seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share 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. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the 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 1039753764  34 LVAGFYLTIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAG 113
Cdd:cd15074     1 IIIGIYLTVIGILSTLGNGTVLFVLYRRRSKLKPAELLTVNLAVSDLGISVFGYPLAIISAFAHRWLFGDIGCVFYGFCG 80

                          90       100
                  ....*....|....*....|....*..
gi 1039753764 114 FFFGCGSLITMTAVSLDRYLKICYLSY 140
Cdd:cd15074    81 FLFGCCSINTLTAISIYRYLKICHPPY 107

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  34 LVAGFYLTIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAG 113
Cdd:cd15074     1 IIIGIYLTVIGILSTLGNGTVLFVLYRRRSKLKPAELLTVNLAVSDLGISVFGYPLAIISAFAHRWLFGDIGCVFYGFCG 80

                          90       100
                  ....*....|....*....|....*..
gi 1039753764 114 FFFGCGSLITMTAVSLDRYLKICYLSY 140
Cdd:cd15074    81 FLFGCCSINTLTAISIYRYLKICHPPY 107

CC chemokine receptor-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  38 FYLtIIGILSTFGNGYVLYMSSRRKKKlRPAEIMTINLAVCDLgISVVGKPFTIISCFcHRWVFGWFGCRWYG---WAGF 114
Cdd:PHA02638  104 FYI-IIFILGLFGNAAIIMILFCKKIK-TITDIYIFNLAISDL-IFVIDFPFIIYNEF-DQWIFGDFMCKVISasyYIGF 179

                          90       100
                  ....*....|....*....|...
gi 1039753764 115 FfgcGSLITMTAVSLDRYLKICY 137
Cdd:PHA02638  180 F---SNMFLITLMSIDRYFAILY 199

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  34 LVAGFYLTIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAG 113
Cdd:cd15074     1 IIIGIYLTVIGILSTLGNGTVLFVLYRRRSKLKPAELLTVNLAVSDLGISVFGYPLAIISAFAHRWLFGDIGCVFYGFCG 80

                          90       100
                  ....*....|....*....|....*..
gi 1039753764 114 FFFGCGSLITMTAVSLDRYLKICYLSY 140
Cdd:cd15074    81 FLFGCCSINTLTAISIYRYLKICHPPY 107

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        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  34 LVAGFYLTIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAG 113
Cdd:cd15073     1 NIVAAYLIVAGIISTISNGIVLVTFVKFRELRTPTNALIINLAVTDLGVSIIGYPFSAASDLHGSWKFGYAGCQWYAFLN 80

                          90       100
                  ....*....|....*....|...
gi 1039753764 114 FFFGCGSLITMTAVSLDRYLKIC 136
Cdd:cd15073    81 IFFGMASIGLLTVVAVDRYLTIC 103

insect photoreceptors R1-R6 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the insect photoreceptors and their closely related proteins. The Drosophila eye is composed of about 800 unit eyes called ommatidia, each of which contains eight photoreceptor cells (R1-R8). The six outer photoreceptors (R1-R6) function like the vertebrate rods and are responsible for motion detection in dim light and image formation. The R1-R6 photoreceptors express a blue-absorbing pigment, Rhodopsin 1(Rh1). The inner photoreceptors (R7 and R8) are considered the equivalent of the color-sensitive vertebrate cone cells, which express a range of different pigments. The R7 photoreceptors express one of two different UV absorbing pigments, either Rh3 or Rh4. Likewise, the R8 photoreceptors express either the blue absorbing pigment Rh5 or green absorbing pigment Rh6. These photoreceptors belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  37 GFYLTIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGIsVVGKPFTIISCFCHRWVFGWFGCRWYGWAGFFF 116
Cdd:cd15079     4 GFIYIFLGIVSLLGNGLVIYIFSTTKSLRTPSNMLVVNLAISDFLM-MIKMPIFIYNSFYEGWALGPLGCQIYAFLGSLS 82

                          90       100
                  ....*....|....*....|.
gi 1039753764 117 GCGSLITMTAVSLDRYLKICY 137
Cdd:cd15079    83 GIGSIWTNAAIAYDRYNVIVK 103

vertebrate melanopsins (Opsin-4), member of the class A family of seven-transmembrane G protein-coupled receptors; Melanopsin (also called Opsin-4) is the G protein-coupled photopigment that mediates non-visual responses to light. In mammals, these photoresponses include the photo-entrainment of circadian rhythm, pupillary constriction, and acute nocturnal melatonin suppression. Mammalian melanopsins are expressed only in the inner retina, whereas non-mammalian vertebrate melanopsins are localized in various extra-retinal tissues such as iris, brain, pineal gland, and skin. Melanopsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  35 VAGFYLTIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAGF 114
Cdd:cd15336     2 TVGSVILIIGITGMLGNALVIYAFCRSKKLRTPANYFIINLAVSDFLMSLTQSPIFFVNSLHKRWIFGEKGCELYAFCGA 81

                          90       100
                  ....*....|....*....|.
gi 1039753764 115 FFGCGSLITMTAVSLDRYLKI 135
Cdd:cd15336    82 LFGITSMITLLAISLDRYLVI 102

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 1039753764  50 GNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIIS-CFCHRWVFGWFGCRWYGWAGFFFGCGSLITMTAVS 128
Cdd:pfam00001   1 GNLLVILVILRNKKLRTPTNIFLLNLAVADLLFSLLTLPFWLVYyLNHGDWPFGSALCKIVGALFVVNGYASILLLTAIS 80

                  ....*....
gi 1039753764 129 LDRYLKICY 137
Cdd:pfam00001  81 IDRYLAIVH 89

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 1039753764  39 YLTIIgILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRwygWAGFFFGC 118
Cdd:cd15203     7 YGLII-VLGVVGNLLVIYVVLRNKSMQTVTNIFILNLAVSDLLLCLVSLPFTLIYTLTKNWPFGSILCK---LVPSLQGV 82

                          90       100
                  ....*....|....*....|..
gi 1039753764 119 G---SLITMTAVSLDRYLKICY 137
Cdd:cd15203    83 SifvSTLTLTAIAIDRYQLIVY 104

amine receptors and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; Amine receptors of the class A family of GPCRs include adrenoceptors, 5-HT (serotonin) receptors, muscarinic cholinergic receptors, dopamine receptors, histamine receptors, and trace amine receptors. The receptors of amine subfamily are major therapeutic targets for the treatment of neurological disorders and psychiatric diseases. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  34 LVAGFYLTIIgILSTFGNGYVLyMSSRRKKKLR-PAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWA 112
Cdd:cd14967     1 LLAVFLSLII-LVTVFGNLLVI-LAVYRNRRLRtVTNYFIVSLAVADLLVALLVMPFSAVYTLLGYWPFGPVLCRFWIAL 78

                          90       100
                  ....*....|....*....|....*....
gi 1039753764 113 GFFFGCGSLITMTAVSLDRYLKICY-LSY 140
Cdd:cd14967    79 DVLCCTASILNLCAISLDRYLAITRpLRY 107

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 1039753764  38 FYLTIIgILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWygwAGFFFG 117
Cdd:cd14993     6 LYVVVF-LLALVGNSLVIAVVLRNKHMRTVTNYFLVNLAVADLLVSLFCMPLTLLENVYRPWVFGEVLCKA---VPYLQG 81

                          90       100
                  ....*....|....*....|...
gi 1039753764 118 ---CGSLITMTAVSLDRYLKICY 137
Cdd:cd14993    82 vsvSASVLTLVAISIDRYLAICY 104

GPRnna14 and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the orphan G-protein coupled receptor GPRnna14 found in body louse (Pediculus humanus humanus) as well as its closely related proteins of unknown function. These receptors are members of the class A rhodopsin-like G-protein coupled receptors. As an obligatory parasite of humans, the body louse is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. GPRnna14 shares significant sequence similarity with the members of the neurotensin receptor family. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  41 TIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAGFF-FGCg 119
Cdd:cd15001     7 VITFVLGLIGNSLVIFVVARFRRMRSVTNVFLASLATADLLLLVFCVPLKTAEYFSPTWSLGAFLCKAVAYLQLLsFIC- 85

                          90
                  ....*....|....*...
gi 1039753764 120 SLITMTAVSLDRYLKICY 137
Cdd:cd15001    86 SVLTLTAISIERYYVILH 103

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  42 IIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLgISVVGKPFTIISCFCH-RWVFGWFGCRwygWAGFFFGC-- 118
Cdd:cd15168     9 VVFLVGLLLNSVVLYRFIFHLKPWNSSAIYMFNLAVSDL-LYLLSLPFLIYYYANGdHWIFGDFMCK---LVRFLFYFnl 84

                          90       100
                  ....*....|....*....|
gi 1039753764 119 -GSLITMTAVSLDRYLKICY 137
Cdd:cd15168    85 yGSILFLTCISVHRYLGICH 104

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 1039753764  34 LVAGFYLTIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAG 113
Cdd:cd15096     1 IVVPVIFGLIFIVGLIGNSLVILVVLSNQQMRSTTNILILNLAVADLLFVVFCVPFTATDYVLPTWPFGDVWCKIVQYLV 80

                          90       100
                  ....*....|....*....|....
gi 1039753764 114 FFFGCGSLITMTAVSLDRYLKICY 137
Cdd:cd15096    81 YVTAYASVYTLVLMSLDRYLAVVH 104

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  33 DLVAGFYlTIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGIsVVGKPF-TIISCFCHRWVFGWFGCRWYGW 111
Cdd:cd14985     1 VVIPALY-IAIFLVGLLGNLFVVWVFLFPRGPKRVADIFIANLAAADLVF-VLTLPLwATYTANQYDWPFGAFLCKVSSY 78

                          90       100
                  ....*....|....*....|....*..
gi 1039753764 112 AGFFFGCGSLITMTAVSLDRYLKICYL 138
Cdd:cd14985    79 VISVNMFASIFLLTCMSVDRYLAIVHP 105

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  42 IIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAGFFFGCGSL 121
Cdd:cd15393     9 IISLVAVVGNFLVIWVVAKNRRMRTVTNIFIANLAVADIIIGLFSIPFQFQAALLQRWVLPRFMCPFCPFVQVLSVNVSV 88

                          90
                  ....*....|....*.
gi 1039753764 122 ITMTAVSLDRYLKICY 137
Cdd:cd15393    89 FTLTVIAVDRYRAVIH 104

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  40 LTIIGILSTFGNGYVLYMSSRRKKKlRPAEIMTINLAVCDLgISVVGKPFTIIS-CFCHRWVFGWFGCRWYGWAGFFFGC 118
Cdd:cd14974     7 YALIFLLGLPGNGLVIWVAGFKMKR-TVNTVWFLNLALADF-LFCLFLPFLIVYiAMGHHWPFGSVLCKLNSFVISLNMF 84

                          90
                  ....*....|....*
gi 1039753764 119 GSLITMTAVSLDRYL 133
Cdd:cd14974    85 ASVFLLTAISLDRCL 99

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 1039753764  41 TIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAGFFFGCGS 120
Cdd:cd15205     8 VLIFVLALFGNSLVIYVVTRKRAMRTATNIFICSLALSDLLITFFCIPFTLLQNISSNWLGGAFMCKMVPFVQSTAVVTS 87

                          90
                  ....*....|....*..
gi 1039753764 121 LITMTAVSLDRYLKICY 137
Cdd:cd15205    88 ILTMTCIAVERHQGIVH 104

vasopressin receptors and its related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Members of this group form a subfamily within the class A G-protein coupled receptors (GPCRs), which includes the vasopressin and oxytocin receptors, the gonadotropin-releasing hormone receptors (GnRHRs), the neuropeptide S receptor (NPSR), and orphan GPR150. These receptors share significant sequence homology with each other, suggesting that they have a common evolutionary origin. Vasopressin, also known as arginine vasopressin or anti-diuretic hormone, is a neuropeptide synthesized in the hypothalamus. The actions of vasopressin are mediated by the interaction of this hormone with three tissue-specific subtypes: V1AR, V1BR, and V2R. Although vasopressin differs from oxytocin by only two amino acids, they have divergent physiological functions. Vasopressin is involved in regulating osmotic and cardiovascular homeostasis, whereas oxytocin plays an important role in the uterus during childbirth and in lactation. GnRHR, also known as luteinizing hormone releasing hormone receptor (LHRHR), plays an central role in vertebrate reproductive function; its activation by binding to GnRH leads to the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. Neuropeptide S (NPS) promotes arousal and anxiolytic-like effects by activating its cognate receptor NPSR. NPSR has also been associated with asthma and allergy. GPR150 is an orphan receptor closely related to the oxytocin and vasopressin receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  40 LTIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAGFFFGCG 119
Cdd:cd14986     7 LGVLFVFTLVGNGLVILVLRRKRKKRSRVNIFILNLAIADLVVAFFTVLTQIIWEATGEWVAGDVLCRIVKYLQVVGLFA 86

                          90
                  ....*....|....*...
gi 1039753764 120 SLITMTAVSLDRYLKICY 137
Cdd:cd14986    87 STYILVSMSLDRYQAIVK 104

invertebrate neuropeptide receptor-like, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes putative neuropeptide receptor found in invertebrates, which is a member of class A of 7-transmembrane G protein-coupled receptors. This orphan receptor shares a significant amino acid sequence identity with the neurokinin 1 receptor (NK1R). The endogenous ligand for NK1R is substance P, an 11-amino acid peptide that functions as a vasodilator and neurotransmitter and is released from the autonomic sensory nerve fibers.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  38 FYLTIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAGFFFG 117
Cdd:cd15391     5 NLYQSTIFLSVGGNYSVIVVFYDGRRSRTDLNYYLINLAVSDLIMALFCMPFTFTQIMLGHWVFPAPMCPIVLYVQLVSV 84

                          90
                  ....*....|....*...
gi 1039753764 118 CGSLITMTAVSLDRYLKI 135
Cdd:cd15391    85 TASVLTNTAIGIDRFFAV 102

G protein-coupled receptor PSP24 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes two human orphan receptors, GPR45 and GPR65, and their closely related proteins found in vertebrates and invertebrates. GPR45 and GPR 65 are also called PSP24-alpha (or PSP24-1) and PSP24-beta (or PSP24-2) in other vertebrates, respectively. These receptors exhibit the highest sequence homology to each other. PSP24 was originally identified as a novel, high-affinity lysophosphatidic acid (LPA) receptor in Xenopus laevis oocytes; however, PSP24 receptors (GPR45 and GPR63) have not been shown to be activated by LPA. Instead, sphingosine 1-phosphate and dioleoylphosphatidic acid have been shown to act as low affinity agonists for GPR63. PSP24 receptors are highly expressed in neuronal cells of cerebellum and their expression level remains constant from the early embryonic stages to adulthood, suggesting the important role of PSP24s in brain neuronal functions. Members of this subgroup contain the highly conserved Asp-Arg-Tyr/Phe (DRY/F) motif found in the third transmembrane helix (TM3) of the rhodopsin-like class A receptors which is important for efficient G protein-coupled signal transduction. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  34 LVAGFYLTIIGIlSTFGNGYVLYMSsRRKKKLRPA-EIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWA 112
Cdd:cd15213     2 TLAILMILMIFV-GFLGNSIVCLIV-YQKPAMRSAiNLLLANLAFSDIMLSLVCMPFAAVTIITGRWIFGDIFCRISAML 79

                          90       100
                  ....*....|....*....|...
gi 1039753764 113 GFFFGCGSLITMTAVSLDRYLKI 135
Cdd:cd15213    80 YWFFVLEGVAILLIISVDRYLII 102

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  42 IIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLgISVVGKPFTIISCFCHRWVFGWFGCRWYGWAGFFFGCGSL 121
Cdd:cd15094     9 LICIVGLVGNGLVIYVVLRYAKMKTVTNLYILNLAVADE-CFLIGLPFLIVTMILKYWPFGAAMCKIYMVLTSINQFTSS 87

                          90
                  ....*....|....*.
gi 1039753764 122 ITMTAVSLDRYLKICY 137
Cdd:cd15094    88 FTLTVMSADRYLAVCH 103

CC chemokine receptor-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  38 FYLtIIGILSTFGNGYVLYMSSRRKKKlRPAEIMTINLAVCDLgISVVGKPFTIISCFcHRWVFGWFGCRWYG---WAGF 114
Cdd:PHA02638  104 FYI-IIFILGLFGNAAIIMILFCKKIK-TITDIYIFNLAISDL-IFVIDFPFIIYNEF-DQWIFGDFMCKVISasyYIGF 179

                          90       100
                  ....*....|....*....|...
gi 1039753764 115 FfgcGSLITMTAVSLDRYLKICY 137
Cdd:PHA02638  180 F---SNMFLITLMSIDRYFAILY 199

melatonin receptor subtype 1A, member of the class A family of seven-transmembrane G protein-coupled receptors; Melatonin (N-acetyl-5-methoxytryptamine) is a naturally occurring sleep-promoting chemical found in vertebrates, invertebrates, bacteria, fungi, and plants. In mammals, melatonin is secreted by the pineal gland and is involved in regulation of circadian rhythms. Its production peaks during the nighttime, and is suppressed by light. Melatonin is shown to be synthesized in other organs and cells of many vertebrates, including the Harderian gland, leukocytes, skin, and the gastrointestinal (GI) tract, which contains several hundred times more melatonin than the pineal gland and is involved in the regulation of GI motility, inflammation, and sensation. Melatonin exerts its pleiotropic physiological effects through specific membrane receptors, named MT1A, MT1B, and MT1C, which belong to the class A rhodopsin-like G-protein coupled receptor family. MT1A and MT1B subtypes are present in mammals, whereas MT1C subtype has been found in amphibians and birds. The melatonin receptors couple to G proteins of the G(i/o) class, leading to the inhibition of adenylate cyclase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  45 ILSTFGNGYVLyMSSRRKKKLRPA-EIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRwygWAGFFFGC---GS 120
Cdd:cd15402    12 VVDILGNLLVI-LSVYRNKKLRNAgNIFVVSLAVADLVVAIYPYPLVLTSIFHNGWNLGYLHCQ---ISGFLMGLsviGS 87

                          90
                  ....*....|....*..
gi 1039753764 121 LITMTAVSLDRYLKICY 137
Cdd:cd15402    88 IFNITGIAINRYCYICH 104

tyramine receptors and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes tyramine-specific receptors and similar proteins found in insects and other invertebrates. These tyramine receptors form a distinct receptor family that is phylogenetically different from the other tyramine/octopamine receptors which also found in invertebrates. Both octopamine and tyramine mediate their actions via G protein-coupled receptors (GPCRs) and are the invertebrate equivalent of vertebrate adrenergic neurotransmitters. In Drosophila, octopamine is involved in ovulation by mediating an egg release from the ovary, while a physiological role for tyramine in this process is not fully understood. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  40 LTIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRWYGWAGFFFGCG 119
Cdd:cd15061     6 LILAIIFTIFGNLLVILAVATTRRLRTITNCYIVSLATADLLVGVLVLPLAIIRQLLGYWPLGSHLCDFWISLDVLLCTA 85

                          90
                  ....*....|....*...
gi 1039753764 120 SLITMTAVSLDRYLKICY 137
Cdd:cd15061    86 SILNLCCISLDRYFAITY 103

CXC chemokine receptor type 5, member of the class A family of seven-transmembrane G protein-coupled receptors; CXCR5 is a B-cell selective receptor that binds specifically to the homeostatic chemokine CXCL13 and regulates adaptive immunity. The receptor is found on all peripheral blood and tonsillar B cells and is involved in lymphocyte migration (homing) to specific tissues and development of normal lymphoid tissue. Chemokines are principal regulators for leukocyte trafficking, recruitment, and activation. Chemokine family membership is defined on the basis of sequence homology and on the presence of variations on a conserved cysteine motif, which allows the family to further divide into four subfamilies (CC, CXC, XC, and CX3C). Chemokines interact with seven-transmembrane receptors which are typically coupled to G protein for signaling. Currently, there are ten known receptors for CC chemokines, seven for CXC chemokines, and single receptors for the XC and CX3C chemokines.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  38 FYLTIIgILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGIsVVGKPFTIISCFCHrWVFGWFGCRWYGWAG-FFF 116
Cdd:cd15181     6 AYSLVF-LLGVVGNGLVLTILLRRRRSRRTTENYLLHLALADLLL-LLTFPFSVVESIAG-WVFGTFLCKLVGAIHkLNF 82

                          90       100
                  ....*....|....*....|.
gi 1039753764 117 GCGSLItMTAVSLDRYLKICY 137
Cdd:cd15181    83 YCSSLL-LACISVDRYLAIVH 102

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 1039753764  42 IIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCFCHRWVFGWFGCRwygWAGFFFGCG-- 119
Cdd:cd15206     9 VIFLLAVVGNILVIVTLVQNKRMRTVTNVFLLNLAVSDLLLAVFCMPFTLVGQLLRNFIFGEVMCK---LIPYFQAVSvs 85

                          90
                  ....*....|....*...
gi 1039753764 120 -SLITMTAVSLDRYLKIC 136
Cdd:cd15206    86 vSTFTLVAISLERYFAIC 103

classical and atypical chemokine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Chemokines are principal regulators for leukocyte trafficking, recruitment, and activation. Chemokine family membership is defined on the basis of sequence homology and on the presence of variations on a conserved cysteine motif, which allows the family to further divide into four subfamilies (CC, CXC, XC, and CX3C). Chemokines interact with seven-transmembrane receptors which are typically coupled to G protein for signaling. Currently, there are ten known receptors for CC chemokines, seven for CXC chemokines, and single receptors for the XC and CX3C chemokines. In addition to these classical chemokine receptors, there exists a subfamily of atypical chemokine receptors (ACKRs) that are unable to couple to G-proteins and, instead, they preferentially mediate beta-arrestin dependent processes, such as receptor internalization, after ligand binding. The classical chemokine receptors contain a conserved DRYLAIV motif in the second intracellular loop, which is required for G-protein coupling. However, the ACKRs lack this conserved motif and fail to couple to G-proteins and induce classical GPCR signaling. Five receptors have been identified for the ACKR family, including CC-chemokine receptors like 1 and 2 (CCRL1 and CCRL2), CXCR7, Duffy antigen receptor for chemokine (DARC), and D6. Both ACKR1 (DARC) and ACKR3 (CXCR7) show low sequence homology to the classic chemokine receptors.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  41 TIIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLgISVVGKPFTIIScFCHRWVFGWFGCRWYGW---AGFFfg 117
Cdd:cd14984     8 SLVFLLGLVGNSLVLLVLLYYRKLRSMTDVYLLNLALADL-LFVLTLPFWAVY-AADGWVFGSFLCKLVSAlytINFY-- 83

                          90
                  ....*....|....*...
gi 1039753764 118 CGSLItMTAVSLDRYLKI 135
Cdd:cd14984    84 SGILF-LACISIDRYLAI 100

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  42 IIGILSTFGNGYVL--YMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPF--TIISCfcHRWVFGWFGCRWYGWAGFFFG 117
Cdd:cd15098     9 LIFCLGVLGNSLVItvLARVKPGKRRSTTNVFILNLSIADLFFLLFCVPFqaTIYSL--PEWVFGAFMCKFVHYFFTVSM 86

                          90       100
                  ....*....|....*....|
gi 1039753764 118 CGSLITMTAVSLDRYLKICY 137
Cdd:cd15098    87 LVSIFTLVAMSVDRYIAVVH 106

G protein-coupled receptor 135, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR135, also known as the somatostatin- and angiotensin-like peptide receptor (SALPR), is found in various tissues including eye, brain, cervix, stomach, and testis. Pharmacological studies have shown that relaxin-3 (R3) is a high-affinity endogenous ligand for GPR135. R3 has recently been identified as a new member of the insulin/relaxin family of peptide hormones and is exclusively expressed in the brain neurons. In addition to GPR135, R3 also acts as an agonist for GPR142, a pseudogene in the rat, and can activate LGR7 (leucine repeat-containing G-protein receptor-7), which is the main receptor for relaxin-1 (R1) and relaxin-2 (R2). While R1 and R2 are hormones primarily associated with reproduction and pregnancy, R3 is involved in neuroendocrine and sensory processing. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  35 VAGFYLTIIGILSTFGNGYVLYM--SSRRKKKLRPAEIMTinLAVCDLGISVVGKPFTIISCFCHR-WVFGWFGCRWYGW 111
Cdd:cd15212     2 AQALVLLAIFLLSSLGNCAVIGVivKHRQLRTVTNAFILS--LSLSDLLTALLCLPFAFLTLFSRPgWLFGDRLCLANGF 79

                          90       100
                  ....*....|....*....|....
gi 1039753764 112 AGFFFGCGSLITMTAVSLDRYLKI 135
Cdd:cd15212    80 FNACFGIVSTLTMTLISFDRYYAI 103

neurotensin receptors and related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes the neurotensin receptors and related G-protein coupled receptors, including neuromedin U receptors, growth hormone secretagogue receptor, motilin receptor, the putative GPR39 and the capa receptors from insects. These receptors all bind peptide hormones with diverse physiological effects. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1039753764  42 IIGILSTFGNGYVLYMSSRRKKKLRPAEIMTINLAVCDLGISVVGKPFTIISCF-CHRWVFGWFGCRWYGWAGFFFGCGS 120
Cdd:cd14979     9 AIFVVGIVGNLLTCIVIARHKSLRTTTNYYLFSLAVSDLLILLVGLPVELYNFWwQYPWAFGDGGCKLYYFLFEACTYAT 88