Table 6.

Published information for Class B GPCRs following mutation of the conserved polar residues assessed in this study. h, human; o, opossum; r, rat. GLP-1(R); glucagon-like peptide-1 (receptor); CLR, calcitonin-like receptor; RAMP, receptor activity modifying protein; CGRP, calcitonin gene related peptide; SecR, secretin receptor; PTH-(R), parathyroid hormone (receptor); GCGR, glucagon receptor; VPAC-(R), vasoactive intestinal polypeptide (receptor); GIP(R), glucose-dependent insulinotropic peptide (receptor). CRE; cAMP response element.

Position (Class B Wootten numbering)	Mutant	Receptor	Effect compared with WT	Reference
2.46	R2.46A	hGLP-1R	Decreased GLP-1 mediated cAMP potency	[38]
	R2.46A	rGCGR	No detectable cell surface expression	[52]
	R2.46A	hCLR-RAMP 1	Reduced CGRP mediated cAMP potency.	[59]
	R2.46A	SecR	Decreased secretin mediated calcium potency but not cAMP potency	[17]
2.52	N2.52A	hCLR-RAMP1	No effect on CGRP affinity or cAMP production	[59]
	H2.52A	oPTH-1R	No effect on PTH-1 cAMP production.	[57]
3.30	R3.30A	rGLP-1R	Reduced GLP-1 mediated cAMP production	[69]
	R3.30A	hGCGR	Reduced expression and glucagon affinity	[15]
	R3.30A	rSecR	Reduced secretin-mediated cAMP production	[14]
	K3.30A	hCLR-RAMP1	No effect on CGRP mediated cAMP production	[59]
	K3.30A	hCLR-RAMP2	Reduced adrenomedullin cAMP production	[60]
	K3.30A	hCLR-RAMP3	Reduced adrenomedullin cAMP production	[60]
3.53	Y3.53A	hVPAC1R	Reduced VIP mediated cAMP production	[55]
4.64	K4.64A	rGLP-1R	Reduced GLP-1 affinity	[1]
	K4.64A	hGLP-1R	Reduced expression, GLP-1 affinity and cAMP efficacy	[15]
	K4.64L	hGCGR	Reduced glucagon affinity	[15]
	R4.64A	oPTH-1R	No effect on PTH mediated cAMP	[57]
	R4.64A	rSecR	Decreased secretin mediated cAMP potency.	[14]
	R4.64A	hCLR-RAMP1	Reduced CGRP mediated cAMP pEC50.	[59]
	R4.64A	hCLR-RAMP2	Reduced adrenomedullin mediated cAMP production	[60]
	R4.64A	hCLR-RAMP3	Reduced adrenomedullin mediated cAMP production	[60]
5.40	R5.40A	hGLP-1R	Reduced expression, GLP-1 affinity and GLP-1 mediated cAMP potency.	[12]
	R5.40A	hGLP-1R	Reduced expression, GLP-1 affinity and cAMP efficacy.	[15]
	R5.40A	hGCGR	Reduced expression and glucagon affinity	[15]
	R5.40A	hGIPR	Reduced GIP mediated cAMP production.	[71]
	H5.40A	hCLR-RAMP1	Reduced CGRP-mediated cAMP pEC50	[59]
5.56	N5.56A	hCLR-RAMP1	No effect on CGRP cAMP mediated production	[59]
6.35	Y6.35A	hVPAC1R	No effect on VIP mediated cAMP	[13]
6.37	K6.37A	hCLR-RAMP1	No effect on CGRP mediated cAMP production	[10]
	R6.37A	hVPAC1R	No effect on VIP mediated cAMP production	[13]
	R6.37A	hSecR	No effect on secretin mediated cAMP production	[8]
	R6.37G	rGLP-1R	Decreased GLP-1 affinity	[20]
	R6.37A	rGLP-1R	No effect on GLP-1 mediated cAMP production	[54]
	R6.37A	rGCGR	Enhanced glucagon mediated CRE reporter activity (potency and Emax)	[52]
	R6.37A	hVPAC2R	Reduced VIP mediated cAMP potency	[35]
	K6.37A	hCRF-1R	Increased CRF mediated cAMP potency (Gs), reduced pERK1/2 (Gi)	[44]
6.37/6.40	R6.37A/K6.40A	hSecR	Reduced secretin mediated cAMP and calcium, no effect on affinity or receptor expression	[17]
6.40	R6.40A	hCLR-RAMP1	5-fold reduction in CGRP affinity, 30-fold reduction in CGRP mediated cAMP production	[10]
	R6.40A	hVPAC1R	Reduced VIP mediated IP3 production, no effect on cAMP	[36]
	K6.40A	rGLP-1R	No effect on GLP-1 mediated cAMP production	[54]
	R6.40A	hVPAC2R	Reduced VIP mediated cAMP potency	[35]
	K6.40A	hCRF-1R	Increased urocortin mediated cAMP (Gs), reduced IP3 (Gq)	[44]
7.61	N7.61A	hGLP-1R	No effect on expression, affinity, cAMP or calcium mobilisation, but reduced GLP-1 and oxyntomodulin mediated pERK1/2 (not exendin-4)	[66]
	N7.61A	rGCGR	Enhanced potency in glucagon mediated CRE reporter activity assay	[52]
7.63	E7.63A	hCLR-RAMP1	Reduced CGRP-mediated cAMP potency	[59]
	E7.63A	rGCGR	Enhanced basal activity and enhanced potency in glucagon mediated CRE reporter activity assay	[52]
	E7.63 K	oPTH-1R	No effect on PTH mediated cAMP	[57]
	E7.63A	hVPAC1R	Decreased VIP mediated cAMP production	[13]