{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRXYLT1, which appears to be functionally analogous to TMEM5 as described in several of the provided abstracts, is a glycosyltransferase that plays a crucial role in the biosynthesis of a unique O‐mannosyl glycan on α‐dystroglycan. Specifically, RXYLT1/TMEM5 catalyzes the transfer of a xylose residue onto a ribitol 5‐phosphate moiety, forming a defined β1,4 linkage that is an essential step in constructing the extracellular matrix–binding glycan structure. This modification permits α‐dystroglycan to act as a functional receptor for extracellular ligands, which is vital for normal muscle and brain development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther structural and biochemical studies demonstrate that RXYLT1/TMEM5 functions as a UDP‐xylose:ribitol‐5‐phosphate xylosyltransferase. Its activity elaborates the glycan chain by extending the phosphotrisaccharide moiety on α‐dystroglycan—a prerequisite for extracellular matrix (ECM) receptor activity. In model systems, including zebrafish and analyses of patient mutations, a loss or reduction in this xylosyltransferase function results in marked deficiencies in glycan assembly, which in turn leads to muscular dystrophy and abnormal brain development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMoreover, additional research indicates that RXYLT1/TMEM5 does not work in isolation but is part of a multi‐enzyme complex that includes other glycosyltransferases such as fukutin and fukutin-related protein (FKRP). The coordinated activity of these enzymes is essential for the correct modification of α‐dystroglycan, and disruption of any component of this complex can lead to a spectrum of severe α‐dystroglycanopathies, including phenotypes seen in Walker–Warburg syndrome and related disorders."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sandrine Vuillaumier-Barrot, Céline Bouchet-Séraphin, Malika Chelbi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of mutations in TMEM5 and ISPD as a cause of severe cobblestone lissencephaly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2012.10.009"}], "href": "https://doi.org/10.1016/j.ajhg.2012.10.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23217329"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23217329"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jeremy L Praissman, Tobias Willer, M Osman Sheikh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The functional O-mannose glycan on α-dystroglycan contains a phospho-ribitol primed for matriglycan addition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.14473"}], "href": "https://doi.org/10.7554/eLife.14473"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27130732"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27130732"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Hiroshi Manya, Yoshiki Yamaguchi, Motoi Kanagawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Muscular Dystrophy Gene TMEM5 Encodes a Ribitol β1,4-Xylosyltransferase Required for the Functional Glycosylation of Dystroglycan."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.751917"}], "href": "https://doi.org/10.1074/jbc.M116.751917"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27733679"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27733679"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ryuta Nishihara, Kazuhiro Kobayashi, Rieko Imae, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cell endogenous activities of fukutin and FKRP coexist with the ribitol xylosyltransferase, TMEM5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2018.02.162"}], "href": "https://doi.org/10.1016/j.bbrc.2018.02.162"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29477842"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29477842"}]}]}]}