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[5] and brain-specific angiogenesis inhibitor receptors[6] 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 Biology. 2 (12): REVIEWS3013. doi:10.1186/gb-2001-2-12-reviews3013. PMC 138994Freely accessible. 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 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 3820480Freely accessible. PMID 23863937.
  4. ↑ 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.
  5. ↑ Universal protein resource accession number O94910 at UniProt.
  6. ↑ Universal protein resource accession number O14514 at UniProt.
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