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 77025118   1 VAAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15076 196 VAAQQQESASTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRDHGLDLRLVTIPAFFSKSSCVYNPIIYCFMNKQ 275

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77025118   1 VAAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15076 196 VAAQQQESASTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRDHGLDLRLVTIPAFFSKSSCVYNPIIYCFMNKQ 275

G protein-coupled chemokine receptor-like protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77025118   13 KAEREVSRMVVVMVGSFCLCYVPYA----ALAMYMVNNRNHGLDLRLVTIPAF----FSKSACVYNPIIYCFMNK 79
Cdd:PHA03087 237 KKNKKAIKLVLIIVILFVIFWLPFNvsvfVYSLHILHFKSGCKAVKYIQYALHvteiISLSHCCINPLIYAFVSE 311

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77025118   1 VAAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15076 196 VAAQQQESASTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRDHGLDLRLVTIPAFFSKSSCVYNPIIYCFMNKQ 275

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 77025118   1 VAAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15084 204 VAAQQKESETTQRAEKEVTRMVIAMVMAFLICWLPYATFAMVVATNKDVVIQPTLASLPSYFSKTATVYNPIIYVFMNKQ 283

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 77025118   2 AAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15080 197 AAQQQESATTQKAEKEVTRMVIIMVIAFLICWVPYASVAFYIFTHQGSDFGPIFMTIPAFFAKSSAVYNPVIYILMNKQ 275

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 77025118   1 VAAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15082 207 VSNTQGRLGNARKPERQVTRMVVVMIVAFMVCWTPYAAFSILVTAHPTIHLDPRLAAIPAFFSKTAAVYNPIIYVFMNKQ 286

non-visual parietopsins, member of the class A family of seven-transmembrane G protein-coupled receptors; Parietopsin is a non-visual green light-sensitive opsin that was initially identified in the parietal eye of lizards. 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. Parietopsin 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        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77025118   4 QQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15085 199 EQQGGKNCPEEEERAVIMVLAMVIAFLICWLPYTVFALIVVVNPELSISPLAATMPTYFAKTSPVYNPIIYIFLNKQ 275

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 77025118  10 TTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15086 201 TARKREQHVLLMVVTMVICYLLCWLPYGVMALLATFGKPGLVTPVASIVPSILAKSSTVVNPIIYVFMNKQ 271

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 77025118  11 TQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCF 76
Cdd:cd15083 217 RRQAEVKTAKIALLLVLLFCLAWTPYAVVALIGQFGYLEVLTPLATAIPAAFAKTSAIYNPVIYAF 282

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 77025118   4 QQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPA-FFSKSACVYNPIIYCFMN 78
Cdd:cd00637 200 SNSSRRRRRRRERKVTKTLLIVVVVFLLCWLPYFILLLLDVFGPDPSPLPRILYFLAlLLAYLNSAINPIIYAFFN 275

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 77025118  13 KAEREVSRMVVVMVGSFCLCYVPYAA--LAMYMVNNRNHGLDLRLVTIpAFF--SKSACVYNPIIYCFMNK 79
Cdd:cd15390 214 RAKRKVVKMMIVVVVIFAICWLPYHLyfILTYLYPDINSWKYIQQIYL-AIYwlAMSNSMYNPIIYCWMNK 283

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 77025118  15 EREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15073 210 QNDVTKMSVIMIVMFLVAWSPYSIVCLWASFGEPKKIPPWMAIIPPLFAKSSTFYNPCIYVIANKK 275

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 77025118  13 KAEREVSRMVVVMVGSFCLCYVPY----AALAMYMVNNRNHGLDLRLVTIpAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd16003 207 RAKRKVVKMMIIVVLTFAICWLPYhiyfIVTGLYQQLNRWKYIQQVYLAS-FWLAMSSTMYNPIIYCCLNKR 277

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77025118   1 VAAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMN 78
Cdd:cd14986 211 VSCVSSRVSLISRAKIKTIKMTLVIILAFILCWTPYFIVQLLDVYAGMQQLENDAYVVSETLASLNSALNPLIYGFFS 288

neuropeptide Y receptor-like found in insect and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes a novel G protein-coupled receptor (also known as PR4 receptor) from Drosophila melanogaster, which can be activated by the members of the neuropeptide Y (NPY) family, including NPY, peptide YY (PYY) and pancreatic polypeptide (PP), when expressed in Xenopus oocytes. These homologous peptides of 36-amino acids in length contain a hairpin-like structural motif, which referred to as the pancreatic polypeptide fold, and function as gastrointestinal hormones and neurotransmitters. The PR4 receptor also shares strong sequence homology to the mammalian tachykinin receptors (NK1R, NK2R, and NK3R), whose endogenous ligands are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), respectively. The tachykinins function as excitatory transmitters on neurons and cells in the gastrointestinal tract.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77025118  13 KAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNN--RNHGLDLRLVTIPA-FFSKSACVYNPIIYCFMN 78
Cdd:cd15392 212 ESKRKLVKMMITVVAIFALCWLPLNILNLVGDHDesIYSWPYIPYLWLAAhWLAMSHCCYNPFIYCWMN 280

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 77025118   3 AQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAF--FSKSACVYNPIIYCFMN 78
Cdd:cd15202 204 ATTERYFALRRKKKKVIKMLMVVVVLFALCWLPFNIYVLLLSSKPDYLIKTINAVYFAFhwLAMSSTCYNPFIYCWLN 281

invertebrate gonadotropin-releasing hormone receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; GnRHR, also known as luteinizing hormone releasing hormone receptor (LHRHR), plays an central role in vertebrate reproductive function; its activation by binding to GnRH leads to the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. GnRHR is expressed predominantly in the gonadotrope membrane of the anterior pituitary as well as found in numerous extrapituitary tissues including lymphocytes, breast, ovary, prostate, and cancer cell lines. There are at least two types of GnRH receptors, GnRHR1 and GnRHR2, which couple primarily to G proteins of the Gq/11 family. GnRHR is closely related to the adipokinetic hormone receptor (AKH), which binds to a lipid-mobilizing hormone that is involved in control of insect metabolism. They share a common ancestor and are members of the class A of the seven-transmembrane, G-protein coupled receptor (GPCR) superfamily.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77025118  13 KAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIY 74
Cdd:cd15384 220 KAKVKSLRMSAVIVTAFILCWTPYYVIMIWFLFFNPYPLNDILFDVIFFFGMSNSCVNPLIY 281

proton-sensing G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Proton/pH-sensing G-protein coupled receptors sense pH of 7.6 to 6.0. They mediate a variety of biological activities in neutral and mildly acidic pH conditions, whereas the acid-sensing ionotropic ion channels typically sense strong acidic pH. The proton/pH-sensing receptor family includes the G2 accumulation receptor (G2A, also known as GPR132), the T cell death associated gene-8 (TDAG8, GPR65) receptor, ovarian cancer G-protein receptor 1 (OGR-1, GPR68), and G-protein-coupled receptor 4 (GPR4).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77025118   8 SATTQKAE-REVSRMVVVMVGSFCLCYVPYAAL-----AMYMVNNRNHGLDLRLVT---IPAFFSKSACVYNPIIYCFMN 78
Cdd:cd15160 194 SPSLEREEkRKIIGLLLSIVVIFLLCFLPYHVVllvrsVIELVQNGLCGFEKRVFTayqISLCLTSLNCVADPILYIFVT 273

                .
gi 77025118  79 K 79
Cdd:cd15160 274 E 274

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77025118   8 SATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNH----GLDLRLVTIPAFFSKSACvyNPIIYCFMNKQ 80
Cdd:cd14971 202 SEGSRRAKRKVTRLVLVVVVLFAACWGPIHAILLLVALGPFPltyaTYALRIWAHCLAYSNSAV--NPVLYAFLSEH 276

allatostatin-A receptor in insects, member of the class A family of seven-transmembrane G protein-coupled receptors; The G protein-coupled AstA receptor binds allatostatin A. Three distinct types of allatostatin have been identified in the insects and crustaceans: AstA, AstB, and AstC. They both inhibit the biosynthesis of juvenile hormone and exert an inhibitory influence on food intake. Therefore, allatostatins are considered as potential targets for insect control.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77025118   8 SATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAF----FSKSaCVyNPIIYCFM 77
Cdd:cd15096 205 SAESQRGKRRVTRLVVVVVVVFAICWLPIHIILLLKYYGVLPETVLYVVIQILSnclaYGNS-CV-NPILYAFL 276

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 77025118  13 KAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVY----NPIIYCFM 77
Cdd:cd15208 227 RSRRKTAKMLIVVVIMFAICYLPVHLLNILRYVFGLFTVDRETIYAWFLFSHWLVYAnsaiNPIIYNFM 295

trissin receptor and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup represents the Drosophila melanogaster trissin receptor and closely related invertebrate proteins which are a member of the class A family of seven-transmembrane G-protein coupled receptors. The cysteine-rich trissin has been shown to be an endogenous ligand for the orphan CG34381 in Drosophila melanogaster. Trissin is a peptide composed of 28 amino acids with three intrachain disulfide bonds with no significant structural similarities to known endogenous peptides. Cysteine-rich peptides are known to have antimicrobial or toxicant activities, although frequently their mechanism of action is poorly understood. Since the expression of trissin and its receptor is reported to predominantly localize to the brain and thoracicoabdominal ganglion, trissin is predicted to behave as a neuropeptide. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77025118   9 ATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMY------MVNNRNHGLDLRLVTIPAFFSKSACvyNPIIYCFMNK 79
Cdd:cd15012 197 SSSIEARRKVVRLLVAVVVSFALCNLPYHARKMWqywsepYRCDSNWNALLTPLTFLVLYFNSAV--NPLLYAFLSK 271

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 77025118   3 AQQQESATTQKAEREVSRMVVVMVGSFCLCYVPY-AALAMYMV---------NNRNHGLDLRLVTIpaFFSKSACVYNPI 72
Cdd:cd14982 193 RRRSKQSQKSVRKRKALRMILIVLAVFLVCFLPYhVTRILYLLvrlsfiadcSARNSLYKAYRITL--CLASLNSCLDPL 270

                ....*..
gi 77025118  73 IYCFMNK 79
Cdd:cd14982 271 IYYFLSK 277

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.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 77025118  13 KAEREVSRMVVVMVGSFCLCYVPYAA---LAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd16004 210 QAKKKFVKTMVVVVVTFAICWLPYHLyfiLGSFNEDIYCQKYIQQVYLAIFWLAMSSTMYNPIIYCCLNQR 280

somatostatin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled somatostatin receptors (SSTRs) are composed of five distinct subtypes (SSTR1-5) that display strong sequence similarity with opioid receptors. All five receptor subtypes bind the natural somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. They share common signaling cascades such as inhibition of adenylyl cyclase, activation of phosphotyrosine phosphatase activity, and G-protein-dependent regulation of MAPKs.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77025118   8 SATTQKAEREVSRMVVVMVGSFCLCYVPYaalamYMVNNRNhgLDLRLVTIPAFFSKS----------ACVyNPIIYCFM 77
Cdd:cd15093 201 WQQRKRSERKVTRMVVMVVVVFVICWLPF-----YVLQLVN--VFVQLPETPALVGVYhfvvilsyanSCA-NPILYGFL 272

G protein-coupled receptor 84 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR84, also known as the inflammation-related G-Protein coupled receptor EX33, is a receptor for medium-chain free fatty acid (FFA) with carbon chain lengths of C9 to C14. Among these medium-chain FFAs, capric acid (C10:0), undecanoic acid (C11:0), and lauric acid (C12:0) are the most potent endogenous agonists of GPR84, whereas short-chain and long-chain saturated and unsaturated FFAs do not activate this receptor. GPR84 contains a [G/N]RY-motif instead of the highly conserved Asp-Arg-Tyr (DRY) motif found in the third transmembrane helix (TM3) of the rhodopsin-like class A receptors and important for efficient G protein-coupled signal transduction. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, which then activate the heterotrimeric G proteins. In the case of GPR84, activation of the receptor couples to a pertussis toxin sensitive G(i/o)-protein pathway. GPR84 knockout mice showed increased Th2 cytokine production including IL-4, IL-5, and IL-13 compared to wild-type mice. It has been also shown that activation of GPR84 augments lipopolysaccharide-stimulated IL-8 production in polymorphonuclear leukocytes and TNF-alpha production in macrophages, suggesting that GPR84 may function as a proinflammatory receptor.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77025118  15 EREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLrLVTIPAFFskSACVyNPIIYCFMNKQ 80
Cdd:cd15210 188 DRRLTRMMLVIFLCFLVCYLPITLVNVFDDEVAPPVLHI-IAYVLIWL--SSCI-NPIIYVAMNRQ 249

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 77025118   7 ESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLV-----TIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd14979 217 ELSLSQQARRQVVKMLGAVVIAFFVCWLPFHAQRLMFSYASKEDTFLFDFyqylyPISGILFYLSSAINPILYNLMSSR 295

platelet-activating factor receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The platelet-activating factor receptor is a G(q/11)-protein coupled receptor, which is linked to p38 MAPK and PI3K signaling pathways. PAF is a phospholipid (1-0-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) which is synthesized by cells especially involved in host defense such as platelets, macrophages, neutrophils, and monocytes. PAF is well-known for its ability to induce platelet aggregation and anaphylaxis, and also plays important roles in allergy, asthma, and inflammatory responses, among many others.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77025118   3 AQQQESATTQkaeREVSRMVVVMVGSFCLCYVPY---------AALAMYMVN--------NRNHGLDLRLVTIpaffsks 65
Cdd:cd15147 202 VQGQRNAGVK---RRALWMVCTVLAVFVICFVPHhvvqgpwtlAVLQQWRYWdcqfrqalNDAHQITLCLMST------- 271

                        90
                ....*....|....*
gi 77025118  66 ACVYNPIIYCFMNKQ 80
Cdd:cd15147 272 NCVLDPVIYCFLTKK 286

bombesin receptor subfamily, member of the class A family of seven-transmembrane G protein-coupled receptors; This bombesin subfamily of G-protein coupled receptors consists of neuromedin B receptor (NMBR), gastrin-releasing peptide receptor (GRPR), and bombesin receptor subtype 3 (BRS-3). Bombesin is a tetradecapeptide, originally isolated from frog skin. Mammalian bombesin-related peptides are widely distributed in the gastrointestinal and central nervous systems. The bombesin family receptors couple mainly to the G proteins of G(q/11) family. NMBR functions as the receptor for the neuropeptide neuromedin B, a potent mitogen and growth factor for normal and cancerous lung and for gastrointestinal epithelial tissues. Gastrin-releasing peptide is an endogenous ligand for GRPR and shares high sequence homology with NMB in the C-terminal region. Both NMB and GRP possess bombesin-like biochemical properties. BRS-3 is classified as an orphan receptor and suggested to play a role in sperm cell division and maturation. BRS-3 interacts with known naturally-occurring bombesin-related peptides with low affinity; however, no endogenous high-affinity ligand to the receptor has been identified. The bombesin receptor family belongs to the seven transmembrane rhodopsin-like G-protein coupled receptors (class A GPCRs), which perceive extracellular signals and transduce them to guanine nucleotide-binding (G) proteins.

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                ....*....|....*....|....*....|....*....|
gi 77025118   4 QQQESATTQ-KAEREVSRMVVVMVGSFCLCYVPYAALAMY 42
Cdd:cd15927 207 GQNQAAQRQiEARKKVAKTVLAFVVLFAVCWLPRHVFMLW 246

FMRFamide (Phe-Met-Arg-Phe) receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes Drosophila melanogaster G-protein coupled FMRFamide (Phe-Met-Arg-Phe-NH2) receptor DrmFMRFa-R and related invertebrate receptors, as well as the vertebrate proteins GPR139 and GPR142. DrmFMRFa-R binds with high affinity to FMRFamide and intrinsic FMRFamide-related peptides. FMRFamide is a neuropeptide from the family of FMRFamide-related peptides (FaRPs), which all containing a C-terminal RFamide (Arg-Phe-NH2) motif and have diverse functions in the central and peripheral nervous systems. FMRFamide is an important neuropeptide in many types of invertebrates such as insects, nematodes, molluscs, and worms. In invertebrates, the FMRFamide-related peptides are involved in the regulation of heart rate, blood pressure, gut motility, feeding behavior, and reproduction. On the other hand, in vertebrates such as mice, they play a role in the modulation of morphine-induced antinociception. Orphan receptors GPR139 and GPR142 are very closely related G protein-coupled receptors, but they have different expression patterns in the brain and in other tissues. These receptors couple to inhibitory G proteins and activate phospholipase C. Studies suggested that dimer formation may be required for their proper function. GPR142 is predominantly expressed in pancreatic beta-cells and mediates enhancement of glucose-stimulated insulin secretion, whereas GPR139 is mostly expressed in the brain and is suggested to play a role in the control of locomotor activity. Tryptophan and phenylalanine have been identified as putative endogenous ligands of GPR139.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77025118  12 QKAEREVSRMVVVMVGSFCLCYVPYA---ALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd14978 223 QRRERRTTIMLIAVVIVFLICNLPAGilnILEAIFGESFLSPIYQLLGDISNLLVVLNSAVNFIIYCLFSSK 294

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 77025118  14 AEREVSRMVVVMVGSFCLCYVPYAA---LAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMN 78
Cdd:cd16002 210 AKRKVVKMMIVVVCTFAICWLPYHIyflLQYFHPELYEQKFIQQVYLAIMWLAMSSTMYNPIIYCCLN 277

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

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77025118  20 RMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIP-----AFFskSACVyNPIIYCFMNKQ 80
Cdd:cd14974 207 RVLLAVVVAFFLCWLPYHVFALLELVAAAGLPEVVLLGLPlatglAYF--NSCL-NPILYVFMGQD 269