Figure 2. Multiple sequence alignment of MRAS in comparison with HRAS, KRAS, and NRAS paralogs.
Multiple sequence alignment was performed using T-COFFEE as previously described (62). Note that, in spite of differences in the sequence among these proteins (HRAS: 57.3%; NRAS: 56.7%; KRAS: 55.4%), the regions corresponding to the switch I and II and helix 3, which are critical for the activation of these proteins, are highly conserved. Additionally, sequence alignment demonstrated that the MRAS variants aligned to critical and conserved regions, matching previously identified disease-associated variants in one or more of the MRAS paralogs.