| Type |
Details |
Score |
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
512
 |
| Fragment?: |
false |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Volz A |
| Year: |
1995 |
| Journal: |
FEBS Lett |
| Title: |
Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. |
| Volume: |
373 |
| Issue: |
1 |
| Pages: |
23-9 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Reagan JD |
| Year: |
1996 |
| Journal: |
Insect Biochem Mol Biol |
| Title: |
Molecular cloning and function expression of a diuretic hormone receptor from the house cricket, Acheta domesticus. |
| Volume: |
26 |
| Issue: |
1 |
| Pages: |
1-6 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Reagan JD |
| Year: |
1994 |
| Journal: |
J Biol Chem |
| Title: |
Expression cloning of an insect diuretic hormone receptor. A member of the calcitonin/secretin receptor family. |
| Volume: |
269 |
| Issue: |
1 |
| Pages: |
9-12 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Kusano S |
| Year: |
2012 |
| Journal: |
Protein Sci |
| Title: |
Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. |
| Volume: |
21 |
| Issue: |
2 |
| Pages: |
199-210 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Mackie DI |
| Year: |
2018 |
| Journal: |
J Exp Med |
| Title: |
hCALCRL mutation causes autosomal recessive nonimmune hydrops fetalis with lymphatic dysplasia. |
| Volume: |
215 |
| Issue: |
9 |
| Pages: |
2339-2353 |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
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-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. Secretin stimulates secretion of enzymes and ions in the pancreas andintestine, and is present in small amounts in the brain (e.g., in thehypothalamus, brainstem and cerebral cortex). Secretin receptors arefound in high levels in the pancreas, stomach and heart. They activateadenylyl cyclase through stimulation of G proteins. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
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-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. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
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-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. Insect diuretic hormones regulate fluid and ion secretion, and the receptorswith which they interact are attractive targets for new insect controlagents []. Diuretic hormone receptors from the moth, Manduca sexta, and thehouse cricket, Acheta domesticus, share 53% sequence identity and have beenshown to be members of the secretin-like family of GPCRs []. The receptorsbind diuretic hormone with high affinity and stimulate adenylate cyclasewith high potency. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| 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-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. This entry represents the family 2 GPCR receptor proteins and Frizzled proteins. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
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-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. Glucose-dependent insulinotropic polypeptide (GIP) plays an important rolein the regulation of postprandial insulin secretion and proinsulin geneexpression of pancreatic beta-cells []. The human GIP-receptor encodes a7TM protein that is similar to the human glucagon-like peptide 1(GLP-1)receptor. It is hoped that an understanding of GIP-receptor regulation andsignal transduction will shed light on the hormone's failure to exert itsbiological action at the pancreatic B-cell in type II diabetes mellitus. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
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-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). |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
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 insequence []. 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 ligandsuch 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. Calcitonin gene-related peptide (CGRP) type 1 receptor (also known as Calcitonin receptor-like receptor) is a neuropeptide with diversebiological 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 []. Mutations in the gene for this protein has been related to pontaneous miscarriage and subfertility []. 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. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Conserved_site |
| 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-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. This entry represents a pair of conserved sites found within family 2 GPCR receptor proteins. The first conserved site spans three of the five highly conserved cysteine residues found within the N-terminal extracellular domain that may be involved in disulphide bonds. The second conserved site within a region spanning the C-terminal part of the last transmembrane region and the beginning of the adjacent intracellular region. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Domain |
| 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 andmice []. 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. This domain is found in the extracellular part of some of the secretin-like (family 2) GPCRs including the calcitonin receptor; corticotropin releasing factor receptor 1; diuretic hormone receptor; glucagon-like peptide 1 receptor; and parathyroid hormone peptide receptor. |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
463
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
169
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
218
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
115
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
79
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
82
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
463
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
409
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
464
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
304
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
462
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
318
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
460
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
423
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
591
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
447
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
375
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
591
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
464
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1014
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
386
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
485
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
485
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
485
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1009
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
524
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
687
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
542
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
908
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Vita N |
| Year: |
1993 |
| Journal: |
FEBS Lett |
| Title: |
Primary structure and functional expression of mouse pituitary and human brain corticotrophin releasing factor receptors. |
| Volume: |
335 |
| Issue: |
1 |
| Pages: |
1-5 |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
698
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
992
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
542
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1147
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
955
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
310
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1009
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
165
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
471
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
698
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
698
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Chen R |
| Year: |
1993 |
| Journal: |
Proc Natl Acad Sci U S A |
| Title: |
Expression cloning of a human corticotropin-releasing-factor receptor. |
| Volume: |
90 |
| Issue: |
19 |
| Pages: |
8967-71 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Hollenstein K |
| Year: |
2013 |
| Journal: |
Nature |
| Title: |
Structure of class B GPCR corticotropin-releasing factor receptor 1. |
| Volume: |
499 |
| Issue: |
7459 |
| Pages: |
438-43 |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
991
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Publication |
| First Author: |
McKnight AJ |
| Year: |
1996 |
| Journal: |
J Biol Chem |
| Title: |
Molecular cloning of F4/80, a murine macrophage-restricted cell surface glycoprotein with homology to the G-protein-linked transmembrane 7 hormone receptor family. |
| Volume: |
271 |
| Issue: |
1 |
| Pages: |
486-9 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Stacey M |
| Year: |
2002 |
| Journal: |
J Biol Chem |
| Title: |
EMR4, a novel epidermal growth factor (EGF)-TM7 molecule up-regulated in activated mouse macrophages, binds to a putative cellular ligand on B lymphoma cell line A20. |
| Volume: |
277 |
| Issue: |
32 |
| Pages: |
29283-93 |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
689
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
153
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
143
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
142
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
213
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
79
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
196
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
264
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
486
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
1251
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
127
|
| Fragment?: |
true |
|
•
•
•
•
•
|
| Protein |
| Organism: |
Mus musculus/domesticus |
| Length: |
681
|
| Fragment?: |
false |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Baud V |
| Year: |
1995 |
| Journal: |
Genomics |
| Title: |
EMR1, an unusual member in the family of hormone receptors with seven transmembrane segments. |
| Volume: |
26 |
| Issue: |
2 |
| Pages: |
334-44 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Hamann J |
| Year: |
2007 |
| Journal: |
Eur J Immunol |
| Title: |
EMR1, the human homolog of F4/80, is an eosinophil-specific receptor. |
| Volume: |
37 |
| Issue: |
10 |
| Pages: |
2797-802 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Kwakkenbos MJ |
| Year: |
2004 |
| Journal: |
Immunogenetics |
| Title: |
The EGF-TM7 family: a postgenomic view. |
| Volume: |
55 |
| Issue: |
10 |
| Pages: |
655-66 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Matmati M |
| Year: |
2007 |
| Journal: |
J Leukoc Biol |
| Title: |
The human EGF-TM7 receptor EMR3 is a marker for mature granulocytes. |
| Volume: |
81 |
| Issue: |
2 |
| Pages: |
440-8 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Hamann J |
| Year: |
2003 |
| Journal: |
Eur J Immunol |
| Title: |
Inactivation of the EGF-TM7 receptor EMR4 after the Pan-Homo divergence. |
| Volume: |
33 |
| Issue: |
5 |
| Pages: |
1365-71 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Yu J |
| Year: |
1996 |
| Journal: |
Endocrinology |
| Title: |
Molecular cloning of a type A chicken corticotropin-releasing factor receptor with high affinity for urotensin I. |
| Volume: |
137 |
| Issue: |
1 |
| Pages: |
192-7 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Lovenberg TW |
| Year: |
1995 |
| Journal: |
Proc Natl Acad Sci U S A |
| Title: |
Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain. |
| Volume: |
92 |
| Issue: |
3 |
| Pages: |
836-40 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Liaw CW |
| Year: |
1996 |
| Journal: |
Endocrinology |
| Title: |
Cloning and characterization of the human corticotropin-releasing factor-2 receptor complementary deoxyribonucleic acid. |
| Volume: |
137 |
| Issue: |
1 |
| Pages: |
72-7 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Bhudia N |
| Year: |
2020 |
| Journal: |
Sci Rep |
| Title: |
G Protein-Coupling of Adhesion GPCRs ADGRE2/EMR2 and ADGRE5/CD97, and Activation of G Protein Signalling by an Anti-EMR2 Antibody. |
| Volume: |
10 |
| Issue: |
1 |
| Pages: |
1004 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Boyden SE |
| Year: |
2016 |
| Journal: |
N Engl J Med |
| Title: |
Vibratory Urticaria Associated with a Missense Variant in ADGRE2. |
| Volume: |
374 |
| Issue: |
7 |
| Pages: |
656-63 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Hsiung HM |
| Year: |
1993 |
| Journal: |
Neuropeptides |
| Title: |
Structure and functional expression of a complementary DNA for porcine growth hormone-releasing hormone receptor. |
| Volume: |
25 |
| Issue: |
1 |
| Pages: |
1-10 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Gaylinn BD |
| Year: |
1993 |
| Journal: |
Mol Endocrinol |
| Title: |
Molecular cloning and expression of a human anterior pituitary receptor for growth hormone-releasing hormone. |
| Volume: |
7 |
| Issue: |
1 |
| Pages: |
77-84 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Zhou F |
| Year: |
2020 |
| Journal: |
Nat Commun |
| Title: |
Structural basis for activation of the growth hormone-releasing hormone receptor. |
| Volume: |
11 |
| Issue: |
1 |
| Pages: |
5205 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Nishimori H |
| Year: |
1997 |
| Journal: |
Oncogene |
| Title: |
A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis. |
| Volume: |
15 |
| Issue: |
18 |
| Pages: |
2145-50 |
|
•
•
•
•
•
|
| Publication |
| First Author: |
Aust G |
| Year: |
2016 |
| Journal: |
Handb Exp Pharmacol |
| Title: |
Adhesion GPCRs in Tumorigenesis. |
| Volume: |
234 |
|
| Pages: |
369-396 |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
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-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. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
Family |
| Description: |
Human epidermal growth factor (EGF)-like module containing mucin-like hormone receptor 1 (EMR1) is a surface receptor of unknown function that belongs to the EGF-seven-transmembrane (EGF-TM7) family of G-protein coupled receptors []. Human EMR1 has been reported to be expressed exclusively on eosinophils []. It is the the human homologue of F4/80, a monoclonal antibody that recognises a Mus musculus (Mouse) macrophage-restricted cell surface glycoprotein that has been extensively used to characterise macrophage populations in a wide range of immunological studies []. Little is known about its possible role in macrophage differentiation and function. The sequence of the F4/80 protein is similar to two protein superfamilies: the N-terminal region contains seven epidermal growth factor (EGF)-like domains, while the C-terminal region contains seven hydrophobic regions whose signature is consistent with membership of the secretin-like superfamily of GPCRs. The EGF and GPCR domains are separated from each other by a serine/threonine-rich domain, a feature reminiscent of mucin-like, single-span, integral membrane glycoproteins with adhesive properties [].This family also comprises EMR3, a marker for mature granulocytes [], and EMR4 [, ].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. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
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-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. Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis, playing an important role in coordinating the endocrine, autonomic and behavioral responses to stress and immune challenge []. The CRF receptor has been found in human cortex tissue, pituitary, brainstem and testis []. The protein comprises 415 amino acid residues with the characteristic 7TM architecture of the secretin-like GPCR superfamily. Three isoforms (designated CRF-R1, CRF-R2 and CRF-R3) are produced as a result of alternative splicing of the same gene: CRF-R1 appears to be the predominant form; CRF-R3 does not bind to CRF with a high affinity []. CRF and the related urocortin peptides (Ucn 1-3, also known as UCN, UCN2 and UCN3) mediate their actions through two CRF1 and CRF2 []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
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-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. The Adhesion G Protein-Coupled Receptors (aGPCRs) constitute an evolutionary ancient membrane protein family. The receptors contain a 7-TM domain with phylogeny suggesting ancestry to the Family B/2 (secretin receptor family, Class B/2) G-Protein-Coupled Receptors. aGPCRs are distinguished by their large amino-terminal regions that typically contain multiple modular motifs such as EGF (Epidermal Growth Factor-like), cadherin and immunoglobulin domains as well as novel lineage-specific structures. A defining feature of aGPCRs is the GPCR Autoproteoolysis-Inducing (GAIN) domain linking the N-terminal structure to the 7-TM region. Most aGPCRs undergo autocatalytic cleavage here, at the GPCR proteolysis site (GPS) into N-terminal and C-terminal fragments [].Adhesion G protein-coupled receptor E2 (ADGRE2) protein is a member of the EGF-7TM subclass of aGPCRs and has an N-terminal extracellular region that consists of 5 tandem EGF-like adhesion domains, an internal mucin-like stalk domain containing a short G-protein proteolytic site and a C-terminal seven-pass transmembrane domain. ADGRE2 undergoes autocatalytic cleavage within its G-protein proteolytic site motif. It is expressed predominantly in myeloid leukocytes but also on the surface of lung mast cells and the HMC1 human mast-cell line. The endogenous ligand is dermatan sulfate. The most closely related paralogue of ADGRE2 is ADGRE5 (also called CD97). Ligand binding of ADGRE5 mediates cell-cell adhesion of leukocytes and mediates an essential role in leukocyte migration []. |
|
•
•
•
•
•
|
| Protein Domain |
| Type: |
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-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. The major physiological role of calcitonin is to inhibit bone resorptionthereby 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 andpituitary). In the CNS, calcitonin has been reported to be analgesicand to suppress feeding and gastric acid secretion. It is used to treatPaget's disease of the bone. Calcitonin receptors are found predominantlyon osteoclasts or on immortal cell lines derived from these cells. It isfound in lower amounts in the brain (e.g. in hypothalamus and pituitarytissues) and in peripheral tissues (e.g. testes, kidney, liver andlymphocytes). It has also been described in lung and breast cancer celllines. The predominant signalling pathway is activation of adenylyl cyclasethrough 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 diversebiological 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. |
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| Protein Domain |
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Family |
| Description: |
Latrophilins are a family of secretin-like GPCRs that can be subdividedinto 3 subtypes: LPH1, LPH2 and LPH3. LPH1 is a brain-specific calciumindependent receptor of alpha-latrotoxin (LTX), a neurotoxin. It is the affinity of this form of the receptor for LTX that gives the family its name. LPH2 and LPH3, whilst sharing extensive sequence similarity to LPH1, do not bind LTX. LPH2 is distributed throughout most tissues, whereas LPH3 is also brain-specific []. The endogenous ligand(s) for these receptors are at present unknown. Binding of LTX to LPH1 stimulates exocytosis and the subsequent release of large amounts of neurotransmitters from neuronal and endocrine cells. The latrophilins possess up to 7 sites of alternative splicing; the resulting number of possible splice variants leads to a highly variable family of proteins.Structurally, these proteins have a seven-transmembrane region and a large extracellular N-terminal region which consists of several domains: a rhamnose binding lectin (RBL) domain, an olfactomedin-like (OLF) domain followed by a Serine/Threonine rich domain that is O-linked glycosylated, a hormone binding (HR) domain; and a GPCR Autoproteolysis INducing (GAIN) domain [].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. |
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| Protein Domain |
| Type: |
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-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. Three human secretin-like GPCRs that are expressed specifically in thebrain, and appear to have a role in the inhibition of angiogenesis, havebeen identified and named BAI (brain-specific angiogenesis inhibitor) 1-3[]. In addition to the characteristic 7 TM domains, the BAIs also have alarge extracellular domain containing a number of thrombospondin type 1 repeats - these have been shown to inhibit in vivo angiogenesis induced bybFGF in rat cornea. BAI1 has been found to be transcriptionally regulated by p53 and is absent in many glioblastoma cell lines, suggestingthat it may play an important role in suppression of the disease.BAI is also known as adhesion G protein-coupled receptor B (ADGRB). Disregulation of these GPCRs (aGPCRs) has been observed in cancer []. |
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| Protein Domain |
| Type: |
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-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. Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis, playing an important role in coordinating the endocrine, autonomic and behavioral responses to stress and immune challenge []. The CRF receptor has been found in human cortex tissue, pituitary, brainstem and testis []. The protein comprises 415 amino acid residues with the characteristic 7TM architecture of the secretin-like GPCR superfamily. Three isoforms (designated CRF-R1, CRF-R2 and CRF-R3) are produced as a result of alternative splicing of the same gene: CRF-R1 appears to be the predominant form; CRF-R3 does not bind to CRF with a high affinity []. CRF and the related urocortin peptides (Ucn 1-3, also known as UCN, UCN2 and UCN3) mediate their actions through two CRF1 and CRF2 [].The sequence of the CRF-R is highly conserved from avian to mammalian species, the majority of the sequence divergence occuring in the putativesignal peptide and extracellular N-terminal domain []. Five additional amino acids are inserted in the N terminus of the avian receptor, and despite its overall similarity to the type 1 mammalian CRF-R, its ligand binding properties are similar to those of the type 2 receptor (i.e., has a higher affinity for urotensin I than for CRF) []. This entry includes CRF1 receptor (CRF1R, also known as CRHR1), which is activated by CRF and Ucn1, is expressed in brain areas including the pituitary, hypothalamus, amygdala and cortex. It is an interesting target to develop drug treatments for stress-related conditions such as anxiety, depression and irritable bowel syndrome []. |
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| Protein Domain |
| Type: |
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-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. Corticotropin-releasing factor (CRF) is the principal neuroregulator of the hypothalamic-pituitary-adrenocortical axis, playing an important role in coordinating the endocrine, autonomic and behavioral responses to stress and immune challenge []. The CRF receptor has been found in human cortex tissue, pituitary, brainstem and testis []. The protein comprises 415 amino acid residues with the characteristic 7TM architecture of the secretin-like GPCR superfamily. Three isoforms (designated CRF-R1, CRF-R2 and CRF-R3) are produced as a result of alternative splicing of the same gene: CRF-R1 appears to be the predominant form; CRF-R3 does not bind to CRF with a high affinity []. CRF and the related urocortin peptides (Ucn 1-3, also known as UCN, UCN2 and UCN3) mediate their actions through two CRF1 and CRF2 [].For the CRF-R2 receptor, at least 2 splice forms with different 5'-coding sequences (CRF2 alpha and CRF2 beta) have been identified in rat []. The sequence of the CRF-R is highly conserved between species, the majority of the sequence divergence occuring in the putative signal peptide and extracellular N-terminal domain. The relative abundance of CRF-R2 messenger RNA appears to be lower in humans than in rats for the heart and skeletal tissues studied to date []. CRF-R2 stimulates cAMP production in response to CRF and known CRF-like agonists []. CRF and the non-mammalian CRF-related peptides sauvagine and urotensin I stimulate adenylate cyclaseactivity in a dose-dependent manner, with a rank order of potency thatdiffers from that of the CRF1 receptor (sauvagine>urotensin>=rat/human CRF>ovine CRF). The differences in the pharmacological profiles and tissue distributions of CRF-R1 and CRF-R2 suggests important functionaldifferences between the two receptors []. |
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| Protein Domain |
| Type: |
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-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. The major physiological role of calcitonin is to inhibit bone resorptionthereby leading to a reduction in plasma Ca2+. Further, it enhancesexcretion of ions in the kidney, prevents absorption of ions in theintestine, and inhibits secretion in endocrine cells (e.g. pancreas andpituitary). In the CNS, calcitonin has been reported to be analgesicand to suppress feeding and gastric acid secretion. It is used to treatPaget's disease of the bone. Calcitonin receptors are found predominantlyon osteoclasts or on immortal cell lines derived from these cells. It isfound in lower amounts in the brain (e.g. in hypothalamus and pituitarytissues) and in peripheral tissues (e.g. testes, kidney, liver andlymphocytes). It has also been described in lung and breast cancer celllines. The predominant signalling pathway is activation of adenylyl cyclasethrough guanine nucleotide-binding proteins (G proteins), but calcitonin has also been described to have both stimulatoryand inhibitory actions on the phosphoinositide pathway. |
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| Protein Domain |
| Type: |
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-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. Growth hormone (GH)-releasing hormone (GHRH) belongs to the family of gut-neuropeptide hormones that includes glucagon, secretin and vasoactive intestinal peptide (VIP) []. The receptors for this peptide family involve similar signal transduction pathways - on hormone binding, they interact with G protein and cause stimulation of adenylate cyclase []. Acting through the GHRH receptor (GHRHR), GH plays a pivotal role in the regulation of GH synthesis and secretion in the pituitary, possibly serving other roles in different tissues []. Cryo-electron microscopy shows a hormone recognition pattern where an α-helical GHRH forms interactions involving all the extracellular loops, most TM helices, and a linker from GHRHR []. The human pituitary GHRHR is a 423-amino acid protein that has the characteristic 7TM signature of the secretin-like GPCR superfamily, sharing 47%, 42%, 35%, and 28% identity with receptors for VIP, secretin, calcitonin and PTH, respectively []. |
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| Protein Domain |
| Type: |
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-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. The glucagon receptor (GR) plays a central role in regulating the level ofblood glucose by controlling the rate of hepatic glucose production and insulin secretion []. GR is expressed predominantly in liver, kidney, adrenal, lung and stomach, with lower levels of expression detected inbrown and white adipose tissue, cerebellum, duodenum and heart []. Their role in the control of blood glucose concentrations makes glucagon and GR especially important to studies of diabetes, in which the loss of control over blood glucose concentrations clinically defines the disease []. GR is similar to the secretin-like receptor superfamily. It can transduce signals leading to the accumulation of two different second messengers - i.e., both cAMP and calcium []. |
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