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Conserved domains on  [gi|1720396771|ref|XP_030102632|]
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neuronal acetylcholine receptor subunit alpha-4 isoform X2 [Mus musculus]

Protein Classification

ligand-gated ion channel family protein( domain architecture ID 13215647)

ligand-gated ion channel family protein similar to Rattus norvegicus acetylcholine receptor subunits delta and epsilon

Graphical summary

 Zoom to residue level

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List of domain hits

Name Accession Description Interval E-value
Neur_chan_memb pfam02932
Neurotransmitter-gated ion-channel transmembrane region; This family includes the four ...
74-442 5.68e-75

Neurotransmitter-gated ion-channel transmembrane region; This family includes the four transmembrane helices that form the ion channel.


:

Pssm-ID: 460753 [Multi-domain]  Cd Length: 232  Bit Score: 234.47  E-value: 5.68e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771  74 LIIPCLLISCLTVLVFYLPSEC-GEKVTLCISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVITVFVL 152
Cdd:pfam02932   1 LIIPCVLISFLSWLVFWLPADAvGEKVTLGITVLLTMTVFLLLIRESLPKTSYVVPLIGKYLLFCMVFVFLSLVETVFVL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771 153 NVHHRSPRTHTMPAWVRRVFLDIVPRLLFMKRPSVVKDNCRRLIESMhkmanaprfwpepesepgilgdicnqglspapt 232
Cdd:pfam02932  81 NVHHRSPSTHKMPPWVRKIFLEKLPRLLGMKRPPEAPPPPASPGYGS--------------------------------- 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771 233 fcnrmdtavetqptcrspshkvpdlktsevekaspcpspgschppnssgapvlikarslsvqhvpssqeAAEGSIRCRSR 312
Cdd:pfam02932 128 ---------------------------------------------------------------------KAEEYILRKPR 138
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771 313 SiqycvsqdgaaslteskptgspASLKTRPSQLPVSDQTSPCKCTCKEPSPVspitvlkaggtkapPQHLPLSPALTRAV 392
Cdd:pfam02932 139 S----------------------ELPFEKQSERHGLGRETTCSYGCSLGNGS--------------SQPRELSPELKKAV 182
                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|
gi 1720396771 393 EGVQYIADHLKAEDTDFSVKEDWKYVAMVIDRIFLWMFIIVCLLGTVGLF 442
Cdd:pfam02932 183 EGVNFIAKHLRSQDEYISVKEDWKYVAMVIDRLSRWIFPIAFVLGTLGYF 232
LGIC_ECD super family cl28912
extracellular domain (ECD) of Cys-loop neurotransmitter-gated ion channels (also known as ...
1-66 1.01e-40

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.


The actual alignment was detected with superfamily member cd19017:

Pssm-ID: 475126  Cd Length: 181  Bit Score: 143.65  E-value: 1.01e-40
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRL 66
Cdd:cd19017   116 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRL 181
 
Name Accession Description Interval E-value
Neur_chan_memb pfam02932
Neurotransmitter-gated ion-channel transmembrane region; This family includes the four ...
74-442 5.68e-75

Neurotransmitter-gated ion-channel transmembrane region; This family includes the four transmembrane helices that form the ion channel.


Pssm-ID: 460753 [Multi-domain]  Cd Length: 232  Bit Score: 234.47  E-value: 5.68e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771  74 LIIPCLLISCLTVLVFYLPSEC-GEKVTLCISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVITVFVL 152
Cdd:pfam02932   1 LIIPCVLISFLSWLVFWLPADAvGEKVTLGITVLLTMTVFLLLIRESLPKTSYVVPLIGKYLLFCMVFVFLSLVETVFVL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771 153 NVHHRSPRTHTMPAWVRRVFLDIVPRLLFMKRPSVVKDNCRRLIESMhkmanaprfwpepesepgilgdicnqglspapt 232
Cdd:pfam02932  81 NVHHRSPSTHKMPPWVRKIFLEKLPRLLGMKRPPEAPPPPASPGYGS--------------------------------- 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771 233 fcnrmdtavetqptcrspshkvpdlktsevekaspcpspgschppnssgapvlikarslsvqhvpssqeAAEGSIRCRSR 312
Cdd:pfam02932 128 ---------------------------------------------------------------------KAEEYILRKPR 138
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771 313 SiqycvsqdgaaslteskptgspASLKTRPSQLPVSDQTSPCKCTCKEPSPVspitvlkaggtkapPQHLPLSPALTRAV 392
Cdd:pfam02932 139 S----------------------ELPFEKQSERHGLGRETTCSYGCSLGNGS--------------SQPRELSPELKKAV 182
                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|
gi 1720396771 393 EGVQYIADHLKAEDTDFSVKEDWKYVAMVIDRIFLWMFIIVCLLGTVGLF 442
Cdd:pfam02932 183 EGVNFIAKHLRSQDEYISVKEDWKYVAMVIDRLSRWIFPIAFVLGTLGYF 232
LGIC_TM_nAChR cd19064
transmembrane domain of nicotinic acetylcholine receptor (nAChR); This family contains ...
68-157 1.03e-44

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.


Pssm-ID: 349866 [Multi-domain]  Cd Length: 113  Bit Score: 151.51  E-value: 1.03e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771  68 LFYTINLIIPCLLISCLTVLVFYLPSECGEKVTLCISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVI 147
Cdd:cd19064     1 LFYTVNLIIPCVLISFLTVLVFYLPADSGEKITLSISVLLALTVFLLLIAEIIPPTSLVVPLIGKYLLFTMILVTLSIIV 80
                          90
                  ....*....|
gi 1720396771 148 TVFVLNVHHR 157
Cdd:cd19064    81 TVIVLNVHHR 90
LGIC_ECD_nAChR_A4 cd19017
extracellular domain of neuronal acetylcholine receptor subunit alpha 4 (CHRNA4); This ...
1-66 1.01e-40

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.


Pssm-ID: 349818  Cd Length: 181  Bit Score: 143.65  E-value: 1.01e-40
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRL 66
Cdd:cd19017   116 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRL 181
LIC TIGR00860
Cation transporter family protein; The Ligand-gated Ion Channel (LIC) Family of ...
1-203 3.91e-40

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]


Pssm-ID: 273305 [Multi-domain]  Cd Length: 459  Bit Score: 149.48  E-value: 3.91e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771   1 MKFGSWTYDKAKIDLV---SMHSRVDQLDFWESGEWVIVDAVGTyNTRKYECCAEIYPDITYAFIIRRLPLFYTINLIIP 77
Cdd:TIGR00860 172 LKFESWGYTTNDIKLEwkeQGAVQVDDSLFISLPEFELLGVYGT-RYCTSETNTGEYPCLTFSFVLRRRPLYYLLQLYIP 250
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771  78 CLLISCLTVLVFYLPSEC-GEKVTLCISVLLSLTVFLLLITEIIPSTSlVIPLIGEYLLFTMIFVTLSIVITVFVLNVHH 156
Cdd:TIGR00860 251 SILIVILSWVSFWLPADAsGARVSLGITTLLTMTTFSSGVRESLPAVS-YVKAIDVYFAVCMAFVFLALLETAFVNYVHH 329
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1720396771 157 RSPRTHTmpawvRRVFLDIVPRLLFMKRPSvvkDNCRRLIESMHKMA 203
Cdd:TIGR00860 330 KDPAQGK-----RHLLLERCAWRLCKQEPG---EDYRRPALDHASLS 368
Neur_chan_LBD pfam02931
Neurotransmitter-gated ion-channel ligand binding domain; This family is the extracellular ...
1-67 5.08e-19

Neurotransmitter-gated ion-channel ligand binding domain; This family is the extracellular ligand binding domain of these ion channels. This domain forms a pentameric arrangement in the known structure.


Pssm-ID: 460752 [Multi-domain]  Cd Length: 215  Bit Score: 85.39  E-value: 5.08e-19
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720396771   1 MKFGSWTYDKAKIDL-------VSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRLP 67
Cdd:pfam02931 142 LKFGSWTYNGEEVDLrwdddppVVELEEIDLSDFWLNGEWDIVDVPAKRREYPYGCYSELTGDVTFYFTLRRKP 215
 
Name Accession Description Interval E-value
Neur_chan_memb pfam02932
Neurotransmitter-gated ion-channel transmembrane region; This family includes the four ...
74-442 5.68e-75

Neurotransmitter-gated ion-channel transmembrane region; This family includes the four transmembrane helices that form the ion channel.


Pssm-ID: 460753 [Multi-domain]  Cd Length: 232  Bit Score: 234.47  E-value: 5.68e-75
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771  74 LIIPCLLISCLTVLVFYLPSEC-GEKVTLCISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVITVFVL 152
Cdd:pfam02932   1 LIIPCVLISFLSWLVFWLPADAvGEKVTLGITVLLTMTVFLLLIRESLPKTSYVVPLIGKYLLFCMVFVFLSLVETVFVL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771 153 NVHHRSPRTHTMPAWVRRVFLDIVPRLLFMKRPSVVKDNCRRLIESMhkmanaprfwpepesepgilgdicnqglspapt 232
Cdd:pfam02932  81 NVHHRSPSTHKMPPWVRKIFLEKLPRLLGMKRPPEAPPPPASPGYGS--------------------------------- 127
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771 233 fcnrmdtavetqptcrspshkvpdlktsevekaspcpspgschppnssgapvlikarslsvqhvpssqeAAEGSIRCRSR 312
Cdd:pfam02932 128 ---------------------------------------------------------------------KAEEYILRKPR 138
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771 313 SiqycvsqdgaaslteskptgspASLKTRPSQLPVSDQTSPCKCTCKEPSPVspitvlkaggtkapPQHLPLSPALTRAV 392
Cdd:pfam02932 139 S----------------------ELPFEKQSERHGLGRETTCSYGCSLGNGS--------------SQPRELSPELKKAV 182
                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|
gi 1720396771 393 EGVQYIADHLKAEDTDFSVKEDWKYVAMVIDRIFLWMFIIVCLLGTVGLF 442
Cdd:pfam02932 183 EGVNFIAKHLRSQDEYISVKEDWKYVAMVIDRLSRWIFPIAFVLGTLGYF 232
LGIC_TM_nAChR cd19064
transmembrane domain of nicotinic acetylcholine receptor (nAChR); This family contains ...
68-157 1.03e-44

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.


Pssm-ID: 349866 [Multi-domain]  Cd Length: 113  Bit Score: 151.51  E-value: 1.03e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771  68 LFYTINLIIPCLLISCLTVLVFYLPSECGEKVTLCISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVI 147
Cdd:cd19064     1 LFYTVNLIIPCVLISFLTVLVFYLPADSGEKITLSISVLLALTVFLLLIAEIIPPTSLVVPLIGKYLLFTMILVTLSIIV 80
                          90
                  ....*....|
gi 1720396771 148 TVFVLNVHHR 157
Cdd:cd19064    81 TVIVLNVHHR 90
LGIC_ECD_nAChR_A4 cd19017
extracellular domain of neuronal acetylcholine receptor subunit alpha 4 (CHRNA4); This ...
1-66 1.01e-40

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.


Pssm-ID: 349818  Cd Length: 181  Bit Score: 143.65  E-value: 1.01e-40
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRL 66
Cdd:cd19017   116 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRL 181
LIC TIGR00860
Cation transporter family protein; The Ligand-gated Ion Channel (LIC) Family of ...
1-203 3.91e-40

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]


Pssm-ID: 273305 [Multi-domain]  Cd Length: 459  Bit Score: 149.48  E-value: 3.91e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771   1 MKFGSWTYDKAKIDLV---SMHSRVDQLDFWESGEWVIVDAVGTyNTRKYECCAEIYPDITYAFIIRRLPLFYTINLIIP 77
Cdd:TIGR00860 172 LKFESWGYTTNDIKLEwkeQGAVQVDDSLFISLPEFELLGVYGT-RYCTSETNTGEYPCLTFSFVLRRRPLYYLLQLYIP 250
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771  78 CLLISCLTVLVFYLPSEC-GEKVTLCISVLLSLTVFLLLITEIIPSTSlVIPLIGEYLLFTMIFVTLSIVITVFVLNVHH 156
Cdd:TIGR00860 251 SILIVILSWVSFWLPADAsGARVSLGITTLLTMTTFSSGVRESLPAVS-YVKAIDVYFAVCMAFVFLALLETAFVNYVHH 329
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1720396771 157 RSPRTHTmpawvRRVFLDIVPRLLFMKRPSvvkDNCRRLIESMHKMA 203
Cdd:TIGR00860 330 KDPAQGK-----RHLLLERCAWRLCKQEPG---EDYRRPALDHASLS 368
LGIC_ECD_nAChR_A2 cd19015
extracellular domain of nicotinic acetylcholine receptor subunit alpha 2 (CHRNA2); This ...
1-67 1.04e-37

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.


Pssm-ID: 349816 [Multi-domain]  Cd Length: 207  Bit Score: 136.33  E-value: 1.04e-37
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRLP 67
Cdd:cd19015   141 MKFGSWTYDKAKIDLEQMEQTVDLKDYWESGEWAIVNATGTYNSKKYDCCTEIYPDITYYFVIRRLP 207
LGIC_TM_cation cd19051
transmembrane domain of Cys-loop neurotransmitter-gated ion channels, includes 5HT3, nAChR, ...
68-182 4.60e-31

transmembrane domain of Cys-loop neurotransmitter-gated ion channels, includes 5HT3, nAChR, and ZAC; This superfamily contains the transmembrane (TM) domain 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. 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. The ligand-gated ion channels (LGICs) in this family 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.


Pssm-ID: 349853 [Multi-domain]  Cd Length: 112  Bit Score: 115.15  E-value: 4.60e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771  68 LFYTINLIIPCLLISCLTVLVFYLPSECGEKVTLCISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVI 147
Cdd:cd19051     1 LFYVFNLILPCVLLSVLALLVFLLPPDSGEKVSLGITVLLSLTVFLLLVSESLPPTSDSVPLIGIYLLATMVLSALSTVL 80
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1720396771 148 TVFVLNVHHRSPRthtMPAWVRRVFLDIVPRLLFM 182
Cdd:cd19051    81 TVIVLNLHHVLDR---LFFWLFLLVTVITTLVLFL 112
LGIC_ECD_nAChR_A3 cd19016
extracellular domain of nicotinic acetylcholine receptor subunit alpha 3 (CHRNA3); This ...
1-67 2.57e-29

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.


Pssm-ID: 349817 [Multi-domain]  Cd Length: 207  Bit Score: 113.88  E-value: 2.57e-29
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRLP 67
Cdd:cd19016   141 MKFGSWSYDKAKIDLVLIGSSMNLKDYWESGEWAIIKAPGYKHDIKYNCCEEIYPDITYSLYIRRLP 207
LGIC_ECD_nAChR_A6 cd19019
extracellular domain of nicotinic acetylcholine receptor subunit alpha 6 (CHRNA6); This ...
1-66 1.61e-25

extracellular domain of nicotinic acetylcholine receptor subunit alpha 6 (CHRNA6); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit alpha 6 (alpha6), encoded by the CHRNA6 gene. Human (alpha6beta2)(alpha4beta2)3 nicotinic acetylcholine receptors (AChRs) are essential for addiction to nicotine and a target for drug development for smoking cessation. In xenopus oocytes, data show efficient expression of (alpha6beta2)2beta3 AChR subunits with only small changes in alpha6 subunits, while not altering AChR pharmacology or channel structure. Alternatively spliced transcript variants have been observed for this gene. Single nucleotide polymorphisms in this gene have been associated with both nicotine and alcohol dependence. CHRNA6 has a cellular expression signature for retinal ganglion cells with high correlation to Thy1, a known marker, and is preferentially expressed by retinal ganglion cells (RGCs) in the young and adult mouse retina and expression is reduced in glaucoma. A genetic variant in CHRNB3#CHRNA6 cluster is associated with esophageal adenocarcinoma.


Pssm-ID: 349820 [Multi-domain]  Cd Length: 181  Bit Score: 102.80  E-value: 1.61e-25
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRL 66
Cdd:cd19019   116 LKFGSWTYDKAKIDLLIIGSKVDMNDFWENSEWEIVDASGYKHDIKYNCCEEIYTDITYSFYIRRL 181
LGIC_ECD_nAChR cd18997
extracellular domain of nicotinic acetylcholine receptor; This family contains the ...
1-65 2.11e-25

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.


Pssm-ID: 349798  Cd Length: 181  Bit Score: 102.18  E-value: 2.11e-25
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRR 65
Cdd:cd18997   116 LKFGSWTYDGSELDLQLKSDTVDLSDYIENGEWDLLGAPAKRNVVKYSCCPEPYPDVTFTIHIRR 180
LGIC_ECD cd03558
extracellular domain (ECD) of Cys-loop neurotransmitter-gated ion channels (also known as ...
1-66 2.52e-23

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.


Pssm-ID: 349787  Cd Length: 179  Bit Score: 96.33  E-value: 2.52e-23
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYEccAEIYPDITYAFIIRRL 66
Cdd:cd03558   116 MKLESWTYDTTDIELVWDSERPDQADFLELPEWDIVEKRGRYCTVVYN--TGIYSDITYRFRLKRQ 179
LGIC_ECD_nAChR_A5 cd19018
extracellular domain of nicotinic acetylcholine receptor subunit alpha 5 (CHRNA5); This ...
1-68 7.66e-20

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.


Pssm-ID: 349819 [Multi-domain]  Cd Length: 207  Bit Score: 87.33  E-value: 7.66e-20
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCaeIYPDITYAFIIRRLPL 68
Cdd:cd19018   142 MKFGSWTYDGSQVDIILEDYDVDKRDFFDNGEWEIVSATGSKGNRTDGCC--WYPFITYSFIIRRLPL 207
Neur_chan_LBD pfam02931
Neurotransmitter-gated ion-channel ligand binding domain; This family is the extracellular ...
1-67 5.08e-19

Neurotransmitter-gated ion-channel ligand binding domain; This family is the extracellular ligand binding domain of these ion channels. This domain forms a pentameric arrangement in the known structure.


Pssm-ID: 460752 [Multi-domain]  Cd Length: 215  Bit Score: 85.39  E-value: 5.08e-19
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720396771   1 MKFGSWTYDKAKIDL-------VSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRLP 67
Cdd:pfam02931 142 LKFGSWTYNGEEVDLrwdddppVVELEEIDLSDFWLNGEWDIVDVPAKRREYPYGCYSELTGDVTFYFTLRRKP 215
LGIC_ECD_nAChR_proto-like cd19033
nicotinic acetylcholine receptor (nAChR) subunit extracellular domain in molluscs and annelids; ...
1-65 4.42e-18

nicotinic acetylcholine receptor (nAChR) subunit extracellular domain in molluscs and annelids; This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit found in molluscs, including several Lymnaea nAChRs, and annelids that are mostly uncharacterized. To date, 12 Lymnaea nAChRs have been identified which can be subdivided in two subtypes according to the residues that may be contributing to the selectivity of ion conductance. Phylogenetic analysis of the nAChR gene sequences suggests that anionic nAChRs in molluscs probably evolved from cationic ancestors through amino acid substitutions in the ion channel pore which is a mechanism different from acetylcholine-gated channels in other invertebrates.


Pssm-ID: 349834  Cd Length: 183  Bit Score: 81.56  E-value: 4.42e-18
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720396771   1 MKFGSWTYDKAKIDL--VSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRR 65
Cdd:cd19033   116 LKFGSWTYDGTRLDItfYDNEEEIDLTDYIESNEWEILAYPAVKNVKYYPCCPEPYPDLTFFLVIKR 182
LGIC_ECD_nAChR_B3 cd19026
extracellular domain of nicotinic acetylcholine receptor subunit beta 3 (CHRNB3); This ...
1-66 2.11e-15

extracellular domain of nicotinic acetylcholine receptor subunit beta 3 (CHRNB3); This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit beta 3 (beta3), encoded by the CHRNB3 gene. CHRNB3 polymorphisms have been reported to potentially affect nicotine-induced upregulation of nicotinic and to be associated with disorders such as schizophrenia, autism, and cancer. Beta3 subunit is depleted in the striatum of Parkinson's disease patients. Rare variants in CHRNB3 are also implicated in risk for alcohol and cocaine dependence and independently associated with bipolar disorder. Human alpha6beta2beta3* (* indicating possible additional assembly partners) nAChRs on dopaminergic neurons are important targets for drugs to treat nicotine addiction and Parkinson's disease; (alpha6beta2)(alpha4beta2)beta3 nAChR is essential for addiction to nicotine and a target for drug development for smoking cessation.


Pssm-ID: 349827  Cd Length: 179  Bit Score: 73.85  E-value: 2.11e-15
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAeiYPDITYAFIIRRL 66
Cdd:cd19026   116 MKFGSWTYDGNMVDLILIDENVDRKDFFDNGEWEILNAKGMKGNRKDGLYS--YPFITYSFVLRRL 179
LGIC_ECD_nAChR_proto_alpha-like cd19031
extracellular domain of nicotinic acetylcholine receptor subunit alpha-like found in ...
1-69 2.75e-14

extracellular domain of nicotinic acetylcholine receptor subunit alpha-like found in protostomia; This subfamily contains the extracellular domain of nicotinic acetylcholine receptor subunit alpha-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 (L-AChR) alpha-subunits, UNC-38, UNC-63, and LEV-8, included in this subfamily, form heteromers with the two non-alpha (also known as beta-like) subunits, UNC-29 and LEV-1. This receptor functions as the main excitatory postsynaptic receptor at neuromuscular junctions, indicating that many are expressed in neurons. Also included is the nicotinic alpha subunit MARA1 (Manduca ACh Receptor Alpha 1) which is expressed in Ca2+ responding neurons and contributes to the nicotinic responses in the neurons. In insects, the receptors supply fast synaptic excitatory transmission and represent a major target for several insecticides. In Drosophila, ten exclusively neuronal nAChRs have been identified, Dalpha1-Dalpha7 and Dbeta1-Dbeta3, and various combinations of these subunits and mutations are key to nAChR function. Alpha5 subunit is involved in alpha-bungarotoxin sensitivity while the alpha6 subunit is essential for the insecticidal effect of spinosad. nAChR agonists acetylcholine, nicotine, and neonicotinoids stimulate dopamine release in Drosophila larval ventral nerve cord and mutations in nAChR subunits affect how insecticides stimulate dopamine release.


Pssm-ID: 349832  Cd Length: 222  Bit Score: 71.93  E-value: 2.75e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSR-----------VDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRRLPLF 69
Cdd:cd19031   143 MKFGSWTYDGFEVDLRHVDQKygsedevidvgIDLSEFYPSVEWDLLEVPARRNEKYYPCCDEPYPDITFNITLRRKTLF 222
LGIC_ECD_nAChR_A10 cd19023
extracellular domain of neuronal acetylcholine receptor subunit alpha 10 (CHRNA10); This ...
1-65 2.34e-12

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.


Pssm-ID: 349824  Cd Length: 181  Bit Score: 65.40  E-value: 2.34e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRR 65
Cdd:cd19023   116 LTFGSWTYNGNQIDILNLLDTGDLTDFVENVEWEVLGMPAKRNVITYGCCSEPYPDVTYTLLLKR 180
LGIC_ECD_nAChR_A7 cd19020
extracellular domain of neuronal acetylcholine receptor subunit alpha 7 (CHRNA7); This ...
1-65 7.52e-12

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.


Pssm-ID: 349821 [Multi-domain]  Cd Length: 180  Bit Score: 63.86  E-value: 7.52e-12
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSrvDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRR 65
Cdd:cd19020   117 LKFGSWTYGGWSLDLQMQEA--DISGYISNGEWDLVGVPGKRNEKFYECCKEPYPDVTFTVTMRR 179
LGIC_ECD_nAChR_A1 cd19014
extracellular domain of nicotinic acetylcholine receptor subunit alpha 1 (CHRNA1); This ...
1-67 1.14e-11

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.


Pssm-ID: 349815  Cd Length: 210  Bit Score: 64.11  E-value: 1.14e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEI-YPDITYAFIIRRLP 67
Cdd:cd19014   143 MKLGTWTYDGTLVVINPESDRPDLSNFMESGEWVMKDYRGWKHWVYYTCCPDTpYLDITYHFLLQRLP 210
LGIC_ECD_nAChR_B2 cd19025
extracellular domain of nicotinic acetylcholine receptor subunit beta 2 (CHRNB2); This ...
1-67 4.95e-11

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.


Pssm-ID: 349826  Cd Length: 204  Bit Score: 61.93  E-value: 4.95e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYEccaEIYPDITYAFIIRRLP 67
Cdd:cd19025   141 LKFRSWTYDRTEIDLVLRSDVASLDDFTPSGEWDIVALPGRRNENPND---STYVDITYDFIIRRKP 204
LGIC_ECD_nAChR_A9 cd19022
extracellular domain of neuronal acetylcholine receptor subunit alpha 9 (CHRNA9); This ...
1-65 6.73e-11

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.


Pssm-ID: 349823  Cd Length: 207  Bit Score: 61.60  E-value: 6.73e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRR 65
Cdd:cd19022   141 LTFGSWTYNGNQVDIINALDSGDLSDFVEDVEWEVHGMPAVKNVITYGCCSEPYPDVTFTLILKR 205
LGIC_ECD_cation cd18989
extracellular domain (LBD) of cationic Cys-loop neurotransmitter-gated ion channels; This ...
1-65 8.87e-11

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.


Pssm-ID: 349790 [Multi-domain]  Cd Length: 180  Bit Score: 60.84  E-value: 8.87e-11
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYecCAEIYPDITYAFIIRR 65
Cdd:cd18989   117 LRFGSWSYTTDEINLTPSSNGVDLEDYEENGEWELLSTSVSREEDKY--CNETYSELTFTITLKR 179
LGIC_TM_5-HT3 cd19063
transmembrane domain of 5-hydroxytryptamine 3 (5-HT3) receptor; This family contains ...
68-181 1.10e-10

transmembrane domain of 5-hydroxytryptamine 3 (5-HT3) receptor; This family contains transmembrane (TM) domain of the serotonin 5-HT3 receptors. 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. The 5-HT3 channel is cation-selective and mediates neuronal depolarization and excitation within the central and peripheral nervous systems. Like other ligand gated ion channels, the 5-HT3 receptor consists of five subunits arranged around a central ion conducting pore, which is permeable to Na+, K+, and Ca2+ ions. Binding of the neurotransmitter 5-hydroxytryptamine (serotonin) to the 5-HT3 receptor opens the channel, which then leads to an excitatory response in neurons, and the rapidly activating, desensitizing, inward current is predominantly carried by Na+ and K+ ions. This receptor is most closely related by homology to the nicotinic acetylcholine receptor (nAChR). Five subunits have been identified for this family: 5-HT3A, 5-HT3B, 5-HT3C, 5-HT3D, and 5-HT3E, encoded by HTR3A-E genes. Only 5-HT3A subunits are able to form functional homomeric receptors, whereas the 5-HT3B, C, D, and E subunits form heteromeric receptors with 5-HT3A. Different receptor subtypes are important mediators of nausea and vomiting during chemotherapy, pregnancy, and following surgery, while some contribute to neuro-gastroenterologic disorders such irritable bowel syndrome (IBS) and eating disorders as well as co-morbid psychiatric conditions. 5-HT3 receptor antagonists are established treatments for emesis and IBS, and are beneficial in the treatment of psychiatric diseases.


Pssm-ID: 349865  Cd Length: 121  Bit Score: 58.79  E-value: 1.10e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771  68 LFYTINLIIPCLLISCLTVLVFYLPSECGEKVTLCISVLLSLTVFLLLITEIIPSTSLVIPLIGEYLLFTMIFVTLSIVI 147
Cdd:cd19063     1 LLYVVNLLIPSIFLMLVDLASFYLPPNSGERLGFKVTLLLGYSVFLLILNDLLPATAIGTPLIGVYFVVCLALMVLSLLE 80
                          90       100       110
                  ....*....|....*....|....*....|....
gi 1720396771 148 TVFVLNVHHrsprthtmpaWVRrvFLDIVPRLLF 181
Cdd:cd19063    81 TILIVKLLH----------WLR--VAYVLDRLLF 102
LGIC_AChBP cd18995
acetylcholine binding protein (AChBP); This family contains acetylcholine binding protein ...
2-65 1.51e-10

acetylcholine binding protein (AChBP); This family contains acetylcholine binding protein (AChBP) which is a soluble extracellular domain homolog secreted by protostomia, and has been widely recognized as a surrogate for the ligand binding domain of nicotinic acetylcholine receptors (nAChRs). AChBP forms a pentameric structure where the interfaces between the subunits provide an acetylcholine (ACh) binding pocket homologous to the binding pocket of nAChRs. Thus far, AChBPs have been characterized only in aquatic mollusks, which have shown low sensitivity to neonicotinoids, the insecticides targeting insect nAChRs. Lymnaea stagnalis acetylcholine binding protein (Ls-AChBP) which has been found in glial cells as a water-soluble protein modulating synaptic ACh concentration has its the binding pocket show better resemblance as it contains all the five aromatic residues fully conserved in nAChR. Five AChBP subunits have been characterized in Pardosa pseudoannulata, a predator enemy against rice insect pests, and share higher sequence similarities with nAChR subunits of both insects and mammals compared with mollusk AChBP subunits.


Pssm-ID: 349796  Cd Length: 180  Bit Score: 60.07  E-value: 1.51e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720396771   2 KFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRR 65
Cdd:cd18995   116 KIGSWTYSGREIDLNTGTDVDLDSYYNQSSKWELLSATQKREVKTYSCCPEPYPDIEFVFTFKK 179
LGIC_ECD_nAChR_B4 cd19027
extracellular domain of nicotinic acetylcholine receptor subunit beta 4 (CHRNB4); This ...
1-65 6.98e-10

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.


Pssm-ID: 349828  Cd Length: 178  Bit Score: 58.09  E-value: 6.98e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDQLDFWESGEWVIVDAVGtyntRKYECCAE-IYPDITYAFIIRR 65
Cdd:cd19027   116 LKFRSWTYDHTEIDMVLKTPTASMDDFTPSGEWDIVALPG----RRTVNPLDpTYVDVTYDFIIKR 177
LGIC_ECD_nAChR_A7L cd19021
extracellular domain of neuronal acetylcholine receptor subunit alpha-7-like; This family ...
1-65 7.74e-10

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.


Pssm-ID: 349822 [Multi-domain]  Cd Length: 179  Bit Score: 58.13  E-value: 7.74e-10
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720396771   1 MKFGSWTYDKAKIDLVSMHSRVDqlDFWESGEWVIVDAVGTYNTRKYECCAEIYPDITYAFIIRR 65
Cdd:cd19021   116 LKFGSWTHSGWLIDLQMLEADIS--NYISNGEWDLVGVPGKRNELYYECCKEPYPDVTYTITMRR 178
LGIC_TM cd03559
transmembrane domain of Cys-loop neurotransmitter-gated ion channels; This superfamily ...
69-173 1.88e-09

transmembrane domain of Cys-loop neurotransmitter-gated ion channels; This superfamily contains the transmembrane domain 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 where the sign of synaptic connections (excitatory or inhibitory) is determined by the charge of the ions that flow through these channels. In general, channels that conduct positive ions are excitatory, whereas channels that conduct negative ions are inhibitory. 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. 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.


Pssm-ID: 349850  Cd Length: 116  Bit Score: 55.23  E-value: 1.88e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771  69 FYTINLIIPCLLISCLTVLVFYLPSECGEKVTLCISVLLSLTVFLLLITEIIPSTSLViPLIGEYLLFTMIFVTLSIVIT 148
Cdd:cd03559     1 YYAVSLLLPSILIMVVSWVGFWLPPDSGERVSFKITLLLTYSVFLIIVSDTLPATPYT-PLIDVYFVVCMALLFIALLET 79
                          90       100
                  ....*....|....*....|....*.
gi 1720396771 149 VFVLNVHHRSPRT-HTMPAWVRRVFL 173
Cdd:cd03559    80 IFIVRLVHKQDRVgYVIDRLLRRIFP 105
LGIC_ECD_nAChR_proto_beta-like cd19032
extracellular domain of nicotinic acetylcholine receptor subunit beta-like found in ...
1-65 1.05e-07

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.


Pssm-ID: 349833 [Multi-domain]  Cd Length: 208  Bit Score: 52.33  E-value: 1.05e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720396771   1 MKFGSWTYDKA--KIDLVSMHSRVDQLDFWESGEWVIVDAVGTYNTRKYECCAEiyPDITYAFIIRR 65
Cdd:cd19032   142 MKFGSWTFNGDevSLDLYNNKKFVDLSDYWKSGTWDIIDVPGQLVNKDDAGPTE--TDIIFKIKIRR 206
LGIC_TM_nAChR cd19064
transmembrane domain of nicotinic acetylcholine receptor (nAChR); This family contains ...
421-443 1.53e-05

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.


Pssm-ID: 349866 [Multi-domain]  Cd Length: 113  Bit Score: 44.04  E-value: 1.53e-05
                          10        20
                  ....*....|....*....|...
gi 1720396771 421 VIDRIFLWMFIIVCLLGTVGLFL 443
Cdd:cd19064    91 VIDRLFLWIFLLVCVIGTLGIFL 113
LGIC_TM_bact cd19050
transmembrane domain of prokaryotic pentameric ligand-gated ion channels (pLGIC); This family ...
69-172 4.30e-04

transmembrane domain of prokaryotic pentameric ligand-gated ion channels (pLGIC); This family contains transmembrane (TM) domain of bacterial pentameric ligand-gated ion channels (pLGICs) including ones from Gloeobacter violaceus (GLIC) and Erwinia chrysanthemi (ELIC). The transmembrane region consists of four transmembrane-spanning alpha-helical segments (M1-M4) that are linked by loops. Studies show that GLIC activation is inhibited by most general anaesthetics at clinical concentrations, including xenon which has been used in clinical practice as a potent gaseous anesthetic for decades. Xenon binding sites have been identified in three distinct regions of the TMD: in a large intra-subunit cavity, in the pore, and at the interface between adjacent subunits. Propofol, the drug used for induction and maintenance of general anesthesia, and desflurane, a negative allosteric modulator of GLIC bind at the entrance in the intra-subunit cavity. Alzheimer's drug memantine, which blocks ion conduction at vertebrate pLGICs by plugging the channel pore, has been shown to have similar potency in ELIC.


Pssm-ID: 349852  Cd Length: 119  Bit Score: 39.88  E-value: 4.30e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720396771  69 FYTINLIIPCLLISCLTVLVFYL-PSECGEKVTLCISVLLSLTVFLLLITEIIPSTSLvIPLIGEYLLFTMIFVTLSIVI 147
Cdd:cd19050     1 YYIWKVILPLLLIVAMSWSVFWIdPESFGPQIGISVTSMLTLIAFNFLISNSLPRLPY-LTFMDAFILASYLLVFLALIE 79
                          90       100
                  ....*....|....*....|....*..
gi 1720396771 148 TVFV--LNVHHRSPRTHTMPAWVRRVF 172
Cdd:cd19050    80 VIVThyLARNGKEALALRIDRISRWAF 106
LGIC_ECD_nAChR_B1 cd19024
extracellular domain of nicotinic acetylcholine receptor subunit beta 1 (CHRNB1); This ...
1-67 3.47e-03

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).


Pssm-ID: 349825  Cd Length: 213  Bit Score: 38.65  E-value: 3.47e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1720396771   1 MKFGSWTYDKAKIDLVS---------MHSRVDQLDFWESGEWVIVDAVGTYNTRKYEccaEIYPDITYAFIIRRLP 67
Cdd:cd19024   141 MVFRSYTYDSSEVSLQHgldpdgkelQEIVIHENTFIENGQWSIEHKPSRKNQLPGD---PLYEDITFYLIIRRKP 213
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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