{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nGlycoprotein 2 (GP2) is a multifunctional protein pivotal to mucosal immunity. It is selectively expressed on the apical surface of M cells in Peyer’s patches where it acts as a transcytotic receptor that binds type‐I piliated bacteria (via the FimH adhesin), thereby facilitating the uptake of both commensal and pathogenic bacteria into lymphoid tissues to trigger antigen‐specific immune responses. Moreover, GP2 expression in these immune cells is regulated in a circadian manner via CREB, ensuring that transcytotic activity peaks during the dark phase to optimally coordinate immune surveillance and response."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the exocrine pancreas, GP2 is the major membrane protein resident in zymogen granules, where it is thought to participate in digestive enzyme sorting, notably binding enzymes such as amylase. While genetic ablation studies indicate that GP2 is not essential for zymogen granule formation or the secretion process, its secreted form plays a protective role along the gastrointestinal tract by binding to adhesive and invasive commensal bacteria such as Escherichia coli, thereby preventing bacterial overgrowth and epithelial barrier disruption in conditions of intestinal inflammation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThe genomic organization of the GP2 gene reveals multiple exons encoding key functional domains—including a signal sequence, an EGF‐like motif, a zona pellucida domain, and a GPI‐anchor site—suggesting an evolutionary divergence from related proteins such as THP by gene duplication. Beyond its roles in the gut and pancreas, GP2 is widely expressed in various mucous glands and secretory cells across different tissues such as the oral cavity, paranasal sinuses, and reproductive organs. In these diverse sites, GP2 is deposited in luminal secretions and appears to contribute to a frontline defense mechanism against pathogen entry."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Koji Hase, Kazuya Kawano, Tomonori Nochi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Uptake through glycoprotein 2 of FimH(+) bacteria by M cells initiates mucosal immune response."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nature08529"}], "href": "https://doi.org/10.1038/nature08529"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19907495"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19907495"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Naoki Kusunose, Akito Tsuruta, Kengo Hamamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circadian expression of Glycoprotein 2 (Gp2) gene is controlled by a molecular clock in mouse Peyer's patches."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Cells (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/gtc.12758"}], "href": "https://doi.org/10.1111/gtc.12758"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32050049"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32050049"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Su Yu, Sara A Michie, Anson W Lowe "}, {"type": "b", "children": [{"type": "t", "text": "Absence of the major zymogen granule membrane protein, GP2, does not affect pancreatic morphology or secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M410599200"}], "href": "https://doi.org/10.1074/jbc.M410599200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15385539"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15385539"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yosuke Kurashima, Takaaki Kigoshi, Sayuri Murasaki, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pancreatic glycoprotein 2 is a first line of defense for mucosal protection in intestinal inflammation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-021-21277-2"}], "href": "https://doi.org/10.1038/s41467-021-21277-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33594081"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33594081"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "K Kobayashi, K Yanagihara, K Ishiguro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GP2/THP gene family of self-binding, GPI-anchored proteins forms a cluster at chromosome 7F1 region in mouse genome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2004.07.197"}], "href": "https://doi.org/10.1016/j.bbrc.2004.07.197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15325280"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15325280"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Shunsuke Kimura, Junko Nio-Kobayashi, Ayuko Kishimoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The broad distribution of GP2 in mucous glands and secretory products."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2220/biomedres.37.351"}], "href": "https://doi.org/10.2220/biomedres.37.351"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28003582"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28003582"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Shunsuke Kimura, Mami Muto, Meri Hisamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel type of cells expressing GP2 in the respiratory epithelium of the paranasal sinuses in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomed Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2220/biomedres.35.329"}], "href": "https://doi.org/10.2220/biomedres.35.329"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25355440"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25355440"}]}]}]}