Due to scheduled maintenance work, this service may not be available on Monday January 22nd between 08.00 am and 9.00 am CEST.
To improve security and privacy, we are moving our web pages and services from HTTP to HTTPS.
To give users of web services time to transition to HTTPS, we will support separate HTTP and HTTPS services until the end of 2017.
From January 2018 most HTTP traffic will be automatically redirected to HTTPS. [more...]
View this page in https
PROSITE documentation PDOC00559 [for PROSITE entry PS00649]

G-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:

Kolakowski L.F. Jr.

Last update:

December 2004 / Pattern and text revised.

Technical section

PROSITE methods (with tools and information) covered by this documentation:

G_PROTEIN_RECEP_F2_1, PS00649; G-protein coupled receptors family 2 signature 1  (PATTERN)

G_PROTEIN_RECEP_F2_3, PS50227; G-protein coupled receptors family 2 profile 1  (MATRIX)

G_PROTEIN_RECEP_F2_4, PS50261; G-protein coupled receptors family 2 profile 2  (MATRIX)

G_PROTEIN_RECEP_F2_2, PS00650; G-protein coupled receptors family 2 signature 2  (PATTERN)


1AuthorsJueppner 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.
SourceScience 254:1024-1026(1991).

2AuthorsHamann J., Hartmann E., van Lier R.A.W.
TitleStructure of the human CD97 gene: exon shuffling has generated a new type of seven-span transmembrane molecule related to the secretin receptor superfamily.
SourceGenomics 32:144-147(1996).
PubMed ID8786105

3AuthorsBockaert J., Pin J.P.
TitleMolecular tinkering of G protein-coupled receptors: an evolutionary success.
SourceEMBO J. 18:1723-1729(1999).
PubMed ID10202136

PROSITE is copyright. It is produced by the SIB Swiss Institute Bioinformatics. There are no restrictions on its use by non-profit institutions as long as its content is in no way modified. Usage by and for commercial entities requires a license agreement. For information about the licensing scheme send an email to
Prosite License or see: prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)