Secretin receptor family

Secretin family of 7 transmembrane receptors
OPM superfamily6
OPM protein4k5y

Secretin family receptor proteins, also known as Family B or family 2 of G-protein coupled receptors[1] are regulated by peptide hormones from the glucagon hormone family. The family is different from adhesion G protein-coupled receptors.[2]

The secretin-receptor family of GPCRs include vasoactive intestinal peptide receptors and receptors for secretin, calcitonin and parathyroid hormone/parathyroid hormone-related peptides. These receptors activate adenylyl cyclase and the phosphatidyl-inositol-calcium pathway. The receptors in this family have 7 transmembrane helices,[3][4] like rhodopsin-like GPCRs. However, there is no significant sequence identity between these two GPCR families and the secretin-receptor family has its own characteristic 7TM signature.[5]

The secretin-receptor family GPCRs exist in many animal species. Data mining with the Pfam signature has identified members in fungi, although due to their presumed non-hormonal function they are more commonly referred to as Adhesion G protein-coupled receptors, making the Adhesion subfamily the more basal group.[6] Three distinct sub-families (B1-B3) are recognized.

Subfamily B1[edit]

Subfamily B1 contains classical hormone receptors, such as receptors for secretin and glucagon, that are all involved in cAMP-mediated signalling pathways.

Subfamily B2[edit]

Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin[7] and brain-specific angiogenesis inhibitor receptors[8] amongst others. They are otherwise known as Adhesion G protein-coupled receptors.

Subfamily B3[edit]

Subfamily B3 includes Methuselah and other Drosophila proteins. Other than the typical seven-transmembrane region, characteristic structural features include an amino-terminal extracellular domain involved in ligand binding, and an intracellular loop (IC3) required for specific G-protein coupling.

Unclassified members[edit]

HCTR-5; HCTR-6; KPG 006; KPG 008


  1. ^ Harmar AJ (2001). "Family-B G-protein-coupled receptors". Genome Biology. 2 (12): REVIEWS3013. doi:10.1186/gb-2001-2-12-reviews3013. PMC 138994. PMID 11790261.
  2. ^ Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, et al. (2015). "International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors". Pharmacological Reviews. 67 (2): 338–67. doi:10.1124/pr.114.009647. PMC 4394687. PMID 25713288.
  3. ^ PDB: 4L6R​; Siu FY, He M, de Graaf C, Han GW, Yang D, Zhang Z, et al. (July 2013). "Structure of the human glucagon class B G-protein-coupled receptor". Nature. 499 (7459): 444–9. Bibcode:2013Natur.499..444S. doi:10.1038/nature12393. PMC 3820480. PMID 23863937.
  4. ^ PDB: 5VEX​; Song G, Yang D, Wang Y, de Graaf C, Zhou Q, Jiang S, et al. (June 2017). "Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators". Nature. 546 (7657): 312–315. Bibcode:2017Natur.546..312S. doi:10.1038/nature22378. PMID 28514449.
  5. ^ Hollenstein K, de Graaf C, Bortolato A, Wang MW, Marshall FH, Stevens RC (January 2014). "Insights into the structure of class B GPCRs". Trends in Pharmacological Sciences. 35 (1): 12–22. doi:10.1016/ PMC 3931419. PMID 24359917.
  6. ^ Krishnan A, Almén MS, Fredriksson R, Schiöth HB (2012). Xue C (ed.). "The origin of GPCRs: identification of mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in fungi". PLOS ONE. 7 (1): e29817. Bibcode:2012PLoSO...729817K. doi:10.1371/journal.pone.0029817. PMC 3251606. PMID 22238661.
  7. ^ Universal protein resource accession number O94910 at UniProt.
  8. ^ Universal protein resource accession number O14514 at UniProt.