Origin and evolution of RAS oncoprotein membrane targeting.

ABSTRACT: KRAS, HRAS and NRAS oncogenes belong to a family of 40 highly homologous genes, which in turn are a subset of a superfamily of >160 genes encoding small GTPases. RAS oncoproteins consist of a globular G-domain (aa1-166) and a 22-23aa unstructured hypervariable region (HVR) that mediates membrane targeting. The evolutionarily origins of the RAS isoforms, their HVRs and alternative splicing of the KRAS locus has not been explored. We found that KRAS is basal to the oncogene family and its duplication generated HRAS in the common ancestor of vertebrates. In a second round of duplication HRAS generated NRAS and KRAS generated an additional RAS gene we have designated KRASBL, absent in mammals and birds. KRAS4A arose through a duplication and insertion of the 4th exon of NRAS into the 3rd intro

SUBMITTER: Garcia-Espana A 

PROVIDER: S-EPMC9882654 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature