F. Haeseleer et al., Molecular characterization of a third member of the guanylyl cyclase-activating protein subfamily, J BIOL CHEM, 274(10), 1999, pp. 6526-6535
The mammalian retina contains at least two guanylyl cyclases (GC1 and GC2)
and two guanylyl cyclase-activating proteins (GCAP1 and GCAP2). Here we pre
sent evidence of the presence of a new photoreceptor-specific GCAP, termed
GCAP3, which is closely related to GCAP1. The sequence similarity of GCAP3
with GCAP1 and GCAP2 is 57 and 49%, respectively. Recombinant GCAP3 and GCA
P2 stimulate GC1 and GC2 in low [Ca2+](free) and inhibit GCs when [Ca2+](fr
ee) is elevated, unlike GCAP1, which only stimulates GC1. GCAP3 is encoded
by a distinct gene present in other mammalian species but could not be dete
cted by genomic Southern blotting in rodents, amphibians, and lower vertebr
ates. The intron/exon arrangement of the GCAP3 gene is identical to that of
the other GCAP genes. While the GCAP1 and GCAP2 genes are arranged in a ta
il-to-tail array on chromosome 6p in human, the GCAP3 gene is located on 3q
13.1, suggesting an ancestral gene duplication/translocation event. The ide
ntification of multiple Ca2+-binding proteins that interact with GC is sugg
estive of complex regulatory mechanisms for photoreceptor GC.