An orphan receptor is an apparent receptor

Receptor (biochemistry)

In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...

 that has a similar structure to other identified receptors but whose endogenous

Endogenous

Endogenous substances are those that originate from within an organism, tissue, or cell. Endogenous retroviruses are caused by ancient infections of germ cells in humans, mammals and other vertebrates...

 ligand

Ligand (biochemistry)

In biochemistry and pharmacology, a ligand is a substance that forms a complex with a biomolecule to serve a biological purpose. In a narrower sense, it is a signal triggering molecule, binding to a site on a target protein.The binding occurs by intermolecular forces, such as ionic bonds, hydrogen...

 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

G protein-coupled receptor

G protein-coupled receptors , also known as seven-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptor, and G protein-linked receptors , comprise a large protein family of transmembrane receptors that sense molecules outside the cell and activate inside signal...

 (GPCR) and nuclear receptor

Nuclear receptor

In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...

 families. GPCR orphan receptors are usually given the name "GPR" followed by a number, for example GPR1

GPR1

G protein-coupled receptor 1, also known as GPR1, is a protein that in humans is encoded by the GPR1 gene.GPR1 is a member of the G protein-coupled receptor family of transmembrane receptors. It functions as a receptor for chemerin. Other receptors for chemerin include CMKLR1 and CCRL2.-Further...

.

If an endogenous ligand is found, the orphan receptor is "adopted". An example is the receptor FXR, which is activated by bile acid

Bile acid

Bile acids are steroid acids found predominantly in the bile of mammals. Bile salts are bile acids compounded with a cation, usually sodium. In humans, the salts of taurocholic acid and glycocholic acid represent approximately eighty percent of all bile salts. The two major bile acids are cholic...

s. Adopted orphan receptors in the nuclear receptor

Nuclear receptor

In the field of molecular biology, nuclear receptors are a class of proteins found within cells that are responsible for sensing steroid and thyroid hormones and certain other molecules...

 group include the farnesoid X receptor

Farnesoid X receptor

The bile acid receptor , also known as farnesoid X receptor or NR1H4 is a nuclear receptor that is encoded by the NR1H4 gene in humans.- Function :...

 (FXR), liver X receptor

Liver X receptor

The liver X receptor is a member of the nuclear receptor family of transcription factors and is closely related to nuclear receptors such as the PPARs, FXR and RXR. Liver X receptors are important regulators of cholesterol, fatty acid, and glucose homeostasis...

 (LXR), and peroxisome proliferator-activated receptor

Peroxisome proliferator-activated receptor

In the field of molecular biology, the peroxisome proliferator-activated receptors are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes...

 (PPAR). Another example of an orphan receptor site is the PCP

Phencyclidine

Phencyclidine , commonly initialized as PCP and known colloquially as angel dust, is a recreational dissociative drug...

 binding site in the NMDA receptor

NMDA receptor

The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....

, a type of ligand-gated ion channel

Ligand-gated ion channel

Ligand-gated ion channels are one type of ionotropic receptor or channel-linked receptor. They are a group of transmembrane ion channels that are opened or closed in response to the binding of a chemical messenger , such as a neurotransmitter.The binding site of endogenous ligands on LGICs...

. This is where the recreational drug PCP works, but no endogenous ligand is known 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

CDNA library

A cDNA library is a combination of cloned cDNA fragments inserted into a collection of host cells, which together constitute some portion of the transcriptome of the organism. cDNA is produced from fully transcribed mRNA found in the nucleus and therefore contains only the expressed genes of an...

, it becomes possible to identify related receptors based on sequence similarity to known receptors without knowing what their ligands are.