IDENTIFICATION OF A SEC4P GTPASE-ACTIVATING PROTEIN (GAP) AS A NOVEL MEMBER OF A RAB GAP FAMILY

A yeast open reading frame sharing homology with the two known yeast R ab GTPase-activating proteins (GAPs), Gyp6p and Gyp7p, was found in a data base search. We have named the gene containing this open reading frame GYP1. Recombinant Gyp1p showed GAP activity on Sec4p, increasing both its steady-state rate and single turnover GTPase activity. Gyp1p also stimulated the GTPase activity of several other yeast Rab protei ns including Ypt1p, Ypt7p, and Ypt51p but showed no GAP activity on Yp t6p and Ypt32p. Deletion of the GYP1 gene or overexpression of Gyp1p d id not alter the growth rate of yeast. However, overexpression of Gyp1 p was inhibitory in combination with a subset of secretory mutants inc luding sec4-8 and several ypt1 mutants. This effect is probably due to the increase in GAP activity, which can be observed in a lysate from cells overexpressing Gyp1p. The finding that yeast Rab GAPs share homo logy with proteins in other species, such as Caenorhabditis elegans an d human, suggests the existence of a conserved Rab GAP family.