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 291480032   5 PGHHRNATFLSCQFRSVIRMDYMVYVSFFAGILIPLVVMCGIYLDIFYIIRNKLSQNFSSSKETSAFYGREFKTAKSLSL 84
Cdd:cd15070  142 SLESVNTTPLQCQFTSVMRMDYMVYFSFFTWILIPLVIMCALYVDIFYIIRNKLSQNATGFRETGAFYGREFKTAKSLAL 221

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 291480032  85 VLFLFAVSWLPLSIMNCVIYFSGEVPRVVLYLGILLSHA 123
Cdd:cd15070  222 VLFLFAVCWLPLSIINCVVYFNPKVPKIALYLGILLSHA 260

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 291480032   5 PGHHRNATFLSCQFRSVIRMDYMVYVSFFAGILIPLVVMCGIYLDIFYIIRNKLSQNFSSSKETSAFYGREFKTAKSLSL 84
Cdd:cd15070  142 SLESVNTTPLQCQFTSVMRMDYMVYFSFFTWILIPLVIMCALYVDIFYIIRNKLSQNATGFRETGAFYGREFKTAKSLAL 221

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 291480032  85 VLFLFAVSWLPLSIMNCVIYFSGEVPRVVLYLGILLSHA 123
Cdd:cd15070  222 VLFLFAVCWLPLSIINCVVYFNPKVPKIALYLGILLSHA 260

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 291480032   5 PGHHRNATFLSCQFRSVIRMDYMVYVSFFAGILIPLVVMCGIYLDIFYIIRNKLSQNFSSSKETSAFYGREFKTAKSLSL 84
Cdd:cd15070  142 SLESVNTTPLQCQFTSVMRMDYMVYFSFFTWILIPLVIMCALYVDIFYIIRNKLSQNATGFRETGAFYGREFKTAKSLAL 221

                         90       100       110
                 ....*....|....*....|....*....|....*....
gi 291480032  85 VLFLFAVSWLPLSIMNCVIYFSGEVPRVVLYLGILLSHA 123
Cdd:cd15070  222 VLFLFAVCWLPLSIINCVVYFNPKVPKIALYLGILLSHA 260

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291480032  14 LSCQFRSVIRMDYMVYVSFFAGILIPLVVMCGIYLDIFYIIRNKLSQNFSS-SKETSAFYGREFKTAKSLSLVLFLFAVS 92
Cdd:cd15071  158 IKCQFETVISMEYMVYFNFFVWVLPPLLLMLLIYLEVFYLIRKQLNKKVSSsSSDPQKYYGKELKIAKSLALILFLFALS 237

                         90       100       110
                 ....*....|....*....|....*....|..
gi 291480032  93 WLPLSIMNCVIYF--SGEVPRVVLYLGILLSH 122
Cdd:cd15071  238 WLPLHILNCITLFcpSCKKPMILTYIAIFLTH 269

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 291480032   4 TPGHHrnATFLSCQFRSVIRMDYMVYVSFFAGILIPLVVMCGIYLDIFYIIRNKLSQN--FSSSKETsafYGREFKTAKS 81
Cdd:cd15069  154 GTNHS--CCLISCLFENVVPMSYMVYFNFFGCVLPPLLIMLVIYIKIFLVACRQLQRTelMDHSRTT---LQREIHAAKS 228

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 291480032  82 LSLVLFLFAVSWLPLSIMNCVIYFSGEV----PRVVLYLGILLSHA 123
Cdd:cd15069  229 LAIIVGIFALCWLPVHILNCITLFQPEFskskPKWAMNVAILLSHA 274

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 291480032  26 YMVYVSFFAGILIPLVVMCGIYLDIFYIIRnklsqnfsssketsafygREFKTAKSLSLVLFLFAVSWLPLSIMNCVIYF 105
Cdd:cd14967  158 IYVLVSSVISFFIPLLIMIVLYARIFRVAR------------------RELKAAKTLAIIVGAFLLCWLPFFIIYLVSAF 219

                 ..
gi 291480032 106 SG 107
Cdd:cd14967  220 CP 221

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 291480032  30 VSFFagilIPLVVMCGIYLDIFYIIRNKL------------SQNFSSSKETSAFygREFKTAKSLSLVLFLFAVSWLPLS 97
Cdd:cd15057  174 ISFY----IPVAIMIVTYTRIYRIARRQIrriaaleraaqeSTNPDSSLRSSLR--RETKALKTLSIIMGVFVCCWLPFF 247

                         90
                 ....*....|
gi 291480032  98 IMNCVIYFSG 107
Cdd:cd15057  248 ILNCVLPFCD 257

trace amine-associated receptor 5 and similar receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Included in this group are mammalian TAAR5, TAAR6, TAAR8, TAAR9, and similar proteins. They are among the 15 identified trace 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 291480032  27 MVYVSFFagilIPLVVMCGIYLDIFYIIRNKLSQ--------NFSSSKETSAFYGREFKTAKSLSLVLFLFAVSWLPLSI 98
Cdd:cd15317  169 LDFLTFF----IPCLIMIGLYAKIFLVARRQARKiqnmedkfRSSEENSSKASASRERKAAKTLAIVMGIFLFCWLPYFI 244

                         90
                 ....*....|....*..
gi 291480032  99 MNCVIYFSGEVPRVVLY 115
Cdd:cd15317  245 DTIVDEYSNFITPAIVF 261

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 291480032  30 VSFFAGILIPLVVMCGIYLDIFY-------IIRNKLSQNFSSSKETSAFyGREFKTAKSLSLVLFLFAVSWLPLSI 98
Cdd:cd15312  169 IASLIAFFIPGTVMIGIYIKIFFvarkhakVINNRPSVTKGDSKNKLSK-KKERKAAKTLSIVMGVFLLCWLPFFV 243

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
                 ....*....|....*....|....*....|....*....|....*...
gi 291480032  60 QNFSSSKETSafYGREFKTAKSLSLVLFLFAVSWLPLSIMNCVIYFSG 107
Cdd:cd15320  232 QQPESSFKMS--FKRETKVLKTLSVIMGVFVCCWLPFFILNCMVPFCK 277

vertebrate melanopsins and related opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represent the Gq-coupled rhodopsin subfamily consists of melanopsins, insect photoreceptors R1-R6, invertebrate Gq opsins as well as their closely related opsins. Melanopsins (also called Opsin-4) are the primary photoreceptor molecules for non-visual functions such as the photo-entrainment of the circadian rhythm and pupillary constriction in mammals. Mammalian melanopsins are expressed only in the inner retina, whereas non-mammalian vertebrate melanopsins are localized in various extra-retinal tissues such as iris, brain, pineal gland, and skin. The outer photoreceptors (R1-R6) are the insect Drosophila equivalent to the vertebrate rods and are responsible for image formation and motion detection. The invertebrate G(q) opsins includes the arthropod and mollusk visual opsins as well as invertebrate melanopsins, which are also found in vertebrates. Arthropods possess color vision by the use of multiple opsins sensitive to different light wavelengths. Members of this subfamily belong to the class A of the G protein-coupled receptors and have seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291480032  26 YMVYVSFFaGILIPLVVMCGIYLDIFYIIRN----------KLSQNFSSSKETSAfyGREFKTAKSLSLVLFLFAVSWLP 95
Cdd:cd15083  165 YVICLLIF-GFVLPLLIIIYCYSFIFRAVRRhekamkemakRFSKSELSSPKARR--QAEVKTAKIALLLVLLFCLAWTP 241

                         90
                 ....*....|
gi 291480032  96 LSIMNCVIYF 105
Cdd:cd15083  242 YAVVALIGQF 251

endothelial differentiation gene family, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents the endothelial differentiation gene (Edg) family of G-protein coupled receptors, melanocortin/ACTH receptors, and cannabinoid receptors as well as their closely related receptors. The Edg GPCRs bind blood borne lysophospholipids including sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA), which are involved in the regulation of cell proliferation, survival, migration, invasion, endothelial cell shape change and cytoskeletal remodeling. The Edg receptors are classified into two subfamilies: the lysophosphatidic acid subfamily that includes LPA1 (Edg2), LPA2 (Edg4), and LPA3 (Edg7); and the S1P subfamily that includes S1P1 (Edg1), S1P2 (Edg5), S1P3 (Edg3), S1P4 (Edg6), and S1P5 (Edg8). Melanocortin receptors bind a group of pituitary peptide hormones known as melanocortins, which include adrenocorticotropic hormone (ACTH) and the different isoforms of melanocyte-stimulating hormones. Two types of cannabinoid receptors, CB1 and CB2, are activated by naturally occurring endocannabinoids, cannabis plant-derived cannabinoids such as tetrahydrocannabinol, or synthetic cannabinoids. The CB receptors are involved in the various physiological processes such as appetite, mood, memory, and pain sensation. CB1 receptor is expressed predominantly in central and peripheral neurons, while CB2 receptor is found mainly in the immune system.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 291480032  24 MDYMVYVSFFagILIPLVVMCGIYLDIFYIIRNKLSQNFSSSKETS-AFYGREFKTAKSLSLVLFLFAVSWLPLSIMNC- 101
Cdd:cd14972  155 KSYLVLILVF--FFIALVIIVFLYVRIFWCLWRHANAIAARQEAAVpAQPSTSRKLAKTVVIVLGVFLVCWLPLLILLVl 232

                         90       100
                 ....*....|....*....|
gi 291480032 102 -VIYFSGEVPRVVLYLGILL 120
Cdd:cd14972  233 dVLCPSVCDIQAVFYYFLVL 252

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 291480032  25 DYMVYVSFFAGILIPLVVMCGIYldifYIIRNKLSQNFSSsketsafygrEFKTAKSLSLVLFLFAVSWLPLSIMNCVIY 104
Cdd:cd15304  158 ENFVLIGSFVAFFIPLTIMVITY----FLTIKSLQQSISN----------EQKASKVLGIVFFLFVVMWCPFFITNVMAV 223

                         90
                 ....*....|....*
gi 291480032 105 FSGEVPRVVLYLGIL 119
Cdd:cd15304  224 ICKESCNEVVIGGLL 238

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 291480032  37 LIPLVVMCGIYLDIFYIIRN----KLSQNFSSSKETSAFYGREFKTAKSLSLVLFLFAVSWLPLSIMNCVIYFSGEVP 110
Cdd:cd15203  177 VIPLLIISFCYFRISLKLRKrvkkKRGKRTLSSRRRRSELRRKRRTNRLLIAMVVVFAVCWLPLNLFNLLRDFEPLPQ 254

prolactin-releasing peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Prolactin-releasing peptide (PrRP) receptor (previously known as GPR10) is expressed in the central nervous system with the highest levels located in the anterior pituitary and is activated by its endogenous ligand PrRP, a neuropeptide possessing a C-terminal Arg-Phe-amide motif. There are two active isoforms of PrRP in mammals: one consists of 20 amino acids (PrRP-20) and the other consists of 31 amino acids (PrRP-31), where PrRP-20 is a C-terminal fragment of PrRP-31. Binding of PrRP to the receptor coupled to G(i/o) proteins activates the extracellular signal-related kinase (ERK) and it can also couple to G(q) protein leading to an increase in intracellular calcium and activation of c-Jun N-terminal protein kinase (JNK). The PrRP receptor shares significant sequence homology with the neuropeptide Y (NPY) receptor, and micromolar levels 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. PrRP has been shown to reduce food intake and body weight and modify body temperature when administered in rats. It also has been shown to decrease circulating growth hormone levels by activating somatostatin-secreting neurons in the hypothalamic periventricular nucleus.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 291480032  37 LIPLVVMCGIYLDIFYIIRNKLSQNFSSSKETSAFYGREFKTAKSLSLVLFLFAVSWLPLSIMN 100
Cdd:cd15394  175 VLPLLAISLSYLRISVKLRNRVVPGSMTQSQAEWDRARRRKTFRLLVVVVVAFAICWLPLHIFN 238

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 291480032  26 YMVYVSFFagilIPLVVMCGIYLDIFYIIRnklsqnfsssketsafygREFKTAKSLSLVLFLFAVSWLPLSIM 99
Cdd:cd15061  160 YSSMGSFF----LPLLLMLFVYLRIFRVIA------------------KERKTAKTLAIVVGCFIVCWLPFFIM 211