7 transmembrane receptor (rhodopsin family); This family contains, amongst other G-protein-coupled receptors (GCPRs), members of the opsin family, which have been considered to be typical members of the rhodopsin superfamily. They share several motifs, mainly the seven transmembrane helices, GCPRs of the rhodopsin superfamily. All opsins bind a chromophore, such as 11-cis-retinal. The function of most opsins other than the photoisomerases is split into two steps: light absorption and G-protein activation. Photoisomerases, on the other hand, are not coupled to G-proteins - they are thought to generate and supply the chromophore that is used by visual opsins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELL-GYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALE 79
Cdd:pfam00001  13 KKLRTPTNIFLLNLAVADLLFSLLTLPFWLVYYLNhGDWPFGSALCKIVGALFVVNGYASILLLTAISIDRYLAIVHPLR 92

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  80 YNSKRTPRRIKCIILTVWLIAAVISLPPLIYKGDQGPQPHGRPQC------KLNQEAWYILASSIGSFFAPCLIMILVYL 153
Cdd:pfam00001  93 YKRRRTPRRAKVLILVIWVLALLLSLPPLLFGWTLTVPEGNVTVCfidfpeDLSKPVSYTLLISVLGFLLPLLVILVCYT 172

                         170       180
                  ....*....|....*....|..
gi 2124345513 154 RIYLIAKRSHRRGPRDKGGPRE 175
Cdd:pfam00001 173 LIIRTLRKSASKQKSSERTQRR 194

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 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd15059    29 RKLRAPQNWFLVSLAVADILVGLLIMPFSLVNELMGYWYFGSVWCEIWLALDVLFCTASIVNLCAISLDRYWSVTQAVEY 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPPLIYKGDQGPQPHGRPQCKLNQEAWYILASSIGSFFAPCLIMILVYLRIYLIAK 160
Cdd:cd15059   109 NLKRTPRRAKAMIAAVWIISAVISLPPLFGWKDEQPWHGAEPQCELSDDPGYVLFSSIGSFYIPLLIMIIVYARIYRAAK 188

                  ....*
gi 2124345513 161 RSHRR 165
Cdd:cd15059   189 RKERR 193

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd15322    29 RALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKVWCEIYLALDVLFCTSSIVHLCAISLDRYWSITQAIEY 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPPLIYKGDQGPQPHGrPQCKLNQEAWYILASSIGSFFAPCLIMILVYLRIYLIAK 160
Cdd:cd15322   109 NLKRTPRRIKCIIFIVWVISAVISFPPLITIEKKSGQPEG-PICKINDEKWYIISSCIGSFFAPCLIMVLVYIRIYQIAK 187

                  ....*
gi 2124345513 161 RSHRR 165
Cdd:cd15322   188 NREKR 192

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd14967    28 RRLRTVTNYFIVSLAVADLLVALLVMPFSAVYTLLGYWPFGPVLCRFWIALDVLCCTASILNLCAISLDRYLAITRPLRY 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPPLIYKGDQGPQPHGRPQCKLNQEAWYILASSIGSFFAPCLIMILVYLRIYLIAK 160
Cdd:cd14967   108 RQLMTKKRALIMIAAVWVYSLLISLPPLVGWRDETQPSVVDCECEFTPNKIYVLVSSVISFFIPLLIMIVLYARIFRVAR 187

                  ....
gi 2124345513 161 RSHR 164
Cdd:cd14967   188 RELK 191

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 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd15064    29 RKLHTPANYLIASLAVADLLVAVLVMPLSAVYELTGRWILGQVLCDIWISLDVTCCTASILHLCVIALDRYWAITDAVEY 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPPLIykGDQGPQPHGRPQCKLNQEAWYILASSIGSFFAPCLIMILVYLRIYLIAK 160
Cdd:cd15064   109 AHKRTPKRAAVMIALVWTLSICISLPPLF--GWRTPDSEDPSECLISQDIGYTIFSTFGAFYIPLLLMLILYWKIYRAAA 186

                  ....
gi 2124345513 161 RSHR 164
Cdd:cd15064   187 RERK 190

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd15060    29 RPLRIVQNFFIVSLAVADLAVAIFVLPLNVAYFLLGKWLFGIHLCQMWLTCDILCCTASILNLCAIALDRYWAIHDPINY 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPPLIYKGDQGPQPHGRPQCKLNQEAWYILASSIGSFFAPCLIMILVYLRIYlIAK 160
Cdd:cd15060   109 AQKRTLKRVLLMIVVVWALSALISVPPLIGWNDWPENFTETTPCTLTEEKGYVIYSSSGSFFIPLLIMTIVYVKIF-IAT 187

                         170
                  ....*....|.
gi 2124345513 161 RSHRRGPRDKG 171
Cdd:cd15060   188 SKERRAARTLG 198

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 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd15061    28 RRLRTITNCYIVSLATADLLVGVLVLPLAIIRQLLGYWPLGSHLCDFWISLDVLLCTASILNLCCISLDRYFAITYPLKY 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPPLIykgdqGPQPHGRP---QCKLNQEAWYILASSIGSFFAPCLIMILVYLRIYL 157
Cdd:cd15061   108 RTKRSRRLAITMILAVWVISLLITSPPLV-----GPSWHGRRglgSCYYTYDKGYRIYSSMGSFFLPLLLMLFVYLRIFR 182

                  ....*..
gi 2124345513 158 IAKRSHR 164
Cdd:cd15061   183 VIAKERK 189

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 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd00637    27 RRLRTVTNYFILNLAVADLLVGLLVIPFSLVSLLLGRWWFGDALCKLLGFLQSVSLLASILTLTAISVDRYLAIVHPLRY 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPPLIYKGDQGPQPHGRPQCKLNQEAW---YILASSIGSFFAPCLIMILVYLRIYL 157
Cdd:cd00637   107 RRRFTRRRAKLLIALIWLLSLLLALPPLLGWGVYDYGGYCCCCLCWPDLTLskaYTIFLFVLLFLLPLLVIIVCYVRIFR 186

                         170       180
                  ....*....|....*....|....*
gi 2124345513 158 IAKRSHRRGPRDKGGPREGESKQSH 182
Cdd:cd00637   187 KLRRHRRRIRSSSSNSSRRRRRRRE 211

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELL-GYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALE 79
Cdd:cd15053    29 RSLQTATNYFIVSLAVADLLVAILVMPFAVYVEVNgGKWYLGPILCDIYIAMDVMCSTASIFNLCAISIDRYIAVTQPIK 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  80 YNSKRTPRRIKCIILTVWLIAAVISLPPLIykGDQGPQPHGRPQCKLnQEAWYILASSIGSFFAPCLIMILVYLRIYLIA 159
Cdd:cd15053   109 YARQKNSKRVLLTIAIVWVVSAAIACPLLF--GLNNVPYRDPEECRF-YNPDFIIYSSISSFYIPCIVMLLLYYRIFRAL 185

                  ....*
gi 2124345513 160 KRSHR 164
Cdd:cd15053   186 RREKK 190

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd15066    28 RKLRVITNYFVVSLAMADMLVALCAMTFNASVEITGRWMFGYFMCDVWNSLDVYFSTASILHLCCISVDRYYAIVQPLEY 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPP-----------LIYKGDqgpQPHgrpQCKLNQEAWYILASSIGSFFAPCLIMI 149
Cdd:cd15066   108 PSKMTKRRVAIMLANVWISPALISFLPiflgwytteehLQYRKT---HPD---QCEFVVNKIYALISSSVSFWIPCIVMI 181

                         170
                  ....*....|....*
gi 2124345513 150 LVYLRIYLIAKRSHR 164
Cdd:cd15066   182 FTYYRIYLEAKREHK 196

D1-like family of dopamine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Dopamine receptors are members of the class A G protein-coupled receptors that are involved in many neurological processes in the central nervous system (CNS). The neurotransmitter dopamine is the primary endogenous agonist for dopamine receptors. Dopamine receptors consist of at least five subtypes: D1, D2, D3, D4, and D5. The D1 and D5 subtypes are members of the D1-like family of dopamine receptors, whereas the D2, D3 and D4 subtypes are members of the D2-like family. The D1-like family receptors are coupled to G proteins of the G(s) family, which activate adenylate cyclase, causing cAMP formation and activation of protein kinase A. In contrast, activation of D2-like family receptors is linked to G proteins of the G(i) family, which inhibit adenylate cyclase. Dopamine receptors are major therapeutic targets for neurological and psychiatric disorders such as drug abuse, depression, schizophrenia, or Parkinson's disease. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513   1 RSLRAP-QNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRtWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALE 79
Cdd:cd15057    29 RHLRSKvTNYFIVSLAVSDLLVAILVMPWAAVNEVAGYWPFGS-FCDVWVSFDIMCSTASILNLCVISVDRYWAISSPFR 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  80 YNSKRTPRRIKCIILTVWLIAAVISLPPL------IYKGDQGPQP-HGRPQCKLNQEAWYILASSIGSFFAPCLIMILVY 152
Cdd:cd15057   108 YERRMTRRRAFIMIAVAWTLSALISFIPVqlgwhrADDTSEALALyADPCQCDSSLNRTYAISSSLISFYIPVAIMIVTY 187

                         170
                  ....*....|...
gi 2124345513 153 LRIYLIAKRSHRR 165
Cdd:cd15057   188 TRIYRIARRQIRR 200

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd15062    29 RHLRTPTHYFIVNLAVADLLLSFTVLPFSATLEVLGYWAFGRIFCDVWAAVDVLCCTASIMSLCVISVDRYIGVRYPLNY 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPPLIykGDQGPQPHGRPQCKLNQEAWYILASSIGSFFAPCLIMILVYLRIYLIAK 160
Cdd:cd15062   109 PTIVTARRATVALLIVWVLSLVISIGPLL--GWKEPAPADEQACGVNEEPGYVLFSSLGSFYLPLAIILVMYCRVYVVAF 186

                  ....
gi 2124345513 161 RSHR 164
Cdd:cd15062   187 KFSR 190

serotonin receptor subtypes 1B and 1D, 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 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd15333    33 RKLHTPANYLIASLAVTDLLVSILVMPISIVYTVTGTWTLGQVVCDIWLSSDITCCTASILHLCVIALDRYWAITDAVEY 112

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPPLIYKgdQGPQPHGRPQCKLNQE-AWYILASSIGSFFAPCLIMILVYLRIYLIA 159
Cdd:cd15333   113 SKKRTPKRAAVMIALVWVISISISLPPFFWR--QAKAEEEVSECVVNTDhILYTVYSTVGAFYIPTLLLIALYGRIYVEA 190

                         170
                  ....*....|..
gi 2124345513 160 KRSHRRGPRDKG 171
Cdd:cd15333   191 RARERKATKTLG 202

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd15325    29 RHLQTVTHYFIVNLAVADLLLTSTVLPFSAIFEILGYWAFGRVFCNIWAAVDVLCCTASIMSLCIISIDRYIGVSYPLRY 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPPLIykGDQGPQPHGRPQCKLNQEAWYILASSIGSFFAPCLIMILVYLRIYLIAK 160
Cdd:cd15325   109 PSIMTERRGLLALLCVWVLSLVISIGPLF--GWKEPAPEDETICQITEEPGYALFSALGSFYLPLAIILVMYCRVYVVAL 186

                  ....
gi 2124345513 161 RSHR 164
Cdd:cd15325   187 KFSR 190

serotonin receptor subtype 1E, 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 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd15335    29 KKLHQPANYLICSLAVTDFLVAVLVMPLSITYIVMDTWTLGYFICEIWLSVDMTCCTCSILHLCVIALDRYWAITDAIEY 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAVISLPPLIYKgdQGPQPHGRPQCKLNQE-AWYILASSIGSFFAPCLIMILVYLRIYLIA 159
Cdd:cd15335   109 ARKRTAKRAGLMILTVWTISIFISIPPLFWR--NHHDANIPSQCIIQHDhVIYTIYSTFGAFYIPLTLILILYYRIYHAA 186

                  ....*
gi 2124345513 160 KRSHR 164
Cdd:cd15335   187 SRERK 191

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 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLG-YWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALE 79
Cdd:cd15052    29 KRLQNVTNYFLMSLAIADLLVGLLVMPLSILTELFGgVWPLPLVLCLLWVTLDVLFCTASIMHLCTISLDRYMAIRYPLR 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  80 YNSKRTPRRIKCIILTVWLIAAVISLP-PLIYKGDQGPQPHgRPQCKLNQEAwYILASSIGSFFAPCLIMILVY-LRIYL 157
Cdd:cd15052   109 TRRNKSRTTVFLKIAIVWLISIGISSPiPVLGIIDTTNVLN-NGTCVLFNPN-FVIYGSIVAFFIPLLIMVVTYaLTIRL 186

                  ....
gi 2124345513 158 IAKR 161
Cdd:cd15052   187 LSNE 190

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 2124345513   1 RSLRAPQNLFLVSLAAADILVATLIIPFSLANELLGYWYFRRTWCEVYLALDVLFCTSSIVHLCAISLDRYWAVSRALEY 80
Cdd:cd15314    29 KQLHTPTNYLILSLAVADLLVGGLVMPPSMVRSVETCWYFGDLFCKIHSSFDITLCTASILNLCFISIDRYYAVCQPLLY 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124345513  81 NSKRTPRRIKCIILTVWLIAAV----ISLPPLIYKGDQGPQPHGRPQCKLNQEAWYILASSIGSFFAPCLIMILVYLRIY 156
Cdd:cd15314   109 RSKITVRVVLVMILISWSVSALvgfgIIFLELNIKGIYYNHVACEGGCLVFFSKVSSVVGSVFSFYIPAVIMLCIYLKIF 188

                  ....*...
gi 2124345513 157 LIAKRSHR 164
Cdd:cd15314   189 LVAQRQAR 196