Secretin receptor family

Secretin receptor family (class B GPCR subfamily^[1]) consists of secretin receptors regulated by peptide hormones from the glucagon hormone family. The family is different from adhesion G protein-coupled receptors.^[2]

Secretin family of 7 transmembrane receptors
Identifiers
Symbol	7tm_2
Pfam	PF00002
InterPro	IPR000832
PROSITE	PDOC00559
TCDB	9.A.14
OPM superfamily	6
OPM protein	4k5y
CDD	cd13952
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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 seven 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.

• Pituitary adenylate cyclase-activating polypeptide type 1 receptor InterPro: IPR002285
  • PACAPR (ADCYAP1R1)
• Calcitonin receptor InterPro: IPR003287
  • CALCR
• Corticotropin-releasing hormone receptor InterPro: IPR003051
  • CRHR1; CRHR2
• Glucose-dependent insulinotropic polypeptide receptor/Gastric inhibitory polypeptide receptor InterPro: IPR001749
  • GIPR
• Glucagon receptor InterPro: IPR003291
  • GCGR
• Glucagon receptor-related InterPro: IPR003290
  • GLP1R; GLP2R;
• Growth hormone releasing hormone receptor InterPro: IPR003288
  • GHRHR
• Parathyroid hormone receptor InterPro: IPR002170
  • PTHR1; PTHR2
• Secretin receptor InterPro: IPR002144
  • SCTR
• Vasoactive intestinal peptide receptor InterPro: IPR001571
  • VIPR1; VIPR2

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.

• Brain-specific angiogenesis inhibitor InterPro: IPR008077
  • BAI1; BAI2; BAI3
• CD97 antigen InterPro: IPR003056
  • CD97
• EMR hormone receptor InterPro: IPR001740
  • CELSR1; CELSR2; CELSR3; EMR1; EMR2; EMR3; EMR4
• GPR56 orphan receptor InterPro: IPR003910
  • GPR56; GPR64; GPR97; GPR110; GPR111; GPR112; GPR113; GPR114; GPR115; GPR123; GPR125; GPR126; GPR128; GPR133; GPR144; GPR157
• Latrophilin receptor InterPro: IPR003924
  • ELTD1; LPHN1; LPHN2; LPHN3
• Ig-hepta receptor InterPro: IPR008078
  • GPR116

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.

• Diuretic hormone receptor InterPro: IPR002001

Unclassified members

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

References

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. Hamann J, Aust G, Araç D, Engel FB, Formstone C, Fredriksson R, et al. (2015). "International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors". Pharmacological Reviews. 67 (2): 338–67. doi:10.1124/pr.114.009647. PMC 4394687. PMID 25713288.
3. PDB: 4L6R​; Siu FY, He M, de Graaf C, Han GW, Yang D, Zhang Z, et al. (July 2013). "Structure of the human glucagon class B G-protein-coupled receptor". Nature. 499 (7459): 444–9. Bibcode:2013Natur.499..444S. doi:10.1038/nature12393. PMC 3820480. PMID 23863937.
4. PDB: 5VEX​; Song G, Yang D, Wang Y, de Graaf C, Zhou Q, Jiang S, et al. (June 2017). "Human GLP-1 receptor transmembrane domain structure in complex with allosteric modulators". Nature. 546 (7657): 312–315. Bibcode:2017Natur.546..312S. doi:10.1038/nature22378. PMID 28514449. S2CID 2141649.
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/j.tips.2013.11.001. 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. Bibcode:2012PLoSO...729817K. 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.