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 148667096  29 PLVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDY 108
Cdd:cd15050    2 PLGIALSTISLITVILNLLVLYAVRTERKLHTVGNLYIVSLSVADLIVGAVVMPLNIVYLLESKWILGRPVCLFWLSMDY 81

                         90
                 ....*....|....*....
gi 148667096 109 VASTASIFSVFILCIDRYR 127
Cdd:cd15050   82 VASTASIFSLFILCIDRYR 100

histamine subtype H1 receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine receptor subtype H1R, a member of histamine receptor family, which belongs to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). H1R selectively interacts with the G(q)-type G protein that activates phospholipase C and the phosphatidylinositol pathway. Antihistamines, a widely used anti-allergy medication, act on the H1 subtype and produce drowsiness as a side effect. 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 148667096  29 PLVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDY 108
Cdd:cd15050    2 PLGIALSTISLITVILNLLVLYAVRTERKLHTVGNLYIVSLSVADLIVGAVVMPLNIVYLLESKWILGRPVCLFWLSMDY 81

                         90
                 ....*....|....*....
gi 148667096 109 VASTASIFSVFILCIDRYR 127
Cdd:cd15050   82 VASTASIFSLFILCIDRYR 100

G protein-coupled chemokine receptor-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  30 LVVVLSSISLVTVGLNLLVLYaVRSERKLHTVGNLYIVSLSVADLIVgAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:PHA03087  43 LIVVYSTIFFFGLVGNIIVIY-VLTKTKIKTPMDIYLLNLAVSDLLF-VMTLPFQIYYYILFQWSFGEFACKIVSGLYYI 120

                         90
                 ....*....|....*..
gi 148667096 110 ASTASIFSVFILCIDRY 126
Cdd:PHA03087 121 GFYNSMNFITVMSVDRY 137

histamine subtype H1 receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine receptor subtype H1R, a member of histamine receptor family, which belongs to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). H1R selectively interacts with the G(q)-type G protein that activates phospholipase C and the phosphatidylinositol pathway. Antihistamines, a widely used anti-allergy medication, act on the H1 subtype and produce drowsiness as a side effect. 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 148667096  29 PLVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDY 108
Cdd:cd15050    2 PLGIALSTISLITVILNLLVLYAVRTERKLHTVGNLYIVSLSVADLIVGAVVMPLNIVYLLESKWILGRPVCLFWLSMDY 81

                         90
                 ....*....|....*....
gi 148667096 109 VASTASIFSVFILCIDRYR 127
Cdd:cd15050   82 VASTASIFSLFILCIDRYR 100

serotonin receptor subtypes 1, 5 and 7, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes serotonin receptor subtypes 1, 5, and 7 that are activated by the neurotransmitter serotonin. The 5-HT1 and 5-HT5 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family. The 5-HT1 receptor subfamily includes 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as 5-HT2C receptor. The 5-HT5A and 5-HT5B receptors have been cloned from rat and mouse, but only the 5-HT5A isoform has been identified in human because of the presence of premature stop codons in the human 5-HT5B gene, which prevents a functional receptor from being expressed. The 5-HT7 receptor is coupled to Gs, which positively stimulates adenylate cyclase activity, leading to increased intracellular cAMP formation and calcium influx. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:cd15064    3 ISVLLSLIILATILGNALVIAAILLTRKLHTPANYLIASLAVADLLVAVLVMPLSAVYELTGRWILGQVLCDIWISLDVT 82

                         90
                 ....*....|....*...
gi 148667096 110 ASTASIFSVFILCIDRYR 127
Cdd:cd15064   83 CCTASILHLCVIALDRYW 100

dopamine 1-like receptor 2 from Drosophila melanogaster and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled dopamine 1-like receptor 2 is expressed in Drosophila heads and it shows significant sequence similarity with vertebrate and invertebrate dopamine receptors. Although the Drosophila Dop1R2 receptor does not cluster into the D1-like structural group, it does show pharmacological properties similar to D1-like receptors. As shown in vertebrate D1-like receptors, agonist stimulation of Dop1R2 activates adenylyl cyclase to increase cAMP levels and also generates a calcium signal through stimulation of phospholipase C.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTK-WSLGRPLCLFWLSMDY 108
Cdd:cd15067    2 LGVVLSLFCLVTVAGNLLVILAVLRERYLRTVTNYFIVSLAVADLLVGSIVMPFSILHEMTGGyWLFGRDWCDVWHSFDV 81

                         90
                 ....*....|....*...
gi 148667096 109 VASTASIFSVFILCIDRY 126
Cdd:cd15067   82 LASTASILNLCVISLDRY 99

histamine subtype H2 receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine receptor subtype H2R, a member of histamine receptor family, which belongs to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). The H2R subtype selectively interacts with the G(s)-type G protein that activates adenylate cyclase, leading to increased cAMP production and activation of Protein Kinase A. H2R is found in various tissues such as the brain, stomach, and heart. Its most prominent role is in histamine-induced gastric acid secretion. 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 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:cd15051    3 LGVVLAVIILLTVIGNVLVCLAVAVNRRLRNLTNYFIVSLAVTDLLLGLLVLPFSAIYELRGEWPLGPVFCNIYISLDVM 82

                         90
                 ....*....|....*..
gi 148667096 110 ASTASIFSVFILCIDRY 126
Cdd:cd15051   83 LCTASILNLFAISLDRY 99

rhodopsin receptor-like class A family of the seven-transmembrane G protein-coupled receptor superfamily; Class A rhodopsin-like receptors constitute about 90% of all GPCRs. The class A GPCRs include the light-sensitive rhodopsin as well as receptors for biogenic amines, lipids, nucleotides, odorants, peptide hormones, 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, 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. Based on sequence similarity, GPCRs can be divided into six major classes: class A (rhodopsin-like family), class B (Methuselah-like, adhesion and secretin-like receptor family), class C (metabotropic glutamate receptor family), class D (fungal mating pheromone receptors), class E (cAMP receptor family), and class F (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 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:cd00637    1 LAVLYILIFVVGLVGNLLVILVILRNRRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRWWFGDALCKLLGFLQSV 80

                         90
                 ....*....|....*...
gi 148667096 110 ASTASIFSVFILCIDRYR 127
Cdd:cd00637   81 SLLASILTLTAISVDRYL 98

tyramine/octopamine receptor-like, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes tyramine/octopamine receptors and similar proteins found in insects and other invertebrates. Both octopamine and tyramine mediate their actions via G protein-coupled receptors (GPCRs) and are the invertebrate equivalent of vertebrate adrenergic neurotransmitters. In Drosophila, octopamine is involved in ovulation by mediating an egg release from the ovary, while a physiological role for tyramine in this process is not fully understood. 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 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:cd15060    3 TTILLSVIIAFTIVGNILVILSVFTYRPLRIVQNFFIVSLAVADLAVAIFVLPLNVAYFLLGKWLFGIHLCQMWLTCDIL 82

                         90
                 ....*....|....*..
gi 148667096 110 ASTASIFSVFILCIDRY 126
Cdd:cd15060   83 CCTASILNLCAIALDRY 99

muscarinic acetylcholine receptor subtype M1, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of mAChRs by agonist (acetylcholine) leads to a variety of biochemical and electrophysiological responses. M1 is the dominant mAChR subtype involved in learning and memory. It is linked to synaptic plasticity, neuronal excitability, and neuronal differentiation during early development. 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 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:cd17790    3 IVITTGILSLVTVTGNLLVLISFKVNSELKTVNNYFLLSLACADLIIGAFSMNLYTTYILMGHWALGTVACDLWLALDYV 82

                         90
                 ....*....|....*..
gi 148667096 110 ASTASIFSVFILCIDRY 126
Cdd:cd17790   83 ASNASVMNLLIISFDRY 99

muscarinic acetylcholine receptor GAR-2 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of mAChRs by agonist (acetylcholine) leads to a variety of biochemical and electrophysiological responses. In general, the exact nature of these responses and the subsequent physiological effects mainly depend on the molecular and pharmacological identity of the activated receptor subtype(s). 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 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIM-TKWSLGRPLCLFWLSMDY 108
Cdd:cd15302    3 LALITAILSIITVIGNILVLLSFYVDRNIRQPSNYFIASLAVSDLLIGLESMPFYTVYVLNgDYWPLGWVLCDLWLSVDY 82

                         90
                 ....*....|....*...
gi 148667096 109 VASTASIFSVFILCIDRY 126
Cdd:cd15302   83 TVCLVSIYTVLLITIDRY 100

muscarinic acetylcholine receptor DM1, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes muscarinic acetylcholine receptor DM1-like from invertebrates. Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of mAChRs by agonist (acetylcholine) leads to a variety of biochemical and electrophysiological responses. In general, the exact nature of these responses and the subsequent physiological effects mainly depend on the molecular and pharmacological identity of the activated receptor subtype(s). 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 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:cd15301    3 IVIVAAVLSLVTVGGNVMVMISFKIDKQLQTISNYFLFSLAVADFAIGVISMPLFTVYTALGYWPLGYEVCDTWLAIDYL 82

                         90
                 ....*....|....*..
gi 148667096 110 ASTASIFSVFILCIDRY 126
Cdd:cd15301   83 ASNASVLNLLIISFDRY 99

serotonin receptor subtypes 1B and 1D, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:cd15333    7 LAVLLALITLATTLSNAFVIATIYLTRKLHTPANYLIASLAVTDLLVSILVMPISIVYTVTGTWTLGQVVCDIWLSSDIT 86

                         90
                 ....*....|....*..
gi 148667096 110 ASTASIFSVFILCIDRY 126
Cdd:cd15333   87 CCTASILHLCVIALDRY 103

7 transmembrane receptor (rhodopsin family); This family contains, amongst other G-protein-coupled receptors (GCPRs), members of the opsin family, which have been considered to be typical members of the rhodopsin superfamily. They share several motifs, mainly the seven transmembrane helices, GCPRs of the rhodopsin superfamily. All opsins bind a chromophore, such as 11-cis-retinal. The function of most opsins other than the photoisomerases is split into two steps: light absorption and G-protein activation. Photoisomerases, on the other hand, are not coupled to G-proteins - they are thought to generate and supply the chromophore that is used by visual opsins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096   45 NLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMT-KWSLGRPLCLFWLSMDYVASTASIFSVFILCI 123
Cdd:pfam00001   2 NLLVILVILRNKKLRTPTNIFLLNLAVADLLFSLLTLPFWLVYYLNHgDWPFGSALCKIVGALFVVNGYASILLLTAISI 81

                  ...
gi 148667096  124 DRY 126
Cdd:pfam00001  82 DRY 84

serotonin receptor subtype 1A from invertebrates, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  32 VVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYVAS 111
Cdd:cd15331    5 IILGLLILATIIGNVFVIAAILLERSLQGVSNYLILSLAVADLMVAVLVMPLSAVYEVSQHWFLGPEVCDMWISMDVLCC 84

                         90
                 ....*....|....*
gi 148667096 112 TASIFSVFILCIDRY 126
Cdd:cd15331   85 TASILHLVAIALDRY 99

serotonin receptor subtype 1E, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  28 LPLVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMD 107
Cdd:cd15335    1 MLIVLTLALITILTTVLNSAVIAAICTTKKLHQPANYLICSLAVTDFLVAVLVMPLSITYIVMDTWTLGYFICEIWLSVD 80

                         90
                 ....*....|....*....
gi 148667096 108 YVASTASIFSVFILCIDRY 126
Cdd:cd15335   81 MTCCTCSILHLCVIALDRY 99

serotonin receptor subtype 1F, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:cd15334    3 ISLTLSILALMTTAINSLVITAIIVTRKLHHPANYLICSLAVTDFLVAVLVMPFSIMYIVKETWIMGQVVCDIWLSVDIT 82

                         90
                 ....*....|....*...
gi 148667096 110 ASTASIFSVFILCIDRYR 127
Cdd:cd15334   83 CCTCSILHLSAIALDRYR 100

trace amine-associated receptor 1 and similar receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The trace amine-associated receptor 1 (TAAR1) is one of the 15 identified trace amine-associated receptor subtypes, which form a distinct subfamily within the class A G protein-coupled receptor family. Trace amines are endogenous amines of unknown function that have strong structural and metabolic similarity to classical monoamine neurotransmitters (serotonin, noradrenaline, adrenaline, dopamine, and histamine), which play critical roles in human and animal physiological activities such as cognition, consciousness, mood, motivation, perception, and autonomic responses. However, trace amines are found in the mammalian brain at very low concentrations compared to classical monoamines. TAAR1 is coupled to the Gs protein, which leads to activation of adenylate cyclase, and is thought to play functional role in the regulation of brain monoamines. TAAR1 is also shown to be activated by psychoactive compounds such as Ecstasy (MDMA), amphetamine and LSD. 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 148667096  28 LPLVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMD 107
Cdd:cd15314    1 VLLYIFLGLISLVTVCGNLLVIISIAHFKQLHTPTNYLILSLAVADLLVGGLVMPPSMVRSVETCWYFGDLFCKIHSSFD 80

                         90
                 ....*....|....*....
gi 148667096 108 YVASTASIFSVFILCIDRY 126
Cdd:cd15314   81 ITLCTASILNLCFISIDRY 99

muscarinic acetylcholine receptor subtype M5, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. M5 mAChR is primarily found in the central nervous system and mediates acetylcholine-induced dilation of cerebral blood vessels. Activation of M5 receptor triggers a variety of cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides, and modulation of potassium channels. 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 148667096  28 LPLVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMD 107
Cdd:cd15300    1 ITIAAVTAVVSLITIVGNVLVMISFKVNSQLKTVNNYYLLSLACADLIIGIFSMNLYTSYILMGYWALGSLACDLWLALD 80

                         90
                 ....*....|....*....
gi 148667096 108 YVASTASIFSVFILCIDRY 126
Cdd:cd15300   81 YVASNASVMNLLVISFDRY 99

alpha-1 adrenergic receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-1 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that primarily mediate smooth muscle contraction: alpha-1A, alpha-1B, and alpha-1D. Activation of alpha-1 receptors by catecholamines such as norepinephrine and epinephrine couples to the G(q) protein, which then activates the phospholipase C pathway, leading to an increase in IP3 and calcium. Consequently, the elevation of intracellular calcium concentration leads to vasoconstriction in smooth muscle of blood vessels. In addition, activation of alpha-1 receptors by phenylpropanolamine (PPA) produces anorexia and may induce appetite suppression in rats.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  32 VVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYVAS 111
Cdd:cd15062    5 VALGAFILFAIGGNLLVILSVACNRHLRTPTHYFIVNLAVADLLLSFTVLPFSATLEVLGYWAFGRIFCDVWAAVDVLCC 84

                         90
                 ....*....|....*
gi 148667096 112 TASIFSVFILCIDRY 126
Cdd:cd15062   85 TASIMSLCVISVDRY 99

octopamine receptors in invertebrates, member of the class A family of seven-transmembrane G protein-coupled receptors; G-protein coupled receptor for octopamine (OA), which functions as a neurotransmitter, neurohormone, and neuromodulator in invertebrate nervous system. Octopamine (also known as beta, 4-dihydroxyphenethylamine) is an endogenous trace amine that is highly similar to norepinephrine, but lacks a hydroxyl group, and has effects on the adrenergic and dopaminergic nervous systems. Based on the pharmacological and signaling profiles, the octopamine receptors can be classified into at least two groups: OA1 receptors elevate intracellular calcium levels in muscle, whereas OA2 receptors activate adenylate cyclase and increase cAMP production.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  31 VVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYVA 110
Cdd:cd15063    4 LLVLTFLNVLVVLGNLLVIAAVLCSRKLRTVTNLFIVSLACADLLVGTLVLPFSAVNEVLDVWIFGHTWCQIWLAVDVWM 83

                         90
                 ....*....|....*.
gi 148667096 111 STASIFSVFILCIDRY 126
Cdd:cd15063   84 CTASILNLCAISLDRY 99

beta-2 adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; Beta-2 AR is activated by adrenaline that plays important roles in cardiac function and pulmonary physiology. While beta-1 AR and beta-2 AR are the major subtypes involved in modulating cardiac contractility and heart rate by positively stimulating the G(s) protein-adenylate cyclase-cAMP-PKA signaling pathway, beta-2 AR can couple to both G(s) and G(i) proteins in the heart. Moreover, beta-2 AR activation leads to smooth muscle relaxation and bronchodilation in the lung. The beta adrenergic receptors are a subfamily of the class A rhodopsin-like G protein-coupled receptors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  32 VVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYVAS 111
Cdd:cd15957    5 IVMSLIVLAIVFGNVLVITAIAKFERLQTVTNYFITSLACADLVMGLAVVPFGAAHILLKTWTFGNFWCEFWTSIDVLCV 84

                         90
                 ....*....|....*
gi 148667096 112 TASIFSVFILCIDRY 126
Cdd:cd15957   85 TASIETLCVIAVDRY 99

Drosophila melanogaster beta-adrenergic receptor-like octopamine receptors and similar receptors in bilateria; member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes Drosophila beta-adrenergic-like octopamine receptors and similar proteins. The biogenic amine octopamine is the invertebrate equivalent of vertebrate adrenergic neurotransmitters and exerts its effects through different G protein-coupled receptor types. Insect octopamine receptors are involved in the modulation of carbohydrate metabolism, muscular tension, cognition and memory. The activation of octopamine receptors mediating these actions leads to an increase in adenylate cyclase activity, thereby increasing cAMP levels. In Drosophila melanogaster, three subgroups have been classified on the basis of their structural homology and functional equivalents with vertebrate beta-adrenergic receptors: DmOctBeta1R, DmOctBeta2R, and DmOctBeta3R.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  33 VLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYVAST 112
Cdd:cd15066    5 AMTLIILAAIFGNLLVIISVMRHRKLRVITNYFVVSLAMADMLVALCAMTFNASVEITGRWMFGYFMCDVWNSLDVYFST 84

                         90
                 ....*....|....
gi 148667096 113 ASIFSVFILCIDRY 126
Cdd:cd15066   85 ASILHLCCISVDRY 98

histamine receptor subtype H4R, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine subtype H4R, a member of the histamine receptor family, which belong to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). The H3 and H4 receptors couple to the G(i)-proteins, which leading to the inhibition of cAMP formation. The H3R receptor functions as a presynaptic autoreceptors controlling histamine release and synthesis. The H4R plays an important role in histamine-mediated chemotaxis in mast cells and eosinophils. 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 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:cd15295    3 LLFLMSLLALVIVLGNALVIIAFVVDKNLRHRSNYFFLNLAISDFFVGAISIPLYIPYTLTNRWDFGRGLCVFWLVIDYL 82

                         90
                 ....*....|....*..
gi 148667096 110 ASTASIFSVFILCIDRY 126
Cdd:cd15295   83 LCTASVYNIVLISYDRY 99

alpha-1 adrenergic receptors subtype B, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-1 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that primarily mediate smooth muscle contraction: alpha-1A, alpha-1B, and alpha-1D. Activation of alpha-1 receptors by catecholamines such as norepinephrine and epinephrine couples to the G(q) protein, which then activates the phospholipase C pathway, leading to an increase in IP3 and calcium. Consequently, the elevation of intracellular calcium concentration leads to vasoconstriction in smooth muscle of blood vessels. In addition, activation of alpha-1 receptors by phenylpropanolamine (PPA) produces anorexia and may induce appetite suppression in rats.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  28 LPLVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMD 107
Cdd:cd15326    1 ILLGLVLGAFILFAIVGNILVILSVVCNRHLRIPTNYFIVNLAIADLLLSFTVLPFSATLEILGYWVFGRIFCDIWAAVD 80

                         90
                 ....*....|....*....
gi 148667096 108 YVASTASIFSVFILCIDRY 126
Cdd:cd15326   81 VLCCTASILSLCAISIDRY 99

serotonin receptor subtype 2A, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT2 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the central nervous system (CNS). The 5-HT2 subfamily is composed of three subtypes that mediate excitatory neurotransmission: 5-HT2A, 5-HT2B, and 5-HT2C. They are selectively linked to G proteins of the G(q/11) family and activate phospholipase C, which leads to activation of protein kinase C and calcium release. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in diseases such as migraine, schizophrenia, and depression. Indeed, 5-HT2 receptors are attractive targets for a variety of psychoactive drugs, ranging from atypical antipsychotic drugs, antidepressants, and anxiolytics, which have an antagonistic action on 5-HT2 receptors, to hallucinogens, which act as agonists at postsynaptic 5-HT2 receptors. 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 148667096  25 PQLLPLVVVLssislVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMT-KWSLGRPLCLFW 103
Cdd:cd15304    3 PALLTVIVII-----LTIAGNILVIMAVSLEKKLQNATNYFLMSLAIADMLLGFLVMPVSMLTILYGyRWPLPSKLCAVW 77

                         90       100
                 ....*....|....*....|...
gi 148667096 104 LSMDYVASTASIFSVFILCIDRY 126
Cdd:cd15304   78 IYLDVLFSTASIMHLCAISLDRY 100

beta-3 adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; The beta-3 adrenergic receptor (beta-3 adrenoceptor), also known as beta-3 AR, is activated by adrenaline and plays important roles in regulating cardiac function and heart rate. The human heart contains three subtypes of the beta AR: beta-1 AR, beta-2 AR, and beta-3 AR. Beta-1 AR and beta-2 AR, which expressed at about a ratio of 70:30, are the major subtypes involved in modulating cardiac contractility and heart rate by positively stimulating the G(s) protein-adenylate cyclase-cAMP-PKA signaling pathway. In contrast, beta-3 AR produces negative inotropic effects by activating inhibitory G(i) proteins. The aberrant expression of betrayers can lead to cardiac dysfunction such as arrhythmias or heart failure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  33 VLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYVAST 112
Cdd:cd15959    6 LLSLAILVIVGGNLLVIVAIAKTPRLQTMTNVFVTSLACADLVMGLLVVPPGATILLTGHWPLGTTVCELWTSVDVLCVT 85

                         90
                 ....*....|....
gi 148667096 113 ASIFSVFILCIDRY 126
Cdd:cd15959   86 ASIETLCAIAVDRY 99

cholecystokinin receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents four G-protein coupled receptors that are members of the RFamide receptor family, including cholecystokinin receptors (CCK-AR and CCK-BR), orexin receptors (OXR), neuropeptide FF receptors (NPFFR), and pyroglutamylated RFamide peptide receptor (QRFPR). These RFamide receptors are activated by their endogenous peptide ligands that share a common C-terminal arginine (R) and an amidated phenylanine (F) motif. CCK-AR (type A, alimentary; also known as CCK1R) is found abundantly on pancreatic acinar cells and binds only sulfated CCK-peptides with very high affinity, whereas CCK-BR (type B, brain; also known as CCK2R), the predominant form in the brain and stomach, binds CCK or gastrin and discriminates poorly between sulfated and non-sulfated peptides. CCK is implicated in regulation of digestion, appetite control, and body weight, and is involved in neurogenesis via CCK-AR. There is some evidence to support that CCK and gastrin, via their receptors, are involved in promoting cancer development and progression, acting as growth and invasion factors. Orexins (OXs; also referred to as hypocretins) are neuropeptide hormones that regulate the sleep-wake cycle and potently influence homeostatic systems regulating appetite and feeding behavior or modulating emotional responses such as anxiety or panic. OXs are synthesized as prepro-orexin (PPO) in the hypothalamus and then proteolytically cleaved into two forms of isoforms: orexin-A (OX-A) and orexin-B (OX-B). OXA is a 33 amino-acid peptide with N-terminal pyroglutamyl residue and two intramolecular disulfide bonds, whereas OXB is a 28 amino-acid linear peptide with no disulfide bonds. OX-A binds orexin receptor 1 (OX1R) with high-affinity, but also binds with somewhat low-affinity to OX2R, and signals primarily to Gq coupling, whereas OX-B shows a strong preference for the orexin receptor 2 (OX2R) and signals through Gq or Gi/o coupling. The 26RFa, also known as QRFP (Pyroglutamylated RFamide peptide), is a 26-amino acid residue peptide that exerts similar orexigenic activity including the regulation of feeding behavior in mammals. It is the ligand for G-protein coupled receptor 103 (GPR103), which is predominantly expressed in paraventricular (PVN) and ventromedial (VMH) nuclei of the hypothalamus. GPR103 shares significant protein sequence homology with orexin receptors (OX1R and OX2R), which have recently shown to produce a neuroprotective effect in Alzheimer's disease by forming a functional heterodimer with GPR103. Neuropeptide FF (NPFF) is a mammalian octapeptide that has been implicated in a wide range of physiological functions in the brain including pain sensitivity, insulin release, food intake, memory, blood pressure, and opioid-induced tolerance and hyperalgesia. The effects of NPFF are mediated through neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R) which are predominantly expressed in the brain. NPFF induces pro-nociceptive effects, mainly through the NPFF1-R, and anti-nociceptive effects, mainly through the NPFF2-R.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:cd14993    3 LIVLYVVVFLLALVGNSLVIAVVLRNKHMRTVTNYFLVNLAVADLLVSLFCMPLTLLENVYRPWVFGEVLCKAVPYLQGV 82

                         90
                 ....*....|....*..
gi 148667096 110 ASTASIFSVFILCIDRY 126
Cdd:cd14993   83 SVSASVLTLVAISIDRY 99

serotonin receptor subtype 2 from insects, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT2 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the central nervous system (CNS). The 5-HT2 subfamily is composed of three subtypes that mediate excitatory neurotransmission: 5-HT2A, 5-HT2B, and 5-HT2C. They are selectively linked to G proteins of the G(q/11) family and activate phospholipase C, which leads to activation of protein kinase C and calcium release. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in diseases such as migraine, schizophrenia, and depression. Indeed, 5-HT2 receptors are attractive targets for a variety of psychoactive drugs, ranging from atypical antipsychotic drugs, antidepressants, and anxiolytics, which have an antagonistic action on 5-HT2 receptors, to hallucinogens, which act as agonists at postsynaptic 5-HT2 receptors. 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 148667096  27 LLPLVVVLssislVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSM 106
Cdd:cd15307    5 LLALVLVL-----GTAAGNILVCLAIAWERRLQNVTNYFLMSLAITDLMVAVLVMPLGILTLVKGHFPLSSEHCLTWICL 79

                         90       100
                 ....*....|....*....|
gi 148667096 107 DYVASTASIFSVFILCIDRY 126
Cdd:cd15307   80 DVLFCTASIMHLCTISVDRY 99

serotonin receptor subtype 1A from vertebrates, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  32 VVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYVAS 111
Cdd:cd15330    5 LFLGTLILCAIFGNACVVAAIALERSLQNVANYLIGSLAVTDLMVSVLVLPMAALYQVLNKWTLGQVTCDLFIALDVLCC 84

                         90
                 ....*....|....*
gi 148667096 112 TASIFSVFILCIDRY 126
Cdd:cd15330   85 TSSILHLCAIALDRY 99

alpha-2 adrenergic receptors subtype D, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 148667096  30 LVVVLSSISLVTVGLNLLVLYAVRSERKLHTVGNLYIVSLSVADLIVGAVVMPMNILYLIMTKWSLGRPLCLFWLSMDYV 109
Cdd:cd15324    3 IVLVVVVIILVTIVGNVLVVVAVFTSRALRAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGSTWCAFYLALDVL 82

                         90
                 ....*....|....*..
gi 148667096 110 ASTASIFSVFILCIDRY 126
Cdd:cd15324   83 FCTSSIVHLCAISLDRY 99