Molecular Analysis of the Human GAR1 Gene
A bovine glutamic acid rich protein (garp) was first reported as a soluble protein of unknown function which copurified with cGMP phosphodiesterase from rod outer segments (1). Characterization of bovine retina cDNA clones encoding garp identified a 65 kD protein with a high overall glutamate composition (24%), including one 109 amino acid domain near the C-terminus especially enriched (68/109 residues) in glutamate. This domain contained four repeats of a glutamate-rich 11 amino acid residue sequence (undecapeptide) and two repeats of a 26 amino acid peptide also rich in glutamic acid. Antibodies against a decamer corresponding to the undecapeptide from the glutamate rich region recognized a 65 kD protein in crude rod outer segment extracts. Northern analysis of poly A+ RNA from a variety of bovine tissues identified a 2.4 kb transcript only in the retina sample, suggesting that the expression may be retina-specific. More recently it was shown that garp is part of the 240 kD integral membrane protein complex that forms part of the cGMP-gated cation channel of bovine rod outer segments, thus identifing it as a third subunit (y) of the channel (2).
KeywordsObesity Codon Retina Neuropathy Polypeptide
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- 2.Illing, M., Colville, C.A., Williams, A.J., and Molday, R.S. (1994). Sequencing, cloning, and characterization of a third subunit of the cyclic nucleotide-gated channel complex of rod outer segments. ARVO ABSTRACTS. Invest. Ophthalmol. Vis. Sci. Suppl., vol 35, 1022.Google Scholar
- 4.Kaupp, U.B., Niidome, T., Tanabe, T., Terada, S., Bönigk, W., Stühmer, Cook, N.J., Kangawa, K., Matsuo, H., Hirose, T., Miyata, T., and Numa, S. (1989). Primary structure and functional expression from complementary DNA of the rod photoreceptor cyclic GMP-gated channel. Nature 342:762–766.PubMedCrossRefGoogle Scholar
- 7.McGee, T.L., Lin, D., Berson, E.L., and Dryja, T.P. (1994). Defects in the rod cGMP-gated channel gene in patients with retinitis pigmentosa. ARVO ABSTRACTS. Invest. Ophthalmol. Vis. Sci. Suppl., vol 35, 2154.Google Scholar
- 9.Chen, T.-Y, Illing, M., Molday, L.L., Hsu, Y-T, Yau, K.-W, and Molday, R.S. (1994). Subunit 2 (or β) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca+2-calmodulin modulation. Proc. Natl. Acad. Sci. USA 91:11757–11761.PubMedCentralPubMedCrossRefGoogle Scholar
- 10.Ardell, M.D., Makhija, A.K., Oliveira, L., Miniou, P., Viegas-Pequignot, E., and Pittler, S.J. cDNA, gene structure, and chromosomal localization of human GAR1 (CNCG3L), a homolog of the third subunit of bovine photoreceptor cGMP-gated channel. (1995) In press, Genomics.Google Scholar
- 12.Liu, M.-Y., Li, J., and Yau, K.W. (1994). Phosphorylation of the N-terminal domain of human rod cyclic nucleotide-gated channel by protein kinase C and the cAMP-dependent protein kinase. ARVO ABSTRACTS. Invest. Ophthalmol. Vis. Sci. Suppl. 35:1474.Google Scholar