D. Eggerickx et al., MOLECULAR-CLONING OF AN ORPHAN G-PROTEIN-COUPLED RECEPTOR THAT CONSTITUTIVELY ACTIVATES ADENYLATE-CYCLASE, Biochemical journal, 309, 1995, pp. 837-843
A human gene encoding an orphan G-protein-coupled receptor named ACCA
(adenylate cyclase constitutive activator) was isolated from a genomic
library using as a probe a DNA fragment obtained by low-stringency PC
R. Human ACCA (hACCA) is a protein of 330 amino acids that exhibits al
l the structural hallmarks of the main family of G-protein-coupled rec
eptors. Expression of hACCA resulted:in a dramatic stimulation of aden
ylate cyclase, similar in amplitude to that obtained with other G(s)-c
oupled receptors fully activated by their respective ligands. This sti
mulation was obtained in a large variety of stable cell lines derived
from various organs, and originating from different mammalian species,
hACCA was found to be the human homologue of a recently reported mous
e orphan receptor (GPCR21). The mouse ACCA (mACCA) was therefore reclo
ned by PCR, and expression of mACCA in Cos-7 cells demonstrated that t
he mouse receptor behaved similarly as a constitutive activator of ade
nylate cyclase. It is not known presently whether the stimulation of a
denylate cyclase is the result of a true constitutive activity of the
receptor or, alternatively, is the consequence of a permanent stimulat
ion by a ubiquitous ligand. The tissue distribution of mACCA was deter
mined by RNase protection assay. Abundant transcripts were found in th
e brain, whereas lower amounts were detected in testis, ovary and eye.
Various hypotheses concerning the constitutive activity of ACCA and t
heir potential biological significance are discussed.