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A sequence comparison of nine functionally different GTP-binding protein families has yielded further information on the general characterization of the conservation and importance of amino acid sequences in the GTP-binding domain, including a consensus sequence composed of three consensus elements GXXXXGK, DXXG, and NKXD with consensus spacings of either 40-80 or approximately equal to 130-170 amino acid residues between the first and second elements and approximately 40-80 amino acid residues between the second and third sequence elements; the sequence NKXW in place of NKXD in the sequence element responsible for base specificity allows the use of ITP as well as GTP; dGTP can be used with essentially the same efficiency as GTP; signal transducing proteins and enzymes have been identified in the nine families; and family conservations allow the identification of the most probable consensus sequence element when more than one is present. Employing these features we have screened the protein sequence data base of the Protein Identification Resource and have identified only known GTP-binding proteins with the exception of protein 2C from foot-and-mouth disease virus as matching the consensus sequence. Based on this finding we predict that foot-and-mouth disease virus protein 2C binds GTP and, by analogy, that protein 2C from several related viruses (polio, rhino, encephalomyocarditis, and cowpea mosaic) will bind a nucleotide as part of its biologic activity.

GTP-binding domain: three consensus sequence elements with distinct spacing.