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 1236486472  97 GNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPIN-VFKLLAGRWPfdhndFGVFLCKLFPFLQKSSVGITVLN 175
Cdd:pfam00001   1 GNLLVILVILRNKKLRTPTNIFLLNLAVADLLFSLLTLPFWlVYYLNHGDWP-----FGSALCKIVGALFVVNGYASILL 75

                  ....*..
gi 1236486472 176 LCALSVD 182
Cdd:pfam00001  76 LTAISID 82

endothelin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Endothelins are 21-amino acid peptides which able to activate a number of signal transduction processes including phospholipase A2, phospholipase C, and phospholipase D, as well as cytosolic protein kinase activation. They play an important role in the regulation of the cardiovascular system and are the most potent vasoconstrictors identified, stimulating cardiac contraction, regulating the release of vasoactive substances, and stimulating mitogenesis in blood vessels. Two endothelin receptor subtypes have been isolated and identified in vertebrates, endothelin A receptor (ET-A) and endothelin B receptor (ET-B), and are members of the seven transmembrane class A G-protein coupled receptor family which activate multiple effectors via different types of G protein. Some vertebrates contain a third subtype, endothelin A receptor (ET-C). ET-A receptors are mainly located on vascular smooth muscle cells, whereas ET-B receptors are present on endothelial cells lining the vessel wall. Endothelin receptors have also been found in the brain.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  81 YINTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPFDHNDFGVFLCKL 160
Cdd:cd15128     1 YINTVVSCLIFIVGIIGNSTLLRIIYQNKCMRNGPNALIASLALGDLLYIVIDLPINVYKLLAMDWPFGDQPFGQFLCKL 80

                          90       100
                  ....*....|....*....|..
gi 1236486472 161 FPFLQKSSVGITVLNLCALSVD 182
Cdd:cd15128    81 VPFIQKASVGITVLNLCALSVD 102

endothelin C receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Endothelins are able to activate a number of signal transduction processes including phospholipase A2, phospholipase C, and phospholipase D, as well as cytosolic protein kinase activation. They play an important role in the regulation of the cardiovascular system and are the most potent vasoconstrictors identified, stimulating cardiac contraction, regulating the release of vasoactive substances, and stimulating mitogenesis in blood vessels. Two endothelin receptor subtypes have been isolated and identified in vertebrates, endothelin A receptor (ET-A) and endothelin B receptor (ET-B), and are members of the seven transmembrane class A G-protein coupled receptor family which activate multiple effectors via different types of G protein. Some vertebrates contain a third subtype, endothelin A receptor (ET-C). ET-A receptors are mainly located on vascular smooth muscle cells, whereas ET-B receptors are present on endothelial cells lining the vessel wall. Endothelin receptors have also been found in the brain. The ET-C receptor is specific for endothelin-3 on frog dermal melanophores; its activation causes dispersion of pigment granules.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  81 YINTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKL 160
Cdd:cd15977     1 YVNTILSCVIFLVGIIGNSTLLRIIYKNKCMRNGPNVLIASLALGDLLYILIAIPINVIKLIAEDWP-----FGVHVCKL 75

                          90       100
                  ....*....|....*....|..
gi 1236486472 161 FPFLQKSSVGITVLNLCALSVD 182
Cdd:cd15977    76 YPFIQKASVGITVLSLCALSID 97

bombesin receptor subfamily, member of the class A family of seven-transmembrane G protein-coupled receptors; This bombesin subfamily of G-protein coupled receptors consists of neuromedin B receptor (NMBR), gastrin-releasing peptide receptor (GRPR), and bombesin receptor subtype 3 (BRS-3). Bombesin is a tetradecapeptide, originally isolated from frog skin. Mammalian bombesin-related peptides are widely distributed in the gastrointestinal and central nervous systems. The bombesin family receptors couple mainly to the G proteins of G(q/11) family. NMBR functions as the receptor for the neuropeptide neuromedin B, a potent mitogen and growth factor for normal and cancerous lung and for gastrointestinal epithelial tissues. Gastrin-releasing peptide is an endogenous ligand for GRPR and shares high sequence homology with NMB in the C-terminal region. Both NMB and GRP possess bombesin-like biochemical properties. BRS-3 is classified as an orphan receptor and suggested to play a role in sperm cell division and maturation. BRS-3 interacts with known naturally-occurring bombesin-related peptides with low affinity; however, no endogenous high-affinity ligand to the receptor has been identified. The bombesin receptor family belongs to the seven transmembrane rhodopsin-like G-protein coupled receptors (class A GPCRs), which perceive extracellular signals and transduce them to guanine nucleotide-binding (G) proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  81 YINTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKL 160
Cdd:cd15927     1 YVVPILFALIFLVGVLGNGTLILIFLRNKSMRNVPNIFILSLALGDLLLLLTCVPFTSTIYTLDSWP-----FGEFLCKL 75

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1236486472 161 FPFLQKSSVGITVLNLCALSVDsRLKA---PFRGQT 193
Cdd:cd15927    76 SEFLKDTSIGVSVFTLTALSAD-RYFAivnPMRKHR 110

gastrin-releasing peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The gastrin-releasing peptide receptor (GRPR) is a G-protein coupled receptor whose endogenous ligand is gastrin releasing peptide. GRP shares high sequence homology with the neuropeptide neuromedin B in the C-terminal region. This receptor is high glycosylated and couples to a pertussis-toxin-insensitive G protein of the family of Gq/11, which leads to the activation of phospholipase C. Gastrin-releasing peptide (GRP) is a potent mitogen for neoplastic tissues and involved in regulating multiple functions of the gastrointestinal and central nervous systems. These include the release of gastrointestinal hormones, the contraction of smooth muscle cells, and the proliferation of epithelial cells. GRPR belongs to the bombesin subfamily of G-protein coupled receptors, whose members also include neuromedin B receptor (NMBR) and bombesin receptor subtype 3 (BRS-3). Bombesin is a tetradecapeptide, originally isolated from frog skin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  90 IFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKLFPFLQKSSV 169
Cdd:cd15124    10 IILIGLIGNITLIKIFCTVKSMRNVPNLFISSLALGDLLLLVTCAPVDASRYLADEWL-----FGRVGCKLIPFIQLTSV 84

                          90       100
                  ....*....|....*....|.
gi 1236486472 170 GITVLNLCALSVDsRLKAPFR 190
Cdd:cd15124    85 GVSVFTLTALSAD-RYKAIVR 104

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 1236486472  84 TVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKLFPF 163
Cdd:cd14993     4 IVLYVVVFLLALVGNSLVIAVVLRNKHMRTVTNYFLVNLAVADLLVSLFCMPLTLLENVYRPWV-----FGEVLCKAVPY 78

                          90
                  ....*....|....*....
gi 1236486472 164 LQKSSVGITVLNLCALSVD 182
Cdd:cd14993    79 LQGVSVSASVLTLVAISID 97

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 1236486472  84 TVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKLFPF 163
Cdd:cd15203     4 ILLYGLIIVLGVVGNLLVIYVVLRNKSMQTVTNIFILNLAVSDLLLCLVSLPFTLIYTLTKNWP-----FGSILCKLVPS 78

                          90
                  ....*....|....*....
gi 1236486472 164 LQKSSVGITVLNLCALSVD 182
Cdd:cd15203    79 LQGVSIFVSTLTLTAIAID 97

GPRnna14 and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the orphan G-protein coupled receptor GPRnna14 found in body louse (Pediculus humanus humanus) as well as its closely related proteins of unknown function. These receptors are members of the class A rhodopsin-like G-protein coupled receptors. As an obligatory parasite of humans, the body louse is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. GPRnna14 shares significant sequence similarity with the members of the neurotensin receptor family. 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 1236486472  89 TIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWpfdhnDFGVFLCKLFPFLQKSS 168
Cdd:cd15001     8 ITFVLGLIGNSLVIFVVARFRRMRSVTNVFLASLATADLLLLVFCVPLKTAEYFSPTW-----SLGAFLCKAVAYLQLLS 82

                          90
                  ....*....|...
gi 1236486472 169 VGITVLNLCALSV 181
Cdd:cd15001    83 FICSVLTLTAISI 95

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 1236486472  90 IFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKLFPFLQKSSV 169
Cdd:cd15202    10 IIVFSLFGNVLVCWIIFKNQRMRTVTNYFIVNLAVADIMITLFNTPFTFVRAVNNTWI-----FGLFMCHFSNFAQYCSV 84

                          90
                  ....*....|...
gi 1236486472 170 GITVLNLCALSVD 182
Cdd:cd15202    85 HVSAYTLTAIAVD 97

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 1236486472  90 IFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWpFdhndFGVFLCKLFPFLQKSSV 169
Cdd:cd15208    10 VFIVGLVGNVLVCFAVWRNHHMRTVTNYFIVNLSLADFLVIIICLPATLLVDVTETW-F----FGQVLCKIIPYLQTVSV 84

                          90
                  ....*....|...
gi 1236486472 170 GITVLNLCALSVD 182
Cdd:cd15208    85 SVSVLTLSCIALD 97

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 1236486472  84 TVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGR-WPfdhndFGVFLCKLFP 162
Cdd:cd14979     4 TAIYVAIFVVGIVGNLLTCIVIARHKSLRTTTNYYLFSLAVSDLLILLVGLPVELYNFWWQYpWA-----FGDGGCKLYY 78

                          90
                  ....*....|....*....
gi 1236486472 163 FLQKSSVGITVLNLCALSV 181
Cdd:cd14979    79 FLFEACTYATVLTIVALSV 97

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 1236486472  82 INTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPFDHndfgvFLCKLF 161
Cdd:cd14992     2 ILGVALVVIILVSVVGNFIVIAALARHKNLRGATNYFIASLAISDLLMALFCTPFNFTYVVSLSWEYGH-----FLCKIV 76

                          90       100
                  ....*....|....*....|.
gi 1236486472 162 PFLQKSSVGITVLNLCALSVD 182
Cdd:cd14992    77 NYLRTVSVYASSLTLTAIAFD 97

growth hormone secretagogue receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Growth hormone secretagogue receptor, GHSR, is also known as GH-releasing peptide receptor (GHRP) or Ghrelin receptor. Ghrelin, the endogenous ligand for GHSR, is an acylated 28-amino acid peptide hormone produced by ghrelin cells in the gastrointestinal tract. Ghrelin, also called hunger hormone, is involved in the regulation of growth hormone release, appetite and feeding, gut motility, lipid and glucose metabolism, and energy balance. It also plays a role in the cardiovascular, immune, and reproductive systems. GHSR couples to G-alpha-11 proteins. Both ghrelin and GHSR are expressed in a wide range of cancer tissues. Recent studies suggested that ghrelin may play a role in processes associated with cancer progression, including cell proliferation, metastasis, apoptosis, and angiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  84 TVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIyVVIDLPINVFKLlagrWPFDHNDFGVFLCKLFPF 163
Cdd:cd15131     4 TVTCVLLFVVGVTGNLMTMLVVSKYRDMRTTTNLYLSSMAFSDLL-IFLCMPLDLYRL----WQYRPWNFGDLLCKLFQF 78

                          90
                  ....*....|....*....
gi 1236486472 164 LQKSSVGITVLNLCALSVD 182
Cdd:cd15131    79 VSESCTYSTILNITALSVE 97

neuropeptide Y receptor type 4, 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  88 CTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKLFPFLQKS 167
Cdd:cd15397     8 SLVMAVGLLGNICLICVIARQKEKTNVTNILIANLSFSDILVCLVCLPFTVVYTLMDYWI-----FGEVLCKMTPFIQCM 82

                  ....*....
gi 1236486472 168 SVGITVLNL 176
Cdd:cd15397    83 SVTVSILSL 91

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 1236486472  84 TVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKLFPF 163
Cdd:cd14967     3 AVFLSLIILVTVFGNLLVILAVYRNRRLRTVTNYFIVSLAVADLLVALLVMPFSAVYTLLGYWP-----FGPVLCRFWIA 77

                          90
                  ....*....|....*....
gi 1236486472 164 LQKSSVGITVLNLCALSVD 182
Cdd:cd14967    78 LDVLCCTASILNLCAISLD 96

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 1236486472  85 VISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKLFPFL 164
Cdd:cd15095     5 LIFAIIFLVGLAGNSLVIYVVSRHREMRTVTNYYIVNLAVTDLAFLVCCVPFTAALYATPSWV-----FGDFMCKFVNYM 79

                          90
                  ....*....|....*...
gi 1236486472 165 QKSSVGITVLNLCALSVD 182
Cdd:cd15095    80 MQVTVQATCLTLTALSVD 97

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 1236486472  90 IFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPFdhndfGVFLCKLFPFLQKSSV 169
Cdd:cd15389    10 IIVISLFGNSLVCHVIFKNKRMHTATNLFIVNLAVSDILITLLNTPFTLVRFVNSTWVF-----GKIMCHLSRFAQYCSV 84

                          90
                  ....*....|...
gi 1236486472 170 GITVLNLCALSVD 182
Cdd:cd15389    85 YVSTLTLTAIALD 97

neurotensin receptor subtype 1, member of the class A family of seven-transmembrane G protein-coupled receptors; Neurotensin (NTS) is a 13 amino-acid neuropeptide that functions as both a neurotransmitter and a hormone in the nervous system and peripheral tissues, respectively. NTS exerts various biological activities through activation of the G protein-coupled neurotensin receptors, NTSR1 and NTSR2. In the brain, NTS is involved in the modulation of dopamine neurotransmission, opioid-independent analgesia, hypothermia, and the inhibition of food intake, while in the periphery NTS promotes the growth of various normal and cancer cells and acts as a paracrine and endocrine modulator of the digestive tract. The third neurotensin receptor, NTSR3 or also called sortilin, is not a G protein-coupled receptor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  84 TVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNAL---IASLALGDLIYVVIDLPINVFKLLAGRWPFdhnDFGVFLCKL 160
Cdd:cd15355     4 TAIYLALFVVGTVGNSITLYTLARKKSLQHLQSTVhyhLASLALSDLLILLLAMPVELYNFIWVHHPW---AFGDAACRG 80

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1236486472 161 FPFLQKSSVGITVLNLCALSVDSRLKA--PFRGQT 193
Cdd:cd15355    81 YYFLRDACTYATALNVASLSVERYLAIchPFKAKS 115

leucokinin-like peptide receptor from tick and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes a leucokinin-like peptide receptor from the Southern cattle tick, Boophilus microplus, a pest of cattle world-wide. Leucokinins are invertebrate neuropeptides that exhibit myotropic and diuretic activity. This receptor is the first neuropeptide receptor known from the Acari and the second known in the subfamily of leucokinin-like peptide G-protein-coupled receptors. The other known leucokinin-like peptide receptor is a lymnokinin receptor from the mollusc Lymnaea stagnalis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  90 IFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPFDHndfgvFLCKLFPFLQKSSV 169
Cdd:cd15393    10 ISLVAVVGNFLVIWVVAKNRRMRTVTNIFIANLAVADIIIGLFSIPFQFQAALLQRWVLPR-----FMCPFCPFVQVLSV 84

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1236486472 170 GITVLNLCALSVDsRLKA---PFRGQTWNCKTSF 200
Cdd:cd15393    85 NVSVFTLTVIAVD-RYRAvihPLKARCSKKSAKI 117

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 1236486472  85 VISCTIFIvGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWpfdhnDFGVFLCKLFPFL 164
Cdd:cd15213     6 LMILMIFV-GFLGNSIVCLIVYQKPAMRSAINLLLANLAFSDIMLSLVCMPFAAVTIITGRW-----IFGDIFCRISAML 79

                          90
                  ....*....|....*...
gi 1236486472 165 QKSSVGITVLNLCALSVD 182
Cdd:cd15213    80 YWFFVLEGVAILLIISVD 97

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 1236486472  82 INTVISCTIFIVGM-VGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWpfdhnDFGVFLCKL 160
Cdd:cd15060     1 VVTTILLSVIIAFTiVGNILVILSVFTYRPLRIVQNFFIVSLAVADLAVAIFVLPLNVAYFLLGKW-----LFGIHLCQM 75

                          90       100
                  ....*....|....*....|..
gi 1236486472 161 FPFLQKSSVGITVLNLCALSVD 182
Cdd:cd15060    76 WLTCDILCCTASILNLCAIALD 97

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 1236486472  89 TIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLagrwpFDHNDFGVFLCKLFPFLQKSS 168
Cdd:cd15395     9 AVIILGVSGNLALIIIILKQKEMHNVTNILIVNLSFSDLLMTIMCLPFTFVYTL-----MDHWVFGEAMCKLNSMVQCIS 83

                          90
                  ....*....|....
gi 1236486472 169 VGITVLNLCALSVD 182
Cdd:cd15395    84 ITVSIFSLVLIAIE 97

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 1236486472  89 TIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKLFPFLQKSS 168
Cdd:cd15390     9 VMVLVAIGGNLIVIWIVLAHKRMRTVTNYFLVNLAVADLLISAFNTVFNFTYLLYNDWP-----FGLFYCKFSNFVAITT 83

                          90
                  ....*....|....
gi 1236486472 169 VGITVLNLCALSVD 182
Cdd:cd15390    84 VAASVFTLMAISID 97

galanin receptor subtype 1, member of the class A family of seven-transmembrane G protein-coupled receptors; The G protein-coupled galanin receptors bind galanin, a neuropeptide that is widely expressed in the brain, peripheral tissues, and endocrine glands. Three receptors subtypes have been so far identified: GAL1, GAL2, and GAL3. The specific functions of each subtype remains mostly unknown, although galanin is thought to be involved in a variety of neuronal functions such as hormone release and food intake. Galanin is implicated in numerous neurological and psychiatric diseases including Alzheimer's disease, depression, eating disorders, epilepsy and stroke, among many others.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  90 IFIVGMVGNATLLRIIYQNKCM--RNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPFdhndfGVFLCKLFPFLQKS 167
Cdd:cd15098    10 IFCLGVLGNSLVITVLARVKPGkrRSTTNVFILNLSIADLFFLLFCVPFQATIYSLPEWVF-----GAFMCKFVHYFFTV 84

                          90
                  ....*....|....*
gi 1236486472 168 SVGITVLNLCALSVD 182
Cdd:cd15098    85 SMLVSIFTLVAMSVD 99

anaphylatoxin receptors and related G protein-coupled chemokine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily of G-protein coupled receptors includes anaphylatoxin receptors, formyl peptide receptors (FPR), prostaglandin D2 receptor 2, GPR1, and related chemokine receptors. The anaphylatoxin receptors are a group of G-protein coupled receptors that bind anaphylatoxins. The members of this group include C3a and C5a receptors. The formyl peptide receptors (FPRs) are chemoattractant GPCRs that involved in mediating immune responses to infection. They are expressed mainly on polymorphonuclear and mononuclear phagocytes and bind N-formyl-methionyl peptides (FMLP), which are derived from the mitochondrial proteins of ruptured host cells or invading pathogens. Chemokine receptor-like 1 (also known as chemerin receptor 23) is a GPCR for the chemoattractant adipokine chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), and for the omega-3 fatty acid derived molecule resolvin E1. Interaction with chemerin induces activation of the MAPK and PI3K signaling pathways leading to downstream functional effects, such as a decrease in immune responses, stimulation of adipogenesis, and angiogenesis. On the other hand, resolvin E1 negatively regulates the cytokine production in macrophages by reducing the activation of MAPK1/3 and NF-kB pathways. Prostaglandin D2 receptor, also known as CRTH2, is a chemoattractant G-protein coupled receptor expressed on T helper type 2 cells that binds prostaglandin D2 (PGD2). PGD2 functions as a mast cell-derived mediator to trigger asthmatic responses and also causes vasodilation. PGD2 exerts its inflammatory effects by binding to two G-protein coupled receptors, the D-type prostanoid receptor (DP) and PD2R2 (CRTH2). PD2R2 couples to the G protein G(i/o) type which leads to a reduction in intracellular cAMP levels and an increase in intracellular calcium. GPR1 is an orphan receptor that can be activated by the leukocyte chemoattractant chemerin, thereby suggesting that some of the anti-inflammatory actions of chemerin may be mediated through GPR1.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  82 INTVISCTIFIVGMVGNATllrIIYQNKC-MRNGPNALIA-SLALGDLIYVVIdLPINVFKLLAGRWPfdhnDFGVFLCK 159
Cdd:cd14974     2 VSLVLYALIFLLGLPGNGL---VIWVAGFkMKRTVNTVWFlNLALADFLFCLF-LPFLIVYIAMGHHW----PFGSVLCK 73

                          90       100
                  ....*....|....*....|...
gi 1236486472 160 LFPFLQKSSVGITVLNLCALSVD 182
Cdd:cd14974    74 LNSFVISLNMFASVFLLTAISLD 96

angiotesin receptor family and its related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the angiotensin receptors, the bradykinin receptors, apelin receptor as well as putative G-protein coupled receptors (GPR15 and GPR25). Angiotensin II (Ang II), the main effector in the renin-angiotensin system, plays a crucial role in the regulation of cardiovascular homeostasis through its type 1 (AT1) and type 2 (AT2) receptors. Ang II contributes to cardiovascular diseases such as hypertension and atherosclerosis via AT1R activation. Ang II increases blood pressure through Gq-mediated activation of phospholipase C, resulting in phosphoinositide (PI) hydrolysis and increased intracellular calcium levels. Through the AT2 receptor, Ang II counteracts the vasoconstrictor action of AT1R and thereby induces vasodilation, sodium excretion, and reduction of blood pressure. Bradykinins (BK) are pro-inflammatory peptides that mediate various vascular and pain responses to tissue injury through its B1 and B2 receptors. Apelin (APJ) receptor binds the endogenous peptide ligands, apelin and Toddler/Elabela. APJ is an adipocyte-derived hormone that is ubiquitously expressed throughout the human body, and Toddler/Elabela is a short secretory peptide that is required for normal cardiac development in zebrafish. Activation of APJ receptor plays key roles in diverse physiological processes including vasoconstriction and vasodilation, cardiac muscle contractility, angiogenesis, and regulation of water balance and food intake. Orphan receptors, GPR15 and GPR25, share strong sequence homology to the angiotensin II type AT1 and AT2 receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  90 IFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIdLPI-NVFKLLAGRWPfdhndFGVFLCKLFPFLQKSS 168
Cdd:cd14985    10 IFLVGLLGNLFVVWVFLFPRGPKRVADIFIANLAAADLVFVLT-LPLwATYTANQYDWP-----FGAFLCKVSSYVISVN 83

                          90
                  ....*....|....
gi 1236486472 169 VGITVLNLCALSVD 182
Cdd:cd14985    84 MFASIFLLTCMSVD 97

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  81 YINTVISCTIFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKL 160
Cdd:cd14969     1 YVLAVYLSLIGVLGVVLNGLVIIVFLKKKKLRTPLNLFLLNLALADLLMSVVGYPLSFYSNLSGRWS-----FGDPGCVI 75

                          90       100
                  ....*....|....*....|...
gi 1236486472 161 FPFLQkSSVGITVL-NLCALSVD 182
Cdd:cd14969    76 YGFAV-TFLGLVSIsTLAALAFE 97

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  90 IFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKLFPFLQKSSV 169
Cdd:cd15083    10 IGLIGVVGNGLVIYAFCRFKSLRTPANYLIINLAISDFLMCILNCPLMVISSFSGRWI-----FGKTGCDMYGFSGGLFG 84

                          90
                  ....*....|...
gi 1236486472 170 GITVLNLCALSVD 182
Cdd:cd15083    85 IMSINTLAAIAVD 97

neuropeptide Y receptor type 6, 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1236486472  90 IFIVGMVGNATLLRIIYQNKCMRNGPNALIASLALGDLIYVVIDLPINVFKLLAGRWPfdhndFGVFLCKLFPFLQKSSV 169
Cdd:cd15396    10 VTIVGLFGNLCLITIIKKQKEEHNVTNILIANLSLSDVLVCVMCIPFTAVYTLMDHWI-----FGETMCKLTSFVQSVSV 84

                          90
                  ....*....|...
gi 1236486472 170 GITVLNLCALSVD 182
Cdd:cd15396    85 SVSIFSLVLIAIE 97

neurotensin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Neurotensin (NTS) is a 13 amino-acid neuropeptide that functions as both a neurotransmitter and a hormone in the nervous system and peripheral tissues, respectively. NTS exerts various biological activities through activation of the G protein-coupled neurotensin receptors, NTSR1 and NTSR2. In the brain, NTS is involved in the modulation of dopamine neurotransmission, opioid-independent analgesia, hypothermia, and the inhibition of food intake, while in the periphery NTS promotes the growth of various normal and cancer cells and acts as a paracrine and endocrine modulator of the digestive tract. The third neurotensin receptor, NTSR3 or also called sortilin, is not a G protein-coupled receptor.