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 323147282   2 TIFMLKQWLNEILPQTLCTTSALLYIFQGFSSNLMGSLIVAYNFYSLSKMGTSQgVTQRPVSMIWAILTIWIVSLLICIL 81
Cdd:cd15011   52 SIFMLMQWETDGLPQPLCTTSALLYLFQGLSSNLKASLIASYNFYTTKKLGWLQ-TTKRSVRVPWAVLTIWAASLLLSAL 130

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 323147282  82 PLCGWGTYISTAWGCLTDCSSSYILFLFAIYSLCFCLLVVLSIPLIYQLLCSDE 135
Cdd:cd15011  131 PLCGWGSFVPTSWGCLVDCQSSYILFLFSLYSLCFCILVVLSVPLTYQLLCSDE 184

G protein-coupled receptor 149, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR149 is predominantly expressed in the ovary and is present at low levels in the brain and the digestive tract (stomach and small intestine). GPR149-null mice are viable and have normal maturation of the ovarian follicle, but show enhanced fertility and ovulation. Additionally, the null mice showed increased expression levels of growth differentiation factor 9 (Gdf9) in oocytes, and upregulated expression of cyclin D2, a downstream target of FSH (follicle-stimulating hormone) receptor signaling pathways that promotes granulosa cell proliferation. GPR149 is an orphan receptor with no known endogenous ligand as yet identified. Although categorized as a member of the class A GPCRs, GPR149 lacks the first two charged amino acids of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of class A receptors which is important for efficient G protein-coupled signal transduction. Moreover, the transmembrane domains and carboxyl terminus of GPR149 show low similarities to other GPCRs. 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, 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 323147282   2 TIFMLKQWLNEILPQTLCTTSALLYIFQGFSSNLMGSLIVAYNFYSLSKMGTSQgVTQRPVSMIWAILTIWIVSLLICIL 81
Cdd:cd15011   52 SIFMLMQWETDGLPQPLCTTSALLYLFQGLSSNLKASLIASYNFYTTKKLGWLQ-TTKRSVRVPWAVLTIWAASLLLSAL 130

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 323147282  82 PLCGWGTYISTAWGCLTDCSSSYILFLFAIYSLCFCLLVVLSIPLIYQLLCSDE 135
Cdd:cd15011  131 PLCGWGSFVPTSWGCLVDCQSSYILFLFSLYSLCFCILVVLSVPLTYQLLCSDE 184

G protein-coupled receptor 149, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR149 is predominantly expressed in the ovary and is present at low levels in the brain and the digestive tract (stomach and small intestine). GPR149-null mice are viable and have normal maturation of the ovarian follicle, but show enhanced fertility and ovulation. Additionally, the null mice showed increased expression levels of growth differentiation factor 9 (Gdf9) in oocytes, and upregulated expression of cyclin D2, a downstream target of FSH (follicle-stimulating hormone) receptor signaling pathways that promotes granulosa cell proliferation. GPR149 is an orphan receptor with no known endogenous ligand as yet identified. Although categorized as a member of the class A GPCRs, GPR149 lacks the first two charged amino acids of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of class A receptors which is important for efficient G protein-coupled signal transduction. Moreover, the transmembrane domains and carboxyl terminus of GPR149 show low similarities to other GPCRs. 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, 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 323147282   2 TIFMLKQWLNEILPQTLCTTSALLYIFQGFSSNLMGSLIVAYNFYSLSKMGTSQgVTQRPVSMIWAILTIWIVSLLICIL 81
Cdd:cd15011   52 SIFMLMQWETDGLPQPLCTTSALLYLFQGLSSNLKASLIASYNFYTTKKLGWLQ-TTKRSVRVPWAVLTIWAASLLLSAL 130

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 323147282  82 PLCGWGTYISTAWGCLTDCSSSYILFLFAIYSLCFCLLVVLSIPLIYQLLCSDE 135
Cdd:cd15011  131 PLCGWGSFVPTSWGCLVDCQSSYILFLFSLYSLCFCILVVLSVPLTYQLLCSDE 184

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 323147282  51 MGTSQGVTQRPVSMIwaILTIWIVSLLICILPLCGWGTYISTawGCLTDCSSSYI-------LFLFAIYSLCFCLLVVLS 123
Cdd:cd15337  107 LEAMKKMTFKRAFIM--IIIIWLWSLLWSIPPFFGWGRYVPE--GFQTSCTFDYLsrdlnnrLFILGLFIFGFLCPLLII 182

                 .
gi 323147282 124 I 124
Cdd:cd15337  183 I 183

vertebrate melanopsins and related opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represent the Gq-coupled rhodopsin subfamily consists of melanopsins, insect photoreceptors R1-R6, invertebrate Gq opsins as well as their closely related opsins. Melanopsins (also called Opsin-4) are the primary photoreceptor molecules for non-visual functions such as the photo-entrainment of the circadian rhythm and pupillary constriction in mammals. Mammalian melanopsins are expressed only in the inner retina, whereas non-mammalian vertebrate melanopsins are localized in various extra-retinal tissues such as iris, brain, pineal gland, and skin. The outer photoreceptors (R1-R6) are the insect Drosophila equivalent to the vertebrate rods and are responsible for image formation and motion detection. The invertebrate G(q) opsins includes the arthropod and mollusk visual opsins as well as invertebrate melanopsins, which are also found in vertebrates. Arthropods possess color vision by the use of multiple opsins sensitive to different light wavelengths. Members of this subfamily belong to the class A of the G protein-coupled receptors and have seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 323147282  64 MIWAILTIWIVSLLICILPLCGWGTYISTawGCLTDCSSSYILFLFAIYSLCFCLLV-VLSIPL 126
Cdd:cd15083  117 ALIVIAVVWLYSLLWVLPPLFGWSRYVLE--GLLTSCSFDYLSRDDANRSYVICLLIfGFVLPL 178

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 323147282  67 AILTIWIVSLLICILPLCGWGTYI--------STAWGCLTDCSSSYILFLFAiyslcFCLLVVLSI 124
Cdd:cd14969  119 LIAFIWLYGLFWALPPLFGWSSYVpegggtscSVDWYSKDPNSLSYIVSLFV-----FCFFLPLAI 179

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 323147282  54 SQGVTQRPVSMIWAILTI---WIVSLLICILPLC-GWGTYIstAWGCLTDCSSSYI-------LFLFAIYSLCFCL 118
Cdd:cd15079  102 VKPLNGNPLTRGKALLLIlfiWLYALPWALLPLLfGWGRYV--PEGFLTSCSFDYLtrdwntrSFVATIFVFAYVI 175