Secretin receptor family
|Secretin family of 7 transmembrane receptors|
|File:PDB 1bl1 EBI.jpg|
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 IPR002285
- Calcitonin receptor IPR003287
- Corticotropin-releasing hormone receptor IPR003051
- Glucose-dependent insulinotropic polypeptide receptor/Gastric inhibitory polypeptide receptor IPR001749
- Glucagon receptor IPR003291
- Glucagon receptor-related IPR003290
- Growth hormone releasing hormone receptor IPR003288
- Parathyroid hormone receptor IPR002170
- Secretin receptor IPR002144
- Vasoactive intestinal peptide receptor IPR001571
Subfamily B2 contains receptors with long extracellular N-termini, such as the leukocyte cell-surface antigen CD97; calcium-independent receptors for latrotoxin (such as , and brain-specific angiogenesis inhibitor receptors (such as ) amongst others.
- Brain-specific angiogenesis inhibitor IPR008077
- CD97 antigen IPR003056
- EMR hormone receptor IPR001740
- GPR56 orphan receptor IPR003910
- Latrophilin receptor 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.
- 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. PMID 9737850. doi:10.1021/bi981265h.
- Harmar AJ (2001). "Family-B G-protein-coupled receptors". Genome Biol. 2 (12): REVIEWS3013. PMC 138994. PMID 11790261. doi:10.1186/gb-2001-2-12-reviews3013.
- 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 M-W, Stevens RC (July 2013). "Structure of the human glucagon class B G-protein-coupled receptor". Nature 499 (7459): 444–449. PMC 3820480. PMID 23863937. doi:10.1038/nature12393.
- Hollenstein K, de Graaf C, Bortolato A, Wang MW, Marshall FH, Stevens RC (2014). "Insights into the structure of class B GPCRs". Trends Pharmacol Sci 35 (1): 12–22. PMID 24359917. doi:10.1016/j.tips.2013.11.001.