Guanylate cyclase-activating proteins: structure, function, and diversity

Biochem Biophys Res Commun. 2004 Oct 1;322(4):1123-30. doi: 10.1016/j.bbrc.2004.07.122.


The guanylate cyclase-activating proteins (GCAPs), Ca2+-binding proteins of the calmodulin gene superfamily, function as regulators of photoreceptor guanylate cyclases. In contrast to calmodulin, which is active in the Ca2+-bound form, GCAPs stimulate GCs in the [Ca2+]-free form and inhibit GCs upon Ca2+ binding. In vertebrate retinas, at least two GCAP1 and two GCs are present, a third GCAP3 is expressed in humans and fish, and at least five additional GCAP4-8 genes have been identified or are predicted in zebrafish and pufferfish. Missense mutations in GCAP1 (Y99C, I143NT, E155G, and P50L) have been associated with autosomal dominant cone dystrophy. Absence of GCAP1/2 in mice delays recovery of the photoresponse, a phenotype consistent with delay in cGMP synthesis. In the absence of GCAP2, GCAP1 supports the generation of wild-type flash responses in both rod and cone cells. Recent progress revealed an unexpected complexity of the GC-GCAP system, pointing, out a number of unsolved questions.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium-Binding Proteins / chemistry*
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / physiology*
  • Guanylate Cyclase-Activating Proteins
  • Humans
  • Mice
  • Models, Animal
  • Molecular Sequence Data
  • Phylogeny
  • Pineal Gland / chemistry
  • Protein Processing, Post-Translational
  • Retina / chemistry
  • Retinal Diseases / genetics
  • Zebrafish Proteins


  • Calcium-Binding Proteins
  • GUCA1A protein, human
  • GUCA1B protein, human
  • GUCA1C protein, human
  • Guanylate Cyclase-Activating Proteins
  • Guca1a protein, mouse
  • Guca1b protein, mouse
  • Zebrafish Proteins
  • guca1a protein, zebrafish
  • guca1b protein, zebrafish
  • guca1c protein, zebrafish