extracellular domain (ECD) of Cys-loop neurotransmitter-gated ion channels (also known as ligand-gated ion channel (LGIC)); This superfamily contains the extracellular domain (ECD) of Cys-loop neurotransmitter-gated ion channels, which include nicotinic acetylcholine receptor (nAChR), serotonin 5-hydroxytryptamine receptor (5-HT3), type-A gamma-aminobutyric acid receptor (GABAAR) and glycine receptor (GlyR). 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. GABAAR and GlyR are anionic channels, both mediating fast inhibitory synaptic transmission. Cl- ions are selectively conducted through the GABAAR receptor pore, resulting in hyperpolarization of the neuron. 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. These ligand-gated chloride channels are critical not only for maintaining appropriate neuronal activity, but have long been important therapeutic targets: benzodiazepines, barbiturates, some intravenous and volatile anaesthetics, alcohol, strychnine, picrotoxin, and ivermectin all derive their biological activity from acting on the inhibitory half of the Cys-loop receptor family. The ECD contains the ligand binding sites for these receptors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517  62 IHFIDDDHGFMSVVINAELTWIDERLKWNPANYSGVREIVEKTFEFrkdnncWMP-IVKYRSYDrrysELDLLEFSDART 140
Cdd:cd18989   12 ILDLDEVEQTLTLSGWLTLTWTDERLTWNPSDYGGITSIVVPSSEI------WTPdIVLYNSVD----SLDLLGDSNTLV 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517 141 LISYKGEIKTALQTMVTTKCQFSFGEYPNDYQNCSI------------MLIPNQNADEFRFVSPNGycnpKFENLEHRAV 208
Cdd:cd18989   82 RVSSDGTVTWVPPGVLTTSCDIDVTYFPFDTQTCSLrfgswsyttdeiNLTPSSNGVDLEDYEENG----EWELLSTSVS 157

                        170
                 ....*....|....*...
gi 392927517 209 RVHDLHLMGVESNIFYTF 226
Cdd:cd18989  158 REEDKYCNETYSELTFTI 175

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 392927517  62 IHFIDDDHGFMSVVINAELTWIDERLKWNPANYSGVREIVEKTFEFrkdnncWMP-IVKYRSYDrrysELDLLEFSDART 140
Cdd:cd18989   12 ILDLDEVEQTLTLSGWLTLTWTDERLTWNPSDYGGITSIVVPSSEI------WTPdIVLYNSVD----SLDLLGDSNTLV 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517 141 LISYKGEIKTALQTMVTTKCQFSFGEYPNDYQNCSI------------MLIPNQNADEFRFVSPNGycnpKFENLEHRAV 208
Cdd:cd18989   82 RVSSDGTVTWVPPGVLTTSCDIDVTYFPFDTQTCSLrfgswsyttdeiNLTPSSNGVDLEDYEENG----EWELLSTSVS 157

                        170
                 ....*....|....*...
gi 392927517 209 RVHDLHLMGVESNIFYTF 226
Cdd:cd18989  158 REEDKYCNETYSELTFTI 175

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 392927517    2 FPIFIVLVIHIHLVVSQWETGKSFTVLTKLRSDLFKNYNGSM-PVGKGEYLEATPSLEVGFIHFIDDDHGFMSVVINAEL 80
Cdd:TIGR00860   5 LLALLLFASLAAVSLAGNAKSNLKEVERKLLDELLKNYDARVrPVFGGPPVTVSFNLFLRSIMDVDEKNMDYTTNIWLRQ 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517   81 TWIDERLKWNPANYSGVREIvekTFEfrkDNNCWMP-IVKYRSYDRRYSELDLlefSDARTLISYKGEIKTALQTMVTTK 159
Cdd:TIGR00860  85 EWTDERLQWNPEEYPGVTLV---RTP---DDSIWVPdIFFYNEKDARFHGITM---TNVLVRIHPNGSVLYSPRITLTLA 155

                         170
                  ....*....|....*..
gi 392927517  160 CQFSFGEYPNDYQNCSI 176
Cdd:TIGR00860 156 CPMDLRNFPFDVQNCSL 172

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 392927517  62 IHFIDDDHGFMSVVINAELTWIDERLKWNPANYSGVREIVEKTFEFrkdnncWMP-IVKYRSYDrrysELDLLEFSDART 140
Cdd:cd18989   12 ILDLDEVEQTLTLSGWLTLTWTDERLTWNPSDYGGITSIVVPSSEI------WTPdIVLYNSVD----SLDLLGDSNTLV 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517 141 LISYKGEIKTALQTMVTTKCQFSFGEYPNDYQNCSI------------MLIPNQNADEFRFVSPNGycnpKFENLEHRAV 208
Cdd:cd18989   82 RVSSDGTVTWVPPGVLTTSCDIDVTYFPFDTQTCSLrfgswsyttdeiNLTPSSNGVDLEDYEENG----EWELLSTSVS 157

                        170
                 ....*....|....*...
gi 392927517 209 RVHDLHLMGVESNIFYTF 226
Cdd:cd18989  158 REEDKYCNETYSELTFTI 175

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 392927517  29 TKLRSDLFKNYNGSM-PVGK-GEYLEATPSLEVgfIHFIDDDHGFMSVVINAEL--TWIDERLKWNPANYSGVREIVEKT 104
Cdd:cd19014    4 TRLVADLFKNYNKVVrPVEHhKDFVVVTVGLQL--IQLINVDEVNQIVTTNVRLkqQWIDVNLKWNPDDYGGIKKIRIPS 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 392927517 105 fefrkdNNCWMP-IVKYRSYDRryselDLLEFSDARTLISYKGEIKTALQTMVTTKCQFSFGEYPNDYQNCSIML 178
Cdd:cd19014   82 ------SDIWRPdLVLYNNADG-----DFAIVKETKVLLEYTGKITWTPPAIFKSYCEIIVTHFPFDQQNCSMKL 145

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 392927517  79 ELTWIDERLKWNPANYSGVREIVektFEFRKdnnCWMP-IVKYRSYDRRYSeldllEFSDARTLISYKGEIKTALQTMVT 157
Cdd:cd18997   29 RQEWNDERLTWNPSDYGGITSIR---VPSDK---IWLPdIVLYNNADGDFD-----SSYKTNVIVYSDGTVTWLPPAIFK 97

                         90
                 ....*....|....*....
gi 392927517 158 TKCQFSFGEYPNDYQNCSI 176
Cdd:cd18997   98 SSCKIDVTYFPFDEQNCTL 116

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 392927517    2 FPIFIVLVIHIHLVVSQWETGKSFTVLTKLRSDLFKNYNGSM-PVGKGEYLEATPSLEVGFIHFIDDDHGFMSVVINAEL 80
Cdd:TIGR00860   5 LLALLLFASLAAVSLAGNAKSNLKEVERKLLDELLKNYDARVrPVFGGPPVTVSFNLFLRSIMDVDEKNMDYTTNIWLRQ 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517   81 TWIDERLKWNPANYSGVREIvekTFEfrkDNNCWMP-IVKYRSYDRRYSELDLlefSDARTLISYKGEIKTALQTMVTTK 159
Cdd:TIGR00860  85 EWTDERLQWNPEEYPGVTLV---RTP---DDSIWVPdIFFYNEKDARFHGITM---TNVLVRIHPNGSVLYSPRITLTLA 155

                         170
                  ....*....|....*..
gi 392927517  160 CQFSFGEYPNDYQNCSI 176
Cdd:TIGR00860 156 CPMDLRNFPFDVQNCSL 172

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 392927517  30 KLRSDLFKNYNGSMPVGKgEYLEATPsLEVGFI--HFI--DDDHGFMSVVINAELTWIDERLKWNPANYSGVrEIVEKTF 105
Cdd:cd19024    3 QLLEKLFENYNPKVRPAR-TVGDRVV-VSVGLTlaQLIslNEKNEEMTTKVYLDLEWTDYRLSWDPAEYDGI-DSLRITS 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 392927517 106 EfrkdnNCWMP-IVKYRSYDRRYsELDLlefsDARTLISYKGEIKTALQTMVTTKCQFSFGEYPNDYQNCSIM 177
Cdd:cd19024   80 D-----SVWLPdIVLMNNNDGNF-DVAL----DVNVLVSSDGSVRWHPPAIYRSSCSIEVTYFPFDWQNCSMV 142

extracellular domain of nicotinic acetylcholine receptor subunit beta 4 (CHRNB4); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit beta 4 (beta4), encoded by the CHRNB4 gene and ubiquitously expressed on lung epithelial cells. The cluster of human neuronal nicotinic receptor gene CHRNA5-CHRNA3-CHRNB4 is related to drug-related behaviors and the development of lung cancer. One of the most broadly expressed subtype is the alpha-3 beta-4 nAChR, also known as the ganglion-type nicotinic receptor, located in the autonomic ganglia and adrenal medulla, where activation yields post- and/or pre-synaptic excitation, mainly by increased Na+ and K+ permeability. Beta4 forms heteromeric nAchRs to modulate receptor affinity for nicotine, but the exact pentameric stochiometry of alpha3beta4 receptor is not known; functional assemblies with varying subunit stoichiometries are possible.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517  82 WIDERLKWNPANYSGVREIVEKTfefrkdNNCWMP-IVKYRSYDRRYsELDLleFSDArtLISYKGEIKTALQTMVTTKC 160
Cdd:cd19027   32 WTDYRLTWNPSDYEGINKLRIPA------KHIWLPdIVLYNNADGTY-EVSV--YTNA--IVQNNGSVAWLPPAIYKSAC 100

                         90
                 ....*....|....*.
gi 392927517 161 QFSFGEYPNDYQNCSI 176
Cdd:cd19027  101 KIEVKHFPFDQQNCTL 116

extracellular domain (ECD) of Cys-loop neurotransmitter-gated ion channels (also known as ligand-gated ion channel (LGIC)); This superfamily contains the extracellular domain (ECD) of Cys-loop neurotransmitter-gated ion channels, which include nicotinic acetylcholine receptor (nAChR), serotonin 5-hydroxytryptamine receptor (5-HT3), type-A gamma-aminobutyric acid receptor (GABAAR) and glycine receptor (GlyR). 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. GABAAR and GlyR are anionic channels, both mediating fast inhibitory synaptic transmission. Cl- ions are selectively conducted through the GABAAR receptor pore, resulting in hyperpolarization of the neuron. 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. These ligand-gated chloride channels are critical not only for maintaining appropriate neuronal activity, but have long been important therapeutic targets: benzodiazepines, barbiturates, some intravenous and volatile anaesthetics, alcohol, strychnine, picrotoxin, and ivermectin all derive their biological activity from acting on the inhibitory half of the Cys-loop receptor family. The ECD contains the ligand binding sites for these receptors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517  62 IHFIDDDHGFMSVVINAELT--WIDERLKWNPANYSGVREIvektfefRKDNN-CWMP-IVKYRSYDRRYSELDLlefSD 137
Cdd:cd03558   10 AQLISVDEVNMDYTTNVFLRqsWIDKRLAYSPADYGGVDSL-------RLPSEqIWLPdLVFYNNKDADFVTTDN---VL 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 392927517 138 ARtlISYKGEIKTALQTMVTTKCQFSFGEYPNDYQNCSIMLI 179
Cdd:cd03558   80 IR--LSPDGTVLYSPRAILKSACPMDLKRFPFDQQNCTMKLE 119

extracellular domain of serotonin 5-hydroxytryptamine receptor (5-HT3) receptor subunit A (5HT3A); This subfamily contains extracellular domain of subunit A of serotonin 5-HT3 receptor (5-HT3AR), encoded by the HTR3A gene. 5-HT3A subunit forms a homopentameric complex or a heterologous combination with other subunits (B-E). Heteromeric combination of A and B subunits provides the full functional features of this receptor, since either subunit alone results in receptors with very low conductance and response amplitude. 5-HT3A receptors are located in the dorsal vagal complex of the brainstem and in the gastrointestinal (GI) tract, and form a channel circuit that controls gut motility, secretion, visceral perception, and the emesis reflex. These receptors are implicated in several GI and psychiatric disorder conditions including anxiety, depression, bipolar disorder, and irritable bowel syndrome (IBS). Several 5-HT3AR antagonists, such as the isoquinoline Palonosetron, are in clinical use to control emetic reflexes associated with gastrointestinal pathologies and cancer therapies. SNPs in the 5-HT3A serotonin receptor gene are associated with psychiatric disorders.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517  65 IDDDHGFMSVVINAELTWIDERLKWNPANYSGVREIVEKTfefrkdNNCWMPivkyrsydrryselDLL--EFSDA---- 138
Cdd:cd19011   40 VDEKNQVLTTYIWYRQYWTDEFLQWNPEDFDNVTQLSIPT------DSIWVP--------------DILinEFVDVgksp 99

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 392927517 139 ---RTLISYKGEIKTALQTMVTTKCQFSFGEYPNDYQNCSI 176
Cdd:cd19011  100 eipYVYVNHEGEVQNYKPIQVVTACSLDIYNFPFDVQNCSL 140

extracellular domain of neuronal acetylcholine receptor subunit alpha 10 (CHRNA10); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit alpha 10 (alpha10), encoded by the CHRNA10 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. Unlike alpha9 nAChR subunits, alpha10 subunits do not generate functional channels when expressed heterologously, suggesting that alpha10 might serve as a structural subunit, much like a beta subunit of heteromeric receptors, providing only complementary components to the agonist binding site. Mammalian alpha10 subunits can form functional heteromeric alpha9alpha10 receptors, an atypical heteromeric receptor since it 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517  82 WIDERLKWNPANYSGVREI-VEKTFEFRKDnncwmpIVKYRSYDRRYSELdllefSDARTLISYKGEIKTALQTMVTTKC 160
Cdd:cd19023   32 WLDAYLAWNKEAYDGLDTIrIPSSYVWRPD------IVLYNNADDRFTGS-----METNVVIRSDGQIMWDSPAITKSSC 100

                         90
                 ....*....|....*.
gi 392927517 161 QFSFGEYPNDYQNCSI 176
Cdd:cd19023  101 KVDVSFFPFDGQQCRL 116

extracellular domain of nicotinic acetylcholine receptor subunit alpha 2 (CHRNA2); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit alpha 2 (alpha2), encoded by the CHRNA2 gene. It is specifically expressed in medial subpallium-derived amygdalar nuclei from early developmental stages to adult. This subunit is incorporated in heteropentameric neuronal nAChRs mainly with beta2 or beta4 subunits and, along with the alpha4 and alpha7, is one of the main nAChR subunits expressed in primate brain. In Xenopus laevis oocytes, when alpha2 is co-expressed with the beta2 subunit, two subtypes of alpha2beta2 nAChR are formed with either low or high ACh sensitivity. Mouse mutation studies show that alpha2 subunits in the nAChRs influence hippocampus-dependent learning and memory as well as CA1 synaptic plasticity in adolescent mice.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517  30 KLRSDLFKNYNG-SMPV-GKGEYLEATPSLEVGFIHFIDDDHGFMSVVINAELTWIDERLKWNPANYSGVREIVEKTfef 107
Cdd:cd19015    3 RLFKHLFTGYNRwSRPVpNTSDVVIVKFGLSIAQLIDVDEKNQMMTTNVWLKQEWSDYKLRWNPTDFDNVTSIRVPS--- 79

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517 108 rkdNNCWMP-IVKYRSYDrrySELDLLEFSDARTLisYKGEIKTALQTMVTTKCQFSFGEYPNDYQNCSI 176
Cdd:cd19015   80 ---EMIWIPdIVLYNNAD---GEFAVTHMTKAHLF--STGKVKWVPPAIYKSSCSIDVTFFPFDQQNCKM 141

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 392927517  65 IDDDHGFMSVVINAELTWIDERLKWNPANYSGVreiveKTFEFrKDNNCWMP-IVKYRSYDRRYseldllefsDA----R 139
Cdd:cd19020   16 VDEKNQVLTTNIWLQMYWTDHYLQWNASEYPGV-----KNVRF-PDGQIWKPdILLYNSADERF---------DAtfhtN 80

                         90       100       110
                 ....*....|....*....|....*....|....*..
gi 392927517 140 TLISYKGEIKTALQTMVTTKCQFSFGEYPNDYQNCSI 176
Cdd:cd19020   81 VLVNSSGHCQYLPPGIFKSSCYIDVRWFPFDVQKCNL 117

extracellular domain of serotonin 5-hydroxytryptamine receptor (5-HT3) receptor subunit B (5HT3B); This subfamily contains extracellular domain of subunit B of serotonin 5-HT3 receptor (5-HT3BR), encoded by the HTR3B gene. 5-HT3B is not functional as a homopentameric complex and is co-expression with the 5-HT3A subunit, resulting in heteromeric 5-HT3AB receptors that are functionally distinct from homomeric 5-HT3A receptors. This receptor causes fast, depolarizing responses in neurons after activation, with affinities of competitive ligands at the two receptor subtypes extracellular domains mostly similar. HTR3B gene variants may contribute to variability in severity of and response to anti-emetic therapy for nausea and vomiting in pregnancy, as well as efficacy of ondansetron in cancer chemotherapy, radiation therapy, or surgery. 5-HT3B subunit affects high-potency inhibition of 5-HT3 receptors by morphine by reducing its affinity at its high-affinity, non-competitive site.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 392927517  82 WIDERLKWNPANYSGVREIVEKTfefrkdNNCWMPIVKYRSY--DRRYSELDLLEFSDARTLISYKgeiktalQTMVTTK 159
Cdd:cd19012   60 WKDEFLVWNSSDFDGINEISLPL------SAIWVPDIVINEFvdVGRYPDLPYVYVNSSGTIKNYK-------PIQVVSA 126

                         90
                 ....*....|....*..
gi 392927517 160 CQFSFGEYPNDYQNCSI 176
Cdd:cd19012  127 CDLETYAFPFDRQNCSL 143

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 392927517  65 IDDDHGFMSVVINAELTWIDERLKWNPANYSGVREI-VEKTFEFRKDnncwmpIVKYRSYDRRYSELDLlefsdARTLIS 143
Cdd:cd19017   15 VDEKNQMMTTNVWVKQEWHDYKLRWDPADYENVTSIrIPSELIWRPD------IVLYNNADGDFAVTHL-----TKAHLF 83

                         90       100       110
                 ....*....|....*....|....*....|...
gi 392927517 144 YKGEIKTALQTMVTTKCQFSFGEYPNDYQNCSI 176
Cdd:cd19017   84 HDGRVQWTPPAIYKSSCSIDVTFFPFDQQNCTM 116