{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Arrington ME"],"funding":["HHS | NIH | National Cancer Institute","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["12130-12142"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7443499"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["295(34)"],"pubmed_abstract":["The RAS-related C3 botulinum toxin substrate 2 (RAC2) is a member of the RHO subclass of RAS superfamily GTPases required for proper immune function. An activating mutation in a key switch II region of RAC2 (RAC2<sup>E62K</sup>) involved in recognizing modulatory factors and effectors has been identified in patients with common variable immune deficiency. To better understand how the mutation dysregulates RAC2 function, we evaluated the structure and stability, guanine nucleotide exchange factor (GEF) and GTPase-activating protein (GAP) activity, and effector binding of RAC2<sup>E62K</sup> Our findings indicate the E62K mutation does not alter RAC2 structure or stability. However, it does alter GEF specificity, as RAC2<sup>E62K</sup> is activated by the DOCK GEF, DOCK2, but not by the Dbl "],"journal":["The Journal of biological chemistry"],"pubmed_title":["The molecular basis for immune dysregulation by the hyperactivated E62K mutant of the GTPase RAC2."],"pmcid":["PMC7443499"],"funding_grant_id":["P30 CA016086","P01 CA203657","R01 CA224428","R35 GM134962"],"pubmed_authors":["Campbell SL","Arrington ME","Temple B","Schaefer A"],"additional_accession":[]},"is_claimable":false,"name":"The molecular basis for immune dysregulation by the hyperactivated E62K mutant of the GTPase RAC2.","description":"The RAS-related C3 botulinum toxin substrate 2 (RAC2) is a member of the RHO subclass of RAS superfamily GTPases required for proper immune function. An activating mutation in a key switch II region of RAC2 (RAC2<sup>E62K</sup>) involved in recognizing modulatory factors and effectors has been identified in patients with common variable immune deficiency. To better understand how the mutation dysregulates RAC2 function, we evaluated the structure and stability, guanine nucleotide exchange factor (GEF) and GTPase-activating protein (GAP) activity, and effector binding of RAC2<sup>E62K</sup> Our findings indicate the E62K mutation does not alter RAC2 structure or stability. However, it does alter GEF specificity, as RAC2<sup>E62K</sup> is activated by the DOCK GEF, DOCK2, but not by the Dbl ","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Aug","modification":"2026-04-14T17:41:59.951Z","creation":"2022-02-11T09:17:43.782Z"},"accession":"S-EPMC7443499","cross_references":{"pubmed":["32636302"],"doi":["10.1074/jbc.ra120.012915","10.1074/jbc.RA120.012915"]}}