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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

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

Subfamily B2

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

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

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. ^ International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G Protein–Coupled Receptors
  3. ^ PDB: 4L6R​; Siu FY, He M, de Graaf C, Han GW, Yang D, Zhang Z, Zhou C, Xu Q, Wacker D, Joseph JS, Liu W, Lau J, Cherezov V, Katritch V, Wang MW, Stevens RC (July 2013). "Structure of the human glucagon class B G-protein-coupled receptor". Nature. 499 (7459): 444–9. doi:10.1038/nature12393. PMC 3820480. PMID 23863937.
  4. ^ PDB: 5VEX​; Song G, Yang D, Wang Y, de Graaf C, Zhou Q, Jiang S, Liu K, Cai X, Dai A, Lin G, Liu D, Wu F, Wu Y, Zhao S, Ye L, Han GW, Lau J, Wu B, Hanson MA, Liu ZJ, Wang MW, Stevens RC (2017). "Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators)". Nature. 546: 312–315. doi:10.1038/nature22378.
  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. 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.