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One of the proteins that accumulates in perinuclear and peripheral regions of muscle fibers is cytosolic 5\u2032-nucleotidase 1A (cN1A), the target of anti-cN1A autoantibodies, which are found in many IBM patients. To shed more light on potential pathogenic aspects of IBM, we identified post-translational modifications of cN1A in human skeletal muscle. Immunoaffinity-purification followed by mass spectrometry resulted in the identification of three monomethylation sites, K178, R223, and K243. Single amino acid substitutions of each of these methylation sites did not detectably affect the accumulation of cN1A in perinuclear regions of cultured human cell lines. Two of these monomethylation sites, R223 and K243, are located within one of the previously identified major linear epitope regions of cN1A. Synthetic peptides, corresponding to aa 219 \u2013 aa 247, were used to investigate the effect of monomethylation on the antigenicity of this epitope by ELISA. The results showed that the simultaneous monomethylation of R223 and K243 may enhance its recognition by IgG autoantibodies. We conclude that cN1A contains at least three amino acids that can be monomethylated and that monomethylation may affect its autoantigenicity.<\/jats:p>","DOI":"10.1177\/22143602261487219","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:36:16Z","timestamp":1788359776000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Monomethylation of cytosolic 5\u2032-nucleotidase 1A affects its recognition by inclusion body myositis autoantibodies"],"prefix":"10.1177","author":[{"given":"Fleur","family":"Brinkman","sequence":"first","affiliation":[{"name":"Radboud University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9178-0720","authenticated-orcid":false,"given":"Marian","family":"Barandica Graciani","sequence":"additional","affiliation":[{"name":"Radboud University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amrah","family":"Weijn","sequence":"additional","affiliation":[{"name":"Radboud University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filine","family":"Swets","sequence":"additional","affiliation":[{"name":"Radboud University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seher","family":"Al Bana","sequence":"additional","affiliation":[{"name":"Radboud University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7697-6374","authenticated-orcid":false,"given":"Chien-Yun","family":"Lee","sequence":"additional","affiliation":[{"name":"Technical University of Munich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ger J. 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