RAS family (RAS)

The RAS family consists of small GTPases encoded by three main human genes (HRAS, NRAS, KRAS producing four isoforms: HRAS, NRAS, KRAS4A, KRAS4B) that function as molecular switches cycling between GDP-bound inactive and GTP-bound active states to regulate key signaling pathways. They share a conserved G-domain for GTP binding/hydrolysis and effector interactions (e.g., RAF kinases via switch I/II regions), with a hypervariable C-terminal region for membrane anchoring. RAS activates downstream cascades like RAF-MEK-ERK for cell proliferation and survival, and mutations locking GTP-bound state drive ~30% of cancers. Structures reveal β-sheet/α-helix folds akin to EF-Tu, with post-translational modifications (prenylation, acetylation) critical for function

Other names

HRASNRASKRAS (including KRAS4A, KRAS4B)H-RasN-RasK-Rasp21rasRat sarcoma virus proteins

Direct binding to switch pockets of mutant KRAS to lock inactive conformation, Inhibition of GTP binding, GAP-mediated GTP hydrolysis enhancement, RAF kinase dimerization blockade, Farnesylation blockade for membrane localization