The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

GUCA1B  -  guanylate cyclase activator 1B (retina)

Homo sapiens

Synonyms: GCAP 2, GCAP2, GUCA2, Guanylate cyclase activator 1B, Guanylyl cyclase-activating protein 2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of GUCA1B

  • The results of this study do not show any evidence so far that GCAP2 is involved in the pathogenesis of autosomal dominant retinal degeneration in this group of patients [1].

High impact information on GUCA1B

  • We generated this mutation in vitro and measured its catalytic activity and sensitivity to guanylyl cyclase activating protein 1 (GCAP-1) and GCAP-2 [2].
  • These results suggest that although GCAP1 is involved in the Ca2+-sensitive regulation of GC in rod and cone outer segments, GCAP2 may have non-phototransduction functions in photoreceptors and inner retinal neurons [3].
  • In human and monkey retinas, the most intense immunolabeling with anti-GCAP2 antibodies was in the cone inner segments, somata, and synaptic terminals and, to a lesser degree, in rod inner segments and inner retinal neurons [3].
  • By using a GCAP2-specific antibody in enzymatic assays, we confirmed that GCAP1 but not GCAP2 is the major component that stimulates GC in bovine rod outer segment homogenates [3].
  • Point mutations within the EF-1 region can interfere with both the activation of the cyclase by the Ca(2+)-free form of GCAP-2 and the inhibition of retGC basal activity by the Ca(2+)-loaded GCAP-2 [4].

Biological context of GUCA1B

  • CONCLUSIONS: The significant lod scores obtained and the absence of mutations in RDS, GUCA1A, and GUCA1B support the existence of a novel, yet unidentified gene responsible for retinal dystrophy within the chromosome 6 cluster [5].
  • The guanylate cyclase activator proteins (GCAP1 and GCAP2) are calcium binding proteins which by activating Ret-GC1 play a key role in the recovery phase of phototransduction [1].
  • The results show that the introns of the GCAP2 gene are positioned exactly as in the GCAP1 gene and are nearly double in size [6].
  • The identical gene structures and loci of GCAP1 and GCAP2, and the identical function of the gene products, are consistent with gene duplication event [6].
  • Apparently, in the course of evolution GCAP-2 exchanged the ability of its first EF-hand motif to bind Ca(2+) for the ability to interact with the target enzyme [4].

Anatomical context of GUCA1B

  • GCAP1 and GCAP2 are related Ca(2+)-binding proteins that activate photoreceptor guanylate cyclase(s) [6].
  • Guanylate cyclase-activating proteins (GCAP1 and GCAP2) are thought to mediate the intracellular stimulation of guanylate cyclase (GC) by Ca2+, a key event in recovery of the dark state of rod photoreceptors after exposure to light [3].

Associations of GUCA1B with chemical compounds

  • 3) Region Val171-Asn189, adjacent to the C-terminal EF-4 contributes to activation of RetGC, but it is not essential for the ability of Ca2+-loaded GCAP-2 to inhibit RetGC [7].
  • This was demonstrated by illumination of dark homogenates and treatments of illuminated homogenates with 11-cis-retinal and hydroxylamine prior to the AMP-PNP incubation and by measurement of the GCAP2 concentration required for 50% activation [8].

Physical interactions of GUCA1B

  • Our results strongly indicate that evolutionary conserved and GCAP-specific amino acid residues within the EF-1 can create a contact surface for binding GCAP-2 to the cyclase [4].

Other interactions of GUCA1B

  • Mutations in the gene coding for guanylate cyclase-activating protein 2 (GUCA1B gene) in patients with autosomal dominant retinal dystrophies [9].
  • The sequence similarity of GCAP3 with GCAP1 and GCAP2 is 57 and 49%, respectively [10].
  • Substitution of these three domains in GCAP-2 with corresponding neurocalcin sequences also affects activation of individual recombinant RetGC-1 and RetGC-2 expressed in HEK293 cells [7].
  • GCAP3 contains two domains with the EF-hand motifs arranged in a tandem array similar to GCAP2 and members of the recoverin subfamily of Ca2+-binding proteins [11].

Analytical, diagnostic and therapeutic context of GUCA1B

  • To identify the chromosomal location of the GCAP2 gene, we first cloned its cDNA and determined its intron-exon distribution by PCR analysis [6].
  • The GCAP1 and GCAP2 genes are transcribed into single mRNA species (1.7 and 2.2 kb, respectively) and are detectable only in the retina by Northern blotting [6].
  • We used in situ hybridization and immunocytochemistry to localize GCAP2 in human, monkey, and bovine retinas [3].
  • Immunohistochemical and Northern and Western blot analyses were used to examine the expression of GCAP1 and GCAP2 in 4- to 5-week-old mice [12].


  1. Genetic analysis of the guanylate cyclase activator 1B (GUCA1B) gene in patients with autosomal dominant retinal dystrophies. Payne, A.M., Downes, S.M., Bessant, D.A., Plant, C., Moore, T., Bird, A.C., Bhattacharya, S.S. J. Med. Genet. (1999) [Pubmed]
  2. Biochemical analysis of a dimerization domain mutation in RetGC-1 associated with dominant cone-rod dystrophy. Tucker, C.L., Woodcock, S.C., Kelsell, R.E., Ramamurthy, V., Hunt, D.M., Hurley, J.B. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  3. Localization of guanylate cyclase-activating protein 2 in mammalian retinas. Otto-Bruc, A., Fariss, R.N., Haeseleer, F., Huang, J., Buczyłko, J., Surgucheva, I., Baehr, W., Milam, A.H., Palczewski, K. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  4. Instead of binding calcium, one of the EF-hand structures in guanylyl cyclase activating protein-2 is required for targeting photoreceptor guanylyl cyclase. Ermilov, A.N., Olshevskaya, E.V., Dizhoor, A.M. J. Biol. Chem. (2001) [Pubmed]
  5. A novel locus for autosomal dominant cone and cone-rod dystrophies maps to the 6p gene cluster of retinal dystrophies. Castori, M., Valente, E.M., Clementi, M., Tormene, A.P., Brancati, F., Caputo, V., Dallapiccola, B. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  6. The human GCAP1 and GCAP2 genes are arranged in a tail-to-tail array on the short arm of chromosome 6 (p21.1). Surguchov, A., Bronson, J.D., Banerjee, P., Knowles, J.A., Ruiz, C., Subbaraya, I., Palczewski, K., Baehr, W. Genomics (1997) [Pubmed]
  7. Mapping functional domains of the guanylate cyclase regulator protein, GCAP-2. Olshevskaya, E.V., Boikov, S., Ermilov, A., Krylov, D., Hurley, J.B., Dizhoor, A.M. J. Biol. Chem. (1999) [Pubmed]
  8. Illuminated rhodopsin is required for strong activation of retinal guanylate cyclase by guanylate cyclase-activating proteins. Yamazaki, A., Yamazaki, M., Yamazaki, R.K., Usukura, J. Biochemistry (2006) [Pubmed]
  9. Mutations in the gene coding for guanylate cyclase-activating protein 2 (GUCA1B gene) in patients with autosomal dominant retinal dystrophies. Sato, M., Nakazawa, M., Usui, T., Tanimoto, N., Abe, H., Ohguro, H. Graefes Arch. Clin. Exp. Ophthalmol. (2005) [Pubmed]
  10. Molecular characterization of a third member of the guanylyl cyclase-activating protein subfamily. Haeseleer, F., Sokal, I., Li, N., Pettenati, M., Rao, N., Bronson, D., Wechter, R., Baehr, W., Palczewski, K. J. Biol. Chem. (1999) [Pubmed]
  11. The crystal structure of GCAP3 suggests molecular mechanism of GCAP-linked cone dystrophies. Stephen, R., Palczewski, K., Sousa, M.C. J. Mol. Biol. (2006) [Pubmed]
  12. Cone cell survival and downregulation of GCAP1 protein in the retinas of GC1 knockout mice. Coleman, J.E., Zhang, Y., Brown, G.A., Semple-Rowland, S.L. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
WikiGenes - Universities