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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387158380  31 SLLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGCY 104
Cdd:cd15080    1 SALAAYMFLLILLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTMYTSMHGYFVFGPTGCN 74

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387158380  31 SLLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGCY 104
Cdd:cd15080    1 SALAAYMFLLILLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTMYTSMHGYFVFGPTGCN 74

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 387158380   48 NFMTLFVTIQHKKLRTPLNYILLNLAFAN-HFMVLCGFTITLYTSLHGYFVFGQSGC 103
Cdd:pfam00001   2 NLLVILVILRNKKLRTPTNIFLLNLAVADlLFSLLTLPFWLVYYLNHGDWPFGSALC 58

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387158380  31 SLLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGCY 104
Cdd:cd15080    1 SALAAYMFLLILLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTMYTSMHGYFVFGPTGCN 74

type 2 opsins in animals, member of the class A family of seven-transmembrane G protein-coupled receptors; This rhodopsin family represents the type 2 opsins found in vertebrates and invertebrates except sponge. Type 2 opsins primarily function as G protein coupled receptors and are responsible for vision as well as for circadian rhythm and pigment regulation. On the contrary, type 1 opsins such as bacteriorhodopsin and proteorhodopsin are found in both prokaryotic and eukaryotic microbes, functioning as light-gated ion channels, proton pumps, sensory receptors and in other unknown functions. Although these two opsin types share seven-transmembrane domain topology and a conserved lysine reside in the seventh helix, type 1 opsins do not activate G-proteins and are not evolutionarily related to type 2. Type 2 opsins can be classified into six distinct subfamilies including the vertebrate opsins/encephalopsins, the G(o) opsins, the G(s) opsins, the invertebrate G(q) opsins, the photoisomerases, and the neuropsins.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387158380  31 SLLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGCY 104
Cdd:cd14969    1 YVLAVYLSLIGVLGVVLNGLVIIVFLKKKKLRTPLNLFLLNLALADLLMSVVGYPLSFYSNLSGRWSFGDPGCV 74

Amino terminal of the G-protein receptor rhodopsin; Rhodopsin is the archetypal G-protein-coupled receptor. Such receptors participate in virtually all physiological processes, as signalling molecules. They utilize heterotrimeric guanosine triphosphate (GTP)-binding proteins to transduce extracellular signals to intracellular events. Rhodopsin is important because of the pivotal role it plays in visual signal transduction. Rhodopsin is a dimeric transmembrane protein and its intradiskal surface consists of this amino terminal domain and three loops connecting six of the seven transmembrane helices. The N-terminus is a compact domain of alpha-helical regions with breaks and bends at proline residues outside the membrane. The transmembrane part of rhodopsin is represented by 7tm_1 (pfam00001). The N-terminal domain is extracellular is and is necessary for successful dimerization and molecular stability.

                          10        20        30
                  ....*....|....*....|....*....|
gi 387158380    1 NFYIPMSNKTGVVRSPFEYPQYYLAEPWKY 30
Cdd:pfam10413   6 NFYIPMSNKTGVVRSPYEYPQYYLAEPWKF 35

short wave-sensitive 1 opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes Short Wave-Sensitive opsin 1 (SWS1), which mediates visual transduction in response to light at short wavelengths (ultraviolet to blue). Vertebrate cone opsins are expressed in cone photoreceptor cells of the retina and involved in mediating photopic vision, which allows color perception. The cone opsins can be classified into four classes according to their peak absorption wavelengths: SWS1 (ultraviolet sensitive), SWS2 (short wave-sensitive), MWS/LWS (medium/long wave-sensitive), and RH2 (medium wave-sensitive, rhodopsin-like opsins). Members of this group belong to the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 387158380  32 LLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGC 103
Cdd:cd15076    2 LQAAFMGFVFIVGTPLNAIVLFVTIKYKKLRQPLNYILVNISLAGFIFCIFSVFPVFVASAQGYFFFGRTVC 73

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 387158380  32 LLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCgFTITLYTSLHGYFVFGQSGCY 104
Cdd:cd15079    2 LLGFIYIFLGIVSLLGNGLVIYIFSTTKSLRTPSNMLVVNLAISDFLMMIK-MPIFIYNSFYEGWALGPLGCQ 73

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 387158380  31 SLLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGC 103
Cdd:cd15073    1 NIVAAYLIVAGIISTISNGIVLVTFVKFRELRTPTNALIINLAVTDLGVSIIGYPFSAASDLHGSWKFGYAGC 73

non-visual parapinopsin, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the non-visual pineal pigment, parapinopsin, which is a member of the class A of the seven transmembrane G protein-coupled receptors. Parapinopsin serves as a UV-sensitive pigment for the wavelength discrimination in the pineal-related organs of lower vertebrates such as reptiles, amphibians, and fish. Although parapinopsin is phylogenetically related to vertebrate visual pigments such as rhodopsin, which releases its retinal chromophore and bleaches, the parapinopsin photoproduct is stable and does not bleach. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extra-retinal tissues and/or in non-rod, non-cone retinal cells.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 387158380  32 LLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGC 103
Cdd:cd15075    2 ILSIIMAVFSIASVVLNATVIIVTLRHKQLRQPLNYALVNLAVADLGTTVFGGLLSVVTNAVGYFNLGRVGC 73

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 387158380  30 YSLLAAYMFMlILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGCY 104
Cdd:cd15203    1 IILILLYGLI-IVLGVVGNLLVIYVVLRNKSMQTVTNIFILNLAVSDLLLCLVSLPFTLIYTLTKNWPFGSILCK 74

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 387158380  32 LLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGCY 104
Cdd:cd14967    1 LLAVFLSLIILVTVFGNLLVILAVYRNRRLRTVTNYFIVSLAVADLLVALLVMPFSAVYTLLGYWPFGPVLCR 73

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387158380  32 LLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGY-FVFGQSGCY 104
Cdd:cd14979    2 LVTAIYVAIFVVGIVGNLLTCIVIARHKSLRTTTNYYLFSLAVSDLLILLVGLPVELYNFWWQYpWAFGDGGCK 75

neuromedin U receptor subtype 2, 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 387158380  40 LILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGY-FVFGQSGCY 104
Cdd:cd15357   10 IFVVGVIGNLLVCLVILKHQNMKTPTNYYLFSLAVSDLLVLLFGMPLEVYEMWSNYpFLFGPVGCY 75

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 387158380  32 LLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGC 103
Cdd:cd15086    2 VVAVFLGFILTFGFLNNLLVLVLFCKYKVLRSPINLLLLNISLSDLLVCVLGTPFSFAASTQGRWLIGEHGC 73

neuromedin-K receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The neuromedin-K receptor (NKR), also known as tachykinin receptor 3 (TACR3) or neurokinin B receptor or NK3R, is a G-protein coupled receptor that specifically binds to neurokinin B. The tachykinins (TKs) 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. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387158380  30 YSLLAAYMFMLILLGlpiNFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGC 103
Cdd:cd16003    3 WSLAYGFVVAVAVFG---NLIVIWIILAHKRMRTVTNYFLVNLAFSDASMAAFNTLINFIYALHSEWYFGEAYC 73

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387158380  32 LLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLcgFTITLYTS--LHGYFVFGQSGC 103
Cdd:cd15048    2 VLAVLISVLILVTVIGNLLVILAFIKDKKLRTVSNFFLLNLAVADFLVGL--VSMPFYIPytLTGKWPFGKVFC 73

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 387158380  40 LILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGCY 104
Cdd:cd15390   10 MVLVAIGGNLIVIWIVLAHKRMRTVTNYFLVNLAVADLLISAFNTVFNFTYLLYNDWPFGLFYCK 74

tachykinin receptors and related receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the neurokinin/tachykinin receptors and its closely related receptors such as orphan GPR83 and leucokinin-like peptide receptor. The tachykinins are widely distributed throughout the mammalian central and peripheral nervous systems and act as excitatory transmitters on neurons and cells in the gastrointestinal tract. The TKs are characterized by a common five-amino acid C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is a hydrophobic residue. The three major mammalian tachykinins are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). The physiological actions of tachykinins are mediated through three types of receptors: neurokinin receptor type 1 (NK1R), NK2R, and NK3R. SP is a high-affinity endogenous ligand for NK1R, which interacts with the Gq protein and activates phospholipase C, leading to elevation of intracellular calcium. NK2R is a high-affinity receptor for NKA, the tachykinin neuropeptide substance K. SP and NKA are found in the enteric nervous system and mediate in the regulation of gastrointestinal motility, secretion, vascular permeability, and pain perception. NK3R is activated by its high-affinity ligand, NKB, which is primarily involved in the central nervous system and plays a critical role in the regulation of gonadotropin hormone release and the onset of puberty.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 387158380  32 LLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGC 103
Cdd:cd15202    2 LLIVAYSFIIVFSLFGNVLVCWIIFKNQRMRTVTNYFIVNLAVADIMITLFNTPFTFVRAVNNTWIFGLFMC 73

tachykinin receptor and closely related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes G-protein coupled receptors for a variety of neuropeptides of the tachykinin (TK) family as well as closely related receptors. 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 387158380  31 SLLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVL--CGFTITLYTSLHGYF 96
Cdd:cd14992    1 IILGVALVVIILVSVVGNFIVIAALARHKNLRGATNYFIASLAISDLLMALfcTPFNFTYVVSLSWEY 68

alpha-1 adrenergic receptors subtype B, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-1 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that primarily mediate smooth muscle contraction: alpha-1A, alpha-1B, and alpha-1D. Activation of alpha-1 receptors by catecholamines such as norepinephrine and epinephrine couples to the G(q) protein, which then activates the phospholipase C pathway, leading to an increase in IP3 and calcium. Consequently, the elevation of intracellular calcium concentration leads to vasoconstriction in smooth muscle of blood vessels. In addition, activation of alpha-1 receptors by phenylpropanolamine (PPA) produces anorexia and may induce appetite suppression in rats.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 387158380  40 LILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGC 103
Cdd:cd15326   10 FILFAIVGNILVILSVVCNRHLRIPTNYFIVNLAIADLLLSFTVLPFSATLEILGYWVFGRIFC 73

KiSS1-derived peptide (kisspeptin) receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The G protein-coupled KiSS1-derived peptide receptor (GPR54 or kisspeptin receptor) binds the peptide hormone kisspeptin (previously known as metastin), which encoded by the metastasis suppressor gene (KISS1) expressed in various endocrine and reproductive tissues. The KiSS1 receptor is coupled to G proteins of the G(q/11) family, which lead to activation of phospholipase C and increase of intracellular calcium. This signaling cascade plays an important role in reproduction by regulating the secretion of gonadotropin-releasing hormone.

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gi 387158380  40 LILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFAN-HFMVLCG-FTITLYTSLHgyFVFGQSGC 103
Cdd:cd15095   10 IFLVGLAGNSLVIYVVSRHREMRTVTNYYIVNLAVTDlAFLVCCVpFTAALYATPS--WVFGDFMC 73

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

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gi 387158380  39 MLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANhFMVLCGFTITLYTSLHGYFVFGQSGC 103
Cdd:cd15072    9 VEALVGFSLNGLTILSFCKTRELRTPSNLLVLSLAVAD-MGISLNALVAASSSLLRRWPYGSEGC 72

neurokinin 1 receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The neurokinin 1 receptor (NK1R), also known as tachykinin receptor 1 (TACR1) or substance P receptor (SPR), is a G-protein coupled receptor found in the mammalian central nervous and peripheral nervous systems. The tachykinins 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. SP is an extremely potent vasodilator through endothelium dependent mechanism and is released from the autonomic sensory nerves. 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.

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gi 387158380  32 LLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQSGC 103
Cdd:cd16002    2 LWAVAYSVIVVVSVVGNIIVMWIILAHKRMRTVTNYFLVNLAFAEASMSAFNTVINFTYAIHNEWYYGLEYC 73

prolactin-releasing peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Prolactin-releasing peptide (PrRP) receptor (previously known as GPR10) is expressed in the central nervous system with the highest levels located in the anterior pituitary and is activated by its endogenous ligand PrRP, a neuropeptide possessing a C-terminal Arg-Phe-amide motif. There are two active isoforms of PrRP in mammals: one consists of 20 amino acids (PrRP-20) and the other consists of 31 amino acids (PrRP-31), where PrRP-20 is a C-terminal fragment of PrRP-31. Binding of PrRP to the receptor coupled to G(i/o) proteins activates the extracellular signal-related kinase (ERK) and it can also couple to G(q) protein leading to an increase in intracellular calcium and activation of c-Jun N-terminal protein kinase (JNK). The PrRP receptor shares significant sequence homology with the neuropeptide Y (NPY) receptor, and micromolar levels 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. PrRP has been shown to reduce food intake and body weight and modify body temperature when administered in rats. It also has been shown to decrease circulating growth hormone levels by activating somatostatin-secreting neurons in the hypothalamic periventricular nucleus.

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gi 387158380  39 MLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANhfMVLCGFTITL---YTSLHGYFVFGQSGCY 104
Cdd:cd15394    9 LVVLVGVVGNYLLIYVICRTKKMHNVTNFLIGNLAFSD--MLMCATCVPLtlaYAFEPRGWVFGRFMCY 75

dopamine 1-like receptor 2 from Drosophila melanogaster and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled dopamine 1-like receptor 2 is expressed in Drosophila heads and it shows significant sequence similarity with vertebrate and invertebrate dopamine receptors. Although the Drosophila Dop1R2 receptor does not cluster into the D1-like structural group, it does show pharmacological properties similar to D1-like receptors. As shown in vertebrate D1-like receptors, agonist stimulation of Dop1R2 activates adenylyl cyclase to increase cAMP levels and also generates a calcium signal through stimulation of phospholipase C.

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gi 387158380  32 LLAAYMFMLILLGLPINFMTLFVTIQHKKLRTPLNYILLNLAFANHFM--VLCGFTITLYTSlHGYFVFGQSGC 103
Cdd:cd15067    1 LLGVVLSLFCLVTVAGNLLVILAVLRERYLRTVTNYFIVSLAVADLLVgsIVMPFSILHEMT-GGYWLFGRDWC 73