Molecular characterization of a third member of the guanylyl cyclase-activating protein subfamily

J Biol Chem. 1999 Mar 5;274(10):6526-35. doi: 10.1074/jbc.274.10.6526.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium-Binding Proteins / genetics*
  • Calcium-Binding Proteins / metabolism
  • Cloning, Molecular
  • Gene Expression Regulation
  • Guanylate Cyclase / metabolism*
  • Guanylate Cyclase-Activating Proteins
  • Humans
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics
  • Photoreceptor Cells / metabolism*
  • Retina / metabolism
  • Sequence Alignment
  • Sequence Analysis
  • Species Specificity


  • Calcium-Binding Proteins
  • GUCA1A protein, human
  • GUCA1B protein, human
  • GUCA1C protein, human
  • Guanylate Cyclase-Activating Proteins
  • Nerve Tissue Proteins
  • Guanylate Cyclase

Associated data

  • GENBANK/AF109998
  • GENBANK/AF109999
  • GENBANK/AF110000
  • GENBANK/AF110001
  • GENBANK/AF110002
  • GENBANK/AF110003