic Inclusion, number, Aminocarbonsaeure, unsegmented paraxial mesoderm, L Isomer, FBN, Gene, Computer, alpha-amino acid, precursor, protein-containing complex, thomson, somitomeric mesoderm, presence, CYTOMEGALOVIRAL DISEASE, GCPII, PHAPII, unspecified (disorder), Human, Discriminant, mass-to-charge ratio, Stable tubule-only polypeptide, polypeptide chain, template-activating factor I, isolation, ECTOL1, Gene Products, L-Methionine, N-acetylated-alpha-linked acidic dipeptidase I, mKIAA1299, Del(8)44H, Lysine, Half-Cystine, Medical, HCMV infection, cytomegalovirus infection, Pedameth, Application, INFECT CYTOMEGALOVIRUS, Open Source Softwares, SH2B, proportion, Viruses, Infections, STOP145, MS3, Software Application, L Cysteine, iones, ipp2a2, beta-Trypsin, Open Source Software, 2pp2a, Cytomegalovirus Infection, mGCP, Salivary gland virus disease, ions, man, kf, CG10574, Computer Software Application, OCTD, Cytomegalovirus, 2PP2A, 2-amino-4-(methylthio)butanoic acid, Tools, 10^[-6], DmelCG11387, taf-ibeta, has or lacks parts of type, Herpesvirus 5, dSET, dSet, Cytomegalic inclusion disease, PGII, peptidos, metionina, Inclusion Disease, thiol methyltransferase activity, Controlled, Applications Software, Open Source, Disease, 2810411E12Rik, Controlling, adequate, Computer Software, DL-Methionine, protein complex, Map-6, Proteins, igaad, alpha-amino acids, compositionality, backward, L-Isomer, Peptide, Tool, GCP2, strain, Glutamate carboxypeptidase II, mereological quality, polypeptide, count in organism, Software Tool, Cell growth-inhibiting gene 27 protein, Experiment, Cytomegalovirus Infections, native protein, Immune Tolerance, natural protein, I-2PP2A, Acetate, Protein, Dm I-2, chemical analysis, I2PP2A, Infection, protein biosynthesis, MFS1, merlin, 145-kDa STOP, segmental plate, Sh2bpsm1, Software, L-Lysine, Library, WMS2, Data Base, Met, SLRR1B, MAP-6, teratoma with malignant transformation, Salivary Gland Viruses, HCMV, PH and SH2 domain-containing signaling mediator, Cytomegalovirus infection, Col4a-1, DSPG2, Cytomagalovirus infection, Protein., Cytomegaloviral disease, Engineering, Tripcellim, Medical School, Amino, Human Herpesvirus 5, Folate hydrolase 1, Noises, Protein Gene Products, incised, Computer Programs, Trypure, Gene Proteins, dSET/TAF-Ibeta, 2610030F17Rik, Medical Schools, Applications Softwares, Ion, Herpesvirus 5 (beta), Discriminant Analyses, SSKS, structure, AI425885, cardinality, alpha-amino-gamma-methylmercaptobutyric acid, quotient, HHV 5, Peptid, assay, quantitative, AA407739, 6-diaminohexanoic acid, INCLUSION DIS, Enisyl, reversed, presence or absence in organism, Immunological Tolerancemulticellular organismal catabolic process, single-organism catabolic process, host organism, 2.7.11.25, passive evasion of immune response of other organism involved in symbiotic interaction, protein, induction of necroptosis of activated-T cells, type I programmed cell death, Inclusion Diseases, Mutations, protein polypeptide chains, unspecified, SALIVARY GLAND VIRUS DIS, Extrinsic Pathway Apoptoses, Programmed, Virus, protein aggregate, Cytomegaloviral infection, WMS, CYTOMEGALOVIRUS INFECT, establishment of necroptosis, Cytomegalic, catabolism, FLICE Protein, establishment of necroptosis of activated-T cells, proteins, pro-survival, Cytomegalic Inclusion Diseases, ecotype, programmed necrotic cell death, Intrinsic Pathway Apoptosis, Cytomegaloviruses, Immune, Classic, induction of necroptosis by extracellular signals, Classical Apoptosis, apoptosis inhibitor activity, active immune evasion, hMLKL, necrosis, Salivary Gland Virus, GPHYSD2, Disease due to Cytomegalovirus, extracellular signal-induced necroptosis, SGS, cellular suicide, Dual leucine zipper bearing kinase, Caspase-Dependent Apoptosis, MLK, downregulation of apoptosis, CYTOMEGALIC INCLUSION DIS, CMV infection, Evasion, late, ACMICD, mitigation of host immune response by virus, signaling (initiator) caspase activity, induction of apoptosis, CMV - Cytomegalovirus infection, Cytomegalovirus infectious disease, Intrinsic Pathway, Extrinsic Pathway Apoptosis, Diseases, passive evasion of host immune response, Caspase-8, NOS, immune evasion, cultivar, Caspase-Dependent, activation, activation of necroptosis in response to extracellular signals, DLK, breakdown, Mch5 Protease, MACH Protein, MASS, Cell Death, negative regulation of apoptosis, MAPK-upstream kinase, RIPK1-mediated regulated necrosis, [X]Cytomegaloviral disease, human, Intrinsic Pathway Apoptoses, execution phase of necroptotic process, TNF-induced necroptosis, inhibition of apoptosis, induction of apoptosis by p53, Leucine zipper-bearing kinase, Extrinsic Pathway, Cytomegalovirus infection (disorder), Classical, Apoptoses, down-regulation of apoptosis, anti-apoptosis, Procaspase-8, human being, Peptidomics, Salivary Gland, Cytomegalic Inclusion, caspase-dependent programmed cell death, FBN, Gene, Caspase Dependent Apoptosis, protein-containing complex, apoptotic programmed cell death, CYTOMEGALOVIRAL DISEASE, activation of apoptosis, unspecified (disorder), Human, Immune Evasions, polypeptide chain, ECTOL1, passive immune evasion, Gene Products, activation of necroptosis of activated-T cells, Type I, HCMV infection, 9130019I15Rik, cytomegalovirus infection, INFECT CYTOMEGALOVIRUS, Viruses, accidental cell death., Infections, inhibiteur, Cytomegalovirus Infection, down regulation of apoptosis, Salivary gland virus disease, apoptosis activator activity, man, OCTD, Cytomegalovirus, inhibidor, Classic Apoptosis, execution phase of apoptotic process, activation of necroptosis, Herpesvirus 5, Cytomegalic inclusion disease, Evasions, Mixed lineage kinase, PARP-dependent cell death, programmed cell death by apoptosis, Inclusion Disease, active evasion of host immune response, Apoptosis, inhibitors, induction of necroptosis, Disease, adequate, cell suicide, degradation, protein complex, Proteins, apoptotic cell death, inhibitor, Procaspase 8, Cell, necroptosis, strain, MUK, CAP4 Protease, mitigation by virus of host immune response, Cytomegalovirus Infections, native protein, necroptotic execution phase, active evasion of immune response of other organism involved in symbiotic interaction, natural protein, activation of necroptosis by extracellular signals, Programmed Cell Death, Protein, Infection, programmed necrosis, MFS1, merlin, parthanatos, Death, WMS2, apoptosis signaling, Salivary Gland Viruses, HCMV, Pro Caspase 8, Cytomegalovirus infection, suppression by virus of host immune response, apoptosis, Cytomagalovirus infection, Cytomegaloviral disease, Pro-Caspase-8, ZPK, Human Herpesvirus 5, Protein Gene Products, Classic Apoptoses, evasion by virus of host immune response, Gene Proteins, mitigation of host immune response, Herpesvirus 5 (beta), apoptotic program, SSKS, commitment to apoptosis, evasion or tolerance of host immune response, HHV 5, INCLUSION DIS, Intrinsic, Leucine-zipper protein kinasefalseHuman cytomegalovirus protein pUL36: a dual cell death pathway inhibitorHuman cytomegalovirus (HCMV) is an important human pathogen and a paradigm of intrinsic, innate and adaptive viral immune evasion. Here, we employ multiplexed tandem mass tag-based proteomics to characterise host proteins targeted for degradation late during HCMV infection. This approach revealed that mixed lineage kinase domain-like protein (MLKL), a key terminal mediator of cellular necroptosis, was rapidly and persistently degraded by the minimally passaged HCMV strain Merlin but not the extensively passaged strain AD169. The strain Merlin viral inhibitor of apoptosis pUL36 was necessary and sufficient both to degrade MLKL and to inhibit necroptosis. Furthermore, mutation of pUL36 Cys131 abrogated MLKL degradation and restored necroptosis. As the same residue is also required for pUL36-mediated inhibition of apoptosis by preventing proteolytic activation of pro-caspase 8, we define pUL36 as a multifunctional inhibitor of both apoptotic and necroptotic cell death.2020-07-102020-01-24PXD0172792806551646099180498511145422492156843544071284218327042363336351198343006636362758385696363688881114301555711452631452623649346131269573666492391619364110665688951136364762723661112329442229555832323122586365434607925193659143205971293865581912502321195774818661968215867225680761755437359253668408169180454278775120108922505836741479564100392369420494334459741420012935293671567593643867716054048313152826930456271639162429204277944762376121810032962922113763948840479NCBITaxon:2157131527310510672059687201651636840717363096989361047821483643204210613204913816937432773204645351111032174592161292886712886764100694569410167634102107612773511316582135843014172981746336754128735675684030135062181301941119294393671104113644591394984320253012701047594120478861347495153721109716529982790513980317585439801260866398081375755518320196447111415542193255521138343911931819813981810269701069955529NCBITaxon:47518502983354764146547798251021699823897648407413735186287054824153NCBITaxon:50557984467525100036433414754803597413708115466547898353221599838106771034819852348780422531488414222863479461571871599191572952929211752719860148840633424951869123423515233598589859886559746499870392021110723635272159874190828743418235024145113969293190259390719017463601237474636172262536001319722119158531058859698951105198997237989772000263419610264266722758858156899628737562690724420237172019998570724074767927459615333554319313355418400513686150596866628666134751536329NCBITaxon:17632862873488376705802718481865368595986075105135294296110098402321000734882412336363071047005187878945556449447NCBITaxon:13356265419591399878168119011478281055524NCBITaxon:96061358584690081979153519307285930085290051184995262254121337591390143811139442370412044143708351581990119519532590841370137023943222774862615835583715371633376057267998086371137121906503714759172073127262981274575727090309031372814243371421044792491108239412NCBITaxon:961514780269266100658137352750454135663816475203750644223669502129349790546322455525365199764990814389923745374726473237602647312887055955362527403271602938511497864794362938247943722511775299167387193844137659393432715910022637674234442345467001287689591198467041464792936528034280382803510803481793922950271131681911265269971028621076015973611431140981087135547743658142450722953379698204232124223321803369822347081645733165467599287770203829314125295508114817448886437452649997283035718308550717629970767892683704151562887651388563924561152086595551655181135491432137159749535026143213858781707683194963401614280053164610466038151845474485009747697477118051240174841855601555479204274201488711053253297261005941289093164359900138943828354232423310829341220585604162991311227317018799152678181871049316407299467303337330485264638301130641399253064236121162065261610337286129940207340115357652611114716133865431201725323712552329935316317NCBITaxon:11084993841063267872862321933486208621160791392227681196125522814953932132232334774121827532917573129948861814084341033519963139248811533811533933043937556992862633911209488624157183997586444237486435332444260665332413439097682127178637863999839986865535291486541042986357358257632884019864982380102868899958665220341632138119380625631886571303443112130886581144889198466645463NCBITaxon:11072NCBITaxon:11071142800628835374375116597145943116598854331116781077854314408043933434NCBITaxon:11082693977382189931824431935128387145953116885311213278695berry86941003335869724436647015011142869215047514991054842047147251208470146497444974311700893062186441930611076323308056603960162179748258539460553965132127905688133775129817660171121478610502366946532051124501897441739412450128853183889198679488531911137910371647351660152943631631198573896939343237956026087121346334323223544314275241433611334565560291699636436802790105603140818838185733703401881274414437552162038713985584081724055986091838272759212744234081702759812744201274426235455382117627594328247480119915095648188229120455148167238473848190695148498101510693731263753405203860186497405224052141856451804NCBITaxon:8134780091522754847938703338499172261756109461614351203258120550523525944732054938646512138803766861206781122022307418670511867057387334869121938791868023980071868012154514683514081861508471206777691838851608611388869152167786721279010087043512317196928123929486771332261262198131882682411229265716329576938124712461485451328388348392949113903631204162665890771514880036942694169436945187901015080817053942065421055687317447127015329242814111946691169601454586953201019812646905505371408157697392830312383911283128212802811010832825253531522811235315349825741948153623142410145481NCBInr 201305192945970647312921288398031309800891496978103690122020756601736548566156641036951187021187052261861299526945656217219565810102865606156596560644329428386567171360416023587001504802100291325291118700144771664180913252926997566556661348879379651431340223926633636336613833663367111764510378905923213143448709767468NCBITaxon:405597674652359093226411320498217870749821634725656905691569256934362872249821187205697111327949928993002014538661410NCBITaxon:49328715568910005898732135248304611308126373039114398872532897187268723872487298727135293324223110677410677330554831791988224454461041059098824974736776787524875217082485578428196194439105402104547815805966100264462NCBITaxon:5486815464143945033077348751526008759875632325933548130573710010772675672675664306154319474492394704721122984476119152361088767NCBITaxon:1297884831398782745412931428986480126283485418985487563041259949529120491146247274601735272855525263852639119813330240976392465732252641109094674694163485131535231523845NCBITaxon:5659951736582200879325731399034651329196114644042479096109760616125732927294227294327294451338510516943146128017646571186961186941436183118698118691443906NCBITaxon:7771566338404330618519080256870325731056870861822305479186786618351350NCBITaxon:78039064515159903164515161040610943129257309193079109446091374944006198258741274707861923915NCBITaxon:714130951334347044830064192389003715908412810840697228233428104392010977974811406862867062004929102633932103480940674109784257546013076376619108049267NCBITaxon:9874276891214822126719411462104905619922595767748371NCBITaxon:7227156974370031263406591090130327697411476130941147013081307383234114793981105268513141313131139655397210184145504539911009845262724153009107662041149013037134441439832747003988435623928668390614404211945999949033657861853365843127531627331627713528086913519948831627550277999487167971820795413496600271306274154967550278044323966002530429257021272134916334916113581716741928434239549414717414718156269857301182590247149456091335626928675722640459537457574057411346761123352378548116851126216131091515429313961392139027148961288101601067574458024025122968335294413936658112086605762576344322066721408272120091140827428231772981843183443226575557575759281081706674442184922311210542111096976529818826331488373184319229438143124110497774438667825317513278042676085111022358801198732518519687916621411408224430491408223264561101411867631854312525985207677376777544580NCBITaxon:5571044722649329NCBITaxon:17731011713463492316633674510116106887313284262658725423188291581954654888391943661233681449855055438264131033884510665411963275625323231685691349409885532642462101736604118565031575018516515715735457157511162348086377216315749620488678629627552319758258458533668510523110091100901009264653234063340621200793596106453913125757469242030690259374580422777919552491313662392410731300146625315684569374515479221198561198571462594NCBITaxon:592012676716248NCBITaxon:104385626994127915422231314781340388722921008810654976717589554930562791292491155748634291202531637616131477115200228569439717265072561177628766920262899315634301922344634338722276343662823667421386388420493211354724473144731169681112902551613983367225279310036NCBITaxon:11266NCBITaxon:439488186794414549413749901004163459106592106590NCBITaxon:662442711239014427010049410289688333295494252826521581094343265215712790852562237270216543605076014355907632003593913054980081795361795351795341322343802218903643950198252898396427113053119252311771895877534605231218948932172697049803113180803014179813052114505338918789184NCBITaxon:970474940804980405788225931914024342712837342561361417997140814062900281315673754331316416315910097146297746714467506013917261450511152496274874968460519260201580021538186256226927561423142227511450520101755275914282664179906914174609111797779408252824582762167539131463977852714273507145134073203696223283580712296213754513678303086783710945801580229535814621333524179819310946194202452787809036809933084581058111524260NCBITaxon:1280561896187263514726403195206574670738538813546158215823903413905333815211809958335851149315242591130832263737NCBITaxon:12721148814855843104300245132668342953195738264530586126683514981496452158554528113208375146208964379504208963137979138712728384400667203275453260264471088036478434216599216597216595455032309821659621659116968331414532183217546271454361517203094980194547752555697815950943984525338551534398990371228577595156226231121088624455513108058884558707791817808431796758144571160488409859NCBITaxon:371626794015059076303555463263331199456545671025426420126420352486769674939254727933428146760945774449176048932191726525792501673428102395598632582788396591604903552527313366366666810242669102431024575741745268012675777641457966313670190832331156180895835510676657192763412359874445622066835070164002113615718006655648433767760207214413792997671400820140082111557110897244447899665349148624614749319292951946751299114127647363267656589363589366192011577271208370265554809664098614098609958676686337137221171101107687834974120280913485851348584502539249910861913249943311711395037117082711708281144522197822446147940210195375939723287581721874202566481219071NCBITaxon:57390507911654564526591774208321387NCBITaxon:615750521028307155864505912466635761311887631088878176179212190659407121906712111044975151950585066NCBITaxon:25068NCBITaxon:120651187036126344695060506150627249124643248784461229417101819430108673101851018457303963558633149246437151458430801321650855534822607101856871416333NCBITaxon:619111218778127645159812847421635775534709514512257864250112607042607052607075730616584573677340541636774831672331505610071337056NCBITaxon:30555044571928751298722282912680631532734171929111167815022830NCBITaxon:208964283661742NCBITaxon:569382688306401794699138995915104352581515140129448242825844160419759272604232816772850120310267386492405360883858115589227054156224882936534036771861568175119350150752211935021678791085791724071329121226628805712561329013335503857917851310078752824NCBITaxon:610172433594633185862607991612432141262200298492670NCBITaxon:1263719281249212528303856838569591130963223756110502582666255151978836009414604223524721401257515115151546170445446415243235965489592022158010019995550884606157915781928650338921162089453593650917389440NCBITaxon:685441275415901090134158955210129661030612967142368715851584515849157592141038419286481928649369113388914792359046133296610914947616436902116022164133159936909108917688149229990894621812144640287889332952828294456861749342273218903821247190400727NCBITaxon:991399782820641112916714537209215358157546266940265619401372060328114319333291292412922725739087267271037908573729214053294128160783931426265489822737792539059620732882735143129793605330797211595564060724144733521509493349334793604676290335670265669771933571580536076994688103761037741627638705200375842826831425685007123038364940813430749414422197857742171598921409239396211577811547569297932447047499061035919051581144527499073129877754699110358NCBITaxon:37296103609833411307981964320133679413367957831034015786582645365059116965478854698134317445861119529745531131316634305521329836031276129938505764261509901979401151345844577151346198351205623411676108077213487995696287782754466778721849620994887322184932097209620951441467761266447NCBITaxon:26970495091693694110312195883205092029061015801813068594588224995252972467411589338528942789426147740535608256737123343551414931740553451445147124546655334188925124679151641373345087713912903912952971962231274869317978911337310548763632712519850762554702225231187813865451655862238NCBITaxon:44664946493139458624212418730364911415167845881087439527031953462322226900516713996695271067889541200308954420665639545300558623355180426430200302284812426428272831102991029841445238626290319541832902586231955757558413101653823525577223823593994636010636010439948399478679005444042376108236355721162296771870547369312818245185579431868240667282493235825523327117062151261557228331314685349390NCBITaxon:1011428450297805952395988267427529595266437322430895938260943274959211222332951605201651087121697952528386972852904427421218707334747132342927816111921929760582181249885469584631220439733163910724358885872520493692955464803834369122432612419355955217493991281612042546551945822819332982972595571143179272843552857164812072413996166018762548296471876143786814904945147254572542725431761012148015410710318799361882945503034166336036165984050569352835352835252702152945669874297225724772585941097677812310061911079450950412694322710279434472568291146136521871448542334937347373495270004466449917591891582580433302448046260499NCBITaxon:12939108061246196290222461973206375229916945090681187947572307741258117578032903111472727909311036839978445972402874751295139126246933995271325210343043196291726448138178189360810802281561005476255759955350111234919222219791111968661979121040728139510802301040145954161934211032644161051160711117022721041170612744321085956210283128316683759729949514106588827114113161058413308794784475174293387709964326303396284179327793294172934106611457551392519232392320640131160620135666160621213324260533952851853478733959135674295105650024261911506218299633941346959753863121170519351626539002134188532216242534833482468822638632121969025016468606885126234777016669121513300305899105884500634349421608823578652224215745246729161321751267934065604642933114342808300181652365262126337175831678733450736544345076166690510894491089448NCBITaxon:2759653552071089444655066897447094287535NCBITaxon:5833300692906526659581211776266595311786654913497675192964417725784544417711581419NCBITaxon:1206638166611746732907365166844689960169944446859600NCBITaxon:58111182263477154119165784584840215530756636164034624136810893112686341428099612NCBITaxon:5820NCBITaxon:58212653115531992115085797552283680198637379196627290589605960644670960322708626659649604570509121045433090504292982938783481061279365448385107445419170113489961526659936916927573640782196325707529835103617120618925777128502330835270142786999141715877962730025110285631267361528696469643964444176874612811345069638171522996569657757501123869351746966222790963787576784218192119562330595216742697961344346360134519678967696771249515330439403224620096699685835547678968934205455760096819320111678078330381719117630247593217181717475933NCBITaxon:102981257118387279694836470384766438467635688NCBITaxon:150270298207621158612184512107496866111495720928520131913840405295071263854614666383379NCBITaxon:10239173610629970547515851744575412NCBITaxon:1024528586NCBITaxon:1024317481565633788067067135622583313618550992452779658334240906112563049495NCBITaxon:63121770707010094086929257074876138176514894232903217602399352146752947462947474376031781446560285321773846451772177437272557153481121532369014726647091317047258520920269785962859631263871214697212035332648373153214693583706903074937608333483333570472851111149708333283331214687108018749200637373505104287828014851750NCBITaxon:1155213992751562259311726231656777351116032932853422NCBITaxon:5759345089998103517307796407148457425457428121536024271875058NCBITaxon:104075678024271535242915954126291589203985781355886755122965879309458041920312410515358153985801331678906902725602725612214272563354422841027256434166379017904NCBITaxon:57963562355522221045775755969959101364CP010395.1224218573232239230741964164027848964472020693771756614403666610400540296543NCBITaxon:1170922469764992297936941638284593556182284590143673340353143673452763922611117957527640985986661362652810442179622490541565050176946996NCBITaxon:13131712507953389427955795942197228722854219253066129457041767240418891220889320889520755966452315217531536879830200465672139269635889NCBITaxon:13156730195388399227166665553256657123055341313590224911799866694006666842157671143535311510429831546891112985932730756604691361651056121491615221785238976336121491597041263082132888113613NCBITaxon:1865381889081916073NCBITaxon:1865366873039376527306855743615295266891057675358231223NCBITaxon:13830595984003585742917616089942917030027340542432327605681786064778161982159739975599802419947427577415593362371303681407340766670133888120410441111707111170829920407265636713914501344084408771117454797787454610740196794967957018640814082380394528135165966861235178616243231243230135992356127108978540964097978821035224327745157409097804092409344713529838615733178100816313625388654155401813416870436486979673239979371379548629916713033456433169173623125924851221282861109464722641988479451332103721284813173144077217913169315557781221119778212215225025518365231818600781131323848546456715916922591333499124961533454224327512047392432745365521340143649571657167849641673124966871601977162NCBITaxon:10357NCBITaxon:103581194881415784NCBITaxon:103591045856170721597652726341859347834113445826276261969471634955913645272621272623272624116071912389931214102403217142118213144032449032483431114778749093238481437113153681286640136841491859799491154373440302282352517429921895192952492949224924126267396731518766153348967301232801360319030414340119110224932493411020531979511211143919045186613907710619813530085592921486917198252157728141444818759449593625NCBITaxon:116762241351634342911045495267989536270000-0003-3196-5545