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 90184294  31 SVLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd15080   1 SALAAYMFLLILLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTMYTSMHGYFVFGPTGCNL 75

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 90184294  31 SVLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd15080   1 SALAAYMFLLILLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTMYTSMHGYFVFGPTGCNL 75

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 90184294    48 NFMTLYVTIQHKKLRTPLNYILLNLAFANH-FMVLCGFTITLYTSLHGYFVFGQTGC 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 90184294  31 SVLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd15080   1 SALAAYMFLLILLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTMYTSMHGYFVFGPTGCNL 75

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 90184294  31 SVLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd14969   1 YVLAVYLSLIGVLGVVLNGLVIIVFLKKKKLRTPLNLFLLNLALADLLMSVVGYPLSFYSNLSGRWSFGDPGCVI 75

non-visual pinopsins, member of the class A family of seven-transmembrane G protein-coupled receptors; Pinopsins are found in the pineal organ of birds, reptiles and amphibians, but are absent from teleosts and mammals. 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. Pinopsins 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 90184294  23 YLAEPWKYSVLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTG 102
Cdd:cd15084   3 HLAPRSTYLTVAVLMGMVVALASFVNGLVIVVSIKYKKLRSPLNYILVNLAVADLLVTLFGSSVSFSNNIVGFFVFGKTM 82

                ...
gi 90184294 103 CYF 105
Cdd:cd15084  83 CEF 85

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 90184294  34 AAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGC 103
Cdd:cd15076   4 AAFMGFVFIVGTPLNAIVLFVTIKYKKLRQPLNYILVNISLAGFIFCIFSVFPVFVASAQGYFFFGRTVC 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 90184294  33 LAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCgFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd15079   3 LGFIYIFLGIVSLLGNGLVIYIFSTTKSLRTPSNMLVVNLAISDFLMMIK-MPIFIYNSFYEGWALGPLGCQI 74

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 90184294  31 SVLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGC 103
Cdd:cd15083   1 YVLGIFILIIGLIGVVGNGLVIYAFCRFKSLRTPANYLIINLAISDFLMCILNCPLMVISSFSGRWIFGKTGC 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 90184294  31 SVLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGC 103
Cdd:cd15073   1 NIVAAYLIVAGIISTISNGIVLVTFVKFRELRTPTNALIINLAVTDLGVSIIGYPFSAASDLHGSWKFGYAGC 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 90184294  39 MLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd15203   9 LIIVLGVVGNLLVIYVVLRNKSMQTVTNIFILNLAVSDLLLCLVSLPFTLIYTLTKNWPFGSILCKL 75

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 90184294  32 VLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd14967   1 LLAVFLSLIILVTVFGNLLVILAVYRNRRLRTVTNYFIVSLAVADLLVALLVMPFSAVYTLLGYWPFGPVLCRF 74

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 90184294  33 LAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd00637   1 LAVLYILIFVVGLVGNLLVILVILRNRRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRWWFGDALCKL 73

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 90184294    48 NFMTLYVTIQHKKLRTPLNYILLNLAFANH-FMVLCGFTITLYTSLHGYFVFGQTGC 103
Cdd:pfam00001   2 NLLVILVILRNKKLRTPTNIFLLNLAVADLlFSLLTLPFWLVYYLNHGDWPFGSALC 58

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 90184294  32 VLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGC 103
Cdd:cd15086   2 VVAVFLGFILTFGFLNNLLVLVLFCKYKVLRSPINLLLLNISLSDLLVCVLGTPFSFAASTQGRWLIGEHGC 73

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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 90184294  32 VLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANH-FMVLCGFTITLYTSLHGYFVFGQTGC 103
Cdd:cd15337   2 LIGIYIAIVGILGVIGNLLVIYLFSKTKSLRTPSNMFIINLAISDFgFSAVNGFPLKTISSFNKKWIWGKVAC 74

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 90184294  30 YSVLAAYMFMLILLGlpiNFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd15390   3 WSIVFVVMVLVAIGG---NLIVIWIVLAHKRMRTVTNYFLVNLAVADLLISAFNTVFNFTYLLYNDWPFGLFYCKF 75

cholecystokinin receptor type B, 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 90184294  32 VLAAYMFMLILLGlpiNFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGC 103
Cdd:cd15979   5 LLYSVIFLLSVFG---NMLIIVVLGLNKRLRTVTNSFLLSLALSDLMLAVFCMPFTLIPNLMGTFIFGEVIC 73

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 90184294  32 VLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd15202   2 LLIVAYSFIIVFSLFGNVLVCWIIFKNQRMRTVTNYFIVNLAVADIMITLFNTPFTFVRAVNNTWIFGLFMCHF 75

putative neuropeptide receptor BNGR-A34 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes putative neuropeptide receptor BNGR-A34 found in silkworm and its closely related proteins from invertebrates. They are members of the class A rhodopsin-like GPCRs, which represent a widespread protein family that includes 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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 90184294  37 MFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd15000   6 FLPVVLFGIFGNFVLLYILASNRSLRTPTNLLIGNMALADLLTLLVCPWMFLVHDFFQNYVLGSVGCKL 74

encephalopsins (opsin-3), member of the class A family of seven-transmembrane G protein-coupled receptors; Encephalopsin, also called Opsin-3 or Panopsin, is a mammalian extra-retinal opsin that is highly localized in the brain. It is thought to play a role in encephalic photoreception. Encephalopsin belongs to the class A of the G protein-coupled receptors and shows strong homology to the vertebrate visual opsins.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 90184294  42 LLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCYF 105
Cdd:cd15078  12 FLGVCNNLLVLILYYKFKRLRTPTNLLLVNISLSDLLVSLLGVTFTFMSCVRGRWVFDVAGCVW 75

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 90184294  40 LILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFAN-HFMVLCG-FTITLYTSLHgyFVFGQTGCYF 105
Cdd:cd15095  10 IFLVGLAGNSLVIYVVSRHREMRTVTNYYIVNLAVTDlAFLVCCVpFTAALYATPS--WVFGDFMCKF 75

galanin receptor and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes G-protein coupled galanin receptors, kisspeptin receptor and allatostatin-A receptor (AstA-R) in insects. These receptors, which are members of the class A of seven transmembrane GPCRs, share a high degree of sequence homology among themselves. The galanin receptors bind galanin, a neuropeptide that is widely expressed in the brain, peripheral tissues, and endocrine glands. Galanin is implicated in numerous neurological and psychiatric diseases including Alzheimer's disease, eating disorders, and epilepsy, among many others. KiSS1-derived peptide receptor (also known as GPR54 or kisspeptin receptor) binds the peptide hormone kisspeptin (metastin), which encoded by the metastasis suppressor gene (KISS1) expressed in various endocrine and reproductive tissues. AstA-R is a G-protein coupled receptor that binds allatostatin A. Three distinct types of allatostatin have been identified in the insects and crustaceans: AstA, AstB, and AstC. They both inhibit the biosynthesis of juvenile hormone and exert an inhibitory influence on food intake. Therefore, allatostatins are considered as potential targets for insect control.

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gi 90184294  32 VLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLC--GFTITLYTSLHgyFVFGQTGCYF 105
Cdd:cd14971   2 IVPLFFALIFLLGLVGNSLVILVVARNKPMRSTTNLFILNLAVADLTFLLFcvPFTATIYPLPG--WVFGDFMCKF 75

neuropeptide Y receptor type 2, 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 G(i) or G(o) 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. When NPY signals through NPY2R in concert with NPY5R, it induces angiogenesis and consequently plays an important role in revascularization and wound healing. On the other hand, when NPY acts through NPY1R and NPYR5, it acts as a vascular mitogen, leading to restenosis and atherosclerosis.

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gi 90184294  40 LILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGCY 104
Cdd:cd15399  10 IILLGVVGNSLVIYVVIKFKNMRTVTNFFIANLAVADLMVNTLCLPFTLVYTLLDEWKFGAVLCH 74

purinoceptor and its related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; Members of this subfamily include lysophosphatidic acid receptor, P2 purinoceptor, protease-activated receptor, platelet-activating factor receptor, Epstein-Barr virus induced gene 2, proton-sensing G protein-coupled receptors, GPR35, and GPR55, among others. 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 90184294  32 VLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGC 103
Cdd:cd14982   2 LFPIVYSLIFILGLLGNILALWVFLRKMKKRSPTTIYMINLALADLLFVLTLPFRIYYYLNGGWWPFGDFLC 73

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.

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gi 90184294  41 ILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGC 103
Cdd:cd15391  11 IFLSVGGNYSVIVVFYDGRRSRTDLNYYLINLAVSDLIMALFCMPFTFTQIMLGHWVFPAPMC 73

orexin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; 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. Thus, activation of OX1R or OX2R will activate phospholipase activity and the phosphatidylinositol and calcium signaling pathways. Additionally, OX2R activation can also lead to inhibition of adenylate cyclase.

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gi 90184294  32 VLAAYMFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGC 103
Cdd:cd15208   2 VLIALYILVFIVGLVGNVLVCFAVWRNHHMRTVTNYFIVNLSLADFLVIIICLPATLLVDVTETWFFGQVLC 73

Drosophila melanogaster beta-adrenergic receptor-like octopamine receptors and similar receptors in bilateria; member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes Drosophila beta-adrenergic-like octopamine receptors and similar proteins. The biogenic amine octopamine is the invertebrate equivalent of vertebrate adrenergic neurotransmitters and exerts its effects through different G protein-coupled receptor types. Insect octopamine receptors are involved in the modulation of carbohydrate metabolism, muscular tension, cognition and memory. The activation of octopamine receptors mediating these actions leads to an increase in adenylate cyclase activity, thereby increasing cAMP levels. In Drosophila melanogaster, three subgroups have been classified on the basis of their structural homology and functional equivalents with vertebrate beta-adrenergic receptors: DmOctBeta1R, DmOctBeta2R, and DmOctBeta3R.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 90184294  37 MFMLILLGLPINFMTLYVTIQHKKLRTPLNYILLNLAFANHFMVLCGFTITLYTSLHGYFVFGQTGC 103
Cdd:cd15066   6 MTLIILAAIFGNLLVIISVMRHRKLRVITNYFVVSLAMADMLVALCAMTFNASVEITGRWMFGYFMC 72