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 705043704  13 VTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYSCLFMTCLLLI 92
Cdd:cd15070    1 VTYISIEILIGLCAVVGNVLVIWVVKLNPSLRTTTFYFIVSLALADIAVGVLVIPLAIVVSLGVTIHFYSCLFMSCLLVV 80

                         90       100
                 ....*....|....*....|....
gi 705043704  93 FTHASIMSLLAIAVDRYLRVKLTV 116
Cdd:cd15070   81 FTHASIMSLLAIAVDRYLRVKLTV 104

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 705043704  13 VTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYSCLFMTCLLLI 92
Cdd:cd15070    1 VTYISIEILIGLCAVVGNVLVIWVVKLNPSLRTTTFYFIVSLALADIAVGVLVIPLAIVVSLGVTIHFYSCLFMSCLLVV 80

                         90       100
                 ....*....|....*....|....
gi 705043704  93 FTHASIMSLLAIAVDRYLRVKLTV 116
Cdd:cd15070   81 FTHASIMSLLAIAVDRYLRVKLTV 104

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 705043704  13 VTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYSCLFMTCLLLI 92
Cdd:cd15070    1 VTYISIEILIGLCAVVGNVLVIWVVKLNPSLRTTTFYFIVSLALADIAVGVLVIPLAIVVSLGVTIHFYSCLFMSCLLVV 80

                         90       100
                 ....*....|....*....|....
gi 705043704  93 FTHASIMSLLAIAVDRYLRVKLTV 116
Cdd:cd15070   81 FTHASIMSLLAIAVDRYLRVKLTV 104

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 705043704  15 YITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYSCLFMTCLLLIFT 94
Cdd:cd15071    3 YIGIEVLIALVSVPGNVLVIWAVKVNQALRDATFCFIVSLAVADVAVGALVIPLAIIINIGPQTEFYSCLMVACPVLILT 82

                         90       100
                 ....*....|....*....|...
gi 705043704  95 HASIMSLLAIAVDRYLRVKLTVS 117
Cdd:cd15071   83 QSSILALLAIAVDRYLRVKIPTR 105

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 705043704  14 TYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYSCLFMTCLLLIF 93
Cdd:cd15069    2 TYVALELIIAALSVAGNVLVCAAVGTNSTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFHSCLFLACFVLVL 81

                         90       100
                 ....*....|....*....|.
gi 705043704  94 THASIMSLLAIAVDRYLRVKL 114
Cdd:cd15069   82 TQSSIFSLLAVAVDRYLAIKV 102

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 705043704  15 YITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLLLI 92
Cdd:cd00637    1 LAVLYILIFVVGLVGNLLVILVILRNRRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRWWFGDalCKLLGFLQSV 80

                         90       100
                 ....*....|....*....|
gi 705043704  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 705043704  20 IFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLG---ITIHFYSCLFMTCLLLIFTHA 96
Cdd:cd15052    8 LLLVIATIGGNILVCLAISLEKRLQNVTNYFLMSLAIADLLVGLLVMPLSILTELFggvWPLPLVLCLLWVTLDVLFCTA 87

                         90
                 ....*....|....*..
gi 705043704  97 SIMSLLAIAVDRYLRVK 113
Cdd:cd15052   88 SIMHLCTISLDRYMAIR 104

serotonin receptor subtype 4, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT4 subtype is a member of the serotonin receptor family that belongs to the class A G protein-coupled receptors, and binds the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the mammalian central nervous system (CNS). 5-HT4 receptors are selectively linked to G proteins of the G(s) family, which positively stimulate adenylate cyclase, causing cAMP formation and activation of protein kinase A. 5-HT4 receptor-specific agonists have been shown to enhance learning and memory in animal studies. Moreover, hippocampal 5-HT4 receptor expression has been reported to be inversely correlated with memory performance in humans. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705043704  13 VTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSL-GITIHFYS-CLFMTCLL 90
Cdd:cd15056    1 VVLSTFLSLVILLTILGNLLVIVAVCTDRQLRKKTNYFVVSLAVADLLVAVLVMPFGAIELVnNRWIYGETfCLVRTSLD 80

                         90       100
                 ....*....|....*....|..
gi 705043704  91 LIFTHASIMSLLAIAVDRYLRV 112
Cdd:cd15056   81 VLLTTASIMHLCCIALDRYYAI 102

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 705043704  24 LCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIV--VSLGITIHFYSCLFMTCLLLIFTHASIMSL 101
Cdd:cd15331   12 LATIIGNVFVIAAILLERSLQGVSNYLILSLAVADLMVAVLVMPLSAVyeVSQHWFLGPEVCDMWISMDVLCCTASILHL 91

                         90
                 ....*....|.
gi 705043704 102 LAIAVDRYLRV 112
Cdd:cd15331   92 VAIALDRYWAV 102

tyramine receptors and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes tyramine-specific receptors and similar proteins found in insects and other invertebrates. These tyramine receptors form a distinct receptor family that is phylogenetically different from the other tyramine/octopamine receptors which also found in invertebrates. Both octopamine and tyramine mediate their actions via G protein-coupled receptors (GPCRs) and are the invertebrate equivalent of vertebrate adrenergic neurotransmitters. In Drosophila, octopamine is involved in ovulation by mediating an egg release from the ovary, while a physiological role for tyramine in this process is not fully understood. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705043704  16 ITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLLLIF 93
Cdd:cd15061    3 ISFLILAIIFTIFGNLLVILAVATTRRLRTITNCYIVSLATADLLVGVLVLPLAIIRQLLGYWPLGShlCDFWISLDVLL 82

                         90
                 ....*....|....*....
gi 705043704  94 THASIMSLLAIAVDRYLRV 112
Cdd:cd15061   83 CTASILNLCCISLDRYFAI 101

serotonin receptor subtypes 1, 5 and 7, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes serotonin receptor subtypes 1, 5, and 7 that are activated by the neurotransmitter serotonin. The 5-HT1 and 5-HT5 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family. The 5-HT1 receptor subfamily includes 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as 5-HT2C receptor. The 5-HT5A and 5-HT5B receptors have been cloned from rat and mouse, but only the 5-HT5A isoform has been identified in human because of the presence of premature stop codons in the human 5-HT5B gene, which prevents a functional receptor from being expressed. The 5-HT7 receptor is coupled to Gs, which positively stimulates adenylate cyclase activity, leading to increased intracellular cAMP formation and calcium influx. 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 705043704  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLLLIFTHASI 98
Cdd:cd15064    9 LIILATILGNALVIAAILLTRKLHTPANYLIASLAVADLLVAVLVMPLSAVYELTGRWILGQvlCDIWISLDVTCCTASI 88

                         90
                 ....*....|.
gi 705043704  99 MSLLAIAVDRY 109
Cdd:cd15064   89 LHLCVIALDRY 99

histamine subtype H2 receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine receptor subtype H2R, a member of histamine receptor family, which belongs to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). The H2R subtype selectively interacts with the G(s)-type G protein that activates adenylate cyclase, leading to increased cAMP production and activation of Protein Kinase A. H2R is found in various tissues such as the brain, stomach, and heart. Its most prominent role is in histamine-induced gastric acid secretion. 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 705043704  22 IGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHF--YSCLFMTCLLLIFTHASIM 99
Cdd:cd15051   10 IILLTVIGNVLVCLAVAVNRRLRNLTNYFIVSLAVTDLLLGLLVLPFSAIYELRGEWPLgpVFCNIYISLDVMLCTASIL 89

                         90
                 ....*....|...
gi 705043704 100 SLLAIAVDRYLRV 112
Cdd:cd15051   90 NLFAISLDRYLAI 102

alpha-2 adrenergic receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705043704  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLLLIFTHASI 98
Cdd:cd15059    9 VVILLIIVGNVLVIVAVLTSRKLRAPQNWFLVSLAVADILVGLLIMPFSLVNELMGYWYFGSvwCEIWLALDVLFCTASI 88

                         90
                 ....*....|.
gi 705043704  99 MSLLAIAVDRY 109
Cdd:cd15059   89 VNLCAISLDRY 99

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 705043704  13 VTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHF--YSCLFMTCLL 90
Cdd:cd15203    1 IILILLYGLIIVLGVVGNLLVIYVVLRNKSMQTVTNIFILNLAVSDLLLCLVSLPFTLIYTLTKNWPFgsILCKLVPSLQ 80

                         90       100
                 ....*....|....*....|
gi 705043704  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 705043704  16 ITMEIFIGLCAIV---GNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLL 90
Cdd:cd15314    1 VLLYIFLGLISLVtvcGNLLVIISIAHFKQLHTPTNYLILSLAVADLLVGGLVMPPSMVRSVETCWYFGDlfCKIHSSFD 80

                         90       100
                 ....*....|....*....|..
gi 705043704  91 LIFTHASIMSLLAIAVDRYLRV 112
Cdd:cd15314   81 ITLCTASILNLCFISIDRYYAV 102

histamine subtype H1 receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine receptor subtype H1R, a member of histamine receptor family, which belongs to the class A of GPCRs. Histamine plays a key role as chemical mediator and neurotransmitter in various physiological and pathophysiological processes in the central and peripheral nervous system. Histamine exerts its functions by binding to four different G protein-coupled receptors (H1-H4). H1R selectively interacts with the G(q)-type G protein that activates phospholipase C and the phosphatidylinositol pathway. Antihistamines, a widely used anti-allergy medication, act on the H1 subtype and produce drowsiness as a side effect. 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 705043704  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVV------SLGITIhfysCLFMTCLLLIFT 94
Cdd:cd15050    9 TISLITVILNLLVLYAVRTERKLHTVGNLYIVSLSVADLIVGAVVMPLNIVYlleskwILGRPV----CLFWLSMDYVAS 84

                         90
                 ....*....|....*....
gi 705043704  95 HASIMSLLAIAVDRYLRVK 113
Cdd:cd15050   85 TASIFSLFILCIDRYRSVQ 103

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 705043704  24 LCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSL---GITIHFYSCLFMTCLLLIFTHASIMS 100
Cdd:cd15304   12 ILTIAGNILVIMAVSLEKKLQNATNYFLMSLAIADMLLGFLVMPVSMLTILygyRWPLPSKLCAVWIYLDVLFSTASIMH 91

                         90
                 ....*....|...
gi 705043704 101 LLAIAVDRYLRVK 113
Cdd:cd15304   92 LCAISLDRYIAIR 104

serotonin receptor subtypes B1 and B2 from Aplysia californica and similar proteins; member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes Aplysia californica serotonin receptors Ap5-HTB1 and Ap5-HTB2, and similar proteins from bilateria including insects, mollusks, annelids, and worms. Ap5-HTB1 is one of the several different receptors for 5-hydroxytryptamine (5HT, serotonin). In Aplysia, serotonin plays important roles in a variety of behavioral and physiological processes mediated by the central nervous system. These include circadian clock, feeding, locomotor movement, cognition and memory, synaptic growth and synaptic plasticity. Both Ap5-HTB1 and Ap5-HTB2 receptors are coupled to G-proteins that stimulate phospholipase C, leading to the activation of phosphoinositide metabolism. Ap5-HTB1 is expressed in the reproductive system, whereas Ap5-HTB2 is expressed in the central nervous system.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705043704  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSL---GITIHFYsCLFMTCLLLIFTHAS 97
Cdd:cd15065    8 LIIVLAIFGNVLVCLAIFTDRRLRKKSNLFIVSLAVADLLVALLVMTFAVVNDLlgyWLFGETF-CNIWISFDVMCSTAS 86

                         90
                 ....*....|....*.
gi 705043704  98 IMSLLAIAVDRYLRVK 113
Cdd:cd15065   87 ILNLCAISLDRYIHIK 102

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 705043704  12 NVTYITMEIFIGLCaIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCL 89
Cdd:cd15055    1 VLLYIVLSSISLLT-VLGNLLVIISISHFKQLHTPTNLLLLSLAVADFLVGLLVMPFSMIRSIETCWYFGDtfCKLHSSL 79

                         90       100
                 ....*....|....*....|...
gi 705043704  90 LLIFTHASIMSLLAIAVDRYLRV 112
Cdd:cd15055   80 DYILTSASIFNLVLIAIDRYVAV 102

beta-1 adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; The beta-1 adrenergic receptor (beta-1 adrenoceptor), also known as beta-1 AR, is activated by adrenaline (epinephrine) 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 705043704  22 IGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLLLIFTHASIM 99
Cdd:cd15958   10 IVLLIVAGNVLVIVAIGRTQRLQTLTNLFITSLACADLVMGLLVVPFGATLVVRGRWLYGSffCELWTSVDVLCVTASIE 89

                         90
                 ....*....|...
gi 705043704 100 SLLAIAVDRYLRV 112
Cdd:cd15958   90 TLCVIAIDRYLAI 102

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 705043704  20 IFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHF--YSCLFMTCLLLIFTHAS 97
Cdd:cd15202    8 SFIIVFSLFGNVLVCWIIFKNQRMRTVTNYFIVNLAVADIMITLFNTPFTFVRAVNNTWIFglFMCHFSNFAQYCSVHVS 87

                         90
                 ....*....|....*
gi 705043704  98 IMSLLAIAVDRYLRV 112
Cdd:cd15202   88 AYTLTAIAVDRYQAI 102

muscarinic acetylcholine receptor subtype M3, 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. The M3 receptor is mainly located in smooth muscle, exocrine glands and vascular endothelium. It induces vomiting in the central nervous system and is a critical regulator of glucose homeostasis by modulating insulin secretion. Generally, M3 receptor causes contraction of smooth muscle resulting in vasoconstriction and increased glandular secretion. 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 705043704  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPL--AIVVSLGITIHFYSCLFMTCLLLIFTHASI 98
Cdd:cd15299   12 ILALVTIIGNILVIVSFKVNKQLKTVNNYFLLSLACADLIIGVISMNLftTYIIMNRWALGNLACDLWLSIDYVASNASV 91

                         90
                 ....*....|....
gi 705043704  99 MSLLAIAVDRYLRV 112
Cdd:cd15299   92 MNLLVISFDRYFSI 105

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 705043704  11 ANVTYITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTC 88
Cdd:cd15321    5 ATAAIAAAITFLILFTIFGNVLVIIAVLTSRSLRAPQNLFLVSLAAADILVATLIIPFSLANELMGYWYFRKtwCEIYLA 84

                         90       100
                 ....*....|....*....|....
gi 705043704  89 LLLIFTHASIMSLLAIAVDRYLRV 112
Cdd:cd15321   85 LDVLFCTSSIVHLCAISLDRYWSV 108

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 705043704  24 LCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAI---VVSLGITIHFYSCLFMTCLLLIFTHASIMS 100
Cdd:cd15308   12 LAIIAGNVLVCLSVCTERALKTTTNYFIVSLAVADLLLALLVLPLYVyseFQGGVWTLSPVLCDALMTMDVMLCTASIFN 91

                         90
                 ....*....|..
gi 705043704 101 LLAIAVDRYLRV 112
Cdd:cd15308   92 LCAISVDRFIAV 103

serotonin receptor subtype 6, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT6 receptors are a subfamily of serotonin receptors that bind the neurotransmitter serotonin (5HT; 5-hydroxytryptamine) in the mammalian central nervous system (CNS). 5-HT6 receptors are selectively linked to G proteins of the G(s) family, which positively stimulate adenylate cyclase, causing cAMP formation and activation of protein kinase A. The 5-HT6 receptors mediates excitatory neurotransmission and are involved in learning and memory; thus they are promising targets for the treatment of cognitive impairment. 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 705043704  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLLLIFTHASI 98
Cdd:cd15054    9 LIILLTVAGNSLLILLIFTQRSLRNTSNYFLVSLFMSDLMVGLVVMPPAMLNALYGRWVLARdfCPIWYAFDVMCCSASI 88

                         90
                 ....*....|....
gi 705043704  99 MSLLAIAVDRYLRV 112
Cdd:cd15054   89 LNLCVISLDRYLLI 102

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 705043704  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVV------SLGITIhfysCLFMTCLLLIFT 94
Cdd:cd15049    9 SLSLVTVGGNILVILSFRVNRQLRTVNNYFLLSLACADLIIGLVSMNLYTVYlvmgywPLGPLL----CDLWLALDYVAS 84

                         90
                 ....*....|....*....
gi 705043704  95 HASIMSLLAIAVDRYLRVK 113
Cdd:cd15049   85 NASVMNLLLISFDRYFSVT 103

orexin receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; 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. Thus, activation of OX1R or OX2R will activate phospholipase activity and the phosphatidylinositol and calcium signaling pathways. Additionally, OX2R activation can also lead to inhibition of adenylate cyclase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 705043704  16 ITMEIFIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHF--YSCLFMTCLLLIF 93
Cdd:cd15208    4 IALYILVFIVGLVGNVLVCFAVWRNHHMRTVTNYFIVNLSLADFLVIIICLPATLLVDVTETWFFgqVLCKIIPYLQTVS 83

                         90
                 ....*....|....*..
gi 705043704  94 THASIMSLLAIAVDRYL 110
Cdd:cd15208   84 VSVSVLTLSCIALDRWY 100

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 705043704  21 FIGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS--CLFMTCLLLIFTHASI 98
Cdd:cd15323    9 FLIVFTIVGNVLVVIAVLTSRALRAPQNLFLVSLASADILVATLVMPFSLANELMGYWYFGQvwCNIYLALDVLFCTSSI 88

                         90
                 ....*....|....*...
gi 705043704  99 MSLLAIAVDRYLRVKLTV 116
Cdd:cd15323   89 VHLCAISLDRYWSVTQAV 106

D3 subtype of the D2-like family of dopamine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. 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 705043704  24 LCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHFYS---CLFMTCLLLIFTHASIMS 100
Cdd:cd15310   12 LAIVFGNVLVCMAVLRERALQTTTNYLVVSLAVADLLVATLVMPWVVYLEVTGGVWNFSricCDVFVTLDVMMCTASILN 91

                         90
                 ....*....|....*.
gi 705043704 101 LLAIAVDRYLRVKLTV 116
Cdd:cd15310   92 LCAISIDRYTAVVMPV 107

muscarinic acetylcholine receptor subtype M1, 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. M1 is the dominant mAChR subtype involved in learning and memory. It is linked to synaptic plasticity, neuronal excitability, and neuronal differentiation during early development. 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 705043704  22 IGLCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPL--AIVVSLGITIHFYSCLFMTCLLLIFTHASIM 99
Cdd:cd17790   10 LSLVTVTGNLLVLISFKVNSELKTVNNYFLLSLACADLIIGAFSMNLytTYILMGHWALGTVACDLWLALDYVASNASVM 89

                         90
                 ....*....|...
gi 705043704 100 SLLAIAVDRYLRV 112
Cdd:cd17790   90 NLLIISFDRYFSI 102

trace amine-associated receptor 5, member of the class A family of seven-transmembrane G protein-coupled receptors; The trace amine-associated receptor 5 is one of the 15 identified amine-activated G protein-coupled receptors (TAARs), a distinct subfamily within the class A G protein-coupled receptors. 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 705043704  24 LCAIVGNVLVICVVKLNPSLQTTTFYFIVSLALADIAVGVLVMPLAIVVSLGITIHF--YSCLFMTCLLLIFTHASIMSL 101
Cdd:cd15318   12 LIIVLGNLFVVVTVSHFKALHTPTNFLLLSLALADMLLGLTVLPFSTIRSVESCWYFgdSFCRLHTCLDTLFCLTSIFHL 91

                 ....*...
gi 705043704 102 LAIAVDRY 109
Cdd:cd15318   92 CFISIDRH 99