{PDOC00559} {PS00649; G_PROTEIN_RECEP_F2_1} {PS00650; G_PROTEIN_RECEP_F2_2} {PS50227; G_PROTEIN_RECEP_F2_3} {PS50261; G_PROTEIN_RECEP_F2_4} {BEGIN} **************************************************************** * 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 ), 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 ). - Cell surface glycoprotein EMR1, a protein that contains, in its N-terminal section, 6 to 7 EGF-like domains (see ). 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. -Consensus pattern: C-x(3)-[FYWLIV]-D-x(3,4)-C-[FW]-x(2)-[STAGV]-x(8,9)-C-[PF] -Sequences known to belong to this class detected by the pattern: ALL, except for the CD97/EMR1 subfamily members whose N-terminal region does not contain this domain. -Other sequence(s) detected in Swiss-Prot: NONE. -Consensus pattern: [QL]-G-[LMFCAV]-[LIVMFTA]-[LIV]-x-[LIVFSTM]-[LIFHV]- [VFYHLG]-C-[LFYAVI]-x-[NKRQDS]-x(2)-[VAI] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the first profile: ALL, except for the CD97/EMR1 subfamily members whose N-terminal region does not contain this domain. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Expert(s) to contact by email: Kolakowski L.F. Jr.; kolakowski@uthsca.edu -Last update: December 2004 / Pattern and text revised. [ 1] 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. Science 254:1024-1026(1991). [ 2] Hamann J., Hartmann E., van Lier R.A.W. "Structure of the human CD97 gene: exon shuffling has generated a new type of seven-span transmembrane molecule related to the secretin receptor superfamily." Genomics 32:144-147(1996). PubMed=8786105 [ 3] Bockaert J., Pin J.P. "Molecular tinkering of G protein-coupled receptors: an evolutionary success." EMBO J. 18:1723-1729(1999). PubMed=10202136; DOI=10.1093/emboj/18.7.1723 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}