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.
Identifiers
Symbol	7tm_2
Pfam	PF00002
InterPro	IPR000832
PROSITE	PDOC00559
TCDB	9.A.14
OPM superfamily	6
OPM protein	4k5y
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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.

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 IPR002285
  • PACAPR (ADCYAP1R1)
• Calcitonin receptor IPR003287
  • CALCR
• Corticotropin-releasing hormone receptor IPR003051
  • CRHR1; CRHR2
• Glucose-dependent insulinotropic polypeptide receptor/Gastric inhibitory polypeptide receptor IPR001749
  • GIPR
• Glucagon receptor IPR003291
  • GCGR
• Glucagon receptor-related IPR003290
  • GLP1R; GLP2R;
• Growth hormone releasing hormone receptor IPR003288
  • GHRHR
• Parathyroid hormone receptor IPR002170
  • PTHR1; PTHR2
• Secretin receptor IPR002144
  • SCTR
• Vasoactive intestinal peptide receptor 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 (such as O94910, and brain-specific angiogenesis inhibitor receptors (such as O14514) amongst others.

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

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 IPR002001

Unclassified subfamilies

• Ig-hepta receptor IPR008078
  • GPR116

Unclassified members

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