Table 1.
Rhodopsin‐like orphan GPCRs and the reach of crystal structure templates for homology modelling
| Rhodopsin‐like GPCRs a | Solved crystal structures (PDB b ) | Orphan GPCR | Best % TM identity within subclass (template) c | Best % TM identity overall (template) |
|---|---|---|---|---|
| α‐subclass 107 GPCRs | Bovine rhodopsin (1F88) | GPR3 | 28% (D3) | — |
| (26 orphans; 24%) | Human β2‐adrenoceptor (2RH1) | GPR6 | 26% (S1P1) | — |
| Turkey β1‐adrenoceptor (2VT4) | GPR12 | 28% (S1P1) | — | |
| Human adenosine A2A (3EML) | GPR21 | 28% (M3) | — | |
| Human dopamine D3 (3PBL) | GPR22 | 23% (H1) | — | |
| Human histamine H1 (3RZE) | GPR45 | 30% (5‐HT1B) | ‐ | |
| Human S1P1 (3V2Y) | GPR50 | 28% (D3) | — | |
| Human M2 muscarinic (3UON) | GPR52 | 28% (M3) | 29% (OX2) | |
| Rat M3 muscarinic (4DAJ) | GPR61 | 25% (D3) | — | |
| Human 5‐HT1B (4IAQ) | GPR62 | 20% (5‐HT1B) | 20% (NTS1) | |
| Human 5‐HT2B (4IB4) | GPR63 | 30% (β1‐adrenoceptor) | — | |
| Human LPA1 (4Z34) | GPR88 | 27% (D3) | — | |
| GPR119 | 29% (S1P1) | — | ||
| GPR135 | 29% (D3) | — | ||
| GPR152 | 21% (D3) | 23% (NTS1) | ||
| GPR153 | 15% (H1) | 19% (δ) | ||
| GPR160 | 15% (5‐HT2B) | 16% (P2Y12) | ||
| GPR162 | 17% (D3) | — | ||
| OPN3 | 35% (Rhodopsin) | — | ||
| OPN4 | 30% (β1‐adrenoceptor) | — | ||
| OPN5 | 28% (Rhodopsin) | — | ||
| TAAR2 | 33% (β2‐adrenoceptor) | — | ||
| TAAR5 | 39% (β1‐adrenoceptor) | — | ||
| TAAR6 | 33% (5‐HT1B) | — | ||
| TAAR8 | 32% (5‐HT1B) | — | ||
| TAAR9 | 35% (β2‐adrenoceptor) | — | ||
| β‐subclass 41 GPCRs | Rat NTS1 (4GRV) | BB3 receptor | 32% (OX2) | — |
| (7 orphans; 17%) | Human OX2 (4RNB) | GPR37 | 21% (OX2) | 24% (CCR5) |
| GPR37L1 | 23% (NTS1) | — | ||
| GPR39 | 38% (NTS1) | — | ||
| GPR75 | 20% (NTS1) | 21% (CXCR4) | ||
| GPR83 | 35% (OX2) | — | ||
| GPR150 | 18% (NTS1) | 19% (δ) | ||
| γ‐subclass 64 GPCRs | Human CXCR4 (3ODU) | GPR1 | 34% (AT1) | — |
| (7 orphans; 11%) | Human μ opioid receptor (4DKL) | GPR15 | 35% (AT1) | — |
| Human κ opioid receptor (4DJH) | GPR20 | 32% (κ) | — | |
| Human NOP receptor (4EA3) | GPR25 | 35% (AT1) | — | |
| Mouse δ opioid receptor (4EJ4) | GPR32 | 31% (δ) | — | |
| Human CCR5 (4MBS) | GPR151 | 22% (NOP) | — | |
| Human AT1 (4YAY) | GPR182 | 28% (NOP) | — | |
| δ‐subclass 74 GPCRs | Human PAR1 (3VW7) | GPR4 | 31% (P2Y1) | — |
| (39 orphans; 53%) | Human FFA1 (4PHU) | GPR17 | 33% (PAR1) | — |
| Human P2Y12 (4NTJ) | GPR18 | 28% (P2Y1) | 28% (AT1) | |
| Human P2Y1 (4XNV) | GPR19 | 20% (P2Y1) | 29% (D3) | |
| GPR26 | 19% (PAR1) | 24% (D3) | ||
| GPR27 | 18% (FFA1) | 28% (5‐HT2B) | ||
| GPR31 | 30% (P2Y1) | — | ||
| GPR34 | 32% (P2Y12) | — | ||
| GPR35 | 27% (P2Y1) | 30% (κ) | ||
| GPR55 | 24% (PAR1) | 29% (CCR5) | ||
| GPR65 | 32% (P2Y1) | — | ||
| GPR68 | 27% (PAR1) | 28% (δ) | ||
| GPR78 | 23% (FFA1) | — | ||
| GPR82 | 22% (P2Y1) | 23% (δ) | ||
| GPR84 | 24% (P2Y12) | 25% (D3) | ||
| GPR85 | 18% (FFA1) | 25% (5‐HT2B) | ||
| GPR87 | 47% (P2Y1) | — | ||
| GPR101 | 14% (PAR1) | 20% (β2‐adrenoceptor) | ||
| GPR132 | 31% (P2Y1) | — | ||
| GPR161 | 22% (P2Y1) | 27% (5‐HT1B) | ||
| GPR171 | 37% (P2Y12) | — | ||
| GPR173 | 16% (PAR1) | 24% (5‐HT2B) | ||
| GPR174 | 33% (P2Y1) | — | ||
| GPR183 | 29% (PAR1) | — | ||
| LGR4 | 19% (P2Y12) | 22% (AT1) | ||
| LGR5 | 16% (P2Y12) | 19% (S1P1) | ||
| LGR6 | 17% (P2Y12) | 20% (CCR5) | ||
| MAS1 | 20% (PAR1) | — | ||
| MAS1L | 17% (FFA1) | 19% (M2) | ||
| MRGPRD | 19% (PAR1) | 20% (κ) | ||
| MRGPRE | 19% (FFA1) | — | ||
| MRGPRF | 17% (FFA1) | 18% (M2) | ||
| MRGPRG | 20% (FFA1) | — | ||
| MRGPRX1 | 19% (P2Y1) | 23% (κ) | ||
| MRGPRX2 | 19% (P2Y1) | 24% (AT1) | ||
| MRGPRX3 | 18% (P2Y12) | 22% (μ) | ||
| MRGPRX4 | 20% (P2Y1) | 24% (μ) | ||
| P2RY8 | 38% (PAR1) | — | ||
| P2RY10 | 32% (P2Y1) | — | ||
| Unclassified orphans | GPR139 | — | 21% (δ) | |
| GPR141 | — | 19% (P2Y12) | ||
| GPR142 | — | 22% (NTS1) | ||
| GPR146 | — | 19% (CXCR4) | ||
| GPR148 | — | 16% (κ) | ||
| GPR149 | — | 14% (FFA1) | ||
| GPR176 | — | 23% (NOP) |
a
Receptor numbers are according to the IUPHAR/BPS Guide to PHARMACOLOGY (Alexander et al., 2015a); probable pseudogenes were excluded.
b
The PDB ID of the first instance of the unique GPCR structure is given.
c
Sequence identity was determined based on the Needleman and Wunch algorithm (Needleman and Wunsch, 1970), following alignment of the orphan receptor sequence to the TM regions of all crystallized GPCRs.