Orphan receptor
An orphan receptor is an apparent receptor that has a similar structure to other identified receptors but whose endogenous ligand has not yet been identified. If a ligand for an orphan receptor is later discovered, the receptor is referred to as an "adopted orphan".
Examples
Examples of orphan receptors are found in the G protein-coupled receptor (GPCR)[1][2][3] and nuclear receptor[4][5][6] families. GPCR orphan receptors are usually given the name "GPR" followed by a number, for example GPR1. Adopted orphan receptors in the nuclear receptor group include the farnesoid X receptor (FXR), liver X receptor (LXR), and peroxisome proliferator-activated receptor (PPAR). Another example of an orphan receptor site is the PCP binding site in the NMDA receptor. This is where the recreational drug PCP works, but no endogenous ligand is know for this site.
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 screening of cDNA libraries, it becomes possible to identify related receptors based on sequence similarity to known receptors without knowing what their ligands are.
References
- ^ Levoye A, Dam J, Ayoub MA, Guillaume JL, Jockers R (2006). "Do orphan G-protein-coupled receptors have ligand-independent functions? New insights from receptor heterodimers". EMBO Rep. 7 (11): 1094–8. doi:10.1038/sj.embor.7400838. PMC 1679777. PMID 17077864.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Civelli O, Saito Y, Wang Z, Nothacker HP, Reinscheid RK (2006). "Orphan GPCRs and their ligands". Pharmacol Ther. 110 (3): 525–32. doi:10.1016/j.pharmthera.2005.10.001. PMID 16289308.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Wise A, Jupe SC, Rees S (2004). "The identification of ligands at orphan G-protein coupled receptors". Annu Rev Pharmacol Toxicol. 44 (February): 43–66. doi:10.1146/annurev.pharmtox.44.101802.121419. PMID 14744238.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Giguère V (1999). "Orphan nuclear receptors: from gene to function". Endocr. Rev. 20 (5): 689–725. doi:10.1210/er.20.5.689. PMID 10529899.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ Benoit G, Cooney A, Giguere V, Ingraham H, Lazar M, Muscat G, Perlmann T, Renaud JP, Schwabe J, Sladek F, Tsai MJ, Laudet V (2006). "International Union of Pharmacology. LXVI. Orphan nuclear receptors". Pharmacol Rev. 58 (4): 798–836. doi:10.1124/pr.58.4.10. PMID 17132856.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Shi Y (2007). "Orphan nuclear receptors in drug discovery". Drug Discov. Today. 12 (11–12): 440–5. doi:10.1016/j.drudis.2007.04.006. PMC 2748783. PMID 17532527.
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External links
- "Class A Orphans GPCRs". IUPHAR Database. International Union of Pharmacology.
{{cite web}}: Cite has empty unknown parameter:|coauthors=(help) - "Class B Orphans GPCRs". IUPHAR Database. International Union of Pharmacology.
{{cite web}}: Cite has empty unknown parameter:|coauthors=(help) - "Class C Orphans GPCRs". IUPHAR Database. International Union of Pharmacology.
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