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 29611457   7 CAMYLIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCD 86
Cdd:cd15312   1 VAMYLFMAGAILLTVFGNLMVIISISHFKQLHSPTNFLILSLAITDFLLGFLVMPYSMVRSVESCWYFGDLFCKIHSSLD 80

                        90       100
                ....*....|....*....|....
gi 29611457  87 IMLCTTSIFHLCFISVDRHYAVCD 110
Cdd:cd15312  81 MMLSTTSIFHLCFIAVDRYYAVCD 104

trace amine-associated receptors 2, 3, 4, and similar receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; TAAR2, TAAR3, and TAAR4 are among 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. 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 29611457   7 CAMYLIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCD 86
Cdd:cd15312   1 VAMYLFMAGAILLTVFGNLMVIISISHFKQLHSPTNFLILSLAITDFLLGFLVMPYSMVRSVESCWYFGDLFCKIHSSLD 80

                        90       100
                ....*....|....*....|....
gi 29611457  87 IMLCTTSIFHLCFISVDRHYAVCD 110
Cdd:cd15312  81 MMLSTTSIFHLCFIAVDRYYAVCD 104

CC chemokine receptor-like protein; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611457   18 VMTMLGNMAVIISIAHfKQLHSPTNFLILSMATTDfLLSCVVMPFSMIRSIEScWYFGDLFCKVHSCCDIMLCTTSIFHL 97
Cdd:PHA02638 110 ILGLFGNAAIIMILFC-KKIKTITDIYIFNLAISD-LIFVIDFPFIIYNEFDQ-WIFGDFMCKVISASYYIGFFSNMFLI 186

                         90
                 ....*....|.
gi 29611457   98 CFISVDRHYAV 108
Cdd:PHA02638 187 TLMSIDRYFAI 197

trace amine-associated receptors 2, 3, 4, and similar receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; TAAR2, TAAR3, and TAAR4 are among 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. 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 29611457   7 CAMYLIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCD 86
Cdd:cd15312   1 VAMYLFMAGAILLTVFGNLMVIISISHFKQLHSPTNFLILSLAITDFLLGFLVMPYSMVRSVESCWYFGDLFCKIHSSLD 80

                        90       100
                ....*....|....*....|....
gi 29611457  87 IMLCTTSIFHLCFISVDRHYAVCD 110
Cdd:cd15312  81 MMLSTTSIFHLCFIAVDRYYAVCD 104

trace amine-associated receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The trace amine-associated receptors (TAARs) are a distinct subfamily within the class A G protein-coupled receptor family. Trace amines are endogenous amines of unknown function that have strong structural and metabolic similarity to classical monoamine neurotransmitters (serotonin, noradrenaline, adrenaline, dopamine, and histamine), which play critical roles in human and animal physiological activities such as cognition, consciousness, mood, motivation, perception, and autonomic responses. However, trace amines are found in the mammalian brain at very low concentrations compared to classical monoamines. Trace amines, including p-tyramine, beta-phenylethylamine, and tryptamine, are also thought to act as chemical messengers to exert their biological effects in vertebrates. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 29611457   9 MYLIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIM 88
Cdd:cd15055   3 LYIVLSSISLLTVLGNLLVIISISHFKQLHTPTNLLLLSLAVADFLVGLLVMPFSMIRSIETCWYFGDTFCKLHSSLDYI 82

                        90       100
                ....*....|....*....|..
gi 29611457  89 LCTTSIFHLCFISVDRHYAVCD 110
Cdd:cd15055  83 LTSASIFNLVLIAIDRYVAVCD 104

trace amine-associated receptors 6, 8, and 9, member of the class A family of seven-transmembrane G protein-coupled receptors; Included in this group are mammalian TAAR6, TAAR8, TAAR9, and similar proteins. They are among the 15 identified amine-associated 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 29611457   9 MYLIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIM 88
Cdd:cd15316   3 LYIVLGFGAVLAVFGNLLVMISILHFKQLHSPTNFLIASLACADFLVGVTVMPFSTVRSVESCWYFGESFCTFHTCCDVS 82

                        90       100
                ....*....|....*....|..
gi 29611457  89 LCTTSIFHLCFISVDRHYAVCD 110
Cdd:cd15316  83 FCYASLFHLCFISVDRYIAVTD 104

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 29611457   8 AMYLIMIgaIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDI 87
Cdd:cd14967   3 AVFLSLI--ILVTVFGNLLVILAVYRNRRLRTVTNYFIVSLAVADLLVALLVMPFSAVYTLLGYWPFGPVLCRFWIALDV 80

                        90       100
                ....*....|....*....|...
gi 29611457  88 MLCTTSIFHLCFISVDRHYAVCD 110
Cdd:cd14967  81 LCCTASILNLCAISLDRYLAITR 103

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 29611457   5 VVCAMYLIMIgaIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSC 84
Cdd:cd15064   1 VLISVLLSLI--ILATILGNALVIAAILLTRKLHTPANYLIASLAVADLLVAVLVMPLSAVYELTGRWILGQVLCDIWIS 78

                        90       100
                ....*....|....*....|....*.
gi 29611457  85 CDIMLCTTSIFHLCFISVDRHYAVCD 110
Cdd:cd15064  79 LDVTCCTASILHLCVIALDRYWAITD 104

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 29611457   5 VVCAMYLIMIgaIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSC 84
Cdd:cd15051   1 IVLGVVLAVI--ILLTVIGNVLVCLAVAVNRRLRNLTNYFIVSLAVTDLLLGLLVLPFSAIYELRGEWPLGPVFCNIYIS 78

                        90       100
                ....*....|....*....|....
gi 29611457  85 CDIMLCTTSIFHLCFISVDRHYAV 108
Cdd:cd15051  79 LDVMLCTASILNLFAISLDRYLAI 102

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 29611457   8 AMYLIMIGAIvmtmLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDI 87
Cdd:cd15066   5 AMTLIILAAI----FGNLLVIISVMRHRKLRVITNYFVVSLAMADMLVALCAMTFNASVEITGRWMFGYFMCDVWNSLDV 80

                        90       100
                ....*....|....*....|.
gi 29611457  88 MLCTTSIFHLCFISVDRHYAV 108
Cdd:cd15066  81 YFSTASILHLCCISVDRYYAI 101

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 29611457   8 AMYLIMIgaIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESC-WYFGDLFCKVHSCCD 86
Cdd:cd15053   4 ALFLLLL--PLLTVFGNVLVIMSVFRERSLQTATNYFIVSLAVADLLVAILVMPFAVYVEVNGGkWYLGPILCDIYIAMD 81

                        90       100
                ....*....|....*....|..
gi 29611457  87 IMLCTTSIFHLCFISVDRHYAV 108
Cdd:cd15053  82 VMCSTASIFNLCAISIDRYIAV 103

alpha-1 adrenergic receptors subtype B, 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 29611457  11 LIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIMLC 90
Cdd:cd15326   5 LVLGAFILFAIVGNILVILSVVCNRHLRIPTNYFIVNLAIADLLLSFTVLPFSATLEILGYWVFGRIFCDIWAAVDVLCC 84

                        90
                ....*....|....*...
gi 29611457  91 TTSIFHLCFISVDRHYAV 108
Cdd:cd15326  85 TASILSLCAISIDRYIGV 102

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 29611457  11 LIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIMLC 90
Cdd:cd15060   5 ILLSVIIAFTIVGNILVILSVFTYRPLRIVQNFFIVSLAVADLAVAIFVLPLNVAYFLLGKWLFGIHLCQMWLTCDILCC 84

                        90       100
                ....*....|....*....|
gi 29611457  91 TTSIFHLCFISVDRHYAVCD 110
Cdd:cd15060  85 TASILNLCAIALDRYWAIHD 104

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 29611457   3 ALVVCAMYLImigaIVMTMLGNMAVIISIAHFKQLHSP-TNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDlFCKV 81
Cdd:cd15057   1 IITGCILYLL----VLLTLLGNALVIAAVLRFRHLRSKvTNYFIVSLAVSDLLVAILVMPWAAVNEVAGYWPFGS-FCDV 75

                        90       100
                ....*....|....*....|....*....
gi 29611457  82 HSCCDIMLCTTSIFHLCFISVDRHYAVCD 110
Cdd:cd15057  76 WVSFDIMCSTASILNLCVISVDRYWAISS 104

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 29611457  11 LIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIMLC 90
Cdd:cd15062   5 VALGAFILFAIGGNLLVILSVACNRHLRTPTHYFIVNLAVADLLLSFTVLPFSATLEVLGYWAFGRIFCDVWAAVDVLCC 84

                        90
                ....*....|....*...
gi 29611457  91 TTSIFHLCFISVDRHYAV 108
Cdd:cd15062  85 TASIMSLCVISVDRYIGV 102

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 29611457  18 VMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIMLCTTSIFHL 97
Cdd:cd15335  12 ILTTVLNSAVIAAICTTKKLHQPANYLICSLAVTDFLVAVLVMPLSITYIVMDTWTLGYFICEIWLSVDMTCCTCSILHL 91

                        90
                ....*....|...
gi 29611457  98 CFISVDRHYAVCD 110
Cdd:cd15335  92 CVIALDRYWAITD 104

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 29611457    23 GNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESC-WYFGDLFCKVHSCCDIMLCTTSIFHLCFIS 101
Cdd:pfam00001   1 GNLLVILVILRNKKLRTPTNIFLLNLAVADLLFSLLTLPFWLVYYLNHGdWPFGSALCKIVGALFVVNGYASILLLTAIS 80

                  ....*...
gi 29611457   102 VDRHYAVC 109
Cdd:pfam00001  81 IDRYLAIV 88

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 29611457  11 LIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIMLC 90
Cdd:cd15061   4 SFLILAIIFTIFGNLLVILAVATTRRLRTITNCYIVSLATADLLVGVLVLPLAIIRQLLGYWPLGSHLCDFWISLDVLLC 83

                        90
                ....*....|....*...
gi 29611457  91 TTSIFHLCFISVDRHYAV 108
Cdd:cd15061  84 TASILNLCCISLDRYFAI 101

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 29611457  17 IVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIMLCTTSIFH 96
Cdd:cd15322  11 MLLTVFGNVLVIIAVFTSRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKVWCEIYLALDVLFCTSSIVH 90

                        90
                ....*....|..
gi 29611457  97 LCFISVDRHYAV 108
Cdd:cd15322  91 LCAISLDRYWSI 102

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 29611457   9 MYLIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIM 88
Cdd:cd15058   3 LLLLLALIILAIVVGNLLVIIAIARTSRLQTMTNIFITSLACADLVMGLLVVPLGATIVVTGKWQLGNFWCELWTSVDVL 82

                        90       100
                ....*....|....*....|
gi 29611457  89 LCTTSIFHLCFISVDRHYAV 108
Cdd:cd15058  83 CVTASIETLCVIAVDRYIAI 102

serotonin receptor subtype 1F, 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 29611457  11 LIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIMLC 90
Cdd:cd15334   5 LTLSILALMTTAINSLVITAIIVTRKLHHPANYLICSLAVTDFLVAVLVMPFSIMYIVKETWIMGQVVCDIWLSVDITCC 84

                        90       100
                ....*....|....*....|
gi 29611457  91 TTSIFHLCFISVDRHYAVCD 110
Cdd:cd15334  85 TCSILHLSAIALDRYRAITD 104

D1A (or D1) subtype dopamine receptor, 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. 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 29611457  17 IVMTMLGNMAVIISIAHFKQLHSP-TNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDlFCKVHSCCDIMLCTTSIF 95
Cdd:cd15320  12 ILSTLLGNTLVCAAVIRFRHLRSKvTNFFVISLAVSDLLVAVLVMPWKAVAEIAGFWPFGS-FCNIWVAFDIMCSTASIL 90

                        90
                ....*....|...
gi 29611457  96 HLCFISVDRHYAV 108
Cdd:cd15320  91 NLCVISVDRYWAI 103

serotonin receptor subtype 1A from vertebrates, 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 29611457  11 LIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIMLC 90
Cdd:cd15330   5 LFLGTLILCAIFGNACVVAAIALERSLQNVANYLIGSLAVTDLMVSVLVLPMAALYQVLNKWTLGQVTCDLFIALDVLCC 84

                        90       100
                ....*....|....*....|
gi 29611457  91 TTSIFHLCFISVDRHYAVCD 110
Cdd:cd15330  85 TSSILHLCAIALDRYWAITD 104

D1B (or D5) subtype dopamine receptor, 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. 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 29611457  17 IVMTMLGNMAVIISIAHFKQLHSP-TNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGdLFCKVHSCCDIMLCTTSIF 95
Cdd:cd15319  11 ILWTLLGNILVCAAVVRFRHLRSKvTNIFIVSLAVSDLFVALLVMPWKAVAEVAGYWPFG-AFCDVWVAFDIMCSTASIL 89

                        90
                ....*....|...
gi 29611457  96 HLCFISVDRHYAV 108
Cdd:cd15319  90 NLCVISVDRYWAI 102

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 29611457  11 LIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIMLC 90
Cdd:cd15307   5 LLALVLVLGTAAGNILVCLAIAWERRLQNVTNYFLMSLAITDLMVAVLVMPLGILTLVKGHFPLSSEHCLTWICLDVLFC 84

                        90
                ....*....|....*...
gi 29611457  91 TTSIFHLCFISVDRHYAV 108
Cdd:cd15307  85 TASIMHLCTISVDRYLSL 102

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 29611457   9 MYLIMIGAIVmtmLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSM-IRSIESCWYFGDLFCKVHSCCDI 87
Cdd:cd15310   6 SYCALILAIV---FGNVLVCMAVLRERALQTTTNYLVVSLAVADLLVATLVMPWVVyLEVTGGVWNFSRICCDVFVTLDV 82

                        90       100
                ....*....|....*....|.
gi 29611457  88 MLCTTSIFHLCFISVDRHYAV 108
Cdd:cd15310  83 MMCTASILNLCAISIDRYTAV 103

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 29611457  17 IVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIMLCTTSIFH 96
Cdd:cd15049  11 SLVTVGGNILVILSFRVNRQLRTVNNYFLLSLACADLIIGLVSMNLYTVYLVMGYWPLGPLLCDLWLALDYVASNASVMN 90

                        90
                ....*....|..
gi 29611457  97 LCFISVDRHYAV 108
Cdd:cd15049  91 LLLISFDRYFSV 102

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 29611457  11 LIMIGAIVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESC-WYFGDLFCKVHSCCDIML 89
Cdd:cd15304   5 LLTVIVIILTIAGNILVIMAVSLEKKLQNATNYFLMSLAIADMLLGFLVMPVSMLTILYGYrWPLPSKLCAVWIYLDVLF 84

                        90
                ....*....|....*....
gi 29611457  90 CTTSIFHLCFISVDRHYAV 108
Cdd:cd15304  85 STASIMHLCAISLDRYIAI 103

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 29611457   9 MYLIMIgaiVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIM 88
Cdd:cd15203   6 LYGLII---VLGVVGNLLVIYVVLRNKSMQTVTNIFILNLAVSDLLLCLVSLPFTLIYTLTKNWPFGSILCKLVPSLQGV 82

                        90
                ....*....|....*...
gi 29611457  89 LCTTSIFHLCFISVDRHY 106
Cdd:cd15203  83 SIFVSTLTLTAIAIDRYQ 100

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 29611457  17 IVMTMLGNMAVIISIAHFKQLHSPTNFLILSMATTDFLLSCVVMPFSMIRSIESCWYFGDLFCKVHSCCDIMLCTTSIFH 96
Cdd:cd14992  11 ILVSVVGNFIVIAALARHKNLRGATNYFIASLAISDLLMALFCTPFNFTYVVSLSWEYGHFLCKIVNYLRTVSVYASSLT 90

                        90
                ....*....|..
gi 29611457  97 LCFISVDRHYAV 108
Cdd:cd14992  91 LTAIAFDRYFAI 102