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 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFTPPGGSAPAAaagpwrgFCAASRFFSSCFGIVST 101
Cdd:cd15212  17 GNCAVIGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPFAFLTLFSRPGWLFGDR-------LCLANGFFNACFGIVST 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578 102 LSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLPWELLGAPRELAAAQSFHGCLYRTSPDPAQLGAAFSV 181
Cdd:cd15212  90 LTMTLISFDRYYAIVRQPQGKIGRRRALQLLAAAWLTALGFSLPWYLLASAPEYYEKLGFYHCLYVLHSGPSRLGAAYSS 169

                .
gi 29611578 182 G 182
Cdd:cd15212 170 V 170

G protein-coupled receptor 135, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR135, also known as the somatostatin- and angiotensin-like peptide receptor (SALPR), is found in various tissues including eye, brain, cervix, stomach, and testis. Pharmacological studies have shown that relaxin-3 (R3) is a high-affinity endogenous ligand for GPR135. R3 has recently been identified as a new member of the insulin/relaxin family of peptide hormones and is exclusively expressed in the brain neurons. In addition to GPR135, R3 also acts as an agonist for GPR142, a pseudogene in the rat, and can activate LGR7 (leucine repeat-containing G-protein receptor-7), which is the main receptor for relaxin-1 (R1) and relaxin-2 (R2). While R1 and R2 are hormones primarily associated with reproduction and pregnancy, R3 is involved in neuroendocrine and sensory processing. 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 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFTPPGGSAPAAaagpwrgFCAASRFFSSCFGIVST 101
Cdd:cd15212  17 GNCAVIGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPFAFLTLFSRPGWLFGDR-------LCLANGFFNACFGIVST 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578 102 LSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLPWELLGAPRELAAAQSFHGCLYRTSPDPAQLGAAFSV 181
Cdd:cd15212  90 LTMTLISFDRYYAIVRQPQGKIGRRRALQLLAAAWLTALGFSLPWYLLASAPEYYEKLGFYHCLYVLHSGPSRLGAAYSS 169

                .
gi 29611578 182 G 182
Cdd:cd15212 170 V 170

G protein-coupled receptor 135, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR135, also known as the somatostatin- and angiotensin-like peptide receptor (SALPR), is found in various tissues including eye, brain, cervix, stomach, and testis. Pharmacological studies have shown that relaxin-3 (R3) is a high-affinity endogenous ligand for GPR135. R3 has recently been identified as a new member of the insulin/relaxin family of peptide hormones and is exclusively expressed in the brain neurons. In addition to GPR135, R3 also acts as an agonist for GPR142, a pseudogene in the rat, and can activate LGR7 (leucine repeat-containing G-protein receptor-7), which is the main receptor for relaxin-1 (R1) and relaxin-2 (R2). While R1 and R2 are hormones primarily associated with reproduction and pregnancy, R3 is involved in neuroendocrine and sensory processing. 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 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFTPPGGSAPAAaagpwrgFCAASRFFSSCFGIVST 101
Cdd:cd15212  17 GNCAVIGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPFAFLTLFSRPGWLFGDR-------LCLANGFFNACFGIVST 89

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578 102 LSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLPWELLGAPRELAAAQSFHGCLYRTSPDPAQLGAAFSV 181
Cdd:cd15212  90 LTMTLISFDRYYAIVRQPQGKIGRRRALQLLAAAWLTALGFSLPWYLLASAPEYYEKLGFYHCLYVLHSGPSRLGAAYSS 169

                .
gi 29611578 182 G 182
Cdd:cd15212 170 V 170

neuropeptide Y receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; NPY is a 36-amino acid peptide neurotransmitter with a C-terminal tyrosine amide residue that is widely distributed in the brain and the autonomic nervous system of many mammalian species. NPY exerts its functions through five, G-protein coupled receptor subtypes including NPY1R, NPY2R, NPY4R, NPY5R, and NPY6R; however, NPY6R is not functional in humans. NYP receptors are also activated by its two other family members, peptide YY (PYY) and pancreatic polypeptide (PP). They typically couple to Gi or Go proteins, which leads to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels, and are involved in diverse physiological roles including appetite regulation, circadian rhythm, and anxiety. Also included in this subgroup is prolactin-releasing peptide (PrRP) receptor (previously known as GPR10), which is activated by its endogenous ligand PrRP, a neuropeptide possessing C-terminal Arg-Phe-amide motif. There are two active isoforms of PrRP in mammals: one consists of 20 amino acid residues (PrRP-20) and the other consists of 31 amino acid residues (PrRP-31). PrRP receptor shows significant sequence homology to the NPY receptors, and a micromolar level of NPY can bind and completely inhibit the PrRP-evoked intracellular calcium response in PrRP receptor-expressing cells, suggesting that the PrRP receptor shares a common ancestor with the NPY receptors.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFTppggsapaaaaGPW---RGFCaasRFFSSCFGI 98
Cdd:cd15203  17 GNLLVIYVVLRNKSMQTVTNIFILNLAVSDLLLCLVSLPFTLIYTLT-----------KNWpfgSILC---KLVPSLQGV 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 29611578  99 ---VSTLSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd15203  83 sifVSTLTLTAIAIDRYQLIVYPTRPRMSKRHALLIIALIWILSLLLSLP 132

tachykinin receptors and related receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the neurokinin/tachykinin receptors and its closely related receptors such as orphan GPR83 and leucokinin-like peptide receptor. The tachykinins are widely distributed throughout the mammalian central and peripheral nervous systems and act as excitatory transmitters on neurons and cells in the gastrointestinal tract. The TKs are characterized by a common five-amino acid C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is a hydrophobic residue. The three major mammalian tachykinins are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). The physiological actions of tachykinins are mediated through three types of receptors: neurokinin receptor type 1 (NK1R), NK2R, and NK3R. SP is a high-affinity endogenous ligand for NK1R, which interacts with the Gq protein and activates phospholipase C, leading to elevation of intracellular calcium. NK2R is a high-affinity receptor for NKA, the tachykinin neuropeptide substance K. SP and NKA are found in the enteric nervous system and mediate in the regulation of gastrointestinal motility, secretion, vascular permeability, and pain perception. NK3R is activated by its high-affinity ligand, NKB, which is primarily involved in the central nervous system and plays a critical role in the regulation of gonadotropin hormone release and the onset of puberty.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFtppggsapaaaAGPW---RGFCAASRFFSSCFGI 98
Cdd:cd15202  17 GNVLVCWIIFKNQRMRTVTNYFIVNLAVADIMITLFNTPFTFVRAV-----------NNTWifgLFMCHFSNFAQYCSVH 85

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 29611578  99 VSTLSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd15202  86 VSAYTLTAIAVDRYQAIMHPLKPRISKTKAKFIIAVIWTLALAFALP 132

neurokinin receptors (or tachykinin receptors), member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents G-protein coupled receptors for a variety of neuropeptides of the tachykinin (TK) family. The tachykinins are widely distributed throughout the mammalian central and peripheral nervous systems and act as excitatory transmitters on neurons and cells in the gastrointestinal tract. The TKs are characterized by a common five-amino acid C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is a hydrophobic residue. The three major mammalian tachykinins are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). The physiological actions of tachykinins are mediated through three types of receptors: neurokinin receptor type 1 (NK1R), NK2R, and NK3R. SP is a high-affinity endogenous ligand for NK1R, which interacts with the Gq protein and activates phospholipase C, leading to elevation of intracellular calcium. NK2R is a high-affinity receptor for NKA, the tachykinin neuropeptide substance K. SP and NKA are found in the enteric nervous system and mediate in the regulation of gastrointestinal motility, secretion, vascular permeability, and pain perception. NK3R is activated by its high-affinity ligand, NKB, which is primarily involved in the central nervous system and plays a critical role in the regulation of gonadotropin hormone release and the onset of puberty.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFIlslslsdlltallcLPAAFLDL----FTPPGGSAPAAAAGPWRG--FCAASRFFSSC 95
Cdd:cd15390  17 GNLIVIWIVLAHKRMRTVTNYFL--------------VNLAVADLlisaFNTVFNFTYLLYNDWPFGlfYCKFSNFVAIT 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 29611578  96 FGIVSTLSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd15390  83 TVAASVFTLMAISIDRYIAIVHPLRPRLSRRTTKIAIAVIWLASFLLALP 132

amine receptors and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; Amine receptors of the class A family of GPCRs include adrenoceptors, 5-HT (serotonin) receptors, muscarinic cholinergic receptors, dopamine receptors, histamine receptors, and trace amine receptors. The receptors of amine subfamily are major therapeutic targets for the treatment of neurological disorders and psychiatric diseases. 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 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFTppggsapaaaaGPW---RGFCAASRFFSSCFGI 98
Cdd:cd14967  16 GNLLVILAVYRNRRLRTVTNYFIVSLAVADLLVALLVMPFSAVYTLL-----------GYWpfgPVLCRFWIALDVLCCT 84

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 29611578  99 VSTLSVALISLDRYCAIVRPP--REKIGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd14967  85 ASILNLCAISLDRYLAITRPLryRQLMTKKRALIMIAAVWVYSLLISLP 133

prokineticin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Prokineticins 1 (PROK1) and 2 (PROK2), also known as endocrine gland vascular endothelial factor and Bombina varigata 8, respectively, are multifunctional chemokine-like peptides that are highly conserved across species. Prokineticins can bind with similar affinities to two closely homologous 7-transmembrane G protein coupled receptors, PROKR1 and PROKR2, which are phylogenetically related to the tachykinin receptors. Prokineticins and their GPCRs are widely distributed in human tissues and are involved in numerous physiological roles, including gastrointestinal motility, generation of circadian rhythms, neuron migration and survival, pain sensation, angiogenesis, inflammation, and reproduction. Moreover, different point mutations in genes encoding PROK2 or its receptor (PROKR2) can lead to Kallmann syndrome, a disease characterized by delayed or absent puberty and impaired olfactory function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAfLDLFTppggsapaAAAGPWR---GFCAASRFFSSCFGI 98
Cdd:cd15204  17 GNLLLIAVLARYKKLRTLTNLLIANLALSDFLVAVFCLPFE-MDYYV--------VRQRSWThgdVLCAVVNYLRTVSLY 87

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 29611578  99 VSTLSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd15204  88 VSTNALLVIAIDRYLVIVHPLKPRMKRRTACVVIALVWVVSLLLAIP 134

orexin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; 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. Thus, activation of OX1R or OX2R will activate phospholipase activity and the phosphatidylinositol and calcium signaling pathways. Additionally, OX2R activation can also lead to inhibition of adenylate cyclase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFTppggsapaaaaGPW---RGFCAASRFFSSCFGI 98
Cdd:cd15208  17 GNVLVCFAVWRNHHMRTVTNYFIVNLSLADFLVIIICLPATLLVDVT-----------ETWffgQVLCKIIPYLQTVSVS 85

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 29611578  99 VSTLSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd15208  86 VSVLTLSCIALDRWYAICHPLMFKSTAKRARVSILIIWIVSLLIMIP 132

ecdysis-triggering hormone receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup represents the ecdysis-triggering hormone receptors found in insects, which are members of the class A family of seven-transmembrane G-protein coupled receptors. Ecdysis-triggering hormones are vital regulatory signals that govern the stereotypic physiological sequence leading to cuticle shedding in insects. Thus, the ETH signaling system has been a target for the design of more sophisticated insect-selective pest control strategies. Two subtypes of ecdysis-triggering hormone receptor were identified in Drosophila melanogaster. Blood-borne ecdysis-triggering hormone (ETH) activates the behavioral sequence through direct actions on the central nervous system. In insects, ecdysis is thought to be controlled by the interaction between peptide hormones; in particular between ecdysis-triggering hormone (ETH) from the periphery and eclosion hormone (EH) and crustacean cardioactive peptide (CCAP) from the central nervous system. 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 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFTppggsapaaaAGPW---RGFCAASRFFSSCFGI 98
Cdd:cd14997  17 GNVLVGIVVWKNKDMRTPTNIFLVNLSVADLLVLLVCMPVALVETWA----------REPWllgEFMCKLVPFVELTVAH 86

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 29611578  99 VSTLSVALISLDRYCAIVRPPREK--IGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd14997  87 ASVLTILAISFERYYAICHPLQAKyvCTKRRALVIIALIWLLALLTSSP 135

G protein-coupled receptor 83, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR83, also known as GPR72, is widely expressed in the brain, including hypothalamic nuclei which is involved in regulating energy balance and food intake. The hypothalamic expression of GPR83 is tightly regulated in response to nutrient availability and is decreased in obese mice. A recent study suggests that GPR83 has a critical role in the regulation of systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms. GPR83 shares a significant amino acid sequence identity with the tachykinin receptors, however its endogenous ligand is unknown.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPaafldlFTppggsAPAAAAGPW---RGFCAASRFFSSCFGI 98
Cdd:cd15389  17 GNSLVCHVIFKNKRMHTATNLFIVNLAVSDILITLLNTP------FT-----LVRFVNSTWvfgKIMCHLSRFAQYCSVY 85

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 29611578  99 VSTLSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd15389  86 VSTLTLTAIALDRHRVILHPLKPRITPCQGVVVIAIIWIMASCLSLP 132

putative neuropeptide receptor BNGR-A34 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes putative neuropeptide receptor BNGR-A34 found in silkworm and its closely related proteins from invertebrates. They are members of the class A rhodopsin-like GPCRs, which represent a widespread protein family that includes 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLClPAAFL--DLFTPPGGSAPAaaagpwrgfCAASRFFSSCFGIV 99
Cdd:cd15000  16 GNFVLLYILASNRSLRTPTNLLIGNMALADLLTLLVC-PWMFLvhDFFQNYVLGSVG---------CKLEGFLEGSLLLA 85

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 29611578 100 STLSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLPWELLGAPRE 154
Cdd:cd15000  86 SVLALCAVSYDRLTAIVLPSEARLTKRGAKIVIVITWIVGLLLALPLAIYRSYRE 140

neuropeptide S receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropeptide S (NPS) promotes arousal and anxiolytic-like effects by activating its cognate receptor NPSR. NPSR is widely expressed in the brain, and its activation induces an elevation of intracellular calcium and cAMP concentrations, presumably by coupling to G(s) and G(q) proteins. Mutations in NPSR have been associated with an increased susceptibility to asthma. NPSR was originally identified as an orphan receptor GPR154 and is also known as G protein receptor for asthma susceptibility (GPRA) or vasopressin receptor-related receptor 1 (VRR1).

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  86 CAASRFFSSCFGIVSTLSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLPWELLGAPREL 155
Cdd:cd15197  73 CKVIRYLQVVVTYASTYVLVALSIDRYDAICHPMNFSQSGRQARVLICVAWILSALFSIPMLIIFEKTGL 142

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 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSlsdlltallclpaaFLDLF--TPPGGSAPAAAAGPWRG---FCAASRFFSSCF 96
Cdd:cd15079  17 GNGLVIYIFSTTKSLRTPSNMLVVNLA--------------ISDFLmmIKMPIFIYNSFYEGWALgplGCQIYAFLGSLS 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 29611578  97 GIVSTLSVALISLDRYCAIVRP-PREKIGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd15079  83 GIGSIWTNAAIAYDRYNVIVKPlNGNPLTRGKALLLILFIWLYALPWALL 132

serotonin receptor subtype 6, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT6 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the mammalian central nervous system (CNS). 5-HT6 receptors are selectively linked to G proteins of the G(s) family, which positively stimulate adenylate cyclase, causing cAMP formation and activation of protein kinase A. The 5-HT6 receptors mediates excitatory neurotransmission and are involved in learning and memory; thus they are promising targets for the treatment of cognitive impairment. 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 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFtppggsapAAAAGPWRGFCAASRFFSSCFGIVST 101
Cdd:cd15054  17 GNSLLILLIFTQRSLRNTSNYFLVSLFMSDLMVGLVVMPPAMLNAL--------YGRWVLARDFCPIWYAFDVMCCSASI 88

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|
gi 29611578 102 LSVALISLDRYCAIVRPPREK--IGRRRALQLLAGAW-LTALGFSLPWEL 148
Cdd:cd15054  89 LNLCVISLDRYLLIISPLRYKlrMTPPRALALILAAWtLAALASFLPIEL 138

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
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 29611578  91 FFSSCFGIVSTLSVALISLDRYCAIVRPPREKIGR-RRALQLLAGAWLTALGFSLP 145
Cdd:cd15086  78 FANSLFGIVSLISLAVLSYERYCTLLRPTEADVSDyRKAWLGVGGSWLYSLLWTLP 133

tachykinin receptor and closely related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes G-protein coupled receptors for a variety of neuropeptides of the tachykinin (TK) family as well as closely related receptors. The tachykinins are widely distributed throughout the mammalian central and peripheral nervous systems and act as excitatory transmitters on neurons and cells in the gastrointestinal tract. The TKs are characterized by a common five-amino acid C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is a hydrophobic residue. The three major mammalian tachykinins are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). The physiological actions of tachykinins are mediated through three types of receptors: neurokinin receptor type 1 (NK1R), NK2R, and NK3R. SP is a high-affinity endogenous ligand for NK1R, which interacts with the Gq protein and activates phospholipase C, leading to elevation of intracellular calcium. NK2R is a high-affinity receptor for NKA, the tachykinin neuropeptide substance K. SP and NKA are found in the enteric nervous system and mediate in the regulation of gastrointestinal motility, secretion, vascular permeability, and pain perception. NK3R is activated by its high-affinity ligand, NKB, which is primarily involved in the central nervous system and plays a critical role in the regulation of gonadotropin hormone release and the onset of puberty.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFTPPGGSAPAaaagpwrgFCAASRFFSSCFGIVST 101
Cdd:cd14992  17 GNFIVIAALARHKNLRGATNYFIASLAISDLLMALFCTPFNFTYVVSLSWEYGHF--------LCKIVNYLRTVSVYASS 88

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 29611578 102 LSVALISLDRYCAIVRP--PREKIGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd14992  89 LTLTAIAFDRYFAIIHPlkPRHRQSYTTTVIIIITIWVVSLLLAIP 134

cholecystokinin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Cholecystokinin receptors (CCK-AR and CCK-BR) are a group of G-protein coupled receptors which bind the peptide hormones cholecystokinin (CCK) or gastrin. CCK, which facilitates digestion in the small intestine, and gastrin, a major regulator of gastric acid secretion, are highly similar peptides. Like gastrin, CCK is a naturally-occurring linear peptide that is synthesized as a preprohormone, then proteolytically cleaved to form a family of peptides with the common C-terminal sequence (Gly-Trp-Met-Asp-Phe-NH2), which is required for full biological activity. 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPaafldlFTPPGGSApaaaagpwRGF------CAASRFFSSC 95
Cdd:cd15206  17 GNILVIVTLVQNKRMRTVTNVFLLNLAVSDLLLAVFCMP------FTLVGQLL--------RNFifgevmCKLIPYFQAV 82

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|..
gi 29611578  96 FGIVSTLSVALISLDRYCAIVRPPREKI--GRRRALQLLAGAWLTALGFSLP 145
Cdd:cd15206  83 SVSVSTFTLVAISLERYFAICHPLKSRVwqTLSHAYKVIAGIWLLSFLIMSP 134

neurotensin receptors and related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes the neurotensin receptors and related G-protein coupled receptors, including neuromedin U receptors, growth hormone secretagogue receptor, motilin receptor, the putative GPR39 and the capa receptors from insects. These receptors all bind peptide hormones with diverse physiological effects. 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 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPaafLDLFTPPGGSAPAAAAgpwrGFCAASRFFSSCFGIVST 101
Cdd:cd14979  17 GNLLTCIVIARHKSLRTTTNYYLFSLAVSDLLILLVGLP---VELYNFWWQYPWAFGD----GGCKLYYFLFEACTYATV 89

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 29611578 102 LSVALISLDRYCAIVRPPREK--IGRRRALQLLAGAWLTALGFSLPWELlgapreLAAAQSFHGCLYRTSPD 171
Cdd:cd14979  90 LTIVALSVERYVAICHPLKAKtlVTKRRVKRFILAIWLVSILCAIPILF------LMGIQYLNGPLPGPVPD 155

serotonin receptor subtype 4, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT4 subtype is a member of the serotonin receptor family that belongs to the class A G protein-coupled receptors, and binds the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the mammalian central nervous system (CNS). 5-HT4 receptors are selectively linked to G proteins of the G(s) family, which positively stimulate adenylate cyclase, causing cAMP formation and activation of protein kinase A. 5-HT4 receptor-specific agonists have been shown to enhance learning and memory in animal studies. Moreover, hippocampal 5-HT4 receptor expression has been reported to be inversely correlated with memory performance in humans. 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 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFTppggsapaaaaGPWR---GFCAASRFFSSCFGI 98
Cdd:cd15056  17 GNLLVIVAVCTDRQLRKKTNYFVVSLAVADLLVAVLVMPFGAIELVN-----------NRWIygeTFCLVRTSLDVLLTT 85

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 29611578  99 VSTLSVALISLDRYCAIVRPP-REKIGRRRALQLLAGAWLT 138
Cdd:cd15056  86 ASIMHLCCIALDRYYAICCQPlVYKMTPLRVAVMLGGCWVI 126

galanin receptor and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes G-protein coupled galanin receptors, kisspeptin receptor and allatostatin-A receptor (AstA-R) in insects. These receptors, which are members of the class A of seven transmembrane GPCRs, share a high degree of sequence homology among themselves. The galanin receptors bind galanin, a neuropeptide that is widely expressed in the brain, peripheral tissues, and endocrine glands. Galanin is implicated in numerous neurological and psychiatric diseases including Alzheimer's disease, eating disorders, and epilepsy, among many others. KiSS1-derived peptide receptor (also known as GPR54 or kisspeptin receptor) binds the peptide hormone kisspeptin (metastin), which encoded by the metastasis suppressor gene (KISS1) expressed in various endocrine and reproductive tissues. AstA-R is a G-protein coupled receptor that binds allatostatin A. Three distinct types of allatostatin have been identified in the insects and crustaceans: AstA, AstB, and AstC. They both inhibit the biosynthesis of juvenile hormone and exert an inhibitory influence on food intake. Therefore, allatostatins are considered as potential targets for insect control.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPaafldlFTPPGGSAPAAAAGPWrgFCAASRFFSSCFGIVST 101
Cdd:cd14971  17 GNSLVILVVARNKPMRSTTNLFILNLAVADLTFLLFCVP------FTATIYPLPGWVFGDF--MCKFVHYFQQVSMHASI 88

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 29611578 102 LSVALISLDRYCAIVRPPREKIGR--RRALQLLAGAWLTALGFSLP 145
Cdd:cd14971  89 FTLVAMSLDRFLAVVYPLRSLHIRtpRNALAASGCIWVVSLAVAAP 134

D1-like family of dopamine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. The D1-like family receptors are coupled to G proteins of the G(s) family, which activate adenylate cyclase, causing cAMP formation and activation of protein kinase A. In contrast, activation of D2-like family receptors is linked to G proteins of the G(i) family, which inhibit adenylate cyclase. Dopamine receptors are major therapeutic targets for neurological and psychiatric disorders such as drug abuse, depression, schizophrenia, or Parkinson's disease. 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 29611578  22 GNCAVMGVIVKHRQLR-TVTNAFILSLSLSDLLTALLCLP-AAFLDLftppggsapaaaAGPWR--GFCAASRFFSSCFG 97
Cdd:cd15057  17 GNALVIAAVLRFRHLRsKVTNYFIVSLAVSDLLVAILVMPwAAVNEV------------AGYWPfgSFCDVWVSFDIMCS 84

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 29611578  98 IVSTLSVALISLDRYCAIVRPPR--EKIGRRRALQLLAGAWLTALGFSL 144
Cdd:cd15057  85 TASILNLCVISVDRYWAISSPFRyeRRMTRRRAFIMIAVAWTLSALISF 133

neuropeptide Y receptor type 1, member of the class A family of seven-transmembrane G protein-coupled receptors; NPY is a 36-amino acid peptide neurotransmitter with a C-terminal tyrosine amide residue that is widely distributed in the brain and the autonomic nervous system of many mammalian species. NPY exerts its functions through five, G-protein coupled receptor subtypes including NPY1R, NPY2R, NPY4R, NPY5R, and NPY6R; however, NPY6R is not functional in humans. NYP receptors are also activated by its two other family members, peptide YY (PYY) and pancreatic polypeptide (PP). They typically couple to G(i) or G(o) proteins, which leads to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels, and are involved in diverse physiological roles including appetite regulation, circadian rhythm, and anxiety. When NPY signals through NPY2R in concert with NPY5R, it induces angiogenesis and consequently plays an important role in revascularization and wound healing. On the other hand, when NPY acts through NPY1R and NPYR5, it acts as a vascular mitogen, leading to restenosis and atherosclerosis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFtppggsapaaaAGPW---RGFCAASRFFSSCFGI 98
Cdd:cd15395  17 GNLALIIIILKQKEMHNVTNILIVNLSFSDLLMTIMCLPFTFVYTL-----------MDHWvfgEAMCKLNSMVQCISIT 85

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 29611578  99 VSTLSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLPW 146
Cdd:cd15395  86 VSIFSLVLIAIERHQLIINPRGWRPNNRHAYVGIAVIWVLAVLTSLPF 133

G protein-coupled receptor PSP24 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes two human orphan receptors, GPR45 and GPR65, and their closely related proteins found in vertebrates and invertebrates. GPR45 and GPR 65 are also called PSP24-alpha (or PSP24-1) and PSP24-beta (or PSP24-2) in other vertebrates, respectively. These receptors exhibit the highest sequence homology to each other. PSP24 was originally identified as a novel, high-affinity lysophosphatidic acid (LPA) receptor in Xenopus laevis oocytes; however, PSP24 receptors (GPR45 and GPR63) have not been shown to be activated by LPA. Instead, sphingosine 1-phosphate and dioleoylphosphatidic acid have been shown to act as low affinity agonists for GPR63. PSP24 receptors are highly expressed in neuronal cells of cerebellum and their expression level remains constant from the early embryonic stages to adulthood, suggesting the important role of PSP24s in brain neuronal functions. Members of this subgroup contain the highly conserved Asp-Arg-Tyr/Phe (DRY/F) motif found in the third transmembrane helix (TM3) of the rhodopsin-like class A receptors which is important for efficient G protein-coupled signal transduction. 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 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPAAFLDLFTPPGGSAPAaaagpwrgFCAASRFFSSCFGIVST 101
Cdd:cd15213  17 GNSIVCLIVYQKPAMRSAINLLLANLAFSDIMLSLVCMPFAAVTIITGRWIFGDI--------FCRISAMLYWFFVLEGV 88

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 29611578 102 LSVALISLDRYCAIVRpPREKIGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd15213  89 AILLIISVDRYLIIVQ-RQDKLNPHRAKILIAVSWVLSFCVSFP 131

vasopressin receptors and its related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Members of this group form a subfamily within the class A G-protein coupled receptors (GPCRs), which includes the vasopressin and oxytocin receptors, the gonadotropin-releasing hormone receptors (GnRHRs), the neuropeptide S receptor (NPSR), and orphan GPR150. These receptors share significant sequence homology with each other, suggesting that they have a common evolutionary origin. Vasopressin, also known as arginine vasopressin or anti-diuretic hormone, is a neuropeptide synthesized in the hypothalamus. The actions of vasopressin are mediated by the interaction of this hormone with three tissue-specific subtypes: V1AR, V1BR, and V2R. Although vasopressin differs from oxytocin by only two amino acids, they have divergent physiological functions. Vasopressin is involved in regulating osmotic and cardiovascular homeostasis, whereas oxytocin plays an important role in the uterus during childbirth and in lactation. GnRHR, also known as luteinizing hormone releasing hormone receptor (LHRHR), plays an central role in vertebrate reproductive function; its activation by binding to GnRH leads to the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. Neuropeptide S (NPS) promotes arousal and anxiolytic-like effects by activating its cognate receptor NPSR. NPSR has also been associated with asthma and allergy. GPR150 is an orphan receptor closely related to the oxytocin and vasopressin receptors.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|..
gi 29611578  95 CFGIV-STLSVALISLDRYCAIVRPPREKIGRRRALQLLAGAWLTALGFSLP 145
Cdd:cd14986  81 VVGLFaSTYILVSMSLDRYQAIVKPMSSLKPRKRARLMIVVAWVLSFLFSIP 132

olfactory receptor family 2 and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes human olfactory receptor families 2 and 13, and related proteins in other mammals, sauropsids, and amphibians. Olfactory receptors (ORs) play a central role in olfaction, the sense of smell. ORs belong to the class A rhodopsin-like family of G protein-coupled receptors and constitute the largest multigene family in mammals of approximately 1,000 genes. More than 60% of human ORs are non-functional pseudogenes compared to only about 20% in mouse. Each OR can recognize structurally similar odorants, and a single odorant can be detected by several ORs. Binding of an odorant to the olfactory receptor induces a conformational change that leads to the activation of the olfactory-specific G protein (Golf). The G protein (Golf and/or Gs) in turn stimulates adenylate cyclase to make cAMP. The cAMP opens cyclic nucleotide-gated ion channels, which allow the influx of calcium and sodium ions, resulting in depolarization of the olfactory receptor neuron and triggering an action potential which transmits this information to the brain. A consensus nomenclature system based on evolutionary divergence is used here to classify the olfactory receptor family. The nomenclature begins with the root name OR, followed by an integer representing a family, a letter denoting a subfamily, and an integer representing the individual gene within the subfamily.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 29611578  86 CAASRFFSSCFGIVSTLSVALISLDRYCAIVRPPREKI--GRRRALQLLAGAW---------LTALGFSLP 145
Cdd:cd15237  73 CAAQMFFFLALGVTECVLLAVMAYDRYVAICNPLRYSVimSRRVCVRLAATSWasgflnslvLTSLTLRLP 143

KiSS1-derived peptide (kisspeptin) receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The G protein-coupled KiSS1-derived peptide receptor (GPR54 or kisspeptin receptor) binds the peptide hormone kisspeptin (previously known as metastin), which encoded by the metastasis suppressor gene (KISS1) expressed in various endocrine and reproductive tissues. The KiSS1 receptor is coupled to G proteins of the G(q/11) family, which lead to activation of phospholipase C and increase of intracellular calcium. This signaling cascade plays an important role in reproduction by regulating the secretion of gonadotropin-releasing hormone.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611578  22 GNCAVMGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPaafldlFTppggsAPAAAAGPW---RGFCAASRFF------ 92
Cdd:cd15095  17 GNSLVIYVVSRHREMRTVTNYYIVNLAVTDLAFLVCCVP------FT-----AALYATPSWvfgDFMCKFVNYMmqvtvq 85

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 29611578  93 SSCfgivstLSVALISLDRYCAIVRPPREKIGR--RRALQLLAGAWLTALGFSLP 145
Cdd:cd15095  86 ATC------LTLTALSVDRYYAIVHPIRSLRFRtpRVAVVVSACIWIVSFLLSIP 134

olfactory receptor subfamily 1A and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes human olfactory receptor subfamily 1A, 1B, 1K, 1L, 1Q and related proteins in other mammals, sauropsids, and amphibians. Olfactory receptors (ORs) play a central role in olfaction, the sense of smell. ORs belong to the class A rhodopsin-like family of G protein-coupled receptors and constitute the largest multigene family in mammals of approximately 1,000 genes. More than 60% of human ORs are non-functional pseudogenes compared to only about 20% in mouse. Each OR can recognize structurally similar odorants, and a single odorant can be detected by several ORs. Binding of an odorant to the olfactory receptor induces a conformational change that leads to the activation of the olfactory-specific G protein (Golf). The G protein (Golf and/or Gs) in turn stimulates adenylate cyclase to make cAMP. The cAMP opens cyclic nucleotide-gated ion channels, which allow the influx of calcium and sodium ions, resulting in depolarization of the olfactory receptor neuron and triggering an action potential which transmits this information to the brain. A consensus nomenclature system based on evolutionary divergence is used here to classify the olfactory receptor family. The nomenclature begins with the root name OR, followed by an integer representing a family, a letter denoting a subfamily, and an integer representing the individual gene within the subfamily.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 29611578  86 CAASRFFSSCFGIVSTLSVALISLDRYCAIVRPPREK--IGRRRALQLLAGAWLTALGFSLPWELL 149
Cdd:cd15235  74 CLAQMYFFIAFGNTDSFLLAVMAYDRYVAICHPLHYAtvMSPKRCLLLVAGSWLLSHLHSLLHTLL 139