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 77025099   2 AAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15076 197 AAQQQESASTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRDHGLDLRLVTIPAFFSKSSCVYNPIIYCFMNKQ 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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77025099   2 AAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15076 197 AAQQQESASTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRDHGLDLRLVTIPAFFSKSSCVYNPIIYCFMNKQ 275

G protein-coupled chemokine receptor-like protein; Provisional

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 77025099   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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 77025099   2 AAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15076 197 AAQQQESASTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRDHGLDLRLVTIPAFFSKSSCVYNPIIYCFMNKQ 275

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 77025099   1 AAAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15080 196 AAAQQQESATTQKAEKEVTRMVIIMVIAFLICWVPYASVAFYIFTHQGSDFGPIFMTIPAFFAKSSAVYNPVIYILMNKQ 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 77025099   1 AAAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15084 204 VAAQQKESETTQRAEKEVTRMVIAMVMAFLICWLPYATFAMVVATNKDVVIQPTLASLPSYFSKTATVYNPIIYVFMNKQ 283

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77025099   9 ATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd15082 215 GNARKPERQVTRMVVVMIVAFMVCWTPYAAFSILVTAHPTIHLDPRLAAIPAFFSKTAAVYNPIIYVFMNKQ 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 77025099   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 77025099  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 77025099  11 TQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCF 76
Cdd:cd15083 217 RRQAEVKTAKIALLLVLLFCLAWTPYAVVALIGQFGYLEVLTPLATAIPAAFAKTSAIYNPVIYAF 282

7 transmembrane receptor (rhodopsin family); This family contains, amongst other G-protein-coupled receptors (GCPRs), members of the opsin family, which have been considered to be typical members of the rhodopsin superfamily. They share several motifs, mainly the seven transmembrane helices, GCPRs of the rhodopsin superfamily. All opsins bind a chromophore, such as 11-cis-retinal. The function of most opsins other than the photoisomerases is split into two steps: light absorption and G-protein activation. Photoisomerases, on the other hand, are not coupled to G-proteins - they are thought to generate and supply the chromophore that is used by visual opsins.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77025099     1 AAAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPA---FFSKSACVYNPIIY 74
Cdd:pfam00001 180 KSASKQKSSERTQRRRKALKTLAVVVVVFILCWLPYHIVNLLDSLALDCELSRLLDKALSvtlWLAYVNSCLNPIIY 256

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 77025099  13 KAEREVSRMVVVMVGSFCLCYVPYAA--LAMYMVNNRNHGLDLRLVTIpAFF--SKSACVYNPIIYCFMNK 79
Cdd:cd15390 214 RAKRKVVKMMIVVVVIFAICWLPYHLyfILTYLYPDINSWKYIQQIYL-AIYwlAMSNSMYNPIIYCWMNK 283

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
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 77025099  12 QKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIY 74
Cdd:cd15079 219 QSAEIRIAKVALTNVFLWFIAWTPYAVVALIGAFGNQSLLTPLVSMIPALFAKTAACYNPIVY 281

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 77025099  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 77025099   1 AAAQQQESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMN 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 77025099  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 77025099   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 77025099  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 77025099   8 SATTQKAE-REVSRMVVVMVGSFCLCYVPYAAL-----AMYMVNNRNHGLDLRLVT---IPAFFSKSACVYNPIIYCFMN 78
Cdd:cd15160 194 SPSLEREEkRKIIGLLLSIVVIFLLCFLPYHVVllvrsVIELVQNGLCGFEKRVFTayqISLCLTSLNCVADPILYIFVT 273

                .
gi 77025099  79 K 79
Cdd:cd15160 274 E 274

relaxin-3 like peptide receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This G protein-coupled receptor subfamily is composed of the relaxin-3 like peptide receptors, RNL3R1 and RNL3R2, and similar proteins. The relaxin-3 like peptide family includes relaxin-1, -2, -3, as well as insulin-like (INSL) peptides 3 to 6. RNL3/relaxin-3 and INSL5 are the endogenous ligands for RNL3R1 and RNL3R2, respectively. RNL3R1, also called GPCR135 or RXFP3, is predominantly expressed in the brain and is implicated in stress, anxiety, feeding, and metabolism. Insulin-like peptide 5 (INSL5), the endogenous ligand for RNL3R2 (also called GPCR142 or RXFP4), plays a role in fat and glucose metabolism. INSL5 is highly expressed in human rectal and colon tissues. Both RNL3R1 and RNL3R2 signal through G(i) protein and inhibit adenylate cyclase, thereby inhibit cAMP accumulation. RNL3R1 is shown to activate Erk1/2 signaling pathway.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 77025099  16 REVSRMVVVMVGSFCLCYVPYAALAMY---------MVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd14976 212 SRVTKSVFIVVLSFFICWLPNQALSLWsalikfddvPFSDAFFAFQTYAFPVAICLAHSNSCLNPVLYCLVRRE 285

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 77025099   8 SATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNH----GLDLRLVTIPAFFSKSACvyNPIIYCFMNKQ 80
Cdd:cd14971 202 SEGSRRAKRKVTRLVLVVVVLFAACWGPIHAILLLVALGPFPltyaTYALRIWAHCLAYSNSAV--NPVLYAFLSEH 276

opioid receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes opioid receptors, somatostatin receptors, melanin-concentrating hormone receptors (MCHRs), and neuropeptides B/W receptors. Together they constitute the opioid receptor-like family, members of the class A G-protein coupled receptors. Opioid receptors are coupled to inhibitory G proteins of the G(i/o) family and are involved in regulating a variety of physiological functions such as pain, addiction, mood, stress, epileptic seizure, and obesity, among many others. G protein-coupled somatostatin receptors (SSTRs), which display strong sequence similarity with opioid receptors, binds 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. MCHR binds melanin concentrating hormone and is presumably involved in the neuronal regulation of food intake. Despite strong homology with somatostatin receptors, MCHR does not appear to bind somatostatin. Neuropeptides B/W receptors are primarily expressed in the CNS and stimulate the cortisol secretion by activating the adenylate cyclase- and the phospholipase C-dependent signaling pathways.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 77025099   8 SATTQKAEREVSRMVVVMVGSFCLCYVPYaalAMYMVNNRNHGLDLRLVTIPAFFSKSACVY-----NPIIYCFMNKQ 80
Cdd:cd14970 203 AREKRRARRKVTRLVLVVVAVFVVCWLPF---HVFQIVRLLIDPPETLTVVGVFLFCIALSYansclNPILYAFLDEN 277

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.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77025099   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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77025099   3 AQQQESATTQKAEREVSRMVVVMVGSFCLCYVPY-AALAMYMV---------NNRNHGLDLRLVTIpaFFSKSACVYNPI 72
Cdd:cd14982 193 RRRSKQSQKSVRKRKALRMILIVLAVFLVCFLPYhVTRILYLLvrlsfiadcSARNSLYKAYRITL--CLASLNSCLDPL 270

                ....*..
gi 77025099  73 IYCFMNK 79
Cdd:cd14982 271 IYYFLSK 277

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

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|
gi 77025099  29 FCLCYVPYAALAMYMVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMN 78
Cdd:cd15072 204 LLICWGPYAILALYAAITDVTSISPKLRMVPALLAKTSPTINAILYALGN 253

somatostatin receptor type 5, 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. SSTR5 is coupled to inward rectifying K channels and phospholipase C, and plays critical roles in growth hormone and insulin secretion. SSTR5 acts as a negative regulator of PDX-1 (pancreatic and duodenal homeobox-1) expression, which is a conserved homeodomain-containing beta cell-specific transcription factor essentially involved in pancreatic development, among many other functions.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77025099   8 SATTQKAEREVSRMVVVMVGSFCLCYVPYaalamYMVNNRNhgLDLRLVTIPAF---------FSKSACVYNPIIYCFMN 78
Cdd:cd15974 198 STKRRKSERKVTRMVVIIVVVFVFCWLPF-----YMLNIVN--LIVILPEEPAFvgvyffvvvLSYANSCANPILYGFLS 270

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.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 77025099  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 77025099   7 ESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNHGLDLRLV-----TIPAFFSKSACVYNPIIYCFMNKQ 80
Cdd:cd14979 217 ELSLSQQARRQVVKMLGAVVIAFFVCWLPFHAQRLMFSYASKEDTFLFDFyqylyPISGILFYLSSAINPILYNLMSSR 295

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

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 77025099  13 KAEREVSRMVVVMVGSFCLCYVPYAALAMY-----MVNNRNHGLDLRLVTIPAFFSKSACVYNPIIYCFMNK 79
Cdd:cd15391 212 KSKRKVIKMLVFVVLMFGICWLPLHLFNLVqdfstVFRNMPQHTTRLIYGACHWIAMSNSFVNPIIYLFMND 283

proton-sensing G protein-coupled receptor 4, member of the class A family of seven-transmembrane G protein-coupled receptors; G-protein-coupled receptor 4 (GPR4) is a member of the proton-sensing G-protein-coupled receptor (GPCR) family which also includes the G2 accumulation receptor (G2A, also known as GPR132), the T cell death associated gene-8 receptor (TDAG8, GPR65), ovarian cancer G-protein receptor 1 (OGR-1, GPR68), and G-protein-coupled receptor 4 (GPR4). Proton-sensing G-protein coupled receptors sense pH of 7.6 to 6.0 and mediates a variety of biological activities in neutral and mildly acidic pH conditions, whereas the acid-sensing ionotropic ion channels typically sense strong acidic pH. GPR4 overexpression in melanoma cells was shown to reduce cell migration, membrane ruffling, and cell spreading under acidic pH conditions. Activation of GPR4 via extracellular acidosis is coupled to the G(s), G(q), and G(12/13) pathways.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77025099   9 ATTQKAEREVSRMVVVMVGSFCLCYVPYAAL-----AMYMVNNRNHGLDLRLvtIPAFFSKSA-----CVYNPIIYCFMN 78
Cdd:cd15366 196 STEQQEKAKIKRLALSLIAIVLLCFAPYHVLllsrsVVYLGKPCDCGFEERV--FTAYHVSLAltslnCVADPILYCLVN 273

pyroglutamylated RFamide peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; 26RFa, also known as QRFP (Pyroglutamylated RFamide peptide), is a 26-amino acid residue peptide that belongs to a family of neuropeptides containing an Arg-Phe-NH2 (RFamide) motif at its C-terminus. 26Rfa/QRFP exerts similar orexigenic activity including the regulation of feeding behavior in mammals. It is the ligand for G-protein coupled receptor 103 (GPR103), which is predominantly expressed in paraventricular (PVN) and ventromedial (VMH) nuclei of the hypothalamus. GPR103 shares significant protein sequence homology with orexin receptors (OX1R and OX2R), which have recently shown to produce a neuroprotective effect in Alzheimer's disease by forming a functional heterodimer with GPR103.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 77025099   7 ESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYM----VNNRNHGLDLRL----VTIPAFFSkSACvyNPIIYCFMN 78
Cdd:cd15205 215 EMSKISRKKKRAVKMMVTVVLLFAVCWAPFHVVHMMIeysnLENKYDGVTIKLifaiVQLIGFSN-SFN--NPIVYAFMN 291

somatostatin-like receptor for allatostatin C, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled somatostatin receptors (SSTRs) are composed of five distinct subtypes (SSTR1-5) that display strong sequence similarity with opioid receptors. All five receptor subtypes bind the natural somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. In Drosophila melanogaster and other insects, a 15-amino-acid peptide named allatostatin C(AstC) binds the somatostatin-like receptors. Two AstC receptors have been identified in Drosophila with strong sequence homology to human somatostatin and opioid receptors.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77025099   7 ESATTQKAEREVSRMVVVMVGSFCLCYVPYAALAMYMVNNRNhGLDLRLVTIPAFFSKSACVY-----NPIIYCFMN 78
Cdd:cd15094 200 KSKEKRRSHRKVTRLVLTVISVYIICWLPYWAFQVHLIFLPP-GTDMPKWEILMFLLLTVLSYansmvNPLLYAFLS 275

serotonin receptor subtype 1A from vertebrates, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. 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        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 77025099  15 EREVSRMVVVMVGSFCLCYVPY--AALAMYMVNNRNHGLDLrLVTIPAFFSKSACVYNPIIYCFMNK 79
Cdd:cd15330 189 ERKTVKTLGIIMGTFILCWLPFfiVALVLPFCESTCHMPEL-LGAIINWLGYSNSLLNPIIYAYFNK 254