Cyclic nucleotide binding domain

Cyclic Nucleotide-binding Domain Cyclic Nucleotide Phosphodiesterases Cyclic Nucleotide-regulated Cation Channels Cyclic Nucleotides Cyclin... 

Cui, J., Kagan, A., Qin, D., Mathew, J., Melman, Y.F. and McDonald, T.V. (2001) Analysis of the cyclic nucleotide binding domain of the HERG potassium channel and interactions with KCNE2. The Journal of Biological Chemistry, 276, 17244-17251. 

The UniProt entry for human NTE lists three variants attributed to alternative splicing (UNIPROT, 2008). Although UniProt has adopted isoform-1 as the canonical sequence, this chapter defines human NTE as isoform-2, which is the sequence initially reported by Lush et al. (1998), consisting of 1,327 amino acids and having a molecular weight without posttranslational modifications of 146 kDa. The protein has a transmembrane domain near the N-terminus (residues 9-31) and three putative cyclic nucleotide binding domains (residues 163-262, 480-573, and 597-689), in addition to the patatin domain (residues 933-1,099), which contains the active site (Wijeyesakere et al., 2007). 

In cyclic nucleotide-regulated channels, this domain serves as a high-affinity binding site for 3-5 cyclic monophosphates. The CNBD of channels has a significant sequence similarity to the CNBD of most other classes of eukaryotic cyclic nucleotide receptors and to the CNBD of the prokaryotic catabolite activator protein (CAP). The primary sequence of CNBDs consists of approximately 120 amino acid residues forming three a-helices (oA-aC) and eight (3-strands ( 31- 38). 

Martinez, S., Beavo, J. A. and Hoi, W. G. J. GAF domains two-biUion-year-old molecular switches that bind cyclic nucleotides. Mol. Interv. 2 317-323,2002. 

Charbonneau H, Prusti RK, LeTrong H, Sonnenburg WK, Mullaney PJ, Walsh KA, Beavo JA. Identification of a non-catalytic cGMP-binding domain conserved in both the cGMP-stimulated and photoreceptor cyclic nucleotide phosphodiesterase. Proc Natl Acad Sci 87 288-292,1990. 

For the receptors that bind atrial natriuretic peptides and the peptides guanylin and uroguanylin, the intracellular domain is not a protein kinase but rather a guanylyl cyclase that synthesizes the second messenger cyclic guanosine monophosphate (cyclic GMP), which activates a cyclic GMP-dependent protein kinase (PKG) and can modulate the activities of several cyclic nucleotide phosphodiesterases, among other effectors. 

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