Secretin receptor family
|Secretin family of 7 transmembrane receptors|
Structure of a 31 amino acid fragment of the extracellular N-terminus of the human parathyroid hormone receptor.
Secretin family of 7 transmembrane receptors is a family of evolutionarily related proteins.
This family is known as Family B, the secretin-receptor family or family 2 of the G-protein-coupled receptors (GPCR). Many secretin receptors are regulated by peptide hormones from the glucagon hormone family.
The secretin-receptor family 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, 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.
The secretin-receptor family GPCRs exist in many animal species, but have not been found in plants, fungi or prokaryotes. Three distinct sub-families (B1-B3) are recognized.
- Pituitary adenylate cyclase-activating polypeptide type 1 receptor InterPro: IPR002285
- Calcitonin receptor InterPro: IPR003287
- Corticotropin-releasing hormone receptor InterPro: IPR003051
- Glucose-dependent insulinotropic polypeptide receptor/Gastric inhibitory polypeptide receptor InterPro: IPR001749
- Glucagon receptor InterPro: IPR003291
- Glucagon receptor-related InterPro: IPR003290
- Growth hormone releasing hormone receptor InterPro: IPR003288
- Parathyroid hormone receptor InterPro: IPR002170
- Secretin receptor InterPro: IPR002144
- Vasoactive intestinal peptide receptor InterPro: IPR001571
Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin and brain-specific angiogenesis inhibitor receptors amongst others.
- Brain-specific angiogenesis inhibitor InterPro: IPR008077
- CD97 antigen InterPro: IPR003056
- EMR hormone receptor InterPro: IPR001740
- GPR56 orphan receptor InterPro: IPR003910
- Latrophilin receptor InterPro: IPR003924
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.
HCTR-5; HCTR-6; KPG 006; KPG 008
- PDB: 1BL1; Pellegrini M, Bisello A, Rosenblatt M, Chorev M, Mierke DF (September 1998). "Binding domain of human parathyroid hormone receptor: from conformation to function". Biochemistry. 37 (37): 12737–43. doi:10.1021/bi981265h. PMID 9737850.
- 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.
- 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.
- 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/j.tips.2013.11.001. PMID 24359917.