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 1632314023  22 ILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMsPAMVINCYYETWVLGPLVCELYGLTGS 101
Cdd:cd15079     2 LLGFIYIFLGIVSLLGNGLVIYIFSTTKSLRTPSNMLVVNLAISDFLMMIKM-PIFIYNSFYEGWALGPLGCQIYAFLGS 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1632314023 102 LFGCGSIWTMTMIAFDRYNVIVKGLSAKPMTINGALLRILGIWFFSLGWTIAPM 155
Cdd:cd15079    81 LSGIGSIWTNAAIAYDRYNVIVKPLNGNPLTRGKALLLILFIWLYALPWALLPL 134

insect photoreceptors R1-R6 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the insect photoreceptors and their closely related proteins. The Drosophila eye is composed of about 800 unit eyes called ommatidia, each of which contains eight photoreceptor cells (R1-R8). The six outer photoreceptors (R1-R6) function like the vertebrate rods and are responsible for motion detection in dim light and image formation. The R1-R6 photoreceptors express a blue-absorbing pigment, Rhodopsin 1(Rh1). The inner photoreceptors (R7 and R8) are considered the equivalent of the color-sensitive vertebrate cone cells, which express a range of different pigments. The R7 photoreceptors express one of two different UV absorbing pigments, either Rh3 or Rh4. Likewise, the R8 photoreceptors express either the blue absorbing pigment Rh5 or green absorbing pigment Rh6. These photoreceptors belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  22 ILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMsPAMVINCYYETWVLGPLVCELYGLTGS 101
Cdd:cd15079     2 LLGFIYIFLGIVSLLGNGLVIYIFSTTKSLRTPSNMLVVNLAISDFLMMIKM-PIFIYNSFYEGWALGPLGCQIYAFLGS 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1632314023 102 LFGCGSIWTMTMIAFDRYNVIVKGLSAKPMTINGALLRILGIWFFSLGWTIAPM 155
Cdd:cd15079    81 LSGIGSIWTNAAIAYDRYNVIVKPLNGNPLTRGKALLLILFIWLYALPWALLPL 134

CC chemokine receptor-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  29 ILGMISVIGNGMVIYIFTTtKSLRTPSNLLVINLAISDFLMMLSMsPAMVINcYYETWVLGPLVCELYGLTGSLFGCGSI 108
Cdd:PHA02638  107 IIFILGLFGNAAIIMILFC-KKIKTITDIYIFNLAISDLIFVIDF-PFIIYN-EFDQWIFGDFMCKVISASYYIGFFSNM 183

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1632314023 109 WTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSL 148
Cdd:PHA02638  184 FLITLMSIDRYFAILYPISfQKYRTFNIGIILCIISWILSL 224

insect photoreceptors R1-R6 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the insect photoreceptors and their closely related proteins. The Drosophila eye is composed of about 800 unit eyes called ommatidia, each of which contains eight photoreceptor cells (R1-R8). The six outer photoreceptors (R1-R6) function like the vertebrate rods and are responsible for motion detection in dim light and image formation. The R1-R6 photoreceptors express a blue-absorbing pigment, Rhodopsin 1(Rh1). The inner photoreceptors (R7 and R8) are considered the equivalent of the color-sensitive vertebrate cone cells, which express a range of different pigments. The R7 photoreceptors express one of two different UV absorbing pigments, either Rh3 or Rh4. Likewise, the R8 photoreceptors express either the blue absorbing pigment Rh5 or green absorbing pigment Rh6. These photoreceptors belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  22 ILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMsPAMVINCYYETWVLGPLVCELYGLTGS 101
Cdd:cd15079     2 LLGFIYIFLGIVSLLGNGLVIYIFSTTKSLRTPSNMLVVNLAISDFLMMIKM-PIFIYNSFYEGWALGPLGCQIYAFLGS 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1632314023 102 LFGCGSIWTMTMIAFDRYNVIVKGLSAKPMTINGALLRILGIWFFSLGWTIAPM 155
Cdd:cd15079    81 LSGIGSIWTNAAIAYDRYNVIVKPLNGNPLTRGKALLLILFIWLYALPWALLPL 134

invertebrate Gq opsins, member of the class A family of seven-transmembrane G protein-coupled receptors; The invertebrate Gq-coupled opsin subfamily includes the arthropod and mollusc visual opsins. Like the vertebrate visual opsins, arthropods possess color vision by the use of multiple opsins sensitive to different light wavelengths. The invertebrate Gq opsins are closely related to the vertebrate melanopsins, the primary photoreceptor molecules for non-visual responses to light, and the R1-R6 photoreceptors, which are the fly equivalent to the vertebrate rods. The Gq opsins belong the class A of the G protein-coupled receptors and possess seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  22 ILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMS-PAMVINCYYETWVLGPLVCELYGLTG 100
Cdd:cd15337     2 LIGIYIAIVGILGVIGNLLVIYLFSKTKSLRTPSNMFIINLAISDFGFSAVNGfPLKTISSFNKKWIWGKVACELYGFAG 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1632314023 101 SLFGCGSIWTMTMIAFDRYNVIVKGL-SAKPMTINGALLRILGIWFFSLGWTIAP 154
Cdd:cd15337    82 GIFGFMSITTLAAISIDRYLVIAKPLeAMKKMTFKRAFIMIIIIWLWSLLWSIPP 136

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  22 ILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGS 101
Cdd:cd14969     2 VLAVYLSLIGVLGVVLNGLVIIVFLKKKKLRTPLNLFLLNLALADLLMSVVGYPLSFYSNLSGRWSFGDPGCVIYGFAVT 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1632314023 102 LFGCGSIWTMTMIAFDRYNVIVKGLSAKPMTINGALLRILGIWFFSLGWTIAP 154
Cdd:cd14969    82 FLGLVSISTLAALAFERYLVIVRPLKAFRLSKRRALILIAFIWLYGLFWALPP 134

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 1632314023  37 GNGMVIYIFTTTKSLRTPSNLLVINLAISDFLM-MLSMSPAMVINCYYETWVLGPLVCELYGLTGSLFGCGSIWTMTMIA 115
Cdd:pfam00001   1 GNLLVILVILRNKKLRTPTNIFLLNLAVADLLFsLLTLPFWLVYYLNHGDWPFGSALCKIVGALFVVNGYASILLLTAIS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1632314023 116 FDRYNVIVKGLSAKP-MTINGALLRILGIWFFSLGWTIAPM 155
Cdd:pfam00001  81 IDRYLAIVHPLRYKRrRTPRRAKVLILVIWVLALLLSLPPL 121

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 1632314023  21 AILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCElygLTG 100
Cdd:cd15203     1 IILILLYGLIIVLGVVGNLLVIYVVLRNKSMQTVTNIFILNLAVSDLLLCLVSLPFTLIYTLTKNWPFGSILCK---LVP 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1632314023 101 SLFGCG---SIWTMTMIAFDRYNVIVKGLSaKPMTINGALLRILGIWFFSL 148
Cdd:cd15203    78 SLQGVSifvSTLTLTAIAIDRYQLIVYPTR-PRMSKRHALLIIALIWILSL 127

retinal pigment epithelium-derived rhodopsin homolog, member of the class A family of seven-transmembrane G protein-coupled receptors; Peropsin, also known as a retinal pigment epithelium-derived rhodopsin homolog (RRH), is a visual pigment-like protein found exclusively in the apical microvilli of the retinal pigment epithelium. Peropsin belongs to the type 2 opsin family of the class A G-protein coupled receptors. Peropsin presumably plays a physiological role in the retinal pigment epithelium either by detecting light directly or monitoring the levels of retinoids, the primary light absorber in visual perception, or other pigment-related compounds in the eye.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  22 ILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGS 101
Cdd:cd15073     2 IVAAYLIVAGIISTISNGIVLVTFVKFRELRTPTNALIINLAVTDLGVSIIGYPFSAASDLHGSWKFGYAGCQWYAFLNI 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1632314023 102 LFGCGSIWTMTMIAFDRYNVIVKGLSAKPMTINGALLRILGIWFFSLGWTIAPM 155
Cdd:cd15073    82 FFGMASIGLLTVVAVDRYLTICRPDLGRKMTTNTYTVMILLAWTNAFFWAAMPL 135

serotonin receptor subtype 7, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT7 receptor, one of 14 mammalian serotonin receptors, is a member of the class A of GPCRs and is activated by the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). 5-HT7 receptor mainly couples to Gs protein, which positively stimulates adenylate cyclase, leading to increased intracellular cAMP formation and calcium influx. 5-HT7 receptor is expressed in various human tissues, mainly in the brain, the lower gastrointestinal tract and in vital blood vessels including the coronary artery. 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 1632314023  21 AILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTG 100
Cdd:cd15329     1 VLIGIVLLIIILGTVVGNALVIIAVCLVKKLRTPSNYLIVSLAVSDLLVALLVMPLAIIYELSGYWPFGEILCDVWISFD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1632314023 101 SLFGCGSIWTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSLGWTIAPM 155
Cdd:cd15329    81 VLLCTASILNLCAISVDRYLVITRPLTyAVKRTPKRMALMIAIVWLLSALISIPPL 136

encephalopsins (opsin-3), member of the class A family of seven-transmembrane G protein-coupled receptors; Encephalopsin, also called Opsin-3 or Panopsin, is a mammalian extra-retinal opsin that is highly localized in the brain. It is thought to play a role in encephalic photoreception. Encephalopsin belongs to the class A of the G protein-coupled receptors and shows strong homology to the vertebrate visual opsins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  23 LGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGSL 102
Cdd:cd15078     3 LALLIATIGFLGVCNNLLVLILYYKFKRLRTPTNLLLVNISLSDLLVSLLGVTFTFMSCVRGRWVFDVAGCVWDGFSNSL 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1632314023 103 FGCGSIWTMTMIAFDRYNVIVKglsAKPMTINGALLRILGIWFFSLGWTIAPM 155
Cdd:cd15078    83 FGIVSIMTLTVLAYERYIRVVH---AKVVNFSWSWRAITYIWLYSLAWTGAPL 132

histamine receptor subtypes H3R and H4R, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine subtypes H3R and H4R, members of the histamine receptor family, which belong 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 H3 and H4 receptors couple to the G(i)-proteins, which leading to the inhibition of cAMP formation. The H3R receptor functions as a presynaptic autoreceptors controlling histamine release and synthesis. The H4R plays an important role in histamine-mediated chemotaxis in mast cells and eosinophils. 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 1632314023  21 AILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTG 100
Cdd:cd15048     1 IVLAVLISVLILVTVIGNLLVILAFIKDKKLRTVSNFFLLNLAVADFLVGLVSMPFYIPYTLTGKWPFGKVFCKAWLVVD 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1632314023 101 SLFGCGSIWTMTMIAFDRYNVIVKGLSAKPM-TINGALLRILGIWFFSL 148
Cdd:cd15048    81 YTLCTASALTIVLISLDRYLSVTKAVKYRAKqTKRRTVLLMALVWILAF 129

tachykinin receptors and related receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the neurokinin/tachykinin receptors and its closely related receptors such as orphan GPR83 and leucokinin-like peptide receptor. 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 1632314023  21 AILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTG 100
Cdd:cd15202     1 VLLIVAYSFIIVFSLFGNVLVCWIIFKNQRMRTVTNYFIVNLAVADIMITLFNTPFTFVRAVNNTWIFGLFMCHFSNFAQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1632314023 101 SLFGCGSIWTMTMIAFDRYNVIVKGLSAKpMTINGALLRILGIWFFSL 148
Cdd:cd15202    81 YCSVHVSAYTLTAIAVDRYQAIMHPLKPR-ISKTKAKFIIAVIWTLAL 127

neurokinin receptors (or tachykinin receptors), member of the class A family of seven-transmembrane G protein-coupled receptors; This group represents G-protein coupled receptors for a variety of neuropeptides of the tachykinin (TK) family. 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 1632314023  24 GFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGSLF 103
Cdd:cd15390     4 SIVFVVMVLVAIGGNLIVIWIVLAHKRMRTVTNYFLVNLAVADLLISAFNTVFNFTYLLYNDWPFGLFYCKFSNFVAITT 83

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1632314023 104 GCGSIWTMTMIAFDRYNVIVKGLSaKPMTINGALLRILGIWFFSLGWTI 152
Cdd:cd15390    84 VAASVFTLMAISIDRYIAIVHPLR-PRLSRRTTKIAIAVIWLASFLLAL 131

neuropeptide Y receptor-like found in insect and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes a novel G protein-coupled receptor (also known as PR4 receptor) from Drosophila melanogaster, which can be activated by the members of the neuropeptide Y (NPY) family, including NPY, peptide YY (PYY) and pancreatic polypeptide (PP), when expressed in Xenopus oocytes. These homologous peptides of 36-amino acids in length contain a hairpin-like structural motif, which referred to as the pancreatic polypeptide fold, and function as gastrointestinal hormones and neurotransmitters. The PR4 receptor also shares strong sequence homology to the mammalian tachykinin receptors (NK1R, NK2R, and NK3R), whose endogenous ligands are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), respectively. The tachykinins function as excitatory transmitters on neurons and cells in the gastrointestinal tract.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  21 AILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSP-AMVINCYYETWVLGPLVCELYGLT 99
Cdd:cd15392     1 VIIILMYSTIFVLAVGGNGLVCYIVVSYPRMRTVTNYFIVNLALSDILMAVFCVPfSFIALLILQYWPFGEFMCPVVNYL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1632314023 100 GSLFGCGSIWTMTMIAFDRYNVIVKGLSAKpMTINGALLRILGIWFFSL 148
Cdd:cd15392    81 QAVSVFVSAFTLVAISIDRYVAIMWPLRPR-MTKRQALLLIAVIWIFAL 128

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 1632314023  21 AILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTG 100
Cdd:cd15051     1 IVLGVVLAVIILLTVIGNVLVCLAVAVNRRLRNLTNYFIVSLAVTDLLLGLLVLPFSAIYELRGEWPLGPVFCNIYISLD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1632314023 101 SLFGCGSIWTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSLGWTIAP 154
Cdd:cd15051    81 VMLCTASILNLFAISLDRYLAITAPLRyPSRVTPRRVAIALAAIWVVSLAVSFLP 135

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 1632314023  22 ILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGS 101
Cdd:cd15055     2 LLYIVLSSISLLTVLGNLLVIISISHFKQLHTPTNLLLLSLAVADFLVGLLVMPFSMIRSIETCWYFGDTFCKLHSSLDY 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1632314023 102 LFGCGSIWTMTMIAFDRYNVIVKGL--SAKpMTINGALLRILGIWFFSLGWTIAPM 155
Cdd:cd15055    82 ILTSASIFNLVLIAIDRYVAVCDPLlyPTK-ITIRRVKICICLCWFVSALYSSVLL 136

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  21 AILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMML-SMSPAMVINCYYETWVLGPLVCELYGLT 99
Cdd:cd14979     1 VLVTAIYVAIFVVGIVGNLLTCIVIARHKSLRTTTNYYLFSLAVSDLLILLvGLPVELYNFWWQYPWAFGDGGCKLYYFL 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1632314023 100 GSLFGCGSIWTMTMIAFDRYNVIVKGLSAKPMTINGALLRILG-IWFFSL 148
Cdd:cd14979    81 FEACTYATVLTIVALSVERYVAICHPLKAKTLVTKRRVKRFILaIWLVSI 130

neuropeptide FF receptor 2, member of the class A family of seven-transmembrane G protein-coupled receptors; Neuropeptide FF (NPFF) is a mammalian octapeptide that belongs to a family of neuropeptides containing an RF-amide motif at their C-terminus that have been implicated in a wide range of physiological functions in the brain including pain sensitivity, insulin release, food intake, memory, blood pressure, and opioid-induced tolerance and hyperalgesia. The effects of these peptides are mediated through neuropeptide FF1 and FF2 receptors (NPFF1-R and NPFF2-R) which are predominantly expressed in the brain. NPFF induces pro-nociceptive effects, mainly through the NPFF1-R, and anti-nociceptive effects, mainly through the NPFF2-R. NPFF has been shown to inhibit adenylate cyclase via the Gi protein coupled to NPFF1-R.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  32 MISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGSLFGCGSIWTM 111
Cdd:cd15980    12 LLCMMGNGVVCFIVLRSKHMRTVTNLFILNLAISDLLVGIFCMPTTLLDNIIAGWPFGSTVCKMSGMVQGISVSASVFTL 91

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 1632314023 112 TMIAFDRYNVIVKGLSAKpMTINGALLRILGIWFFSL 148
Cdd:cd15980    92 VAIAVDRFRCIVYPFKQK-LTISTAVVIIVIIWVLAI 127

histamine subtype H1 receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine receptor subtype H1R, 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). H1R selectively interacts with the G(q)-type G protein that activates phospholipase C and the phosphatidylinositol pathway. Antihistamines, a widely used anti-allergy medication, act on the H1 subtype and produce drowsiness as a side effect. 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 1632314023  21 AILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTG 100
Cdd:cd15050     1 APLGIALSTISLITVILNLLVLYAVRTERKLHTVGNLYIVSLSVADLIVGAVVMPLNIVYLLESKWILGRPVCLFWLSMD 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1632314023 101 SLFGCGSIWTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSLGWTI 152
Cdd:cd15050    81 YVASTASIFSLFILCIDRYRSVQQPLKyLKYRTKTRASLMISGAWLLSFLWVI 133

muscarinic acetylcholine receptor DM1, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes muscarinic acetylcholine receptor DM1-like from invertebrates. 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 1632314023  22 ILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGS 101
Cdd:cd15301     2 LIVIVAAVLSLVTVGGNVMVMISFKIDKQLQTISNYFLFSLAVADFAIGVISMPLFTVYTALGYWPLGYEVCDTWLAIDY 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1632314023 102 LFGCGSIWTMTMIAFDRYNVIVKGLSAKP-MTINGALLRILGIWFFSL 148
Cdd:cd15301    82 LASNASVLNLLIISFDRYFSVTRPLTYRArRTTKKAAVMIASAWIISL 129

purinoceptor and its related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; Members of this subfamily include lysophosphatidic acid receptor, P2 purinoceptor, protease-activated receptor, platelet-activating factor receptor, Epstein-Barr virus induced gene 2, proton-sensing G protein-coupled receptors, GPR35, and GPR55, among others. 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 1632314023  33 ISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMsPAMVIncYY---ETWVLGPLVCELYGLTGSLFGCGSIW 109
Cdd:cd14982    13 LGLLGNILALWVFLRKMKKRSPTTIYMINLALADLLFVLTL-PFRIY--YYlngGWWPFGDFLCRLTGLLFYINMYGSIL 89

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1632314023 110 TMTMIAFDRYNVIVKGL-SAKPMTINGALLRILGIWFFSLGWTI 152
Cdd:cd14982    90 FLTCISVDRYLAVVHPLkSRRLRRKRYAVGVCAGVWILVLVASV 133

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 1632314023  27 IGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGSLFGCG 106
Cdd:cd15335     7 LALITILTTVLNSAVIAAICTTKKLHQPANYLICSLAVTDFLVAVLVMPLSITYIVMDTWTLGYFICEIWLSVDMTCCTC 86

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1632314023 107 SIWTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSLGWTIAPM 155
Cdd:cd15335    87 SILHLCVIALDRYWAITDAIEyARKRTAKRAGLMILTVWTISIFISIPPL 136

serotonin receptor subtypes 1B and 1D, member of the class A family of seven-transmembrane G protein-coupled receptors; The 5-HT1 receptors, one of 14 mammalian 5-HT receptors, is a member of the class A of GPCRs and is activated by the endogenous neurotransmitter and peripheral signal mediator serotonin (5-hydroxytryptamine, 5-HT). The 5-HT1 receptors mediate inhibitory neurotransmission by coupling to G proteins of the G(i/o) family, which lead to a decrease in adenylate cyclase activity, thereby decreasing intracellular cAMP levels and calcium influx. The 5-HT1 receptor subfamily includes 5 subtypes: 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, and 5-HT1F. There is no 5-HT1C receptor subtype, as it has been reclassified as the 5-HT2C receptor. In the CNS, serotonin is involved in the regulation of appetite, mood, sleep, cognition, learning and memory, as well as implicated in neurologic disorders such as migraine, schizophrenia, and depression.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  19 WHAILGFVIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGL 98
Cdd:cd15333     3 LKISLAVLLALITLATTLSNAFVIATIYLTRKLHTPANYLIASLAVTDLLVSILVMPISIVYTVTGTWTLGQVVCDIWLS 82

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1632314023  99 TGSLFGCGSIWTMTMIAFDRYNVIVKGLS-AKPMTINGALLRILGIWFFSLGWTIAPM 155
Cdd:cd15333    83 SDITCCTASILHLCVIALDRYWAITDAVEySKKRTPKRAAVMIALVWVISISISLPPF 140

putative neuropeptide receptor BNGR-A34 and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes putative neuropeptide receptor BNGR-A34 found in silkworm and its closely related proteins from invertebrates. They are members of the class A rhodopsin-like GPCRs, which represent a widespread protein family that includes 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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  30 LGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGSLFGCGSIW 109
Cdd:cd15000     9 VVLFGIFGNFVLLYILASNRSLRTPTNLLIGNMALADLLTLLVCPWMFLVHDFFQNYVLGSVGCKLEGFLEGSLLLASVL 88

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1632314023 110 TMTMIAFDRYNVIVKGLSAKpMTINGALLRILGIWFFSL 148
Cdd:cd15000    89 ALCAVSYDRLTAIVLPSEAR-LTKRGAKIVIVITWIVGL 126

gastrin-releasing peptide receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; The gastrin-releasing peptide receptor (GRPR) is a G-protein coupled receptor whose endogenous ligand is gastrin releasing peptide. GRP shares high sequence homology with the neuropeptide neuromedin B in the C-terminal region. This receptor is high glycosylated and couples to a pertussis-toxin-insensitive G protein of the family of Gq/11, which leads to the activation of phospholipase C. Gastrin-releasing peptide (GRP) is a potent mitogen for neoplastic tissues and involved in regulating multiple functions of the gastrointestinal and central nervous systems. These include the release of gastrointestinal hormones, the contraction of smooth muscle cells, and the proliferation of epithelial cells. GRPR belongs to the bombesin subfamily of G-protein coupled receptors, whose members also include neuromedin B receptor (NMBR) and bombesin receptor subtype 3 (BRS-3). Bombesin is a tetradecapeptide, originally isolated from frog skin.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1632314023  26 VIGILGMISVIGNGMVIYIFTTTKSLRTPSNLLVINLAISDFLMMLSMSPAMVINCYYETWVLGPLVCELYGLTGSLFGC 105
Cdd:cd15124     6 VYGIIILIGLIGNITLIKIFCTVKSMRNVPNLFISSLALGDLLLLVTCAPVDASRYLADEWLFGRVGCKLIPFIQLTSVG 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1632314023 106 GSIWTMTMIAFDRYNVIVKGLSAK-PMTINGALLRILGIWFFSL 148
Cdd:cd15124    86 VSVFTLTALSADRYKAIVRPMDIQaSNALMKICLKAALIWILSM 129