A protein with a receptor structure but with unidentified ligand
This article needs to be updated. The reason given is: Ligands are now partially identified along with a few other new discoveries. Please help update this article to reflect recent events or newly available information.(March 2024)
In
biochemistry, an orphan receptor is a protein that has a similar structure to other identified
receptors but whose
endogenousligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred to as an "adopted orphan".[1] Conversely, the term orphan ligand refers to a biological ligand whose cognate receptor has not yet been identified.
GPCR orphan receptors are usually given the name "GPR" followed by a number, for example
GPR1. In the GPCR family, nearly 100 receptor-like genes remain orphans.[11]
Discovery
Historically, receptors were discovered by using ligands to "fish" for their receptors. Hence, by definition, these receptors were not orphans. However, with modern molecular biology techniques such as
reverse pharmacology, screening of
cDNA libraries, and
whole genome sequencing, receptors have been identified based on sequence similarity to known receptors, without knowing what their ligands are.
^Fagg GE (May 1987). "Phencyclidine and related drugs bind to the activated N-methyl-D-aspartate receptor-channel complex in rat brain membranes". Neurosci. Lett. 76 (2): 221–7.
doi:
10.1016/0304-3940(87)90719-1.
PMID2438606.
S2CID23177400.