title: The CASR gene: alternative splicing and transcriptional control, and calcium-sensing receptor (CaSR) protein: structure and ligand binding sites.
abstract: The calcium-sensing receptor (CaSR) is a G protein-coupled receptor encoded by a single copy gene. The human CASR gene spans ~103-kb and has eight exons. Promoters P1 and P2 drive transcription of exons 1A and 1B, respectively, encoding alternative 5'-UTRs that splice to exon 2 encoding the common part of the 5'-UTR. Exons 2-7 encode the CaSR protein of 1078 amino acids. Functional elements responsive to 1,25-dihydroxyvitamin D, proinflammatory cytokines, and glial cells missing-2 are present in the CASR promoters. Evolutionarily, the exon structure, first seen in aquatic vertebrates, is well-conserved with a single linkage disequilibrium haplotype block for protein coding exons 2-7. Structural features of the human CaSR protein are: an N-terminal signal peptide (19 amino acids (aa)); an extracellular domain (~600 aa) having a bi-lobed Venus Flytrap (VFT) domain with several Ca(2+)-binding sites; and a nine-cysteines domain that transduces the activation signal to the 7-transmembrane domain (250 aa) and the C-terminal tail (216 aa).
authors.affiliation: Calcium Research Laboratory, and Hormones and Cancer Research Unit, Royal Victoria Hospital and McGill University Health Centre, Montreal, QC H3A 1A1, Canada. geoffrey.hendy@mcgill.ca
authors.forename: Geoffrey N
authors.initials: GN
authors.lastname: Hendy
authors.forename: Lucie
authors.initials: L
authors.lastname: Canaff
authors.forename: David E C
authors.initials: DE
authors.lastname: Cole
mesh_terms: D017398:Alternative Splicing; D001665:Binding Sites / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D011485:Protein Binding; D011487:Protein Conformation; D044169:Receptors, Calcium-Sensing / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D044169:Receptors, Calcium-Sensing; D002118:Calcium
keywords: 1α,25-dihydroxyvitamin D; Class C G protein-coupled receptor; Venus-flytrap domain; alternative splicing; calcium-sensing receptor; glial cells missing-2; ligand binding; nine-cysteines domain; proinflammatory cytokines; seven-transmembrane domain; transcription