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Conserved domains on  [gi|555992511|ref|XP_005908031|]
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PREDICTED: zinc-activated ligand-gated ion channel [Bos mutus]

Protein Classification

ligand-gated ion channel( domain architecture ID 13040344)

ligand-gated ion channel (LIC or LGIC) is a member of a family of neurotransmitter receptors vital for communication throughout the nervous system; similar to Mus musculus gamma-aminobutyric acid receptor subunit delta

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
LGIC_TM_ZAC cd19065
transmembrane domain of zinc-activated ligand-gated ion channel; This family contains ...
 230-404 3.18e-123

transmembrane domain of zinc-activated ligand-gated ion channel; This family contains transmembrane (TM) domain of zinc-activated ligand-gated ion channel (ZAC). 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. ZAC displays low sequence similarity to other members in the superfamily, with closest matches to the human serotonin 5-HT3 receptor (5-HT3R) subunits 5-HT3A and 5-HT3B, and nAChR alpha7 subunits that exhibit approximately 15% amino acid sequence identity to ZAC. Expression of ZAC has been detected in human fetal whole brain, spinal cord, pancreas, placenta, prostate, thyroid, trachea, and stomach, as well as in adult hippocampus, striatum, amygdala, and thalamus. 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 is as yet unknown.


:

Pssm-ID: 349867  Cd Length: 176  Bit Score: 353.90  E-value: 3.18e-123
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 230 LKAILTLLVPGEALLLADLCGGLLPLH-TERIAYKVTLLLSYLVFHSSLIQALPSSSSCNPLLVYYFTVLLLLLFVSTTE 308
Cdd:cd19065    1 LKAIIALLVPGEALLLADVCGGLLPLRaTERIAYKVTLLLSYLVFHSSLVQALPSSSSCNPLLIYYFTVLLLLLFLSTIE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 309 TVLLTGLLARGNLRAEDSPSPALNGEQHDRGKPGPNPEEAPGAGKGSRRSWAEAADRIFFQVYVVGVACSQFIFIALWMW 388
Cdd:cd19065   81 TVLLAGLLARGNLGAKSSPSPAPRGEQREHGNPGPHPEEAPGRGKGSQRSWAEAADRIFFLVYVVGVLCSQFVFIGIWMW 160

                        170
                 ....*....|....*.
gi 555992511 389 ATCKSDPAPGAASPHG 404
Cdd:cd19065  161 ATCKSDPAPGEAAPHG 176
LGIC_ECD_ZAC cd18994
extracellular domain of zinc-activated ligand-gated ion channel; This family is the ...
 59-228 4.00e-92

extracellular domain of zinc-activated ligand-gated ion channel; This family is the extracellular domain of zinc-activated ligand-gated ion channel (ZAC), a cationic ion channel belonging to the superfamily of Cys-loop receptors, which consists of pentameric ligand-gated ion channels. ZAC displays low sequence similarity to other members in the superfamily, with closest matches to the human serotonin 5-HT3 receptor (5-HT3R) subunits 5-HT3A and 5-HT3B, and nAChR alpha7 subunits that exhibit approximately 15% amino acid sequence identity to ZAC. Expression of ZAC has been detected in human fetal whole brain, spinal cord, pancreas, placenta, prostate, thyroid, trachea, and stomach, as well as in adult hippocampus, striatum, amygdala, and thalamus. 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 is as yet unknown.


:

Pssm-ID: 349795  Cd Length: 170  Bit Score: 274.73  E-value: 4.00e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  59 LVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQRNPVMLPWDVLWMSRLTVREALWVNWQDKSPQARV 138
Cdd:cd18994    1 LLVDVTVFVSNVFNVDILEYTMSSRLLLNLSWLDPRLAWNENISPMSAVTLPWDSLWTPGLTIQEALWVTWRPQSPDARV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 139 DRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQVHAVNEIVSVKREFVVQDLKTQIPPQHLVPC 218
Cdd:cd18994   81 TRDGHVELYLALTTETNCDFELFHFPRDTSDCPLSFFALSNTVLELEFSNHIVNEIVSVKREYVVRVLITQVPPFQLVPC 160

                        170
                 ....*....|
gi 555992511 219 FQVTLSLQNT 228
Cdd:cd18994  161 FQVTLSLKNT 170
 
Name Accession Description Interval E-value
LGIC_TM_ZAC cd19065
transmembrane domain of zinc-activated ligand-gated ion channel; This family contains ...
 230-404 3.18e-123

transmembrane domain of zinc-activated ligand-gated ion channel; This family contains transmembrane (TM) domain of zinc-activated ligand-gated ion channel (ZAC). 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. ZAC displays low sequence similarity to other members in the superfamily, with closest matches to the human serotonin 5-HT3 receptor (5-HT3R) subunits 5-HT3A and 5-HT3B, and nAChR alpha7 subunits that exhibit approximately 15% amino acid sequence identity to ZAC. Expression of ZAC has been detected in human fetal whole brain, spinal cord, pancreas, placenta, prostate, thyroid, trachea, and stomach, as well as in adult hippocampus, striatum, amygdala, and thalamus. 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 is as yet unknown.


Pssm-ID: 349867  Cd Length: 176  Bit Score: 353.90  E-value: 3.18e-123
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 230 LKAILTLLVPGEALLLADLCGGLLPLH-TERIAYKVTLLLSYLVFHSSLIQALPSSSSCNPLLVYYFTVLLLLLFVSTTE 308
Cdd:cd19065    1 LKAIIALLVPGEALLLADVCGGLLPLRaTERIAYKVTLLLSYLVFHSSLVQALPSSSSCNPLLIYYFTVLLLLLFLSTIE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 309 TVLLTGLLARGNLRAEDSPSPALNGEQHDRGKPGPNPEEAPGAGKGSRRSWAEAADRIFFQVYVVGVACSQFIFIALWMW 388
Cdd:cd19065   81 TVLLAGLLARGNLGAKSSPSPAPRGEQREHGNPGPHPEEAPGRGKGSQRSWAEAADRIFFLVYVVGVLCSQFVFIGIWMW 160

                        170
                 ....*....|....*.
gi 555992511 389 ATCKSDPAPGAASPHG 404
Cdd:cd19065  161 ATCKSDPAPGEAAPHG 176
LGIC_ECD_ZAC cd18994
extracellular domain of zinc-activated ligand-gated ion channel; This family is the ...
 59-228 4.00e-92

extracellular domain of zinc-activated ligand-gated ion channel; This family is the extracellular domain of zinc-activated ligand-gated ion channel (ZAC), a cationic ion channel belonging to the superfamily of Cys-loop receptors, which consists of pentameric ligand-gated ion channels. ZAC displays low sequence similarity to other members in the superfamily, with closest matches to the human serotonin 5-HT3 receptor (5-HT3R) subunits 5-HT3A and 5-HT3B, and nAChR alpha7 subunits that exhibit approximately 15% amino acid sequence identity to ZAC. Expression of ZAC has been detected in human fetal whole brain, spinal cord, pancreas, placenta, prostate, thyroid, trachea, and stomach, as well as in adult hippocampus, striatum, amygdala, and thalamus. 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 is as yet unknown.


Pssm-ID: 349795  Cd Length: 170  Bit Score: 274.73  E-value: 4.00e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  59 LVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQRNPVMLPWDVLWMSRLTVREALWVNWQDKSPQARV 138
Cdd:cd18994    1 LLVDVTVFVSNVFNVDILEYTMSSRLLLNLSWLDPRLAWNENISPMSAVTLPWDSLWTPGLTIQEALWVTWRPQSPDARV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 139 DRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQVHAVNEIVSVKREFVVQDLKTQIPPQHLVPC 218
Cdd:cd18994   81 TRDGHVELYLALTTETNCDFELFHFPRDTSDCPLSFFALSNTVLELEFSNHIVNEIVSVKREYVVRVLITQVPPFQLVPC 160

                        170
                 ....*....|
gi 555992511 219 FQVTLSLQNT 228
Cdd:cd18994  161 FQVTLSLKNT 170
Neur_chan_LBD pfam02931
Neurotransmitter-gated ion-channel ligand binding domain; This family is the extracellular ...
 54-205 4.66e-06

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: 47.26  E-value: 4.66e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511   54 NGSKPLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTG-HQRNPVMLPWDVLWMSRLTVR----EALWVN 128
Cdd:pfam02931  21 NGSDPVTVSIGLYLQQIIDVDEKNQDLTTNVWLRQTWTDPRLAWNPEDyGGITSLRLPSDKIWKPDIVLYnkadGIHEVT 100

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 555992511  129 WQDKSpqARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQvHAVNEIVSVKREFVVQD 205
Cdd:pfam02931 101 TPNTN--VRVYYDGTVLWSPPAIYKSSCSIDVTYFPFDEQNCSLKFGSWTYNGEEVDLR-WDDDPPVVELEEIDLSD 174
 
Name Accession Description Interval E-value
LGIC_TM_ZAC cd19065
transmembrane domain of zinc-activated ligand-gated ion channel; This family contains ...
 230-404 3.18e-123

transmembrane domain of zinc-activated ligand-gated ion channel; This family contains transmembrane (TM) domain of zinc-activated ligand-gated ion channel (ZAC). 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. ZAC displays low sequence similarity to other members in the superfamily, with closest matches to the human serotonin 5-HT3 receptor (5-HT3R) subunits 5-HT3A and 5-HT3B, and nAChR alpha7 subunits that exhibit approximately 15% amino acid sequence identity to ZAC. Expression of ZAC has been detected in human fetal whole brain, spinal cord, pancreas, placenta, prostate, thyroid, trachea, and stomach, as well as in adult hippocampus, striatum, amygdala, and thalamus. 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 is as yet unknown.


Pssm-ID: 349867  Cd Length: 176  Bit Score: 353.90  E-value: 3.18e-123
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 230 LKAILTLLVPGEALLLADLCGGLLPLH-TERIAYKVTLLLSYLVFHSSLIQALPSSSSCNPLLVYYFTVLLLLLFVSTTE 308
Cdd:cd19065    1 LKAIIALLVPGEALLLADVCGGLLPLRaTERIAYKVTLLLSYLVFHSSLVQALPSSSSCNPLLIYYFTVLLLLLFLSTIE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 309 TVLLTGLLARGNLRAEDSPSPALNGEQHDRGKPGPNPEEAPGAGKGSRRSWAEAADRIFFQVYVVGVACSQFIFIALWMW 388
Cdd:cd19065   81 TVLLAGLLARGNLGAKSSPSPAPRGEQREHGNPGPHPEEAPGRGKGSQRSWAEAADRIFFLVYVVGVLCSQFVFIGIWMW 160

                        170
                 ....*....|....*.
gi 555992511 389 ATCKSDPAPGAASPHG 404
Cdd:cd19065  161 ATCKSDPAPGEAAPHG 176
LGIC_ECD_ZAC cd18994
extracellular domain of zinc-activated ligand-gated ion channel; This family is the ...
 59-228 4.00e-92

extracellular domain of zinc-activated ligand-gated ion channel; This family is the extracellular domain of zinc-activated ligand-gated ion channel (ZAC), a cationic ion channel belonging to the superfamily of Cys-loop receptors, which consists of pentameric ligand-gated ion channels. ZAC displays low sequence similarity to other members in the superfamily, with closest matches to the human serotonin 5-HT3 receptor (5-HT3R) subunits 5-HT3A and 5-HT3B, and nAChR alpha7 subunits that exhibit approximately 15% amino acid sequence identity to ZAC. Expression of ZAC has been detected in human fetal whole brain, spinal cord, pancreas, placenta, prostate, thyroid, trachea, and stomach, as well as in adult hippocampus, striatum, amygdala, and thalamus. 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 is as yet unknown.


Pssm-ID: 349795  Cd Length: 170  Bit Score: 274.73  E-value: 4.00e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  59 LVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQRNPVMLPWDVLWMSRLTVREALWVNWQDKSPQARV 138
Cdd:cd18994    1 LLVDVTVFVSNVFNVDILEYTMSSRLLLNLSWLDPRLAWNENISPMSAVTLPWDSLWTPGLTIQEALWVTWRPQSPDARV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 139 DRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQVHAVNEIVSVKREFVVQDLKTQIPPQHLVPC 218
Cdd:cd18994   81 TRDGHVELYLALTTETNCDFELFHFPRDTSDCPLSFFALSNTVLELEFSNHIVNEIVSVKREYVVRVLITQVPPFQLVPC 160

                        170
                 ....*....|
gi 555992511 219 FQVTLSLQNT 228
Cdd:cd18994  161 FQVTLSLKNT 170
LGIC_ECD_cation cd18989
extracellular domain (LBD) of cationic Cys-loop neurotransmitter-gated ion channels; This ...
 59-190 1.01e-13

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: 68.93  E-value: 1.01e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  59 LVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGH-QRNPVMLPWDVLWMSRLTVREALWVNWQ--DKSPQ 135
Cdd:cd18989    1 VNVNVSFSLYSILDLDEVEQTLTLSGWLTLTWTDERLTWNPSDYgGITSIVVPSSEIWTPDIVLYNSVDSLDLlgDSNTL 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 555992511 136 ARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQVHA 190
Cdd:cd18989   81 VRVSSDGTVTWVPPGVLTTSCDIDVTYFPFDTQTCSLRFGSWSYTTDEINLTPSS 135
LGIC_ECD_5-HT3 cd18996
extracellular domain of serotonin 5-HT3 receptor; This family contains extracellular domain of ...
 38-185 3.14e-12

extracellular domain of serotonin 5-HT3 receptor; This family contains extracellular domain of serotonin 5-HT3 receptor which belongs to the Cys-loop superfamily of ligand-gated ion channels (LGICs). This ion 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: 349797  Cd Length: 215  Bit Score: 65.48  E-value: 3.14e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  38 NLNSPQEVPDPIQIPNNGSKPLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNST---GHQRnpVMLPWDVL 114
Cdd:cd18996   12 NKTFNSLHLTYTRPVKNWTPPTTVYLDLTLYAILDVDEKLQTLTTYIWLEMVWFNEFLSWNPEqfcGISK--VSVPEDTL 89

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 555992511 115 WMSRLTVREALWVNWQDKSPQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELE 185
Cdd:cd18996   90 WKPDILIYEMTDKDKSPKIPYVYVSNNGTVRNYKPLQVVSTCSLDIYKFPFDTQNCNLTFSSFLHTVNDII 160
LGIC_TM_5-HT3 cd19063
transmembrane domain of 5-hydroxytryptamine 3 (5-HT3) receptor; This family contains ...
 233-386 3.17e-11

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: 60.33  E-value: 3.17e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 233 ILTLLVPGEALLLADLCGGLLPLHT-ERIAYKVTLLLSYLVFHSSLIQALPSSSSCNPLLVYYFTVLLLLLFVSTTETVL 311
Cdd:cd19063    4 VVNLLIPSIFLMLVDLASFYLPPNSgERLGFKVTLLLGYSVFLLILNDLLPATAIGTPLIGVYFVVCLALMVLSLLETIL 83

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 555992511 312 LTGLLArgnlraedspspalngeqhdrgkpgpnpeeapgagkgsrrsW---AEAADRIFFQVYVVGVACSQFIFIALW 386
Cdd:cd19063   84 IVKLLH-----------------------------------------WlrvAYVLDRLLFRLYLLTVLAYAITLGLLW 120
LGIC_ECD_5-HT3B cd19012
extracellular domain of serotonin 5-hydroxytryptamine receptor (5-HT3) receptor subunit B ...
 54-202 9.41e-10

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.


Pssm-ID: 349813  Cd Length: 210  Bit Score: 58.00  E-value: 9.41e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  54 NGSKPLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQR-NPVMLPWDVLWMSRLTVREALWVNWQDK 132
Cdd:cd19012   24 NWTDATTVYIDLFVHAVLDVDGQNQKLTTSIWYRQIWKDEFLVWNSSDFDGiNEISLPLSAIWVPDIVINEFVDVGRYPD 103

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 555992511 133 SPQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQV-HAVNEIVSVKREFV 202
Cdd:cd19012  104 LPYVYVNSSGTIKNYKPIQVVSACDLETYAFPFDRQNCSLTFRSWLHTVGDVDLALwRSPEEIANDKREFL 174
LGIC_ECD_5-HT3C_E cd19013
extracellular domain of serotonin 5-hydroxytryptamine receptor (5-HT3) receptor subunit E ...
 54-200 1.34e-09

extracellular domain of serotonin 5-hydroxytryptamine receptor (5-HT3) receptor subunit E (5HT3E); may include subunits C and D (5-HT3C,D); This subfamily contains extracellular domain of subunit E of serotonin 5-HT3 receptor (5-HT3ER), encoded by the HTR3E gene, and may also contain subunits C and D, all three encoding genes forming a cluster on chromosome 3. Data show that 5-HT3C, 5-HT3D, and 5-HT3E subunits are co-expressed with 5-HT3A in cell bodies of myenteric neurons, and that 5-HT3A and 5-HT3D are expressed in submucosal plexus of the human large intestine while HTR3E is restricted to the colon, intestine, and stomach. None of these subunits can form functional homopentamers, but, upon co-expression with the 5-HT3A subunit, they give rise to functional receptors that differ in maximal responses to 5-HT, and thus modulate 5-HT3 receptor's pharmacological profile. HTR3A and HTR3E polymorphisms have been shown to remarkably up-regulate the expression of 5-HT3 receptors, which have been proved to cause the gastric functional disorders including emesis, eating disorders and IBS-D.


Pssm-ID: 349814  Cd Length: 215  Bit Score: 57.79  E-value: 1.34e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  54 NGSKPLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNS---TGHQRnpVMLPWDVLWMSRLTVREALWVNWQ 130
Cdd:cd19013   28 NLSTPTNVNISFTLYAILGVNEKAQLLTTFLWLRLVWDNEFLSWDPeecEGVTK--ISVPRENLWVPDIFINEFMDEDKS 105

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 555992511 131 DKSPQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELE-FQVHAVNEIVSVKRE 200
Cdd:cd19013  106 PKVPYVYVSHTGRVRDDKPVRVVSSCNLDIFTFPFDIQNCTLTFGSYLHTVDDIKlFLLLSVEEILKNSRK 176
LGIC_TM_cation cd19051
transmembrane domain of Cys-loop neurotransmitter-gated ion channels, includes 5HT3, nAChR, ...
 233-311 2.17e-09

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: 54.68  E-value: 2.17e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 233 ILTLLVPGEALLLADLCGGLLPLHT-ERIAYKVTLLLSYLVFHSSLIQALPSSSSCNPLLVYYFTVLLLLLFVSTTETVL 311
Cdd:cd19051    4 VFNLILPCVLLSVLALLVFLLPPDSgEKVSLGITVLLSLTVFLLLVSESLPPTSDSVPLIGIYLLATMVLSALSTVLTVI 83
LGIC_ECD_anion cd18987
extracellular domain (ECD) of anionic Cys-loop neurotransmitter-gated ion channels; This ...
 59-187 6.01e-09

extracellular domain (ECD) of anionic Cys-loop neurotransmitter-gated ion channels; This family contains the extracellular domain (ECD) of anionic Cys-loop neurotransmitter-gated ion channels which include type-A gamma-aminobutyric acid receptor (GABAAR), glycine receptor (GlyR), invertebrate glutamate-gated chloride channel (GluCl), and histimine-gated chloride channel (HisCl). These neurotransmitter receptors directly mediate chloride permeability and constitute one half of the Cys-loop receptor family. Receptors in this family are composed of five either identical or homologous subunits, which generate diversity in functional profiles and pharmacological preferences. GABAAR and GlyR, both mediate fast inhibitory synaptic transmission. Cl- ions are selectively conducted through the GABAAR receptor pore, resulting in hyperpolarization of the neuron. GluCl channels are found only in protostomia, but are closely related to mammalian glycine receptors (GlyRs). They have several roles in these invertebrates, including controlling locomotion and feeding, and mediating sensory inputs into behavior. 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 this inhibitory half of the Cys-loop receptor family. Many of the therapeutically useful compounds acting at Cys-loop receptors target an allosteric site. The sites in Cys-loop receptors at which these allosteric ligands bind and their structure-based mechanisms of action are largely unresolved.


Pssm-ID: 349788 [Multi-domain]  Cd Length: 185  Bit Score: 55.38  E-value: 6.01e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  59 LVVDVQVFVSNVFSVD--ILRYTVssTLLLRLSWLNTRLAlNSTGHQRNPVMLP---WDVLWMSRLTVREALWVNWQDKS 133
Cdd:cd18987    1 TNVKVSIYIESISSIDeqTMDFTV--DMYLRQRWTDPRLA-YPDRNGTDPILLPsdkFDKIWLPDLYFRNEKSSSFHDVT 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 555992511 134 PQ---ARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQ 187
Cdd:cd18987   78 TPnvlVRIFPNGTVLYSQRLTLTLSCPMNLQKFPFDTQVCTLRLESYGYTTDQVVLH 134
LGIC_ECD cd03558
extracellular domain (ECD) of Cys-loop neurotransmitter-gated ion channels (also known as ...
 59-211 6.22e-09

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: 55.12  E-value: 6.22e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  59 LVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGH-QRNPVMLPWDVLWMSrltvrEALWVNWQD------ 131
Cdd:cd03558    1 VTVTVNISLAQLISVDEVNMDYTTNVFLRQSWIDKRLAYSPADYgGVDSLRLPSEQIWLP-----DLVFYNNKDadfvtt 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 132 KSPQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFqvhavneivSVKREFVVQDLKTQIP 211
Cdd:cd03558   76 DNVLIRLSPDGTVLYSPRAILKSACPMDLKRFPFDQQNCTMKLESWTYDTTDIEL---------VWDSERPDQADFLELP 146
LGIC_ECD_GABAAR cd18990
gamma-aminobutyric acid receptor extracellular domain; This family contains extracellular ...
 59-208 1.03e-07

gamma-aminobutyric acid receptor extracellular domain; This family contains extracellular domain (ECD) of type-A gamma-aminobutyric acid receptor (GABAAR), a member of the pentameric "Cys-loop" superfamily of transmitter-gated ion channels. This family includes 19 isoforms in human; six alpha, 3 beta, 3 gamma, one of delta, epsilon, pi, and theta, known to form heteropentameric GABAARs, and 3 rho subunits that only form homopentameric channels (also known as GABAA rho or GABAC receptor) or pseudoheteromeric if consisting of different rho subunits. The majority of GABAA receptor pentamers contain two alpha subunits, two beta subunits, and a gamma subunit, with different isoforms affecting potency of the neurotransmitter. GABAAR is an anionic channel, mediating fast inhibitory synaptic transmission. Upon gamma-aminobutyric acid (GABA) binding to its site on the ECD, Cl- ions are selectively conducted through the GABAAR pore, resulting in hyperpolarization of the neuron. GABAAR is the principal mediator of rapid inhibitory synaptic transmission in the human brain. Benzodiazepine and barbiturates each bind to their own distinct sites on the ECD. The channels have to contain the gamma subunit and alpha subunits in order to respond to benzodiazepines. Specific combinations of alpha, beta, and gamma subunits exhibit ethanol sensitivity. All these major classes of drugs favor channel-opening. A decline in GABAAR signaling triggers hyperactive neurological disorders such as insomnia, anxiety, and epilepsy.


Pssm-ID: 349791 [Multi-domain]  Cd Length: 184  Bit Score: 51.79  E-value: 1.03e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  59 LVVDVQVFVSNVFSVDILR--YTVssTLLLRLSWLNTRLALNSTGHQRNPVMLPWDvlwMSRLTVREALWVNwqDKSPQA 136
Cdd:cd18990    1 VVVTVEIWVQSIGSISEINmdFTL--DIYFRQYWRDPRLAFDHNGCNKNLTLSGEM---LSKIWTPDTFFVN--SKKAKF 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 137 ----------RVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQVHAVNEIVSVKR-----EF 201
Cdd:cd18990   74 hdvttpnillRIYPNGTVLYSYRLTVTAPCSMDLRKFPMDTQTCSLVFESYGYTTDDVVYKWKEGDTPVTILEkielpQF 153


                 ....*..
gi 555992511 202 VVQDLKT 208
Cdd:cd18990  154 DLTGVTT 160
LGIC_ECD_GABAAR_G3 cd19045
extracellular domain of gamma-aminobutyric acid receptor subunit gamma-3 (GABAAR-G3 or GABRG3); ...
 60-187 2.64e-07

extracellular domain of gamma-aminobutyric acid receptor subunit gamma-3 (GABAAR-G3 or GABRG3); This family contains extracellular domain of gamma-aminobutyric acid receptor subunit gamma-3 (GABAAR-G3), a protein that is encoded by the GABRG3 gene in humans. GABAAR is an anionic channel, mediating fast inhibitory synaptic transmission. Upon gamma-aminobutyric acid (GABA) binding to the ligand binding site on the ECD, Cl- ions are selectively conducted through the GABAAR pore, resulting in hyperpolarization of the neuron. GABAAR is the principal mediator of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signaling triggers hyperactive neurological disorders such as insomnia, anxiety, and epilepsy. The gamma-3 subunit forms heteropentamers with other GABAAR subunits, likely expressed as alpha1-beta3-gamma3. This subunit contains the benzodiazepine binding site. Polymorphisms in GABG3 show consistent evidence of alcohol dependence.


Pssm-ID: 349846  Cd Length: 182  Bit Score: 50.44  E-value: 2.64e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  60 VVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGH----QRNPVMLPW--DVLWMSRLTVrEALWVNWQDKs 133
Cdd:cd19045    2 VIDVDIYVNSIGPVSSINMEYQIDIFFAQTWTDSRLRFNSTMKiltlNSNMVGLIWipDTIFRNSKTA-EAHWITTPNQ- 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 555992511 134 pQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQ 187
Cdd:cd19045   80 -LLRIWNDGKILYTLRLTINAECQLQLHNFPMDEHSCPLIFSSYGYPKEEMIYR 132
LGIC_ECD_GABAAR_G cd19000
extracellular domain of gamma-aminobutyric acid receptor subunit gamma; This family contains ...
 60-187 6.75e-07

extracellular domain of gamma-aminobutyric acid receptor subunit gamma; This family contains extracellular domain (ECD) of the theta subunit of type-A gamma-aminobutyric acid receptor (GABAAR). GABAAR is an anionic channel, mediating fast inhibitory synaptic transmission. Cl- ions are selectively conducted through the GABAAR pore, resulting in hyperpolarization of the neuron. GABAAR is the principal mediator of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signaling triggers hyperactive neurological disorders such as insomnia, anxiety, and epilepsy. GABA stimulates human hepatocellular carcinoma growth through overexpressed GABAA receptor theta subunit. Also, two autism spectrum disorder (ASD)-associated protein truncation variants have been identified in alpha 3 (GABRA3) and theta (GABRQ) genes.


Pssm-ID: 349801  Cd Length: 182  Bit Score: 49.16  E-value: 6.75e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  60 VVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGH----QRNPVMLPW--DVLWMSRLTVrEALWVNWQDKs 133
Cdd:cd19000    2 VIHTDMYVNSIGPVNAINMEYTIDIFFAQTWYDSRLKFNSTMKvlrlNSNMVGKIWipDTFFRNSKKA-DAHWITTPNR- 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 555992511 134 pQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQ 187
Cdd:cd19000   80 -LLRIWNDGRVLYTLRLTINAECQLQLHNFPMDEHSCPLEFSSYGYPKEEIIYK 132
LGIC_ECD_GABAAR_theta cd19003
extracellular domain of gamma-aminobutyric acid receptor subunit theta (GABRQ); This family ...
 58-184 9.57e-07

extracellular domain of gamma-aminobutyric acid receptor subunit theta (GABRQ); This family contains extracellular domain (ECD) of the theta subunit of type-A gamma-aminobutyric acid receptor (GABAAR), and encoded by the GABRQ gene, which is mapped to chromosome Xq28 in a cluster of genes that also that encode the alpha 3 and epsilon subunits. 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 is an anionic channel, mediating fast inhibitory synaptic transmission. Cl- ions are selectively conducted through the GABAAR pore, resulting in hyperpolarization of the neuron. GABAAR is the principal mediator of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signaling triggers hyperactive neurological disorders such as insomnia, anxiety, and epilepsy. GABA stimulates human hepatocellular carcinoma growth through overexpressed GABAAR theta subunit. Also, two autism spectrum disorder (ASD)-associated protein truncation variants have been identified in alpha 3 (GABRA3) and theta (GABRQ) genes.


Pssm-ID: 349804  Cd Length: 183  Bit Score: 48.83  E-value: 9.57e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  58 PLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGhqrnpVMLPWDVLWMSRLTVREALWVNWQDK----- 132
Cdd:cd19003    1 PVPVRISIYVSSIEQISEMNMDYTITMFFHQTWKDSRLAYYETT-----LNLTLDYRMHEKLWVPDCYFLNSKDAfvhdv 75

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 555992511 133 SPQARVDR---DGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTEL 184
Cdd:cd19003   76 TVENRVFQlhpDGTVRYGIRLTTTAACSLDLHKFPMDKQACKLEVESYGYTVEDI 130
LGIC_ECD_GABAAR_E cd19002
extracellular domain of gamma-aminobutyric acid receptor subunit epsilon (GABRE); This family ...
 60-187 2.10e-06

extracellular domain of gamma-aminobutyric acid receptor subunit epsilon (GABRE); This family contains extracellular domain of epsilon subunit of type-A gamma-aminobutyric acid receptor (GABAAR), a protein that is encoded by the GABRE gene in humans. GABAAR is an anionic channel, mediating fast inhibitory synaptic transmission. Upon gamma-aminobutyric acid (GABA) binding to the ligand binding site on the ECD, Cl- ions are selectively conducted through the GABAAR pore, resulting in hyperpolarization of the neuron. GABAAR is the principal mediator of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signaling triggers hyperactive neurological disorders such as insomnia, anxiety, and epilepsy. The epsilon subunits form heteropentamers with other GABAAR subunits, possibly with alpha3, beta4, and theta subunits since their genes are clustered on the same human chromosome. Various combinations of alpha3-, theta-, and epsilon-subunits may be assembled at a regional and developmental level in the brain. Brainstem expression of epsilon subunit-containing GABAA receptors is upregulated during pregnancy, particularly in the ventral respiratory neurons, thus protecting breathing, despite increased neurosteroid levels during pregnancy.


Pssm-ID: 349803  Cd Length: 182  Bit Score: 47.68  E-value: 2.10e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  60 VVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNST-------GHQRNPVMLPWDVLWMSRLTVREALWVNWQdk 132
Cdd:cd19002    2 VVTVEISVNSLGPLSILDMEYTIDIIFSQTWYDERLRYNDTfeslvlnGNVVSQLWIPDTFFRNSKRTHEHEITMPNQ-- 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 555992511 133 spQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQ 187
Cdd:cd19002   80 --MVRIHKDGKVLYTIRMTIDAGCSLHMLRFPMDSHSCPLSFSSFSYPENEMIYK 132
LGIC_ECD_GABAAR_G2 cd19044
extracellular domain of gamma-aminobutyric acid receptor subunit gamma-2 (GABAAR-G2 or GABRG2); ...
 57-187 2.93e-06

extracellular domain of gamma-aminobutyric acid receptor subunit gamma-2 (GABAAR-G2 or GABRG2); This family contains extracellular domain of gamma-aminobutyric acid receptor subunit gamma-2 (GABAAR-G2), a protein that is encoded by the GABRG2 gene in humans. GABAAR is an anionic channel, mediating fast inhibitory synaptic transmission. Upon gamma-aminobutyric acid (GABA) binding to the ligand binding site on the ECD, Cl- ions are selectively conducted through the GABAAR pore, resulting in hyperpolarization of the neuron. GABAAR is the principal mediator of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signaling triggers hyperactive neurological disorders such as insomnia, anxiety, and epilepsy. The gamma-2 subunit forms heteropentamers with other GABAAR subunits, most prevalently expressed as alpha1-beta2-gamma2. The gamma2 subunit also coassembles with other alpha and beta variants in the brain, but these receptors are found in considerably less abundance and are restricted in their regional, e.g. the alpha2-beta3-gamma2 and alpha3-beta3-gamma2 subtypes are highly enriched in hippocampal pyramidal neurons and cholinergic neurons of the basal forebrain, respectively. Pathogenic missense and truncating variants in this gene have been associated with spectrum of epilepsies, from Dravet syndrome to milder simple febrile seizures, while a recurrent GABRG2 missense variant is associated with early-onset seizures, significant motor and speech delays, intellectual disability, hypotonia, movement disorder, dysmorphic features, and vision/ocular issues.


Pssm-ID: 349845  Cd Length: 184  Bit Score: 47.36  E-value: 2.93e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  57 KPLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGH--QRNPVMLpwDVLWMSRLTVR-----EALWVNW 129
Cdd:cd19044    1 KPTVIHTDMYVNSIGPVNAINMEYTIDIFFAQTWYDRRLKFNSTIKvlRLNSNMV--GKIWIPDTFFRnskkaDAHWITT 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 555992511 130 QDKspQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQ 187
Cdd:cd19044   79 PNR--MLRIWNDGRVLYTLRLTIDAECQLQLHNFPMDEHSCPLEFSSYGYPREEIVYQ 134
LGIC_ECD_GABAAR_G1 cd19043
extracellular domain of gamma-aminobutyric acid receptor subunit gamma-1 (GABAAR-G1 or GABRG1); ...
 60-187 3.22e-06

extracellular domain of gamma-aminobutyric acid receptor subunit gamma-1 (GABAAR-G1 or GABRG1); This family contains extracellular domain of gamma-aminobutyric acid receptor subunit gamma-1 (GABAAR-G1), a protein that is encoded by the GABRG1 gene in humans, clustered with the alpha2 gene GABRA2, which is associated with alcohol dependence. GABAAR is an anionic channel, mediating fast inhibitory synaptic transmission. Upon gamma-aminobutyric acid (GABA) binding to the ligand binding site on the ECD, Cl- ions are selectively conducted through the GABAAR pore, resulting in hyperpolarization of the neuron. GABAAR is the principal mediator of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signaling triggers hyperactive neurological disorders such as insomnia, anxiety, and epilepsy. The gamma-1 subunit forms heteropentamers with other GABAAR subunits, likely expressed as combination of alpha1/2-beta-gamma1 subunits. A variant in GABRG1 shows the strongest statistical evidence of association of recovery from eating disorders. Studies show that upregulating or preserving GABAA gamma1/3 and gamma2 receptors may protect neurons against neurofibrillary pathology in Alzheimer's disease.


Pssm-ID: 349844  Cd Length: 182  Bit Score: 47.35  E-value: 3.22e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  60 VVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNST-------GHQRNPVMLPWDVLWMSRLTvrEALWVNWQDK 132
Cdd:cd19043    2 VIETDVYVNSIGPVDPINMEYTIDIIFAQTWFDSRLKFNSTmkvlmlnSNMVGKIWIPDTFFRNSRKS--DAHWITTPNR 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 555992511 133 spQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQ 187
Cdd:cd19043   80 --LLRIWSDGRVLYTLRLTINAECYLQLHNFPMDEHSCPLEFSSYGYPKNEIEYK 132
Neur_chan_LBD pfam02931
Neurotransmitter-gated ion-channel ligand binding domain; This family is the extracellular ...
 54-205 4.66e-06

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: 47.26  E-value: 4.66e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511   54 NGSKPLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTG-HQRNPVMLPWDVLWMSRLTVR----EALWVN 128
Cdd:pfam02931  21 NGSDPVTVSIGLYLQQIIDVDEKNQDLTTNVWLRQTWTDPRLAWNPEDyGGITSLRLPSDKIWKPDIVLYnkadGIHEVT 100

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 555992511  129 WQDKSpqARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQvHAVNEIVSVKREFVVQD 205
Cdd:pfam02931 101 TPNTN--VRVYYDGTVLWSPPAIYKSSCSIDVTYFPFDEQNCSLKFGSWTYNGEEVDLR-WDDDPPVVELEEIDLSD 174
LGIC_ECD_GABAAR_delta cd19001
extracellular domain of gamma-aminobutyric acid receptor subunit delta; This family contains ...
 58-172 5.33e-06

extracellular domain of gamma-aminobutyric acid receptor subunit delta; This family contains extracellular domain of delta subunit of type-A gamma-aminobutyric acid receptor (GABAAR). GABAAR is an anionic channel, mediating fast inhibitory synaptic transmission. Upon gamma-aminobutyric acid (GABA) binding to the ligand binding site on the ECD, Cl- ions are selectively conducted through the GABAAR pore, resulting in hyperpolarization of the neuron. GABAAR is the principal mediator of rapid inhibitory synaptic transmission in the human brain. A decline in GABAAR signaling triggers hyperactive neurological disorders such as insomnia, anxiety, and epilepsy. Receptors containing the delta subunit (GABRD) are expressed exclusively extra-synaptically (in the cortex, hippocampus, thalamus, striatum, and cerebellum) and mediate tonic inhibition. Studies suggest that delta subunits form heteropentamers in similar stoichiometry and arrangement as alpha/beta/gamma receptors, with the delta subunit replacing the gamma subunit (2alpha:2beta:1delta), although other stoichiometries have also been detected. The delta subunit is flexible in its positioning in the pentameric complex, producing receptors with diverse pharmacological properties. Mutations in GABRD have been associated with susceptibility to generalized epilepsy with febrile seizures, type 5. GABRD gene may also be associated with childhood-onset mood disorders.


Pssm-ID: 349802  Cd Length: 184  Bit Score: 46.60  E-value: 5.33e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  58 PLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQRNPVMLPWDVLWMSRLTVREALWVNWQDKSPQAR 137
Cdd:cd19001    1 PVNVALAIEVASIDHISEVNMEYTMTVFLHQSWRDERLSYNHTNETLGLDSRFVDKLWLPDTFIVNAKSAWFHDVTVENK 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 555992511 138 VDR---DGHIEFDLALTTETNCDFELFHFPRDQSDCHL 172
Cdd:cd19001   81 LIRlqpDGVILYSSRITSTVACDMDLTKYPMDEQECML 118
LGIC_ECD_GABAAR_rho2 cd19047
extracellular domain of gamma-aminobutyric acid receptor subunit rho-2 (GABA-rho2 or GABRR2); ...
 58-184 8.83e-06

extracellular domain of gamma-aminobutyric acid receptor subunit rho-2 (GABA-rho2 or GABRR2); This family contains extracellular domain (ECD) of the rho subunit 2 of type-A gamma-aminobutyric acid receptor (GABAAR), encoded by the GABRR2 gene which exists next to GABRR1 (encoding rho subunit 1) on the chromosome region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Close proximity of the rho1 and rho2 subunit genes suggests that they emerged via a local duplication event. Rho1 is expressed in many areas of the brain, but especially high in the retina. This subunit homo-oligomerizes to form GABAA-rho receptors (formerly classified as GABA-rho or GABAc receptor), but does not co-assemble with any of the classical GABAAR subunits. In humans, mutations in the GABRR2 gene may be responsible for some cases of autosomal recessive retinitis pigmentosa. Variation in GABRR2 is also associated with susceptibility to bipolar schizoaffective disorder, as well as alcohol dependence and general cognitive ability. GABA-rho2 receptors expressed pre-synaptically in the spinal dorsal horn have been implicated in pain perception and identified as a novel target for analgesia.


Pssm-ID: 349848  Cd Length: 186  Bit Score: 45.86  E-value: 8.83e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  58 PLVVDVQVfvSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQRnpvmLPWDVLWMSRLTVREALWVNWQ------- 130
Cdd:cd19047    3 PVGVDVQV--ESLDSISEVDMDFTMTLYLRHYWKDERLSFPSTTNKS----MTFDGRLVKKIWVPDVFFVHSKrsfihdt 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 555992511 131 -DKSPQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTEL 184
Cdd:cd19047   77 tTDNIMLRVFPDGHVLYSMRITVTAMCNMDFSRFPLDSQTCSLELESYAYTDEDL 131
LGIC_ECD_bact cd18988
extracellular domain of prokaryotic pentameric ligand-gated ion channels (pLGIC); This family ...
 58-204 1.59e-05

extracellular domain of prokaryotic pentameric ligand-gated ion channels (pLGIC); This family contains extracellular domain (ECD) of bacterial pentameric ligand-gated ion channels (pLGICs), including ones from Gloebacter violaceus (GLIC) and Erwinia chrysanthemi (ELIC). These prokaryotic homologs of Cys-loop receptors have been useful in understanding their eukaryotic counterparts. The largely beta-sheet ECD in this family is similar to other pLGICs, but lacks the cysteine loop and an intracellular domain. While most pLGICs undergo desensitization on prolonged exposure to the agonist, GLIC is activated by protons, but does not desensitize, even at proton concentrations eliciting maximal electrophysiological response (pH 4.5). 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.


Pssm-ID: 349789  Cd Length: 182  Bit Score: 45.36  E-value: 1.59e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  58 PLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQRNPVM---LPWDVLWMSRLTVrealwVNWQDKS- 133
Cdd:cd18988    1 PTEVSVGIYLIDIYGIDEVNETFEADGYLRLRWQDPRLAFDPAAGKEYRLGeaeKQLDEIWNPQIEF-----INQRGLRd 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 555992511 134 ---PQARVDRDGHIE----FDLALTTEtncdFELFHFPRDQSDCHLTFFAFSNTVTELEFQVHAvNEIVSVKREFVVQ 204
Cdd:cd18988   76 tlnRRLRVFPDGTVTyrqrFTGTFSTP----MDLRRFPFDRQTLTIELESFSYDPDEVVLVVDQ-DDTGLSDDLSLPE 148
LGIC_ECD_nAChR_A10 cd19023
extracellular domain of neuronal acetylcholine receptor subunit alpha 10 (CHRNA10); This ...
 59-174 4.02e-05

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: 43.83  E-value: 4.02e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  59 LVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQR-NPVMLPWDVLWMSRLTvreaLWVNWQDK----- 132
Cdd:cd19023    1 LNVTLQITLSQIIDMDERNQILTAYLWIRQVWLDAYLAWNKEAYDGlDTIRIPSSYVWRPDIV----LYNNADDRftgsm 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 555992511 133 SPQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTF 174
Cdd:cd19023   77 ETNVVIRSDGQIMWDSPAITKSSCKVDVSFFPFDGQQCRLTF 118
LGIC_ECD_nAChR_A9 cd19022
extracellular domain of neuronal acetylcholine receptor subunit alpha 9 (CHRNA9); This ...
 57-174 5.66e-05

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: 43.88  E-value: 5.66e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  57 KPLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQ-RNPVMLPWDVLWMSRLTVrealwVNWQDKSPQ 135
Cdd:cd19022   24 KVLNVTLQITLSQIKDMDERNQILTAYLWIRQSWYDAYLKWDRDEYDgLDSIRIPSNLVWRPDIVL-----YNKADDEFS 98

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 555992511 136 ARVDR------DGHIEFDLALTTETNCDFELFHFPRDQSDCHLTF 174
Cdd:cd19022   99 EPVNTnvvlryDGKITWDAPAITKSSCVVDVSYFPFDNQQCNLTF 143
LGIC_ECD_GABAAR_rho cd19005
extracellular domain of gamma-aminobutyric acid receptor subunit rho; This family contains ...
 58-208 1.40e-04

extracellular domain of gamma-aminobutyric acid receptor subunit rho; This family contains extracellular domain of rho subunits (rho1, rho2, and rho3, encoded by GABRR1, GABRR2, and GABRR3, respectively) of type-A gamma-aminobutyric acid receptor (GABAAR). These subunits homo-oligomerize to form GABAA-rho receptors (formerly classified as GABA-rho or GABAC receptor), but do not co-assemble with any of the classical GABAA subunits. They are especially high expression in the retina and their distinctive pharmacological properties are unique; they are not modulated by many GABAA receptor modulators such as barbiturates, benzodiazepines, and neuroactive steroids. In humans, mutations in the GABRR1 and GABRR2 genes may be responsible for some cases of autosomal recessive retinitis pigmentosa. Variation in GABRR1 is also associated with susceptibility to bipolar schizoaffective disorder while a SNP in GABRR2 has been reported to show association with autism.


Pssm-ID: 349806  Cd Length: 186  Bit Score: 42.31  E-value: 1.40e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  58 PLVVDVQVfvSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQRnpvmLPWDVLWMSRLTVREALWVNWQ-----DK 132
Cdd:cd19005    3 PVGVDVQV--ESLDSISEVDMDFTMTLYLRHYWKDERLSFPSTANKS----MTFDGRLVKKIWVPDVFFVHSKrsfihDT 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 133 SPQ---ARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQVHAVNEIVSVKR-----EFVVQ 204
Cdd:cd19005   77 TTDnimLRVFPDGHVLYSLRITVTAMCNMDFSRFPLDTQTCSLELESYAYTEDDLMLYWKNGNESLKTDEkislsQFLIQ 156


                 ....
gi 555992511 205 DLKT 208
Cdd:cd19005  157 KFHT 160
LGIC_ECD_5-HT3A cd19011
extracellular domain of serotonin 5-hydroxytryptamine receptor (5-HT3) receptor subunit A ...
 54-199 2.09e-04

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.


Pssm-ID: 349812  Cd Length: 208  Bit Score: 42.14  E-value: 2.09e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  54 NGSKPLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQR-NPVMLPWDVLWMSRLTVREALWVNWQDK 132
Cdd:cd19011   21 DWRKPTTVSIDVMVYAILNVDEKNQVLTTYIWYRQYWTDEFLQWNPEDFDNvTQLSIPTDSIWVPDILINEFVDVGKSPE 100

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 555992511 133 SPQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQVHAVNEIVSVKR 199
Cdd:cd19011  101 IPYVYVNHEGEVQNYKPIQVVTACSLDIYNFPFDVQNCSLTFTSWLHTIQDINISLWRSPEEVKSDK 167
LGIC_ECD_nAChR_B4 cd19027
extracellular domain of nicotinic acetylcholine receptor subunit beta 4 (CHRNB4); This ...
 61-185 4.25e-04

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: 40.75  E-value: 4.25e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  61 VDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQR-NPVMLPWDVLWMSRL--------TVREALWVNwqd 131
Cdd:cd19027    3 IKLQLSLAQLISVNEREQIMTTNVWLNQEWTDYRLTWNPSDYEGiNKLRIPAKHIWLPDIvlynnadgTYEVSVYTN--- 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 555992511 132 kspqARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELE 185
Cdd:cd19027   80 ----AIVQNNGSVAWLPPAIYKSACKIEVKHFPFDQQNCTLKFRSWTYDHTEID 129
LGIC_ECD_GlyR_beta cd19010
extracellular domain of glycine receptor beta subunit; This subfamily contains extracellular ...
 58-186 1.36e-03

extracellular domain of glycine receptor beta subunit; This subfamily contains extracellular domain of glycine receptor (GlyR or GLR) beta subunit of the amino acid neurotransmitter glycine encoded by GLRB gene. These subunits form heteropentamers with a combination of alpha and beta subunits, either a 2alpha-3beta or 3alpha-2beta stoichiometry. While the alpha subunits contain binding sites for agonists and antagonists and are responsible for ion channel formation, the beta subunit displays structural and regulatory functions, such as GlyR clustering in synaptic locations by interaction between intracellular loop domains with the scaffolding protein gephyrin, and control of pharmacologic responses to agonist or allosteric modulators due in part to the presence of interfaces alpha/beta and beta/beta. GLRB gene mutations are associated with the neurological disorder hyperekplexia, a rare neurological disorder characterized by neonatal hypertonia and exaggerated startle responses to unexpected stimuli, as well as agoraphobic cognitions.


Pssm-ID: 349811  Cd Length: 187  Bit Score: 39.62  E-value: 1.36e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  58 PLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQR-----NPVMlpWDVLWMSRLTVREALWVNWQDK 132
Cdd:cd19010    1 PVDVVVNIFINSFGSIQETTMDYRVNIFLRQKWNDPRLKLPNDFRGSdaltvDPTM--FKCLWKPDLFFANEKSANFHDV 78

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 555992511 133 SPQ---ARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEF 186
Cdd:cd19010   79 TQEnilLFIFRDGDVLVSMRLSITLSCPLDLTLFPMDTQRCKMQLESFGYTTDDLRF 135
LGIC_ECD_GABAR_RDL-like cd19008
gamma-aminobutyric acid receptor subunit beta-like extracellular domain in protostomia, such ...
 61-207 2.55e-03

gamma-aminobutyric acid receptor subunit beta-like extracellular domain in protostomia, such as RDL (resistant to dieldrin); This family contains extracellular domain of beta-like subunits of type-A gamma-aminobutyric acid receptor (GABAAR) found in protostomia, similar to Drosophila melanogaster resistant to dieldrin (RDL) subunits. Drosophila melanogaster expresses three GABA-receptor subunit orthologs: (RDL, resistant to dieldrin; GRD, GABA/glycine-like receptor of Drosophila; LCCH3, ligand-gated chloride channel homolog 3), and may possibly form homo- and/or heteropentameric associations. GABAARs are known to be the molecular targets of a class of insecticides. The resulting pentameric receptors in this family have been shown to be activated by insect GABA-receptor agonists muscimol and CACA, and blocked by antagonists fipronil, dieldrin, and picrotoxin, but not bicuculline. GABAARs are abundant in the CNS, where their physiological role is to mediate fast inhibitory neurotransmission. In insects, this inhibitory transmission plays a crucial role in olfactory information processing. Bombyx mori includes three RDL (RD1, RD2, RD3), one LCCH3, and one GRD subunits. Its RDL1 gene has RNA-editing sites, and the RDL1 and RDL3 genes possess alternative splicing, enhancing the diversity of its GABA-receptor gene family. The three RDL subunits may have arisen from two duplication events.


Pssm-ID: 349809  Cd Length: 184  Bit Score: 38.58  E-value: 2.55e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  61 VDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALnstghQRNPVM--LPWDVLWMSRLTVREALWVNwqDKSPQ--- 135
Cdd:cd19008    3 VGVTMYVLSISSVSEVDMDFTLDFYFRQFWTDPRLAF-----KKSPGVesLTVGSEFIKNIWVPDTFFPN--EKQSYfhi 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511 136 -------ARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFSNTVTELEFQVHAVNEIVSVKRE-----FVV 203
Cdd:cd19008   76 attsnefLRIHHSGSITRSIRLTITASCPMNLQYFPMDRQLCHIEIESFGYTMRDIRYKWNGGPNSVGISPEvelpqFKV 155


                 ....
gi 555992511 204 QDLK 207
Cdd:cd19008  156 LGHR 159
LGIC_ECD_GABAAR_rho3 cd19048
extracellular domain of gamma-aminobutyric acid receptor subunit rho-3 (GABAA-rho3); This ...
 58-178 7.06e-03

extracellular domain of gamma-aminobutyric acid receptor subunit rho-3 (GABAA-rho3); This family contains extracellular domain (ECD) of the rho subunit 3 of type-A gamma-aminobutyric acid receptor (GABAAR), encoded by the GABRR3 gene which maps to a different chromosome to that of GABRR1 and GABRR2. While close proximity of the rho1 and rho2 subunit genes suggests that they emerged via a local duplication event, GABRR3 may have arisen by duplication of a GABRR1/GABRR2 progenitor. This subunit homo-oligomerizes to form GABAA-rho receptors (formerly classified as GABA-rho or GABAc receptor), but does not co-assemble with any of the classical GABAAR subunits. In humans, some individuals contain a variant that is predicted to inactivate this gene product.


Pssm-ID: 349849  Cd Length: 186  Bit Score: 37.32  E-value: 7.06e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 555992511  58 PLVVDVQVFVSNVFSVDILRYTVSSTLLLRLSWLNTRLALNSTGHQRnpvmLPWDVLWMSRLTVREALWVNWQD------ 131
Cdd:cd19048    1 PIPVGIDVQVESIDSISEVDMDFTMTLYLRHYWKDERLSFPSTKNKS----MTFDGRLIKKIWVPDVFFVHSKRsfihdt 76

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 555992511 132 --KSPQARVDRDGHIEFDLALTTETNCDFELFHFPRDQSDCHLTFFAFS 178
Cdd:cd19048   77 tmENVMLRVYPDGNVLFSLRITVSAMCFMDFSRFPLDTQNCSLELESYA 125
 
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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