{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTMPRSS15, which encodes enteropeptidase, is a membrane‐anchored serine protease that plays a critical role in the initiation of protein digestion by specifically cleaving and activating trypsinogen into trypsin. This enzyme is expressed on the brush border of duodenal enterocytes and goblet cells, ensuring that the proteolytic cascade required for digestion is efficiently triggered. Its precise cellular localization facilitates rapid conversion of digestive zymogens, thereby underpinning effective nutrient processing and absorption."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural studies of enteropeptidase have highlighted the importance of conserved residues at the N‐terminus in maintaining the enzyme’s active conformation. Mutational analyses have revealed that substitutions at key positions—such as replacing an essential isoleucine residue—can dramatically impair enzymatic function, underscoring the precise molecular requirements for substrate recognition and catalysis. High‐resolution crystal structures of the light chain further confirm that the proper organization of these domains is fundamental to its proteolytic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in the gastrointestinal tract, alternative splicing and isoform variation of TMPRSS15 have been documented in non‐intestinal tissues such as keratinocytes, suggesting that enteropeptidase activity may contribute to cell differentiation processes in other organs. Moreover, emerging research indicates that modulation of TMPRSS15 function could have therapeutic potential in conditions like obesity, where altering the efficiency of nutrient absorption may influence overall energy homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Takahisa Imamura, Yasunori Kitamoto "}, {"type": "b", "children": [{"type": "t", "text": "Expression of enteropeptidase in differentiated enterocytes, goblet cells, and the tumor cells in human duodenum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Gastrointest Liver Physiol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajpgi.00198.2003"}], "href": "https://doi.org/10.1152/ajpgi.00198.2003"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12907431"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12907431"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hye-Won Song, Sung-Il Choi, Baik L Seong "}, {"type": "b", "children": [{"type": "t", "text": "Engineered recombinant enteropeptidase catalytic subunit: effect of N-terminal modification."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Biochem Biophys (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1006/abbi.2001.2737"}], "href": "https://doi.org/10.1006/abbi.2001.2737"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11913964"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11913964"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Peter Simeonov, Michael Zahn, Norbert Sträter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of a supercharged variant of the human enteropeptidase light chain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proteins (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/prot.24084"}], "href": "https://doi.org/10.1002/prot.24084"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22488687"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22488687"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jotaro Nakanishi, Mami Yamamoto, Junichi Koyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Keratinocytes synthesize enteropeptidase and multiple forms of trypsinogen during terminal differentiation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2009.364"}], "href": "https://doi.org/10.1038/jid.2009.364"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19924134"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19924134"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sandrine Braud, Marco A Ciufolini, Itzik Harosh "}, {"type": "b", "children": [{"type": "t", "text": "Enteropeptidase: a gene associated with a starvation human phenotype and a novel target for obesity treatment."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0049612"}], "href": "https://doi.org/10.1371/journal.pone.0049612"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23185382"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23185382"}]}]}]}