{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nReticulocalbin‐3 (RCN3) is a member of the CREC family of multiple EF‐hand Ca²⁺–binding proteins that localizes to the secretory pathway. Notably, RCN3 has been shown to transiently associate with proprotein convertase precursors, such as proPACE4, thereby modulating their biosynthesis by facilitating autoactivation and secretion. This interaction underscores a role for RCN3 in the precise control of proteolytic processing during protein maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its involvement in protein processing, RCN3 is emerging as a critical regulator of tissue homeostasis. In cardiac fibroblasts, for example, a reduction in RCN3 levels in response to profibrotic stimuli (including aldosterone, galectin‐3, and cardiotrophin‐1) correlates with increased collagen production. Conversely, treatment with recombinant RCN3 can decrease collagen expression via Akt phosphorylation, thereby attenuating fibrosis. In addition, elevated levels of RCN3 in the secretome of dermal fibroblasts have been proposed as a potential biomarker in systemic sclerosis, highlighting its relevance in disease monitoring."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRCN3’s functional repertoire also extends to pulmonary physiology, where its deficiency in type II alveolar epithelial cells has been associated with impaired injury‐repair mechanisms and the development of emphysema in chronic obstructive pulmonary disease (COPD). Furthermore, genetic association studies have identified variants near RCN3 that correlate with glycemic biomarkers such as fructosamine, suggesting that RCN3 may play broader roles in metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Akihiko Tsuji, Yayoi Kikuchi, Yukimi Sato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A proteomic approach reveals transient association of reticulocalbin-3, a novel member of the CREC family, with the precursor of subtilisin-like proprotein convertase, PACE4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20051524"}], "href": "https://doi.org/10.1042/BJ20051524"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16433634"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16433634"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Paul Bălănescu, Anca Lădaru, Eugenia Bălănescu, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Differential Proteomics Identifies Reticulocalbin-3 as a Novel Negative Mediator of Collagen Production in Human Cardiac Fibroblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-017-12305-7"}], "href": "https://doi.org/10.1038/s41598-017-12305-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28939891"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28939891"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qianyu Zhang, Tong Wang, Jiawei Jin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rcn3 Suppression Was Responsible for Partial Relief of Emphysema as Shown by Specific Type II Alveolar Epithelial Cell Rcn3 CKO Mouse Model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Chron Obstruct Pulmon Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2147/COPD.S272711"}], "href": "https://doi.org/10.2147/COPD.S272711"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33531801"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33531801"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Fernando Riveros-Mckay, David Roberts, Emanuele Di Angelantonio, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An Expanded Genome-Wide Association Study of Fructosamine Levels Identifies RCN3 as a Replicating Locus and Implicates FCGRT as the Effector Transcript."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db21-0320"}], "href": "https://doi.org/10.2337/db21-0320"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34753797"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34753797"}]}]}]}