{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ALG14 is an evolutionarily conserved, endoplasmic reticulum (ER)‐resident protein that plays an essential role during the early steps of N‐linked glycosylation. It functions primarily as a membrane anchor that recruits the soluble catalytic subunit ALG13 to the cytosolic face of the ER, thereby enabling the formation of an active UDP–N‐acetylglucosamine transferase complex. This hetero‐oligomeric complex catalyzes the addition of the second GlcNAc moiety to the lipid‐linked oligosaccharide precursor, a critical step in the biosynthesis of the dolichol‐linked oligosaccharide required for proper protein glycosylation (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Detailed studies in yeast have established that ALG14 not only anchors ALG13 but also helps to stabilize and correctly localize the glycosyltransferase complex, ensuring efficient transfer of the GlcNAc molecule. Mutagenesis and biochemical analyses indicate that specific domains or short α‐helical regions in ALG14 are critical for its interaction with ALG13 and for its ER membrane association, highlighting its importance in the formation of the multienzyme complex responsible for initiating N‐linked glycosylation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In higher eukaryotes, the proper functioning of the ALG13/ALG14 glycosyltransferase complex is vital for neuromuscular junction integrity. Defects or mutations in ALG14 have been causally linked to congenital myasthenic syndromes (CMS), where impaired glycosylation leads to reduced acetylcholine receptor expression at the muscle endplate, resulting in significant neuromuscular transmission defects and muscle weakness."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In addition, studies in patient‐derived cells and animal models have demonstrated that pathogenic variants of ALG14 can markedly diminish its protein expression, thereby disturbing the assembly of the glycosylation machinery and contributing to multisystem disorders that may also include myopathic features."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the dual role of ALG14 in both the fundamental process of protein N‐glycosylation and in the maintenance of neuromuscular function. Its crucial function as a membrane tether for ALG13 ensures the proper synthesis of the oligosaccharide precursor, while mutations that compromise this role lead directly to defects in glycosylation with severe clinical consequences.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Judith Cossins, Katsiaryna Belaya, Debbie Hicks, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Congenital myasthenic syndromes due to mutations in ALG2 and ALG14."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/brain/awt010"}], "href": "https://doi.org/10.1093/brain/awt010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23404334"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23404334"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Xiao-Dong Gao, Hiroyuki Tachikawa, Takashi Sato, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alg14 recruits Alg13 to the cytoplasmic face of the endoplasmic reticulum to form a novel bipartite UDP-N-acetylglucosamine transferase required for the second step of N-linked glycosylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M507569200"}], "href": "https://doi.org/10.1074/jbc.M507569200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16100110"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16100110"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nicole Averbeck, Sabine Keppler-Ross, Neta Dean "}, {"type": "b", "children": [{"type": "t", "text": "Membrane topology of the Alg14 endoplasmic reticulum UDP-GlcNAc transferase subunit."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M704410200"}], "href": "https://doi.org/10.1074/jbc.M704410200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17686769"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17686769"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiao-Dong Gao, Satoru Moriyama, Nobuaki Miura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction between the C termini of Alg13 and Alg14 mediates formation of the active UDP-N-acetylglucosamine transferase complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M804060200"}], "href": "https://doi.org/10.1074/jbc.M804060200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18809682"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18809682"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jishun Lu, Tetsuo Takahashi, Atsuko Ohoka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alg14 organizes the formation of a multiglycosyltransferase complex involved in initiation of lipid-linked oligosaccharide biosynthesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glycobiology (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/glycob/cwr162"}], "href": "https://doi.org/10.1093/glycob/cwr162"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22061998"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22061998"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Yu Katata, Saki Uneoka, Naoya Saijyo, et al. 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