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Using N-terminomics\/TAILS (terminal amine isotopic labeling of substrates), we compared proteases, along with their substrates and inhibitors, between colonic mucosal biopsies of healthy patients and those with ulcerative colitis (UC). Among the 1642 N-termini enriched using TAILS, increased endogenous processing of proteins was identified in UC compared to healthy patients. Changes in the reactome pathways for proteins associated with metabolism, adherens junction proteins (E-cadherin, liver-intestinal cadherin, catenin alpha-1, and catenin delta-1), and neutrophil degranulation were identified between the two groups. Increased neutrophil infiltration and distinct proteases observed in ulcerative colitis may result in extensive break down, altered processing, or increased remodeling of adherens junctions and other cellular functions. Analysis of the preferred proteolytic cleavage sites indicated that the majority of proteolytic activity and processing comes from host proteases, but that key microbial proteases may also play a role in maintaining homeostasis. Thus, the identification of distinct proteases and processing of their substrates improves the understanding of dysregulated proteolysis in normal intestinal physiology and ulcerative colitis.<\/jats:p>","DOI":"10.1021\/acschembio.9b00608","type":"journal-article","created":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T12:56:15Z","timestamp":1565268975000},"page":"2471-2483","source":"Crossref","is-referenced-by-count":31,"title":["N-Terminomics\/TAILS Profiling of Proteases\nand Their Substrates in Ulcerative Colitis"],"prefix":"10.1021","volume":"14","author":[{"given":"Marilyn H.","family":"Gordon","sequence":"first","affiliation":[{"name":"University of Calgary , , , ,","place":["Calgary, Alberta, Canada, T2N 4N1"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthonia","family":"Anowai","sequence":"additional","affiliation":[{"name":"University of Calgary , , , ,","place":["Calgary, Alberta, Canada, T2N 4N1"]},{"name":"University of Calgary , , , 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1Z2"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gurmeet","family":"Bindra","sequence":"additional","affiliation":[{"name":"University of Calgary , , , ,","place":["Calgary, Alberta, Canada, T2N 4N1"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Humberto B.","family":"Jijon","sequence":"additional","affiliation":[{"name":"University of Calgary , , , ,","place":["Calgary, Alberta, Canada, T2N 4N1"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Heitman","sequence":"additional","affiliation":[{"name":"University of Calgary , , , ,","place":["Calgary, Alberta, Canada, T2N 4N1"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin","family":"Yates","sequence":"additional","affiliation":[{"name":"University of Calgary , , , ,","place":["Calgary, Alberta, Canada, T2N 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