Point mutations of several amino acids of HRAS, including gly12, ala59, or glu63, render the protein constitutively active.human ERAS has serine, alanine, and asparagine at the positions corresponding to gly12, ala59, and glu63 of HRAS, suggesting that it is constitutively active. 95% of mouse and human ERAS was in a GTP-bound form. In contrast, about 90% of wildtype HRAS existed in a GTP-bound form, whereas 80% of a constitutively active HRAS
mutant was in a GTP-bound form. The predicted 227-amino acid ERas protein shares 43%, 46%, and 47% identity with HRas, KRas, and NRas, respectively, and 5 domains essential for small G proteins are highly conserved. ERas contains a CAAX motif and is located in a cytoplasmic membrane. Northern blot analysis detected a 1.2-kb ERas transcript in several undifferentiated mouse ES cell lines.