Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse.
The human formylpeptide receptor (FPR) gene cluster has three members: FPR1 and FPRL1, which are expressed in neutrophils and monocytes and encode seven-transmembrane-domain chemotactic receptors specific for N-formylpeptides, and FPRL2, whose function is unknown. The FPRL1 receptor is also a lipoxin A4 receptor. Using probes for the three human genes we have cloned six distinct mouse genes, designated Fpr1 and Fpr-rs1 through Fpr-rs5, which form a cluster on chromosome 17 in a region of conserved synteny with human chromosome 19. Fpr1 encodes a functional receptor and is clearly the orthologue of FPR1. Both Fpr-rs1 and Fpr-rs2 have higher sequence homology to FPRL1 than to FPRL2; Fpr-rs1 is 97% identical in amino acid sequence to a previously reported cDNA that encodes a lipoxin A4 receptor, whereas the putative ligand for Fpr-rs2 is unknown. Fpr-rs3, Fpr-rs4, and Fpr-rs5 appear to lack human counterparts and are most similar in sequence to FPRL1. RNA for Fpr1, Fpr-rs1, and Fpr-rs2 is present in leukocytes, spleen, and lung, whereas RNA for Fpr-rs3 was detected only in skeletal muscle. We did not detect Fpr-rs4 or Fpr-rs5 RNA in any tissue tested. Moreover, Fpr-rs5 has a stop codon in the protein-coding region corresponding to transmembrane domain VI and may not encode a functional receptor. These results suggest that the FPR gene cluster has undergone differential expansion in mammals with FPRL2, Fpr-rs2, Fpr-rs3, Fpr-rs4, and Fpr-rs5 arising after divergence of human and mouse.
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. jgao@nih.gov
J L
JL
Gao
H
H
Chen
J D
JD
Filie
C A
CA
Kozak
P M
PM
Murphy
D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000235:genetics*; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide / Q000235:genetics*; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
C105101:FPR2 protein, human; D012333:RNA, Messenger; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D018000:Receptors, Peptide