DNA polymerase III subunit gamma/tau;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768040362 261 PATSHAEPTTADYPKPATTSHPKPTAADNPElSASHCPEIPAIAHPVSDDSDLPESASSPAAGPTKPAASQLESDTIADL 340
Cdd:PRK14950 368 PAKPTAAAPSPVRPTPAPSTRPKAAAAANIP-PKEPVRETATPPPVPPRPVAPPVPHTPESAPKLTRAAIPVDEKPKYTP 446

                 ....
gi 768040362 341 PDPT 344
Cdd:PRK14950 447 PAPP 450

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
                  ....*....|....*....|....*....|....*....|....*..
gi 768040362    2 CWCPINVLTVL-VAVSPKEMAGKIPNWLYLAaYFIAYFNSCLNAVIY 47
Cdd:pfam00001 211 CWLPYHIVNLLdSLALDCELSRLLDKALSVT-LWLAYVNSCLNPIIY 256

melatonin receptor subtype 1B, member of the class A family of seven-transmembrane G protein-coupled receptors; Melatonin (N-acetyl-5-methoxytryptamine) is a naturally occurring sleep-promoting chemical found in vertebrates, invertebrates, bacteria, fungi, and plants. In mammals, melatonin is secreted by the pineal gland and is involved in regulation of circadian rhythms. Its production peaks during the nighttime, and is suppressed by light. Melatonin is shown to be synthesized in other organs and cells of many vertebrates, including the Harderian gland, leukocytes, skin, and the gastrointestinal (GI) tract, which contains several hundred times more melatonin than the pineal gland and is involved in the regulation of GI motility, inflammation, and sensation. Melatonin exerts its pleiotropic physiological effects through specific membrane receptors, named MT1A, MT1B, and MT1C, which belong to the class A rhodopsin-like G-protein coupled receptor family. MT1A and MT1B subtypes are present in mammals, whereas MT1C subtype has been found in amphibians and birds. The melatonin receptors couple to G proteins of the G(i/o) class, leading to the inhibition of adenylate cyclase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768040362   1 MCWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15400  222 ICWAPLNLIGLAVAINPQEMAPKVPEWLFVVSYFMAYFNSCLNAIIYGLLNQNFRKEY 279

melatonin receptor subtype 1C, member of the class A family of seven-transmembrane G protein-coupled receptors; Melatonin (N-acetyl-5-methoxytryptamine) is a naturally occurring sleep-promoting chemical found in vertebrates, invertebrates, bacteria, fungi, and plants. In mammals, melatonin is secreted by the pineal gland and is involved in regulation of circadian rhythms. Its production peaks during the nighttime, and is suppressed by light. Melatonin is shown to be synthesized in other organs and cells of many vertebrates, including the Harderian gland, leukocytes, skin, and the gastrointestinal (GI) tract, which contains several hundred times more melatonin than the pineal gland and is involved in the regulation of GI motility, inflammation, and sensation. Melatonin exerts its pleiotropic physiological effects through specific membrane receptors, named MT1A, MT1B, and MT1C, which belong to the class A rhodopsin-like G-protein coupled receptor family. MT1A and MT1B subtypes are present in mammals, whereas MT1C subtype has been found in amphibians and birds. The melatonin receptors couple to G proteins of the G(i/o) class, leading to the inhibition of adenylate cyclase.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768040362   1 MCWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15401  222 VCWGPLNFIGLAVAINPLKVAPKIPEWLFVLSYFMAYFNSCLNAVIYGVLNQNFRKEY 279

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
                 ....*....|....*....|....*....|....*....|....*....|.
gi 768040362   1 MCWCPINVLTVLVAVSPKEmaGKIPNWLYLAAYFIAYFNSCLNAVIYGLLN 51
Cdd:cd00637  227 LCWLPYFILLLLDVFGPDP--SPLPRILYFLALLLAYLNSAINPIIYAFFN 275

leucokinin-like peptide receptor from tick and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subgroup includes a leucokinin-like peptide receptor from the Southern cattle tick, Boophilus microplus, a pest of cattle world-wide. Leucokinins are invertebrate neuropeptides that exhibit myotropic and diuretic activity. This receptor is the first neuropeptide receptor known from the Acari and the second known in the subfamily of leucokinin-like peptide G-protein-coupled receptors. The other known leucokinin-like peptide receptor is a lymnokinin receptor from the mollusc Lymnaea stagnalis.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768040362   1 MCWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15393  231 LCWLPLQTYNLLNEIKPEINKYKYINIIWFCSHWLAMSNSCYNPFIYGLYNEKFKREF 288

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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 768040362   2 CWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRR 56
Cdd:cd15095  232 CWLPNHVLNLWQRFDPNFPETYATYALKIAALCLSYANSAVNPFVYAFMGENFRK 286

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
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 768040362   1 MCWCPINVLT-VLVAVSPKEMagkiPNWLYLAAYFIA--YFNSCLNAVIYGLLNENFRR 56
Cdd:cd14970  226 VCWLPFHVFQiVRLLIDPPET----LTVVGVFLFCIAlsYANSCLNPILYAFLDENFRK 280

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
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 768040362   3 WCPINVLTVLVAVSPKEMAgkIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15301  217 WTPYNVLVLIKAFFPCSDT--IPTELWDFSYYLCYINSTINPLCYALCNAAFRRTY 270

galanin receptor and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes G-protein coupled galanin receptors, kisspeptin receptor and allatostatin-A receptor (AstA-R) in insects. These receptors, which are members of the class A of seven transmembrane GPCRs, share a high degree of sequence homology among themselves. The galanin receptors bind galanin, a neuropeptide that is widely expressed in the brain, peripheral tissues, and endocrine glands. Galanin is implicated in numerous neurological and psychiatric diseases including Alzheimer's disease, eating disorders, and epilepsy, among many others. KiSS1-derived peptide receptor (also known as GPR54 or kisspeptin receptor) binds the peptide hormone kisspeptin (metastin), which encoded by the metastasis suppressor gene (KISS1) expressed in various endocrine and reproductive tissues. AstA-R is a G-protein coupled receptor that binds allatostatin A. Three distinct types of allatostatin have been identified in the insects and crustaceans: AstA, AstB, and AstC. They both inhibit the biosynthesis of juvenile hormone and exert an inhibitory influence on food intake. Therefore, allatostatins are considered as potential targets for insect control.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768040362   2 CWCPINVLTVLVAVSPKEmagkIPNWLYLA---AYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd14971  226 CWGPIHAILLLVALGPFP----LTYATYALriwAHCLAYSNSAVNPVLYAFLSEHFRKAF 281

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
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768040362   1 MCWCPINVLTVLVAVSPKEMA-GKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRRE 57
Cdd:cd15203  235 VCWLPLNLFNLLRDFEPLPQIdGRHFYLIFLICHLIAMSSACVNPLLYGWLNDNFRKE 292

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768040362   2 CWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15329  204 CWLPFFILALLRPFLKPIKCSCIPLWLSRLFLWLGYANSFLNPIIYAKFNREFRTPF 260

gonadotropin-releasing hormone and adipokinetic hormone receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; Gonadotropin-releasing hormone (GnRH) and adipokinetic hormone (AKH) receptors share strong sequence homology to each other, suggesting that they have a common evolutionary origin. GnRHR, also known as luteinizing hormone releasing hormone receptor (LHRHR), plays an central role in vertebrate reproductive function; its activation by binding to GnRH leads to the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. Adipokinetic hormone (AKH) is a lipid-mobilizing hormone that is involved in control of insect metabolism. Generally, AKH behaves as a typical stress hormone by mobilizing lipids, carbohydrates and/or certain amino acids such as proline. Thus, it utilizes the body's energy reserves to fight the immediate stress problems and subdue processes that are less important. Although AKH is known to responsible for regulating the energy metabolism during insect flying, it is also found in insects that have lost its functional wings and predominantly walk for their locomotion. Both GnRH and AKH receptors are members of the class A of the seven-transmembrane, G-protein coupled receptor (GPCR) superfamily.

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gi 768040362   1 MCWCPINVLTVLVAVSPkEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRRE 57
Cdd:cd15195  237 VCWGPYYVLGLWYWFDK-ESIKNLPPALSHIMFLLGYLNPCLHPIIYGVFMKEIRNW 292

alpha-2 adrenergic receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The alpha-2 adrenergic receptors (or adrenoceptors) are a subfamily of the class A rhodopsin-like GPCRs that share a common architecture of seven transmembrane helices. This subfamily consists of three highly homologous receptor subtypes that have a key role in neurotransmitter release: alpha-2A, alpha-2B, and alpha-2C. In addition, a fourth subtype, alpha-2D is present in ray-finned fishes and amphibians, but is not found in humans. The alpha-2 receptors are found in both central and peripheral nervous system and serve to produce inhibitory functions through the G(i) proteins. Thus, the alpha-2 receptors inhibit adenylate cyclase, which decreases cAMP production and thereby decreases calcium influx during the action potential. Consequently, lowered levels of calcium will lead to a decrease in neurotransmitter release by negative feedback. All GPCRs have a common structural architecture comprising of seven-transmembrane (TM) alpha-helices interconnected by three extracellular and three intracellular loops. A general feature of GPCR signaling is agonist-induced conformational changes in the receptors, leading to activation of the heterotrimeric G proteins, which consist of the guanine nucleotide-binding G-alpha subunit and the dimeric G-beta-gamma subunits. The activated G proteins then bind to and activate numerous downstream effector proteins, which generate second messengers that mediate a broad range of cellular and physiological processes.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 768040362   2 CWCPINVLTVLVAVSPkemAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRR 56
Cdd:cd15059  208 CWLPFFFTYPLVVVCK---TCGVPELLFKFFFWLGYCNSALNPVIYTIFNKDFRR 259

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.

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gi 768040362   1 MCWCPINVLTVLVAVSPKEMAGKIPNW--LYLAAYFIAYFNSCLNAVIYGLLNENFRRE 57
Cdd:cd14993  237 LSWLPYYVLSILLDFGPLSSEESDENFllILPFAQLLGYSNSAINPIIYCFMSKKFRRG 295

tachykinin receptor and closely related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily includes G-protein coupled receptors for a variety of neuropeptides of the tachykinin (TK) family as well as closely related receptors. The tachykinins are widely distributed throughout the mammalian central and peripheral nervous systems and act as excitatory transmitters on neurons and cells in the gastrointestinal tract. The TKs are characterized by a common five-amino acid C-terminal sequence, Phe-X-Gly-Leu-Met-NH2, where X is a hydrophobic residue. The three major mammalian tachykinins are substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). The physiological actions of tachykinins are mediated through three types of receptors: neurokinin receptor type 1 (NK1R), NK2R, and NK3R. SP is a high-affinity endogenous ligand for NK1R, which interacts with the Gq protein and activates phospholipase C, leading to elevation of intracellular calcium. NK2R is a high-affinity receptor for NKA, the tachykinin neuropeptide substance K. SP and NKA are found in the enteric nervous system and mediate in the regulation of gastrointestinal motility, secretion, vascular permeability, and pain perception. NK3R is activated by its high-affinity ligand, NKB, which is primarily involved in the central nervous system and plays a critical role in the regulation of gonadotropin hormone release and the onset of puberty.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 768040362   1 MCWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRR 56
Cdd:cd14992  234 ICWLPFHLFFLLRDFFPLIMKEKHTLQVYYFLHWIAMSNSMYNPIIYVTLNNNFRK 289

neuropeptide Y receptor type 4, 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.

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gi 768040362   1 MCWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRRE 57
Cdd:cd15397  236 LCWLPLNVFNAIADWNHEAIPHCQHNLIFSLCHLAAMASTCVNPIIYGFLNSNFKKE 292

opioid receptor subtype mu, member of the class A family of seven-transmembrane G protein-coupled receptors; The mu-opioid receptor binds endogenous opioids such as beta-endorphin and endomorphin. The opioid receptor family is composed of four major subtypes: mu (MOP), delta (DOP), kappa (KOP) opioid receptors, and the nociceptin/orphanin FQ peptide receptor (NOP). They are distributed widely in the central nervous system and respond to classic alkaloid opiates, such as morphine and heroin, as well as to endogenous peptide ligands, which include dynorphins, enkephalins, endorphins, endomorphins, and nociceptin. Opioid receptors are coupled to inhibitory G proteins of the G(i/o) family and involved in regulating a variety of physiological functions such as pain, addiction, mood, stress, epileptic seizure, and obesity, among many others.

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gi 768040362   1 MCWCPINVLTVLVA-VSPKEMAGKIPNWLYLAAyfIAYFNSCLNAVIYGLLNENFRR 56
Cdd:cd15090  223 VCWTPIHIYVIIKAlVTIPETTFQTVSWHFCIA--LGYTNSCLNPVLYAFLDENFKR 277

type 1 angiotensin II receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Angiotensin II (Ang II), the main effector in the renin-angiotensin system, plays a crucial role in the regulation of cardiovascular homeostasis through its type 1 (AT1) and type 2 (AT2) receptors. Ang II contributes to cardiovascular diseases such as hypertension and atherosclerosis via AT1R activation. Ang II increases blood pressure through Gq-mediated activation of phospholipase C, resulting in phosphoinositide (PI) hydrolysis and increased intracellular calcium levels. Through the AT2R, Ang II counteracts the vasoconstrictor action of AT1R and thereby induces vasodilation, sodium excretion, and reduction of blood pressure. Moreover, AT1R promotes cell proliferation, whereas AT2R inhibits proliferation and stimulates cell differentiation. The AT2R is highly expressed during fetal development, however it is scarcely present in adult tissues and is induced in pathological conditions. Generally, the AT1R mediates many actions of Ang II, while the AT2R is involved in the regulation of blood pressure and renal function.

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gi 768040362   1 MCWCPINVLTVLVAVSPKEMAG--KIPNWLYLAAYF---IAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15192  223 FCWIPHQIFTFLDVLIQLKVIQdcHIADIVDTAMPFticIAYFNSCLNPILYGFVGKNFRKKF 285

galanin receptor subtype 1, member of the class A family of seven-transmembrane G protein-coupled receptors; The G protein-coupled galanin receptors bind galanin, a neuropeptide that is widely expressed in the brain, peripheral tissues, and endocrine glands. Three receptors subtypes have been so far identified: GAL1, GAL2, and GAL3. The specific functions of each subtype remains mostly unknown, although galanin is thought to be involved in a variety of neuronal functions such as hormone release and food intake. Galanin is implicated in numerous neurological and psychiatric diseases including Alzheimer's disease, depression, eating disorders, epilepsy and stroke, among many others.

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gi 768040362   1 MCWCPINVLTVLV--AVSPKEMAGKIpnwLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15098  226 ISWLPHHIIHLWVefGDFPLTQASFV---LRITAHCLAYANSCVNPIIYAFLSENFRKAY 282

anaphylatoxin receptors and related G protein-coupled chemokine receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily of G-protein coupled receptors includes anaphylatoxin receptors, formyl peptide receptors (FPR), prostaglandin D2 receptor 2, GPR1, and related chemokine receptors. The anaphylatoxin receptors are a group of G-protein coupled receptors that bind anaphylatoxins. The members of this group include C3a and C5a receptors. The formyl peptide receptors (FPRs) are chemoattractant GPCRs that involved in mediating immune responses to infection. They are expressed mainly on polymorphonuclear and mononuclear phagocytes and bind N-formyl-methionyl peptides (FMLP), which are derived from the mitochondrial proteins of ruptured host cells or invading pathogens. Chemokine receptor-like 1 (also known as chemerin receptor 23) is a GPCR for the chemoattractant adipokine chemerin, also known as retinoic acid receptor responder protein 2 (RARRES2), and for the omega-3 fatty acid derived molecule resolvin E1. Interaction with chemerin induces activation of the MAPK and PI3K signaling pathways leading to downstream functional effects, such as a decrease in immune responses, stimulation of adipogenesis, and angiogenesis. On the other hand, resolvin E1 negatively regulates the cytokine production in macrophages by reducing the activation of MAPK1/3 and NF-kB pathways. Prostaglandin D2 receptor, also known as CRTH2, is a chemoattractant G-protein coupled receptor expressed on T helper type 2 cells that binds prostaglandin D2 (PGD2). PGD2 functions as a mast cell-derived mediator to trigger asthmatic responses and also causes vasodilation. PGD2 exerts its inflammatory effects by binding to two G-protein coupled receptors, the D-type prostanoid receptor (DP) and PD2R2 (CRTH2). PD2R2 couples to the G protein G(i/o) type which leads to a reduction in intracellular cAMP levels and an increase in intracellular calcium. GPR1 is an orphan receptor that can be activated by the leukocyte chemoattractant chemerin, thereby suggesting that some of the anti-inflammatory actions of chemerin may be mediated through GPR1.

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gi 768040362   2 CWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYFiAYFNSCLNAVIYGLLNENFRR 56
Cdd:cd14974  219 CWLPYHVFALLELVAAAGLPEVVLLGLPLATGL-AYFNSCLNPILYVFMGQDFRK 272

angiotesin receptor family and its related G protein-coupled receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes the angiotensin receptors, the bradykinin receptors, apelin receptor as well as putative G-protein coupled receptors (GPR15 and GPR25). Angiotensin II (Ang II), the main effector in the renin-angiotensin system, plays a crucial role in the regulation of cardiovascular homeostasis through its type 1 (AT1) and type 2 (AT2) receptors. Ang II contributes to cardiovascular diseases such as hypertension and atherosclerosis via AT1R activation. Ang II increases blood pressure through Gq-mediated activation of phospholipase C, resulting in phosphoinositide (PI) hydrolysis and increased intracellular calcium levels. Through the AT2 receptor, Ang II counteracts the vasoconstrictor action of AT1R and thereby induces vasodilation, sodium excretion, and reduction of blood pressure. Bradykinins (BK) are pro-inflammatory peptides that mediate various vascular and pain responses to tissue injury through its B1 and B2 receptors. Apelin (APJ) receptor binds the endogenous peptide ligands, apelin and Toddler/Elabela. APJ is an adipocyte-derived hormone that is ubiquitously expressed throughout the human body, and Toddler/Elabela is a short secretory peptide that is required for normal cardiac development in zebrafish. Activation of APJ receptor plays key roles in diverse physiological processes including vasoconstriction and vasodilation, cardiac muscle contractility, angiogenesis, and regulation of water balance and food intake. Orphan receptors, GPR15 and GPR25, share strong sequence homology to the angiotensin II type AT1 and AT2 receptors.

                         10        20        30        40        50        60
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gi 768040362   2 CWCPINVLTVLVAVS------PKEMAGKIPNWLYLAAyFIAYFNSCLNAVIYGLLNENFRR 56
Cdd:cd14985  223 CWLPFHFFKFLDFLAqlgairPCFWELFLDLGLPIAT-CLAFTNSCLNPFIYVFVDRRFRQ 282

neuropeptide Y receptor type 1, 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.

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768040362   1 MCWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRRE 57
Cdd:cd15395  236 VCWLPLNIFNAVFDWNHEAIATCNHNLLFLICHLTAMISTCVNPIFYGFLNKNFQRD 292

endothelin receptors and related proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; This subfamily of G-protein coupled receptors includes endothelin receptors, bombesin receptor subtype 3 (BRS-3), gastrin-releasing peptide receptor (GRPR), neuromedin B receptor (NMB-R), endothelin B receptor-like 2 (ETBR-LP-2), and GRP37. The endothelin receptors and related proteins are members of the seven transmembrane rhodopsin-like G-protein coupled receptor family (class A GPCRs) which activate multiple effectors via different types of G protein.

                         10        20        30        40        50
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gi 768040362   2 CWCPINVLTVLVAVSPKEMAGKIPNWLYLAAY---FIAYFNSCLNAVIYGLLNENFRR 56
Cdd:cd14977  233 CWLPEHISNILRATLYNEVLIDTRSTLDILDLigqFLSFFNSCVNPIALYLLSEPFRR 290

adipokinetic hormone receptor, member of the class A family of seven-transmembrane G protein-coupled receptors; Adipokinetic hormone (AKH) is a lipid-mobilizing hormone that is involved in control of insect metabolism. Generally, AKH behaves as a typical stress hormone by mobilizing lipids, carbohydrates and/or certain amino acids such as proline. Thus, it utilizes the body's energy reserves to fight the immediate stress problems and subdue processes that are less important. Although AKH is known to responsible for regulating the energy metabolism during insect flight, it is also found in insects that have lost its functional wings and predominantly walk for their locomotion. AKH is structurally related to the mammalian gonadotropin-releasing hormone (GnRH) and they share a common ancestor. Both GnRH and AKH receptors are members of the class A of the seven-transmembrane, G-protein coupled receptor (GPCR) superfamily.

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                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 768040362   1 MCWCPINVLTVLVAVSpKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRRE 57
Cdd:cd15382  242 ICWTPYFIMSLWYWFD-RESASKVDPRIQKGLFLFAVSNSCMNPIVYGYFSIDLRRE 297

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

                         10        20        30        40        50
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gi 768040362   1 MCWCPINVLTVLVAVSPKemAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15323  206 VCWFPFFFSYSLYGICRE--ACEVPEPLFKFFFWIGYCNSSLNPVIYTIFNQDFRRSF 261

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

                         10        20        30        40        50
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gi 768040362   1 MCWCPINVLTVLVAVSPKEMAgkIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15324  201 LCWFPFFFTYSLHAVCRKRCG--IPDALFNLFFWIGYCNSSVNPIIYTIFNRDFRKAF 256

somatostatin receptor type 5, 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. SSTR5 is coupled to inward rectifying K channels and phospholipase C, and plays critical roles in growth hormone and insulin secretion. SSTR5 acts as a negative regulator of PDX-1 (pancreatic and duodenal homeobox-1) expression, which is a conserved homeodomain-containing beta cell-specific transcription factor essentially involved in pancreatic development, among many other functions.

                         10        20        30        40        50        60
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gi 768040362   2 CWCPINVLTV--LVAVSPKE--MAGkipnwLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15974  222 CWLPFYMLNIvnLIVILPEEpaFVG-----VYFFVVVLSYANSCANPILYGFLSDNFKQSF 277

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
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gi 768040362   2 CWCPINVLTVLVAVSPKemagKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15051  235 CWFPYFTYFTYRGLCGD----NINETALSVVLWLGYANSALNPILYAFLNRDFRRAF 287

vertebrate gonadotropin-releasing hormone receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; GnRHR, also known as luteinizing hormone releasing hormone receptor (LHRHR), plays an central role in vertebrate reproductive function; its activation by binding to GnRH leads to the release of follicle stimulating hormone (FSH) and luteinizing hormone (LH) from the pituitary gland. GnRHR is expressed predominantly in the gonadotrope membrane of the anterior pituitary as well as found in numerous extrapituitary tissues including lymphocytes, breast, ovary, prostate, and cancer cell lines. There are at least two types of GnRH receptors, GnRHR1 and GnRHR2, which couple primarily to G proteins of the Gq/11 family. GnRHR is closely related to the adipokinetic hormone receptor (AKH), which binds to a lipid-mobilizing hormone that is involved in control of insect metabolism. They share a common ancestor and are members of the class A of the seven-transmembrane, G-protein coupled receptor (GPCR) superfamily.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 768040362   2 CWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRRE 57
Cdd:cd15383  239 CWTPYYLLGLWYWFSPEMLEQTVPESLSHILFLFGLLNACLDPLIYGLFTISFRRG 294

muscarinic acetylcholine receptor GAR-2 and similar proteins, 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
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 768040362   2 CWCPINVLTVLVAVSpkEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRR 56
Cdd:cd15302  212 CWTPYHILATIYGFC--EAPPCVNETLYTISYYLCYMNSPINPFCYALANQQFKK 264

G protein-coupled receptor 25, member of the class A family of seven-transmembrane G protein-coupled receptors; GPR25 is an orphan G-protein coupled receptor that shares strong sequence homology to GPR15 and the angiotensin II receptors. These closely related receptors form a group within the class A G-protein coupled receptors (GPCRs). GPR15 controls homing of T cells, especially FOXP3(+) regulatory T cells, to the large intestine mucosa and thereby mediates local immune homeostasis. Moreover, GRP15-deficient mice were shown to be prone to develop more severe large intestine inflammation. Angiotensin II (Ang II), the main effector in the renin-angiotensin system, plays a crucial role in the regulation of cardiovascular homeostasis through its type 1 (AT1) and type 2 (AT2) receptors.

                         10        20        30        40        50        60
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gi 768040362   3 WCPINVLTVLVAVSPKEMaGKIP-------NWLYLAAYFIAYFNSCLNAVIYGLLNENFRR 56
Cdd:cd15193  218 WLPFNTLKAVRLLLELGG-GVLPchttvaiRQGLTITACLAFVNSCVNPLIYSLLDRHFRR 277

somatostatin receptor type 4, 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. SSTR4 plays a critical role in mediating inflammation. Unlike other SSTRs, SSTR4 subtype is not detected in all pituitary adenomas while it is expressed in the normal human pituitary.

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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768040362   1 MCWCPINVLTVLVAVSPKeMAGKIPNwlylAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15973  222 ICWMPFYVVQLLNLFLPR-LDATVNH----ASLILSYANSCANPILYGFLSDNFRRSF 274

somatostatin receptor type 3, 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. SSTR3 is coupled to inward rectifying potassium channels. SSTR3 plays critical roles in growth hormone secretion, endothelial cell cycle arrest and apoptosis. Furthermore, SSTR3 is expressed in the normal human pituitary and in nearly half of pituitary growth hormone adenomas.

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                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 768040362   1 MCWCPINVLTVLVAVSPKEMAGKIPNwLYLAAYFIAYFNSCLNAVIYGLLNENFRR 56
Cdd:cd15972  223 LCWLPFYALNIVNLVCPLPEEPSLFG-LYFFVVVLSYANSCANPIIYGFLSDNFKQ 277

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

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768040362   1 MCWCPINVLTVLVAVSPkemAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15325  207 LCWLPFFLVMPIGSIFP---AYKPSDTVFKITFWLGYFNSCINPIIYPCSSQEFKKAF 261

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768040362   1 MCWCPINVLtVLVAVSPKEMagkIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd17790  209 LTWTPYNIM-VLVSTFCKDC---VPKTLWELGYWLCYVNSTVNPMCYALCNKSFRDTF 262

complement component 3a anaphylatoxin chemotactic receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; The anaphylatoxin receptors are a group of G-protein coupled receptors which bind anaphylatoxins; members of this group include C3a receptors and C5a receptors. Anaphylatoxins are also known as complement peptides (C3a, C4a and C5a) that are produced from the activation of the complement system cascade. These complement anaphylatoxins can trigger degranulation of endothelial cells, mast cells, or phagocytes, which induce a local inflammatory response and stimulate smooth muscle cell contraction, histamine release, and increased vascular permeability. They are potent mediators involved in chemotaxis, inflammation, and generation of cytotoxic oxygen-derived free radicals. In humans, a single receptor for C3a (C3AR1) and two receptors for C5a (C5AR1 and C5AR2, also known as C5L2 or GPR77) have been identified, but there is no known receptor for C4a.

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                 ....*....|....*....|....*....|....*....|....*....|....*
gi 768040362   1 MCWCPINVLTVLVAVSPKEMAGKIPNWLYLAAYfIAYFNSCLNAVIYGLLNENFR 55
Cdd:cd15115  209 VCWAPYHIIGILSLYGDPPLSKVLMSWDHLSIA-LAYANSCLNPVLYVFMGKDFK 262

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 768040362   1 MCWCPINVLTvLVAVspkeMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15970  224 ICWMPFYVVQ-LVSV----FVGQHDATVSQLSVILGYANSCANPILYGFLSDNFKRSF 276

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

                         10        20        30        40        50        60
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gi 768040362   1 MCWCPINVL----TVLVAVSPKEMAGKIPNWLylaayfiAYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15327  207 LCWFPFFFVlplgSFFPALKPSEMVFKVIFWL-------GYFNSCVNPIIYPCSSKEFKRAF 261

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.

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gi 768040362   2 CWCPINVLTVLVAVSPKEMAGK--IPNWLYLAAYFIAYFNSCLNAVIYGlLNENFRR 56
Cdd:cd15057  242 CWLPFFILNCVLPFCDLRTAQFpcVPDTTFIVFVWLGWANSSLNPIIYA-FNADFRK 297

dopamine 1-like receptor 2 from Drosophila melanogaster and similar proteins, member of the class A family of seven-transmembrane G protein-coupled receptors; G protein-coupled dopamine 1-like receptor 2 is expressed in Drosophila heads and it shows significant sequence similarity with vertebrate and invertebrate dopamine receptors. Although the Drosophila Dop1R2 receptor does not cluster into the D1-like structural group, it does show pharmacological properties similar to D1-like receptors. As shown in vertebrate D1-like receptors, agonist stimulation of Dop1R2 activates adenylyl cyclase to increase cAMP levels and also generates a calcium signal through stimulation of phospholipase C.

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gi 768040362   1 MCWCPINVLTVLVA------VSPKEMAGKIPNWLylaayfiAYFNSCLNAVIYGLLNENFRR 56
Cdd:cd15067  206 LCWLPFFVTNILIGfcpsncVSNPDILFPLVTWL-------GYINSGMNPIIYACSSRDFRR 260

histamine receptor subtype H4R, member of the class A family of seven-transmembrane G protein-coupled receptors; This group includes histamine subtype H4R, a member 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
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 768040362   1 MCWCPINVLTVLVAVSPKemaGKIPNWlYLAAYFIAYFNSCLNAVIYGLLNENFRREYWTIF 62
Cdd:cd15295  209 ICWAPYSLFTIIRAACEK---HRGSPW-YNFAFWLQWFNSFINPFLYPLCHKRFRKAFLKIF 266

relaxin-3 like peptide receptors, member of the class A family of seven-transmembrane G protein-coupled receptors; This G protein-coupled receptor subfamily is composed of the relaxin-3 like peptide receptors, RNL3R1 and RNL3R2, and similar proteins. The relaxin-3 like peptide family includes relaxin-1, -2, -3, as well as insulin-like (INSL) peptides 3 to 6. RNL3/relaxin-3 and INSL5 are the endogenous ligands for RNL3R1 and RNL3R2, respectively. RNL3R1, also called GPCR135 or RXFP3, is predominantly expressed in the brain and is implicated in stress, anxiety, feeding, and metabolism. Insulin-like peptide 5 (INSL5), the endogenous ligand for RNL3R2 (also called GPCR142 or RXFP4), plays a role in fat and glucose metabolism. INSL5 is highly expressed in human rectal and colon tissues. Both RNL3R1 and RNL3R2 signal through G(i) protein and inhibit adenylate cyclase, thereby inhibit cAMP accumulation. RNL3R1 is shown to activate Erk1/2 signaling pathway.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 768040362   1 MCWCPINVLTV------LVAVSPKEMAGKIPNWLYLAAYFIAYFNSCLNAVIYGLLNENFR 55
Cdd:cd14976  227 ICWLPNQALSLwsalikFDDVPFSDAFFAFQTYAFPVAICLAHSNSCLNPVLYCLVRREFR 287

DNA polymerase III subunits gamma and tau; Provisional

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768040362 261 PATSHAEPTTADYPKPATTSHPKPTAADNPElSASHCPEIPAIAHPVSDDSDLPESASSPAAGPTKPAASQLESDTIADL 340
Cdd:PRK14950 368 PAKPTAAAPSPVRPTPAPSTRPKAAAAANIP-PKEPVRETATPPPVPPRPVAPPVPHTPESAPKLTRAAIPVDEKPKYTP 446

                 ....
gi 768040362 341 PDPT 344
Cdd:PRK14950 447 PAPP 450

sphingosine-1-phosphate receptor subtype 3 (S1PR3 or S1P3), also called endothelial differentiation gene 3 (Edg3), member of the class A family of seven-transmembrane G protein-coupled receptors; The endothelial differentiation gene (Edg) family of G-protein coupled receptors binds 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). The Edg receptors couple and activate at least three different G protein subtypes including G(i/o), G(q/11), and G(12/13).

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 768040362   2 CWCPINVLTVL-VAVSPKEMAgkipnWLYLAAYFI--AYFNSCLNAVIYGLLNENFRREY 58
Cdd:cd15345  216 CWSPLFILLLIdVACEVKQCP-----ILYKADWFIalAVLNSAMNPIIYTLASKEMRRAF 270