MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v08/MSV000095873/primaryOK200Chantal Guillemettehttps://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=825e6abe7bb145aab083dc7eddfb836bchantal.guillemette@crchudequebec.ulaval.caMassIVE33UNIMOD:765 - "Removal of initiator methionine from protein N-terminus."MOD:00935 - "Oxidation of methionine to methionine sulfoxide with neutral loss of CH3SOH."MOD:01060 - "A protein modification that effectively converts an L-cysteine residue to S-carboxamidomethyl-L-cysteine."MOD:00768 - "Oxidation of methionine to methionine sulfone with neutral loss of CH3SO2H."ProteomicstimsTOF ProHomo Sapiens (ncbitaxon:9606)CHU de Quebec Research Center - Universite LavalGlucuronidation is a crucial pathway for the metabolism and detoxification of drugs and endobiotics, and primarily occurs in the liver. UGT2B17 is one of the 22 glycosyltransferases (UGT) that catalyze this reaction. In a large proportion of the population, UGT2B17 is absent due to complete gene deletion. We hypothesized that a UGT2B17 human deficiency affects the composition and function of the liver proteome, potentially provoking compensatory responses, and altering interconnected pathways and regulatory networks. The objective was to elucidate the liver proteome of UGT2B17-deficient individuals. Liver specimens from UGT2B17-deficient and proficient individuals were compared by mass spectrometry-based proteomics using data-independent acquisition. In UGT2B17-deficient livers, 80% of altered proteins showed increased abundance with a notable enrichment in various metabolic and chemical defense pathways, cellular stress and immune-related responses. Enzymes involved in the homeostasis of steroids, nicotinamide, carbohydrate and energy metabolism, and sugar pathways were also more abundant. Some of these changes support compensatory mechanisms, but do not involve other UGTs. An increased abundance of non-metabolic proteins suggests an adaptation to endoplasmic reticulum stress, and activation of immune responses. Data implies a disrupted hepatocellular homeostasis in UGT2B17-deficient individuals and offers new perspectives on functions and phenotypes associated with a complete UGT2B17 deficiency.The liver proteome of individuals with a natural UGT2B17 complete deficiency.Rouleau Michèle M, Schwab Matthias M, Klein Kathrin K, Tremmel Roman R, Haag Mathias M, Schaeffeler Elke E, Guillemette Chantal CAutoregulation, Metabolic Networks, Networks, Udpgt2b5, Udpgt-3, Pathway, Udpgt, total expressed protein, Udpgtr2., Network, Metabolic Network, dIKK-gamma, UDPGT2B17, jecur, BMND12, IKKgamma, DmIKKgamma, AI118071, positive regulation of homeostatic process, dIKK, DmIKK-gamma, Kenny, M-1, dmIKKgamma, Ugt2b17, IKK[[gamma]], Udpgtr-3, regulation of homeostatic process, Metabolic Pathways, IKKg, KEY, Key, Udpgtr2, UDPGT 2B5, Rlug38, Metabolic, Dmikkgamma, IKK-gamma, iecur, Pathways, inhibition of homeostatic process, CG16910, 2B1, Livers, activation of homeostatic process, DmelCG16910, IKK, Ugt2b3, Ugt2b5, negative regulation of homeostatic process, homeostasis, Metabolic Pathway, Proteomesbiochemical pathways, big, Metabolic Process, Udpgt2b5, Udpgt-3, human being, Product, Processes, Biocatalysts, Metabolic Concepts, Mbp1, Gene, Spectrum Analyses, Metabolic Processes, Ximpact, froggy, Gene Deletions, Gyltl1a, protrusion, jecur, Human, BMND12, School-Age, large, AI118071, Homo sapiens, Metabolism, Pharmaceutical Product, Mass, Concepts, Analysis, Metabolism Concept, Ugt2b17, Phenomenon, Udpgtr-3, myd, Metabolism Phenomena, Man, Mass Spectroscopy, Drugs, imprinted and ancient gene protein, Mass Spectrum Analysis, UDPGT 2B5, average, School-Age Populations, Man (Taxonomy), enzymes, Analyses, catabolism, MDDGB6, Tissue, iecur, Metabolic Concept, Mbp-1, metabolic process resulting in cell growth, LARGE, Deletions, Deletion, Population, DIA, BPFD#36, drugs, Enzyme, medicine, Pharmaceutical, Ugt2b3, great, Ugt2b5, biotransformation, Preparation, School Age Population, Catabolism, Pharmaceuticals, Products, anatomical protrusion, degradation, Process, gyltl1b-b, metabolism resulting in cell growth, Modern, Udpgt, total expressed protein, enzyme activity, Medications, Spectrum Analysis, Glycoside Transferases, impact-a, UDPGT2B17, Concept, Metabolic Phenomena, Spectroscopy, Metabolism Concepts, MS, MDDGA6, School Age, mKIAA0609, Phenomena, M-1, IMPACT, imprinted and ancient gene protein homolog, secretion, Pharmaceutic, KIAA0609, metabolism, Mass Spectrum Analyses, Metabolic Phenomenon, Udpgtr2, fg, Mass Spectrum, Populations, multicellular organism metabolic process, Glycosyltransferase, Rlug38, gyltl1b, biodegradation, Metabolic, Pharmaceutic Preparations, mdc1d, expanded, Spectrometry, Glycoside, School Age Populations, human, Drug, 2B1, Livers, MDC1D, Preparations, Transferases, enr, enlarged, spine, Modern Man, Biocatalyst, Mass., School-Age Population, Pharmaceutical Products, E430016J11Rik, Proteomes, RWDD5, humans, Pharmaceutical Preparation, Anabolismjecur, 2B1, UDPGT 2B5, Livers, BMND12, Udpgt2b5, Udpgt-3, AI118071, Rlug38, Ugt2b3, Ugt2b5, M-1, Udpgt, iecur, total expressed protein, Udpgtr2., Ugt2b17, Udpgtr-3, Proteomes, UDPGT2B17biochemical pathways, UGT, nicotinamidum, Metabolic Process, Udpgt2b5, Catatoxic, Product, 3-Pyridinecarboxamide, Metabolisms, Metabolic Concepts, Mbp1, Bioenergetics, hydrates de carbone, DmNST, UDP-Gal/UDP-GalNAc, glucide, carbohydrates, BMND12, ugt, School-Age, dNST-2, AI118071, anon-WO0172774.75, Nicobion, Endoplasmic Reticulum Stresses, glucido, Pharmaceutical Product, anon-WO0172774.73, Concepts, B3, vitamin B3, Analysis, Metabolism Concept, Expenditure, Phenomenon, Udpgtr-3, dNST-1, myd, Mass Spectrum Analysis, Steroid, Immune Processes, Kohlenhydrate, Immune Responses, UGT1, Man (Taxonomy), enzymes, beta-pyridinecarboxamide, Analyses, a steroid, catabolism, Moods, iecur, Mbp-1, metabolic process resulting in cell growth, UGT2, Deletions, inhibition of homeostatic process, 3 Pyridinecarboxamide, Nicotinamid, DIA, Niacinamide, UGAT, reaction, Immune, DmelCG2675, medicine, Pharmaceutical, Ugt2b3, Ugt2b5, homeostasis, Nicotinsaeureamid, biotransformation, Catabolism, mUGT1, Process, gyltl1b-b, metabolism resulting in cell growth, Modern, Solute carrier family 35 member A2, Udpgt, saccharides, Spectrum Analysis, Glycoside Transferases, Spectroscopy, niacin, ER stress, positive regulation of homeostatic process, MDDGA6, School Age, nicotinic acid amide, UGTL, mKIAA0609, ER, M-1, secretion, Pharmaceutic, KIAA0609, CSAT, activation, Kohlenhydrat, saccharidum, fg, Populations, Vitamin B3, Glycosyltransferase, gyltl1b, Vitamin, Endoplasmic Reticulum, mdc1d, CG2675, expanded, Spectrometry, 3-pyridinecarboxamide, Glycoside, carbohidratos, human, Phenotypes, MDC1D, carbohidrato, Energy Metabolisms, Transferases, enr, enlarged, nicotinic amide, GT, Biocatalyst, Reticulum Stresses, Vitamin PP, School-Age Population, a carbohydrate, glucidos, steroids, Proteomes, humans, m-(aminocarbonyl)pyridine, Steroids, big, Had1, Udpgt-3, Nikotinsaeureamid, human being, Peptidomics, Processes, Biocatalysts, CDGX, carbohydrate, Enduramide, saccharide, Gene, CG6850, Spectrum Analyses, Metabolic Processes, DUGT, froggy, Gene Deletions, Vitamin B 3, Gyltl1a, jecur, Human, pyridine-3-carboxylic acid amide, Stresses, large, Homo sapiens, Metabolism, Mass, Gene Products, CDG2M, Mood, ER Stress, Ugt2b17, Metabolism Phenomena, Nicotinamide, Man, Mass Spectroscopy, Drugs, Nicotinsäureamid Jenapharm, UDPGT 2B5, School-Age Populations, DmUGT, MDDGB6, Papulex, UDP-Gal-Tr, Metabolic Concept, Energy, LARGE, Deletion, Population, Expenditures, nicotine acid amide, BPFD#36, drugs, Enzyme, Immune Response, Ugalt, Had-1, great, negative regulation of homeostatic process, Preparation, School Age Population, UGALT, Immune Process, Pharmaceuticals, Autoregulation, Products, nicotinamida, nicotinamide, niamide, Reticulum Stress, degradation, nicotine amide, Catatoxic Steroids, Affects, Proteins, total expressed protein, Udpgtr2., enzyme activity, AI327289, function, Medications, UDP-galactose transporter, UDPGT2B17, anon-3Bb, Concept, Metabolic Phenomena, DmelCG6850, Metabolism Concepts, MS, Protein, Phenomena, 3-carbamoylpyridine, regulation of homeostatic process, glucides, metabolism, Jenapharm, Mass Spectrum Analyses, Metabolic Phenomenon, Udpgtr2, Energy Expenditure, Mass Spectrum, multicellular organism metabolic process, EG:100G10.5, Rlug38, Nikotinamid, biodegradation, Metabolic, Pharmaceutic Preparations, Sfc8, ER Stresses, Energy Expenditures, B 3, Carbohydrate, nicotylamide, School Age Populations, Bioenergetic, Sugar, Drug, Protein Gene Products, 2B1, Livers, Gene Proteins, Preparations, Nicotinsäureamid, activation of homeostatic process, Endoplasmic, Modern Man, Stress, Response, Pharmaceutical Products, Pharmaceutical Preparation, AnabolismPXD055894falseThe UGT2B17 metabolic pathway as a key determinant of liver homeostasis: evidence from the hepatic proteome of individuals naturally deficient in UGT2B17One of the most crucial pathways involved in the metabolism and detoxification of drugs and endobiotics is the glucuronidation process, primarily occurring in the liver. This pathway is catalyzed by glycosyltransferases comprising 22 enzymes such as UGT2B17, which is entirely absent in a large proportion of the population, due to complete gene deletion. We defined the impact of a UGT2B17 deficiency on the proteome of normal human liver tissues by data-independent acquisition mass spectrometry.MSV00009587339953065