In
biochemistry, an orphan receptor is a protein that has a similar structure to other identified
receptors but whose
endogenous
Endogenous substances and processes are those that originate from within a living system such as an organism, tissue, or cell.
In contrast, exogenous substances and processes are those that originate from outside of an organism.
For example, es ...
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".
Conversely, the term orphan ligand refers to a biological ligand whose cognate receptor has not yet been identified.
Examples
Examples of orphan receptors are found in the
G protein-coupled receptor (GPCR)
and
nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of speci ...
families.
If an endogenous ligand is found, the orphan receptor is "adopted" or "de-orphanized".
An example is the nuclear receptor
Farnesoid X receptor (FXR) and the GPCR
TGR5/GPCR19/G protein-coupled bile acid receptor, both of which are activated by
bile acid
Bile acids are steroid acids found predominantly in the bile of mammals and other vertebrates. Diverse bile acids are synthesized in the liver. Bile acids are conjugated with taurine or glycine residues to give anions called bile salts.
Primary b ...
s.
Adopted orphan receptors in the
nuclear receptor
In the field of molecular biology, nuclear receptors are a class of proteins responsible for sensing steroids, thyroid hormones, vitamins, and certain other molecules. These receptors work with other proteins to regulate the expression of speci ...
group include 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
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ...
,
a type of
ligand-gated ion channel. This site is where the recreational drug PCP works, but no endogenous ligand is known to bind to this site.
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.
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.
References
External links
*
*
*
{{G protein-coupled receptors
Receptors