Molecular characterization of a third member of the guanylyl cyclase-activating protein subfamily.
The mammalian retina contains at least two guanylyl cyclases (GC1 and GC2) and two guanylyl cyclase-activating proteins (GCAP1 and GCAP2). Here we present 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 GCAP2 stimulate GC1 and GC2 in low [Ca2+]free and inhibit GCs when [Ca2+]free is elevated, unlike GCAP1, which only stimulates GC1. GCAP3 is encoded by a distinct gene present in other mammalian species but could not be detected by genomic Southern blotting in rodents, amphibians, and lower vertebrates. 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 tail-to-tail array on chromosome 6p in human, the GCAP3 gene is located on 3q13.1, suggesting an ancestral gene duplication/translocation event. The identification of multiple Ca2+-binding proteins that interact with GC is suggestive of complex regulatory mechanisms for photoreceptor GC.
Department of Ophthalmology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
F
F
Haeseleer
I
I
Sokal
N
N
Li
M
M
Pettenati
N
N
Rao
D
D
Bronson
R
R
Wechter
W
W
Baehr
K
K
Palczewski
D000595:Amino Acid Sequence; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006162:Guanylate Cyclase / Q000378:metabolism*; D051604:Guanylate Cyclase-Activating Proteins; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D010786:Photoreceptor Cells / Q000378:metabolism*; D012160:Retina / Q000378:metabolism; D016415:Sequence Alignment; D017421:Sequence Analysis; D013045:Species Specificity
D002135:Calcium-Binding Proteins; C496736:GUCA1A protein, human; C496739:GUCA1B protein, human; C496742:GUCA1C protein, human; D051604:Guanylate Cyclase-Activating Proteins; D009419:Nerve Tissue Proteins; D006162:Guanylate Cyclase