PROSITE documentation PDOC00559G-protein coupled receptors family 2 signatures and profiles
A number of peptide hormones bind to G-protein coupled receptors that, while structurally similar to family 1 of G-protein coupled receptors (R7G) (see <PDOC00210>), do not show any similarity at the level of their sequence, thus representing a new family whose current known members [1,2] are listed below:
- Calcitonin receptor.
- Calcitonin gene-related peptide receptor.
- Corticotropin releasing factor receptor types 1 and 2.
- Gastric inhibitory polypeptide receptor.
- Glucagon receptor.
- Glucagon-like peptide 1 receptor.
- Growth hormone-releasing hormone receptor.
- Parathyroid hormone / parathyroid hormone-related peptide types 1 and 2.
- Pituitary adenylate cyclase activating polypeptide receptor.
- Secretin receptor.
- Vasoactive intestinal peptide receptor types 1 and 2.
- Insects diuretic hormone receptor.
In addition to the above characterized receptors, this family also includes:
- Caenorhabditis elegans putative receptor C13B9.4.
- Caenorhabditis elegans putative receptor ZK643.3.
- Leucocyte antigen CD97, a protein that contains, in its N-terminal section, 3 EGF-like domains (see <PDOC00021>).
- Cell surface glycoprotein EMR1, a protein that contains, in its N-terminal section, 6 to 7 EGF-like domains (see <PDOC00021>).
All the characterized receptors are coupled to G-proteins which activate both adenylyl cyclase and the phosphatidylinositol-calcium pathway.
Like family 1 R7G they seem to contain seven transmembrane regions. Their N-terminus is probably located on the extracellular side of the membrane and potentially glycosylated, while their C-terminus 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.
Family two G protein coupled receptors contain a long conserved region in their N terminal extracellular part which allow the binding of large peptidic ligand such as glucagon, secretin, VIP and PACAP [3]. This region contains five conserved cysteines residues which could be involved in disulfide bonds; we have developed a pattern in the region that spans the first three cysteines. We also developed a profile that covers the whole extracellular domain.
One of the most highly conserved regions spans the C-terminal part of the last transmembrane region and the beginning of the adjacent intracellular region. We have used this region as a second signature pattern. We also developed a profile that spans the seven transmembrane regions.
Expert(s) to contact by email: Last update:December 2004 / Pattern and text revised.
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PROSITE methods (with tools and information) covered by this documentation:
1 | Authors | Jueppner H. Abou-Samra A.-B. Freeman M. Kong X.-F. Schipani E. Richards J. Kolakowski L.F. Jr. Hock J. Potts J.T. Jr. Kronenberg H.M. Segre G.V. |
Source | Science 254:1024-1026(1991). |
2 | Authors | Hamann J. Hartmann E. van Lier R.A.W. |
Title | Structure of the human CD97 gene: exon shuffling has generated a new type of seven-span transmembrane molecule related to the secretin receptor superfamily. | |
Source | Genomics 32:144-147(1996). | |
PubMed ID | 8786105 |
3 | Authors | Bockaert J. Pin J.P. |
Title | Molecular tinkering of G protein-coupled receptors: an evolutionary success. | |
Source | EMBO J. 18:1723-1729(1999). | |
PubMed ID | 10202136 | |
DOI | 10.1093/emboj/18.7.1723 |
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