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 67867336  21 S*LA*YMF*LILL*LPINFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGFFA 100
Cdd:cd15080   1 SALAAYMFLLILLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTMYTSMHGYFVFGPTGCNLEGFFA 80

                .
gi 67867336 101 T 101
Cdd:cd15080  81 T 81

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67867336  21 S*LA*YMF*LILL*LPINFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGFFA 100
Cdd:cd15080   1 SALAAYMFLLILLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTMYTSMHGYFVFGPTGCNLEGFFA 80

                .
gi 67867336 101 T 101
Cdd:cd15080  81 T 81

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67867336  21 S*LA*YMF*LILL*LPINFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGFFA 100
Cdd:cd15080   1 SALAAYMFLLILLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTMYTSMHGYFVFGPTGCNLEGFFA 80

                .
gi 67867336 101 T 101
Cdd:cd15080  81 T 81

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 67867336  23 LA*YMF*LILL*LPINFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGFFAT 101
Cdd:cd14969   3 LAVYLSLIGVLGVVLNGLVIIVFLKKKKLRTPLNLFLLNLALADLLMSVVGYPLSFYSNLSGRWSFGDPGCVIYGFAVT 81

non-visual VA (vertebrate ancient) opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; The vertebrate ancient (VA) opsin photopigments were originally identified in salmon and they appear to have diverged early in the evolution of vertebrate opsins. VA opsins are localized in the inner retina and the brain in teleosts. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extraretinal tissues and/or in non-rod, non-cone retinal cells. They are thought to be involved in light-dependent physiological functions such as photo-entrainment of circadian rhythm, photoperiodicity, and body color change. The VA opsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67867336  18 W*YS*LA*YMF*LILL*LPINFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEG 97
Cdd:cd15082  11 WNFTVLAALMFVVTSLSLAENFAVMLVTFRFKQLRQPLNYIIVNLSVADFLVSLTGGTISFLTNARGYFFLGVWACVLEG 90

                ....
gi 67867336  98 FFAT 101
Cdd:cd15082  91 FAVT 94

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 67867336  12 YYLAE*W*YS*LA*YMF*LILL*LPINFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQT 91
Cdd:cd15081   4 YHIAPRWVYNLTSVWMIFVVFASVFTNGLVLVATLKFKKLRHPLNWILVNLAIADLGETVIASTISVVNQIFGYFILGHP 83

                ....*..
gi 67867336  92 GCYFEGF 98
Cdd:cd15081  84 MCVLEGF 90

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 67867336  23 LA*YMF*LILL*LPINFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGF 98
Cdd:cd15075   3 LSIIMAVFSIASVVLNATVIIVTLRHKQLRQPLNYALVNLAVADLGTTVFGGLLSVVTNAVGYFNLGRVGCVLEGF 78

vertebrate melanopsins and related opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represent the Gq-coupled rhodopsin subfamily consists of melanopsins, insect photoreceptors R1-R6, invertebrate Gq opsins as well as their closely related opsins. Melanopsins (also called Opsin-4) are the primary photoreceptor molecules for non-visual functions such as the photo-entrainment of the circadian rhythm and pupillary constriction in mammals. Mammalian melanopsins are expressed only in the inner retina, whereas non-mammalian vertebrate melanopsins are localized in various extra-retinal tissues such as iris, brain, pineal gland, and skin. The outer photoreceptors (R1-R6) are the insect Drosophila equivalent to the vertebrate rods and are responsible for image formation and motion detection. The invertebrate G(q) opsins includes the arthropod and mollusk visual opsins as well as invertebrate melanopsins, which are also found in vertebrates. Arthropods possess color vision by the use of multiple opsins sensitive to different light wavelengths. Members of this subfamily belong to the class A of the G protein-coupled receptors and have seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGF 98
Cdd:cd15083  18 NGLVIYAFCRFKSLRTPANYLIINLAISDFLMCILNCPLMVISSFSGRWIFGKTGCDMYGF 78

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGY-FVFGQTGCYFEGFFA 100
Cdd:cd14979  18 NLLTCIVIARHKSLRTTTNYYLFSLAVSDLLILLVGLPVELYNFWWQYpWAFGDGGCKLYYFLF 81

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGF 98
Cdd:cd15073  18 NGIVLVTFVKFRELRTPTNALIINLAVTDLGVSIIGYPFSAASDLHGSWKFGYAGCQWYAF 78

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 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGY-FVFGQTGCYFE 96
Cdd:cd15357  18 NLLVCLVILKHQNMKTPTNYYLFSLAVSDLLVLLFGMPLEVYEMWSNYpFLFGPVGCYFK 77

rhodopsin receptor-like class A family of the seven-transmembrane G protein-coupled receptor superfamily; Class A rhodopsin-like receptors constitute about 90% of all GPCRs. The class A GPCRs include the light-sensitive rhodopsin as well as receptors for biogenic amines, lipids, nucleotides, odorants, peptide hormones, and a variety of other ligands. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. Based on sequence similarity, GPCRs can be divided into six major classes: class A (rhodopsin-like family), class B (Methuselah-like, adhesion and secretin-like receptor family), class C (metabotropic glutamate receptor family), class D (fungal mating pheromone receptors), class E (cAMP receptor family), and class F (frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGFFAT 101
Cdd:cd00637  16 NLLVILVILRNRRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRWWFGDALCKLLGFLQS 79

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
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGF 98
Cdd:cd15086  18 NLLVLVLFCKYKVLRSPINLLLLNISLSDLLVCVLGTPFSFAASTQGRWLIGEHGCRWYGF 78

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANhfMILCGFTV--TMYTSLHGYFVFGQTGCYFEGFF 99
Cdd:cd15203  18 NLLVIYVVLRNKSMQTVTNIFILNLAVSD--LLLCLVSLpfTLIYTLTKNWPFGSILCKLVPSL 79

invertebrate Gq opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; The invertebrate Gq-coupled opsin subfamily includes the arthropod and mollusc visual opsins. Like the vertebrate visual opsins, arthropods possess color vision by the use of multiple opsins sensitive to different light wavelengths. The invertebrate Gq opsins are closely related to the vertebrate melanopsins, the primary photoreceptor molecules for non-visual responses to light, and the R1-R6 photoreceptors, which are the fly equivalent to the vertebrate rods. The Gq opsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANH-FMILCGFTVTMYTSLHGYFVFGQTGCYFEGF 98
Cdd:cd15337  18 NLLVIYLFSKTKSLRTPSNMFIINLAISDFgFSAVNGFPLKTISSFNKKWIWGKVACELYGF 79

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
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGFF 99
Cdd:cd15202  18 NVLVCWIIFKNQRMRTVTNYFIVNLAVADIMITLFNTPFTFVRAVNNTWIFGLFMCHFSNFA 79

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYF 95
Cdd:cd14967  17 NLLVILAVYRNRRLRTVTNYFIVSLAVADLLVALLVMPFSAVYTLLGYWPFGPVLCRF 74

substance-K receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The substance-K receptor (SKR), also known as tachykinin receptor 2 (TACR2) or neurokinin A receptor or NK2R, is a G-protein coupled receptor that specifically binds to neurokinin A. 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 the regulation of gastrointestinal motility, secretion, vascular permeability, and pain perception.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGFF 99
Cdd:cd16004  18 NATVIWIILAHRRMRTVTNYFIVNLALADLSMAAFNTAFNFVYASHNDWYFGLEFCRFQNFF 79

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
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGCYFEGFF 99
Cdd:cd15206  18 NILVIVTLVQNKRMRTVTNVFLLNLAVSDLLLAVFCMPFTLVGQLLRNFIFGEVMCKLIPYF 79

serotonin receptor subtype 7, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT7 receptor, one of 14 mammalian serotonin receptors, is a member of the class A of GPCRs and is activated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). 5-HT7 receptor mainly couples to Gs protein, which positively stimulates adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. 5-HT7 receptor is expressed in various human tissues, mainly in the brain, the lower gastrointestinal tract and in vital blood vessels including the coronary artery. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|....*
gi 67867336  49 KKLRTPLNYILLNLAFANHFMILCGFTVTMYTSLHGYFVFGQTGC 93
Cdd:cd15329  29 KKLRTPSNYLIVSLAVSDLLVALLVMPLAIIYELSGYWPFGEILC 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.

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gi 67867336  38 NFMTLFVT*QHKKLRTPLNYILLNLAFANHFMILcgFTVTMYTS--LHGYFVFGQTGC 93
Cdd:cd15048  18 NLLVILAFIKDKKLRTVSNFFLLNLAVADFLVGL--VSMPFYIPytLTGKWPFGKVFC 73