seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  13 RQLAWDTAIPLVLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSYRFME 92
Cdd:cd15072  105 SKLQWSTAISLVLFVWLFSAFWAAMPLLGWGEYDYEPLGTCCTLDYSKGDRNYVSYLFTMAFFNFILPLFILLTSYSSIE 184

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 678246455  93 QKFSRSGHLPVNTTLPGRMLLLGWGPYALLYLYAAIADVSFISPKLQMVPALIAKTMPTINAINYALHREMvCRGTW 169
Cdd:cd15072  185 QKLKKEGHLRFNTGLPLLTLLICWGPYAILALYAAITDVTSISPKLRMVPALLAKTSPTINAILYALGNEN-YRGGI 260

retinal G protein coupled receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents the retinal G-protein coupled receptor (RGR) found exclusively in retinal pigment epithelium (RPE) and Muller cells. RGR is a member of the class A rhodopsin-like receptor family. As with other opsins, RGR binds all-trans retinal and contains a conserved lysine reside on the seventh helix. RGR functions as a photoisomerase to catalyze the conversion of all-trans-retinal to 11-cis-retinal. Two mutations in RGR gene are found in patients with retinitis pigmentosa, indicating that RGR is essential to the visual process.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  13 RQLAWDTAIPLVLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSYRFME 92
Cdd:cd15072  105 SKLQWSTAISLVLFVWLFSAFWAAMPLLGWGEYDYEPLGTCCTLDYSKGDRNYVSYLFTMAFFNFILPLFILLTSYSSIE 184

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 678246455  93 QKFSRSGHLPVNTTLPGRMLLLGWGPYALLYLYAAIADVSFISPKLQMVPALIAKTMPTINAINYALHREMvCRGTW 169
Cdd:cd15072  185 QKLKKEGHLRFNTGLPLLTLLICWGPYAILALYAAITDVTSISPKLRMVPALLAKTSPTINAILYALGNEN-YRGGI 260

retinal G protein coupled receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents the retinal G-protein coupled receptor (RGR) found exclusively in retinal pigment epithelium (RPE) and Muller cells. RGR is a member of the class A rhodopsin-like receptor family. As with other opsins, RGR binds all-trans retinal and contains a conserved lysine reside on the seventh helix. RGR functions as a photoisomerase to catalyze the conversion of all-trans-retinal to 11-cis-retinal. Two mutations in RGR gene are found in patients with retinitis pigmentosa, indicating that RGR is essential to the visual process.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  13 RQLAWDTAIPLVLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSYRFME 92
Cdd:cd15072  105 SKLQWSTAISLVLFVWLFSAFWAAMPLLGWGEYDYEPLGTCCTLDYSKGDRNYVSYLFTMAFFNFILPLFILLTSYSSIE 184

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 678246455  93 QKFSRSGHLPVNTTLPGRMLLLGWGPYALLYLYAAIADVSFISPKLQMVPALIAKTMPTINAINYALHREMvCRGTW 169
Cdd:cd15072  185 QKLKKEGHLRFNTGLPLLTLLICWGPYAILALYAAITDVTSISPKLRMVPALLAKTSPTINAILYALGNEN-YRGGI 260

type 2 opsins in animals, member of the class A family of seven-transmembrane G protein-coupled receptors; This rhodopsin family represents the type 2 opsins found in vertebrates and invertebrates except sponge. Type 2 opsins primarily function as G protein coupled receptors and are responsible for vision as well as for circadian rhythm and pigment regulation. On the contrary, type 1 opsins such as bacteriorhodopsin and proteorhodopsin are found in both prokaryotic and eukaryotic microbes, functioning as light-gated ion channels, proton pumps, sensory receptors and in other unknown functions. Although these two opsin types share seven-transmembrane domain topology and a conserved lysine reside in the seventh helix, type 1 opsins do not activate G-proteins and are not evolutionarily related to type 2. Type 2 opsins can be classified into six distinct subfamilies including the vertebrate opsins/encephalopsins, the G(o) opsins, the G(s) opsins, the invertebrate G(q) opsins, the photoisomerases, and the neuropsins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  13 RQLAWDTAIPLVLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSY---- 88
Cdd:cd14969  109 FRLSKRRALILIAFIWLYGLFWALPPLFGWSSYVPEGGGTSCSVDWYSKDPNSLSYIVSLFVFCFFLPLAIIIFCYykiy 188

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  89 RFMEQKFSRSGHLPVNTTLPGR----------------MLLLGWGPYALLYLYAAIADVSFISPKLQMVPALIAKTMPTI 152
Cdd:cd14969  189 RTLRKMSKRAARRKNSAITKRTkkaekkvakmvlvmivAFLIAWTPYAVVSLYVSFGGESTIPPLLATIPALFAKSSTIY 268

                 ....*..
gi 678246455 153 NAINYAL 159
Cdd:cd14969  269 NPIIYVF 275

invertebrate Gq opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; The invertebrate Gq-coupled opsin subfamily includes the arthropod and mollusc visual opsins. Like the vertebrate visual opsins, arthropods possess color vision by the use of multiple opsins sensitive to different light wavelengths. The invertebrate Gq opsins are closely related to the vertebrate melanopsins, the primary photoreceptor molecules for non-visual responses to light, and the R1-R6 photoreceptors, which are the fly equivalent to the vertebrate rods. The Gq opsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  20 AIPLVLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSY----------- 88
Cdd:cd15337  118 AFIMIIIIWLWSLLWSIPPFFGWGRYVPEGFQTSCTFDYLSRDLNNRLFILGLFIFGFLCPLLIIIFCYvniiravrnhe 197

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  89 --------------RFMEQKFSRSGHLPVNTT-LPGRMLLLGWGPYALLYLYAAIADVSFISPKLQMVPALIAKTMPTIN 153
Cdd:cd15337  198 kemtqtaksgmgkdTEKNDARKKAEIRIAKVAiILISLFLLSWTPYAVVALLGQFGPAYWITPYVSELPVMFAKASAIYN 277

                 ....*.
gi 678246455 154 AINYAL 159
Cdd:cd15337  278 PIIYAL 283

insect photoreceptors R1-R6 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the insect photoreceptors and their closely related proteins. The Drosophila eye is composed of about 800 unit eyes called ommatidia, each of which contains eight photoreceptor cells (R1-R8). The six outer photoreceptors (R1-R6) function like the vertebrate rods and are responsible for motion detection in dim light and image formation. The R1-R6 photoreceptors express a blue-absorbing pigment, Rhodopsin 1(Rh1). The inner photoreceptors (R7 and R8) are considered the equivalent of the color-sensitive vertebrate cone cells, which express a range of different pigments. The R7 photoreceptors express one of two different UV absorbing pigments, either Rh3 or Rh4. Likewise, the R8 photoreceptors express either the blue absorbing pigment Rh5 or green absorbing pigment Rh6. These photoreceptors belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  11 SGRQLAWDTAIPLVLFVWMSSAFWASLPLM-GWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSYR 89
Cdd:cd15079  106 NGNPLTRGKALLLILFIWLYALPWALLPLLfGWGRYVPEGFLTSCSFDYLTRDWNTRSFVATIFVFAYVIPLIIIIYCYS 185

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  90 F------------------MEQKFSRSGHLPVNTTLPGR----------MLLLGWGPYALLYLYAAIADVSFISPKLQMV 141
Cdd:cd15079  186 FivkavfahekalreqakkMNVVSLRSNADANKQSAEIRiakvaltnvfLWFIAWTPYAVVALIGAFGNQSLLTPLVSMI 265

                        170
                 ....*....|....*...
gi 678246455 142 PALIAKTMPTINAINYAL 159
Cdd:cd15079  266 PALFAKTAACYNPIVYAI 283

non-visual VA (vertebrate ancient) opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; The vertebrate ancient (VA) opsin photopigments were originally identified in salmon and they appear to have diverged early in the evolution of vertebrate opsins. VA opsins are localized in the inner retina and the brain in teleosts. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extraretinal tissues and/or in non-rod, non-cone retinal cells. They are thought to be involved in light-dependent physiological functions such as photo-entrainment of circadian rhythm, photoperiodicity, and body color change. The VA opsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  24 VLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSYRFMEQKFSRSGHLPV 103
Cdd:cd15082  133 LLFVWTFSFIWTIPPVLGWSSYTVSKIGTTCEPNWYSGNMHDHTYIITFFTTCFILPLGVIFVSYGKLLQKLRKVSNTQG 212

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 678246455 104 ---NTTLPGRML-----------LLGWGPYALLYLYAAIADVSFISPKLQMVPALIAKTMPTINAINY 157
Cdd:cd15082  213 rlgNARKPERQVtrmvvvmivafMVCWTPYAAFSILVTAHPTIHLDPRLAAIPAFFSKTAAVYNPIIY 280

teleost multiple tissue (tmt) opsin, member of the class A family of seven-transmembrane G protein-coupled receptors; Teleost multiple tissue (tmt) opsins are homologs of encephalopsin. Mouse encephalopsin (or panopsin) is highly expressed in the brain and testes, whereas the teleost homologs are localized to multiple tissues. The exact functions of the encephalopsins and tmt-opsins are unknown. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extra-retinal tissues and/or in non-rod, non-cone retinal cells. They are thought to be involved in light-dependent physiological functions such as photo-entrainment of circadian rhythm, photoperiodicity and body color change. Tmt opsins belong to the class A of the G protein-coupled receptors and show strong homology to the vertebrate visual opsins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  24 VLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSYRFMEQKFSRSGHLPV 103
Cdd:cd15086  120 VGGSWLYSLLWTLPPLLGWSSYGPEGPGTTCSVQWTSRSANSISYIICLFIFCLLLPFLVMVYCYGRLLYAIKQVGKINK 199

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 678246455 104 NTT--LPGRML----------LLGWGPYALLYLYAAIADVSFISPKLQMVPALIAKTMPTINAINYAL 159
Cdd:cd15086  200 STArkREQHVLlmvvtmvicyLLCWLPYGVMALLATFGKPGLVTPVASIVPSILAKSSTVVNPIIYVF 267

encephalopsins (opsin-3), member of the class A family of seven-transmembrane G protein-coupled receptors; Encephalopsin, also called Opsin-3 or Panopsin, is a mammalian extra-retinal opsin that is highly localized in the brain. It is thought to play a role in encephalic photoreception. Encephalopsin belongs to the class A of the G protein-coupled receptors and shows strong homology to the vertebrate visual opsins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  24 VLFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSYRFM------------ 91
Cdd:cd15078  117 ITYIWLYSLAWTGAPLLGWNRYTLEVHGLGCSFDWKSKDPNDTSFVLLFFLGCLVVPLGIMAYCYGHIlyeirmlrsved 196

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 678246455  92 ------------EQKFSRSGHLPVNTtlpgrmLLLGWGPYALLYLYAAIADVSFISPKLQMVPALIAKTMPTINAINYA 158
Cdd:cd15078  197 lqtfqvikilkyEKKVAKMCLLMIST------FLICWMPYAVVSLLVTSGYSKLVTPTIAIIPSLFAKSSTAYNPVIYI 269

non-visual pinopsins, member of the class A family of seven-transmembrane G protein-coupled receptors; Pinopsins are found in the pineal organ of birds, reptiles and amphibians, but are absent from teleosts and mammals. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extra-retinal tissues and/or in non-rod, non-cone retinal cells. They are thought to be involved in light-dependent physiological functions such as photo-entrainment of circadian rhythm, photoperiodicity and body color change. Pinopsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  25 LFVWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGDRNFISFLFTMAFFNFLVPLFITHTSYRFM------------E 92
Cdd:cd15084  131 AFTWGWSLLWTSPPLFGWSSYVPEGLRTSCGPNWYTGGTNNNSYILALFVTCFALPLSTIIFSYSNLlltlravaaqqkE 210

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 678246455  93 QKFSRSGHLPVNTTLPGRML--LLGWGPYALLYLYAAIADVSFISPKLQMVPALIAKTMPTINAINY 157
Cdd:cd15084  211 SETTQRAEKEVTRMVIAMVMafLICWLPYATFAMVVATNKDVVIQPTLASLPSYFSKTATVYNPIIY 277

G protein-coupled receptors 61 and 62, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes the orphan receptors GPR61 and GPR62, which are both constitutively active and predominantly expressed in the brain. While GPR61 couples to G(s) subtype of G proteins, the signaling pathway and function of GPR 62 are unknown. GPR61-deficient mice displayed significant hyperphagia and heavier body weight compared to wild-type mice, suggesting that GPR61 is involved in the regulation of food intake and body weight. GPR61 transcript expression was found in the caudate, putamen, and thalamus of human brain, whereas GPR62 transcript expression was found in the basal forebrain, frontal cortex, caudate, putamen, thalamus, and hippocampus. Both receptors share the highest sequence homology with each other and comprise a conserved subgroup within the class A family of GPCRs, which includes receptors for hormones, neurotransmitters, sensory stimuli, and a variety of other ligands. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, which then activate the heterotrimeric G proteins. Members of this subgroup contain [A/E]RY motif, a variant of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of the class A GPCRs and important for efficient G protein-coupled signal transduction.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455  20 AIPLVLFVWMSSAFWASLPLMGWGHYDYEP--VGTCCTLDYSRGdRNFISFLFTMAFFNFLVPLFITHTSYRFMEQKFSr 97
Cdd:cd15220  116 VAAVLVGVWVKALLLGLLPVLGWPSYGGPApiAARHCSLHWSHS-GHRGVFVVLFALVCFLLPLLLILVVYCGVFKVFG- 193

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 678246455  98 SGHLPVNTTLPGRMLLLGWGPYALLYLYAAIADVSFISPKLQMVPALIAKTMPTINAINYAL 159
Cdd:cd15220  194 GGKAALTLAAIVGQFLCCWLPYFAFHLYSALAASPVSGGEAEEVVTWLAYSCFAVNPFFYGL 255

G protein-coupled receptors for prostanoids, member of the class A family of seven-transmembrane G protein-coupled receptors; Prostanoids are the cyclooxygenase (COX) metabolites of arachidonic acid, which include the prostaglandins (PGD2, PGE2, PGF2alpha), prostacyclin (PGI2), and thromboxane A2 (TxA2). These five major bioactive prostanoids acts as mediators or modulators in a wide range of physiological and pathophysiological processes within the kidney and play important roles in inflammation, platelet aggregation, and vasoconstriction/relaxation, among many others. They act locally by preferentially interacting with G protein-coupled receptors designated DP, EP. FP, IP, and TP, respectively. The phylogenetic tree suggests that the prostanoid receptors can be grouped into two major branches: G(s)-coupled (DP1, EP2, EP4, and IP) and G(i)- (EP3) or G(q)-coupled (EP1, FP, and TP), forming three clusters.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 678246455   7 YPASSGRQLAWdtaipLVLF-VWMSSAFWASLPLMGWGHYDYEPVGTCCTLDYSRGD--RNFISFLF---------TMAF 74
Cdd:cd14981  111 YNSHVKKRRAR-----LMLGaVWAFALLIASLPLLGLGSYVLQYPGTWCFLDFYSKNtgDAAYAYLYsilgllillVTLL 185

                         90       100
                 ....*....|....*....|....*.
gi 678246455  75 FNFLVPLFITHTSYRFMEQKFSRSGH 100
Cdd:cd14981  186 CNLLVIITLLRMRRRKKRHRRSRRSA 211