PROSITE documentation PDOC00559
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_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_1, PS00649; G-protein coupled receptors family 2 signature 1  (PATTERN)

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

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