We present the cloning and sequencing of the human gene for a novel G-protein coupled receptor (GPR4), from the critical myotonic dystrophy (DM) region on chromosome 19q13.3. The homologous porcine gene was isolated and sequenced as well. The genes of both species are intronless and contain an open reading frame encoding a protein of 362 amino acids. In human, two isoforms of GPR4 are expressed, differing in their 3' untranslated region due to the use of alternate polyadenylation signals and measuring approximately 2.8 and 1.8 kb, respectively. Northern blot analysis showed that GPR4 is widely expressed, with higher levels in kidney, heart, and especially lung, where it is at least fivefold greater than in other tissues. Sequence analysis suggests that GPR4 is a peptide receptor and shares strongest homologies with purinergic receptors and receptors for angiotensin II, platelet activating factor, thrombin, and bradykinin.