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 296024825    3 NMKMTPGHHRNATFLSCQFRSVIRMDYMIYVSFFaGILLPLVVMCGIYLDIFYVIRNKLSQNFSSSKEtsafyGREFKTA 82
Cdd:pfam00001 125 WTLTVPEGNVTVCFIDFPEDLSKPVSYTLLISVL-GFLLPLLVILVCYTLIIRTLRKSASKQKSSERT-----QRRRKAL 198

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 296024825   83 KSLSLVLLLFAVSWLPLSIMNCVIYFSGEVP-----PVVLYLGILLSHANS 128
Cdd:pfam00001 199 KTLAVVVVVFILCWLPYHIVNLLDSLALDCElsrllDKALSVTLWLAYVNS 249

adenosine receptor subfamily, member of the class A family of seven-transmembrane G protein-coupled receptors; The adenosine receptors (or P1 receptors), a family of G protein-coupled purinergic receptors, bind adenosine as their endogenous ligand. There are four types of adenosine receptors in human, designated as A1, A2A, A2B, and A3. Each type is encoded by a different gene and has distinct functions with some overlap. For example, both A1 and A2A receptors are involved in regulating myocardial oxygen consumption and coronary blood flow in the heart, while the A2A receptor also has a broad spectrum of anti-inflammatory effects in the body. These two receptors also expressed in the brain, where they have important roles in the release of other neurotransmitters such as dopamine and glutamate, while the A2B and A3 receptors found primarily in the periphery and play important roles in inflammation and immune responses. The A1 and A3 receptors preferentially interact with G proteins of the G(i/o) family, thereby lowering the intracellular cAMP levels, whereas the A2A and A2B receptors interact with G proteins of the G(s) family, activating adenylate cyclase to elevate cAMP levels.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296024825   1 GWNMKMTPGHHRNATFLSCQFRSVIRMDYMIYVSFFAGILLPLVVMCGIYLDIFYVIRNKLSQNFS--SSKETSAFYGRE 78
Cdd:cd14968  136 GWNNGAPLESGCGEGGIQCLFEEVIPMDYMVYFNFFACVLVPLLIMLVIYLRIFRVIRKQLRQIESllRSRRSRSTLQKE 215

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 296024825  79 FKTAKSLSLVLLLFAVSWLPLSIMNCVIYFSGE--VPPVVLYLGILLSHANS 128
Cdd:cd14968  216 VKAAKSLAIILFLFALCWLPLHIINCITLFCPEckVPKILTYIAILLSHANS 267

adenosine receptor subtype A2A, member of the class A family of seven-transmembrane G protein-coupled receptors; The A2A receptor, a member of the adenosine receptor family of G protein-coupled receptors, binds adenosine as its endogenous ligand and is involved in regulating myocardial oxygen consumption and coronary blood flow. High-affinity A2A and low-affinity A2B receptors are preferentially coupled to G proteins of the stimulatory (Gs) family, which lead to activation of adenylate cyclase and thereby increasing the intracellular cAMP levels. The A2A receptor activation protects against tissue injury and acts as anti-inflammatory agent. In human skin endothelial cells, activation of A2B receptor, but not the A2A receptor, promotes angiogenesis. Alternatively, activated A2A receptor, but not the A2B receptor, promotes angiogenesis in human umbilical vein and lung microvascular endothelial cells. The A2A receptor alters cardiac contractility indirectly by modulating the anti-adrenergic effect of A1 receptor, while the A2B receptor exerts direct effects on cardiac contractile function, but does not modulate beta-adrenergic or A1 anti-adrenergic effects.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296024825   1 GWNMKMTPGHHRNAT------FLSCQFRSVIRMDYMIYVSFFAGILLPLVVMCGIYLDIFYVIRNKLSQNFSSS---KET 71
Cdd:cd15068  136 GWNNCGQPKEGKNHSqgcgegQVACLFEDVVPMNYMVYFNFFACVLVPLLLMLGVYLRIFLAARRQLKQMESQPlpgERA 215

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 296024825  72 SAFYGREFKTAKSLSLVLLLFAVSWLPLSIMNCVIYFSGEV---PPVVLYLGILLSHANS 128
Cdd:cd15068  216 RSTLQKEVHAAKSLAIIVGLFALCWLPLHIINCFTFFCPDCshaPLWLMYLAIVLSHTNS 275

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 296024825  10 HHRNATFLSCQFRSVIRMDYMIYVsFFAGILLPLVVMCGIYLDIFYVIR--NKLSQNFSSSKETSAFYGREFKTAKSLSL 87
Cdd:cd00637  142 YGGYCCCCLCWPDLTLSKAYTIFL-FVLLFLLPLLVIIVCYVRIFRKLRrhRRRIRSSSSNSSRRRRRRRERKVTKTLLI 220

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 296024825  88 VLLLFAVSWLPLSIMNCVIYFSGE---VPPVVLYLGILLSHANS 128
Cdd:cd00637  221 VVVVFLLCWLPYFILLLLDVFGPDpspLPRILYFLALLLAYLNS 264

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 296024825  29 YMIYVSFFAgILLPLVVMCGIYLDIFYVIR------NKLSQNFSSSKETSAFYGREFKTAKSLSLVLLLFAVSWLPLSIM 102
Cdd:cd15051  164 YVLLVAIGT-FYLPLLIMCGVYLRIFRIAReqakriNALTPASTANSSKSAATAREHKATVTLAAVLGAFIICWFPYFTY 242

                         90       100
                 ....*....|....*....|....*..
gi 296024825 103 NCVIYFSGEVPPVVLYLGIL-LSHANS 128
Cdd:cd15051  243 FTYRGLCGDNINETALSVVLwLGYANS 269

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 296024825  29 YMIYVSFFAGILLPLVVMCGIYLDIFyvirnklsqnfsssKETSafygREFKTAKSLSLVLLLFAVSWLPLSIMNCVIYF 108
Cdd:cd15049  162 AITFGTAIAAFYLPVLVMTILYWRIY--------------RETA----RERKAARTLSAILLAFIITWTPYNILVLVSTF 223

                         90       100
                 ....*....|....*....|.
gi 296024825 109 SGEVPPVVLY-LGILLSHANS 128
Cdd:cd15049  224 CAKCIPDTLWsFGYWLCYINS 244

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 296024825  33 VSFFAGILLPLVVMCGIYLDIFYVIR------NKLSQNFSSSKETSAFYGREFKTAKSLSLVLLLFAVSWLPLSIMNCVI 106
Cdd:cd15312  169 IASLIAFFIPGTVMIGIYIKIFFVARkhakviNNRPSVTKGDSKNKLSKKKERKAAKTLSIVMGVFLLCWLPFFVATLID 248

                         90
                 ....*....|..
gi 296024825 107 YFSGEVPPVVLY 118
Cdd:cd15312  249 PFLNFSTPVDLF 260

cholecystokinin receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents four G-protein coupled receptors that are members of the RFamide receptor family, including cholecystokinin receptors (CCK-AR and CCK-BR), orexin receptors (OXR), neuropeptide FF receptors (NPFFR), and pyroglutamylated RFamide peptide receptor (QRFPR). These RFamide receptors are activated by their endogenous peptide ligands that share a common C-terminal arginine (R) and an amidated phenylanine (F) motif. CCK-AR (type A, alimentary; also known as CCK1R) is found abundantly on pancreatic acinar cells and binds only sulfated CCK-peptides with very high affinity, whereas CCK-BR (type B, brain; also known as CCK2R), the predominant form in the brain and stomach, binds CCK or gastrin and discriminates poorly between sulfated and non-sulfated peptides. CCK is implicated in regulation of digestion, appetite control, and body weight, and is involved in neurogenesis via CCK-AR. There is some evidence to support that CCK and gastrin, via their receptors, are involved in promoting cancer development and progression, acting as growth and invasion factors. Orexins (OXs; also referred to as hypocretins) are neuropeptide hormones that regulate the sleep-wake cycle and potently influence homeostatic systems regulating appetite and feeding behavior or modulating emotional responses such as anxiety or panic. OXs are synthesized as prepro-orexin (PPO) in the hypothalamus and then proteolytically cleaved into two forms of isoforms: orexin-A (OX-A) and orexin-B (OX-B). OXA is a 33 amino-acid peptide with N-terminal pyroglutamyl residue and two intramolecular disulfide bonds, whereas OXB is a 28 amino-acid linear peptide with no disulfide bonds. OX-A binds orexin receptor 1 (OX1R) with high-affinity, but also binds with somewhat low-affinity to OX2R, and signals primarily to Gq coupling, whereas OX-B shows a strong preference for the orexin receptor 2 (OX2R) and signals through Gq or Gi/o coupling. The 26RFa, also known as QRFP (Pyroglutamylated RFamide peptide), is a 26-amino acid residue peptide that exerts similar orexigenic activity including the regulation of feeding behavior in mammals. It is the ligand for G-protein coupled receptor 103 (GPR103), which is predominantly expressed in paraventricular (PVN) and ventromedial (VMH) nuclei of the hypothalamus. GPR103 shares significant protein sequence homology with orexin receptors (OX1R and OX2R), which have recently shown to produce a neuroprotective effect in Alzheimer's disease by forming a functional heterodimer with GPR103. Neuropeptide FF (NPFF) is a mammalian octapeptide that has been implicated in a wide range of physiological functions in the brain including pain sensitivity, insulin release, food intake, memory, blood pressure, and opioid-induced tolerance and hyperalgesia. The effects of NPFF are mediated through neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R) which are predominantly expressed in the brain. NPFF induces pro-nociceptive effects, mainly through the NPFF1-R, and anti-nociceptive effects, mainly through the NPFF2-R.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296024825  40 LLPLVVMCGIYLDIFYV--IRNKLSQNFSSSKETSAFYGRE-FKTAKSLSLVLLLFAVSWLPLSIMNCVIYFSGEVP--- 113
Cdd:cd14993  180 VLPLLIISVAYSLIGRRlwRRKPPGDRGSANSTSSRRILRSkKKVARMLIVVVVLFALSWLPYYVLSILLDFGPLSSees 259

                         90
                 ....*....|....*....
gi 296024825 114 ----PVVLYLGILLSHANS 128
Cdd:cd14993  260 denfLLILPFAQLLGYSNS 278

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 296024825  29 YMIYvSFFAGILLPLVVMCGIYLDIFYVIRnklsqnfsssketsafygREFKTAKSLSLVLLLFAVSWLPLSIMN----- 103
Cdd:cd15061  157 YRIY-SSMGSFFLPLLLMLFVYLRIFRVIA------------------KERKTAKTLAIVVGCFIVCWLPFFIMYliepf 217

                         90       100
                 ....*....|....*....|....
gi 296024825 104 CVIYFSGEVPPVVLYLGILLSHAN 127
Cdd:cd15061  218 CDCQFSEALSTAFTWLGYFNSVIN 241

muscarinic acetylcholine receptor subtype M1, member of the class A family of seven-transmembrane G protein-coupled receptors; Muscarinic acetylcholine receptors (mAChRs) regulate the activity of many fundamental central and peripheral functions. The mAChR family consists of 5 subtypes M1-M5, which can be further divided into two major groups according to their G-protein coupling preference. The M1, M3 and M5 receptors selectively interact with G proteins of the G(q/11) family, whereas the M2 and M4 receptors preferentially link to the G(i/o) types of G proteins. Activation of mAChRs by agonist (acetylcholine) leads to a variety of biochemical and electrophysiological responses. M1 is the dominant mAChR subtype involved in learning and memory. It is linked to synaptic plasticity, neuronal excitability, and neuronal differentiation during early development. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296024825  37 AGILLPLVVMCGIYLDIFyvirnklsqnfsssKETSafygREFKTAKSLSLVLLLFAVSWLPLSIMNCVIYFSGEVPPVV 116
Cdd:cd17790  170 AAFYLPVTIMIILYWRIY--------------RETI----KEKKAARTLSAILLAFILTWTPYNIMVLVSTFCKDCVPKT 231

                         90
                 ....*....|...
gi 296024825 117 LY-LGILLSHANS 128
Cdd:cd17790  232 LWeLGYWLCYVNS 244

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 296024825  27 MDYMIYVSFFagILLPLVVMCGIYLDIFYVIRNKLSQNFSSSKETS-AFYGREFKTAKSLSLVLLLFAVSWLPLSIMNC- 104
Cdd:cd14972  155 KSYLVLILVF--FFIALVIIVFLYVRIFWCLWRHANAIAARQEAAVpAQPSTSRKLAKTVVIVLGVFLVCWLPLLILLVl 232

                         90       100
                 ....*....|....*....|....*
gi 296024825 105 -VIYFSGEVPPVVLYLGILLSHANS 128
Cdd:cd14972  233 dVLCPSVCDIQAVFYYFLVLALLNS 257

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 296024825  30 MIYVSFFAGI--LLPLVVMCGIYLDIFYVIRNKLSQNFSSSKETSAFYGREFKTAKSLSLVLLLFAVSWLPLSIMN 103
Cdd:cd15394  163 LAYACSTLLItyVLPLLAISLSYLRISVKLRNRVVPGSMTQSQAEWDRARRRKTFRLLVVVVVAFAICWLPLHIFN 238

neuropeptide Y receptor type 2, 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 G(i) or G(o) 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. When NPY signals through NPY2R in concert with NPY5R, it induces angiogenesis and consequently plays an important role in revascularization and wound healing. On the other hand, when NPY acts through NPY1R and NPYR5, it acts as a vascular mitogen, leading to restenosis and atherosclerosis.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 296024825  40 LLPLVVMCGIYLDIFyvirNKLSQNFSSSKETSAFYGREFKTAKSLSLVLLLFAVSWLPLSIMNCVIYFSGEV 112
Cdd:cd15399  178 VLPLAIISYAYIRIW----TKLKNHVSPGGGNDHYHQRRRKTTKMLVCVVVVFAVSWLPFHAFQLASDIDSKV 246

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 296024825  63 QNFSSSKETSafYGREFKTAKSLSLVLLLFAVSWLPLSIMNCVIYFSG 110
Cdd:cd15320  232 QQPESSFKMS--FKRETKVLKTLSVIMGVFVCCWLPFFILNCMVPFCK 277

KiSS1-derived peptide (kisspeptin) receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The G protein-coupled KiSS1-derived peptide receptor (GPR54 or kisspeptin receptor) binds the peptide hormone kisspeptin (previously known as metastin), which encoded by the metastasis suppressor gene (KISS1) expressed in various endocrine and reproductive tissues. The KiSS1 receptor is coupled to G proteins of the G(q/11) family, which lead to activation of phospholipase C and increase of intracellular calcium. This signaling cascade plays an important role in reproduction by regulating the secretion of gonadotropin-releasing hormone.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296024825  29 YMIYVsFFAGILLPLVVMCGIY-LDIFYVIRNKLSQNFSSSKETSAFYGREFKTAKSLSLVLLLFAVSWLPLSIMNCVIY 107
Cdd:cd15095  166 YMIYT-VLLTYVIPLAIIAVCYgLILRRLWRRSVDGNNQSEQLSERALRQKRKVTRMVIVVVVLFAICWLPNHVLNLWQR 244

                         90       100
                 ....*....|....*....|....*.
gi 296024825 108 FSGEVPP-----VVLYLGILLSHANS 128
Cdd:cd15095  245 FDPNFPEtyatyALKIAALCLSYANS 270

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

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 296024825  40 LLPLVVMCGIYLDIFYVIRNK--LSQNFSSSKETSAFYGREFKTAKSLSLVLLLFAVSWLPLSIMNCVIYF 108
Cdd:cd15207  176 VAPLLIIAVLYVRIGYRLWFKpvPGGGSASREAQAAVSKKKVRVIKMLIVVVVLFALSWLPLHTVTMLDDF 246

somatostatin receptor type 1, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled somatostatin receptors (SSTRs) are composed of five distinct subtypes (SSTR1-5) that display strong sequence similarity with opioid receptors. All five receptor subtypes bind the natural somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. SSTR1 is coupled to a Na/H exchanger, voltage-dependent calcium channels, and AMPA/kainate glutamate channels. SSTR1 is expressed in the normal human pituitary and in nearly half of all pituitary adenoma subtypes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296024825  29 YMIYvSFFAGILLPLVVMCGIYLDIFYVIRN-KLSQNFSSSKETsafygrEFKTAKSLSLVLLLFAVSWLPLSIMNCVIY 107
Cdd:cd15970  165 FVVY-TFLMGFLLPVIAICLCYILIIVKMRVvALKAGWQQRKRS------ERKITLMVMMVVTVFVICWMPFYVVQLVSV 237

                         90       100
                 ....*....|....*....|.
gi 296024825 108 FSGEVPPVVLYLGILLSHANS 128
Cdd:cd15970  238 FVGQHDATVSQLSVILGYANS 258

opioid receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes opioid receptors, somatostatin receptors, melanin-concentrating hormone receptors (MCHRs), and neuropeptides B/W receptors. Together they constitute the opioid receptor-like family, members of the class A G-protein coupled receptors. Opioid receptors are coupled to inhibitory G proteins of the G(i/o) family and are involved in regulating a variety of physiological functions such as pain, addiction, mood, stress, epileptic seizure, and obesity, among many others. G protein-coupled somatostatin receptors (SSTRs), which display strong sequence similarity with opioid receptors, binds somatostatin (somatotropin release inhibiting factor), a polypeptide hormone that regulates a wide variety of physiological functions such as neurotransmission, cell proliferation, contractility of smooth muscle cells, and endocrine signaling as well as inhibition of the release of many secondary hormones. MCHR binds melanin concentrating hormone and is presumably involved in the neuronal regulation of food intake. Despite strong homology with somatostatin receptors, MCHR does not appear to bind somatostatin. Neuropeptides B/W receptors are primarily expressed in the CNS and stimulate the cortisol secretion by activating the adenylate cyclase- and the phospholipase C-dependent signaling pathways.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 296024825  34 SFFAGILLPLVVMCGIYLDIFYVIRNKLSQNFSSSKETSafyGREFKTAKSLSLVLLLFAVSWLPLSIMNcVIYFSGEVP 113
Cdd:cd14970  169 TFVLGFAVPLLVITVCYSLIIRRLRSSRNLSTSGAREKR---RARRKVTRLVLVVVAVFVVCWLPFHVFQ-IVRLLIDPP 244

                         90       100
                 ....*....|....*....|
gi 296024825 114 P-----VVLYLGILLSHANS 128
Cdd:cd14970  245 EtltvvGVFLFCIALSYANS 264