We have cloned an orphan G protein-coupled receptor from a human pitui
tary cDNA library using a probe generated by PCR, The cDNA, designated
H9, encodes a protein of 613 amino acids that is 45% identical at the
amino acid level to the recently cloned human Mel(1a) and Mel(1b) mel
atonin receptors. Structural analyses of the encoded protein and its g
ene, along,vith phylogenetic analysis, further show that H9 is closely
related to the G protein-coupled melatonin receptor family, Unusual f
eatures of the protein encoded by H9 include a lack of N-linked glycos
ylation sites and a carboxyl tail >300 amino acids long, H9 transientl
y expressed in COS-1 cells did not bind [I-125]melatonin or [H-3]melat
onin, H9 mRNA is expressed in hypothalamus and pituitary, suggesting t
hat the encoded receptor and its natural ligand are involved in neuroe
ndocrine function.