G Protein-coupled Receptor - Classification

Classification

The exact size of the GPCR superfamily is unknown but nearly 800 different human genes (or ≈4% of the entire protein-coding genome) have been predicted from genome sequence analysis. Although numerous classification schemes have been proposed, the superfamily is classically divided into three main classes (A, B, and C) with no detectable shared sequence homology between classes. The largest class by far is class A, which accounts for nearly 85% of the GPCR genes. Of class A GPCRs, over half of these are predicted to encode olfactory receptors while the remaining receptors are liganded by known endogenous compounds or are classified as orphan receptors. Despite the lack of sequence homology between classes, all GPCRs share a common structure and mechanism of signal transduction.

In all, GPCRs can be grouped into 6 classes based on sequence homology and functional similarity:

• Class A (or 1) (Rhodopsin-like)
• Class B (or 2) (Secretin receptor family)
• Class C (or 3) (Metabotropic glutamate/pheromone)
• Class D (or 4) (Fungal mating pheromone receptors)
• Class E (or 5) (Cyclic AMP receptors)
• Class F (or 6) (Frizzled/Smoothened)

The very large rhodopsin A group has been further subdivided into 19 subgroups (A1-A19). More recently, an alternative classification system called GRAFS (Glutamate, Rhodopsin, Adhesion, Frizzled/Taste2, Secretin) has been proposed.

The human genome encodes thousands of G protein-coupled receptors, about 350 of which detect hormones, growth factors, and other endogenous ligands. Approximately 150 of the GPCRs found in the human genome have unknown functions.

Some web-servers and bioinformatics prediction methods have been used for predicting the classification of GPCRs according to their amino acid sequence alone, by means of the pseudo amino acid composition approach.