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 1129879005  38 GNGMVIYIFTTTKSLRTPSNLLVINLAISDFLM-MLSMSPAMVINCYYETWVLGPLVCELYGLTGSLFGCGSIWTMTMIA 116
Cdd:pfam00001   1 GNLLVILVILRNKKLRTPTNIFLLNLAVADLLFsLLTLPFWLVYYLNHGDWPFGSALCKIVGALFVVNGYASILLLTAIS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1129879005 117 FDRYNVIVKGLSAKP-MTINGALLRILGIWFFSLGWTIAPM 156
Cdd:pfam00001  81 IDRYLAIVHPLRYKRrRTPRRAKVLILVIWVLALLLSLPPL 121

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 1129879005  23 VLGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGS 102
Cdd:cd15083     2 VLGIFILIIGLIGVVGNGLVIYAFCRFKSLRTPANYLIINLAISDFLMCILNCPLMVISSFSGRWIFGKTGCDMYGFSGG 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1129879005 103 LFGCGSIWTMTMIAFDRYNVIVKGL-SAKPMTINGALLRILGIWFFSLGWTIAP 155
Cdd:cd15083    82 LFGIMSINTLAAIAVDRYLVITRPMkASVRISHRRALIVIAVVWLYSLLWVLPP 135

vertebrate melanopsins (Opsin-4), member of the class A family of seven-transmembrane G protein-coupled receptors; Melanopsin (also called Opsin-4) is the G protein-coupled photopigment that mediates non-visual responses to light. In mammals, these photoresponses include the photo-entrainment of circadian rhythm, pupillary constriction, and acute nocturnal melatonin suppression. 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. Melanopsins 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 1129879005  23 VLGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGS 102
Cdd:cd15336     2 TVGSVILIIGITGMLGNALVIYAFCRSKKLRTPANYFIINLAVSDFLMSLTQSPIFFVNSLHKRWIFGEKGCELYAFCGA 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1129879005 103 LFGCGSIWTMTMIAFDRYNVIVKGLSA-KPMTINGALLRILGIWFFSLGWTIAPM 156
Cdd:cd15336    82 LFGITSMITLLAISLDRYLVITKPLASiRWVSKKRAMIIILLVWLYSLAWSLPPL 136

neuropsin (Opsin-5), member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropsin, also known as Opsin-5, is a photoreceptor protein expressed in the retina, brain, testes, and spinal cord. Neuropsin belongs to the type 2 opsin family of the class A G-protein coupled receptors. Mammalian neuropsin activates Gi protein-mediated photo-transduction pathway in a UV-dependent manner, whereas, in non-mammalian vertebrates, neuropsin is involved in regulating the photoperiodic control of seasonal reproduction in birds such as quail. As with other opsins, it may also act as a retinal photoisomerase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1129879005  23 VLGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGS 102
Cdd:cd15074     2 IIGIYLTVIGILSTLGNGTVLFVLYRRRSKLKPAELLTVNLAVSDLGISVFGYPLAIISAFAHRWLFGDIGCVFYGFCGF 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1129879005 103 LFGCGSIWTMTMIAFDRYNVIVKGLSAKPMTINGALLRILGIWFFSLGWTIAP 155
Cdd:cd15074    82 LFGCCSINTLTAISIYRYLKICHPPYGPKLSRRHVCIVIVAIWLYALFWAVAP 134

rhodopsin receptor-like class A family of the seven-transmembrane G protein-coupled receptor superfamily; Class A rhodopsin-like receptors constitute about 90% of all GPCRs. The class A GPCRs include the light-sensitive rhodopsin as well as receptors for biogenic amines, lipids, nucleotides, odorants, peptide hormones, and a variety of other ligands. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. Based on sequence similarity, GPCRs can be divided into six major classes: class A (rhodopsin-like family), class B (Methuselah-like, adhesion and secretin-like receptor family), class C (metabotropic glutamate receptor family), class D (fungal mating pheromone receptors), class E (cAMP receptor family), and class F (frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1129879005  24 LGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGSL 103
Cdd:cd00637     1 LAVLYILIFVVGLVGNLLVILVILRNRRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRWWFGDALCKLLGFLQSV 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1129879005 104 FGCGSIWTMTMIAFDRYNVIVKGLSAK-PMTINGALLRILGIWFFSLGWTIAPM 156
Cdd:cd00637    81 SLLASILTLTAISVDRYLAIVHPLRYRrRFTRRRAKLLIALIWLLSLLLALPPL 134

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 1129879005  23 VLGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLM-MLSMsPAMVINCYYETWVLGPLVCELYGLTG 101
Cdd:cd14967     1 LLAVFLSLIILVTVFGNLLVILAVYRNRRLRTVTNYFIVSLAVADLLVaLLVM-PFSAVYTLLGYWPFGPVLCRFWIALD 79

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1129879005 102 SLFGCGSIWTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSLGWTIAPM 156
Cdd:cd14967    80 VLCCTASILNLCAISLDRYLAITRPLRyRQLMTKKRALIMIAAVWVYSLLISLPPL 135

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 1129879005  23 VLGFVIGVLGmisVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGS 102
Cdd:cd14993     5 VLYVVVFLLA---LVGNSLVIAVVLRNKHMRTVTNYFLVNLAVADLLVSLFCMPLTLLENVYRPWVFGEVLCKAVPYLQG 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1129879005 103 LFGCGSIWTMTMIAFDRYNVIVKGLSAKP-MTINGALLRILGIWFFSLG 150
Cdd:cd14993    82 VSVSASVLTLVAISIDRYLAICYPLKARRvSTKRRARIIIVAIWVIAII 130

serotonin receptor subtype 7, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT7 receptor, one of 14 mammalian serotonin receptors, is a member of the class A of GPCRs and is activated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). 5-HT7 receptor mainly couples to Gs protein, which positively stimulates adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. 5-HT7 receptor is expressed in various human tissues, mainly in the brain, the lower gastrointestinal tract and in vital blood vessels including the coronary artery. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1129879005  22 AVLGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTG 101
Cdd:cd15329     1 VLIGIVLLIIILGTVVGNALVIIAVCLVKKLRTPSNYLIVSLAVSDLLVALLVMPLAIIYELSGYWPFGEILCDVWISFD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1129879005 102 SLFGCGSIWTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSLGWTIAPM 156
Cdd:cd15329    81 VLLCTASILNLCAISVDRYLVITRPLTyAVKRTPKRMALMIAIVWLLSALISIPPL 136

histamine receptor subtypes H3R and H4R, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine subtypes H3R and H4R, members of the histamine receptor family, which belong to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). The H3 and H4 receptors couple to the G(i)-proteins, which leading to the inhibition of cAMP formation. The H3R receptor functions as a presynaptic autoreceptors controlling histamine release and synthesis. The H4R plays an important role in histamine-mediated chemotaxis in mast cells and eosinophils. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1129879005  22 AVLGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTG 101
Cdd:cd15048     1 IVLAVLISVLILVTVIGNLLVILAFIKDKKLRTVSNFFLLNLAVADFLVGLVSMPFYIPYTLTGKWPFGKVFCKAWLVVD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1129879005 102 SLFGCGSIWTMTMIAFDRYNVIVKGLSAKPM-TINGALLRILGIWFFSL 149
Cdd:cd15048    81 YTLCTASALTIVLISLDRYLSVTKAVKYRAKqTKRRTVLLMALVWILAF 129

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1129879005  22 AVLGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTG 101
Cdd:cd15064     1 VLISVLLSLIILATILGNALVIAAILLTRKLHTPANYLIASLAVADLLVAVLVMPLSAVYELTGRWILGQVLCDIWISLD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1129879005 102 SLFGCGSIWTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSLGWTIAPM 156
Cdd:cd15064    81 VTCCTASILHLCVIALDRYWAITDAVEyAHKRTPKRAAVMIALVWTLSICISLPPL 136

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 1129879005  19 LWHAVLGFVIgvlgMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYG 98
Cdd:cd15202     2 LLIVAYSFII----VFSLFGNVLVCWIIFKNQRMRTVTNYFIVNLAVADIMITLFNTPFTFVRAVNNTWIFGLFMCHFSN 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1129879005  99 LTGSLFGCGSIWTMTMIAFDRYNVIVKGLSAKpMTINGALLRILGIWFFSL 149
Cdd:cd15202    78 FAQYCSVHVSAYTLTAIAVDRYQAIMHPLKPR-ISKTKAKFIIAVIWTLAL 127

neuropeptide FF receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropeptide FF (NPFF) is a mammalian octapeptide that belongs to a family of neuropeptides containing an RF-amide motif at their C-terminus that have 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 these peptides 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. NPFF has been shown to inhibit adenylate cyclase via the Gi protein coupled to NPFF1-R.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1129879005  35 SVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGSLFGCGSIWTMTM 114
Cdd:cd15207    14 CVVGNVLVCLVVAKNPRMRTVTNYFILNLAVSDLLVGVFCMPFTLVDNILTGWPFGDVMCKLSPLVQGVSVAASVFTLVA 93

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1129879005 115 IAFDRYNVIVKGLSAKpMTINGALLRILGIWFFSL 149
Cdd:cd15207    94 IAVDRYRAVVHPTEPK-LTNRQAFVIIVAIWVLAL 127

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1129879005  27 VIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGSLFGC 106
Cdd:cd15084    16 LMGMVVALASFVNGLVIVVSIKYKKLRSPLNYILVNLAVADLLVTLFGSSVSFSNNIVGFFVFGKTMCEFEGFMVSLTGI 95

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1129879005 107 GSIWTMTMIAFDRYNVIVKGLSAKPMTINGALLRILGIWFFSLGWTIAPM 156
Cdd:cd15084    96 VGLWSLAILAFERYLVICKPMGDFRFQQRHAVSGCAFTWGWSLLWTSPPL 145

G protein-coupled receptor 84 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR84, also known as the inflammation-related G-Protein coupled receptor EX33, is a receptor for medium-chain free fatty acid (FFA) with carbon chain lengths of C9 to C14. Among these medium-chain FFAs, capric acid (C10:0), undecanoic acid (C11:0), and lauric acid (C12:0) are the most potent endogenous agonists of GPR84, whereas short-chain and long-chain saturated and unsaturated FFAs do not activate this receptor. GPR84 contains a [G/N]RY-motif instead of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of the rhodopsin-like class A receptors and 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, which then activate the heterotrimeric G proteins. In the case of GPR84, activation of the receptor couples to a pertussis toxin sensitive G(i/o)-protein pathway. GPR84 knockout mice showed increased Th2 cytokine production including IL-4, IL-5, and IL-13 compared to wild-type mice. It has been also shown that activation of GPR84 augments lipopolysaccharide-stimulated IL-8 production in polymorphonuclear leukocytes and TNF-alpha production in macrophages, suggesting that GPR84 may function as a proinflammatory receptor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1129879005  22 AVLGFVIGVLGmisVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTG 101
Cdd:cd15210     4 AVWGIVFMVVG---VPGNLLTVLALLRSKKLRTRTNAFIINLSISDLLFCAFNLPLAASTFLHQAWIHGETLCRVFPLLR 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1129879005 102 SLFGCGSIWTMTMIAFDRYNVIV-KGLSAKPMTINGALLRILGIWFFSLGWTIAP 155
Cdd:cd15210    81 YGLVAVSLLTLVLITLNRYILIAhPSLYPRIYTRRGLALMIAGTWIFSFGSFLPL 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 1129879005  22 AVLGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTG 101
Cdd:cd15389     1 ALLIVAYSIIIVISLFGNSLVCHVIFKNKRMHTATNLFIVNLAVSDILITLLNTPFTLVRFVNSTWVFGKIMCHLSRFAQ 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1129879005 102 SLFGCGSIWTMTMIAFDRYNVIVKGLSAKpMTINGALLRILGIW----FFSL 149
Cdd:cd15389    81 YCSVYVSTLTLTAIALDRHRVILHPLKPR-ITPCQGVVVIAIIWimasCLSL 131

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 1129879005  31 LGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMML-SMSPAMVINCYYETWVLGPLVCELYGLTGSLFGCGSI 109
Cdd:cd14979    10 IFVVGIVGNLLTCIVIARHKSLRTTTNYYLFSLAVSDLLILLvGLPVELYNFWWQYPWAFGDGGCKLYYFLFEACTYATV 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1129879005 110 WTMTMIAFDRYNVIVKGLSAKPMTINGALLRILG-IWFFSL 149
Cdd:cd14979    90 LTIVALSVERYVAICHPLKAKTLVTKRRVKRFILaIWLVSI 130

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 1129879005  22 AVLGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFL-MMLSMSPAMVINCYYETWVLGPLVCELYGLT 100
Cdd:cd15212     1 AAQALVLLAIFLLSSLGNCAVIGVIVKHRQLRTVTNAFILSLSLSDLLtALLCLPFAFLTLFSRPGWLFGDRLCLANGFF 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1129879005 101 GSLFGCGSIWTMTMIAFDRYNVIVKGLSAKPMTiNGALLRILGIWFFSLG 150
Cdd:cd15212    81 NACFGIVSTLTMTLISFDRYYAIVRQPQGKIGR-RRALQLLAAAWLTALG 129

alpha-2 adrenergic receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback. 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 1129879005  22 AVLGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTG 101
Cdd:cd15059     1 VAISSIVSVVILLIIVGNVLVIVAVLTSRKLRAPQNWFLVSLAVADILVGLLIMPFSLVNELMGYWYFGSVWCEIWLALD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1129879005 102 SLFGCGSIWTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSLGWTIAPM 156
Cdd:cd15059    81 VLFCTASIVNLCAISLDRYWSVTQAVEyNLKRTPRRAKAMIAAVWIISAVISLPPL 136

purinoceptor and its related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; Members of this subfamily include lysophosphatidic acid receptor, P2 purinoceptor, protease-activated receptor, platelet-activating factor receptor, Epstein-Barr virus induced gene 2, proton-sensing G protein-coupled receptors, GPR35, and GPR55, among others. 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 1129879005  34 ISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMsPAMVIncYY---ETWVLGPLVCELYGLTGSLFGCGSIW 110
Cdd:cd14982    13 LGLLGNILALWVFLRKMKKRSPTTIYMINLALADLLFVLTL-PFRIY--YYlngGWWPFGDFLCRLTGLLFYINMYGSIL 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1129879005 111 TMTMIAFDRYNVIVKGL-SAKPMTINGALLRILGIWFFSLGWTI 153
Cdd:cd14982    90 FLTCISVDRYLAVVHPLkSRRLRRKRYAVGVCAGVWILVLVASV 133

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1129879005  28 IGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYgLTGSLFGCG 107
Cdd:cd15335     7 LALITILTTVLNSAVIAAICTTKKLHQPANYLICSLAVTDFLVAVLVMPLSITYIVMDTWTLGYFICEIW-LSVDMTCCT 85

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1129879005 108 -SIWTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSLGWTIAPM 156
Cdd:cd15335    86 cSILHLCVIALDRYWAITDAIEyARKRTAKRAGLMILTVWTISIFISIPPL 136

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1129879005  20 WHAVLGFVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGL 99
Cdd:cd15333     3 LKISLAVLLALITLATTLSNAFVIATIYLTRKLHTPANYLIASLAVTDLLVSILVMPISIVYTVTGTWTLGQVVCDIWLS 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1129879005 100 TGSLFGCGSIWTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSLGWTIAPM 156
Cdd:cd15333    83 SDITCCTASILHLCVIALDRYWAITDAVEySKKRTPKRAAVMIALVWVISISISLPPF 140

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 1129879005  26 FVIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCY-YETWVLGPLVCELYGLTGSLF 104
Cdd:cd14997     5 VVYGVIFVVGVLGNVLVGIVVWKNKDMRTPTNIFLVNLSVADLLVLLVCMPVALVETWaREPWLLGEFMCKLVPFVELTV 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1129879005 105 GCGSIWTMTMIAFDRYNVIVKGLSAK-PMTINGALLRILGIWFFSL 149
Cdd:cd14997    85 AHASVLTILAISFERYYAICHPLQAKyVCTKRRALVIIALIWLLAL 130

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 1129879005  27 VIGVLGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGSLFGC 106
Cdd:cd14971     6 FFALIFLLGLVGNSLVILVVARNKPMRSTTNLFILNLAVADLTFLLFCVPFTATIYPLPGWVFGDFMCKFVHYFQQVSMH 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1129879005 107 GSIWTMTMIAFDRYNVIVKGLSAKPM-TINGALLRILGIWFFSLG 150
Cdd:cd14971    86 ASIFTLVAMSLDRFLAVVYPLRSLHIrTPRNALAASGCIWVVSLA 130