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.