Identification of a human rasGAP-related protein containing calmodulin-binding motifs.
Conversion of active GTP-bound Ras to its inactive GDP-bound form is catalyzed by GTPase-activating proteins (GAPs). Two mammalian Ras-specific GAPs, p120GAP and neurofibromin, the product of the NF1 tumor suppressor gene, have been previously described. We report here the identification of a new human cDNA clone, IQGAP1, which predicts a 1657-amino acid protein that displays extensive sequence similarity to the catalytic domain of all previously reported RasGAPs. IQGAP1 is most closely related to the Schizosaccharomyces pombe RasGAP-like protein, Sar1. Sequence similarity to IQGAP1 is seen throughout the entire Sar1 protein. The N-terminal half of IQGAP1, which does not overlap with Sar1, contains six copies of a unique amino acid motif, as well as four so-called IQ motifs. The latter motifs are found in several proteins, including conventional and unconventional myosins, and mediate the interaction with calmodulin and calmodulin-related proteins. Thus, IQGAP1 appears to represent a novel RasGAP-like protein that may link Ras signaling to some calmodulin-mediated process.
Weissbach
L
L
Orthopaedic Research Laboratories, Massachusetts General Hospital, Boston 02114.
Settleman
J
J
Kalady
M F
MF
Snijders
A J
AJ
Murthy
A E
AE
Yan
Y X
YX
Bernards
A
A
D000595:Amino Acid Sequence; D001665:Binding Sites; D002147:Calmodulin / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D018076:DNA, Complementary; D006801:Humans; D008969:Molecular Sequence Data; D020703:ras GTPase-Activating Proteins
D002147:Calmodulin; D002352:Carrier Proteins; D018076:DNA, Complementary; C101203:IQ motif containing GTPase activating protein 1; D020703:ras GTPase-Activating Proteins