GPR1 associate with GPA2 and acts as G protein-coupled receptor that senses glucose and controls filamentous growth [, ]. This entry represents the conserved C-terminal domain.
This family of evolutionary related proteins includes Yarrowia lipolytica (Candida lipolytica)glyxoxylate pathway regulator GPR1 [], Saccharomyces cerevisiae Ady2 and Fun34 (also known as Ato2); fission yeast hypothetical protein SpAC5D6.09c; Escherichia coli SatP (YaaH); and Aspergillus nidulans AcpA (AN5226). They are predicted to contain six transmembrane regions that may be involved in transport.Saccharomyces cerevisiae Ady2 is necessary for the expression of an acetate permease []. Gpr1p affects sensitivity to acetic acid in the yeast Yarrowia lipolytica []. AcpA may be a acetate transporter that is essential for acetate permease activity in the hyphal fungus Aspergillus nidulans []. SatP is involved in the uptake of acetate and succinate [].
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 [].The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [, , ].Chemerin-like receptor 2 (CML2, also known as GPCR1), is a receptor for chemoattractant adipokine chemerin/RARRES2 that may have a role for in the regulation of inflammation and energy homeostasis [, ]. This protein also acts also as a receptor for TAFA1, mediates its effects on neuronal stem-cell proliferation and differentiation via the activation of ROCK/ERK and ROCK/STAT3 signaling pathway []. In humans, GPR1 is expressed in the human hippocampus []. By contrast, the rat GPR1 gene is not expressed in hippocampus, demonstrating a functional variation for this receptor in these species [].
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 [].The secretin-like GPCRs include secretin [], calcitonin [], parathyroid hormone/parathyroid hormone-related peptides []and vasoactive intestinal peptide [], all of which activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. These receptors contain seven transmembrane regions, in a manner reminiscent of the rhodopsins and other receptors believed to interact with G-proteins (however there is no significant sequence identity between these families, the secretin-like receptors thus bear their own unique '7TM' signature). Their N-terminal is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allows the binding of large peptidic ligand such as glucagon, secretin, VIP and PACAP; this region contains five conserved cysteines residues which could be involved in disulphide bond. The C-terminal region of these receptor is probably cytoplasmic. Every receptor gene in this family is encoded on multiple exons, and several of these genes are alternatively spliced to yield functionally distinct products. Several 7TM receptors have been cloned but their endogenous ligands are unknown; these have been termed orphan receptors. GPR1 (formerly GPR56) was isolated from a human heart cDNA library using oligonucleotide primers corresponding to TM domains 4 and 7 of the secretin-like receptor family. The mRNA transcript is widely distributed throughout most tissues, the highest levels being found in thyroid, brain and heart. Within the brain, the hippocampus and hypothalamic nuclei express GPR1 in particularly high levels. This entry also include other orphan receptors, such as human adhesion G-protein coupled receptor G3 and G5 (AGRG3/5).
