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Alpha-synuclein and tau are representative disease-related IDPs with low complexity regions in their sequences, accumulating in the brains of patients with Parkinson disease and Alzheimer disease, respectively. Their heat resistance in particular was what attracted our attention. We assumed that there exist many other unidentified proteins that are resistant to heat-treatment, referred to as heat-stable proteins, which would also have low sequence complexity. In this study, we performed proteomic analysis of heat-stable proteins of mouse brains and found that proteins with compositionally biased regions are abundant in the heat-stable proteins. The proteins related to neurodegeneration are known to undergo different types of post-translational modifications (PTMs) such as phosphorylation and ubiquitination. We then investigated the heat-stability and aggregation properties of phosphorylated synuclein and tau with different phosphorylation sites. We suggest that PTMs can be important factors that determine the heat-stability and aggregation properties of a protein. IDPs identified in the heat-stable proteins of mouse brains would be candidates for the pathogenic proteins for neurodegeneration.<\/jats:p>","DOI":"10.1038\/s41598-022-08044-z","type":"journal-article","created":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T13:17:30Z","timestamp":1647263850000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Proteomic analysis of heat-stable proteins revealed an increased proportion of proteins with compositionally biased regions"],"prefix":"10.1038","volume":"12","author":[{"given":"Hongsun","family":"Park","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Yamanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4545-5100","authenticated-orcid":false,"given":"Nobuyuki","family":"Nukina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"8044_CR1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a009399","volume":"2","author":"L Stefanis","year":"2012","unstructured":"Stefanis, L. 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