G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine, and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. GPCRs are usually described as "superfamily" because they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence. The currently known superfamily members include the rhodopsin-like GPCRs (this family), the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs.
The rhodopsin-like GPCRs themselves represent a widespread protein family that includes hormones, neurotransmitters, and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices.
Rhodopsin-like GPCRs have been classified into the following 19 subgroups (A1-A19) based on a phylogenetic analysis.
Chemokine receptor InterPro: IPR000355Chemokine (C-C motif) receptor 1 (CCR1, CKR1)Chemokine (C-C motif) receptor 2 (CCR2, CKR2)Chemokine (C-C motif) receptor 3 (CCR3, CKR3)Chemokine (C-C motif) receptor 4 (CCR4, CKR4)Chemokine (C-C motif) receptor 5 (CCR5, CKR5)Chemokine (C-C motif) receptor 8 (CCR8, CKR8)Chemokine (C-C motif) receptor-like 2 (CCRL2, CKRX)chemokine (C motif) receptor 1 (XCR1, CXC1) InterPro: IPR005393chemokine (C-X3-C motif) receptor 1 (CX3CR1, C3X1) InterPro: IPR005387GPR137B (GPR137B, TM7SF1)Chemokine receptor InterPro: IPR000355Chemokine (C-C motif) receptor-like 1 (CCRL1 CCRL1, CCR11)Chemokine (C-C motif) receptor 6 (CCR6, CKR6)Chemokine (C-C motif) receptor 7 (CCR7, CKR7)Chemokine (C-C motif) receptor 9 (CCR9, CKR9)Chemokine (C-C motif) receptor 10 (CCR10, CKRA)CXC chemokine receptors InterPro: IPR001053Chemokine (C-X-C motif) receptor 3 (CXCR3)Chemokine (C-X-C motif) receptor 4 (CXCR4, Fusin)Chemokine (C-X-C motif) receptor 5 (CXCR5)Chemokine (C-X-C motif) receptor 6 (CXCR6, BONZO)Chemokine (C-X-C motif) receptor 7 (CXCR7, RDC1) InterPro: IPR001416Interleukin-8 InterPro: IPR000174 (IL8R)IL8R-α (IL8RA, CXCR1)IL8R-β (IL8RB, CXCR2)Adrenomedullin receptor (GPR182)Duffy blood group, chemokine receptor (DARC, DUFF)G Protein-coupled Receptor 30 (GPER, CML2, GPCR estrogen receptor)Angiotensin II receptor InterPro: IPR000248Angiotensin II receptor, type 1 (AGTR1, AG2S)Angiotensin II receptor, type 2 (AGTR2, AG22)Apelin receptor (AGTRL1, APJ) InterPro: IPR003904Bradykinin receptor InterPro: IPR000496Bradykinin receptor B1 (BDKRB1, BRB1)Bradykinin receptor B2 (BDKRB2, BRB2)GPR15 (GPR15, GPRF)GPR25 (GPR25)Opioid receptor InterPro: IPR001418delta Opioid receptor (OPRD1, OPRD)kappa Opioid receptor (OPRK1, OPRK)mu Opioid receptor (OPRM1, OPRM)Nociceptin receptor (OPRL1, OPRX)Somatostatin receptor InterPro: IPR000586Somatostatin receptor 1 (SSTR1, SSR1)Somatostatin receptor 2 (SSTR2, SSR2)Somatostatin receptor 3 (SSTR3, SSR3)Somatostatin receptor 4 (SSTR4, SSR4)Somatostatin receptor 5 (SSTR5, SSR5)GPCR neuropeptide receptor InterPro: IPR009150Neuropeptides B/W receptor 1 (NPBWR1, GPR7)Neuropeptides B/W receptor 2 (NPBWR2, GPR8)GPR1 orphan receptor (GPR1) InterPro: IPR002275Galanin receptor InterPro: IPR000405Galanin receptor 1 (GALR1, GALR)Galanin receptor 2 (GALR2, GALS)Galanin receptor 3 (GALR3, GALT)Cysteinyl leukotriene receptor InterPro: IPR004071Cysteinyl leukotriene receptor 1 (CYSLTR1)Cysteinyl leukotriene receptor 2 (CYSLTR2)Leukotriene B4 receptor InterPro: IPR003981Leukotriene B4 receptor (LTB4R, P2Y7)Leukotriene B4 receptor 2 (LTB4R2)Relaxin receptor InterPro: IPR008112Relaxin/insulin-like family peptide receptor 1 (RXFP1, LGR7)Relaxin/insulin-like family peptide receptor 2 (RXFP2, GPR106)Relaxin/insulin-like family peptide receptor 3 (RXFP3, SALPR)Relaxin/insulin-like family peptide receptor 4 (RXFP4, GPR100/GPR142)KiSS1-derived peptide receptor (GPR54) (KISS1R) InterPro: IPR008103Melanin-concentrating hormone receptor 1 (MCHR1, GPRO) InterPro: IPR008361Urotensin-II receptor (UTS2R, UR2R) InterPro: IPR000670Cholecystokinin receptor InterPro: IPR009126Cholecystokinin A receptor (CCKAR, CCKR)Cholecystokinin B receptor (CCKBR, GASR)Neuropeptide FF receptor InterPro: IPR005395Neuropeptide FF receptor 1 (NPFFR1, FF1R)Neuropeptide FF receptor 2 (NPFFR2, FF2R)Orexin receptor InterPro: IPR000204Hypocretin (orexin) receptor 1 (HCRTR1, OX1R)Hypocretin (orexin) receptor 2 (HCRTR2, OX2R)Vasopressin receptor InterPro: IPR001817Arginine vasopressin receptor 1A (AVPR1A, V1AR)Arginine vasopressin receptor 1B (AVPR1B, V1BR)Arginine vasopressin receptor 2 (AVPR2, V2R)Gonadotrophin releasing hormone receptor (GNRHR, GRHR) InterPro: IPR001658Pyroglutamylated RFamide peptide receptor (QRFPR, GPR103)GPR22 (GPR22, GPRM)GPR176 (GPR176, GPR)Bombesin receptor InterPro: IPR001556Bombesin-like receptor 3 (BRS3)Neuromedin B receptor (NMBR)Gastrin-releasing peptide receptor (GRPR)Endothelin receptor InterPro: IPR000499Endothelin receptor type A (EDNRA, ET1R)Endothelin receptor type B (EDNRB, ETBR)GPR37 (GPR37, ETBR-LP2) InterPro: IPR003909Neuromedin U receptor InterPro: IPR005390Neuromedin U receptor 1 (NMUR1)Neuromedin U receptor 2 (NMUR2)Neurotensin receptor InterPro: IPR003984Neurotensin receptor 1 (NTSR1, NTR1)Neurotensin receptor 2 (NTSR2, NTR2)Thyrotropin-releasing hormone receptor (TRHR, TRFR) InterPro: IPR009144Growth hormone secretagogue receptor (GHSR) InterPro: IPR003905GPR39 (GPR39)Motilin receptor (MLNR, GPR38)Anaphylatoxin receptors InterPro: IPR002234C3a receptor (C3AR1, C3AR)C5a receptor (C5AR1, C5AR)Chemokine-like receptor 1 (CMKLR1, CML1) InterPro: IPR002258Formyl peptide receptor InterPro: IPR000826Formyl peptide receptor 1 (FPR1, FMLR)Formyl peptide receptor-like 1 (FPRL1, FML2)Formyl peptide receptor-like 2 (FPRL2, FML1)MAS1 oncogene InterPro: IPR000820MAS1 (MAS1, MAS)MAS1L (MAS1L, MRG)GPR1 (GPR1)GPR32 (GPR32, GPRW)GPR44 (GPR44)GPR77 (GPR77, C5L2)Melatonin receptor InterPro: IPR000025Melatonin receptor 1A (MTNR1A, ML1A)Melatonin receptor 1B (MTNR1B, ML1B)Neurokinin receptor InterPro: IPR001681Tachykinin receptor 1 (TACR1, NK1R)Tachykinin receptor 2 (TACR2, NK2R)Tachykinin receptor 3 (TACR3, NK3R)Neuropeptide Y receptor InterPro: IPR000611Neuropeptide Y receptor Y1 (NPY1R, NY1R)Neuropeptide Y receptor Y2 (NPY2R, NY2R)Pancreatic polypeptide receptor 1 (PPYR1, NY4R)Neuropeptide Y receptor Y5 (NPY5R, NY5R)Prolactin-releasing peptide receptor (PRLHR, GPRA) InterPro: IPR001402Prokineticin receptor 1 (PROKR1, GPR73)Prokineticin receptor 2 (PROKR2, PKR2)GPR19 (GPR19, GPRJ)GPR50 (GPR50, ML1X)GPR75 (GPR75)GPR83 (GPR83, GPR72)Glycoprotein hormone receptor InterPro: IPR002131FSH-receptor (FSHR)Luteinizing hormone/choriogonadotropin receptor (LHCGR, LSHR)Thyrotropin receptor (TSHR)Leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4, GPR48)Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5, GPR49)Leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6)GPR40-related receptor InterPro: IPR013312Free fatty acid receptor 1 (FFAR1, GPR40)Free fatty acid receptor 2 (FFAR2, GPR43)Free fatty acid receptor 3 (FFAR3, GPR41)GPR42 (GPR42, FFAR1L)P2 purinoceptor InterPro: IPR002286Purinergic receptor P2Y1 (P2RY1)Purinergic receptor P2Y2 (P2RY2)Purinergic receptor P2Y4 (P2RY4)Purinergic receptor P2Y6 (P2RY6)Purinergic receptor P2Y8 (P2RY8)Purinergic receptor P2Y11 (P2RY11)Hydroxycarboxylic acid receptor 1 (HCAR1, GPR81)Hydroxycarboxylic acid receptor 2, Niacin receptor 1 (HCAR2, GPR109A)Hydroxycarboxylic acid receptor 3, Niacin receptor 2 (HCAR3, GPR109B, HM74)GPR31 (GPR31, GPRV)GPR82 (GPR82)Oxoglutarate (alpha-ketoglutarate) receptor 1 (OXGR1, GPR80)Succinate receptor 1 (SUCNR1, GPR91)P2 purinoceptor InterPro: IPR002286Purinergic receptor P2Y12 (P2RY12)Purinergic receptor P2Y13 (P2RY13, GPR86) InterPro: IPR008109Purinergic receptor P2Y14 (P2RY14, UDP-glucose receptor, KI01) InterPro: IPR005466GPR34 (GPR34)GPR87 (GPR87)GPR171 (GPR171, H963)Platelet-activating factor receptor (PTAFR, PAFR) InterPro: IPR002282Cannabinoid receptor InterPro: IPR002230Cannabinoid receptor 1 (brain) (CNR1, CB1R)Cannabinoid receptor 2 (macrophage) (CNR2, CB2R)Lysophosphatidic acid receptor InterPro: IPR004065Lysophosphatidic acid receptor 1 (LPAR1)Lysophosphatidic acid receptor 2 (LPAR2)Lysophosphatidic acid receptor 3 (LPAR3)Sphingosine 1-phosphate receptor InterPro: IPR004061Sphingosine 1-phosphate receptor 1 (S1PR1)Sphingosine 1-phosphate receptor 2 (S1PR2)Sphingosine 1-phosphate receptor 3 (S1PR3)Sphingosine 1-phosphate receptor 4 (S1PR4)Sphingosine 1-phosphate receptor 5 (S1PR5)Melanocortin/ACTH receptor InterPro: IPR001671Melanocortin 1 receptor (MC1R, MSHR)Melanocortin 3 receptor (MC3R)Melanocortin 4 receptor (MC4R)Melanocortin 5 receptor (MC5R)ACTH receptor (MC2R), ACTR)GPR3 (GPR3)GPR6 (GPR6)GPR12 (GPR12, GPRC)Eicosanoid receptor InterPro: IPR008365Prostaglandin D2 receptor (PTGDR, PD2R)Prostaglandin E1 receptor (PTGER1, PE21)Prostaglandin E2 receptor (PTGER2, PE22)Prostaglandin E3 receptor (PTGER3, PE23)Prostaglandin E4 receptor (PTGER4, PE24)Prostaglandin F receptor (PTGFR, PF2R)Prostaglandin I2 (prostacyclin) receptor (PTGIR, PI2R)Thromboxane A2 receptor (TBXA2R, TA2R)Lysophosphatidic acid receptor InterPro: IPR004065Lysophosphatidic acid receptor 4 (LPAR4)Lysophosphatidic acid receptor 5 (LPAR5)Lysophosphatidic acid receptor 6 (LPAR6) InterPro: IPR002188P2 purinoceptor InterPro: IPR002286Purinergic receptor P2Y10 (P2RY10, P2Y10)Protease-activated receptor InterPro: IPR003912Coagulation factor II (thrombin) receptor-like 1 (F2RL1, PAR2)Coagulation factor II (thrombin) receptor-like 2 (F2RL2, PAR3)Coagulation factor II (thrombin) receptor-like 3 (F2RL3, PAR4)Epstein-Barr virus induced gene 2 (lymphocyte-specific G protein-coupled receptor) (GPR183)Proton-sensing G protein-coupled receptorsGPR4 (GPR4) InterPro: IPR002276GPR65 (GPR65) InterPro: IPR005464GPR68 (GPR68) InterPro: IPR005389GPR132 (GPR132, G2A) InterPro: IPR005388GPR17 (GPR17, GPRH)GPR18 (GPR18, GPRI)GPR20 (GPR20, GPRK)GPR35 (GPR35)GPR55 (GPR55)Coagulation factor II receptor (F2R, THRR)Opsins InterPro: IPR001760Rhodopsin (RHO, OPSD)Opsin 1 (cone pigments), short-wave-sensitive (color blindness, tritan) (OPN1SW, OPSB) (blue-sensitive opsin)Opsin 1 (cone pigments), medium-wave-sensitive (color blindness, deutan) (OPN1MW, OPSG) (green-sensitive opsin)Opsin 1 (cone pigments), long-wave-sensitive (color blindness, protan) (OPN1LW, OPSR) (red-sensitive opsin)Opsin 3, Panopsin (OPN3)Opsin 4, Melanopsin (OPN4)Opsin 5 (OPN5, GPR136)Retinal G protein coupled receptor (RGR)Retinal pigment epithelium-derived rhodopsin homolog (RRH, OPSX) (visual pigment-like receptor opsin) InterPro: IPR0017935-Hydroxytryptamine (5-HT) receptor InterPro: IPR0022315-HT2A (HTR2A, 5H2A)5-HT2B (HTR2B, 5H2B)5-HT2C (HTR2C, 5H2C)5-HT6 (HTR6, 5H6) InterPro: IPR002232Adrenergic receptor InterPro: IPR002233Alpha1A (ADRA1A, A1AA)Alpha1B (ADRA1B, A1AB)Alpha1D (ADRA1D, A1AD)Alpha2A (ADRA2A, A2AA)Alpha2B (ADRA2B, A2AB)Alpha2C (ADRA2C, A2AC)Beta1 (ADRB1, B1AR)Beta2 (ADRB2, B2AR)Beta3 (ADRB3, B3AR)Dopamine receptor InterPro: IPR000929D1 (DRD1, DADR)D2 (DRD2, D2DR)D3 (DRD3, D3DR)D4 (DRD4, D4DR)D5 (DRD5, DBDR)Trace amine receptor InterPro: IPR009132TAAR1 (TAAR1, TAR1)TAAR2 (TAAR2, GPR58)TAAR3 (TAAR3, GPR57)TAAR5 (TAAR5, PNR)TAAR6 (TAAR6, TAR4)TAAR8 (TAAR8, GPR102)TAAR9 (TAAR9, TAR3)Histamine H2 receptor (HRH2, HH2R) InterPro: IPR000503Histamine H1 receptor (HRH1, HH1R) InterPro: IPR000921Histamine H3 receptor (HRH3) InterPro: IPR003980Histamine H4 receptor (HRH4) InterPro: IPR008102Adenosine receptor InterPro: IPR001634A1 (ADORA1, AA1R)A2a (ADORA2A, AA2A)A2b (ADORA2B, AA2B)A3 (ADORA3, AA3R)Muscarinic acetylcholine receptor InterPro: IPR000995M1 (CHRM1, ACM1)M2 (CHRM2, ACM2)M3 (CHRM3, ACM3)M4 (CHRM4, ACM4)M5 (CHRM5, ACM5)GPR21 (GPR21, GPRL)GPR27 (GPR27)GPR45 (GPR45, PSP24)GPR52 (GPR52)GPR61 (GPR61)GPR62 (GPR62)GPR63 (GPR63)GPR78 (GPR78)GPR84 (GPR84)GPR85 (GPR85)GPR88 (GPR88)GPR101 (GPR101)GPR161 (GPR161, RE2)GPR173 (GPR173, SREB3)5-Hydroxytryptamine (5-HT) receptor InterPro: IPR0022315-HT1A (HTR1A, 5H1A)5-HT1B (HTR1B, 5H1B)5-HT1D (HTR1D, 5H1D)5-HT1E (HTR1E, 5H1E)5-HT1F (HTR1F, 5H1F)5-HT4 (HTR4) InterPro: IPR0015205-HT5A (HTR5A, 5H5A)5-HT7 (HTR7, 5H7) InterPro: IPR001069Olfactory receptor InterPro: IPR000725Vomeronasal receptor InterPro: IPR004072VN1R1VN1R2VN1R3VN1R4VN1R5