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 262359994   30 YVSLVVCILGTIANTLNIIVLTRREMR-SPTNAILTGLAVADLAVML----EYIPYTIHDYILTDSLPreeKLSYSWACF 104
Cdd:pfam10324   1 KVEFILSFIGFIINIFHLIILTRKSMRtSSINIIMIGIAICDIITMLltiyNFIPEFIISYENSECIP---PDSYLKVLL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  105 IKFHSIFAQVLHTISIWLTVTLAVWRYIAVGYPQKNRVWCgmrttiitittayvvcvLVVSPSLYLITAITeyvdqldmn 184
Cdd:pfam10324  78 DWILESLQDYSRRCSTWLGVFMALIRTLVVKNPMSNKIQK-----------------LSKPKFGLIIIIIV--------- 131

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  185 gkVINSIPMTqyVIDY-RNELLSartaalnatptsaplNETVWLNASTLLTSTTTAapptpspvvrNVTVYRLYHSDLAL 263
Cdd:pfam10324 132 --FILSLPIS--IFYYfRYEIVE---------------VGGIWKPPPNCAGFPPNY----------TETRYVLVVSELFT 182

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  264 HNASLQNATF-LIYSVVIKLIPCIALTILSVRLILALLEAKRRRKKLTSKpatpgasngtkspangkaadrprknsktle 342
Cdd:pfam10324 183 ANDGLLLKIFlLIDGIFSKIIPCILLPILTILLIIELRKAKKSRKNLSSS------------------------------ 232

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  343 KEKQTDRTTRMLLAVLLLFLITEFPQGIMGLLNAVLGDVFYLQCYLR-LSDLMDILALINSSINFILYCSMSKQFRTTFT 421
Cdd:pfam10324 233 SKNKSDRTTKLVIFMTISFFIAEFPLGISYIIQFFFTDNPGIRRILTyLSVIFSLLFTINSISHCFICFLMSSQYRKTAK 312

                  ....
gi 262359994  422 LLFR 425
Cdd:pfam10324 313 KLFG 316

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 262359994   30 YVSLVVCILGTIANTLNIIVLTRREMR-SPTNAILTGLAVADLAVML----EYIPYTIHDYILTDSLPreeKLSYSWACF 104
Cdd:pfam10324   1 KVEFILSFIGFIINIFHLIILTRKSMRtSSINIIMIGIAICDIITMLltiyNFIPEFIISYENSECIP---PDSYLKVLL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  105 IKFHSIFAQVLHTISIWLTVTLAVWRYIAVGYPQKNRVWCgmrttiitittayvvcvLVVSPSLYLITAITeyvdqldmn 184
Cdd:pfam10324  78 DWILESLQDYSRRCSTWLGVFMALIRTLVVKNPMSNKIQK-----------------LSKPKFGLIIIIIV--------- 131

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  185 gkVINSIPMTqyVIDY-RNELLSartaalnatptsaplNETVWLNASTLLTSTTTAapptpspvvrNVTVYRLYHSDLAL 263
Cdd:pfam10324 132 --FILSLPIS--IFYYfRYEIVE---------------VGGIWKPPPNCAGFPPNY----------TETRYVLVVSELFT 182

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  264 HNASLQNATF-LIYSVVIKLIPCIALTILSVRLILALLEAKRRRKKLTSKpatpgasngtkspangkaadrprknsktle 342
Cdd:pfam10324 183 ANDGLLLKIFlLIDGIFSKIIPCILLPILTILLIIELRKAKKSRKNLSSS------------------------------ 232

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  343 KEKQTDRTTRMLLAVLLLFLITEFPQGIMGLLNAVLGDVFYLQCYLR-LSDLMDILALINSSINFILYCSMSKQFRTTFT 421
Cdd:pfam10324 233 SKNKSDRTTKLVIFMTISFFIAEFPLGISYIIQFFFTDNPGIRRILTyLSVIFSLLFTINSISHCFICFLMSSQYRKTAK 312

                  ....
gi 262359994  422 LLFR 425
Cdd:pfam10324 313 KLFG 316

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 262359994  34 VVCILGTIANTLNIIV-LTRREMRSPTNAILTGLAVADLAVMLEYIPYTIHDYILTD-SLPReeklsysWACfiKFHSIF 111
Cdd:cd15096    9 LIFIVGLIGNSLVILVvLSNQQMRSTTNILILNLAVADLLFVVFCVPFTATDYVLPTwPFGD-------VWC--KIVQYL 79

                         90       100
                 ....*....|....*....|....*.
gi 262359994 112 AQVLHTISIWLTVTLAVWRYIAVGYP 137
Cdd:cd15096   80 VYVTAYASVYTLVLMSLDRYLAVVHP 105

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 262359994  33 LVVCILGTIANTLNIIVLTR-REMRSPTNAILTGLAVADLAVMLEYIPYTIHDYILTDSLpreeklsYSWA-CfiKFHSI 110
Cdd:cd14993    8 VVVFLLALVGNSLVIAVVLRnKHMRTVTNYFLVNLAVADLLVSLFCMPLTLLENVYRPWV-------FGEVlC--KAVPY 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 262359994 111 FAQVLHTISIWLTVTLAVWRYIAVGYPQKNRVWCGMRTTIITITTAYVVCVLVVSPSLY 169
Cdd:cd14993   79 LQGVSVSASVLTLVAISIDRYLAICYPLKARRVSTKRRARIIIVAIWVIAIIIMLPLLV 137

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 262359994  37 ILGTIANTLNIIVLTR-REMRSPTNAILTGLAVADLAVMLEYIPYTIHDYiltdSLPREekLSYSWACfiKFHSIFAQVL 115
Cdd:cd14971   12 LLGLVGNSLVILVVARnKPMRSTTNLFILNLAVADLTFLLFCVPFTATIY----PLPGW--VFGDFMC--KFVHYFQQVS 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 262359994 116 HTISIWLTVTLAVWRYIAVGYPQKNRVWCGMRTTIITITTAYVVCVLVVSPSLYL 170
Cdd:cd14971   84 MHASIFTLVAMSLDRFLAVVYPLRSLHIRTPRNALAASGCIWVVSLAVAAPVLAL 138

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 262359994  33 LVVCILGTIANTLNIIVLTR-REMRSPTNAILTGLAVADLAVMLEYIPYTIHdYILTDSLPreekLSySWACfiKFHSIF 111
Cdd:cd15203    8 GLIIVLGVVGNLLVIYVVLRnKSMQTVTNIFILNLAVSDLLLCLVSLPFTLI-YTLTKNWP----FG-SILC--KLVPSL 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 262359994 112 AQVLHTISIWLTVTLAVWRYIAVGYPQKNRVwcGMRTTIITITTAYVVCVLVVSPSLYLITAITEYVDQLDMNG 185
Cdd:cd15203   80 QGVSIFVSTLTLTAIAIDRYQLIVYPTRPRM--SKRHALLIIALIWILSLLLSLPLAIFQELSDVPIEILPYCG 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 262359994  34 VVCILGTIANTL-NIIVLTRREMRSPTNAILTGLAVADLAVMLEYIPytihdYILTDSLPREEKLSYSWAC----FIKFH 108
Cdd:cd14997    9 VIFVVGVLGNVLvGIVVWKNKDMRTPTNIFLVNLSVADLLVLLVCMP-----VALVETWAREPWLLGEFMCklvpFVELT 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994 109 SIFAQVLHTISIwltvtlAVWRYIAVGYPQKNRVWCGMRTTIITITTAYVVCVLVVSPSLylitAITEYVDQLDMNGKVI 188
Cdd:cd14997   84 VAHASVLTILAI------SFERYYAICHPLQAKYVCTKRRALVIIALIWLLALLTSSPVL----FITEFKEEDFNDGTPV 153

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 262359994   43 NTLNIIVLTR-REMRSPTNAILTGLAVADLAVMLEYIPYTIHDYILTDSLPREEKLsyswaCfiKFHSIFAQVLHTISIW 121
Cdd:pfam00001   2 NLLVILVILRnKKLRTPTNIFLLNLAVADLLFSLLTLPFWLVYYLNHGDWPFGSAL-----C--KIVGALFVVNGYASIL 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 262359994  122 LTVTLAVWRYIAVGYPQKNRVWCGMRTTIITITTAYVVCVLVVSPSLYLIT 172
Cdd:pfam00001  75 LLTAISIDRYLAIVHPLRYKRRRTPRRAKVLILVIWVLALLLSLPPLLFGW 125

motilin receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Motilin receptor, also known as GPR38, is a G-protein coupled receptor that binds the endogenous ligand motilin. Motilin is a 22 amino acid peptide hormone expressed throughout the gastrointestinal tract and stimulates contraction of gut smooth muscle. Motilin is also called as the housekeeper of the gut because it is responsible for the proper filling and emptying of the gastrointestinal tract in response to food intake, and for stimulating the production of pepsin. Motilin receptor shares significant amino acid sequence identity with the growth hormone secretagogue receptor (GHSR) and neurotensin receptors (NTS-R1 and 2).

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  31 VSLVVCILGTIANTLNIIVLTR-REMRSPTNAILTGLAVADLAVMLEyIPYTIhdYILTDSLPreeklsysWAcfikFHS 109
Cdd:cd15132    6 VCLILFVVGVTGNTMTVLIIRRyKDMRTTTNLYLSSMAVSDLLILLC-LPFDL--YRLWKSRP--------WI----FGE 70

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 262359994 110 IFAQVLHTIS-------IWLTVTLAVWRYIAVGYPQKNRVWCGMRTTIITITTAYVVCVLVVSPSLYLI 171
Cdd:cd15132   71 FLCRLYHYISegctyatILHITALSIERYLAICFPLRAKVLVTRRRVKCVIAALWAFALLSAGPFLFLV 139

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 262359994  34 VVCILGTIANTLNIIVLTR-REMRSPTNAILTGLAVADLAVMLEYIPYTIHDYILTDSLPREEklsyswacFIKFHSIFA 112
Cdd:cd15206    9 VIFLLAVVGNILVIVTLVQnKRMRTVTNVFLLNLAVSDLLLAVFCMPFTLVGQLLRNFIFGEV--------MCKLIPYFQ 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 262359994 113 QVLHTISIWLTVTLAVWRYIAVGYPQKNRVWCGMRTTIITITTAYVVCVLVVSPSL 168
Cdd:cd15206   81 AVSVSVSTFTLVAISLERYFAICHPLKSRVWQTLSHAYKVIAGIWLLSFLIMSPIL 136

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 262359994  37 ILGTIANTLNIIVLTR-REMRSPTNAILTGLAVADLAVMLEYIPYTIHDYILTDSlpreekLSYSWACfiKFHSIFAQVL 115
Cdd:cd15978   12 LLSVLGNSLIIAVLIRnKRMRTVTNIFLLSLAVSDLMLCLFCMPFTLIPNLLKDF------IFGSAVC--KTATYFMGIS 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 262359994 116 HTISIWLTVTLAVWRYIAVGYPQKNRVWCGMRTTIITITTAYVVCVLVVSP 166
Cdd:cd15978   84 VSVSTFNLVAISLERYSAICKPLKSRVWQTKSHALKVIAATWCLSFTIMLP 134

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 262359994  31 VSLVVCILGTIANTLNIIVLTR-REMRSPTNAILTGLAVADLAVMLEYIPYTIhdYILTDSLPReekLSYSWACFikFHS 109
Cdd:cd15133    6 TYLLIFVVGVVGNVLTCLVIARhKAMRTPTNYYLFSLAVSDLLVLLLGMPLEL--YELWQNYPF---LLGSGGCY--FKT 78

                         90       100       110
                 ....*....|....*....|....*....|..
gi 262359994 110 IFAQVLHTISIWLTVTLAVWRYIAVGYPQKNR 141
Cdd:cd15133   79 FLFETVCLASILNVTALSVERYIAVVHPLAAR 110

trissin receptor and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup represents the Drosophila melanogaster trissin receptor and closely related invertebrate proteins which are a member of the class A family of seven-transmembrane G-protein coupled receptors. The cysteine-rich trissin has been shown to be an endogenous ligand for the orphan CG34381 in Drosophila melanogaster. Trissin is a peptide composed of 28 amino acids with three intrachain disulfide bonds with no significant structural similarities to known endogenous peptides. Cysteine-rich peptides are known to have antimicrobial or toxicant activities, although frequently their mechanism of action is poorly understood. Since the expression of trissin and its receptor is reported to predominantly localize to the brain and thoracicoabdominal ganglion, trissin is predicted to behave as a neuropeptide. 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 262359994  34 VVCILGtiaNTLNIIVLT-RREMRSPTNAILTGLAVADLAV-MLEYIPYTIHdyILTDSLPREEKLSYSwacFIKFHSIf 111
Cdd:cd15012   11 CCCFFG---NLLVILVVTsHRRMRTITNFFLANLAVADLCVgIFCVLQNLSI--YLIPSWPFGEVLCRM---YQFVHSL- 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 262359994 112 aqvLHTISIWLTVTLAVWRYIAVGYPQKNRVWCGMRTTIITITTAYVVCVLVVSP 166
Cdd:cd15012   82 ---SYTASIGILVVISVERYIAILHPLRCKQLLTAARLRVTIVTVWLTSAVYNTP 133

G protein-coupled receptor 35, GPR55, and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily is composed of GPR35, GPR55, and similar proteins. GPR35 shares closest homology with GPR55, and they belong to the class A G protein-coupled receptor superfamily, which all have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A number of studies have suggested that GPR35 may play important physiological roles in hypertension, atherosclerosis, nociception, asthma, glucose homeostasis and diabetes, and inflammatory bowel disease. GPR35 is thought to be responsible for brachydactyly mental retardation syndrome, which is associated with a deletion comprising chromosome 2q37 in human, and is also implicated as a potential oncogene in stomach cancer. GPR35 couples to G(13) and G(i/o) proteins, whereas GPR55 has been reported to couple to G(13), G(12), or G(q) proteins. Activation of GPR55 leads to activation of phospholipase C, RhoA, ROCK, ERK, p38MAPK, and calcium release. Recently, lysophosphatidylinositol (LPI) has been identified as an endogenous ligand for GPR55, while several endogenous ligands for GPR35 have been identified including kynurenic acid, 2-oleoyl lysophosphatidic acid, and zaprinast.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  31 VSLVVCILGTIANTLNIIVL-TRREMRSPTNAILTGLAVADLAVMLeYIPYTIHDYilTDSLPREEKLsyswaCFikfhs 109
Cdd:cd15923    6 IYIPTFVLGLLLNILALWVFcWRLKKWTETNIYMTNLAVADLLLLI-SLPFKMHSY--RRESAGLQKL-----CN----- 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 262359994 110 iFAQVLHTISIWLTVTL----AVWRYIAVGYPQKNRVWCGMRttiititTAYVVC----VLVVSPS 167
Cdd:cd15923   73 -FVLSLYYINMYVSIFTitaiSVDRYVAIRYPLRARELRSPR-------KAAVVCaviwVLVVTIS 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 262359994  34 VVCILGTIANTLNIIVLTRRE-MRSPTNAILTGLAVADLAVMLEyIPYTIHDYILTdslpreeklsySWAcfikfhsiFA 112
Cdd:cd14970    9 VVCVVGLTGNSLVIYVILRYSkMKTVTNIYILNLAVADELFLLG-LPFLATSYLLG-----------YWP--------FG 68

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 262359994 113 QVLHTI-----------SIWLTVTLAVWRYIAVGYPQKNRVW 143
Cdd:cd14970   69 EVMCKIvlsvdaynmftSIFCLTVMSVDRYLAVVHPVKSLRF 110

trace amine-associated receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The trace amine-associated receptors (TAARs) are a distinct subfamily within the class A G protein-coupled receptor family. Trace amines are endogenous amines of unknown function that have strong structural and metabolic similarity to classical monoamine neurotransmitters (serotonin, noradrenaline, adrenaline, dopamine, and histamine), which play critical roles in human and animal physiological activities such as cognition, consciousness, mood, motivation, perception, and autonomic responses. However, trace amines are found in the mammalian brain at very low concentrations compared to classical monoamines. Trace amines, including p-tyramine, beta-phenylethylamine, and tryptamine, are also thought to act as chemical messengers to exert their biological effects in vertebrates. 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 262359994  30 YVSLVVCILGTIanTLNIIVLTR----REMRSPTNAILTGLAVADLAVMLEYIPYTIhdyILTDslpreEKLSYSWACFI 105
Cdd:cd15055    4 YIVLSSISLLTV--LGNLLVIISishfKQLHTPTNLLLLSLAVADFLVGLLVMPFSM---IRSI-----ETCWYFGDTFC 73

                         90       100       110
                 ....*....|....*....|....*....|..
gi 262359994 106 KFHSIFAQVLHTISIWLTVTLAVWRYIAVGYP 137
Cdd:cd15055   74 KLHSSLDYILTSASIFNLVLIAIDRYVAVCDP 105

pyroglutamylated RFamide peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; 26RFa, also known as QRFP (Pyroglutamylated RFamide peptide), is a 26-amino acid residue peptide that belongs to a family of neuropeptides containing an Arg-Phe-NH2 (RFamide) motif at its C-terminus. 26Rfa/QRFP 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  34 VVCILGTIANTLNIIVLTR-REMRSPTNAILTGLAVADLAVMLEYIPYTIHDYILTDSLpreeklsysWACFIKFHSIFA 112
Cdd:cd15205    9 LIFVLALFGNSLVIYVVTRkRAMRTATNIFICSLALSDLLITFFCIPFTLLQNISSNWL---------GGAFMCKMVPFV 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 262359994 113 QVLHTISIWLTVT-LAVWRYIAVGYPQKNRVWCGMRTTIITITTAYVVCVLVVSPSLYLITAITEY 177
Cdd:cd15205   80 QSTAVVTSILTMTcIAVERHQGIVHPLKMKWQYTNRRAFTMLGLVWIVSVIVGSPMLFVQQLEVKY 145

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  33 LVVCILGTIANTLNI-IVLTRREMRSPTNAILTGLAVADLAVMLEYIPYTiHDYILTDSLPREEKlsyswacFIKFHSIF 111
Cdd:cd15390    8 VVMVLVAIGGNLIVIwIVLAHKRMRTVTNYFLVNLAVADLLISAFNTVFN-FTYLLYNDWPFGLF-------YCKFSNFV 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 262359994 112 AQVLHTISIWLTVTLAVWRYIAVGYPQKNRVwcGMRTTIITITTAYVVCVLVVSPSLYLITAITEYV 178
Cdd:cd15390   80 AITTVAASVFTLMAISIDRYIAIVHPLRPRL--SRRTTKIAIAVIWLASFLLALPQLLYSTTETYYY 144

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 262359994  32 SLVVCILGTIANTLNIIVLTR-REMRSPTNAILTGLAVADLAV 73
Cdd:cd15073    7 LIVAGIISTISNGIVLVTFVKfRELRTPTNALIINLAVTDLGV 49

growth hormone secretagogue receptor, motilin receptor, and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes growth hormone secretagogue receptor (GHSR or ghrelin receptor), motilin receptor (also called GPR38), and related proteins. Both GHSR and GPR38 bind peptide hormones. Ghrelin, the endogenous ligand for GHSR, is an acylated 28-amino acid peptide hormone produced by ghrelin cells in the gastrointestinal tract. Ghrelin is also called the hunger hormone and is involved in the regulation of growth hormone release, appetite and feeding, gut motility, lipid and glucose metabolism, and energy balance. Motilin, the ligand for GPR38, is a 22 amino acid peptide hormone expressed throughout the gastrointestinal tract and stimulates contraction of gut smooth muscle. It is involved in the regulation of digestive tract motility.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 262359994  31 VSLVVCILGTIANTLNIIVLTR-REMRSPTNAILTGLAVADLAVMLE-----YIPYTIHDYILTDSLPReekLSYswacF 104
Cdd:cd15928    6 VCSVLMLVGASGNLLTVLVIGRsRDMRTTTNLYLSSLAVSDLLIFLVlpldlYRLWRYRPWRFGDLLCR---LMY----F 78