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Gene Review

GUCA1A  -  guanylate cyclase activator 1A (retina)

Homo sapiens

Synonyms: C6orf131, COD3, CORD14, GCAP, GCAP 1, ...
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Disease relevance of GUCA1A

  • Lentivirus vectors carrying GCAP1 promoter-nlacZ transgenes were used to examine the cell specificities and temporal expression characteristics of selected promoter fragments in developing retina [1].

Psychiatry related information on GUCA1A

  • A permanent ROS-GC1/GCAP-1 complex is physiologically significant, since it allows a very short response time of cyclase activity when the intracellular Ca2+-concentration changes [2].

High impact information on GUCA1A


Biological context of GUCA1A

  • CONCLUSIONS: The phenotype associated with the Y99C mutation in GUCA1A is distinctive, with little variation in expression [5].
  • The 4 coding exons of GUCA1A were screened for mutations in affected and unaffected family members [6].
  • 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 [7].
  • Five point mutations in the closely related GCAP1 have been linked to the etiology of cone dystrophies [8].
  • The results show that the introns of the GCAP2 gene are positioned exactly as in the GCAP1 gene and are nearly double in size [9].

Anatomical context of GUCA1A

  • We suggest that the gain-of-function effects of R838C on RetGC-1 stimulated by GCAP-1, which are dominant in vitro and may cause an abnormal increase in cGMP synthesis in dark-adapted photoreceptors, may be the cause of the cone-rod degeneration [10].
  • 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 [11].
  • 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 [11].
  • The expression of GCAP1 and S100B in spermatocytes and spermatids is mutually exclusive [12].
  • Other significantly upregulated mRNAs included chicken ovalbumin upstream promoter-transcription factor (COUP-TF1), retinoid X receptor (RXR)-gamma, thyroid hormone receptor (TR)-beta2, and guanylyl cyclase-activating protein (GCAP)-1 [13].

Associations of GUCA1A with chemical compounds

  • GCAP1 and GCAP2 are related Ca(2+)-binding proteins that activate photoreceptor guanylate cyclase(s) [9].
  • 1. It was screened for mutations, and all affected individuals showed a single base pair missense mutation (A-->G) at codon 99 in exon 2 of this gene generating a tyrosine-to-cysteine change in the GCAP1 protein [14].
  • In the absence of Ca(2+) GCAP stimulates and in the presence of Ca(2+) it inhibits cyclase activity [15].
  • However, the response of the individual pinealocyte neuron to the norepinephrine signal depends on whether the GCAP1-linked (results in hyperpolarization) or S100beta-linked (results in depolarization) pathway is operational in the pinealocyte [16].

Physical interactions of GUCA1A

  • 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 [17].

Regulatory relationships of GUCA1A

  • Recombinant Fugu GCAP1 failed to activate human retinal guanylate cyclase (retGC) in vitro although CD spectroscopy shows that the protein is folded with a similar secondary structure to that of human GCAP1 [18].

Other interactions of GUCA1A


Analytical, diagnostic and therapeutic context of GUCA1A

  • 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 [9].


  1. Analyses of the guanylate cyclase activating protein-1 gene promoter in the developing retina. Coleman, J.E., Fuchs, G.E., Semple-Rowland, S.L. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  2. Target recognition of guanylate cyclase by guanylate cyclase-activating proteins. Koch, K.W. Adv. Exp. Med. Biol. (2002) [Pubmed]
  3. GCAP1 (Y99C) mutant is constitutively active in autosomal dominant cone dystrophy. Sokal, I., Li, N., Surgucheva, I., Warren, M.J., Payne, A.M., Bhattacharya, S.S., Baehr, W., Palczewski, K. Mol. Cell (1998) [Pubmed]
  4. Identification and functional consequences of a new mutation (E155G) in the gene for GCAP1 that causes autosomal dominant cone dystrophy. Wilkie, S.E., Li, Y., Deery, E.C., Newbold, R.J., Garibaldi, D., Bateman, J.B., Zhang, H., Lin, W., Zack, D.J., Bhattacharya, S.S., Warren, M.J., Hunt, D.M., Zhang, K. Am. J. Hum. Genet. (2001) [Pubmed]
  5. Autosomal dominant cone and cone-rod dystrophy with mutations in the guanylate cyclase activator 1A gene-encoding guanylate cyclase activating protein-1. Downes, S.M., Holder, G.E., Fitzke, F.W., Payne, A.M., Warren, M.J., Bhattacharya, S.S., Bird, A.C. Arch. Ophthalmol. (2001) [Pubmed]
  6. Mutation in the gene GUCA1A, encoding guanylate cyclase-activating protein 1, causes cone, cone-rod, and macular dystrophy. Michaelides, M., Wilkie, S.E., Jenkins, S., Holder, G.E., Hunt, D.M., Moore, A.T., Webster, A.R. Ophthalmology (2005) [Pubmed]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. Calcium-modulated rod outer segment membrane guanylate cyclase type 1 transduction machinery in the testes. Jankowska, A., Burczynska, B., Duda, T., Warchol, J.B., Sharma, R.K. J. Androl. (2007) [Pubmed]
  13. Gene expression networks underlying retinoic acid-induced differentiation of human retinoblastoma cells. Li, A., Zhu, X., Brown, B., Craft, C.M. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  14. A mutation in guanylate cyclase activator 1A (GUCA1A) in an autosomal dominant cone dystrophy pedigree mapping to a new locus on chromosome 6p21.1. Payne, A.M., Downes, S.M., Bessant, D.A., Taylor, R., Holder, G.E., Warren, M.J., Bird, A.C., Bhattacharya, S.S. Hum. Mol. Genet. (1998) [Pubmed]
  15. Regulation of photoreceptor membrane guanylyl cyclases by guanylyl cyclase activator proteins. Dizhoor, A.M., Hurley, J.B. Methods (1999) [Pubmed]
  16. Calcium-sensitive ROS-GC1 signaling outside of photoreceptors: a common theme. Venkataraman, V., Nagele, R.G. Mol. Cell. Biochem. (2002) [Pubmed]
  17. 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]
  18. Characterisation of two genes for guanylate cyclase activator protein (GCAP1 and GCAP2) in the Japanese pufferfish, Fugu rubripes. Wilkie, S.E., Stinton, I., Cottrill, P., Deery, E., Newbold, R., Warren, M.J., Bhattacharya, S.S., Hunt, D.M. Biochim. Biophys. Acta (2002) [Pubmed]
  19. 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]
  20. Dominant cone and cone-rod dystrophies: functional analysis of mutations in retGC1 and GCAP1. Hunt, D.M., Wilkie, S.E., Newbold, R., Deery, E., Warren, M.J., Bhattacharya, S.S., Zhang, K. Novartis Found. Symp. (2004) [Pubmed]
  21. Regulation of cGMP synthesis in photoreceptors: role in signal transduction and congenital diseases of the retina. Dizhoor, A.M. Cell. Signal. (2000) [Pubmed]
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