GPCR fungal pheromone A receptor (GPCR_Pheromne_A_rcpt)
Type: Family

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups . The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence . The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) . GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice . Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs .

GPCR Fungal pheromone mating factor receptors form a distinct family of G-protein-coupled receptors, and are also known as Class D GPCRs.

The Fungal pheromone mating factor receptors STE2 and STE3 are integral membrane proteins that may be involved in the response to mating factors on the cell membrane . The amino acid sequences of both receptors contain high proportions of hydrophobic residues grouped into 7 domains,in a manner reminiscent of the rhodopsins and other receptors believed tointeract with G-proteins. However, while a similar 3D framework has been proposed to account for this, there is no significant sequence similarity either between STE2 and STE3, or between these and the rhodopsin-type family: the receptors thereofore bear their own unique '7TM' signatures which is why they have been given their own GPCR group: Class D Fungal mating pheromone receptors.

The STE3 gene in Saccharomyces cerevisiae is the cell-surface receptor that binds the 13-residue lipopeptide a-factor. Several related fungal pheromone receptor sequences are known: these include pheromone B alpha 1 and B alpha 3, and pheromone B beta 1 receptors from Schizophyllum commune; pheromone receptor 1 from Ustilago hordei; and pheromone receptors 1 and 2 from Ustilago maydis. Members of the family share about 20% sequence identity.

U. maydis, a tetrapolar fungal species, has two genetically unlinked loci that encode the distinct mating functions of cell fusion (the a locus) and subsequent sexual development and pathogenicity (the b locus) . The a locus exists in two alleles, the mating type in each of which is determined by a set of two genes; one encodes a precursor for a lipopeptide mating factor, while the other specifies the receptor for the pheromone secreted by cells of opposite mating type . U. maydis thus employs a novel strategy to determine its mating type by providing the primary determinants of cell-cell recognition directly from the mating type locus . The bipolar species, U. hordei, contains both a and b loci; physical linkage of these loci in this bipolar fungus accounts for its distinct mating system .

This entry represents mating-type a receptors.