glycine receptor subunit alpha-3 isoform X6 [Homo sapiens]
Protein Classification
ligand-gated ion channel( domain architecture ID 1903566)
ligand-gated ion channel (LIC or LGIC) is a member of a family of neurotransmitter receptors vital for communication throughout the nervous system
List of domain hits
| Name | Accession | Description | Interval | E-value | |||||
| LIC super family | cl42365 | Cation transporter family protein; The Ligand-gated Ion Channel (LIC) Family of ... |
1-256 | 1.86e-97 | |||||
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] The actual alignment was detected with superfamily member TIGR00860: Pssm-ID: 455710 [Multi-domain] Cd Length: 459 Bit Score: 293.16 E-value: 1.86e-97
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| Name | Accession | Description | Interval | E-value | |||||
| LIC | TIGR00860 | Cation transporter family protein; The Ligand-gated Ion Channel (LIC) Family of ... |
1-256 | 1.86e-97 | |||||
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: 293.16 E-value: 1.86e-97
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| LGIC_TM_GlyR_alpha | cd19060 | transmembrane domain of alpha subunits of glycine receptor (GlyR); This family contains ... |
59-257 | 2.66e-74 | |||||
transmembrane domain of alpha subunits of glycine receptor (GlyR); This family contains transmembrane (TM) domain of the alpha subunit of glycine receptor (GlyR or GLR) of the amino acid neurotransmitter glycine. 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. GlyR has four known isoforms of the alpha-subunit (alpha1-4, encoded by GLRA1, GLRA2, GLRA3, GLRA4) that are essential to bind ligands and, along with the GlyR beta subunit, have been described to have a regionally and temporally controlled expression during development and maturation of the central nervous system (CNS). These alpha subunits are highly homologous but differ in their kinetic properties, temporal and regional expression and physiological functions. They can form functional chloride-permeable GlyR ion channels by forming homopentamers with 5 alpha subunits or heteropentamers with a combination of alpha and beta subunits, either a 2alpha-3beta or 3alpha-2beta stoichiometry. In human, mutations in glycine receptor alpha subunits cause disruption of GlyR surface expression or reduced ability of expressed GlyRs to conduct chloride ions. Mutations in GlyR alpha1 subunit leads to hyperekplexia, a rare neurological disorder characterized by neonatal hypertonia and exaggerated startle responses to unexpected stimuli, while mutations in GlyR alpha2 are known to cause cortical neuronal migration/autism spectrum disorder and in GlyR alpha3 to cause inflammatory pain sensitization/rhythmic breathing. GlyR alpha1 and alpha2 subunits have an important role in regulation of the excitatory-inhibitory balance, control of motor actions, modulation of sedative ethanol effects and probably regulation of ethanol preference and consumption. Pssm-ID: 349862 Cd Length: 120 Bit Score: 222.50 E-value: 2.66e-74
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| Neur_chan_memb | pfam02932 | Neurotransmitter-gated ion-channel transmembrane region; This family includes the four ... |
65-253 | 1.25e-52 | |||||
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: 170.91 E-value: 1.25e-52
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| Name | Accession | Description | Interval | E-value | |||||
| LIC | TIGR00860 | Cation transporter family protein; The Ligand-gated Ion Channel (LIC) Family of ... |
1-256 | 1.86e-97 | |||||
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: 293.16 E-value: 1.86e-97
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| LGIC_TM_GlyR_alpha | cd19060 | transmembrane domain of alpha subunits of glycine receptor (GlyR); This family contains ... |
59-257 | 2.66e-74 | |||||
transmembrane domain of alpha subunits of glycine receptor (GlyR); This family contains transmembrane (TM) domain of the alpha subunit of glycine receptor (GlyR or GLR) of the amino acid neurotransmitter glycine. 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. GlyR has four known isoforms of the alpha-subunit (alpha1-4, encoded by GLRA1, GLRA2, GLRA3, GLRA4) that are essential to bind ligands and, along with the GlyR beta subunit, have been described to have a regionally and temporally controlled expression during development and maturation of the central nervous system (CNS). These alpha subunits are highly homologous but differ in their kinetic properties, temporal and regional expression and physiological functions. They can form functional chloride-permeable GlyR ion channels by forming homopentamers with 5 alpha subunits or heteropentamers with a combination of alpha and beta subunits, either a 2alpha-3beta or 3alpha-2beta stoichiometry. In human, mutations in glycine receptor alpha subunits cause disruption of GlyR surface expression or reduced ability of expressed GlyRs to conduct chloride ions. Mutations in GlyR alpha1 subunit leads to hyperekplexia, a rare neurological disorder characterized by neonatal hypertonia and exaggerated startle responses to unexpected stimuli, while mutations in GlyR alpha2 are known to cause cortical neuronal migration/autism spectrum disorder and in GlyR alpha3 to cause inflammatory pain sensitization/rhythmic breathing. GlyR alpha1 and alpha2 subunits have an important role in regulation of the excitatory-inhibitory balance, control of motor actions, modulation of sedative ethanol effects and probably regulation of ethanol preference and consumption. Pssm-ID: 349862 Cd Length: 120 Bit Score: 222.50 E-value: 2.66e-74
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| LGIC_TM_anion | cd19049 | transmembrane domain of anionic Cys-loop neurotransmitter-gated ion channels, includes GABAAR, ... |
60-253 | 4.35e-62 | |||||
transmembrane domain of anionic Cys-loop neurotransmitter-gated ion channels, includes GABAAR, GlyR and GluCl; This family contains transmembrane domain of type-A gamma-aminobutyric acid receptor (GABAAR) as well as glycine receptor (GlyR) subunits. Thus far, there are 18 vertebrate receptor subunits categorized in 7 families: alpha1-6, beta1-4, gamma1-4, delta, epsilon, theta, rho, and pi. 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. GlyR, with a similar structure as GABAAR, is concentrated in the brain stem and spinal cord in the CNS and can be activated by glycine, beta-alanine, or taurine. It is selectively blocked by the high-affinity competitive antagonist strychnine, which causes death by asphyxiation. An autosomal dominant R271Q mutation in GLRA1 causes hyperekplexia (Startle disease or Stiff Baby Syndrome) by decreasing glycine sensitivity. Pssm-ID: 349851 Cd Length: 111 Bit Score: 190.74 E-value: 4.35e-62
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| Neur_chan_memb | pfam02932 | Neurotransmitter-gated ion-channel transmembrane region; This family includes the four ... |
65-253 | 1.25e-52 | |||||
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: 170.91 E-value: 1.25e-52
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| LGIC_TM_GluCl | cd19062 | transmembrane domain of glutamate gated chloride channel (GluCl); This family contains ... |
60-256 | 9.42e-47 | |||||
transmembrane domain of glutamate gated chloride channel (GluCl); This family contains transmembrane (TM) domain of the glutamate-gated chloride channel (GluCl) found only in protostomia but are closely related to mammalian glycine 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. These GluCl channels have several roles in these invertebrates, including controlling locomotion and feeding, and mediating sensory inputs into behavior. Comparison of the GluCl gene families between organisms shows that insect gene family is relatively simple, while that found in nematodes tends to be larger and more diverse. Glutamate is an inhibitory neurotransmitter that shapes the responses of projection neurons to olfactory stimuli in the Drosophila. GluCls are targeted by the macrocyclic lactone family of anthelmintics and pesticides in arthropods and nematodes, thus making the GluCls of considerable medical and economic importance. In Drosophila melanogaster, GluCl mediates sensitivity to the antiparasitic agents ivermectin and nodulisporic acid, suggesting that their drug target is the same throughout the Ecdysozoa. Pssm-ID: 349864 Cd Length: 116 Bit Score: 152.12 E-value: 9.42e-47
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| LGIC_TM_GABAAR_gamma | cd19054 | transmembrane domain of gamma subunits of type-A gamma-aminobutyric acid receptor (GABAAR); ... |
60-144 | 4.20e-38 | |||||
transmembrane domain of gamma subunits of type-A gamma-aminobutyric acid receptor (GABAAR); This family contains transmembrane (TM) domain of the gamma subunit of type-A beta-aminobutyric acid receptor (GABAAR), which includes gamma1-gamma3 in vertebrates. 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. Studies show upregulating or preserving GABAA gamma1/3 and gamma2 receptors may protect neurons against neurofibrillary pathology in Alzheimer's disease. Pathogenic missense and truncating variants in GABRG2 have been associated with spectrum of epilepsies, from Dravet syndrome to milder simple febrile seizures. Polymorphisms in GABG3 show consistent evidence of alcohol dependence. Pssm-ID: 349856 Cd Length: 111 Bit Score: 129.69 E-value: 4.20e-38
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| LGIC_TM_GABAAR_beta | cd19053 | transmembrane domain of beta subunits of type-A gamma-aminobutyric acid receptor (GABAAR); ... |
60-145 | 2.96e-37 | |||||
transmembrane domain of beta subunits of type-A gamma-aminobutyric acid receptor (GABAAR); This family contains transmembrane (TM) domain of the beta subunit of type-A beta-aminobutyric acid receptor (GABAAR), which includes beta1-beta4 in vertebrates. 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. Mutations or genetic variations of the genes encoding beta2 (GABRB2) and beta3 (GABRB3) have been associated with human epilepsy, both with and without febrile seizures. Mutations in GABRB2, and GABRB3 have been associated with infantile spasms and Lennox-Gastaut syndrome. A de novo missense mutation of GABRB2 causes early myoclonic encephalopathy, a disease with a devastating prognosis, characterized by neonatal onset of seizures. Another de novo heterozygous missense variant in exon 4 of GABRB2 is associated with intellectual disability and epilepsy. Mutations in the GABRB1 gene encoding beta1 promote alcohol consumption through increased tonic inhibition. Pssm-ID: 349855 Cd Length: 111 Bit Score: 127.39 E-value: 2.96e-37
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| LGIC_ECD_GlyR_alpha | cd19009 | extracellular domain of glycine receptor alpha subunit; This subfamily contains extracellular ... |
1-57 | 1.00e-35 | |||||
extracellular domain of glycine receptor alpha subunit; This subfamily contains extracellular domain of glycine receptor (GlyR or GLR) alpha subunits of the amino acid neurotransmitter glycine. GlyR has four known isoforms of alpha-subunit (alpha1-4, encoded by GLRA1, GLRA2, GLRA3, GLRA4) that are essential to bind ligands, and, along with the GlyR beta subunit, have been described to have a regionally and temporally controlled expression during development and maturation of the central nervous system (CNS). These alpha subunits are highly homologous, but differ in their kinetic properties, temporal and regional expression and physiological functions. They can form functional chloride-permeable GlyR ion channels by forming homopentamers with 5 alpha subunits or heteropentamers with a combination of alpha and beta subunits, either a 2alpha-3beta or 3alpha-2beta stoichiometry. In human, mutations in glycine receptor alpha subunits cause disruption of GlyR surface expression or reduced ability of expressed GlyRs to conduct chloride ions. Mutations in GlyR alpha1 subunit leads to hyperekplexia, a rare neurological disorder characterized by neonatal hypertonia and exaggerated startle responses to unexpected stimuli, while mutations in GlyR alpha2 are known to cause cortical neuronal migration/autism spectrum disorder and in GlyR alpha3 to cause inflammatory pain sensitization/rhythmic breathing. GlyR alpha1 and alpha2 subunits have an important role in regulation of the excitatory-inhibitory balance, control of motor actions, modulation of sedative ethanol effects and probably regulation ethanol preference and consumption. Pssm-ID: 349810 Cd Length: 184 Bit Score: 125.86 E-value: 1.00e-35
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| LGIC_TM_GABAAR_rho | cd19059 | transmembrane domain of rho subunits of type-A gamma-aminobutyric acid receptor (GABAAR); This ... |
60-146 | 1.89e-33 | |||||
transmembrane domain of rho subunits of type-A gamma-aminobutyric acid receptor (GABAAR); This family contains transmembrane (TM) domain of the rho subunit of type-A gamma-aminobutyric acid receptor (GABAAR), which includes rho1-3. 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. These rho 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 rho-1 and rho genes, GABRR1 and GABRR2, 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: 349861 Cd Length: 113 Bit Score: 117.74 E-value: 1.89e-33
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| LGIC_TM_GABAAR_alpha | cd19052 | transmembrane domain of alpha subunits of type-A gamma-aminobutyric acid receptor (GABAAR); ... |
60-149 | 2.50e-33 | |||||
transmembrane domain of alpha subunits of type-A gamma-aminobutyric acid receptor (GABAAR); This family contains transmembrane domain of type-A gamma-aminobutyric acid receptor (GABAAR) as well as glycine receptor (GlyR) subunits. Thus far, there are 18 vertebrate receptor subunits categorized in 7 families: alpha1-6, beta1-4, gamma1-4, delta, epsilon, theta, rho, and pi. 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. GlyR, with a similar structure as GABAAR, is concentrated in the brain stem and spinal cord in the CNS and can be activated by glycine, beta-alanine or taurine. It is selectively blocked by the high-affinity competitive antagonist strychnine, which causes death by asphyxiation. An autosomal dominant R271Q mutation in GLRA1 causes hyperekplexia (Startle disease or Stiff Baby Syndrome) by decreasing glycine sensitivity. Pssm-ID: 349854 Cd Length: 111 Bit Score: 117.27 E-value: 2.50e-33
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| LGIC_TM_GABAAR_delta | cd19055 | transmembrane domain of delta subunits of type-A gamma-aminobutyric acid receptor (GABAAR); ... |
61-144 | 2.62e-30 | |||||
transmembrane domain of delta subunits of type-A gamma-aminobutyric acid receptor (GABAAR); This family contains transmembrane (TM) domain of the delta subunit of type-A gamma-aminobutyric acid receptor (GABAAR), encoded by the gene GABRD. 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. 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: 349857 Cd Length: 121 Bit Score: 109.79 E-value: 2.62e-30
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| LGIC_TM_GABAAR_pi | cd19058 | transmembrane domain of pi subunits of type-A gamma-aminobutyric acid receptor (GABAAR); This ... |
60-146 | 3.23e-30 | |||||
transmembrane domain of pi subunits of type-A gamma-aminobutyric acid receptor (GABAAR); This family contains transmembrane (TM) domain of the pi subunit of type-A gamma-aminobutyric acid receptor (GABAAR), encoded my the gene GABRP. 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. GABRP is expressed mainly in non-neuronal tissues such as the mammary gland, prostate gland, lung, thymus, and uterus. It is also highly expressed in certain types of cancer such as basal-like breast cancer and pancreatic ductal adenocarcinoma. GABRP is involved in inhibitory synaptic transmission in the central nervous system. Its assembly with other GABAAR subunits alters the sensitivity of recombinant receptors to modulatory agents such as pregnanolone. Studies suggest that polymorphisms in the GABRP gene may be associated with the susceptibility to systematic lupus erythematosus (SLE). Pssm-ID: 349860 Cd Length: 123 Bit Score: 109.56 E-value: 3.23e-30
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| LGIC_TM_GABAAR_epsilon | cd19057 | transmembrane domain of epsilon subunits of type-A gamma-aminobutyric acid receptor (GABAAR); ... |
60-145 | 1.33e-27 | |||||
transmembrane domain of epsilon subunits of type-A gamma-aminobutyric acid receptor (GABAAR); This family contains transmembrane (TM) domain of type-A gamma-aminobutyric acid receptor (GABAAR) subunits as well as glycine receptor (GlyR). Thus far, there are 18 vertebrate receptor subunits categorized in 7 families: alpha1-6, beta1-4, gamma1-4, delta, epsilon, theta, rho, and pi. 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. GlyR, with a similar structure as GABAAR, is concentrated in the brain stem and spinal cord in the CNS and can be activated by glycine, beta-alanine, or taurine. It is selectively blocked by the high-affinity competitive antagonist strychnine, which causes death by asphyxiation. An autosomal dominant R271Q mutation in GLRA1 causes hyperekplexia (Startle disease or Stiff Baby Syndrome) by decreasing glycine sensitivity. Pssm-ID: 349859 Cd Length: 115 Bit Score: 102.70 E-value: 1.33e-27
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| LGIC_TM_GABAAR_theta | cd19056 | transmembrane domain of theta subunits of type-A gamma-aminobutyric acid receptor (GABAAR); ... |
61-145 | 8.83e-27 | |||||
transmembrane domain of theta subunits of type-A gamma-aminobutyric acid receptor (GABAAR); This family contains transmembrane (TM) domain of the theta subunit of type-A gamma-aminobutyric acid receptor (GABAAR). 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 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: 349858 Cd Length: 118 Bit Score: 100.78 E-value: 8.83e-27
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| LGIC_TM_GlyR_beta | cd19061 | transmembrane domain of beta subunits of glycine receptor (GlyR); This family contains ... |
60-152 | 5.24e-26 | |||||
transmembrane domain of beta subunits of glycine receptor (GlyR); This family contains transmembrane (TM) domain of the beta subunit of glycine receptor (GlyR or GLR) of the amino acid neurotransmitter glycine, encoded by GLRB gene. 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. 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: 349863 Cd Length: 114 Bit Score: 98.54 E-value: 5.24e-26
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| LGIC_TM | cd03559 | transmembrane domain of Cys-loop neurotransmitter-gated ion channels; This superfamily ... |
60-151 | 2.09e-22 | |||||
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: 89.12 E-value: 2.09e-22
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| LGIC_ECD_GlyR | cd18991 | extracellular domain of glycine receptor (GlyR); This subfamily contains extracellular domain ... |
1-57 | 9.44e-18 | |||||
extracellular domain of glycine receptor (GlyR); This subfamily contains extracellular domain of glycine receptor (GlyR or GLR) of the amino acid neurotransmitter glycine. GlyR has four known isoforms of the alpha-subunit (alpha1-4, encoded by GLRA1, GLRA2, GLRA3, GLRA4) that are essential to bind ligands and a single beta-subunit (encoded by GLRB), all of which have been described to have a regionally and temporally controlled expression during development and maturation of the central nervous system (CNS). Functional chloride-permeable GlyR ion channels are formed by 5 alpha subunit homopentamers or by alpha and beta subunit heteropentamers, which form complexes with either a 2alpha-3beta or 3alpha-2beta stoichiometry. The receptor can be activated by glycine as well as beta-alanine and taurine, and can be selectively blocked by the high-affinity competitive antagonist strychnine. Caffeine is also a competitive antagonist of GlyR. In human, glycine receptor alpha1 and beta subunits are the major targets of mutations that cause disruption of GlyR surface expression or reduced ability of expressed GlyRs to conduct chloride ions, leading to hyperekplexia, a rare neurological disorder characterized by neonatal hypertonia and exaggerated startle responses to unexpected stimuli. Mutations in GlyR alpha2 are known to cause cortical neuronal migration/autism spectrum disorder and in GlyR alpha3 to cause inflammatory pain sensitization/rhythmic breathing. Pssm-ID: 349792 Cd Length: 185 Bit Score: 78.79 E-value: 9.44e-18
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| LGIC_ECD | cd03558 | extracellular domain (ECD) of Cys-loop neurotransmitter-gated ion channels (also known as ... |
1-57 | 1.08e-16 | |||||
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: 75.53 E-value: 1.08e-16
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| LGIC_TM_bact | cd19050 | transmembrane domain of prokaryotic pentameric ligand-gated ion channels (pLGIC); This family ... |
60-158 | 1.20e-16 | |||||
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: 73.78 E-value: 1.20e-16
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| LGIC_ECD_GluCl | cd18993 | glutamate-gated chloride channel (GluCl) extracellular domain; This subfamily contains ... |
2-57 | 2.48e-14 | |||||
glutamate-gated chloride channel (GluCl) extracellular domain; This subfamily contains extracellular domain of glutamate-gated chloride channel (GluCl) found only in protostomia, but are closely related to mammalian glycine receptors. They have several roles in these invertebrates, including controlling locomotion and feeding, and mediating sensory inputs into behavior. Comparison of the GluCl gene families between organisms shows that insect gene family is relatively simple, while that found in nematodes tends to be larger and more diverse. Glutamate is an inhibitory neurotransmitter that shapes the responses of projection neurons to olfactory stimuli in the Drosophila. GluCls are targeted by the macrocyclic lactone family of anthelmintics and pesticides in arthropods and nematodes, thus making the GluCls of considerable medical and economic importance. In Drosophila melanogaster, GluCl mediates sensitivity to the antiparasitic agents ivermectin and nodulisporic acid, suggesting that their drug target is the same throughout the Ecdysozoa. Pssm-ID: 349794 Cd Length: 183 Bit Score: 69.16 E-value: 2.48e-14
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| LGIC_ECD_GlyR_beta | cd19010 | extracellular domain of glycine receptor beta subunit; This subfamily contains extracellular ... |
2-57 | 2.72e-08 | |||||
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: 52.71 E-value: 2.72e-08
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| LGIC_ECD_anion | cd18987 | extracellular domain (ECD) of anionic Cys-loop neurotransmitter-gated ion channels; This ... |
1-57 | 3.33e-08 | |||||
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: 52.30 E-value: 3.33e-08
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| LGIC_ECD_HisCl | cd18992 | extracellular domain of histimine-gated chloride channel (HisCl or HGCC); This family contains ... |
2-57 | 3.43e-08 | |||||
extracellular domain of histimine-gated chloride channel (HisCl or HGCC); This family contains extracellular domain (ECD) of histamine-gated chloride channel (HisCl), a member of the Cys-loop receptor superfamily of ligand-gated ion channels and is closely related to the mammalian GABAA receptor and glycine receptor (GlyR). Histamine (HA) is a neurotransmitter that activates GPCRs in vertebrates, but in arthropods, it is a photoreceptor neurotransmitter, directly gating chloride channels on large monopolar cells (LMCs), postsynaptic to photoreceptors in the lamina. It has also been reported to play important roles in mechanosensory reception, temperature preference, and sleep in insects. HA activates its receptor channels to cause an inward chloride flux in the insect nervous system. In Drosophila, HA acts on two histamine-gated chloride channel (HGCC) subunits called HisCl1 (HisClalpha2, HCLB) and HisCl2 (HisClalpha1, Ort, HCLA). HisCl1 (HCLB) and HisCl2 (HCLA) are expressed predominantly in the insect eye, sharing 60% sequence identity, and forming homomeric and heteromeric HGCCs. HCLA homomers are involved in synaptic transmission in the lamina, while HCLB homomers, localized in the glia cells, have a role in shaping the transmission. HCLB channels, but not HCLA channels, are also responsible for the activation and maintenance of wake state in D. melanogaster. In Manduca sexta, HCLB channels in the flight sensory-motor have been shown to be involved in olfactory processing circuit. Studies show that HCLB channels are more sensitive to agonists when compared with HCLA channels, but insensitive to known LGCC insecticides. Pssm-ID: 349793 Cd Length: 185 Bit Score: 52.23 E-value: 3.43e-08
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| LGIC_ECD_GABAR_GRD-like | cd19007 | gamma-aminobutyric acid receptor subunit alpha-like extracellular domain in protostomia, such ... |
2-57 | 1.65e-06 | |||||
gamma-aminobutyric acid receptor subunit alpha-like extracellular domain in protostomia, such as GRD (GABA/glycine-like receptor of Drosophila); This family contains extracellular domain of alpha-like subunits of type-A gamma-aminobutyric acid receptor (GABAAR) found in protostomia, similar to Drosophila melanogaster GABA/ glycine-like receptor of Drosophila (GRD) 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. LCCH3 has been shown to combine with subunit GRD to form cation-selective GABA-gated ion channels when co-expressed in Xenopus laevis oocytes. 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. Pssm-ID: 349808 Cd Length: 183 Bit Score: 47.24 E-value: 1.65e-06
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| LGIC_TM_cation | cd19051 | transmembrane domain of Cys-loop neurotransmitter-gated ion channels, includes 5HT3, nAChR, ... |
60-102 | 2.01e-03 | |||||
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: 36.96 E-value: 2.01e-03
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