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 665389612   57 GNSVSIYVLTR-KRMRCTTNIYLTALAITDIAYLTCQLILSLQHYDYPKYhfklyWQLyGYFvwLCDSFGYI-------S 128
Cdd:pfam00001   1 GNLLVILVILRnKKLRTPTNIFLLNLAVADLLFSLLTLPFWLVYYLNHGD-----WPF-GSA--LCKIVGALfvvngyaS 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 665389612  129 IYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLSTL 174
Cdd:pfam00001  73 ILLLTAISIDRYLAIVHPLRYKRRRTPRRAKVLILVIWVLALLLSL 118

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 665389612  45 ILVPCVFVIGLLGNSVSIYVLTR-KRMRCTTNIYLTALAITDIAYLTCQLILSLQHYDYPKYHF-KLYWQLYGYfvwLCD 122
Cdd:cd00637    3 VLYILIFVVGLVGNLLVILVILRnRRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRWWFgDALCKLLGF---LQS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612 123 SFGYISIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLstlstafehtitigtrqiddayqpcnqtvan 202
Cdd:cd00637   80 VSLLASILTLTAISVDRYLAIVHPLRYRRRFTRRRAKLLIALIWLLSLL------------------------------- 128

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612 203 ispmppppvavtpplatpplptpatiwqspdsamesttsgssnqlvdwgsgsgdgepeniprhrrhwqssgfVTLPTLrk 282
Cdd:cd00637  129 ------------------------------------------------------------------------LALPPL-- 134

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612 283 tleeqdqkvadaaqrsgvtesllqlwrrkrsaenhninntdaFAFNVTEYcqnvtYYNHGLSELGYDELYSYLWNLFTLL 362
Cdd:cd00637  135 ------------------------------------------LGWGVYDY-----GGYCCCCLCWPDLTLSKAYTIFLFV 167

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612 363 VFVVFPLLLLATFNS-ILILLVHRSKNLRGDLTNASSIRRTKRksnsglkgsvsqENRVTITLIAVVLMFIVCQLPWAIY 441
Cdd:cd00637  168 LLFLLPLLVIIVCYVrIFRKLRRHRRRIRSSSSNSSRRRRRRR------------ERKVTKTLLIVVVVFLLCWLPYFIL 235

                        410       420       430       440
                 ....*....|....*....|....*....|....*....|
gi 665389612 442 LIVNQYMEIQIGTQVVAGNVCNLLASLHAASNFFLYCVLS 481
Cdd:cd00637  236 LLLDVFGPDPSPLPRILYFLALLLAYLNSAINPIIYAFFN 275

thyrotropin-releasing hormone receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; TRH-R is a member of the class A rhodopsin-like G protein-coupled receptors, which binds the tripeptide thyrotropin releasing hormone. The TRH-R activates phosphoinositide metabolism through a pertussis-toxin-insensitive G-protein, the G(q)/G(11) class. TRH stimulates the synthesis and release of thyroid-stimulating hormone in the anterior pituitary. TRH is produced in many other tissues, especially within the nervous system, where it appears to act as a neurotransmitter/neuromodulator. It also stimulates the synthesis and release of prolactin. In the CNS, TRH stimulates a number of behavioral and pharmacological actions, including increased turnover of catecholamines in the nucleus accumbens. There are two thyrotropin-releasing hormone receptors in some mammals, thyrotropin-releasing hormone receptor 1 (TRH1) which has been found in a number of species including rat, mouse, and human and thyrotropin-releasing hormone receptor 2 (TRH2) which has, only been found in rodents. These TRH receptors are found in high levels in the anterior pituitary, and are also found in the retina and in certain areas of the brain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612  41 VVQRILVPCVFVIGLLGNS-VSIYVLTRKRMRCTTNIYLTALAITDIAYLTCQLILSLQHYDYPKYHFklywqLYGYFVW 119
Cdd:cd14995    1 VVATFLVLLICGVGIVGNImVVLVVLRTRHMRTPTNCYLVSLAVADLMVLVAAGLPNEIESLLGPDSW-----IYGYAGC 75

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 665389612 120 LCDSF-GYISIYIAVC----FTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLL 171
Cdd:cd14995   76 LLITYlQYLGINASSLsitaFTIERYIAICHPMKAQFICTVSRAKKIICFVWIFTSL 132

allatostatin-A receptor in insects, member of the class A family of seven-transmembrane G protein-coupled receptors; The G protein-coupled AstA receptor 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 665389612  45 ILVPCVF----VIGLLGNSVSIYV-LTRKRMRCTTNIYLTALAITDIAYLTcqLILSLQHYDY--PKYHFKLYW-QLYGY 116
Cdd:cd15096    1 IVVPVIFglifIVGLIGNSLVILVvLSNQQMRSTTNILILNLAVADLLFVV--FCVPFTATDYvlPTWPFGDVWcKIVQY 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612 117 FVWLCdsfGYISIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLSTLSTAFEHTITIGTrQIDDAYQPC 196
Cdd:cd15096   79 LVYVT---AYASVYTLVLMSLDRYLAVVHPITSMSIRTERNTLIAIVGIWIVILVANIPVLFLHGVVSYG-FSSEAYSYC 154

                 .
gi 665389612 197 N 197
Cdd:cd15096  155 T 155

neuropeptide capa receptor and similar invertebrate proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; CapaR is a G-protein coupled receptor for the Drosophila melanogaster capa neuropeptides (Drm-capa-1 and -2), which act on the Malpighian tubules to increase fluid transport. The capa peptides are evolutionarily related to vertebrate Neuromedin U neuropeptide and contain a C-terminal FPRXamide motif. CapaR regulates fluid homeostasis through its ligands, thereby acts as a desiccation stress-responsive receptor. CapaR undergoes desensitization, with internalization mediated by beta-arrestin-2.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612  50 VFVIGLLGNSVSIYVLTRKR-MRCTTNIYLTALAITDIAYLtcqlILSLqhydypKYHFKLYWQLYGYF---------VW 119
Cdd:cd15134   10 IFVTGVVGNLCTCIVIARNRsMHTATNYYLFSLAVSDLLLL----ILGL------PFELYTIWQQYPWVfgevfcklrAF 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665389612 120 LCDSFGYISIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLSTLSTAFEHTI 182
Cdd:cd15134   80 LSEMSSYASVLTITAFSVERYLAICHPLRSHTMSKLSRAIRIIIAIWIIAFVCALPFAIQTRI 142

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 665389612  50 VFVIGLLGNSVSIYVLTR-KRMRCTTNIYLTALAITDIAY-LTCQLILSLQHYdypkyhFKLYWqlYGYFvwLCDSFGYI 127
Cdd:cd14993   10 VFLLALVGNSLVIAVVLRnKHMRTVTNYFLVNLAVADLLVsLFCMPLTLLENV------YRPWV--FGEV--LCKAVPYL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 665389612 128 -------SIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAV 165
Cdd:cd14993   80 qgvsvsaSVLTLVAISIDRYLAICYPLKARRVSTKRRARIIIVAI 124

Serpentine type 7TM GPCR chemoreceptor Srw; Chemoreception is mediated in Caenorhabditis elegans by members of the seven-transmembrane G-protein-coupled receptor class (7TM GPCRs) of proteins which are of the serpentine type. Srw is a solo family amongst the superfamilies of chemoreceptors. Chemoperception is one of the central senses of soil nematodes like C. elegans which are otherwise 'blind' and 'deaf'. The genes encoding Srw do not appear to be under as strong an adaptive evolutionary pressure as those of Srz.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612   52 VIGLLGNSVSIYVLTRKRMR-CTTNIYLTALAITDIAYLTCQLILSLQHYDY---------PKYHFKLYwqLYGYFVWLC 121
Cdd:pfam10324   8 FIGFIINIFHLIILTRKSMRtSSINIIMIGIAICDIITMLLTIYNFIPEFIIsyensecipPDSYLKVL--LDWILESLQ 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 665389612  122 DSFGYISIYIAVCFTIERFIAIRYPL--KRQTFCTESLAKKVIAAVAIFCLLSTLSTAFEHTIT 183
Cdd:pfam10324  86 DYSRRCSTWLGVFMALIRTLVVKNPMsnKIQKLSKPKFGLIIIIIVFILSLPISIFYYFRYEIV 149

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 665389612  50 VFVIGLLGNSVSIYVLTR-KRMRCTTNIYLTALAITDIAYLTCQLILSLQHYDYPKYHFKLYW-QLYGYFVWLCdsfGYI 127
Cdd:cd14971   10 IFLLGLVGNSLVILVVARnKPMRSTTNLFILNLAVADLTFLLFCVPFTATIYPLPGWVFGDFMcKFVHYFQQVS---MHA 86

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 665389612 128 SIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLSTLSTAFEHTITigtrqiddAYQPCNQTV 200
Cdd:cd14971   87 SIFTLVAMSLDRFLAVVYPLRSLHIRTPRNALAASGCIWVVSLAVAAPVLALHRLR--------NYTPGNRTV 151

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 665389612  50 VFVIGLLGN-SVSIYVLTRKRMRCTTNIYLTALAITDIAYLTCQLILSLQhydypKYHFKLYWQLyGYFvwLCDSFGYIS 128
Cdd:cd14997   10 IFVVGVLGNvLVGIVVWKNKDMRTPTNIFLVNLSVADLLVLLVCMPVALV-----ETWAREPWLL-GEF--MCKLVPFVE 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 665389612 129 IYIA-------VCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLSTLSTAF 178
Cdd:cd14997   82 LTVAhasvltiLAISFERYYAICHPLQAKYVCTKRRALVIIALIWLLALLTSSPVLF 138

cysteinyl leukotriene receptor 1, member of the class A family of seven-transmembrane G protein-coupled receptors; Cysteinyl leukotrienes (LTC4, LTD4, and LTE4) are the most potent inflammatory lipid mediators that play an important role in human asthma. They are synthesized in the leucocytes (cells of immune system) from arachidonic acid by the actions of 5-lipoxygenase and induce bronchial constriction through G protein-coupled receptors, CysLTR1 and CysLTR2. Activation of CysLTR1 by LTD4 induces airway smooth muscle contraction and proliferation, eosinophil migration, and damage to the lung tissue. They belong to the class A GPCR superfamily, which all 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 665389612  50 VFVIGLLGNSVSIYVLTR-KRMRCTTNIYLTALAITDiayLTCQLILSLQHYDYPKyhfKLYWqLYGYFVWLCDSFG--- 125
Cdd:cd15158   10 ITVFGLVGNGFALYVLIKtYRQKSAFHIYMLNLAVSD---LLCVCTLPLRVVYYVH---KGQW-LFGDFLCRISSYAlyv 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 665389612 126 --YISIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLST 173
Cdd:cd15158   83 nlYCSIYFMTAMSFTRFLAIVFPVQNLNLVTVKKARIVCVGIWIFVTLTS 132

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612  50 VFVIGLLGNSVSIYVLTR-KRMRCTTNIYLTALAITDIayLTCQLILSLQhydyPKYHFKLYWQLYGyfvWLCDSFGY-- 126
Cdd:cd15203   10 IIVLGVVGNLLVIYVVLRnKSMQTVTNIFILNLAVSDL--LLCLVSLPFT----LIYTLTKNWPFGS---ILCKLVPSlq 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 665389612 127 -ISIYIaVCFT-----IERFIAIRYPLKRQTFCTesLAKKVIAAVAIFCLLSTL 174
Cdd:cd15203   81 gVSIFV-STLTltaiaIDRYQLIVYPTRPRMSKR--HALLIIALIWILSLLLSL 131

neuromedin U receptor subtype 1, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuromedin U (NMU) is a highly conserved neuropeptide with a common C-terminal heptapeptide sequence (FLFRPRN-amide) found at the highest levels in the gastrointestinal tract and pituitary gland of mammals. Disruption or replacement of residues in the conserved heptapeptide region can result in the reduced ability of NMU to stimulate smooth-muscle contraction. Two G-protein coupled receptor subtypes, NMU-R1 and NMU-R2, with a distinct expression pattern, have been identified to bind NMU. NMU-R1 is expressed primarily in the peripheral nervous system, while NMU-R2 is mainly found in the central nervous system. Neuromedin S, a 36 amino-acid neuropeptide that shares a conserved C-terminal heptapeptide sequence with NMU, is a highly potent and selective NMU-R2 agonist. Pharmacological studies have shown that both NMU and NMS inhibit food intake and reduce body weight, and that NMU increases energy expenditure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612  50 VFVIGLLGNSVSIYVLTRKR-MRCTTNIYLTALAITDIAYLTCQLILSLqhYD-YPKYHFkLYWQLYGYF-VWLCDSFGY 126
Cdd:cd15358   10 IFVVGAVGNGLTCIVILRHKvMRTPTNYYLFSLAVSDLLVLLLGMPLEL--YEmWSNYPF-LLGAGGCYFkTLLFETVCF 86

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 665389612 127 ISIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLSTLSTAFEHTI 182
Cdd:cd15358   87 ASILNVTALSVERYIAVVHPLKAKYVVTRTHAKRVIGAVWVVSILCSIPNTSLHGI 142

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 665389612  45 ILVPCVFVIGLLGNSVSIYVLTR-KRMRCTTNIYLTALAITDiaYLTCQLILSLQHYD--YPKYHF-KLYWQLYGYFVWL 120
Cdd:cd15083    5 IFILIIGLIGVVGNGLVIYAFCRfKSLRTPANYLIINLAISD--FLMCILNCPLMVISsfSGRWIFgKTGCDMYGFSGGL 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 665389612 121 cdsFGYISIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLSTLSTAF 178
Cdd:cd15083   83 ---FGIMSINTLAAIAVDRYLVITRPMKASVRISHRRALIVIAVVWLYSLLWVLPPLF 137

cholecystokinin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Cholecystokinin receptors (CCK-AR and CCK-BR) are a group of G-protein coupled receptors which bind the peptide hormones cholecystokinin (CCK) or gastrin. CCK, which facilitates digestion in the small intestine, and gastrin, a major regulator of gastric acid secretion, are highly similar peptides. Like gastrin, CCK is a naturally-occurring linear peptide that is synthesized as a preprohormone, then proteolytically cleaved to form a family of peptides with the common C-terminal sequence (Gly-Trp-Met-Asp-Phe-NH2), which is required for full biological activity. CCK-AR (type A, alimentary; also known as CCK1R) is found abundantly on pancreatic acinar cells and binds only sulfated CCK-peptides with very high affinity, whereas CCK-BR (type B, brain; also known as CCK2R), the predominant form in the brain and stomach, binds CCK or gastrin and discriminates poorly between sulfated and non-sulfated peptides. CCK is implicated in regulation of digestion, appetite control, and body weight, and is involved in neurogenesis via CCK-AR. There is some evidence to support that CCK and gastrin, via their receptors, are involved in promoting cancer development and progression, acting as growth and invasion factors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612  50 VFVIGLLGNSVSIYVLTR-KRMRCTTNIYLTALAITDIayLTCQLILSlqhydypkyhFKLYWQLYGYFVW---LCDSFG 125
Cdd:cd15206   10 IFLLAVVGNILVIVTLVQnKRMRTVTNVFLLNLAVSDL--LLAVFCMP----------FTLVGQLLRNFIFgevMCKLIP 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 665389612 126 Y-------ISIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLL 171
Cdd:cd15206   78 YfqavsvsVSTFTLVAISLERYFAICHPLKSRVWQTLSHAYKVIAGIWLLSFL 130

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612  50 VFVIGLLGNSVSIYVLTRK-RMRCTTNIYLTALAITDIAYLtcqLILSLQHYDYpkyhFKLYW---QLYGYFVWLCDSF- 124
Cdd:cd14970   10 VCVVGLTGNSLVIYVILRYsKMKTVTNIYILNLAVADELFL---LGLPFLATSY----LLGYWpfgEVMCKIVLSVDAYn 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 665389612 125 GYISIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLSTL 174
Cdd:cd14970   83 MFTSIFCLTVMSVDRYLAVVHPVKSLRFRTPRKAKLVSLCVWALSLVLGL 132

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612  45 ILVPCVFVIGLLGNSVSIYVLTRKR-MRCTTNIYLTALAITDIAYLTCQLILSLQHYDYPKYhfklywqLYGYFvwLCDS 123
Cdd:cd15927    5 ILFALIFLVGVLGNGTLILIFLRNKsMRNVPNIFILSLALGDLLLLLTCVPFTSTIYTLDSW-------PFGEF--LCKL 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 665389612 124 FGYI---SIYIAVcFT-----IERFIAIRYPLKRQTfcTESLAKKVIAAVAIF---CLLSTLSTAFEHTITI 184
Cdd:cd15927   76 SEFLkdtSIGVSV-FTltalsADRYFAIVNPMRKHR--SQATRRTLVTAASIWivsILLAIPEAIFSHVVTF 144

neuromedin U receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuromedin U (NMU) is a highly conserved neuropeptide with a common C-terminal heptapeptide sequence (FLFRPRN-amide) found at the highest levels in the gastrointestinal tract and pituitary gland of mammals. Disruption or replacement of residues in the conserved heptapeptide region can result in the reduced ability of NMU to stimulate smooth-muscle contraction. Two G-protein coupled receptor subtypes, NMU-R1 and NMU-R2, with a distinct expression pattern, have been identified to bind NMU. NMU-R1 is expressed primarily in the peripheral nervous system, while NMU-R2 is mainly found in the central nervous system. Neuromedin S, a 36 amino-acid neuropeptide that shares a conserved C-terminal heptapeptide sequence with NMU, is a highly potent and selective NMU-R2 agonist. Pharmacological studies have shown that both NMU and NMS inhibit food intake and reduce body weight, and that NMU increases energy expenditure.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612  50 VFVIGLLGNSVSIYVLTR-KRMRCTTNIYLTALAITDIAYLTCQLILSL----QHYDYPKYHFKLYWQLYgyfvwLCDSF 124
Cdd:cd15133   10 IFVVGVVGNVLTCLVIARhKAMRTPTNYYLFSLAVSDLLVLLLGMPLELyelwQNYPFLLGSGGCYFKTF-----LFETV 84

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 665389612 125 GYISIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLSTLSTAFEHTI 182
Cdd:cd15133   85 CLASILNVTALSVERYIAVVHPLAARTCSTRPRVTRVLGCVWGVSMLCALPNTSLHGI 142

somatostatin receptor type 4, 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. SSTR4 plays a critical role in mediating inflammation. Unlike other SSTRs, SSTR4 subtype is not detected in all pituitary adenomas while it is expressed in the normal human pituitary.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612  41 VVQRILVPCVFVIGLLGNSVSIYVLTR-KRMRCTTNIYLTALAITDIAYLTCQLILS----LQHYDYPKyhfklywqlyg 115
Cdd:cd15973    1 VVIQFIYALVCLVGLIGNSMVIFVILRyAKMKTATNIYILNLAIADELFMLSVPFLAasaaLQHWPFGS----------- 69

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612 116 yfvWLCDSF-------GYISIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAAVAIFCLLSTLSTAfehtITIGTRQ 188
Cdd:cd15973   70 ---AMCRTVlsvdginMFTSVFCLTVLSVDRYIAVVHPLRAARYRRPTVAKMINICVWILSLLVISPII----IFADTAT 142

                 ....*....
gi 665389612 189 IDDAYQPCN 197
Cdd:cd15973  143 RKGQAVACN 151

cholecystokinin receptor type A, member of the class A family of seven-transmembrane G protein-coupled receptors; Cholecystokinin receptors (CCK-AR and CCK-BR) are a group of G-protein coupled receptors which bind the peptide hormones cholecystokinin (CCK) or gastrin. CCK, which facilitates digestion in the small intestine, and gastrin, a major regulator of gastric acid secretion, are highly similar peptides. Like gastrin, CCK is a naturally-occurring linear peptide that is synthesized as a preprohormone, then proteolytically cleaved to form a family of peptides with the common C-terminal sequence (Gly-Trp-Met-Asp-Phe-NH2), which is required for full biological activity. CCK-AR (type A, alimentary; also known as CCK1R) is found abundantly on pancreatic acinar cells and binds only sulfated CCK-peptides with very high affinity, whereas CCK-BR (type B, brain; also known as CCK2R), the predominant form in the brain and stomach, binds CCK or gastrin and discriminates poorly between sulfated and non-sulfated peptides. CCK is implicated in regulation of digestion, appetite control, and body weight, and is involved in neurogenesis via CCK-AR. There is some evidence to support that CCK and gastrin, via their receptors, are involved in promoting cancer development and progression, acting as growth and invasion factors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 665389612  42 VQRILVPCVFVIGLLGNSVSIYVLTR-KRMRCTTNIYLTALAITDIayLTCQLILSlqhydypkyhFKLYWQLYGYFVW- 119
Cdd:cd15978    2 VRILLYSLIFLLSVLGNSLIIAVLIRnKRMRTVTNIFLLSLAVSDL--MLCLFCMP----------FTLIPNLLKDFIFg 69

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 665389612 120 --LCDSFGY-------ISIYIAVCFTIERFIAIRYPLKRQTFCTESLAKKVIAA 164
Cdd:cd15978   70 saVCKTATYfmgisvsVSTFNLVAISLERYSAICKPLKSRVWQTKSHALKVIAA 123