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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2374221995   1 ESYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAEKeVTRMVILMVLGFMLAWTPYAVVAF 73
Cdd:pfam00001 149 VSYTLLISVLGFLLPLLVILVCYTLIIRTLRKSASKQKSSERTQRRRK-ALKTLAVVVVVFILCWLPYHIVNL 220

short wave-sensitive 2 opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes Short Wave-Sensitive opsin 2 (SWS2), which mediates visual transduction in response to light at short wavelengths (violet to blue). Vertebrate cone opsins are expressed in cone photoreceptor cells of the retina and involved in mediating photopic vision, which allows color perception. The cone opsins can be classified into four classes according to their peak absorption wavelengths: SWS1 (ultraviolet sensitive), SWS2 (short wave-sensitive), MWS/LWS (medium/long wave-sensitive), and RH2 (medium wave-sensitive, rhodopsin-like opsins). Members of this group belong to the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2374221995   1 ESYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAEKEVTRMVILMVLGFMLAWTPYAVVA 72
Cdd:cd15077   164 ESYVMFLFCFCFGVPLSIIVFSYGRLLLTLRAVAKQQEQSASTQKAEREVTKMVVVMVLGFLVCWLPYASFA 235

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAEKEVTRMVILMVLGFMLAWTPYAVVA 72
Cdd:cd15084   173 SYILALFVTCFALPLSTIIFSYSNLLLTLRAVAAQQKESETTQRAEKEVTRMVIAMVMAFLICWLPYATFA 243

non-visual VA (vertebrate ancient) opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; The vertebrate ancient (VA) opsin photopigments were originally identified in salmon and they appear to have diverged early in the evolution of vertebrate opsins. VA opsins are localized in the inner retina and the brain in teleosts. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extraretinal 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. The VA opsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAEKEVTRMVILMVLGFMLAWTPYAV 70
Cdd:cd15082   176 TYIITFFTTCFILPLGVIFVSYGKLLQKLRKVSNTQGRLGNARKPERQVTRMVVVMIVAFMVCWTPYAA 244

long wave-sensitive opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; Long Wave-Sensitive opsin is also called red-sensitive opsin or red cone photoreceptor pigment, which mediates visual transduction in response to light at long wavelengths. Vertebrate cone opsins are expressed in cone photoreceptor cells of the retina and involved in mediating photopic vision, which allows color perception. The cone opsins can be classified into four classes according to their peak absorption wavelengths: SWS1 (ultraviolet sensitive), SWS2 (short wave-sensitive), MWS/LWS (medium/long wave-sensitive), and RH2 (medium wave-sensitive, rhodopsin-like opsins). Members of this group belong to the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2374221995   1 ESYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAEKEVTRMVILMVLGFMLAWTPYAVVA 72
Cdd:cd15081   176 QSYMIVLMITCCIIPLAIIILCYLQVWLAIRAVAQQQKESESTQKAEKEVSRMVVVMIFAYCFCWGPYTFFA 247

teleost multiple tissue (tmt) opsin, member of the class A family of seven-transmembrane G protein-coupled receptors; Teleost multiple tissue (tmt) opsins are homologs of encephalopsin. Mouse encephalopsin (or panopsin) is highly expressed in the brain and testes, whereas the teleost homologs are localized to multiple tissues. The exact functions of the encephalopsins and tmt-opsins are unknown. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extra-retinal tissues and/or in non-rod, non-cone retinal cells. They are thought to be involved in light-dependent physiological functions such as photo-entrainment of circadian rhythm, photoperiodicity and body color change. Tmt opsins belong to the class A of the G protein-coupled receptors and show strong homology to the vertebrate visual opsins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESAttQKAEKEVTRMVILMVLGFMLAWTPYAVVA 72
Cdd:cd15086   163 SYIICLFIFCLLLPFLVMVYCYGRLLYAIKQVGKINKSTA--RKREQHVLLMVVTMVICYLLCWLPYGVMA 231

retinal pigment epithelium-derived rhodopsin homolog, member of the class A family of seven-transmembrane G protein-coupled receptors; Peropsin, also known as a retinal pigment epithelium-derived rhodopsin homolog (RRH), is a visual pigment-like protein found exclusively in the apical microvilli of the retinal pigment epithelium. Peropsin belongs to the type 2 opsin family of the class A G-protein coupled receptors. Peropsin presumably plays a physiological role in the retinal pigment epithelium either by detecting light directly or monitoring the levels of retinoids, the primary light absorber in visual perception, or other pigment-related compounds in the eye.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQ--KAEKEVTRMVILMVLGFMLAWTPYAVV 71
Cdd:cd15073   163 SYTMSVIVVNFIVPLAVMFYCYYNVSRFVKKVLASDCLESVNIdwTDQNDVTKMSVIMIVMFLVAWSPYSIV 234

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQ------KAEKEVTRMVILMVLGFMLAWTPYAVVAF 73
Cdd:cd00637   160 AYTIFLFVLLFLLPLLVIIVCYVRIFRKLRRHRRRIRSSSSNSsrrrrrRRERKVTKTLLIVVVVFLLCWLPYFILLL 237

non-visual parietopsins, member of the class A family of seven-transmembrane G protein-coupled receptors; Parietopsin is a non-visual green light-sensitive opsin that was initially identified in the parietal eye of lizards. 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. Parietopsin belongs to the class A of the G protein-coupled receptors and shows strong homology to the vertebrate visual opsins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLICKVRE--AAAQQQESATTQKAEKEVTRMVILMVLGFMLAWTPYAVVA 72
Cdd:cd15085   163 SYLILYFLMCFVIPVAIIGFSYGNVLRSLHKlnKKIEQQGGKNCPEEEERAVIMVLAMVIAFLICWLPYTVFA 235

opioid receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes opioid receptors, somatostatin receptors, melanin-concentrating hormone receptors (MCHRs), and neuropeptides B/W receptors. Together they constitute the opioid receptor-like family, members of the class A G-protein coupled receptors. Opioid receptors are coupled to inhibitory G proteins of the G(i/o) family and are involved in regulating a variety of physiological functions such as pain, addiction, mood, stress, epileptic seizure, and obesity, among many others. G protein-coupled somatostatin receptors (SSTRs), which display strong sequence similarity with opioid receptors, binds somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. MCHR binds melanin concentrating hormone and is presumably involved in the neuronal regulation of food intake. Despite strong homology with somatostatin receptors, MCHR does not appear to bind somatostatin. Neuropeptides B/W receptors are primarily expressed in the CNS and stimulate the cortisol secretion by activating the adenylate cyclase- and the phospholipase C-dependent signaling pathways.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2374221995   4 VLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATT-QKAEKEVTRMVILMVLGFMLAWTPYAV 70
Cdd:cd14970   166 TIYTFVLGFAVPLLVITVCYSLIIRRLRSSRNLSTSGAREkRRARRKVTRLVLVVVAVFVVCWLPFHV 233

melanin concentrating hormone receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Melanin-concentrating hormone receptor (MCHR) binds melanin concentrating hormone and is presumably involved in the neuronal regulation of food intake and energy homeostasis. Despite strong homology with somatostatin receptors, MCHR does not appear to bind somatostatin. Two MCHRs have been characterized in vertebrates, MCHR1 and MCHR2. MCHR1 is expressed in all mammals, whereas MCHR2 is only expressed in the higher order mammals, such as humans, primates, and dogs, and is not found in rodents. 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2374221995   3 YVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAeKEVTRMVILMVLGFMLAWTPYAVVA 72
Cdd:cd15088   164 FTIYHFILGFAVPLVVITVCYILILHRLARGVAPGNQSHGSSRT-KRVTKMVILIVVVFIVCWLPFHVVQ 232

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2374221995   8 FVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAEKE--------VTRMVILMVLGFMLAWTPYAVVAF 73
Cdd:cd15203   172 LVLQFVIPLLIISFCYFRISLKLRKRVKKKRGKRTLSSRRRRselrrkrrTNRLLIAMVVVFAVCWLPLNLFNL 245

encephalopsins (opsin-3), member of the class A family of seven-transmembrane G protein-coupled receptors; Encephalopsin, also called Opsin-3 or Panopsin, is a mammalian extra-retinal opsin that is highly localized in the brain. It is thought to play a role in encephalic photoreception. Encephalopsin belongs to the class A of the G protein-coupled receptors and shows strong homology to the vertebrate visual opsins.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAA----QQQESATTQKAEKEVTRMVILMVLGFMLAWTPYAVVAF 73
Cdd:cd15078   160 SFVLLFFLGCLVVPLGIMAYCYGHILYEIRMLRSvedlQTFQVIKILKYEKKVAKMCLLMISTFLICWMPYAVVSL 235

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2374221995   3 YVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQ-------QQESATTQKAEKEVTRMVILMVLGFMLAWTPYAVV 71
Cdd:cd14993   170 YNVALFVVLYVLPLLIISVAYSLIGRRLWRRKPPgdrgsanSTSSRRILRSKKKVARMLIVVVVLFALSWLPYYVL 245

urotensin-II receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The urotensin-II receptor (UII-R, also known as the hypocretin receptor) is a member of the class A rhodopsin-like G-protein coupled receptors, which binds the peptide hormone urotensin-II. Urotensin II (UII) is a vasoactive somatostatin-like or cortistatin-like peptide hormone. However, despite the apparent structural similarity to these peptide hormones, they are not homologous to UII. Urotensin II was first identified in fish spinal cord, but later found in humans and other mammals. In fish, UII is secreted at the back part of the spinal cord, in a neurosecretory centre called uroneurapophysa, and is involved in the regulation of the renal and cardiovascular systems. In mammals, urotensin II is the most potent mammalian vasoconstrictor identified to date and causes contraction of arterial blood vessels, including the thoracic aorta. The urotensin II receptor is a rhodopsin-like G-protein coupled receptor, which binds urotensin-II. The receptor was previously known as GPR14, or sensory epithelial neuropeptide-like receptor (SENR). The UII receptor is expressed in the CNS (cerebellum and spinal cord), skeletal muscle, pancreas, heart, endothelium and vascular smooth muscle. It is involved in the pathophysiological control of cardiovascular function and may also influence CNS and endocrine functions. Binding of urotensin II to the receptor leads to activation of phospholipase C, through coupling to G(q/11) family proteins. The resulting increase in intracellular calcium may cause the contraction of vascular smooth muscle.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2374221995   3 YVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAEKEVTRMVILMVLGFMLAWTPYAV 70
Cdd:cd14999   164 YLTLLFSTSIVIPGLVIGYLYIRLARKYWLSQAAASNSSRKRLPKQKVLKMIFTIVLVFWACFLPFWI 231

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2374221995   3 YVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAEKEVTRMVILMVLGFMLAWTP 67
Cdd:cd14971   165 FALCTFLFGYLLPLLLICVCYAAMLRHLWRVAVRPVLSEGSRRAKRKVTRLVLVVVVLFAACWGP 229

galanin receptor subtypes 2 and 3, 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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2374221995   8 FVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAEKEVTRMVILMVLGFMLAWTPYAVV 71
Cdd:cd15097   168 FAFGYLIPVLVVSLSYTRTIKYLWTAVDPLEAMSESKRAKRKVTKMIIIVTALFCLCWLPHHVV 231

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2374221995   4 VLYMFVIHFIIPVVVIFFSY----GRLICKVREAAAQQQESATTQ-KAEKEVTRMVILMVLGFMLAWTPYAV 70
Cdd:cd15927   171 VLLRFLVYYLIPLLIIGVFYvlmaRHLIRSTRNIGSGQNQAAQRQiEARKKVAKTVLAFVVLFAVCWLPRHV 242

somatostatin receptor type 5, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled somatostatin receptors (SSTRs) are composed of five distinct subtypes (SSTR1-5) that display strong sequence similarity with opioid receptors. All five receptor subtypes bind the natural somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. SSTR5 is coupled to inward rectifying K channels and phospholipase C, and plays critical roles in growth hormone and insulin secretion. SSTR5 acts as a negative regulator of PDX-1 (pancreatic and duodenal homeobox-1) expression, which is a conserved homeodomain-containing beta cell-specific transcription factor essentially involved in pancreatic development, among many other functions.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQeSATTQKAEKEVTRMVILMVLGFMLAWTPYAVV 71
Cdd:cd15974   161 AFIIYTAVLGFFGPLLVICLCYLLIVIKVKSSGLRVG-STKRRKSERKVTRMVVIIVVVFVFCWLPFYML 229

somatostatin receptor type 3, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled somatostatin receptors (SSTRs) are composed of five distinct subtypes (SSTR1-5) that display strong sequence similarity with opioid receptors. All five receptor subtypes bind the natural somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. SSTR3 is coupled to inward rectifying potassium channels. SSTR3 plays critical roles in growth hormone secretion, endothelial cell cycle arrest and apoptosis. Furthermore, SSTR3 is expressed in the normal human pituitary and in nearly half of pituitary growth hormone adenomas.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2374221995   3 YVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATT-QKAEKEVTRMVILMVLGFMLAWTPYAVV 71
Cdd:cd15972   162 FIIYTATLGFFCPLLVICLCYLLIVVKVRSSGRRVRATSTKrRGSERKVTRMVVIVVAAFVLCWLPFYAL 231

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLI----CKVREAaaqqqeSATTQKAEKEVTRMVILMVLGFMLAWTPYAVVA 72
Cdd:cd15098   167 VYVVCTFVFGYLLPLLLITFCYAKVLnhlhKKLKNM------SKKSERSKKKTAQTVLVVVVVFGISWLPHHIIH 235

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2374221995   3 YVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAekevTRMVILMVLGFMLAWTPYAVV 71
Cdd:cd14982   165 IVLIALVVGFLIPLLIILVCYSLIIRALRRRSKQSQKSVRKRKA----LRMILIVLAVFLVCFLPYHVT 229

neuropeptide B/W receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropeptide B/W receptor 1 and 2 are members of the class A G-protein coupled receptors that bind the neuropeptides B and W, respectively. NPBWR1 (previously known as GPR7) is expressed predominantly in cerebellum and frontal cortex, while NPBWR2 (previously known as GPR8) is located mostly in the frontal cortex and is present in human, but not in rat and mice. These receptors are suggested to be involved in the regulation of food intake, neuroendocrine function, and modulation of inflammatory pain, among many 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2374221995   5 LYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATtQKAEKEVTRMVILMVLGFMLAWTPY 68
Cdd:cd15087   169 IYTLVLGFAIPVSTICILYTMMLYKLRNMRLNSNAKAL-DKAKKKVTLMVLVVLAVCLFCWTPF 231

G protein-coupled receptor 151, member of the class A family of seven-transmembrane G protein-coupled receptors; G-protein coupled receptor 151 (GRP151) is an orphan receptor of unknown function. Its expression is conserved in habenular axonal projections of vertebrates and may be a promising novel target for psychiatric drug development. GPR151 shows high sequence similarity with galanin receptors (GALR). GPR151 is a member of the class A rhodopsin-like GPCRs, which represent a widespread protein family that includes the light-sensitive rhodopsin as well as receptors for biogenic amines, lipids, nucleotides, odorants, peptide hormones, and a variety of other ligands. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2374221995   3 YVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESaTTQKAEKEVTRMVILMVLGFMLAWTP 67
Cdd:cd15002   165 FVKLYPLFVFCLPLTFALFYFWRAYGQCQRRGTKTQNL-RNQIRSRKLTHMLLSVVLAFTILWLP 228

complement component 5a anaphylatoxin chemotactic receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The anaphylatoxin receptors are a group of G-protein coupled receptors which bind anaphylatoxins; members of this group include C3a receptors and C5a receptors. Anaphylatoxins are also known as complement peptides (C3a, C4a and C5a) that are produced from the activation of the complement system cascade. These complement anaphylatoxins can trigger degranulation of endothelial cells, mast cells, or phagocytes, which induce a local inflammatory response and stimulate smooth muscle cell contraction, histamine release, and increased vascular permeability. They are potent mediators involved in chemotaxis, inflammation, and generation of cytotoxic oxygen-derived free radicals. In humans, a single receptor for C3a (C3AR1) and two receptors for C5a (C5AR1 and C5AR2, also known as C5L2 or GPR77) have been identified, but there is no known receptor for C4a.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2374221995   8 FVIHFIIPVVVIFFSYGRLICKVREAAAQQQesattqkaeKEVTRMVILMVLGFMLAWTPYAVV 71
Cdd:cd15114   170 FLLGFLGPLVVIASCHGVLLVRTWSRRRQKS---------RRTLKVVTAVVVGFFLCWTPYHVV 224

G protein-coupled receptor 150, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR150 is an orphan receptor closely related to the oxytocin and vasopressin receptors. Its endogenous ligand is not known. These receptors share a significant amino acid sequence similarity, suggesting that they have a common evolutionary origin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2374221995   3 YVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQ-----------QQESATTQ------KAEKEVTRMVILMVLGFMLAW 65
Cdd:cd15198   168 YATYEAVVGFVAPVVILGVCYGRLLLKWWERANQapgakkpwkkpSKSHLRATapsalpRAKVKTLKMTLVIALLFVGCS 247

                  ....*.
gi 2374221995  66 TPYAVV 71
Cdd:cd15198   248 LPYFIA 253

somatostatin-like receptor for allatostatin C, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled somatostatin receptors (SSTRs) are composed of five distinct subtypes (SSTR1-5) that display strong sequence similarity with opioid receptors. All five receptor subtypes bind the natural somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. In Drosophila melanogaster and other insects, a 15-amino-acid peptide named allatostatin C(AstC) binds the somatostatin-like receptors. Two AstC receptors have been identified in Drosophila with strong sequence homology to human somatostatin and opioid receptors.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQeSATTQKAEKEVTRMVILMVLGFMLAWTPY 68
Cdd:cd15094   164 AFTLYTFLLGFAIPLLLISVFYTLVILRLRTVGPKNK-SKEKRRSHRKVTRLVLTVISVYIICWLPY 229

opioid receptor subtype mu, member of the class A family of seven-transmembrane G protein-coupled receptors; The mu-opioid receptor binds endogenous opioids such as beta-endorphin and endomorphin. The opioid receptor family is composed of four major subtypes: mu (MOP), delta (DOP), kappa (KOP) opioid receptors, and the nociceptin/orphanin FQ peptide receptor (NOP). They are distributed widely in the central nervous system and respond to classic alkaloid opiates, such as morphine and heroin, as well as to endogenous peptide ligands, which include dynorphins, enkephalins, endorphins, endomorphins, and nociceptin. Opioid receptors are coupled to inhibitory G proteins of the G(i/o) family and involved in regulating a variety of physiological functions such as pain, addiction, mood, stress, epileptic seizure, and obesity, among many others.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2374221995   7 MFVIHFIIPVVVIFFSYGRLICKVReAAAQQQESATTQKAEKEVTRMVILMVLGFMLAWTP 67
Cdd:cd15090   168 VFIFAFIMPVLIITVCYGLMILRLK-SVRMLSGSKEKDRNLRRITRMVLVVVAVFIVCWTP 227

proton-sensing G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Proton/pH-sensing G-protein coupled receptors sense pH of 7.6 to 6.0. They mediate a variety of biological activities in neutral and mildly acidic pH conditions, whereas the acid-sensing ionotropic ion channels typically sense strong acidic pH. The proton/pH-sensing receptor family includes the G2 accumulation receptor (G2A, also known as GPR132), the T cell death associated gene-8 (TDAG8, GPR65) receptor, ovarian cancer G-protein receptor 1 (OGR-1, GPR68), and G-protein-coupled receptor 4 (GPR4).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLICKVReaaaqqqESATTQKAEK-EVTRMVILMVLGFMLAWTPYAVVAF 73
Cdd:cd15160   163 SYNYARFLVGFLIPLSLILFFYRRVLRAVR-------QSPSLEREEKrKIIGLLLSIVVIFLLCFLPYHVVLL 228

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2374221995  12 FIIPVVVIFFSYGRLICKVREAAAQQQESattQKAEKEVTRMVILMVLGFMLAWTPYAVVAF 73
Cdd:cd14985   174 FVLPLLIILTCYFHIARSLRKRYERTGKN---GRKRRKSLKIIFALVVAFLVCWLPFHFFKF 232

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESAT-----TQKAEKEVTRMVILMVLGFMLAWTPYAVV 71
Cdd:cd14997   167 AYILSTIVVFFVVPLAILSGLYSVICRRLVGHPALESRRADaanrhTLRSRRQVVYMLITVVVLFFVCLLPFRVV 241

neuropeptide Y receptor type 2, 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2374221995   3 YVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAEKEVTRMVILMVLGFMLAWTPYAV 70
Cdd:cd15399   168 YSVSMLLIQYVLPLAIISYAYIRIWTKLKNHVSPGGGNDHYHQRRRKTTKMLVCVVVVFAVSWLPFHA 235

succinate receptor 1, member of the class A family of seven-transmembrane G protein-coupled receptors; Succinate receptor (SUCNR1) GPR91 exclusively couples to G(i) protein to inhibit cAMP production and also activates PLC-beta to increase intracellular calcium concentrations in an inositol phosphate dependent mechanism. Succinate, an intermediate molecule of the citric cycle, is shown to cause cardiac hypertrophy via GPR91 activation. Furthermore, succinate-induced GPR91 activation is involved in the regulation of renin-angiotensin system and is suggested to play an important role in the development of renovascular hypertension and diabetic nephropathy. SUCNR1 belongs to the class A GPCR superfamily and is phylogenetically related to the purinergic P2Y1-like receptor subfamily, whose members are coupled to G(q) protein to activate phospholipase C (PLC).

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2374221995   3 YVLYMFVIHFIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAekevTRMVILMVLGFMLAWTPYAV 70
Cdd:cd15378   164 YSLFLTVTGFLIPLCVMCFFYYKIALFLKNRNRQLANATSFEKP----LTLVILAVVIFSVLFTPYHV 227

P2Y purinoceptors 1, 2, 4, 6, 11 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; The P2Y receptor family is composed of eight subtypes, which are activated by naturally occurring extracellular nucleotides such as ATP, ADP, UTP, UDP, and UDP-glucose. These eight receptors are ubiquitous in human tissues and can be further classified into two subfamilies based on sequence homology and second messenger coupling: a subfamily of five P2Y1-like receptors (P2Y1, P2Y2, P2Y4, P2Y6, and P2Y11Rs) that are coupled to G(q) protein to activate phospholipase C (PLC) and a second subfamily of three P2Y12-like receptors (P2Y12, P2YR13, and P2Y14Rs) that are coupled to G(i) protein to inhibit adenylate cyclase. Several cloned subtypes, such as P2Y3, P2Y5, and P2Y7-10, are not functional mammalian nucleotide receptors. The native agonists for P2Y receptors are: ATP (P2Y2, P2Y12), ADP (P2Y1, P2Y12, and P2Y13), UTP (P2Y2, P2Y4), UDP (P2Y6, P2Y14), and UDP-glucose (P2Y14). This cluster only includes P2Y1-like receptors as well as other closely related orphan receptors, such as GPR91 (a succinate receptor) and GPR80/GPR99 (an alpha-ketoglutarate receptor).

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2374221995   2 SYVLYMFVIH---FIIPVVVIFFSYGRLICKVREAAAQQQESATTQKAekevTRMVILMVLGFMLAWTPYAV 70
Cdd:cd15168   161 DYVIYSMVLTglgFLLPLLIILACYGLIVRALIRKLGEGVTSALRRKS----IRLVIIVLALFAVCFLPFHV 228

complement component 3a anaphylatoxin chemotactic receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The anaphylatoxin receptors are a group of G-protein coupled receptors which bind anaphylatoxins; members of this group include C3a receptors and C5a receptors. Anaphylatoxins are also known as complement peptides (C3a, C4a and C5a) that are produced from the activation of the complement system cascade. These complement anaphylatoxins can trigger degranulation of endothelial cells, mast cells, or phagocytes, which induce a local inflammatory response and stimulate smooth muscle cell contraction, histamine release, and increased vascular permeability. They are potent mediators involved in chemotaxis, inflammation, and generation of cytotoxic oxygen-derived free radicals. In humans, a single receptor for C3a (C3AR1) and two receptors for C5a (C5AR1 and C5AR2, also known as C5L2 or GPR77) have been identified, but there is no known receptor for C4a.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2374221995   8 FVIHFIIPVVVIFFSYGRLICKVReaaaqqqeSATTQKAEKEVTRMVILMVLGFMLAWTPYAVV 71
Cdd:cd15115   162 AVFGFLLPLLIIAACYSFIAFRMQ--------RGRFAKSQSKTFRVIIAVVVAFFVCWAPYHII 217

nociceptin/orphanin FQ peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The nociceptin (NOP) receptor binds nociceptin or orphanin FQ, a 17 amino acid endogenous neuropeptide. The NOP receptor is involved in the modulation of various brain activities including instinctive and emotional behaviors. The opioid receptor family is composed of four major subtypes: mu (MOP), delta (DOP), kappa (KOP) opioid receptors, and the nociceptin/orphanin FQ peptide receptor (NOP). They are distributed widely in the central nervous system and respond to classic alkaloid opiates, such as morphine and heroin, as well as to endogenous peptide ligands, which include dynorphins, enkephalins, endorphins, endomorphins, and nociceptin. Opioid receptors are coupled to inhibitory G proteins of the G(i/o) family and involved in regulating a variety of physiological functions such as pain, addiction, mood, stress, epileptic seizure, and obesity, among many others.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2374221995   7 MFVIHFIIPVVVIFFSYGRLICKVREAAAQQQeSATTQKAEKEVTRMVILMVLGFMLAWTPYAVVAF 73
Cdd:cd15092   168 VFLFSFIIPVLIISVCYSLMIRRLRGVRLLSG-SKEKDRNLRRITRLVLVVVAVFVGCWTPIQIFVL 233

neuropeptide Y receptor-like found in insect and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes a novel G protein-coupled receptor (also known as PR4 receptor) from Drosophila melanogaster, which can be activated by the members of the neuropeptide Y (NPY) family, including NPY, peptide YY (PYY) and pancreatic polypeptide (PP), when expressed in Xenopus oocytes. These homologous peptides of 36-amino acids in length contain a hairpin-like structural motif, which referred to as the pancreatic polypeptide fold, and function as gastrointestinal hormones and neurotransmitters. The PR4 receptor also shares strong sequence homology to the mammalian tachykinin receptors (NK1R, NK2R, and NK3R), whose endogenous ligands are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), respectively. The tachykinins function as excitatory transmitters on neurons and cells in the gastrointestinal tract.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2374221995   3 YVLYMFVIHFIIPVVVIFFSYGRLICKV--REAAAQQQESATTQKAE--KEVTRMVILMVLGFMLAWTPYAVV 71
Cdd:cd15392   166 YSLVLMILQYFVPLAVLVFTYTRIGIVVwaKRTPGEAENNRDQRMAEskRKLVKMMITVVAIFALCWLPLNIL 238

muscarinic acetylcholine receptor subfamily, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of mAChRs by agonist (acetylcholine) leads to a variety of biochemical and electrophysiological responses. In general, the exact nature of these responses and the subsequent physiological effects mainly depend on the molecular and pharmacological identity of the activated receptor subtype(s). All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2374221995   9 VIHFIIPVVVIFFSYGRLickVREAAAqqqesattqkaEKEVTRMVILMVLGFMLAWTPYAVVA 72
Cdd:cd15049   169 IAAFYLPVLVMTILYWRI---YRETAR-----------ERKAARTLSAILLAFIITWTPYNILV 218

retinal G protein coupled receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents the retinal G-protein coupled receptor (RGR) found exclusively in retinal pigment epithelium (RPE) and Muller cells. RGR is a member of the class A rhodopsin-like receptor family. As with other opsins, RGR binds all-trans retinal and contains a conserved lysine reside on the seventh helix. RGR functions as a photoisomerase to catalyze the conversion of all-trans-retinal to 11-cis-retinal. Two mutations in RGR gene are found in patients with retinitis pigmentosa, indicating that RGR is essential to the visual process.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2374221995   2 SYVLYMFVIHFIIPVVVIFFSYgrlickvreaaaqqQESATTQKAEKEVTRMVILMVLGFMLAWTPYAVVAF 73
Cdd:cd15072   159 SYLFTMAFFNFILPLFILLTSY--------------SSIEQKLKKEGHLRFNTGLPLLTLLICWGPYAILAL 216