MOLECULAR-CLONING AND CHARACTERIZATION OF THE HUMAN ANAPHYLATOXIN C3ARECEPTOR

In a human neutrophil cDNA library, an orphan G-protein-coupled recept or, HNFAG09, with 37% nucleotide identity to the C5a receptor (C5a-R, CD88) was identified. A novel feature of this gene, unlike C5a-R and o ther G-protein-coupled receptors, is the presence of an extraordinaril y large predicted extracellular loop comprised of in excess of 160 ami no acid residues between transmembrane domains 4 and 5. Northern blot analysis revealed that expression of mRNA for this receptor in human t issues, while similar, was distinct from C5a-R expression. Although th ere were differences in expression, transcripts for both receptors wer e detected in tissues throughout the body and the central nervous syst em. Mammalian cells stably expressing HNFAG09 specifically bound I-125 -C3a and responded to a C3a carboxyl-terminal analogue synthetic pepti de and to human C3a but not to rC5a with a robust calcium mobilization response. HNFAG09 encodes the human anaphylatoxin C3a receptor.