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 1907149508  26 SVIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQGRN 104
Cdd:cd15073     1 NIVAAYLIVAGIISTISNGIVLVTFVKFRELRTPTNALIINLAVTDLGVSIIGYPFSAASDLHGSWKFGYAGCQWYAFL 79

retinal pigment epithelium-derived rhodopsin homolog, member of the class A family of seven-transmembrane G protein-coupled receptors; Peropsin, also known as a retinal pigment epithelium-derived rhodopsin homolog (RRH), is a visual pigment-like protein found exclusively in the apical microvilli of the retinal pigment epithelium. Peropsin belongs to the type 2 opsin family of the class A G-protein coupled receptors. Peropsin presumably plays a physiological role in the retinal pigment epithelium either by detecting light directly or monitoring the levels of retinoids, the primary light absorber in visual perception, or other pigment-related compounds in the eye.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907149508  26 SVIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQGRN 104
Cdd:cd15073     1 NIVAAYLIVAGIISTISNGIVLVTFVKFRELRTPTNALIINLAVTDLGVSIIGYPFSAASDLHGSWKFGYAGCQWYAFL 79

retinal pigment epithelium-derived rhodopsin homolog, member of the class A family of seven-transmembrane G protein-coupled receptors; Peropsin, also known as a retinal pigment epithelium-derived rhodopsin homolog (RRH), is a visual pigment-like protein found exclusively in the apical microvilli of the retinal pigment epithelium. Peropsin belongs to the type 2 opsin family of the class A G-protein coupled receptors. Peropsin presumably plays a physiological role in the retinal pigment epithelium either by detecting light directly or monitoring the levels of retinoids, the primary light absorber in visual perception, or other pigment-related compounds in the eye.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1907149508  26 SVIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQGRN 104
Cdd:cd15073     1 NIVAAYLIVAGIISTISNGIVLVTFVKFRELRTPTNALIINLAVTDLGVSIIGYPFSAASDLHGSWKFGYAGCQWYAFL 79

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907149508  26 SVIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQG 102
Cdd:cd15083     1 YVLGIFILIIGLIGVVGNGLVIYAFCRFKSLRTPANYLIINLAISDFLMCILNCPLMVISSFSGRWIFGKTGCDMYG 77

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

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907149508  27 VIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVS-SIGYPMSAASDLHGSWKFGHAGCQFQG 102
Cdd:cd15337     2 LIGIYIAIVGILGVIGNLLVIYLFSKTKSLRTPSNMFIINLAISDFGFSaVNGFPLKTISSFNKKWIWGKVACELYG 78

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 1907149508  28 IAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQG 102
Cdd:cd00637     1 LAVLYILIFVVGLVGNLLVILVILRNRRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRWWFGDALCKLLG 75

insect photoreceptors R1-R6 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the insect photoreceptors and their closely related proteins. The Drosophila eye is composed of about 800 unit eyes called ommatidia, each of which contains eight photoreceptor cells (R1-R8). The six outer photoreceptors (R1-R6) function like the vertebrate rods and are responsible for motion detection in dim light and image formation. The R1-R6 photoreceptors express a blue-absorbing pigment, Rhodopsin 1(Rh1). The inner photoreceptors (R7 and R8) are considered the equivalent of the color-sensitive vertebrate cone cells, which express a range of different pigments. The R7 photoreceptors express one of two different UV absorbing pigments, either Rh3 or Rh4. Likewise, the R8 photoreceptors express either the blue absorbing pigment Rh5 or green absorbing pigment Rh6. These photoreceptors belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907149508  28 IAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVsSIGYPMSAASDLHGSWKFGHAGCQFQG 102
Cdd:cd15079     3 LGFIYIFLGIVSLLGNGLVIYIFSTTKSLRTPSNMLVVNLAISDFLM-MIKMPIFIYNSFYEGWALGPLGCQIYA 76

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907149508  43 NVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDL-HGSWKFGHAGCQFQG 102
Cdd:pfam00001   2 NLLVILVILRNKKLRTPTNIFLLNLAVADLLFSLLTLPFWLVYYLnHGDWPFGSALCKIVG 62

serotonin receptor subtype 4, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT4 subtype is a member of the serotonin receptor family that belongs to the class A G protein-coupled receptors, and binds the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the mammalian central nervous system (CNS). 5-HT4 receptors are selectively linked to G proteins of the G(s) family, which positively stimulate adenylate cyclase, causing cAMP formation and activation of protein kinase A. 5-HT4 receptor-specific agonists have been shown to enhance learning and memory in animal studies. Moreover, hippocampal 5-HT4 receptor expression has been reported to be inversely correlated with memory performance in humans. 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 1907149508  27 VIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQGRNDR 106
Cdd:cd15056     2 VLSTFLSLVILLTILGNLLVIVAVCTDRQLRKKTNYFVVSLAVADLLVAVLVMPFGAIELVNNRWIYGETFCLVRTSLDV 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1907149508 107 QVTgclyTCLVPHVCNAGGAKRRAVDLLKLTLQMDVSDHVVMGIDLWVL 155
Cdd:cd15056    82 LLT----TASIMHLCCIALDRYYAICCQPLVYKMTPLRVAVMLGGCWVI 126

cholecystokinin receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents four G-protein coupled receptors that are members of the RFamide receptor family, including cholecystokinin receptors (CCK-AR and CCK-BR), orexin receptors (OXR), neuropeptide FF receptors (NPFFR), and pyroglutamylated RFamide peptide receptor (QRFPR). These RFamide receptors are activated by their endogenous peptide ligands that share a common C-terminal arginine (R) and an amidated phenylanine (F) motif. CCK-AR (type A, alimentary; also known as CCK1R) is found abundantly on pancreatic acinar cells and binds only sulfated CCK-peptides with very high affinity, whereas CCK-BR (type B, brain; also known as CCK2R), the predominant form in the brain and stomach, binds CCK or gastrin and discriminates poorly between sulfated and non-sulfated peptides. CCK is implicated in regulation of digestion, appetite control, and body weight, and is involved in neurogenesis via CCK-AR. There is some evidence to support that CCK and gastrin, via their receptors, are involved in promoting cancer development and progression, acting as growth and invasion factors. 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. The 26RFa, also known as QRFP (Pyroglutamylated RFamide peptide), is a 26-amino acid residue peptide that 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. Neuropeptide FF (NPFF) is a mammalian octapeptide that has 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 NPFF 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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907149508  28 IAAYLIVAgITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQF 100
Cdd:cd14993     4 IVLYVVVF-LLALVGNSLVIAVVLRNKHMRTVTNYFLVNLAVADLLVSLFCMPLTLLENVYRPWVFGEVLCKA 75

non-visual pinopsins, member of the class A family of seven-transmembrane G protein-coupled receptors; Pinopsins are found in the pineal organ of birds, reptiles and amphibians, but are absent from teleosts and mammals. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extra-retinal tissues and/or in non-rod, non-cone retinal cells. They are thought to be involved in light-dependent physiological functions such as photo-entrainment of circadian rhythm, photoperiodicity and body color change. Pinopsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149508  21 SRTEHSVIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQF 100
Cdd:cd15084     6 PRSTYLTVAVLMGMVVALASFVNGLVIVVSIKYKKLRSPLNYILVNLAVADLLVTLFGSSVSFSNNIVGFFVFGKTMCEF 85

                  ..
gi 1907149508 101 QG 102
Cdd:cd15084    86 EG 87

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 1907149508  30 AYLIVAGItSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQ 101
Cdd:cd16003     6 AYGFVVAV-AVFGNLIVIWIILAHKRMRTVTNYFLVNLAFSDASMAAFNTLINFIYALHSEWYFGEAYCRFH 76

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 1907149508  26 SVIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQG 102
Cdd:cd15080     1 SALAAYMFLLILLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVFGGFTTTMYTSMHGYFVFGPTGCNLEG 77

non-visual parapinopsin, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the non-visual pineal pigment, parapinopsin, which is a member of the class A of the seven transmembrane G protein-coupled receptors. Parapinopsin serves as a UV-sensitive pigment for the wavelength discrimination in the pineal-related organs of lower vertebrates such as reptiles, amphibians, and fish. Although parapinopsin is phylogenetically related to vertebrate visual pigments such as rhodopsin, which releases its retinal chromophore and bleaches, the parapinopsin photoproduct is stable and does not bleach. The vertebrate non-visual opsin family includes pinopsins, parapinopsin, VA (vertebrate ancient) opsins, and parietopsins. These non-visual opsins are expressed in various extra-retinal tissues and/or in non-rod, non-cone retinal cells.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907149508  27 VIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQG 102
Cdd:cd15075     2 ILSIIMAVFSIASVVLNATVIIVTLRHKQLRQPLNYALVNLAVADLGTTVFGGLLSVVTNAVGYFNLGRVGCVLEG 77

alpha-1 adrenergic receptors subtype B, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-1 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that primarily mediate smooth muscle contraction: alpha-1A, alpha-1B, and alpha-1D. Activation of alpha-1 receptors by catecholamines such as norepinephrine and epinephrine couples to the G(q) protein, which then activates the phospholipase C pathway, leading to an increase in IP3 and calcium. Consequently, the elevation of intracellular calcium concentration leads to vasoconstriction in smooth muscle of blood vessels. In addition, activation of alpha-1 receptors by phenylpropanolamine (PPA) produces anorexia and may induce appetite suppression in rats.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907149508  27 VIAAYLIVAgitsILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGC 98
Cdd:cd15326     6 VLGAFILFA----IVGNILVILSVVCNRHLRIPTNYFIVNLAIADLLLSFTVLPFSATLEILGYWVFGRIFC 73

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        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907149508  26 SVIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQF 100
Cdd:cd14992     1 IILGVALVVIILVSVVGNFIVIAALARHKNLRGATNYFIASLAISDLLMALFCTPFNFTYVVSLSWEYGHFLCKI 75

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907149508  36 GITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQG 102
Cdd:cd15078    11 GFLGVCNNLLVLILYYKFKRLRTPTNLLLVNISLSDLLVSLLGVTFTFMSCVRGRWVFDVAGCVWDG 77

substance-K receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The substance-K receptor (SKR), also known as tachykinin receptor 2 (TACR2) or neurokinin A receptor or NK2R, is a G-protein coupled receptor that specifically binds to neurokinin A. The tachykinins are widely distributed throughout the mammalian central and peripheral nervous systems and act as excitatory transmitters on neurons and cells in the gastrointestinal tract. The TKs are characterized by a common five-amino acid C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is a hydrophobic residue. The three major mammalian tachykinins are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). The physiological actions of tachykinins are mediated through three types of receptors: neurokinin receptor type 1 (NK1R), NK2R, and NK3R. SP is a high-affinity endogenous ligand for NK1R, which interacts with the Gq protein and activates phospholipase C, leading to elevation of intracellular calcium. NK2R is a high-affinity receptor for NKA, the tachykinin neuropeptide substance K. SP and NKA are found in the enteric nervous system and mediate the regulation of gastrointestinal motility, secretion, vascular permeability, and pain perception.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907149508  28 IAAYLIVagITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQ 101
Cdd:cd16004     5 IAYSLIV--LVAVTGNATVIWIILAHRRMRTVTNYFIVNLALADLSMAAFNTAFNFVYASHNDWYFGLEFCRFQ 76

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 1907149508  26 SVIAAYLIVAgITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQ 101
Cdd:cd15390     2 LWSIVFVVMV-LVAIGGNLIVIWIVLAHKRMRTVTNYFLVNLAVADLLISAFNTVFNFTYLLYNDWPFGLFYCKFS 76

dopamine 1-like receptor 2 from Drosophila melanogaster and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled dopamine 1-like receptor 2 is expressed in Drosophila heads and it shows significant sequence similarity with vertebrate and invertebrate dopamine receptors. Although the Drosophila Dop1R2 receptor does not cluster into the D1-like structural group, it does show pharmacological properties similar to D1-like receptors. As shown in vertebrate D1-like receptors, agonist stimulation of Dop1R2 activates adenylyl cyclase to increase cAMP levels and also generates a calcium signal through stimulation of phospholipase C.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907149508  27 VIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGS-WKFGHAGC 98
Cdd:cd15067     1 LLGVVLSLFCLVTVAGNLLVILAVLRERYLRTVTNYFIVSLAVADLLVGSIVMPFSILHEMTGGyWLFGRDWC 73

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 1907149508  29 AAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGC 98
Cdd:cd15210     4 AVWGIVFMVVGVPGNLLTVLALLRSKKLRTRTNAFIINLSISDLLFCAFNLPLAASTFLHQAWIHGETLC 73

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1907149508  27 VIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTD--IGVSSIgyPMSAASDLHGSWKFGHAGCQF 100
Cdd:cd15048     2 VLAVLISVLILVTVIGNLLVILAFIKDKKLRTVSNFFLLNLAVADflVGLVSM--PFYIPYTLTGKWPFGKVFCKA 75

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907149508  28 IAAYLIVAgITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQFQG 102
Cdd:cd15207     4 IVSYSLIF-LLCVVGNVLVCLVVAKNPRMRTVTNYFILNLAVSDLLVGVFCMPFTLVDNILTGWPFGDVMCKLSP 77

alpha-2 adrenergic receptors subtype C, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907149508  26 SVIAAYLIVagiTSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGC 98
Cdd:cd15323     4 AAVVGFLIV---FTIVGNVLVVIAVLTSRALRAPQNLFLVSLASADILVATLVMPFSLANELMGYWYFGQVWC 73

G protein-coupled receptor 135, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR135, also known as the somatostatin- and angiotensin-like peptide receptor (SALPR), is found in various tissues including eye, brain, cervix, stomach, and testis. Pharmacological studies have shown that relaxin-3 (R3) is a high-affinity endogenous ligand for GPR135. R3 has recently been identified as a new member of the insulin/relaxin family of peptide hormones and is exclusively expressed in the brain neurons. In addition to GPR135, R3 also acts as an agonist for GPR142, a pseudogene in the rat, and can activate LGR7 (leucine repeat-containing G-protein receptor-7), which is the main receptor for relaxin-1 (R1) and relaxin-2 (R2). While R1 and R2 are hormones primarily associated with reproduction and pregnancy, R3 is involved in neuroendocrine and sensory processing. 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 1907149508  29 AAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHG-SWKFGHAGC 98
Cdd:cd15212     4 ALVLLAIFLLSSLGNCAVIGVIVKHRQLRTVTNAFILSLSLSDLLTALLCLPFAFLTLFSRpGWLFGDRLC 74

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

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907149508  27 VIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQF 100
Cdd:cd15329     2 LIGIVLLIIILGTVVGNALVIIAVCLVKKLRTPSNYLIVSLAVSDLLVALLVMPLAIIYELSGYWPFGEILCDV 75

XC chemokine receptor 1, member of the class A family of seven-transmembrane G protein-coupled receptors; XCR1 is a chemokine receptor specific for XCL1 and XCL2 (previously called lymphotactin alpha/beta), which differ in only two amino acids. XCL1/2 is the only member of the C chemokine subfamily, which is unique as containing only two of the four cysteines that are found in other chemokine families. Human XCL1/2 has been shown to be secreted by activated CD8+ T cells and upon activation of the innate immune system. 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.

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gi 1907149508  39 SILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIgVSSIGYPMSAASDLHGsWKFGHAGCQF 100
Cdd:cd15182    14 SLLGNGLVLWILVKYEKLKTLTNIFILNLAISDL-LFTFTLPFWASYHSSG-WIFGEILCKA 73

alpha-1 adrenergic receptors subtype D, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-1 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that primarily mediate smooth muscle contraction: alpha-1A, alpha-1B, and alpha-1D. Activation of alpha-1 receptors by catecholamines such as norepinephrine and epinephrine couples to the G(q) protein, which then activates the phospholipase C pathway, leading to an increase in IP3 and calcium. Consequently, the elevation of intracellular calcium concentration leads to vasoconstriction in smooth muscle of blood vessels. In addition, activation of alpha-1 receptors by phenylpropanolamine (PPA) produces anorexia and may induce appetite suppression in rats.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1907149508  27 VIAAYLIVAgitsILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGC 98
Cdd:cd15327     6 FLAIFILMA----IVGNILVILSVACNRHLQTVTNYFIVNLAIADLLLSTTVLPFSATLEVLGFWAFGRVFC 73

opioid receptor subtype kappa, member of the class A family of seven-transmembrane G protein-coupled receptors; The kappa-opioid receptor binds the opioid peptide dynorphin as the primary endogenous ligand. The opioid receptor family is composed of four major subtypes: mu (MOP), delta (DOP), kappa (KOP) opioid receptors, and the nociceptin/orphanin FQ peptide receptor (NOP). They are distributed widely in the central nervous system and respond to classic alkaloid opiates, such as morphine and heroin, as well as to endogenous peptide ligands, which include dynorphins, enkephalins, endorphins, endomorphins, and nociceptin. Opioid receptors are coupled to inhibitory G proteins of the G(i/o) family and involved in regulating a variety of physiological functions such as pain, addiction, mood, stress, epileptic seizure, and obesity, among many others.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1907149508  27 VIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIgYPMSAASDLHGSWKFGHAGCQ 99
Cdd:cd15091     2 IITAVYSVVFVVGLVGNSLVMFVIIRYTKMKTATNIYIFNLALADALVTTT-MPFQSTVYLMNSWPFGDVLCK 73

tyramine/octopamine receptor-like, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes tyramine/octopamine receptors and similar proteins found in insects and other invertebrates. Both octopamine and tyramine mediate their actions via G protein-coupled receptors (GPCRs) and are the invertebrate equivalent of vertebrate adrenergic neurotransmitters. In Drosophila, octopamine is involved in ovulation by mediating an egg release from the ovary, while a physiological role for tyramine in this process is not fully understood. 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 1907149508  27 VIAAYLIVAGITSILSNV-VVLGIFIkYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQF 100
Cdd:cd15060     2 VTTILLSVIIAFTIVGNIlVILSVFT-YRPLRIVQNFFIVSLAVADLAVAIFVLPLNVAYFLLGKWLFGIHLCQM 75

adenosine receptor subfamily, member of the class A family of seven-transmembrane G protein-coupled receptors; The adenosine receptors (or P1 receptors), a family of G protein-coupled purinergic receptors, bind adenosine as their endogenous ligand. There are four types of adenosine receptors in human, designated as A1, A2A, A2B, and A3. Each type is encoded by a different gene and has distinct functions with some overlap. For example, both A1 and A2A receptors are involved in regulating myocardial oxygen consumption and coronary blood flow in the heart, while the A2A receptor also has a broad spectrum of anti-inflammatory effects in the body. These two receptors also expressed in the brain, where they have important roles in the release of other neurotransmitters such as dopamine and glutamate, while the A2B and A3 receptors found primarily in the periphery and play important roles in inflammation and immune responses. The A1 and A3 receptors preferentially interact with G proteins of the G(i/o) family, thereby lowering the intracellular cAMP levels, whereas the A2A and A2B receptors interact with G proteins of the G(s) family, activating adenylate cyclase to elevate cAMP levels.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1907149508  28 IAAYLIVAgITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDL 87
Cdd:cd14968     4 IVLEVLIA-VLSVLGNVLVIWAVKLNRALRTVTNYFIVSLAVADILVGALAIPLAILISL 62

alpha-2 adrenergic receptors subtype A, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1907149508  39 SILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQ 99
Cdd:cd15322    14 TVFGNVLVIIAVFTSRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKVWCE 74

octopamine receptors in invertebrates, member of the class A family of seven-transmembrane G protein-coupled receptors; G-protein coupled receptor for octopamine (OA), which functions as a neurotransmitter, neurohormone, and neuromodulator in invertebrate nervous system. Octopamine (also known as beta, 4-dihydroxyphenethylamine) is an endogenous trace amine that is highly similar to norepinephrine, but lacks a hydroxyl group, and has effects on the adrenergic and dopaminergic nervous systems. Based on the pharmacological and signaling profiles, the octopamine receptors can be classified into at least two groups: OA1 receptors elevate intracellular calcium levels in muscle, whereas OA2 receptors activate adenylate cyclase and increase cAMP production.

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gi 1907149508  27 VIAAYLIVAGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQ 99
Cdd:cd15063     2 ISLLVLTFLNVLVVLGNLLVIAAVLCSRKLRTVTNLFIVSLACADLLVGTLVLPFSAVNEVLDVWIFGHTWCQ 74

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1907149508  26 SVIAAYLIVAGItsiLSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQ 99
Cdd:cd15123     4 YVTYAVIISVGI---LGNAILIKVFFKIKSMQTVPNIFITSLAFGDLLLLLTCVPVDATRYIADTWLFGRIGCK 74

D1-like family of dopamine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. The D1-like family receptors are coupled to G proteins of the G(s) family, which activate adenylate cyclase, causing cAMP formation and activation of protein kinase A. In contrast, activation of D2-like family receptors is linked to G proteins of the G(i) family, which inhibit adenylate cyclase. Dopamine receptors are major therapeutic targets for neurological and psychiatric disorders such as drug abuse, depression, schizophrenia, or Parkinson's disease. 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 1907149508  31 YLIVagITSILSNVVVLGIFIKYKELRTP-TNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFG 94
Cdd:cd15057     8 YLLV--LLTLLGNALVIAAVLRFRHLRSKvTNYFIVSLAVSDLLVAILVMPWAAVNEVAGYWPFG 70

D1A (or D1) subtype dopamine receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. The D1-like family receptors are coupled to G proteins of the G(s) family, which activate adenylate cyclase, causing cAMP formation and activation of protein kinase A. Dopamine receptors are major therapeutic targets for neurological and psychiatric disorders such as drug abuse, depression, schizophrenia, or Parkinson's disease.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1907149508  29 AAYLIVAGITSILSNVVVLGIFIKYKELRTP-TNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFG 94
Cdd:cd15320     5 GCFLSVLILSTLLGNTLVCAAVIRFRHLRSKvTNFFVISLAVSDLLVAVLVMPWKAVAEIAGFWPFG 71

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1907149508  27 VIAAYLIVaGITSILSNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHG-SWKFGHAGCQF 100
Cdd:cd14979     3 VTAIYVAI-FVVGIVGNLLTCIVIARHKSLRTTTNYYLFSLAVSDLLILLVGLPVELYNFWWQyPWAFGDGGCKL 76

alpha-2 adrenergic receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback. 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 1907149508  32 LIVAGitsilsNVVVLGIFIKYKELRTPTNAVIINLAFTDIGVSSIGYPMSAASDLHGSWKFGHAGCQF 100
Cdd:cd15059    13 LIIVG------NVLVIVAVLTSRKLRAPQNWFLVSLAVADILVGLLIMPFSLVNELMGYWYFGSVWCEI 75