biochemistry Biochemistry or biological chemistry is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology and ...

, an orphan receptor is a protein that has a similar structure to other identified

receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

but whose endogenous

ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

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 G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related p ...

(GPCR) and nuclear receptor 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 acids. Adopted orphan receptors in the nuclear receptor group include FXR,

liver X receptor The liver X receptor (LXR) 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 (LXRs) are important regulators of cholesterol, fat ...

(LXR), and

peroxisome proliferator-activated receptor In the field of molecular biology, the peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that function as transcription factors regulating the expression of genes. PPARs play essential roles in the regu ...

(PPAR). Another example of an orphan receptor site is the PCP binding site in the NMDA receptor, a type of

ligand-gated ion channel Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

. 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 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 G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane ...

. 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 In the field of drug discovery, reverse pharmacology also known as target-based drug discovery (TDD), a hypothesis is first made that modulation of the activity of a specific protein target thought to be disease modifying will have beneficial t ...

, screening of cDNA libraries, and

whole genome sequencing Whole genome sequencing (WGS), also known as full genome sequencing, complete genome sequencing, or entire genome sequencing, is the process of determining the entirety, or nearly the entirety, of the DNA sequence of an organism's genome at a ...

, 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