Human RAS Superfamily Proteins and Related GTPases

Sci. STKE, 14 September 2004
Vol. 2004, Issue 250, p. re13
DOI: 10.1126/stke.2502004re13

Human RAS Superfamily Proteins and Related GTPases

  1. John Colicelli*
  1. Department of Biological Chemistry and Molecular Biology Institute, University of California Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
  1. *To whom correspondence should be addressed. E-mail: colicelli{at}


The tumor oncoproteins HRAS, KRAS, and NRAS are the founding members of a larger family of at least 35 related human proteins. Using a somewhat broader definition of sequence similarity reveals a more extended superfamily of more than 170 RAS-related proteins. The RAS superfamily of GTP (guanosine triphosphate) hydrolysis–coupled signal transduction relay proteins can be subclassified into RAS, RHO, RAB, and ARF families, as well as the closely related Gα family. The members of each family can, in turn, be arranged into evolutionarily conserved branches. These groupings reflect structural, biochemical, and functional conservation. Recent findings have provided insights into the signaling characteristics of representative members of most RAS superfamily branches. The analysis presented here may serve as a guide for predicting the function of numerous uncharacterized superfamily members. Also described are guanosine triphosphatases (GTPases) distinct from members of the RAS superfamily. These related proteins employ GTP binding and GTPase domains in diverse structural contexts, expanding the scope of their function in humans.


J. Colicelli, Human RAS Superfamily Proteins and Related GTPases. Sci. STKE 2004, re13 (2004).

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