{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The endothelin‐converting enzyme 2 (ECE2) locus has long been associated with proteolytic activities in the nervous system, particularly with the intracellular degradation of β‐amyloid peptides and the production of the vasoconstrictive peptide endothelin‐1. In several studies, loss or dysregulation of ECE2 activity has been shown to lead to increased amyloid‐β accumulation and altered endothelin‐1 levels, processes that are implicated in Alzheimer’s disease pathogenesis and cerebrovascular dysfunction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Recent work has, however, redefined this locus by demonstrating that an uncharacterized human seven‐β‐strand methyltransferase—originally annotated as part of ECE2—is in fact a distinct enzyme now named eukaryotic translation elongation factor 1 alpha lysine methyltransferase 4 (eEF1A‐KMT4; gene symbol EEF1AKMT4). This novel lysine‐specific methyltransferase catalyzes the methylation of lysine 36 on eEF1A in vitro and in vivo, and its activity has been shown to influence translation dynamics by altering the speed of codon translation on ribosomes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, while canonical ECE2 functions as a protease that limits neuronal β‐amyloid accumulation and regulates endothelin‐1 production, the reannotated EEF1AKMT4 represents a functionally distinct enzyme that modulates protein synthesis through targeted methylation of eEF1A. Together, these findings underscore the multifaceted roles encoded at the ECE2 locus, with significant implications both for neurodegenerative disease mechanisms and for the regulation of translation.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Elizabeth A Eckman, Mona Watson, Laura Marlow, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alzheimer's disease beta-amyloid peptide is increased in mice deficient in endothelin-converting enzyme."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C200642200"}], "href": "https://doi.org/10.1074/jbc.C200642200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12464614"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12464614"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jennifer C Palmer, Shabnam Baig, Patrick G Kehoe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endothelin-converting enzyme-2 is increased in Alzheimer's disease and up-regulated by Abeta."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2009.081054"}], "href": "https://doi.org/10.2353/ajpath.2009.081054"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19541930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19541930"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Javier Pacheco-Quinto, Christopher B Eckman, Elizabeth A Eckman "}, {"type": "b", "children": [{"type": "t", "text": "Major amyloid-β-degrading enzymes, endothelin-converting enzyme-2 and neprilysin, are expressed by distinct populations of GABAergic interneurons in hippocampus and neocortex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Aging (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neurobiolaging.2016.08.011"}], "href": "https://doi.org/10.1016/j.neurobiolaging.2016.08.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27644077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27644077"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Magnus E Jakobsson, Jedrzej Malecki, Benedikt S Nilges, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Methylation of human eukaryotic elongation factor alpha (eEF1A) by a member of a novel protein lysine methyltransferase family modulates mRNA translation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nucleic Acids Res (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/nar/gkx432"}], "href": "https://doi.org/10.1093/nar/gkx432"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28520920"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28520920"}]}]}]}