extracellular domain of nicotinic acetylcholine receptor subunit beta-like found in protostomia; This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit beta-like in organisms that include arthropods, mollusks, annelid worms, and flat worms, and have their cholinergic system limited to the central nervous system. C. elegans genome encodes 29 acetylcholine receptor subunits, of which the levamisole-sensitive receptor alpha-subunits (L-AChR), UNC-38, UNC-63, and LEV-8, form heteromers with the two non-alpha (also known as beta-like) subunits, UNC-29 and LEV-1 found in this subfamily. This receptor functions as the main excitatory postsynaptic receptor at neuromuscular junctions, indicating that many are expressed in neurons. In insects, the receptors supply fast synaptic excitatory transmission and represent a major target for several insecticides. In Drosophila, ten exclusively neuronal nAChR subunits have been identified, Dalpha1-Dalpha7 and Dbeta1-Dbeta3, and various combinations of these subunits and mutations are key to nAChR function. Dbeta1 subunits in dopaminergic neurons play a role in acute locomotor hyperactivity caused by nicotine in male Drosophila. Mutations of Dbeta2 or Dalpha1 nAChR subunits in Drosophila strains have significantly lower neonicotinoid-stimulated release, but no changes in nicotine-stimulated release; they are highly resistant to the neonicotinoids nitenpyram and imidacloprid. This family also includes a novel nAChR found in Aplysia bag cell neurons (neuroendocrine cells that control reproduction) which is a cholinergic ionotropic receptor that is both, nicotine insensitive and acetylcholine sensitive.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  29 DEERLMVDVFRGYNSLIQPVRNSSElPLIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVS 108
Cdd:cd19032   1 DEERLVRDLFRGYNYLIRPVRNMSE-PVEVNFGLALIQLINVDEKNQIMKTNVWLTMYWNDYQLKWDPADYGGIKVIRVP 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 109 PDKVWLPDIVLFNNADGNYEVSFMCNVVINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLEFV 188
Cdd:cd19032  80 PDKVWKPDIVLFNNADGNYEVSYKSNVLIYSTGEVLWVPPAIYKSSCTIDVEYFPFDQQECEMKFGSWTFNGDEVSLDLY 159

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 17509393 189 QA-ELVDVSEYSASSIWDVIDVPASLVNK------RSRIEFQVRIRRKT 230
Cdd:cd19032 160 NNkKFVDLSDYWKSGTWDIIDVPGQLVNKddagptETDIIFKIKIRRKT 208

extracellular domain of nicotinic acetylcholine receptor subunit beta-like found in protostomia; This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit beta-like in organisms that include arthropods, mollusks, annelid worms, and flat worms, and have their cholinergic system limited to the central nervous system. C. elegans genome encodes 29 acetylcholine receptor subunits, of which the levamisole-sensitive receptor alpha-subunits (L-AChR), UNC-38, UNC-63, and LEV-8, form heteromers with the two non-alpha (also known as beta-like) subunits, UNC-29 and LEV-1 found in this subfamily. This receptor functions as the main excitatory postsynaptic receptor at neuromuscular junctions, indicating that many are expressed in neurons. In insects, the receptors supply fast synaptic excitatory transmission and represent a major target for several insecticides. In Drosophila, ten exclusively neuronal nAChR subunits have been identified, Dalpha1-Dalpha7 and Dbeta1-Dbeta3, and various combinations of these subunits and mutations are key to nAChR function. Dbeta1 subunits in dopaminergic neurons play a role in acute locomotor hyperactivity caused by nicotine in male Drosophila. Mutations of Dbeta2 or Dalpha1 nAChR subunits in Drosophila strains have significantly lower neonicotinoid-stimulated release, but no changes in nicotine-stimulated release; they are highly resistant to the neonicotinoids nitenpyram and imidacloprid. This family also includes a novel nAChR found in Aplysia bag cell neurons (neuroendocrine cells that control reproduction) which is a cholinergic ionotropic receptor that is both, nicotine insensitive and acetylcholine sensitive.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  29 DEERLMVDVFRGYNSLIQPVRNSSElPLIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVS 108
Cdd:cd19032   1 DEERLVRDLFRGYNYLIRPVRNMSE-PVEVNFGLALIQLINVDEKNQIMKTNVWLTMYWNDYQLKWDPADYGGIKVIRVP 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 109 PDKVWLPDIVLFNNADGNYEVSFMCNVVINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLEFV 188
Cdd:cd19032  80 PDKVWKPDIVLFNNADGNYEVSYKSNVLIYSTGEVLWVPPAIYKSSCTIDVEYFPFDQQECEMKFGSWTFNGDEVSLDLY 159

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 17509393 189 QA-ELVDVSEYSASSIWDVIDVPASLVNK------RSRIEFQVRIRRKT 230
Cdd:cd19032 160 NNkKFVDLSDYWKSGTWDIIDVPGQLVNKddagptETDIIFKIKIRRKT 208

Cation transporter family protein; The Ligand-gated Ion Channel (LIC) Family of Neurotransmitter Receptors TC 1.A.9)Members of the LIC family of ionotropic neurotransmitter receptors are found only in vertebrate and invertebrate animals. They exhibit receptor specificity for (1)acetylcholine, (2) serotonin, (3) glycine, (4) glutamate and (5) g-aminobutyric acid (GABA). All of these receptor channels are probably hetero- orhomopentameric. The best characterized are the nicotinic acetyl-choline receptors which are pentameric channels of a2bgd subunit composition. All subunits arehomologous. The three dimensional structures of the protein complex in both the open and closed configurations have been solved at 0.9 nm resolution.The channel protein complexes of the LIC family preferentially transport cations or anions depending on the channel (e.g., the acetylcholine receptors are cationselective while glycine receptors are anion selective). [Transport and binding proteins, Cations and iron carrying compounds]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393     6 LSWILVLSVVIFLVIINTINASDDEERLMVD-VFRGYNSLIQPVRNSSelPLIVKMALQLVLLINVDEKDQVMHTNVWLT 84
Cdd:TIGR00860   6 LALLLFASLAAVSLAGNAKSNLKEVERKLLDeLLKNYDARVRPVFGGP--PVTVSFNLFLRSIMDVDEKNMDYTTNIWLR 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393    85 LQWHDFQMKWNPVNYGEIKQIRVSPDKVWLPDIVLFNNADGNYEVSFMCNVVINHKGD--MLWVPPAIYKSSCIIDVEFF 162
Cdd:TIGR00860  84 QEWTDERLQWNPEEYPGVTLVRTPDDSIWVPDIFFYNEKDARFHGITMTNVLVRIHPNgsVLYSPRITLTLACPMDLRNF 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393   163 PFDEQVCTLVFGSWTYNENEIKLEFVQAELVDVSEYSASSI--WDVIDVPASLVNKR-------SRIEFQVRIRRKTLFY 233
Cdd:TIGR00860 164 PFDVQNCSLKFESWGYTTNDIKLEWKEQGAVQVDDSLFISLpeFELLGVYGTRYCTSetntgeyPCLTFSFVLRRRPLYY 243

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393   234 TVVLIIPTVLMAFLSMAVFFLPTD-SGEKITLTISVLLSIVVFLLLVSKILPPTSSTiPLMAKYLLLTFVLNVITILVTV 312
Cdd:TIGR00860 244 LLQLYIPSILIVILSWVSFWLPADaSGARVSLGITTLLTMTTFSSGVRESLPAVSYV-KAIDVYFAVCMAFVFLALLETA 322

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393   313 IIINVYFRGPrthrmPQWVRVVFLQFLPKLVCMKRPksasersavrSGMAQLPGVGQFTLSPSAHHPLCPSADDRTTTIR 392
Cdd:TIGR00860 323 FVNYVHHKDP-----AQGKRHLLLERCAWRLCKQEP----------GEDYRRPALDHASLSSVEMRAKDGGRGLESPTER 387

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17509393   393 NTASNetsAYYPLSTD-ALRAIDAIEYITEHLKRDEQHKSFRDDWKYVAMIIDRLLLYVFFGITVGGTCGILFSA 466
Cdd:TIGR00860 388 QRLLH---SPPPAEGDlDLAGILEEVRIAHRFRKRDESEEVVRDWKFRAKVIDKLSRMAFPLAFLLFNIGYWMSY 459

transmembrane domain of nicotinic acetylcholine receptor (nAChR); This family contains transmembrane (TM) domain of the nicotinic acetylcholine receptor (nAChR). The transmembrane region consists of four transmembrane-spanning alpha-helical segments (M1-M4) that are linked by loops. The intracellular loop that links M1 and M2 determines the ion selectivity of the channel. nAChR is found in high concentrations at the nerve-muscle synapse, where it mediates fast chemical transmission of electrical signals in response to the endogenous neurotransmitter acetylcholine (ACh) released from the nerve terminal into the synaptic cleft. Thus far, seventeen nAChR subunits have been identified, including ten alpha subunits, four beta subunits and one gamma, delta, and epsilon subunit each, all found on the cell membrane that non-selectively conducts cations (Na+, K+, Ca++). These nAChR subunits combine in several different ways to form functional nAChR subtypes which are broadly categorized as either muscle subtype located at the neuromuscular junction or neuronal subtype that are found on neurons and on other cell types throughout the body. The muscle type of nAChRs are formed by the alpha1, beta1, gamma, delta, and epsilon subunits while the neuronal type are composed of nine alpha subunits and three beta subunits, which combine in various permutations and combinations to form functional receptors. Among various subtypes of neuronal nAChRs, the homomeric alpha7 and the heteromeric alpha4beta2 receptors are the main subtypes widely distributed in the brain and implicated in the pathophysiology of neurodevelopmental disorders such as schizophrenia and autism and neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Among subtypes of muscle nAChRs, the heteromeric subunits (alpha1)2, beta, gamma, and delta in fetal muscle, and the gamma subunit replaced by epsilon in adult muscle have been implicated in congenital myasthenic syndromes and multiple pterygium syndromes due to various mutations. This family also includes alpha- and beta-like nAChRs found in protostomia.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 231 LFYTVVLIIPTVLMAFLSMAVFFLPTDSGEKITLTISVLLSIVVFLLLVSKILPPTSSTIPLMAKYLLLTFVLNVITILV 310
Cdd:cd19064   1 LFYTVNLIIPCVLISFLTVLVFYLPADSGEKITLSISVLLALTVFLLLIAEIIPPTSLVVPLIGKYLLFTMILVTLSIIV 80

                        90
                ....*....|
gi 17509393 311 TVIIINVYFR 320
Cdd:cd19064  81 TVIVLNVHHR 90

extracellular domain of nicotinic acetylcholine receptor subunit beta-like found in protostomia; This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit beta-like in organisms that include arthropods, mollusks, annelid worms, and flat worms, and have their cholinergic system limited to the central nervous system. C. elegans genome encodes 29 acetylcholine receptor subunits, of which the levamisole-sensitive receptor alpha-subunits (L-AChR), UNC-38, UNC-63, and LEV-8, form heteromers with the two non-alpha (also known as beta-like) subunits, UNC-29 and LEV-1 found in this subfamily. This receptor functions as the main excitatory postsynaptic receptor at neuromuscular junctions, indicating that many are expressed in neurons. In insects, the receptors supply fast synaptic excitatory transmission and represent a major target for several insecticides. In Drosophila, ten exclusively neuronal nAChR subunits have been identified, Dalpha1-Dalpha7 and Dbeta1-Dbeta3, and various combinations of these subunits and mutations are key to nAChR function. Dbeta1 subunits in dopaminergic neurons play a role in acute locomotor hyperactivity caused by nicotine in male Drosophila. Mutations of Dbeta2 or Dalpha1 nAChR subunits in Drosophila strains have significantly lower neonicotinoid-stimulated release, but no changes in nicotine-stimulated release; they are highly resistant to the neonicotinoids nitenpyram and imidacloprid. This family also includes a novel nAChR found in Aplysia bag cell neurons (neuroendocrine cells that control reproduction) which is a cholinergic ionotropic receptor that is both, nicotine insensitive and acetylcholine sensitive.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  29 DEERLMVDVFRGYNSLIQPVRNSSElPLIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVS 108
Cdd:cd19032   1 DEERLVRDLFRGYNYLIRPVRNMSE-PVEVNFGLALIQLINVDEKNQIMKTNVWLTMYWNDYQLKWDPADYGGIKVIRVP 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 109 PDKVWLPDIVLFNNADGNYEVSFMCNVVINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLEFV 188
Cdd:cd19032  80 PDKVWKPDIVLFNNADGNYEVSYKSNVLIYSTGEVLWVPPAIYKSSCTIDVEYFPFDQQECEMKFGSWTFNGDEVSLDLY 159

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 17509393 189 QA-ELVDVSEYSASSIWDVIDVPASLVNK------RSRIEFQVRIRRKT 230
Cdd:cd19032 160 NNkKFVDLSDYWKSGTWDIIDVPGQLVNKddagptETDIIFKIKIRRKT 208

extracellular domain of nicotinic acetylcholine receptor; This family contains the extracellular domain of nicotinic acetylcholine receptor (nAChR), a member of the pentameric "Cys-loop" superfamily of transmitter-gated ion channels. nAChR is found in high concentrations at the nerve-muscle synapse, where it mediates fast chemical transmission of electrical signals in response to the endogenous neurotransmitter acetylcholine (ACh) released from the nerve terminal into the synaptic cleft. Thus far, seventeen nAChR subunits have been identified, including ten alpha subunits, four beta subunits, and one gamma, delta, and epsilon subunit each, all found on the cell membrane that non-selectively conducts cations (Na+, K+, Ca++). These nAChR subunits combine in several different ways to form functional nAChR subtypes which are broadly categorized as either muscle subtype located at the neuromuscular junction or neuronal subtype that are found on neurons and on other cell types throughout the body. The muscle type of nAChRs are formed by the alpha1, beta1, gamma, delta, and epsilon subunits while the neuronal type are composed of nine alpha subunits and three beta subunits, which combine in various permutations and combinations to form functional receptors. Among various subtypes of neuronal nAChRs, the homomeric alpha7 and the heteromeric alpha4beta2 receptors are the main subtypes widely distributed in the brain and implicated in the pathophysiology of neurodevelopmental disorders such as schizophrenia and autism and neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Among subtypes of muscle nAChRs, the heteromeric subunits (alpha1)2, beta, gamma, and delta in fetal muscle, and the gamma subunit replaced by epsilon in adult muscle have been implicated in congenital myasthenic syndromes and multiple pterygium syndromes due to various mutations. This family also includes alpha- and beta-like nAChRs found in protostomia.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  56 LIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVSPDKVWLPDIVLFNNADGNYEVSFMCNV 135
Cdd:cd18997   1 VNVTFGLTLRQIIDVDEKNQVLTTNVWLRQEWNDERLTWNPSDYGGITSIRVPSDKIWLPDIVLYNNADGDFDSSYKTNV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 136 VINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLEFVQAElVDVSEYSASSIWDVIDVPASLVN 215
Cdd:cd18997  81 IVYSDGTVTWLPPAIFKSSCKIDVTYFPFDEQNCTLKFGSWTYDGSELDLQLKSDT-VDLSDYIENGEWDLLGAPAKRNV 159

                       170       180
                ....*....|....*....|..
gi 17509393 216 KR--------SRIEFQVRIRRK 229
Cdd:cd18997 160 VKysccpepyPDVTFTIHIRRK 181

Cation transporter family protein; The Ligand-gated Ion Channel (LIC) Family of Neurotransmitter Receptors TC 1.A.9)Members of the LIC family of ionotropic neurotransmitter receptors are found only in vertebrate and invertebrate animals. They exhibit receptor specificity for (1)acetylcholine, (2) serotonin, (3) glycine, (4) glutamate and (5) g-aminobutyric acid (GABA). All of these receptor channels are probably hetero- orhomopentameric. The best characterized are the nicotinic acetyl-choline receptors which are pentameric channels of a2bgd subunit composition. All subunits arehomologous. The three dimensional structures of the protein complex in both the open and closed configurations have been solved at 0.9 nm resolution.The channel protein complexes of the LIC family preferentially transport cations or anions depending on the channel (e.g., the acetylcholine receptors are cationselective while glycine receptors are anion selective). [Transport and binding proteins, Cations and iron carrying compounds]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393     6 LSWILVLSVVIFLVIINTINASDDEERLMVD-VFRGYNSLIQPVRNSSelPLIVKMALQLVLLINVDEKDQVMHTNVWLT 84
Cdd:TIGR00860   6 LALLLFASLAAVSLAGNAKSNLKEVERKLLDeLLKNYDARVRPVFGGP--PVTVSFNLFLRSIMDVDEKNMDYTTNIWLR 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393    85 LQWHDFQMKWNPVNYGEIKQIRVSPDKVWLPDIVLFNNADGNYEVSFMCNVVINHKGD--MLWVPPAIYKSSCIIDVEFF 162
Cdd:TIGR00860  84 QEWTDERLQWNPEEYPGVTLVRTPDDSIWVPDIFFYNEKDARFHGITMTNVLVRIHPNgsVLYSPRITLTLACPMDLRNF 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393   163 PFDEQVCTLVFGSWTYNENEIKLEFVQAELVDVSEYSASSI--WDVIDVPASLVNKR-------SRIEFQVRIRRKTLFY 233
Cdd:TIGR00860 164 PFDVQNCSLKFESWGYTTNDIKLEWKEQGAVQVDDSLFISLpeFELLGVYGTRYCTSetntgeyPCLTFSFVLRRRPLYY 243

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393   234 TVVLIIPTVLMAFLSMAVFFLPTD-SGEKITLTISVLLSIVVFLLLVSKILPPTSSTiPLMAKYLLLTFVLNVITILVTV 312
Cdd:TIGR00860 244 LLQLYIPSILIVILSWVSFWLPADaSGARVSLGITTLLTMTTFSSGVRESLPAVSYV-KAIDVYFAVCMAFVFLALLETA 322

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393   313 IIINVYFRGPrthrmPQWVRVVFLQFLPKLVCMKRPksasersavrSGMAQLPGVGQFTLSPSAHHPLCPSADDRTTTIR 392
Cdd:TIGR00860 323 FVNYVHHKDP-----AQGKRHLLLERCAWRLCKQEP----------GEDYRRPALDHASLSSVEMRAKDGGRGLESPTER 387

                         410       420       430       440       450       460       470
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 17509393   393 NTASNetsAYYPLSTD-ALRAIDAIEYITEHLKRDEQHKSFRDDWKYVAMIIDRLLLYVFFGITVGGTCGILFSA 466
Cdd:TIGR00860 388 QRLLH---SPPPAEGDlDLAGILEEVRIAHRFRKRDESEEVVRDWKFRAKVIDKLSRMAFPLAFLLFNIGYWMSY 459

extracellular domain of nicotinic acetylcholine receptor subunit beta 2 (CHRNB2); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit beta 2 (beta2), encoded by the CHRNB2 gene. The most abundant nicotinic subtype in the human brain is alpha4beta2 receptor which is known to assemble in two functional subunit stoichiometries, (alpha4)3(beta2)2 and (alpha4)2(beta2)3, the latter having a much higher affinity for both acetylcholine and nicotine. This subtype is implicated in the pathophysiology of neurodevelopmental disorders such as schizophrenia and autism, and neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. Thus, pharmacological ligands targeting this subtype have been researched and developed as a treatment approach implicated in these diseases. They include agonists such as varenicline and cytisine used as smoking cessation aids, as well as positive allosteric modulators (PAMs) such as desformylflustrabromine (dFBr), which are ligands that bind to nicotinic receptors at sites other than the orthosteric site where acetylcholine binds, and are not able to act as agonists on nAChR.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  41 YNSLIQPVRNSSELpLIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVSPDKVWLPDIVLF 120
Cdd:cd19025  12 YNKLIRPATNGSQL-VTVQLMVSLAQLISVHEREQIMTTNVWLTQEWEDYRLTWDPAEFDNMKKVRLPSKHIWLPDVVLY 90

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 121 NNADGNYEVSFMCNVVINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLeFVQAELVDVSEYSA 200
Cdd:cd19025  91 NNADGMYEVSFYSNAVVSYDGSIFWLPPAIYKSACKIEVKHFPFDQQNCTLKFRSWTYDRTEIDL-VLRSDVASLDDFTP 169

                       170
                ....*....|
gi 17509393 201 SSIWDVIDVP 210
Cdd:cd19025 170 SGEWDIVALP 179

extracellular domain of nicotinic acetylcholine receptor subunit alpha 3 (CHRNA3); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit alpha 3 (alpha3), encoded by the CHRNA3 gene, and likely plays a role in neurotransmission. The alpha3 subunit is expressed in the aorta and macrophages, and may play a regulatory role in the process of vascular inflammation. One of the most broadly expressed subtype is the alpha3beta4 nAChR, also known as the ganglion-type nicotinic receptor, located in the autonomic ganglia and adrenal medulla, where activation yields post- and/or presynaptic excitation, mainly by increased Na+ and K+ permeability. The exact pentameric stochiometry of alpha3beta4 receptor is not known and functional assemblies with varying subunit stoichiometries are possible. Alpha4 plays a pivotal role in regulating the inflammatory responses in endothelial cells and macrophages, via mechanisms involving the modulations of multiple cell signaling pathways. Polymorphisms in this gene (CHRNA3) have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  30 EERLMVDVFRGYNSLIQPVRNSSElPLIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVSP 109
Cdd:cd19016   1 EHRLFERLFEDYNEIIRPVANVSD-PVIIQFEVSMSQLVKVDEVNQIMETNLWLKHIWNDYKLKWNPSDYGGAEFMRVPA 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 110 DKVWLPDIVLFNNADGNYEVSFMCNVVINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLEFVQ 189
Cdd:cd19016  80 EKIWKPDIVLYNNAVGDFQVDDKTKALLKYTGEVTWIPPAIFKSSCKIDVTYFPFDYQNCTMKFGSWSYDKAKIDLVLIG 159

                       170       180
                ....*....|....*....|.
gi 17509393 190 AElVDVSEYSASSIWDVIDVP 210
Cdd:cd19016 160 SS-MNLKDYWESGEWAIIKAP 179

extracellular domain of nicotinic acetylcholine receptor subunit beta 1 (CHRNB1); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit beta 1 (beta1), encoded by the CHRNB1 gene. It is a muscle type subunit found predominantly in the neuromuscular junction (NMJ), but also in other tissues and cell lines such as adrenal glands, carcinomas, brain, and lung. Simultaneous mRNA and protein expression of beta1 nAChR subunit is present in human placenta and skeletal muscle. The beta1 nAChR subunit forms a heteropentamer with either (alpha1)2, gamma and delta subunits in embryonic type or (alpha1)2, epsilon and delta subunits in adult type receptors. nAChRs containing beta1 subunits have been attributed to efficient clustering and anchoring of the receptors to the cytoskeleton which is important for formation of synapses in the NMJ. Mutations in the transmembrane domain region of this gene are associated with slow-channel congenital myasthenic syndrome (CMS).

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  30 EERLMVDVFRGYNSLIQPVRNSSElPLIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVSP 109
Cdd:cd19024   1 EGQLLEKLFENYNPKVRPARTVGD-RVVVSVGLTLAQLISLNEKNEEMTTKVYLDLEWTDYRLSWDPAEYDGIDSLRITS 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 110 DKVWLPDIVLFNNADGNYEVSFMCNVVINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLEF-- 187
Cdd:cd19024  80 DSVWLPDIVLMNNNDGNFDVALDVNVLVSSDGSVRWHPPAIYRSSCSIEVTYFPFDWQNCSMVFRSYTYDSSEVSLQHgl 159

                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 17509393 188 ------VQAELVDVSEYSASSIWDVIDVPASLVNK-----RSRIEFQVRIRRK 229
Cdd:cd19024 160 dpdgkeLQEIVIHENTFIENGQWSIEHKPSRKNQLpgdplYEDITFYLIIRRK 212

extracellular domain (LBD) of cationic Cys-loop neurotransmitter-gated ion channels; This superfamily contains the extracellular domain (ECD) of cationic Cys-loop neurotransmitter-gated ion channels, which include nicotinic acetylcholine receptor (nAChR), serotonin 5-hydroxytryptamine receptor (5-HT3), and zinc-activated ligand-gated ion channel (ZAC) receptor. These ligand-gated ion channels (LGICs) are found across metazoans and have close homologs in bacteria. They are vital for communication throughout the nervous system. nAChR is a non-selective cation channel that is permeable to Na+ and K+, and some subunit combinations are also permeable to Ca2+. Na+ enters and K+ exits to allow net flow of positively charged ions inward. 5-HT3, a cation-selective channel, binds serotonin and is permeable to Na+, K+, and Ca2+. It mediates neuronal depolarization and excitation within the central and peripheral nervous systems. ZAC forms an ion channel gated by Zn2+, Cu2+, and H+ and is non-selectively permeable to monovalent cations. However, the role of ZAC in Zn2+, Cu2+, and H+ signaling require is as yet unknown.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  56 LIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVSPDKVWLPDIVLFNNADGNYEVSFMC-N 134
Cdd:cd18989   1 VNVNVSFSLYSILDLDEVEQTLTLSGWLTLTWTDERLTWNPSDYGGITSIVVPSSEIWTPDIVLYNSVDSLDLLGDSNtL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 135 VVINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLEFVQAElVDVSEYSASSIWDVIDVPASLV 214
Cdd:cd18989  81 VRVSSDGTVTWVPPGVLTTSCDIDVTYFPFDTQTCSLRFGSWSYTTDEINLTPSSNG-VDLEDYEENGEWELLSTSVSRE 159

                       170       180
                ....*....|....*....|.
gi 17509393 215 NKR------SRIEFQVRIRRK 229
Cdd:cd18989 160 EDKycnetySELTFTITLKRR 180

extracellular domain of nicotinic acetylcholine receptor subunit alpha 1 (CHRNA1); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit alpha 1 (alpha1), encoded by the CHRNA1 gene. These muscle type nicotinic subunits form heteropentamers with other nAChR subunits, most broadly expressed as combination of two alpha1, beta1, delta, and epsilon subunits in mature muscles, and of two alpha1, beta1, delta, and gamma in embryonic cells. The alpha1 subunit in human nAChR is the primary target of Myasthenia gravis antibodies that disrupt communication between the nervous system and the muscle, causing chronic muscle weakness.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  28 DDEERLMVDVFRGYNSLIQPVRNSSElPLIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRV 107
Cdd:cd19014   1 EHETRLVADLFKNYNKVVRPVEHHKD-FVVVTVGLQLIQLINVDEVNQIVTTNVRLKQQWIDVNLKWNPDDYGGIKKIRI 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 108 SPDKVWLPDIVLFNNADGNYEVSFMCNVVINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLEf 187
Cdd:cd19014  80 PSSDIWRPDLVLYNNADGDFAIVKETKVLLEYTGKITWTPPAIFKSYCEIIVTHFPFDQQNCSMKLGTWTYDGTLVVIN- 158

                       170
                ....*....|....*..
gi 17509393 188 VQAELVDVSEYSASSIW 204
Cdd:cd19014 159 PESDRPDLSNFMESGEW 175

extracellular domain of nicotinic acetylcholine receptor subunit alpha 5 (CHRNA5); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit alpha 5 (alpha5), encoded by the CHRNA5 gene, which is part of the CHRNA5/A3/B4 gene cluster. Polymorphisms in this gene cluster have been identified as risk factors for nicotine dependence, lung cancer, chronic obstructive pulmonary disease, alcoholism, and peripheral arterial disease. A loss-of-function polymorphism in CHRNA5 is strongly linked to nicotine abuse and schizophrenia; the alpha5 nAChR subunit is strategically situated in the prefrontal cortex (PFC), where a loss-of-function in this subunit may contribute to cognitive disruptions in both disorders. Alpha5 forms heteropentamers with alpha3beta2 or alpha3beta4 nAChRs which increases the calcium permeability of the resulting receptors possibly playing significant roles in the initiation of ACh-induced signaling cascades under normal and pathological condition. Acetylcholine (ACh) release and signaling via alpha4/beta2 nAChR subunits plays a central role in the control of attention, but a subset of these oligomers also contains alpha5 subunit. A strong association is seen between a CHRNA5 polymorphism and the risk of lung cancer, especially in smokers.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  30 EERLMVDVFRGYNSLIQPVRNSSElPLIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVSP 109
Cdd:cd19018   3 EDRLFKHLFQDYQRWVRPVEHLND-TIKIKFGLAISQLVDVDEKNQLMTTNVWLKQEWIDVKLRWNPDDYAGITSIRVPS 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 110 DKVWLPDIVLFNNADGNYEVSfMCNVVINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLeFVQ 189
Cdd:cd19018  82 DSIWIPDIVLYDNADGRFEGT-STKTVVRYDGTITWTPPANYKSSCTIDVTFFPFDLQNCSMKFGSWTYDGSQVDI-ILE 159

                       170       180
                ....*....|....*....|....*...
gi 17509393 190 AELVDVSEYSASSIWDVIDVPASLVNKR 217
Cdd:cd19018 160 DYDVDKRDFFDNGEWEIVSATGSKGNRT 187

extracellular domain of neuronal acetylcholine receptor subunit alpha 7 (CHRNA7); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit alpha 7 (alpha7), encoded by the CHRNA7 gene. Alpha7 subunits form a homo-pentameric channel, displays marked permeability to calcium ions and is a major component of brain nicotinic receptors that are blocked by, and highly sensitive to, alpha-bungarotoxin. This protein is ubiquitously expressed in both the central nervous system and in the periphery, in several tissues, including adrenal, small intestine, testis, and stomach. CHRNA7 is located in a region identified as a major susceptibility locus for juvenile myoclonic epilepsy and a chromosomal location involved in the genetic transmission of schizophrenia. It is also genetically linked to other disorders with cognitive deficits, including bipolar disorder, ADHD, Alzheimer's disease, and Rett syndrome. An evolutionarily recent partial duplication of CHRNA7 on chromosome 15 forms a new gene, CHRFAM7A or FAM7A, which encodes the protein dup-alpha7. This protein assembles with alpha7 subunits, results in fewer binding sites and is a dominant negative regulator of alpha7 nAChR function.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  55 PLIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVSPDKVWLPDIVLFNNADGNYEVSFMCN 134
Cdd:cd19020   1 PLTVYFSLSLMQIMDVDEKNQVLTTNIWLQMYWTDHYLQWNASEYPGVKNVRFPDGQIWKPDILLYNSADERFDATFHTN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 135 VVINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLEFVQAelvDVSEYSASSIWDVIDVPAslv 214
Cdd:cd19020  81 VLVNSSGHCQYLPPGIFKSSCYIDVRWFPFDVQKCNLKFGSWTYGGWSLDLQMQEA---DISGYISNGEWDLVGVPG--- 154

                       170       180
                ....*....|....*....|....*..
gi 17509393 215 nKRSR------------IEFQVRIRRK 229
Cdd:cd19020 155 -KRNEkfyecckepypdVTFTVTMRRR 180

extracellular domain of neuronal acetylcholine receptor subunit alpha 4 (CHRNA4); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit alpha 4 (alpha4), encoded by the CHRNA4 gene. Alpha4 forms a functional nAChR by interacting with either nAChR beta2 or beta4 subunits. Alpha4beta2, the major heteropentameric nAChR in the brain, exists in two isoforms, (alpha4)3(beta2)2 and (alpha4)2(beta2)3, with the latter believed to constitute the majority of alpha4beta2 nAChR in the cortex. Both isoforms contain two canonical alpha4:beta2 ACh-binding sites with either low or high ACh sensitivity. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene (CHRNA4) cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene may provide protection against nicotine addiction.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  56 LIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVSPDKVWLPDIVLFNNADGNYEVSFMCNV 135
Cdd:cd19017   1 VLVRFGLSIAQLIDVDEKNQMMTTNVWVKQEWHDYKLRWDPADYENVTSIRIPSELIWRPDIVLYNNADGDFAVTHLTKA 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 17509393 136 VINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLEFVQAElVDVSEYSASSIWDVID 208
Cdd:cd19017  81 HLFHDGRVQWTPPAIYKSSCSIDVTFFPFDQQNCTMKFGSWTYDKAKIDLVSMHSR-VDQLDFWESGEWVIVD 152

extracellular domain of neuronal acetylcholine receptor subunit alpha 9 (CHRNA9); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit alpha 9 (alpha9), encoded by the CHRNA9 gene. This protein is involved in cochlea hair cell development and is also expressed in the outer hair cells (OHCs) of the adult cochlea as well as in keratinocytes, the pituitary gland, B-cells, and T-cells. Mammalian alpha9 subunits can form functional homomeric alpha9 receptors as well as the heteromeric alpha9alpha10 receptors, the latter being atypical since the heteromeric alpha9alpha10 receptor is composed only of alpha subunits compared to nAChRs typically assembled from alpha and beta subunits. A stoichiometry of (alpha9)2(alpha10)3 has been determined for the rat recombinant receptor. The alpha9alpha10 nAChR is an important therapeutic target for pain; selective block of alpha9alpha10 nicotinic acetylcholine receptors by the conotoxin RgIA has been shown to be analgesic in an animal model of nerve injury pain, and accelerates recovery of nerve function after injury, possibly through immune/inflammatory-mediated mechanisms. CHRNA9 polymorphisms are associated with non-small cell lung cancer, and effect of a particular SNP (rs73229797) and passive smoking exposure on risk of breast malignancy has been observed.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  31 ERLMVDVFRGYNSLIQPVRNSSELpLIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVSPD 110
Cdd:cd19022   2 QKLFNDLFEDYSNALRPVEDTDKV-LNVTLQITLSQIKDMDERNQILTAYLWIRQSWYDAYLKWDRDEYDGLDSIRIPSN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393 111 KVWLPDIVLFNNADGNYEVSFMCNVVINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLeFVQA 190
Cdd:cd19022  81 LVWRPDIVLYNKADDEFSEPVNTNVVLRYDGKITWDAPAITKSSCVVDVSYFPFDNQQCNLTFGSWTYNGNQVDI-INAL 159

                       170       180
                ....*....|....*....|.
gi 17509393 191 ELVDVSEYSASSIWDVIDVPA 211
Cdd:cd19022 160 DSGDLSDFVEDVEWEVHGMPA 180

extracellular domain of neuronal acetylcholine receptor subunit alpha-7-like; This family contains the extracellular domain of nicotinic acetylcholine receptor (nAChR), a member of the pentameric "Cys-loop" superfamily of transmitter-gated ion channels. nAChR is found in high concentrations at the nerve-muscle synapse, where it mediates fast chemical transmission of electrical signals in response to the endogenous neurotransmitter acetylcholine (ACh) released from the nerve terminal into the synaptic cleft. Thus far, seventeen nAChR subunits have been identified, including ten alpha subunits, four beta subunits and one gamma, delta, and epsilon subunit each, all found on the cell membrane that non-selectively conducts cations (Na+, K+, Ca++). These nAChR subunits combine in several different ways to form functional nAChR subtypes which are broadly categorized as either muscle subtype located at the neuromuscular junction or neuronal subtype that are found on neurons and on other cell types throughout the body. The muscle type of nAChRs are formed by the alpha1, beta1, gamma, delta, and epsilon subunits while the neuronal type are composed of nine alpha subunits and three beta subunits, which combine in various permutations and combinations to form functional receptors. Among various subtypes of neuronal nAChRs, the homomeric alpha7 and the heteromeric alpha4beta2 receptors are the main subtypes widely distributed in the brain and implicated in the pathophysiology of neurodevelopmental disorders such as schizophrenia and autism and neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 17509393  56 LIVKMALQLVLLINVDEKDQVMHTNVWLTLQWHDFQMKWNPVNYGEIKQIRVSPDKVWLPDIVLFNNADGNYEVSFMCNV 135
Cdd:cd19021   1 IVVELQLSLLQIIDVDEKNQVLITNAWLQMYWVDIYLSWDQYEYPGVQNLRFPSDQIWVPDILLYNSADERFDATFHTNV 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 17509393 136 VINHKGDMLWVPPAIYKSSCIIDVEFFPFDEQVCTLVFGSWTYNENEIKLEFVQAelvDVSEYSASSIWDVIDVPA 211
Cdd:cd19021  81 LVNYSGSCQYIPPGILKSTCYIDVRWFPFDVQKCDLKFGSWTHSGWLIDLQMLEA---DISNYISNGEWDLVGVPG 153