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 46559769  13 VTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYSCLFMTCLLLI 92
Cdd:cd15070   1 VTYISIEILIGLCAVVGNVLVIWVVKLNPSLRTTTFYFIVSLALADIAVGVLVIPLAIVVSLGVTIHFYSCLFMSCLLVV 80

                        90       100
                ....*....|....*....|....*...
gi 46559769  93 FTHASIMSLLAIAVDRYLRVKLTVRFRI 120
Cdd:cd15070  81 FTHASIMSLLAIAVDRYLRVKLTVRYRI 108

adenosine receptor subtype A3, member of the class A family of seven-transmembrane G protein-coupled receptors; The A3 receptor, a member of the adenosine receptor family of G protein-coupled receptors, is coupled to G proteins of the inhibitory G(i) family, which lead to inhibition of adenylate cyclase and thereby lowering the intracellular cAMP levels. The A3 receptor has a sustained protective function in the heart during cardiac ischemia and contributes to inhibition of neutrophil degranulation in neutrophil-mediated tissue injury. Moreover, activation of A3 receptor by adenosine protects astrocytes from cell death induced by hypoxia.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  13 VTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYSCLFMTCLLLI 92
Cdd:cd15070   1 VTYISIEILIGLCAVVGNVLVIWVVKLNPSLRTTTFYFIVSLALADIAVGVLVIPLAIVVSLGVTIHFYSCLFMSCLLVV 80

                        90       100
                ....*....|....*....|....*...
gi 46559769  93 FTHASIMSLLAIAVDRYLRVKLTVRFRI 120
Cdd:cd15070  81 FTHASIMSLLAIAVDRYLRVKLTVRYRI 108

Immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain in the polymeric Ig receptor (pIgR) and similar proteins. pIgR delivers dimeric IgA and pentameric IgM to mucosal secretions. Polymeric immunoglobulin (pIgs) are the first defense against pathogens and toxins. IgA and IgM can form polymers via an 18-residue extension at their C-termini referred to as the tailpiece. pIgR transports pIgs across mucosal epithelia into mucosal secretions. Human pIgR is a glycosylated type I transmembrane protein, comprised of a 620-residue extracellular region, a 23-residue transmembrane region, and a 103-residue cytoplasmic tail. The extracellular region contains five domains that share sequence similarity with Ig variable (v) regions. This group also contains the Ig-like extracellular domains of other receptors such as NK cell receptor Nkp44 and myeloid receptors, among others.

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 46559769 174 CNYNAHYKNHPKYWCRGYfRDYCNIIAFSP--NSTNHVALRD--TGNQLIVTMSCLTKEDTGWYWCGI 237
Cdd:cd05716  19 CPYPPKYASSRKYWCKWG-SEGCQTLVSSEgvVPGGRISLTDdpDNGVFTVTLNQLRKEDAGWYWCGV 85

adenosine receptor subtype A3, member of the class A family of seven-transmembrane G protein-coupled receptors; The A3 receptor, a member of the adenosine receptor family of G protein-coupled receptors, is coupled to G proteins of the inhibitory G(i) family, which lead to inhibition of adenylate cyclase and thereby lowering the intracellular cAMP levels. The A3 receptor has a sustained protective function in the heart during cardiac ischemia and contributes to inhibition of neutrophil degranulation in neutrophil-mediated tissue injury. Moreover, activation of A3 receptor by adenosine protects astrocytes from cell death induced by hypoxia.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  13 VTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYSCLFMTCLLLI 92
Cdd:cd15070   1 VTYISIEILIGLCAVVGNVLVIWVVKLNPSLRTTTFYFIVSLALADIAVGVLVIPLAIVVSLGVTIHFYSCLFMSCLLVV 80

                        90       100
                ....*....|....*....|....*...
gi 46559769  93 FTHASIMSLLAIAVDRYLRVKLTVRFRI 120
Cdd:cd15070  81 FTHASIMSLLAIAVDRYLRVKLTVRYRI 108

adenosine receptor subtype A1, member of the class A family of seven-transmembrane G protein-coupled receptors; The adenosine A1 receptor, a member of the adenosine receptor family of G protein-coupled receptors, binds adenosine as its endogenous ligand. The A1 receptor has primarily inhibitory function on the tissues in which it is located. The A1 receptor slows metabolic activity in the brain and has a strong anti-adrenergic effects in the heart. Thus, it antagonizes beta1-adrenergic receptor-induced stimulation and thereby reduces cardiac contractility. The A1 receptor preferentially couples to G proteins of the G(i/o) family, which lead to inhibition of adenylate cyclase and thereby lowering the intracellular cAMP levels.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  15 YITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYSCLFMTCLLLIFT 94
Cdd:cd15071   3 YIGIEVLIALVSVPGNVLVIWAVKVNQALRDATFCFIVSLAVADVAVGALVIPLAIIINIGPQTEFYSCLMVACPVLILT 82

                        90       100
                ....*....|....*....|....*
gi 46559769  95 HASIMSLLAIAVDRYLRVKLTVRFR 119
Cdd:cd15071  83 QSSILALLAIAVDRYLRVKIPTRYK 107

adenosine receptor subtype 2AB, member of the class A family of seven-transmembrane G protein-coupled receptors; The A2B receptor, a member of the adenosine receptor family of G protein-coupled receptors, binds adenosine as its endogenous ligand and is involved in regulating myocardial oxygen consumption and coronary blood flow. High-affinity A2A and low-affinity A2B receptors are preferentially coupled to G proteins of the stimulatory (Gs) family, which lead to activation of adenylate cyclase and thereby increasing the intracellular cAMP levels. The A2A receptor activation protects against tissue injury and acts as anti-inflammatory agent. In human skin endothelial cells, activation of A2B receptor, but not the A2A receptor, promotes angiogenesis. Alternatively, activated A2A receptor, but not the A2B receptor, promotes angiogenesis in human umbilical vein and lung microvascular endothelial cells. The A2A receptor alters cardiac contractility indirectly by modulating the anti-adrenergic effect of A1 receptor, while the A2B receptor exerts direct effects on cardiac contractile function, but does not modulate beta-adrenergic or A1 anti-adrenergic effects.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  14 TYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYSCLFMTCLLLIF 93
Cdd:cd15069   2 TYVALELIIAALSVAGNVLVCAAVGTNSTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFHSCLFLACFVLVL 81

                        90       100
                ....*....|....*....|....*.
gi 46559769  94 THASIMSLLAIAVDRYLRVKLTVRFR 119
Cdd:cd15069  82 TQSSIFSLLAVAVDRYLAIKVPLRYK 107

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 46559769  15 YITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLLLI 92
Cdd:cd00637   1 LAVLYILIFVVGLVGNLLVILVILRNRRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRWWFGDalCKLLGFLQSV 80

                        90       100
                ....*....|....*....|
gi 46559769  93 FTHASIMSLLAIAVDRYLRV 112
Cdd:cd00637  81 SLLASILTLTAISVDRYLAI 100

serotonin receptor subtype 2, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT2 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the central nervous system (CNS). The 5-HT2 subfamily is composed of three subtypes that mediate excitatory neurotransmission: 5-HT2A, 5-HT2B, and 5-HT2C. They are selectively linked to G proteins of the G(q/11) family and activate phospholipase C, which leads to activation of protein kinase C and calcium release. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in diseases such as migraine, schizophrenia, and depression. Indeed, 5-HT2 receptors are attractive targets for a variety of psychoactive drugs, ranging from atypical antipsychotic drugs, antidepressants, and anxiolytics, which have an antagonistic action on 5-HT2 receptors, to hallucinogens, which act as agonists at postsynaptic 5-HT2 receptors. 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 46559769  20 IFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLG---ITIHFYSCLFMTCLLLIFTHA 96
Cdd:cd15052   8 LLLVIATIGGNILVCLAISLEKRLQNVTNYFLMSLAIADLLVGLLVMPLSILTELFggvWPLPLVLCLLWVTLDVLFCTA 87

                        90       100
                ....*....|....*....|...
gi 46559769  97 SIMSLLAIAVDRYLRVKLTVRFR 119
Cdd:cd15052  88 SIMHLCTISLDRYMAIRYPLRTR 110

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        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  13 VTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITiHFYS---CLFMTCL 89
Cdd:cd14993   1 IVLIVLYVVVFLLALVGNSLVIAVVLRNKHMRTVTNYFLVNLAVADLLVSLFCMPLTLLENVYRP-WVFGevlCKAVPYL 79

                        90       100       110
                ....*....|....*....|....*....|.
gi 46559769  90 LLIFTHASIMSLLAIAVDRYLRVKLTVRFRI 120
Cdd:cd14993  80 QGVSVSASVLTLVAISIDRYLAICYPLKARR 110

beta adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; The beta adrenergic receptor (beta adrenoceptor), also known as beta AR, is activated by hormone adrenaline (epinephrine) and plays important roles in regulating cardiac function and heart rate, as well as pulmonary physiology. The human heart contains three subtypes of the beta AR: beta-1 AR, beta-2 AR, and beta-3 AR. Beta-1 AR and beta-2 AR, which expressed at about a ratio of 70:30, are the major subtypes involved in modulating cardiac contractility and heart rate by positively stimulating the G(s) protein-adenylate cyclase-cAMP-PKA signaling pathway. In contrast, beta-3 AR produces negative inotropic effects by activating inhibitory G(i) proteins. The aberrant expression of beta-ARs can lead to cardiac dysfunction such as arrhythmias or heart failure. 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 46559769  20 IFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLA--IVVSLGITIHFYSCLFMTCLLLIFTHAS 97
Cdd:cd15058   8 ALIILAIVVGNLLVIIAIARTSRLQTMTNIFITSLACADLVMGLLVVPLGatIVVTGKWQLGNFWCELWTSVDVLCVTAS 87

                        90       100
                ....*....|....*....|.
gi 46559769  98 IMSLLAIAVDRYLRVKLTVRF 118
Cdd:cd15058  88 IETLCVIAVDRYIAITRPLRY 108

serotonin receptor subtype 1A from invertebrates, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  13 VTYITMEIFIgLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIV--VSLGITIHFYSCLFMTCLL 90
Cdd:cd15331   2 LTSIILGLLI-LATIIGNVFVIAAILLERSLQGVSNYLILSLAVADLMVAVLVMPLSAVyeVSQHWFLGPEVCDMWISMD 80

                        90       100
                ....*....|....*....|..
gi 46559769  91 LIFTHASIMSLLAIAVDRYLRV 112
Cdd:cd15331  81 VLCCTASILHLVAIALDRYWAV 102

D2-like 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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  20 IFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVV-------SLG-ITIHFYSCLFMTClll 91
Cdd:cd15053   8 LLLPLLTVFGNVLVIMSVFRERSLQTATNYFIVSLAVADLLVAILVMPFAVYVevnggkwYLGpILCDIYIAMDVMC--- 84

                        90       100
                ....*....|....*....|....*..
gi 46559769  92 ifTHASIMSLLAIAVDRYLRVKLTVRF 118
Cdd:cd15053  85 --STASIFNLCAISIDRYIAVTQPIKY 109

serotonin receptor subtype 2 from insects, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT2 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the central nervous system (CNS). The 5-HT2 subfamily is composed of three subtypes that mediate excitatory neurotransmission: 5-HT2A, 5-HT2B, and 5-HT2C. They are selectively linked to G proteins of the G(q/11) family and activate phospholipase C, which leads to activation of protein kinase C and calcium release. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in diseases such as migraine, schizophrenia, and depression. Indeed, 5-HT2 receptors are attractive targets for a variety of psychoactive drugs, ranging from atypical antipsychotic drugs, antidepressants, and anxiolytics, which have an antagonistic action on 5-HT2 receptors, to hallucinogens, which act as agonists at postsynaptic 5-HT2 receptors. 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 46559769  24 LCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLLLIFTHASIMSL 101
Cdd:cd15307  12 LGTAAGNILVCLAIAWERRLQNVTNYFLMSLAITDLMVAVLVMPLGILTLVKGHFPLSSehCLTWICLDVLFCTASIMHL 91

                        90
                ....*....|....*..
gi 46559769 102 LAIAVDRYLRVKLTVRF 118
Cdd:cd15307  92 CTISVDRYLSLRYPMRF 108

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  13 VTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHF--YSCLFMTCLL 90
Cdd:cd15203   1 IILILLYGLIIVLGVVGNLLVIYVVLRNKSMQTVTNIFILNLAVSDLLLCLVSLPFTLIYTLTKNWPFgsILCKLVPSLQ 80

                        90       100
                ....*....|....*....|
gi 46559769  91 LIFTHASIMSLLAIAVDRYL 110
Cdd:cd15203  81 GVSIFVSTLTLTAIAIDRYQ 100

trace amine-associated receptor 1 and similar receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The trace amine-associated receptor 1 (TAAR1) is one of the 15 identified trace amine-associated receptor subtypes, which form a distinct subfamily within the class A G protein-coupled receptor family. Trace amines are endogenous amines of unknown function that have strong structural and metabolic similarity to classical monoamine neurotransmitters (serotonin, noradrenaline, adrenaline, dopamine, and histamine), which play critical roles in human and animal physiological activities such as cognition, consciousness, mood, motivation, perception, and autonomic responses. However, trace amines are found in the mammalian brain at very low concentrations compared to classical monoamines. TAAR1 is coupled to the Gs protein, which leads to activation of adenylate cyclase, and is thought to play functional role in the regulation of brain monoamines. TAAR1 is also shown to be activated by psychoactive compounds such as Ecstasy (MDMA), amphetamine and LSD. 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 46559769  16 ITMEIFIGLCAIV---GNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLL 90
Cdd:cd15314   1 VLLYIFLGLISLVtvcGNLLVIISIAHFKQLHTPTNYLILSLAVADLLVGGLVMPPSMVRSVETCWYFGDlfCKIHSSFD 80

                        90       100       110
                ....*....|....*....|....*....|..
gi 46559769  91 LIFTHASIMSLLAIAVDRYLRV--KLTVRFRI 120
Cdd:cd15314  81 ITLCTASILNLCFISIDRYYAVcqPLLYRSKI 112

serotonin receptor subtype 2A, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT2 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the central nervous system (CNS). The 5-HT2 subfamily is composed of three subtypes that mediate excitatory neurotransmission: 5-HT2A, 5-HT2B, and 5-HT2C. They are selectively linked to G proteins of the G(q/11) family and activate phospholipase C, which leads to activation of protein kinase C and calcium release. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in diseases such as migraine, schizophrenia, and depression. Indeed, 5-HT2 receptors are attractive targets for a variety of psychoactive drugs, ranging from atypical antipsychotic drugs, antidepressants, and anxiolytics, which have an antagonistic action on 5-HT2 receptors, to hallucinogens, which act as agonists at postsynaptic 5-HT2 receptors. 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 46559769  24 LCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSL---GITIHFYSCLFMTCLLLIFTHASIMS 100
Cdd:cd15304  12 ILTIAGNILVIMAVSLEKKLQNATNYFLMSLAIADMLLGFLVMPVSMLTILygyRWPLPSKLCAVWIYLDVLFSTASIMH 91

                        90
                ....*....|...
gi 46559769 101 LLAIAVDRYLRVK 113
Cdd:cd15304  92 LCAISLDRYIAIR 104

trace amine-associated receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The trace amine-associated receptors (TAARs) are a distinct subfamily within the class A G protein-coupled receptor family. Trace amines are endogenous amines of unknown function that have strong structural and metabolic similarity to classical monoamine neurotransmitters (serotonin, noradrenaline, adrenaline, dopamine, and histamine), which play critical roles in human and animal physiological activities such as cognition, consciousness, mood, motivation, perception, and autonomic responses. However, trace amines are found in the mammalian brain at very low concentrations compared to classical monoamines. Trace amines, including p-tyramine, beta-phenylethylamine, and tryptamine, are also thought to act as chemical messengers to exert their biological effects in vertebrates. 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 46559769  12 NVTYITMEIFIGLCaIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCL 89
Cdd:cd15055   1 VLLYIVLSSISLLT-VLGNLLVIISISHFKQLHTPTNLLLLSLAVADFLVGLLVMPFSMIRSIETCWYFGDtfCKLHSSL 79

                        90       100
                ....*....|....*....|...
gi 46559769  90 LLIFTHASIMSLLAIAVDRYLRV 112
Cdd:cd15055  80 DYILTSASIFNLVLIAIDRYVAV 102

muscarinic acetylcholine receptor DM1, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes muscarinic acetylcholine receptor DM1-like from invertebrates. Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of mAChRs by agonist (acetylcholine) leads to a variety of biochemical and electrophysiological responses. In general, the exact nature of these responses and the subsequent physiological effects mainly depend on the molecular and pharmacological identity of the activated receptor subtype(s). 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 46559769  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVS------LGITIhfysCLFMTCLLLIFT 94
Cdd:cd15301   9 VLSLVTVGGNVMVMISFKIDKQLQTISNYFLFSLAVADFAIGVISMPLFTVYTalgywpLGYEV----CDTWLAIDYLAS 84

                        90       100
                ....*....|....*....|....*
gi 46559769  95 HASIMSLLAIAVDRYLRVKLTVRFR 119
Cdd:cd15301  85 NASVLNLLIISFDRYFSVTRPLTYR 109

serotonin receptor subtype 2B, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT2 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the central nervous system (CNS). The 5-HT2 subfamily is composed of three subtypes that mediate excitatory neurotransmission: 5-HT2A, 5-HT2B, and 5-HT2C. They are selectively linked to G proteins of the G(q/11) family and activate phospholipase C, which leads to activation of protein kinase C and calcium release. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in diseases such as migraine, schizophrenia, and depression. Indeed, 5-HT2 receptors are attractive targets for a variety of psychoactive drugs, ranging from atypical antipsychotic drugs, antidepressants, and anxiolytics, which have an antagonistic action on 5-HT2 receptors, to hallucinogens, which act as agonists at postsynaptic 5-HT2 receptors. 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 46559769  27 IVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIvvslgITIHFYS--------CLFMTCLLLIFTHASI 98
Cdd:cd15306  15 IGGNILVILAVSLEKKLQYATNYFLMSLAVADLLVGLFVMPIAL-----LTILFEAmwplplvlCPIWLFLDVLFSTASI 89

                        90
                ....*....|....*
gi 46559769  99 MSLLAIAVDRYLRVK 113
Cdd:cd15306  90 MHLCAISLDRYIAIK 104

tachykinin receptors and related receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the neurokinin/tachykinin receptors and its closely related receptors such as orphan GPR83 and leucokinin-like peptide receptor. The tachykinins are widely distributed throughout the mammalian central and peripheral nervous systems and act as excitatory transmitters on neurons and cells in the gastrointestinal tract. The TKs are characterized by a common five-amino acid C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is a hydrophobic residue. The three major mammalian tachykinins are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). The physiological actions of tachykinins are mediated through three types of receptors: neurokinin receptor type 1 (NK1R), NK2R, and NK3R. SP is a high-affinity endogenous ligand for NK1R, which interacts with the Gq protein and activates phospholipase C, leading to elevation of intracellular calcium. NK2R is a high-affinity receptor for NKA, the tachykinin neuropeptide substance K. SP and NKA are found in the enteric nervous system and mediate in the regulation of gastrointestinal motility, secretion, vascular permeability, and pain perception. NK3R is activated by its high-affinity ligand, NKB, which is primarily involved in the central nervous system and plays a critical role in the regulation of gonadotropin hormone release and the onset of puberty.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  20 IFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHF--YSCLFMTCLLLIFTHAS 97
Cdd:cd15202   8 SFIIVFSLFGNVLVCWIIFKNQRMRTVTNYFIVNLAVADIMITLFNTPFTFVRAVNNTWIFglFMCHFSNFAQYCSVHVS 87

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 46559769  98 IMSLLAIAVDRYLRVKLTVRFRIPGLPGCILsfqlkVCFLPVMWLFILLSLALIS--DAMVMDEKVKRSFVL 167
Cdd:cd15202  88 AYTLTAIAVDRYQAIMHPLKPRISKTKAKFI-----IAVIWTLALAFALPHAICSklETFKYSEDIVRSLCL 154

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  16 ITMEIFIgLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLgitIHFYS-----CLFMTCLL 90
Cdd:cd15327   5 VFLAIFI-LMAIVGNILVILSVACNRHLQTVTNYFIVNLAIADLLLSTTVLPFSATLEV---LGFWAfgrvfCDIWAAVD 80

                        90       100
                ....*....|....*....|....*...
gi 46559769  91 LIFTHASIMSLLAIAVDRYLRVKLTVRF 118
Cdd:cd15327  81 VLCCTASILSLCVISVDRYVGVKHSLKY 108

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAI---VVSLGITIHFYSCLFMTCLLLIFThAS 97
Cdd:cd15063   9 FLNVLVVLGNLLVIAAVLCSRKLRTVTNLFIVSLACADLLVGTLVLPFSAvneVLDVWIFGHTWCQIWLAVDVWMCT-AS 87

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 46559769  98 IMSLLAIAVDRYLRVKLTVRFripglPGCILSFQLKvCFLPVMWLF 143
Cdd:cd15063  88 ILNLCAISLDRYLAITRPIRY-----PSLMSTKRAK-CLIAGVWVL 127

Drosophila melanogaster beta-adrenergic receptor-like octopamine receptors and similar receptors in bilateria; member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes Drosophila beta-adrenergic-like octopamine receptors and similar proteins. The biogenic amine octopamine is the invertebrate equivalent of vertebrate adrenergic neurotransmitters and exerts its effects through different G protein-coupled receptor types. Insect octopamine receptors are involved in the modulation of carbohydrate metabolism, muscular tension, cognition and memory. The activation of octopamine receptors mediating these actions leads to an increase in adenylate cyclase activity, thereby increasing cAMP levels. In Drosophila melanogaster, three subgroups have been classified on the basis of their structural homology and functional equivalents with vertebrate beta-adrenergic receptors: DmOctBeta1R, DmOctBeta2R, and DmOctBeta3R.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLLLIFTHASI 98
Cdd:cd15066   8 LIILAAIFGNLLVIISVMRHRKLRVITNYFVVSLAMADMLVALCAMTFNASVEITGRWMFGYfmCDVWNSLDVYFSTASI 87

                        90
                ....*....|.
gi 46559769  99 MSLLAIAVDRY 109
Cdd:cd15066  88 LHLCCISVDRY 98

beta-3 adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; The beta-3 adrenergic receptor (beta-3 adrenoceptor), also known as beta-3 AR, is activated by adrenaline and plays important roles in regulating cardiac function and heart rate. The human heart contains three subtypes of the beta AR: beta-1 AR, beta-2 AR, and beta-3 AR. Beta-1 AR and beta-2 AR, which expressed at about a ratio of 70:30, are the major subtypes involved in modulating cardiac contractility and heart rate by positively stimulating the G(s) protein-adenylate cyclase-cAMP-PKA signaling pathway. In contrast, beta-3 AR produces negative inotropic effects by activating inhibitory G(i) proteins. The aberrant expression of betrayers can lead to cardiac dysfunction such as arrhythmias or heart failure.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  24 LCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAivVSLGITIHF----YSCLFMTCLLLIFTHASIM 99
Cdd:cd15959  12 LVIVGGNLLVIVAIAKTPRLQTMTNVFVTSLACADLVMGLLVVPPG--ATILLTGHWplgtTVCELWTSVDVLCVTASIE 89

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 46559769 100 SLLAIAVDRYLRVKLTVRFRIPGLPGC-------ILSFQLKVCFLPVM 140
Cdd:cd15959  90 TLCAIAVDRYLAITNPLRYEALVTKRRartavclVWAISAAISFLPIM 137

D4 dopamine receptor of the D2-like family, 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. Activation of D2-like family receptors is linked to G proteins of the G(i) family. This leads to a decrease in adenylate cyclase activity, thereby decreasing cAMP levels. 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  24 LCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAI---VVSLGITIHFYSCLFMTCLLLIFTHASIMS 100
Cdd:cd15308  12 LAIIAGNVLVCLSVCTERALKTTTNYFIVSLAVADLLLALLVLPLYVyseFQGGVWTLSPVLCDALMTMDVMLCTASIFN 91

                        90
                ....*....|....*...
gi 46559769 101 LLAIAVDRYLRVKLTVRF 118
Cdd:cd15308  92 LCAISVDRFIAVSVPLNY 109

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  13 VTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLgiTIHFYSCLFMTCLLLI 92
Cdd:cd15392   1 VIIILMYSTIFVLAVGGNGLVCYIVVSYPRMRTVTNYFIVNLALSDILMAVFCVPFSFIALL--ILQYWPFGEFMCPVVN 78

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 46559769  93 FTHA-----SIMSLLAIAVDRY------LRVKLTVRF 118
Cdd:cd15392  79 YLQAvsvfvSAFTLVAISIDRYvaimwpLRPRMTKRQ 115

alpha-2 adrenergic receptors subtype B, 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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  11 ANVTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTC 88
Cdd:cd15321   5 ATAAIAAAITFLILFTIFGNVLVIIAVLTSRSLRAPQNLFLVSLAAADILVATLIIPFSLANELMGYWYFRKtwCEIYLA 84

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 46559769  89 LLLIFTHASIMSLLAIAVDRYLRVKLTVRF---RIPGLPGCIL 128
Cdd:cd15321  85 LDVLFCTSSIVHLCAISLDRYWSVSRAIEYnskRTPRRIKCII 127

muscarinic acetylcholine receptor subfamily, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of mAChRs by agonist (acetylcholine) leads to a variety of biochemical and electrophysiological responses. In general, the exact nature of these responses and the subsequent physiological effects mainly depend on the molecular and pharmacological identity of the activated receptor subtype(s). 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 46559769  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVV------SLGITIhfysCLFMTCLLLIFT 94
Cdd:cd15049   9 SLSLVTVGGNILVILSFRVNRQLRTVNNYFLLSLACADLIIGLVSMNLYTVYlvmgywPLGPLL----CDLWLALDYVAS 84

                        90       100
                ....*....|....*....|....*
gi 46559769  95 HASIMSLLAIAVDRYLRVKLTVRFR 119
Cdd:cd15049  85 NASVMNLLLISFDRYFSVTRPLTYR 109

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 46559769  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLLLIFTHASI 98
Cdd:cd15323   9 FLIVFTIVGNVLVVIAVLTSRALRAPQNLFLVSLASADILVATLVMPFSLANELMGYWYFGQvwCNIYLALDVLFCTSSI 88

                        90       100
                ....*....|....*....|....*.
gi 46559769  99 MSLLAIAVDRYLRVKLTVRFRIPGLP 124
Cdd:cd15323  89 VHLCAISLDRYWSVTQAVEYNLKRTP 114

muscarinic acetylcholine receptor subtype M2, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of M2 receptor causes a decrease in cAMP production, generally leading to inhibitory-type effects. This causes an outward current of potassium in the heart, resulting in a decreased heart rate. 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 46559769  22 IGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVslgITIHFYSCLFMTCLL-----LIFTHA 96
Cdd:cd15297  10 LSLVTIIGNILVMVSIKVNRHLQTVNNYFLFSLACADLIIGVFSMNLYTLY---TVIGYWPLGPVVCDLwlaldYVVSNA 86

                        90
                ....*....|....*.
gi 46559769  97 SIMSLLAIAVDRYLRV 112
Cdd:cd15297  87 SVMNLLIISFDRYFCV 102