{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Sallah S"],"funding":["Biotechnology and Biological Sciences Research Council"],"pagination":["e0314022"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11575792"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(11)"],"pubmed_abstract":["Metabolic changes during tumour development lead to acidification of the extracellular environment and a smaller increase of intracellular pH. Searches for somatic missense mutations that could reveal adaptation to altered pH have focussed on arginine to histidine changes, part of a general arginine depletion that originates from DNA mutational mechanisms. Analysis of mutations to histidine, potentially a simple route to the introduction of pH-sensing, shows no clear biophysical separation overall of subsets that are more and less frequently mutated in cancer genomes. Within the more frequently mutated subset, individual sites predicted to mediate pH-dependence upon mutation include NDST1 (a Golgi-resident heparan sulphate modifying enzyme), the HLA-C chain of MHCI complex, and the water c"],"journal":["PloS one"],"pubmed_title":["Computational investigation of missense somatic mutations in cancer and potential links to pH-dependence and proteostasis."],"pmcid":["PMC11575792"],"funding_grant_id":["BB/V0065921/1"],"pubmed_authors":["Sallah S","Warwicker J"],"additional_accession":[]},"is_claimable":false,"name":"Computational investigation of missense somatic mutations in cancer and potential links to pH-dependence and proteostasis.","description":"Metabolic changes during tumour development lead to acidification of the extracellular environment and a smaller increase of intracellular pH. Searches for somatic missense mutations that could reveal adaptation to altered pH have focussed on arginine to histidine changes, part of a general arginine depletion that originates from DNA mutational mechanisms. Analysis of mutations to histidine, potentially a simple route to the introduction of pH-sensing, shows no clear biophysical separation overall of subsets that are more and less frequently mutated in cancer genomes. Within the more frequently mutated subset, individual sites predicted to mediate pH-dependence upon mutation include NDST1 (a Golgi-resident heparan sulphate modifying enzyme), the HLA-C chain of MHCI complex, and the water c","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024","modification":"2026-06-01T15:23:06.258Z","creation":"2025-04-06T10:12:14.384Z"},"accession":"S-EPMC11575792","cross_references":{"pubmed":["39561123"],"doi":["10.1371/journal.pone.0314022"]}}