seven-transmembrane G protein-coupled receptor superfamily; This hierarchical evolutionary model represents the seven-transmembrane (7TM) receptors, often referred to as G protein-coupled receptors (GPCRs), which transmit physiological signals from the outside of the cell to the inside via G proteins. GPCRs constitute the largest known superfamily of transmembrane receptors across the three kingdoms of life that respond to a wide variety of extracellular stimuli including peptides, lipids, neurotransmitters, amino acids, hormones, and sensory stimuli such as light, smell and taste. All GPCRs share a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes. However, some 7TM receptors, such as the type 1 microbial rhodopsins, do not activate G proteins. Based on sequence similarity, GPCRs can be divided into six major classes: class A (the rhodopsin-like family), class B (the Methuselah-like, adhesion and secretin-like receptor family), class C (the metabotropic glutamate receptor family), class D (the fungal mating pheromone receptors), class E (the cAMP receptor family), and class F (the frizzled/smoothened receptor family). Nearly 800 human GPCR genes have been identified and are involved essentially in all major physiological processes. Approximately 40% of clinically marketed drugs mediate their effects through modulation of GPCR function for the treatment of a variety of human diseases including bacterial infections.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  25 YGIAFCVGLPAFIFTVVRLARSRSSRQhlvlaARLFSYKISLSVADCIVLFIYAPTQFAWIHSYWWFGGDIGCRLFKFIS 104
Cdd:cd15382     7 YSVLFLIAAVGNLTVLLILLRNRRRKR-----SRVNILLMHLAIADLLVTFIMMPLEIGWAATVAWLAGDFLCRLMLFFR 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1734339383 105 TFGFHLTANMQVLVAADRLL-ITAKMNrvTRNIKKRqynTRLSLAAAWILALICAGPQLILFRQKTTPQ--GYPQCIS 179
Cdd:cd15382    82 AFGLYLSSFVLVCISLDRYFaILKPLR--LSDARRR---GRIMLAVAWVISFLCSIPQSFIFHVESHPCvtWFSQCVT 154

adipokinetic hormone receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Adipokinetic hormone (AKH) is a lipid-mobilizing hormone that is involved in control of insect metabolism. Generally, AKH behaves as a typical stress hormone by mobilizing lipids, carbohydrates and/or certain amino acids such as proline. Thus, it utilizes the body's energy reserves to fight the immediate stress problems and subdue processes that are less important. Although AKH is known to responsible for regulating the energy metabolism during insect flight, it is also found in insects that have lost its functional wings and predominantly walk for their locomotion. AKH is structurally related to the mammalian gonadotropin-releasing hormone (GnRH) and they share a common ancestor. Both GnRH and AKH receptors are members of the class A of the seven-transmembrane, G-protein coupled receptor (GPCR) superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  25 YGIAFCVGLPAFIFTVVRLARSRSSRQhlvlaARLFSYKISLSVADCIVLFIYAPTQFAWIHSYWWFGGDIGCRLFKFIS 104
Cdd:cd15382     7 YSVLFLIAAVGNLTVLLILLRNRRRKR-----SRVNILLMHLAIADLLVTFIMMPLEIGWAATVAWLAGDFLCRLMLFFR 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1734339383 105 TFGFHLTANMQVLVAADRLL-ITAKMNrvTRNIKKRqynTRLSLAAAWILALICAGPQLILFRQKTTPQ--GYPQCIS 179
Cdd:cd15382    82 AFGLYLSSFVLVCISLDRYFaILKPLR--LSDARRR---GRIMLAVAWVISFLCSIPQSFIFHVESHPCvtWFSQCVT 154

adipokinetic hormone receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Adipokinetic hormone (AKH) is a lipid-mobilizing hormone that is involved in control of insect metabolism. Generally, AKH behaves as a typical stress hormone by mobilizing lipids, carbohydrates and/or certain amino acids such as proline. Thus, it utilizes the body's energy reserves to fight the immediate stress problems and subdue processes that are less important. Although AKH is known to responsible for regulating the energy metabolism during insect flight, it is also found in insects that have lost its functional wings and predominantly walk for their locomotion. AKH is structurally related to the mammalian gonadotropin-releasing hormone (GnRH) and they share a common ancestor. Both GnRH and AKH receptors are members of the class A of the seven-transmembrane, G-protein coupled receptor (GPCR) superfamily.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  25 YGIAFCVGLPAFIFTVVRLARSRSSRQhlvlaARLFSYKISLSVADCIVLFIYAPTQFAWIHSYWWFGGDIGCRLFKFIS 104
Cdd:cd15382     7 YSVLFLIAAVGNLTVLLILLRNRRRKR-----SRVNILLMHLAIADLLVTFIMMPLEIGWAATVAWLAGDFLCRLMLFFR 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1734339383 105 TFGFHLTANMQVLVAADRLL-ITAKMNrvTRNIKKRqynTRLSLAAAWILALICAGPQLILFRQKTTPQ--GYPQCIS 179
Cdd:cd15382    82 AFGLYLSSFVLVCISLDRYFaILKPLR--LSDARRR---GRIMLAVAWVISFLCSIPQSFIFHVESHPCvtWFSQCVT 154

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  40 VVRLARSRSSRqhlvlaarLFSYKISLSVADCIVLFIYAPTQFAWIHSYWWFGGDIGCRLFKFISTFGFHLTANMQVLVA 119
Cdd:cd14986    24 VLRRKRKKRSR--------VNIFILNLAIADLVVAFFTVLTQIIWEATGEWVAGDVLCRIVKYLQVVGLFASTYILVSMS 95

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734339383 120 ADR-LLITAKMNRVtrnikKRQYNTRLSLAAAWILALICAGPQLILFRQKTTPQGYPQCISIW 181
Cdd:cd14986    96 LDRyQAIVKPMSSL-----KPRKRARLMIVVAWVLSFLFSIPQLVIFVERELGDGVHQCWSSF 153

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  24 MYGIAFCVGLP--AFIFTVVRLARSRSSRQHLVLAarlfsykiSLSVADCIVLFIYAPTQFAWIHSYWWFGGDIGCRLFK 101
Cdd:cd00637     4 LYILIFVVGLVgnLLVILVILRNRRLRTVTNYFIL--------NLAVADLLVGLLVIPFSLVSLLLGRWWFGDALCKLLG 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383 102 FISTFGFHLTANMQVLVAADRLLITAKMNRVTRNIKKRqyNTRLSLAAAWILALICAGPQLILFRQKTTPQGYPQCISIW 181
Cdd:cd00637    76 FLQSVSLLASILTLTAISVDRYLAIVHPLRYRRRFTRR--RAKLLIALIWLLSLLLALPPLLGWGVYDYGGYCCCCLCWP 153

                  ....*...
gi 1734339383 182 TEHRVDFY 189
Cdd:cd00637   154 DLTLSKAY 161

vasopressin and oxytocin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Vasopressin (also known as arginine vasopressin or anti-diuretic hormone) and oxytocin are synthesized in the hypothalamus and are released from the posterior pituitary gland. The actions of vasopressin are mediated by the interaction of this hormone with three receptor subtypes: V1aR, V1bR, and V2R. These subtypes are differ in localization, function, and signaling pathways. Activation of V1aR and V1bR stimulate phospholipase C, while activation of V2R stimulates adenylate cyclase. Although vasopressin and oxytocin differ only by two amino acids and stimulate the same cAMP/PKA pathway, they have divergent physiological functions. Vasopressin is involved in regulating blood pressure and the balance of water and sodium ions, whereas oxytocin plays an important role in the uterus during childbirth and in lactation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  35 AFIFTVVRLARSRSSRQHLVLaarlfsykISLSVADCIVLFIYAPTQFAWIHSYWWFGGDIGCRLFKFISTFGFHLTANM 114
Cdd:cd15196    19 SCVLLVLYRRRRKLSRMHLFI--------LHLSVADLLVALFNVLPQLIWDITYRFYGGDLLCRLVKYLQVVGMYASSYV 90

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1734339383 115 QVLVAADRLLITAKMNRVTRNIKKRqynTRLSLAAAWILALICAGPQLILFRQKTTPQGYPQC 177
Cdd:cd15196    91 LVATAIDRYIAICHPLSSHRWTSRR---VHLMVAIAWVLSLLLSIPQLFIFSYQEVGSGVYDC 150

neurotensin receptor subtype 2, member of the class A family of seven-transmembrane G protein-coupled receptors; Neurotensin (NTS) is a 13 amino-acid neuropeptide that functions as both a neurotransmitter and a hormone in the nervous system and peripheral tissues, respectively. NTS exerts various biological activities through activation of the G protein-coupled neurotensin receptors, NTSR1 and NTSR2. In the brain, NTS is involved in the modulation of dopamine neurotransmission, opioid-independent analgesia, hypothermia, and the inhibition of food intake, while in the periphery NTS promotes the growth of various normal and cancer cells and acts as a paracrine and endocrine modulator of the digestive tract. The third neurotensin receptor, NTSR3 or also called sortilin, is not a G protein-coupled receptor.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  24 MYGIAFCVGLPAFIFTVVRLARSRSSRQhlvLAARLFSYKISLSVADCIVLFIYAPTQ---FAWIHsYWWFGGDIGCRLF 100
Cdd:cd15356     6 VYALIWALGAAGNALTIHLVLKKRSLRG---LQGTVHYHLVSLALSDLLILLISVPIElynFVWFH-YPWVFGDLVCRGY 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1734339383 101 KFISTFGFHLTANMQVLVAADRLLITAKMNRVTRNIKKRQynTRLSLAAAWILALICAGPQLILFRQK---TTPQGYPQ 176
Cdd:cd15356    82 YFVRDICSYATVLNIASLSAERYLAICQPLRAKRLLSKRR--TKWLLALIWASSLGFALPMAFIMGQKyelETADGEPE 158

neuropeptide S receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropeptide S (NPS) promotes arousal and anxiolytic-like effects by activating its cognate receptor NPSR. NPSR is widely expressed in the brain, and its activation induces an elevation of intracellular calcium and cAMP concentrations, presumably by coupling to G(s) and G(q) proteins. Mutations in NPSR have been associated with an increased susceptibility to asthma. NPSR was originally identified as an orphan receptor GPR154 and is also known as G protein receptor for asthma susceptibility (GPRA) or vasopressin receptor-related receptor 1 (VRR1).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  22 LWMYGIAFCVGLPAFIFTVVRlARSRSSRQHLVLaarlfsykISLSVADCIVLFIYAPTQFAWIHSYWWFGGDIGCRLFK 101
Cdd:cd15197     7 LWVLFVFIVVGNSSVLFALWM-RKAKKSRMNFFI--------TQLAIADLCVGLINVLTDIIWRITVEWRAGDFACKVIR 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383 102 FIStfGFHLTANMQVLVA--ADRLLITAKMNRVTRNIKKrqynTRLSLAAAWILALICAGPQLILFRQKTTPQGYPQCIS 179
Cdd:cd15197    78 YLQ--VVVTYASTYVLVAlsIDRYDAICHPMNFSQSGRQ----ARVLICVAWILSALFSIPMLIIFEKTGLSNGEVQCWI 151

                  ....
gi 1734339383 180 IWTE 183
Cdd:cd15197   152 LWPE 155

amine receptors and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; Amine receptors of the class A family of GPCRs include adrenoceptors, 5-HT (serotonin) receptors, muscarinic cholinergic receptors, dopamine receptors, histamine receptors, and trace amine receptors. The receptors of amine subfamily are major therapeutic targets for the treatment of neurological disorders and psychiatric diseases. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  64 ISLSVADCIVLFIYAPTQFAW-IHSYWWFgGDIGCRLFKFISTFG-----FHLTAnmqvlVAADRLLItakmnrVTRNIK 137
Cdd:cd14967    39 VSLAVADLLVALLVMPFSAVYtLLGYWPF-GPVLCRFWIALDVLCctasiLNLCA-----ISLDRYLA------ITRPLR 106

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1734339383 138 KRQYNTR----LSLAAAWILALICAGPQLILFRQKTTPQGYPQCISIWTE 183
Cdd:cd14967   107 YRQLMTKkralIMIAAVWVYSLLISLPPLVGWRDETQPSVVDCECEFTPN 156

vasopressin receptor subtype 1B, member of the class A family of seven-transmembrane G protein-coupled receptors; The V1b receptor is specifically expressed in corticotropes of the anterior pituitary and plays a critical role in regulating the activity of hypothalamic-pituitary-adrenal axis, a key part of the neuroendocrine system that controls reactions to stress, by maintaining adrenocorticotropic hormone (ACTH) and corticosterone levels. Vasopressin (also known as arginine vasopressin or anti-diuretic hormone) is synthesized in the hypothalamus and is released from the posterior pituitary gland. The actions of vasopressin are mediated by the interaction of this hormone with three receptor subtypes: V1aR, V1bR, and V2R. These subtypes are differ in localization, function, and signaling pathways. Activation of V1aR and V1bR stimulate phospholipase C, while activation of V2R stimulates adenylate cyclase. Although vasopressin and oxytocin differ only by two amino acids and stimulate the same cAMP/PKA pathway, they have divergent physiological functions. Vasopressin is involved in regulating blood pressure and the balance of water and sodium ions, whereas oxytocin plays an important role in the uterus during childbirth and in lactation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  31 VGLPAFIFTVVRLARSRSsRQHLvlaarlfsYKISLSVAD-CIVLFIYAPtQFAWIHSYWWFGGDIGCRLFKFISTFGFH 109
Cdd:cd15386    16 AGNLAVLLAMYRMRRKMS-RMHL--------FVLHLALTDlVVALFQVLP-QLIWEITYRFQGPDLLCRAVKYLQVLSMF 85

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1734339383 110 LTANMQVLVAADRLLITAKMNRVTRNIKKRQYntrLSLAAAWILALICAGPQLILFRQKTTPQG 173
Cdd:cd15386    86 ASTYMLIMMTVDRYIAVCHPLRTLQQPSRQAY---LMIGATWLLSCILSLPQVFIFSLREVDQG 146

GPRnna14 and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the orphan G-protein coupled receptor GPRnna14 found in body louse (Pediculus humanus humanus) as well as its closely related proteins of unknown function. These receptors are members of the class A rhodopsin-like G-protein coupled receptors. As an obligatory parasite of humans, the body louse is an important vector for human diseases, including epidemic typhus, relapsing fever, and trench fever. GPRnna14 shares significant sequence similarity with the members of the neurotensin receptor family. 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 1734339383  25 YGIAFCVGLPA---FIFTVVRLARSRSSRQHLVLaarlfsykiSLSVADCIVLFIYAPTQFAWIHSYWWFGGDIGCRLFK 101
Cdd:cd15001     6 YVITFVLGLIGnslVIFVVARFRRMRSVTNVFLA---------SLATADLLLLVFCVPLKTAEYFSPTWSLGAFLCKAVA 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383 102 FISTFGFHLTANMQVLVAADR-LLITAKMNRVTRNIKKRqynTRLSLAAAWILALICAGPqlILFRQKTTP------QGY 174
Cdd:cd15001    77 YLQLLSFICSVLTLTAISIERyYVILHPMKAKSFCTIGR---ARKVALLIWILSAILASP--VLFGQGLVRyesengVTV 151

                         170
                  ....*....|....*
gi 1734339383 175 PQCISIWTEHRVDFY 189
Cdd:cd15001   152 YHCQKAWPSTLYSRL 166

vasopressin receptor 2, member of the class A family of seven-transmembrane G protein-coupled receptors; The vasopressin type 2 receptor (V2R) is a G(s)-coupled receptor that controls balance of water and sodium ion by regulating their reabsorption in the renal collecting duct. Mutations of V2R is responsible for nephrogenic diabetes insipidus. Vasopressin (also known as arginine vasopressin or anti-diuretic hormone) is synthesized in the hypothalamus and is released from the posterior pituitary gland. The actions of vasopressin are mediated by the interaction of this hormone with three receptor subtypes: V1aR, V1bR, and V2R. These subtypes are differ in localization, function, and signaling pathways. Activation of V1aR and V1bR stimulate phospholipase C, while activation of V2R stimulates adenylate cyclase. Although vasopressin and oxytocin differ only by two amino acids and stimulate the same cAMP/PKA pathway, they have divergent physiological functions. Vasopressin is involved in regulating blood pressure and the balance of water and sodium ions, whereas oxytocin plays an important role in the uterus during childbirth and in lactation.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  21 ELWMYGIAF-CVGLPAFIFTVVRLARSRssrqhlvLAARLFSYKISLSVADCIVLFIYAPTQFAWIHSYWWFGGDIGCRL 99
Cdd:cd15388     3 EIAVLAIIFaCALLSNSLVLLVLWRRRK-------QLARMHVFMLHLCIADLVVAFFQVLPQLVWDITDRFRGPDVLCRL 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1734339383 100 FKFISTFGFHLTANMQVLVAADR-LLITAKMnrVTRNIKKRQYNtrLSLAAAWILALICAGPQLILFRQKTTPQGYPQC 177
Cdd:cd15388    76 VKYLQVVGMFASSYMIVAMTFDRhQAICRPM--VTFQKGRARWN--GPVCVAWAISLILSLPQVFIFSKVEVAPGVYEC 150

neurotensin receptors and related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes the neurotensin receptors and related G-protein coupled receptors, including neuromedin U receptors, growth hormone secretagogue receptor, motilin receptor, the putative GPR39 and the capa receptors from insects. These receptors all bind peptide hormones with diverse physiological effects. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  25 YGIAFCVGLPAFIFTVVRLARSRSSRQHLVLaarlfsYKISLSVADCIVLFIYAPTQ-FAWIHSYWWFGGDIGCRLFKFI 103
Cdd:cd14979     7 YVAIFVVGIVGNLLTCIVIARHKSLRTTTNY------YLFSLAVSDLLILLVGLPVElYNFWWQYPWAFGDGGCKLYYFL 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1734339383 104 STFGFHLTANMQVLVAADRLL-ITAKMNRVTRNIKKRqynTRLSLAAAWILALICAGPQLILFR 166
Cdd:cd14979    81 FEACTYATVLTIVALSVERYVaICHPLKAKTLVTKRR---VKRFILAIWLVSILCAIPILFLMG 141

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        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  62 YKISLSVADCIVLFIYAP-TQFAWIHSYWWFGgDIGCRLFKFISTFG-----FHLTAnmqvlVAADRLL-ITAKMNRVTR 134
Cdd:cd15927    38 FILSLALGDLLLLLTCVPfTSTIYTLDSWPFG-EFLCKLSEFLKDTSigvsvFTLTA-----LSADRYFaIVNPMRKHRS 111

                          90       100       110
                  ....*....|....*....|....*....|
gi 1734339383 135 NIKKRqynTRLSLAAAWILALICAGPQLIL 164
Cdd:cd15927   112 QATRR---TLVTAASIWIVSILLAIPEAIF 138

medium wave-sensitive opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes Medium Wave-Sensitive opsin, which mediates visual transduction in response to light at medium wavelengths (green). Vertebrate cone opsins are expressed in cone photoreceptor cells of the retina and involved in mediating photopic vision, which allows color perception. The cone opsins can be classified into four classes according to their peak absorption wavelengths: SWS1 (ultraviolet sensitive), SWS2 (short wave-sensitive), MWS/LWS (medium/long wave-sensitive), and RH2 (medium wave-sensitive, rhodopsin-like opsins). Members of this group belong to the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  51 QHLVLAARLFSYKISLSVAD-CIVLFIYAPTQFAWIHSYWWFGgDIGCRLFKFISTFGFHLTANMQVLVAADRLLITAKm 129
Cdd:cd15080    27 QHKKLRTPLNYILLNLAVADlFMVFGGFTTTMYTSMHGYFVFG-PTGCNLEGFFATLGGEIALWSLVVLAIERYVVVCK- 104

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1734339383 130 nrVTRNIKKRQYNTRLSLAAAWILALICAGPQLI 163
Cdd:cd15080   105 --PMSNFRFGENHAIMGVAFTWVMALACAAPPLV 136

urotensin-II receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The urotensin-II receptor (UII-R, also known as the hypocretin receptor) is a member of the class A rhodopsin-like G-protein coupled receptors, which binds the peptide hormone urotensin-II. Urotensin II (UII) is a vasoactive somatostatin-like or cortistatin-like peptide hormone. However, despite the apparent structural similarity to these peptide hormones, they are not homologous to UII. Urotensin II was first identified in fish spinal cord, but later found in humans and other mammals. In fish, UII is secreted at the back part of the spinal cord, in a neurosecretory centre called uroneurapophysa, and is involved in the regulation of the renal and cardiovascular systems. In mammals, urotensin II is the most potent mammalian vasoconstrictor identified to date and causes contraction of arterial blood vessels, including the thoracic aorta. The urotensin II receptor is a rhodopsin-like G-protein coupled receptor, which binds urotensin-II. The receptor was previously known as GPR14, or sensory epithelial neuropeptide-like receptor (SENR). The UII receptor is expressed in the CNS (cerebellum and spinal cord), skeletal muscle, pancreas, heart, endothelium and vascular smooth muscle. It is involved in the pathophysiological control of cardiovascular function and may also influence CNS and endocrine functions. Binding of urotensin II to the receptor leads to activation of phospholipase C, through coupling to G(q/11) family proteins. The resulting increase in intracellular calcium may cause the contraction of vascular smooth muscle.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  24 MYGIAFCVGLPAFIFTVVRLARSRSSRqhlvlaARLFSYKISLSVADCIVLF---IYAPTQFAwihSYWWFGgDIGCRLF 100
Cdd:cd14999     5 VLSLMCVVGVAGNVYTLVVMCLSMRPR------ASMYVYILNLALADLLYLLtipFYVSTYFL---KKWYFG-DVGCRLL 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383 101 KFISTFGFHLTANMQVLVAADRLLItakmnrVTRNIKKRQYNTRLSLAAA---WILALICAGPQLILFRQKT----TPQG 173
Cdd:cd14999    75 FSLDFLTMHASIFTLTVMSTERYLA------VVKPLDTVKRSKSYRKLLAgviWLLSLLLTLPMAIMIRLVTvedkSGGS 148

                         170
                  ....*....|
gi 1734339383 174 YPQCISIWTE 183
Cdd:cd14999   149 KRICLPTWSE 158

purinoceptor and its related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; Members of this subfamily include lysophosphatidic acid receptor, P2 purinoceptor, protease-activated receptor, platelet-activating factor receptor, Epstein-Barr virus induced gene 2, proton-sensing G protein-coupled receptors, GPR35, and GPR55, among others. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  24 MYGIAFCVGLPAFIFTVVRLARSRSSRQHLVLaarlfsYKISLSVADciVLFIYA-PTqfaWIHSY----WWFGGDIGCR 98
Cdd:cd14982     6 VYSLIFILGLLGNILALWVFLRKMKKRSPTTI------YMINLALAD--LLFVLTlPF---RIYYYlnggWWPFGDFLCR 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1734339383  99 lfkfISTFGFHLtaNMQ------VLVAADRLLITAKMNRvTRNIKKRQYNTRLSlAAAWILALICAGPQLIL 164
Cdd:cd14982    75 ----LTGLLFYI--NMYgsilflTCISVDRYLAVVHPLK-SRRLRRKRYAVGVC-AGVWILVLVASVPLLLL 138

leukotriene B4 receptor subtype 1 (LTB4R1 or BLT1), 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 Gq-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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  27 IAFCVGLPAFIF---TVVRLARSRSSRQHLVLaarlfsykiSLSVADCIVLfIYAPTQFAWIHSYWWFGGDIGCRLFKFI 103
Cdd:cd15121     9 LAFILGFPGNLFvvwSVLCRMKKRSVTCILVL---------NLALADAAVL-LTAPFFLHFLSGGGWEFGSVVCKLCHYV 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1734339383 104 STFGFHLTANMQVLVAADRLLITAKmnRVTRNIKKRQYNTRLSLAAAWILALICAGP 160
Cdd:cd15121    79 CGVSMYASIFLITLMSMDRCLAVAK--PFLSQKMRTKRSVRALLLAIWIVAFLLSLP 133

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  62 YKISLSVADCIVLFIYAPTQFAWIHSYWWFGGDIGCRLFKFISTFGFHLTANMQVLVAADRLLITAKMNRVtrniKKRQY 141
Cdd:cd14992    38 FIASLAISDLLMALFCTPFNFTYVVSLSWEYGHFLCKIVNYLRTVSVYASSLTLTAIAFDRYFAIIHPLKP----RHRQS 113

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1734339383 142 NTRLS--LAAAWILALICAGPQLILFRQKTTPQ 172
Cdd:cd14992   114 YTTTViiIITIWVVSLLLAIPQLYYATTEVLFS 146

leukotriene B4 receptor subtype 2 (LTB4R2 or BLT2), 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 Gq-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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  27 IAFCVGLPAFIFTVVRLARSRSSRQHLVLAARLfsykISLSVADCIVLFIyAPTQFAWIHSYWWFGGDIGCRLFKFISTF 106
Cdd:cd15122     9 LAALLGLPGNGFIIWSILWKMKARGRSVTCILI----LNLAVADGAVLLL-TPFFITFLTRKTWPFGQAVCKAVYYLCCL 83

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1734339383 107 GFHLTANMQVLVAADRLLITAKmNRVTRNIKKRQYNTRLsLAAAWILALICAGPQLIlFRQKTTPQG 173
Cdd:cd15122    84 SMYASIFIIGLMSLDRCLAVTR-PYLAQSLRKKALVRKI-LLAIWLLALLLALPAFV-YRHVWKDEG 147

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  29 FCVGLPAFIFTVVRLARSRSSRQHLVLaarlfsYKISLSVADCIVLFIYAPTQFA-WIHSYWWFGgDIGCRLFKFISTFG 107
Cdd:cd15131    11 FVVGVTGNLMTMLVVSKYRDMRTTTNL------YLSSMAFSDLLIFLCMPLDLYRlWQYRPWNFG-DLLCKLFQFVSESC 83

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1734339383 108 FHLTANMQVLVAADRLLITAKMNRVTRNIKKRQynTRLSLAAAWILALICAGPQLIL 164
Cdd:cd15131    84 TYSTILNITALSVERYFAICFPLRAKVVVTKRR--VKLVILVLWAVSFLSAGPIFVL 138

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383  24 MYGIAFCVGLPAFIFTVVRLARSRssrqhlvLAARLFSYKISLSVADCIVLFIYAPtqFAWIHSYWWFGGDIGCRLFKFI 103
Cdd:cd14978     6 VLPVICIFGIIGNILNLVVLTRKS-------MRSSTNVYLAALAVSDILVLLSALP--LFLLPYIADYSSSFLSYFYAYF 76

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1734339383 104 STFGFHLTANMQ-------VLVAADRLLITAKMNRVTRNIKKRqyNTRLSLAAAWILALICAGPQLILFR 166
Cdd:cd14978    77 LPYIYPLANTFQtasvwltVALTVERYIAVCHPLKARTWCTPR--RARRVILIIIIFSLLLNLPRFFEYE 144