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A recent homology-based search for additional PDI family members identified anterior gradient homolog 2 (AGR2), a protein originally presumed to be secreted by intestinal epithelial cells. Here, we show that AGR2 is present within the ER of intestinal secretory epithelial cells and is essential for in vivo production of the intestinal mucin MUC2, a large, cysteine-rich glycoprotein that forms the protective mucus gel lining the intestine. A cysteine residue within the AGR2 thioredoxin-like domain forms mixed disulfide bonds with MUC2, indicating a direct role for AGR2 in mucin processing. Mice lacking AGR2 were viable but were highly susceptible to colitis, indicating a critical role for AGR2 in protection from disease. We conclude that AGR2 is a unique member of the PDI family, with a specialized and nonredundant role in intestinal mucus production.<\/jats:p>","DOI":"10.1073\/pnas.0808722106","type":"journal-article","created":{"date-parts":[[2009,4,9]],"date-time":"2009-04-09T21:51:56Z","timestamp":1239313916000},"page":"6950-6955","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":383,"title":["The protein disulfide isomerase AGR2 is essential for production of intestinal mucus"],"prefix":"10.1073","volume":"106","author":[{"given":"Sung-Woo","family":"Park","sequence":"first","affiliation":[{"name":"Lung Biology Center and"},{"name":"Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Kyeonggi-Do 420-020, Korea; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohua","family":"Zhen","sequence":"additional","affiliation":[{"name":"Lung Biology Center and"},{"name":"Department of Internal 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