Parathyroid hormone (PTH) is a polypeptidic hormone that elevates calcium level by dissolving the salts in bone and preventing their renal excretion. It stimulates [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblastic cells []. Defects in PTH are a cause of familial isolated hypoparathyroidism [].
Peptidyl-tRNA hydrolase () (PTH) is a bacterial enzyme that cleaves peptidyl-tRNA or N-acyl-aminoacyl-tRNA to yield free peptides or N-acyl-amino acids and tRNA. The natural substrate for this enzyme may be peptidyl-tRNA which drop off the ribosome during protein synthesis [, ]. Bacterial PTH has been found to be evolutionary related to a yeast protein [].
Parathyroid hormone (PTH) is a polypeptidic hormone that elevates calcium level by dissolving the salts in bone and preventing their renal excretion. Parathyroid hormone-related protein (PTH-rP) is structurally related to PTH []and seems to play a physiological role in lactation, possibly as a hormone for the mobilisation and/or transfer of calcium to the milk. It also regulates chondrocytic differentiation and endochondral bone formation [].PTH and PTH-rP bind to the same G-protein coupled receptor.This entry represents parathyroid hormone and parathyroid hormone-related protein.
Parathyroid hormone-related protein (PTH-rP) is structurally related to parathyroid hormone (PTH) []and seems to play a physiological role in lactation, possibly as a hormone for the mobilisation and/or transfer of calcium to the milk. It also regulates chondrocytic differentiation and bone formation [].This family also includes the zebrafish PTH family member Pth4, unique to noneutherian vertebrates, which is a regulator of bone mineral accrual acting through phosphate homeostasis []..
Peptidyl-tRNA hydrolase () (PTH) is a bacterial enzyme that cleaves peptidyl-tRNA or N-acyl-aminoacyl-tRNA to yield free peptides or N-acyl-amino acids and tRNA. The natural substrate for this enzyme may be peptidyl-tRNA which drop off the ribosome during protein synthesis [, ]. Bacterial PTH has been found to be evolutionary related to a yeast protein [].This group also contains chloroplast RNA splicing 2 (CRS2), which is closely related nuclear-encoded protein required for the splicing of nine group II introns in chloroplasts [, , ].
Peptidyl-tRNA hydrolase () (PTH) is a bacterial enzyme that cleaves peptidyl-tRNA or N-acyl-aminoacyl-tRNA to yield free peptides or N-acyl-amino acids and tRNA. The natural substrate for this enzyme may be peptidyl-tRNA which drop off the ribosome during protein synthesis [, ]. Bacterial PTH has been found to be evolutionary related to a yeast protein [].This group also contains chloroplast RNA splicing 2 (CRS2), which is closely related nuclear-encoded protein required for the splicing of nine group II introns in chloroplasts [, , ].The structure of hydrolases consists of three layers (alpha/beta/alpha) with mixed sheets of five strands where the strand 4 is antiparallel to the rest, and contains crossover loops.
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. Parathyroid hormone (PTH) is involved in calcium homeostasis within the body in combination with calcitonin and vitamin D. PTH is released in response to hypocalcaemia and stimulates a rise in blood calcium; the converse is true for calcitonin. The principle targets for PTH are bone and kidney. Antagonists at the PTH receptor are of potential clinical use in the treatment of hyperparathyroidism and short-term hypercalcaemic states. In addition to its presence in bone and kidney, the receptor is found in lower levels in blood vessels, where it mediates vasodilation. The principle second messenger pathway is activation of adenylyl cyclase through G proteins. In addition, PTH stimulates phosphoinositide metabolism on the expressed receptor.
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 ofapproximately 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 metabotropic glutamate receptors are functionally and pharmacologically distinct from the ionotropic glutamate receptors. They are coupled to G-proteins and stimulate the inositol phosphate/Ca2+intracellular signalling pathway [, , , ]. At least eight sub-types of metabotropic receptor (GRM1-8) have been identified in cloning studies. The sub-types differ in their agonist pharmacology and signal transduction pathways.The calcium-sensing receptor (CaSR) is an integral membrane protein thatsenses changes in the extracellular concentration of calcium ions. Theactivity of the receptor is mediated by a G-protein that activates aphosphatidyl-inositol-calcium second messenger system. The sequences of thereceptors show a high degree of similarity to the TM signature thatcharacterises the metabotropic glutamate receptors. In addition, thesequences contain a large extracellular domain that includes clusters ofacidic amino acid residues, which may be involved in calcium binding [].Defects in CaSR that result in reduced activity of the receptor causefamilial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), inherited conditions characterised by altered calciumhomeostasis [, ]. FHH-affected individuals exhibit mild or modest hypercalcemia, relative hypocalciuria and inappropriately normal PTH levels. Bycontrast, NSHPT is a rare autosomal recessive life-threatening disordercharacterised by high serum calcium concentrations, skeletal demineralisation and parathyroid hyperplasia. In addition, defects resulting fromreceptor activation at subnormal Ca2+levels cause autosomal dominanthypocalcemia [].This entry represents the extracellular calcium-sensing receptors and related proteins in GPCR family 3, such as the taste receptors.
