Two new cDNAs, human GPR107 and murine GPR108, were cloned from mammalian lung that are members of a novel gene family encoding proteins that are predicted to have an amino-terminal hydrophobic signal peptide sequence, a long extracellular domain and a carboxy-terminal seven transmembrane domain (LUSTR domain) similar to GPCRs. The 18-exon human GPR107 gene is located at 9q34.2-3 and spans 86.4 kb and the cDNA encodes a 552 residue protein. The closely related, but not homologous, 17-exon murine Gpr108 gene is located at 17C-D and spans 12.8 kb. The murine Gpr108 cDNA encodes a 562 residue protein that has 49% identity to human GPR107. They are distantly related to two other genes, transmembrane protein 87A and 87B that encode LUSTR domain-containing proteins in the human genome. LUSTR proteins are also found in Drosophila, Saccharomyces and Arabidopsis, but are absent from bacteria, archaea and viruses. This suggests that GPCRs are present in higher plants.