Location of naturally occurring, loss-of-function GPCRs mutations that compromise or involve believed ER export motifs [YS amino-terminal motif; E(X)3LL carboxyl-terminal motif], the Arg-X-Arg retention motif, the NxS/T consensus for N-glycosylation ( Tan et al., 2004 ; Dong et al., 2007 ), the AFNGT motif (present in the gonadotropin receptors that comprise the NxT consensus for glycosylation) ( Huhtaniemi and Themmen, 2005 ), the BBxxB or BBxB motifs [involved in G protein activation ( Okamoto and Nishimoto, 1992 )], the E/DRYxxI/V and N/DPxxY highly conserved motifs [involved in receptor activation and G protein coupling/recognition ( Gether and Kobilka, 1998 ; Rovati et al., 2007 )], and the predicted disulfide bridge between the ECL1 and ECL2. Mutations at sites in bold letters resulted in reported traffic-defective or plasma membrane expression-deficient mutant receptors

GPCR YS Motif NxS/T Consensus AFNGT Sequence ECL1-ECL2 Disulfide Bridge Formation E(X)3LL Motif RxR Motif E/DRYxxI/V Motif N/DpxxY Motif BBxxB, BBxB Motifs
Rhodopsin N15 C110 R135
V2R C112 R337 E242 R137 N321 (not tested)
R113 P322
GnRHR C200 R262 (in ICL3) R139 P320
LHR F194
FSHR A189 R573C
E-BR P383
MC1R R160 (in TM4) R142 D294
R162 (in TM4)
R163 (in TM4)
MC2R (ACTHR) R128 (not tested) P273 (not tested)
MC3R I183
MC4R Y35 T150 P299
CCR5 C178, C101 R223 (ICL3) Y299 ΔK228
  • LHR, lutropin (luteinizing hormone) receptor; FSHR, follitropin (follicle-stimulating hormone) receptor; TSHR, thyrotropin receptor; E-BR, endothelin-B receptor; MC1R, melanocortin-1 receptor; MC2R, melanocortin-2 receptor [or adrenocorticotropin receptor (ACTHR)]; MC3R, melanocortin-3 receptor; MC4R, melanocortin-4 receptor; CCR5, chemokine receptor-5