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.[1]
Identifiers
Symbol 7tm_2
Pfam PF00002
InterPro IPR000832
PROSITE PDOC00559
TCDB 9.A.14
OPM superfamily 6
OPM protein 4k5y

Secretin family of 7 transmembrane receptors is a family of evolutionarily related proteins.[2]

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,[3] 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.[4]

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.

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 (such as O94910, and brain-specific angiogenesis inhibitor receptors (such as O14514) amongst others.

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 subfamilies

Unclassified members

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

References

  1. ↑ 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.
  2. ↑ Harmar AJ (2001). "Family-B G-protein-coupled receptors". Genome Biol. 2 (12): REVIEWS3013. doi:10.1186/gb-2001-2-12-reviews3013. PMC 138994. PMID 11790261.
  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 M-W, Stevens RC (July 2013). "Structure of the human glucagon class B G-protein-coupled receptor". Nature 499 (7459): 444–449. doi:10.1038/nature12393. PMC 3820480. PMID 23863937.
  4. ↑ 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. doi:10.1016/j.tips.2013.11.001. PMID 24359917.
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