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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 763708755   1 GMQIALSDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTIYDEKDPNRCELL 56
Cdd:cd15976  205 GMQIALNDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTIYDEKDPNRCELL 260

endothelin B receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Endothelins are able to activate a number of signal transduction processes including phospholipase A2, phospholipase C, and phospholipase D, as well as cytosolic protein kinase activation. They play an important role in the regulation of the cardiovascular system and are the most potent vasoconstrictors identified, stimulating cardiac contraction, regulating the release of vasoactive substances, and stimulating mitogenesis in blood vessels. Two endothelin receptor subtypes have been isolated and identified in vertebrates, endothelin A receptor (ET-A) and endothelin B receptor (ET-B), and are members of the seven transmembrane class A G-protein coupled receptor family which activate multiple effectors via different types of G protein. Some vertebrates contain a third subtype, endothelin A receptor (ET-C). ET-A receptors are mainly located on vascular smooth muscle cells, whereas ET-B receptors are present on endothelial cells lining the vessel wall. Endothelin receptors have also been found in the brain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 763708755   1 GMQIALSDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTIYDEKDPNRCELL 56
Cdd:cd15976  205 GMQIALNDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTIYDEKDPNRCELL 260

G protein-coupled chemokine receptor-like protein; Provisional

                         10        20        30
                 ....*....|....*....|....*....|
gi 763708755  11 KQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:PHA03087 237 KKNKKAIKLVLIIVILFVIFWLPFNVSVFV 266

endothelin B receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Endothelins are able to activate a number of signal transduction processes including phospholipase A2, phospholipase C, and phospholipase D, as well as cytosolic protein kinase activation. They play an important role in the regulation of the cardiovascular system and are the most potent vasoconstrictors identified, stimulating cardiac contraction, regulating the release of vasoactive substances, and stimulating mitogenesis in blood vessels. Two endothelin receptor subtypes have been isolated and identified in vertebrates, endothelin A receptor (ET-A) and endothelin B receptor (ET-B), and are members of the seven transmembrane class A G-protein coupled receptor family which activate multiple effectors via different types of G protein. Some vertebrates contain a third subtype, endothelin A receptor (ET-C). ET-A receptors are mainly located on vascular smooth muscle cells, whereas ET-B receptors are present on endothelial cells lining the vessel wall. Endothelin receptors have also been found in the brain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 763708755   1 GMQIALSDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTIYDEKDPNRCELL 56
Cdd:cd15976  205 GMQIALNDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTIYDEKDPNRCELL 260

endothelin C receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Endothelins are able to activate a number of signal transduction processes including phospholipase A2, phospholipase C, and phospholipase D, as well as cytosolic protein kinase activation. They play an important role in the regulation of the cardiovascular system and are the most potent vasoconstrictors identified, stimulating cardiac contraction, regulating the release of vasoactive substances, and stimulating mitogenesis in blood vessels. Two endothelin receptor subtypes have been isolated and identified in vertebrates, endothelin A receptor (ET-A) and endothelin B receptor (ET-B), and are members of the seven transmembrane class A G-protein coupled receptor family which activate multiple effectors via different types of G protein. Some vertebrates contain a third subtype, endothelin A receptor (ET-C). ET-A receptors are mainly located on vascular smooth muscle cells, whereas ET-B receptors are present on endothelial cells lining the vessel wall. Endothelin receptors have also been found in the brain. The ET-C receptor is specific for endothelin-3 on frog dermal melanophores; its activation causes dispersion of pigment granules.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 763708755   1 GMQIALSDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTIYDEKDPNRCELL 56
Cdd:cd15977  205 GMRIALNDHMKQRREVAKTVFCLVVIFALCWLPLHLSRILKKTIYDVKDPQRCELL 260

endothelin receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily of G-protein coupled receptors includes endothelin receptors, bombesin receptor subtype 3 (BRS-3), gastrin-releasing peptide receptor (GRPR), neuromedin B receptor (NMB-R), endothelin B receptor-like 2 (ETBR-LP-2), and GRP37. The endothelin receptors and related proteins are members of the seven transmembrane rhodopsin-like G-protein coupled receptor family (class A GPCRs) which activate multiple effectors via different types of G protein.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 763708755   1 GMQIALSDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTIYDE 47
Cdd:cd14977  204 EYTRGTKKHMKQRRQLAKTVLCLVLVFAFCWLPEHISNILRATLYNE 250

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.

                         10        20
                 ....*....|....*....|....
gi 763708755  13 RREVAKTVFCLVLVFALCWLPLHL 36
Cdd:cd15927  219 RKKVAKTVLAFVVLFAVCWLPRHV 242

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
                 ....*....|....*....|....*....|..
gi 763708755   9 HLKQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd00637  207 RRRRERKVTKTLLIVVVVFLLCWLPYFILLLL 238

neuromedin U receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuromedin U (NMU) is a highly conserved neuropeptide with a common C-terminal heptapeptide sequence (FLFRPRN-amide) found at the highest levels in the gastrointestinal tract and pituitary gland of mammals. Disruption or replacement of residues in the conserved heptapeptide region can result in the reduced ability of NMU to stimulate smooth-muscle contraction. Two G-protein coupled receptor subtypes, NMU-R1 and NMU-R2, with a distinct expression pattern, have been identified to bind NMU. NMU-R1 is expressed primarily in the peripheral nervous system, while NMU-R2 is mainly found in the central nervous system. Neuromedin S, a 36 amino-acid neuropeptide that shares a conserved C-terminal heptapeptide sequence with NMU, is a highly potent and selective NMU-R2 agonist. Pharmacological studies have shown that both NMU and NMS inhibit food intake and reduce body weight, and that NMU increases energy expenditure.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 763708755   6 LSDHLKQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd15133  216 LLQHPRTRAQVTKMLFILVVVFAICWAPFHIDRLM 250

neuropeptide FF receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropeptide FF (NPFF) is a mammalian octapeptide that belongs to a family of neuropeptides containing an RF-amide motif at their C-terminus that have been implicated in a wide range of physiological functions in the brain including pain sensitivity, insulin release, food intake, memory, blood pressure, and opioid-induced tolerance and hyperalgesia. The effects of these peptides are mediated through neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R) which are predominantly expressed in the brain. NPFF induces pro-nociceptive effects, mainly through the NPFF1-R, and anti-nociceptive effects, mainly through the NPFF2-R. NPFF has been shown to inhibit adenylate cyclase via the Gi protein coupled to NPFF1-R.

                         10        20        30
                 ....*....|....*....|....*....|....*.
gi 763708755   5 ALSDHLKQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd15207  208 AQAAVSKKKVRVIKMLIVVVVLFALSWLPLHTVTML 243

neuromedin U receptor subtype 2, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuromedin U (NMU) is a highly conserved neuropeptide with a common C-terminal heptapeptide sequence (FLFRPRN-amide) found at the highest levels in the gastrointestinal tract and pituitary gland of mammals. Disruption or replacement of residues in the conserved heptapeptide region can result in the reduced ability of NMU to stimulate smooth-muscle contraction. Two G-protein coupled receptor subtypes, NMU-R1 and NMU-R2, with a distinct expression pattern, have been identified to bind NMU. NMU-R1 is expressed primarily in the peripheral nervous system, while NMU-R2 is mainly found in the central nervous system. Neuromedin S, a 36 amino-acid neuropeptide that shares a conserved C-terminal heptapeptide sequence with NMU, is a highly potent and selective NMU-R2 agonist. Pharmacological studies have shown that both NMU and NMS inhibit food intake and reduce body weight, and that NMU increases energy expenditure.

                         10        20
                 ....*....|....*....|....*...
gi 763708755  13 RREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd15357  218 RKSVTKMLFVLVLVFAICWAPFHVDRLF 245

apelin receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Apelin (APJ) receptor is a G protein-coupled receptor that binds the endogenous peptide ligands, apelin and Toddler/Elabela. APJ is an adipocyte-derived hormone that is ubiquitously expressed throughout the human body and Toddler/Elabela is a short secretory peptide that is required for normal cardiac development in zebrafish. Activation of APJ receptor plays key roles in diverse physiological processes including vasoconstriction and vasodilation, cardiac muscle contractility, angiogenesis, and regulation of water balance and food intake.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 763708755   6 LSDHLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTIYDEKDPNRC 53
Cdd:cd15190  218 RRKEDKKKRRLLKIIITLVVTFALCWLPFHLVKTLYALMYLGILPFSC 265

bombesin receptor subtype 3, member of the class A family of seven-transmembrane G protein-coupled receptors; BRS-3 is classified as an orphan receptor and belongs to the bombesin subfamily of G-protein coupled receptors, whose members also include neuromedin B receptor (NMBR) and gastrin-releasing peptide receptor (GRPR). 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 primarily to the G proteins of G(q/11) family. 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. BRS-3 is suggested to play a role in sperm cell division and maturation.

                         10        20
                 ....*....|....*....|....*...
gi 763708755   9 HLKQRREVAKTVFCLVLVFALCWLPLHL 36
Cdd:cd15123  215 QIESRKRVAKTVLVLVALFAFCWLPNHI 242

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
                 ....*....|....*....|....*....|...
gi 763708755   8 DHLKQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd16003  204 EQLRAKRKVVKMMIIVVLTFAICWLPYHIYFIV 236

gastrin-releasing peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The gastrin-releasing peptide receptor (GRPR) is a G-protein coupled receptor whose endogenous ligand is gastrin releasing peptide. GRP shares high sequence homology with the neuropeptide neuromedin B in the C-terminal region. This receptor is high glycosylated and couples to a pertussis-toxin-insensitive G protein of the family of Gq/11, which leads to the activation of phospholipase C. Gastrin-releasing peptide (GRP) is a potent mitogen for neoplastic tissues and involved in regulating multiple functions of the gastrointestinal and central nervous systems. These include the release of gastrointestinal hormones, the contraction of smooth muscle cells, and the proliferation of epithelial cells. GRPR belongs to the bombesin subfamily of G-protein coupled receptors, whose members also include neuromedin B receptor (NMBR) and bombesin receptor subtype 3 (BRS-3). Bombesin is a tetradecapeptide, originally isolated from frog skin.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 763708755   9 HLKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTIYDEKD 49
Cdd:cd15124  215 QIESRKRLAKTVLVFVGLFAFCWLPNHIIYLYRSYHYSEVD 255

leucokinin-like peptide receptor from tick and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes a leucokinin-like peptide receptor from the Southern cattle tick, Boophilus microplus, a pest of cattle world-wide. Leucokinins are invertebrate neuropeptides that exhibit myotropic and diuretic activity. This receptor is the first neuropeptide receptor known from the Acari and the second known in the subfamily of leucokinin-like peptide G-protein-coupled receptors. The other known leucokinin-like peptide receptor is a lymnokinin receptor from the mollusc Lymnaea stagnalis.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 763708755  10 LKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTI 44
Cdd:cd15393  212 LKNKKKVIKMLIIVVALFALCWLPLQTYNLLNEIK 246

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

                         10        20        30
                 ....*....|....*....|....*....|..
gi 763708755   9 HLKQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd14992  214 RLKCKRRVIKMLVCVVVLFVICWLPFHLFFLL 245

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
                 ....*....|....*....|....*....|.
gi 763708755  10 LKQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd15202  213 RRKKKKVIKMLMVVVVLFALCWLPFNIYVLL 243

growth hormone secretagogue receptor, motilin receptor, and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes growth hormone secretagogue receptor (GHSR or ghrelin receptor), motilin receptor (also called GPR38), and related proteins. Both GHSR and GPR38 bind peptide hormones. Ghrelin, the endogenous ligand for GHSR, is an acylated 28-amino acid peptide hormone produced by ghrelin cells in the gastrointestinal tract. Ghrelin is also called the hunger hormone and is involved in the regulation of growth hormone release, appetite and feeding, gut motility, lipid and glucose metabolism, and energy balance. Motilin, the ligand for GPR38, is a 22 amino acid peptide hormone expressed throughout the gastrointestinal tract and stimulates contraction of gut smooth muscle. It is involved in the regulation of digestive tract motility.

                         10        20
                 ....*....|....*....|....*...
gi 763708755  13 RREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd15928  213 HRQTVRMLAVIVLAFVLCWLPFHVGRVI 240

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

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 763708755   8 DHLKQRREVAKTVFCLVLVFALCWLPLHLSRILkLTIYDEKDPN 51
Cdd:cd15048  221 VKLRRDRKAAKSLAILVLVFLICWAPYTILTII-RSFCSGSCVD 263

neuromedin B receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The neuromedin B receptor (NMBR), also known as BB1, is a G-protein coupled receptor whose endogenous ligand is the neuropeptide neuromedin B. Neuromedin B is a potent mitogen and growth factor for normal and cancerous lung and for gastrointestinal epithelial tissues. NMBR is widely distributed in the CNS, with especially high levels in olfactory nucleus and thalamic regions. The receptor couples primarily to a pertussis-toxin-insensitive G protein of the Gq/11 family, which leads to the activation of phospholipase C. NMBR belongs to the bombesin subfamily of G-protein coupled receptors, whose members also include gastrin-releasing peptide receptor (GRPR) and bombesin receptor subtype 3 (BRS-3). Bombesin is a tetradecapeptide, originally isolated from frog skin.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 763708755   7 SDHLKQ----RREVAKTVFCLVLVFALCWLPLHLSRILKLTIYDEKDPN 51
Cdd:cd15125  208 SEHSKRqmetRKRLAKIVLVFVGLFAFCWFPNHVLYMYRSFNYNEIDSS 256

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
                 ....*....|....*....|....*....|....*.
gi 763708755  11 KQRREVAKTVFCLVLVFALCWLPLHLSRILKLTIYD 46
Cdd:cd15392  212 ESKRKLVKMMITVVAIFALCWLPLNILNLVGDHDES 247

G protein-coupled receptor 83, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR83, also known as GPR72, is widely expressed in the brain, including hypothalamic nuclei which is involved in regulating energy balance and food intake. The hypothalamic expression of GPR83 is tightly regulated in response to nutrient availability and is decreased in obese mice. A recent study suggests that GPR83 has a critical role in the regulation of systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms. GPR83 shares a significant amino acid sequence identity with the tachykinin receptors, however its endogenous ligand is unknown.

                         10        20        30
                 ....*....|....*....|....*....|..
gi 763708755   9 HLKQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd15389  212 QRRKKKKTIKMLMLVVLLFAICWLPLNCYHVL 243

CXC chemokine receptor types 1 and 2, member of the class A family of seven-transmembrane G protein-coupled receptors; CXCR1 and CXCR2 are closely related chemotactic receptors for a group of CXC chemokines distinguished by the presence of the amino acid motif ELR immediately adjacent to their CXC motif. Expression of CXCR1 and CXCR2 is strictly controlled in neutrophils by external stimuli such as lipopolysaccharide (LPS), tumor necrosis factor (TNF)-alpha, Toll-like receptor agonists, and nitric oxide. CXCL8 (formerly known as interleukin-8) binds with high-affinity and activates both receptors. CXCR1 also binds CXCL7 (neutrophil-activating protein-2), whereas CXCR2 non-selectively binds to all seven ELR-positive chemokines (CXCL1-7). Chemokines are principal regulators for leukocyte trafficking, recruitment, and activation. Chemokine family membership is defined on the basis of sequence homology and on the presence of variations on a conserved cysteine motif, which allows the family to further divide into four subfamilies (CC, CXC, XC, and CX3C). Chemokines interact with seven-transmembrane receptors which are typically coupled to G protein for signaling. Currently, there are ten known receptors for CC chemokines, seven for CXC chemokines, and single receptors for the XC and CX3C chemokines.

                         10        20        30
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gi 763708755   6 LSDHLKQRREVAKTVFCLVLVFALCWLPLHLS 37
Cdd:cd15178  193 LQTRSFQKHRAMRVIFAVVLAFLLCWLPYNVT 224

neuropeptide Y receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; NPY is a 36-amino acid peptide neurotransmitter with a C-terminal tyrosine amide residue that is widely distributed in the brain and the autonomic nervous system of many mammalian species. NPY exerts its functions through five, G-protein coupled receptor subtypes including NPY1R, NPY2R, NPY4R, NPY5R, and NPY6R; however, NPY6R is not functional in humans. NYP receptors are also activated by its two other family members, peptide YY (PYY) and pancreatic polypeptide (PP). They typically couple to Gi or Go proteins, which leads to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels, and are involved in diverse physiological roles including appetite regulation, circadian rhythm, and anxiety. Also included in this subgroup is prolactin-releasing peptide (PrRP) receptor (previously known as GPR10), which is activated by its endogenous ligand PrRP, a neuropeptide possessing C-terminal Arg-Phe-amide motif. There are two active isoforms of PrRP in mammals: one consists of 20 amino acid residues (PrRP-20) and the other consists of 31 amino acid residues (PrRP-31). PrRP receptor shows significant sequence homology to the NPY receptors, and a micromolar level of NPY can bind and completely inhibit the PrRP-evoked intracellular calcium response in PrRP receptor-expressing cells, suggesting that the PrRP receptor shares a common ancestor with the NPY receptors.

                         10        20        30
                 ....*....|....*....|....*....|.
gi 763708755  10 LKQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd15203  216 LRRKRRTNRLLIAMVVVFAVCWLPLNLFNLL 246

growth hormone secretagogue receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Growth hormone secretagogue receptor, GHSR, is also known as GH-releasing peptide receptor (GHRP) or Ghrelin receptor. Ghrelin, the endogenous ligand for GHSR, is an acylated 28-amino acid peptide hormone produced by ghrelin cells in the gastrointestinal tract. Ghrelin, also called hunger hormone, is involved in the regulation of growth hormone release, appetite and feeding, gut motility, lipid and glucose metabolism, and energy balance. It also plays a role in the cardiovascular, immune, and reproductive systems. GHSR couples to G-alpha-11 proteins. Both ghrelin and GHSR are expressed in a wide range of cancer tissues. Recent studies suggested that ghrelin may play a role in processes associated with cancer progression, including cell proliferation, metastasis, apoptosis, and angiogenesis.

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gi 763708755  11 KQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd15131  213 KNNRQTVKMLAVVVFAFVLCWLPFHVGRYL 242

leukotriene B4 receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Leukotriene B4 (LTB4), a metabolite of arachidonic acid, is a powerful chemotactic activator for granulocytes and macrophages. Two receptors for LTB4 have been identified: a high-affinity receptor (LTB4R1 or BLT1) and a low-affinity receptor (TB4R2 or BLT2). Both BLT1 and BLT2 receptors belong to the rhodopsin-like G-protein coupled receptor superfamily and primarily couple to G(i) proteins, which lead to chemotaxis, calcium mobilization, and inhibition of adenylate cyclase. In some cells, they can also couple to the G(q)-like protein, G16, and activate phospholipase C. LTB4 is involved in mediating inflammatory processes, immune responses, and host defense against infection. Studies have shown that LTB4 stimulates leukocyte extravasation, neutrophil degranulation, lysozyme release, and reactive oxygen species generation.

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gi 763708755  10 LKQRREVAKTVFCLVLVFALCWLPLHLSRILKLTI 44
Cdd:cd14975  194 FRRRRRTGRLIASVVVAFAACWLPYHVGNLLEVVS 228

G protein-coupled chemokine receptor-like protein; Provisional

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gi 763708755  11 KQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:PHA03087 237 KKNKKAIKLVLIIVILFVIFWLPFNVSVFV 266

angiotesin receptor family and its related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the angiotensin receptors, the bradykinin receptors, apelin receptor as well as putative G-protein coupled receptors (GPR15 and GPR25). Angiotensin II (Ang II), the main effector in the renin-angiotensin system, plays a crucial role in the regulation of cardiovascular homeostasis through its type 1 (AT1) and type 2 (AT2) receptors. Ang II contributes to cardiovascular diseases such as hypertension and atherosclerosis via AT1R activation. Ang II increases blood pressure through Gq-mediated activation of phospholipase C, resulting in phosphoinositide (PI) hydrolysis and increased intracellular calcium levels. Through the AT2 receptor, Ang II counteracts the vasoconstrictor action of AT1R and thereby induces vasodilation, sodium excretion, and reduction of blood pressure. Bradykinins (BK) are pro-inflammatory peptides that mediate various vascular and pain responses to tissue injury through its B1 and B2 receptors. Apelin (APJ) receptor binds the endogenous peptide ligands, apelin and Toddler/Elabela. APJ is an adipocyte-derived hormone that is ubiquitously expressed throughout the human body, and Toddler/Elabela is a short secretory peptide that is required for normal cardiac development in zebrafish. Activation of APJ receptor plays key roles in diverse physiological processes including vasoconstriction and vasodilation, cardiac muscle contractility, angiogenesis, and regulation of water balance and food intake. Orphan receptors, GPR15 and GPR25, share strong sequence homology to the angiotensin II type AT1 and AT2 receptors.

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gi 763708755   9 HLKQRREVAKTVFCLVLVFALCWLPLHLSRIL 40
Cdd:cd14985  202 NGRKRRKSLKIIFALVVAFLVCWLPFHFFKFL 233

neuropeptide B/W receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropeptide B/W receptor 1 and 2 are members of the class A G-protein coupled receptors that bind the neuropeptides B and W, respectively. NPBWR1 (previously known as GPR7) is expressed predominantly in cerebellum and frontal cortex, while NPBWR2 (previously known as GPR8) is located mostly in the frontal cortex and is present in human, but not in rat and mice. These receptors are suggested to be involved in the regulation of food intake, neuroendocrine function, and modulation of inflammatory pain, among many 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 763708755  11 KQRREVAKTVFCLVLVFALCWLPLHLSRILKLT 43
Cdd:cd15087  208 KAKKKVTLMVLVVLAVCLFCWTPFHLSTVVALT 240

neuropeptide capa receptor and similar invertebrate proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; CapaR is a G-protein coupled receptor for the Drosophila melanogaster capa neuropeptides (Drm-capa-1 and -2), which act on the Malpighian tubules to increase fluid transport. The capa peptides are evolutionarily related to vertebrate Neuromedin U neuropeptide and contain a C-terminal FPRXamide motif. CapaR regulates fluid homeostasis through its ligands, thereby acts as a desiccation stress-responsive receptor. CapaR undergoes desensitization, with internalization mediated by beta-arrestin-2.

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gi 763708755   9 HLKQRREVAKTVFCLVLVFALCWLPLHLSRIlkLTIY 45
Cdd:cd15134  219 SSQSRRTVLRMLVAVVVAFFICWAPFHAQRL--LTVY 253