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 767991624   8 ALYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFYGCLFLACFVLV 87
Cdd:cd15069    1 ATYVALELIIAALSVAGNVLVCAAVGTNSTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFHSCLFLACFVLV 80

                         90       100
                 ....*....|....*....|....*
gi 767991624  88 LTQSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15069   81 LTQSSIFSLLAVAVDRYLAIKVPLR 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 767991624   8 ALYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFYGCLFLACFVLV 87
Cdd:cd15069    1 ATYVALELIIAALSVAGNVLVCAAVGTNSTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFHSCLFLACFVLV 80

                         90       100
                 ....*....|....*....|....*
gi 767991624  88 LTQSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15069   81 LTQSSIFSLLAVAVDRYLAIKVPLR 105

G protein-coupled chemokine receptor-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991624  20 LSVAGNVLVCAaVGTANTLQTPTNYFLVSLAAADVaVGLFAIPFAITISLGFCTDF--YGCLFLACFVLVLTQSSIFSLL 97
Cdd:PHA03087  53 FGLVGNIIVIY-VLTKTKIKTPMDIYLLNLAVSDL-LFVMTLPFQIYYYILFQWSFgeFACKIVSGLYYIGFYNSMNFIT 130

                         90
                 ....*....|....*.
gi 767991624  98 AVAVDRYLAICVPLRS 113
Cdd:PHA03087 131 VMSVDRYIAIVHPVKS 146

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 767991624   8 ALYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFYGCLFLACFVLV 87
Cdd:cd15069    1 ATYVALELIIAALSVAGNVLVCAAVGTNSTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFHSCLFLACFVLV 80

                         90       100
                 ....*....|....*....|....*
gi 767991624  88 LTQSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15069   81 LTQSSIFSLLAVAVDRYLAIKVPLR 105

adenosine receptor subtype A2A, member of the class A family of seven-transmembrane G protein-coupled receptors; The A2A 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 767991624   9 LYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFYGCLFLACFVLVL 88
Cdd:cd15068    2 VYITVELAIAVLAILGNVLVCWAVWLNSNLQNVTNYFVVSLAAADIAVGVLAIPFAITISTGFCAACHGCLFIACFVLVL 81

                         90       100
                 ....*....|....*....|....
gi 767991624  89 TQSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15068   82 TQSSIFSLLAIAIDRYIAIRIPLR 105

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 767991624   8 ALYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFYGCLFLACFVLV 87
Cdd:cd15070    1 VTYISIEILIGLCAVVGNVLVIWVVKLNPSLRTTTFYFIVSLALADIAVGVLVIPLAIVVSLGVTIHFYSCLFMSCLLVV 80

                         90       100
                 ....*....|....*....|....*
gi 767991624  88 LTQSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15070   81 FTHASIMSLLAIAVDRYLRVKLTVR 105

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 767991624   9 LYVALELVIAaLSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTdFYG---CLFLACFV 85
Cdd:cd15055    3 LYIVLSSISL-LTVLGNLLVIISISHFKQLHTPTNLLLLSLAVADFLVGLLVMPFSMIRSIETCW-YFGdtfCKLHSSLD 80

                         90       100
                 ....*....|....*....|....*..
gi 767991624  86 LVLTQSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15055   81 YILTSASIFNLVLIAIDRYVAVCDPLL 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 767991624  10 YVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDF--YGCLFLACFVLV 87
Cdd:cd00637    1 LAVLYILIFVVGLVGNLLVILVILRNRRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRWWFgdALCKLLGFLQSV 80

                         90       100
                 ....*....|....*....|....*
gi 767991624  88 LTQSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd00637   81 SLLASILTLTAISVDRYLAIVHPLR 105

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 767991624   9 LYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAItISLGFCTDFYG---CLFLACFV 85
Cdd:cd14993    2 VLIVLYVVVFLLALVGNSLVIAVVLRNKHMRTVTNYFLVNLAVADLLVSLFCMPLTL-LENVYRPWVFGevlCKAVPYLQ 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 767991624  86 LVLTQSSIFSLLAVAVDRYLAICVPLRSFPW 116
Cdd:cd14993   81 GVSVSASVLTLVAISIDRYLAICYPLKARRV 111

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 767991624   8 ALYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLG--FCTDFYGC-LFLACF 84
Cdd:cd15058    1 PGLLLLLALIILAIVVGNLLVIIAIARTSRLQTMTNIFITSLACADLVMGLLVVPLGATIVVTgkWQLGNFWCeLWTSVD 80

                         90       100
                 ....*....|....*....|....*...
gi 767991624  85 VLVLTqSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15058   81 VLCVT-ASIETLCVIAVDRYIAITRPLR 107

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991624  16 VIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDF--YGCLFlACFVLVLTQS-S 92
Cdd:cd15393    9 IISLVAVVGNFLVIWVVAKNRRMRTVTNIFIANLAVADIIIGLFSIPFQFQAALLQRWVLprFMCPF-CPFVQVLSVNvS 87

                         90       100
                 ....*....|....*....|...
gi 767991624  93 IFSLLAVAVDRYLAICVPLRSFP 115
Cdd:cd15393   88 VFTLTVIAVDRYRAVIHPLKARC 110

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 767991624  13 LELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLG---FCTDFYGCLFLACFVLVLT 89
Cdd:cd15052    6 LLLLLVIATIGGNILVCLAISLEKRLQNVTNYFLMSLAIADLLVGLLVMPLSILTELFggvWPLPLVLCLLWVTLDVLFC 85

                         90       100
                 ....*....|....*....|...
gi 767991624  90 QSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15052   86 TASIMHLCTISLDRYMAIRYPLR 108

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991624   8 ALYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFYGCLflaCFVLV 87
Cdd:cd15207    1 VLFIVSYSLIFLLCVVGNVLVCLVVAKNPRMRTVTNYFILNLAVSDLLVGVFCMPFTLVDNILTGWPFGDVM---CKLSP 77

                         90       100       110
                 ....*....|....*....|....*....|.
gi 767991624  88 LTQ-----SSIFSLLAVAVDRYLAICVPLRS 113
Cdd:cd15207   78 LVQgvsvaASVFTLVAIAVDRYRAVVHPTEP 108

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991624  16 VIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFYG---CLFLACFVLVLTQSS 92
Cdd:cd15067    8 LFCLVTVAGNLLVILAVLRERYLRTVTNYFIVSLAVADLLVGSIVMPFSILHEMTGGYWLFGrdwCDVWHSFDVLASTAS 87

                         90
                 ....*....|....*....
gi 767991624  93 IFSLLAVAVDRYLAICVPL 111
Cdd:cd15067   88 ILNLCVISLDRYWAITDPI 106

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 767991624   8 ALYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFYGCL---FLACF 84
Cdd:cd15059    1 VAISSIVSVVILLIIVGNVLVIVAVLTSRKLRAPQNWFLVSLAVADILVGLLIMPFSLVNELMGYWYFGSVWceiWLALD 80

                         90       100
                 ....*....|....*....|...
gi 767991624  85 VLVLTqSSIFSLLAVAVDRYLAI 107
Cdd:cd15059   81 VLFCT-ASIVNLCAISLDRYWSV 102

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 767991624  16 VIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITislgfcTDFYG--------CLFLACFVLV 87
Cdd:cd15065    8 LIIVLAIFGNVLVCLAIFTDRRLRKKSNLFIVSLAVADLLVALLVMTFAVV------NDLLGywlfgetfCNIWISFDVM 81

                         90       100
                 ....*....|....*....|....*....
gi 767991624  88 LTQSSIFSLLAVAVDRYLAICVPLRSFPW 116
Cdd:cd15065   82 CSTASILNLCAISLDRYIHIKKPLKYERW 110

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 767991624   8 ALYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFYG---CLFLACF 84
Cdd:cd15392    1 VIIILMYSTIFVLAVGGNGLVCYIVVSYPRMRTVTNYFIVNLALSDILMAVFCVPFSFIALLILQYWPFGefmCPVVNYL 80

                         90       100
                 ....*....|....*....|....*...
gi 767991624  85 VLVLTQSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15392   81 QAVSVFVSAFTLVAISIDRYVAIMWPLR 108

type 2 opsins in animals, member of the class A family of seven-transmembrane G protein-coupled receptors; This rhodopsin family represents the type 2 opsins found in vertebrates and invertebrates except sponge. Type 2 opsins primarily function as G protein coupled receptors and are responsible for vision as well as for circadian rhythm and pigment regulation. On the contrary, type 1 opsins such as bacteriorhodopsin and proteorhodopsin are found in both prokaryotic and eukaryotic microbes, functioning as light-gated ion channels, proton pumps, sensory receptors and in other unknown functions. Although these two opsin types share seven-transmembrane domain topology and a conserved lysine reside in the seventh helix, type 1 opsins do not activate G-proteins and are not evolutionarily related to type 2. Type 2 opsins can be classified into six distinct subfamilies including the vertebrate opsins/encephalopsins, the G(o) opsins, the G(s) opsins, the invertebrate G(q) opsins, the photoisomerases, and the neuropsins.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991624  15 LVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAIT--ISLGFCTDFYGCLFLACFVLVLTQSS 92
Cdd:cd14969    8 SLIGVLGVVLNGLVIIVFLKKKKLRTPLNLFLLNLALADLLMSVVGYPLSFYsnLSGRWSFGDPGCVIYGFAVTFLGLVS 87

                         90       100
                 ....*....|....*....|...
gi 767991624  93 IFSLLAVAVDRYLAICVPLRSFP 115
Cdd:cd14969   88 ISTLAALAFERYLVIVRPLKAFR 110

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 767991624  16 VIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLG--------FCTdfygcLFLACFVLV 87
Cdd:cd15064    9 LIILATILGNALVIAAILLTRKLHTPANYLIASLAVADLLVAVLVMPLSAVYELTgrwilgqvLCD-----IWISLDVTC 83

                         90       100
                 ....*....|....*....|....
gi 767991624  88 LTqSSIFSLLAVAVDRYLAICVPL 111
Cdd:cd15064   84 CT-ASILHLCVIALDRYWAITDAV 106

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 767991624   8 ALYVALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISL---GFCTDFYGCLFLACF 84
Cdd:cd15308    1 AAALVGGVLLILAIIAGNVLVCLSVCTERALKTTTNYFIVSLAVADLLLALLVLPLYVYSEFqggVWTLSPVLCDALMTM 80

                         90       100
                 ....*....|....*....|....*...
gi 767991624  85 VLVLTQSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15308   81 DVMLCTASIFNLCAISVDRFIAVSVPLN 108

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991624  16 VIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAIT--ISLGFCTDFYGCLFLACFVLVLTQSSI 93
Cdd:cd14992    9 VIILVSVVGNFIVIAALARHKNLRGATNYFIASLAISDLLMALFCTPFNFTyvVSLSWEYGHFLCKIVNYLRTVSVYASS 88

                         90       100
                 ....*....|....*....|
gi 767991624  94 FSLLAVAVDRYLAICVPLRS 113
Cdd:cd14992   89 LTLTAIAFDRYFAIIHPLKP 108

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 767991624   8 ALYVALELVIAALsVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLG--FCTDFYGCLFLACFV 85
Cdd:cd15959    2 LAGALLSLAILVI-VGGNLLVIVAIAKTPRLQTMTNVFVTSLACADLVMGLLVVPPGATILLTghWPLGTTVCELWTSVD 80

                         90       100
                 ....*....|....*....|....*..
gi 767991624  86 LVLTQSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15959   81 VLCVTASIETLCAIAVDRYLAITNPLR 107

beta-2 adrenergic receptors (adrenoceptors), member of the class A family of seven-transmembrane G protein-coupled receptors; Beta-2 AR is activated by adrenaline that plays important roles in cardiac function and pulmonary physiology. While beta-1 AR and beta-2 AR 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, beta-2 AR can couple to both G(s) and G(i) proteins in the heart. Moreover, beta-2 AR activation leads to smooth muscle relaxation and bronchodilation in the lung. The beta adrenergic receptors are a subfamily of the class A rhodopsin-like G protein-coupled receptors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991624  16 VIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDF--YGCLFLACFVLVLTQSSI 93
Cdd:cd15957    9 LIVLAIVFGNVLVITAIAKFERLQTVTNYFITSLACADLVMGLAVVPFGAAHILLKTWTFgnFWCEFWTSIDVLCVTASI 88

                         90
                 ....*....|....*....
gi 767991624  94 FSLLAVAVDRYLAICVPLR 112
Cdd:cd15957   89 ETLCVIAVDRYFAITSPFK 107

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 767991624  16 VIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAIT---ISLGFCTDFYGCLFLACFVLVLTqSS 92
Cdd:cd15063    9 FLNVLVVLGNLLVIAAVLCSRKLRTVTNLFIVSLACADLLVGTLVLPFSAVnevLDVWIFGHTWCQIWLAVDVWMCT-AS 87

                         90       100
                 ....*....|....*....|
gi 767991624  93 IFSLLAVAVDRYLAICVPLR 112
Cdd:cd15063   88 ILNLCAISLDRYLAITRPIR 107

ecdysis-triggering hormone receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup represents the ecdysis-triggering hormone receptors found in insects, which are members of the class A family of seven-transmembrane G-protein coupled receptors. Ecdysis-triggering hormones are vital regulatory signals that govern the stereotypic physiological sequence leading to cuticle shedding in insects. Thus, the ETH signaling system has been a target for the design of more sophisticated insect-selective pest control strategies. Two subtypes of ecdysis-triggering hormone receptor were identified in Drosophila melanogaster. Blood-borne ecdysis-triggering hormone (ETH) activates the behavioral sequence through direct actions on the central nervous system. In insects, ecdysis is thought to be controlled by the interaction between peptide hormones; in particular between ecdysis-triggering hormone (ETH) from the periphery and eclosion hormone (EH) and crustacean cardioactive peptide (CCAP) from the central nervous system. 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 767991624  16 VIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDFYG---CLFLACFVLVLTQSS 92
Cdd:cd14997    9 VIFVVGVLGNVLVGIVVWKNKDMRTPTNIFLVNLSVADLLVLLVCMPVALVETWAREPWLLGefmCKLVPFVELTVAHAS 88

                         90       100
                 ....*....|....*....|.
gi 767991624  93 IFSLLAVAVDRYLAICVPLRS 113
Cdd:cd14997   89 VLTILAISFERYYAICHPLQA 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 767991624  13 LELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAI-TISLG-FCTDFYGCLFLACFVLVLTQ 90
Cdd:cd15307    6 LALVLVLGTAAGNILVCLAIAWERRLQNVTNYFLMSLAITDLMVAVLVMPLGIlTLVKGhFPLSSEHCLTWICLDVLFCT 85

                         90       100
                 ....*....|....*....|..
gi 767991624  91 SSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd15307   86 ASIMHLCTISVDRYLSLRYPMR 107

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 767991624  20 LSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLGFCTDF--YGCLFLACFVLVLTQSSIFSLL 97
Cdd:cd15318   13 IIVLGNLFVVVTVSHFKALHTPTNFLLLSLALADMLLGLTVLPFSTIRSVESCWYFgdSFCRLHTCLDTLFCLTSIFHLC 92

                         90
                 ....*....|....*
gi 767991624  98 AVAVDRYLAICVPLR 112
Cdd:cd15318   93 FISIDRHCAICDPLL 107

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991624   8 ALYVALELViaalSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAIPFAITISLG---FCTDFYGCLFLACF 84
Cdd:cd14979    5 AIYVAIFVV----GIVGNLLTCIVIARHKSLRTTTNYYLFSLAVSDLLILLVGLPVELYNFWWqypWAFGDGGCKLYYFL 80

                         90       100
                 ....*....|....*....|....*...
gi 767991624  85 VLVLTQSSIFSLLAVAVDRYLAICVPLR 112
Cdd:cd14979   81 FEACTYATVLTIVALSVERYVAICHPLK 108

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991624  11 VALELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAI--PFAITISLGFCTDFYGCLFLACFVLVL 88
Cdd:cd15196    4 IAVLATILVLALFGNSCVLLVLYRRRRKLSRMHLFILHLSVADLLVALFNVlpQLIWDITYRFYGGDLLCRLVKYLQVVG 83

                         90       100
                 ....*....|....*....|....*...
gi 767991624  89 TQSSIFSLLAVAVDRYLAICVPLRSFPW 116
Cdd:cd15196   84 MYASSYVLVATAIDRYIAICHPLSSHRW 111

thyrotropin-releasing hormone receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; TRH-R is a member of the class A rhodopsin-like G protein-coupled receptors, which binds the tripeptide thyrotropin releasing hormone. The TRH-R activates phosphoinositide metabolism through a pertussis-toxin-insensitive G-protein, the G(q)/G(11) class. TRH stimulates the synthesis and release of thyroid-stimulating hormone in the anterior pituitary. TRH is produced in many other tissues, especially within the nervous system, where it appears to act as a neurotransmitter/neuromodulator. It also stimulates the synthesis and release of prolactin. In the CNS, TRH stimulates a number of behavioral and pharmacological actions, including increased turnover of catecholamines in the nucleus accumbens. There are two thyrotropin-releasing hormone receptors in some mammals, thyrotropin-releasing hormone receptor 1 (TRH1) which has been found in a number of species including rat, mouse, and human and thyrotropin-releasing hormone receptor 2 (TRH2) which has, only been found in rodents. These TRH receptors are found in high levels in the anterior pituitary, and are also found in the retina and in certain areas of the brain.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767991624  13 LELVIAALSVAGNVLVCAAVGTANTLQTPTNYFLVSLAAADVAVGLFAI-PFAITISLGFCTDFY---GCLFLACFVLVL 88
Cdd:cd14995    6 LVLLICGVGIVGNIMVVLVVLRTRHMRTPTNCYLVSLAVADLMVLVAAGlPNEIESLLGPDSWIYgyaGCLLITYLQYLG 85

                         90       100
                 ....*....|....*....|....*
gi 767991624  89 TQSSIFSLLAVAVDRYLAICVPLRS 113
Cdd:cd14995   86 INASSLSITAFTIERYIAICHPMKA 110