Protein Domain : IPR003287

Type:  Family Name:  GPCR, family 2, calcitonin receptor family
Description:  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 terminus is probably located on the extracellular side of the membrane and potentially glycosylated. This N-terminal region contains a long conserved region which allow 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. The major physiological role of calcitonin is to inhibit bone resorption thereby leading to a reduction in plasma Ca2+. Further, it enhances excretion of ions in the kidney, prevents absorption of ions in the intestine, and inhibits secretion in endocrine cells (e.g. pancreas and pituitary). In the CNS, calcitonin has been reported to be analgesicand to suppress feeding and gastric acid secretion. It is used to treat Paget's disease of the bone. Calcitonin receptors are found predominantlyon osteoclasts or on immortal cell lines derived from these cells. It is found in lower amounts in the brain (e.g. in hypothalamus and pituitarytissues) and in peripheral tissues (e.g. testes, kidney, liver and lymphocytes). It has also been described in lung and breast cancer celllines. The predominant signalling pathway is activation of adenylyl cyclase through G proteins, but calcitonin has also been described to have both stimulatoryand inhibitory actions on the phosphoinositide pathway. Calcitonin gene-related peptide (CGRP) is a neuropeptide with diverse biological effects including potent vasodilator activity []. Messenger RNA for this receptor is predominantly expressed in the lung and heart, with specific localisation to lung alveolar cells and cardiac myocytes []. In the rat lung, it is associated with blood vessels; the gene may therefore play an important role in the maintenance of vascular tone []. mRNA is also found in the cerebellum []. The ligand for this receptor-like protein remains to be discovered. Short Name:  GCPR_2_calcitonin_rcpt_fam

2 Child Features

DB identifier Type Name
IPR001688 Family GPCR, family 2, calcitonin receptor
IPR003289 Family GPCR, family 2, calcitonin gene-related peptide, type 1 receptor

2 Contains

DB identifier Type Name
IPR017981 Domain GPCR, family 2-like
IPR017983 Conserved_site GPCR, family 2, secretin-like, conserved site

1 Cross References

Identifier
PR01350

0 Found In

3 GO Annotations

GO Term Gene Name
GO:0004948 IPR003287
GO:0007186 IPR003287
GO:0016020 IPR003287

3 Ontology Annotations

GO Term Gene Name
GO:0004948 IPR003287
GO:0007186 IPR003287
GO:0016020 IPR003287

1 Parent Features

DB identifier Type Name
IPR000832 Family GPCR, family 2, secretin-like

0 Proteins

14 Publications

First Author Title Year Journal Volume Pages PubMed ID
            8170923
            16753280
            23020293
            12679517
            8081729
            15914470
            18948278
            1646711
            1314625
            1658940
            1658941
            8222502
            8626685
            7818539