{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ERG28 encodes an endoplasmic reticulum–resident transmembrane protein that plays a critical role in ergosterol biosynthesis in yeast by serving as a scaffold to assemble and stabilize a multi‐enzyme complex. In particular, Erg28p is essential for the proper removal of C‑4 methyl groups from sterol intermediates—it facilitates the C‑4 demethylation reaction by tethering enzymes such as Erg25p, Erg26p, and Erg27p to the ER. In addition, Erg28p interacts with downstream enzymes like Erg6p to ensure a coordinated progression through the sterol pathway. Disruption of ERG28 results in accumulation of 3‑keto and carboxylic acid intermediates, highlighting its importance in channeling substrates through C‑4 demethylation and subsequent steps in ergosterol production."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n From an evolutionary perspective, ERG28 (also known as C14orf1 in mammals) is highly conserved among organisms capable of de novo sterol synthesis. Notably, although insect orthologues have diverged—consistent with their reliance on dietary cholesterol—the conservation in other eukaryotic lineages underlines its fundamental role in lipid metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, detailed mutational and structural analyses have identified a short, conserved amino acid motif within Erg28p that is essential for its function, likely by mediating critical protein–protein interactions needed for effective C‑4 demethylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Overall, ERG28 functions as a central organizer or “bridge” within the ergosterol biosynthetic assembly line, ensuring proper enzyme localization, substrate channeling, and efficient sterol production.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "D Gachotte, J Eckstein, R Barbuch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel gene conserved from yeast to humans is involved in sterol biosynthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2001)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11160377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11160377"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Caiqing Mo, Martin Valachovic, Martin Bard "}, {"type": "b", "children": [{"type": "t", "text": "The ERG28-encoded protein, Erg28p, interacts with both the sterol C-4 demethylation enzyme complex as well as the late biosynthetic protein, the C-24 sterol methyltransferase (Erg6p)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbalip.2004.08.001"}], "href": "https://doi.org/10.1016/j.bbalip.2004.08.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15522820"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15522820"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Caiqing Mo, Martin Bard "}, {"type": "b", "children": [{"type": "t", "text": "Erg28p is a key protein in the yeast sterol biosynthetic enzyme complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M500153-JLR200"}], "href": "https://doi.org/10.1194/jlr.M500153-JLR200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15995173"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15995173"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "R A Veitia, L D Hurst "}, {"type": "b", "children": [{"type": "t", "text": "Accelerated molecular evolution of insect orthologues of ERG28/C14orf1: a link with ecdysteroid metabolism?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Genet (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/BF02811414"}], "href": "https://doi.org/10.1007/BF02811414"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11910120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11910120"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xia Ke, Xiao-Yuan Xia, Ren-Chao Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a consensus motif in Erg28p required for C-4 demethylation in yeast ergosterol biosynthesis based on mutation analysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEMS Microbiol Lett (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/femsle/fny002"}], "href": "https://doi.org/10.1093/femsle/fny002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29319811"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29319811"}]}]}]}