biostudies-literatureEhrencrona ESahlgrenska AcademyEuropean Research CouncilSwedish Cancer FoundationIngaBritt and Arne Lundberg FoundationNIAID NIH HHSKnut and Alice Wallenberg FoundationSahlgrenska universitetssjukhusetSwedish Cancer SocietyNational Institutes of HealthSwedish Research CouncilNIAID100871https://www.ebi.ac.uk/biostudies/studies/S-EPMC8267560biostudies-literatureUnknown297(1)Mucus forms an important protective barrier that minimizes bacterial contact with the colonic epithelium. Intestinal mucus is organized in a complex network with several specific proteins, including the mucin-2 (MUC2) and the abundant IgGFc-binding protein, FCGBP. FCGBP is expressed in all intestinal goblet cells and is secreted into the mucus. It is comprised of repeated von Willebrand D (vWD) domain assemblies, most of which have a GDPH amino acid sequence that can be autocatalytically cleaved, as previously observed in the mucins MUC2 and mucin-5AC. However, the functions of FCGBP in the mucus are not understood. We show that all vWD domains of FCGBP with a GDPH sequence are cleaved and that these cleavages occur early during biosynthesis in the endoplasmic reticulum. All cleaved fragmeThe Journal of biological chemistryThe IgGFc-binding protein FCGBP is secreted with all GDPH sequences cleaved but maintained by interfragment disulfide bonds.PMC82675602017/3602019-01134U01AI095473U01 AI0954732018-0117ALFGBG-4407412017-009582015-03047694181CAN2016/4872015-0702017-0028ALFGBG-724681Ehrencrona Evan der Post STrillo-Muyo SRodriguez-Pineiro AMBackstrom MRecktenwald CVHansson GCGallego PJohansson MEVGarcia-Bonete MJfalseThe IgGFc-binding protein FCGBP is secreted with all GDPH sequences cleaved but maintained by interfragment disulfide bonds.Mucus forms an important protective barrier that minimizes bacterial contact with the colonic epithelium. Intestinal mucus is organized in a complex network with several specific proteins, including the mucin-2 (MUC2) and the abundant IgGFc-binding protein, FCGBP. FCGBP is expressed in all intestinal goblet cells and is secreted into the mucus. It is comprised of repeated von Willebrand D (vWD) domain assemblies, most of which have a GDPH amino acid sequence that can be autocatalytically cleaved, as previously observed in the mucins MUC2 and mucin-5AC. However, the functions of FCGBP in the mucus are not understood. We show that all vWD domains of FCGBP with a GDPH sequence are cleaved and that these cleavages occur early during biosynthesis in the endoplasmic reticulum. All cleaved fragme2021-01-01T00:00:00Z2021 Jul2026-05-09T07:40:42.072Z2022-02-10T21:49:54.517ZS-EPMC82675603412606810.1016/j.jbc.2021.100871