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GABRA6 Membrane Protein Introduction

Introduction of GABRA6

Gamma-aminobutyric acid receptor subunit alpha-6 (GABRA6), also known as GABA-A receptor subunit alpha 5, is a protein that in humans is encoded by the GABRA6 gene. It belongs to the big GABA receptors family which has always been identified as an important target in the etiology and the treatment of epileptic seizures.

Basic Information of GABRA6
Protein Name Gamma-aminobutyric acid receptor subunit alpha-6
Gene Name GABRA6
Aliases GABA(A) receptor subunit alpha-6
Organism Homo sapiens (Human)
UniProt ID Q16445
Transmembrane Times 7
Length (aa) 453
Sequence MASSLPWLCIILWLENALGKLEVEGNFYSENVSRILDNLLEGYDNRLRPGFGGAVTEVKTDIYVTSFGPVSDVEMEYTMDVFFRQTWTDERLKFGGPTEILSLNNLMVSKIWTPDTFFRNGKKSIAHNMTTPNKLFRIMQNGTILYTMRLTINADCPMRLVNFPMDGHACPLKFGSYAYPKSEIIYTWKKGPLYSVEVPEESSSLLQYDLIGQTVSSETIKSNTGEYVIMTVYFHLQRKMGYFMIQIYTPCIMTVILSQVSFWINKESVPARTVFGITTVLTMTTLSISARHSLPKVSYATAMDWFIAVCFAFVFSALIEFAAVNYFTNLQTQKAKRKAQFAAPPTVTISKATEPLEAEIVLHPDSKYHLKKRITSLSLPIVSSSEANKVLTRAPILQSTPVTPPPLSPAFGGTSKIDQYSRILFPVAFAGFNLVYWVVYLSKDTMEVSSSVE

Function of GABRA6 Membrane Protein

GABA is the chief inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors. Studies have shown that GABA-A receptors play a central role in the control of neuronal maturation and hippocampal neurogenesis, as well as reducing neuronal excitability throughout the central nervous system. Recently, it has been reported that there is an association between disturbed γ-amino butyric acid (GABA)-mediated inhibition and neuropsychiatric disorders. As a member of the GABA receptors family, GABRA6 is preferentially expressed in cerebellar granule neurons. It participates in both synaptic and extrasynaptic inhibition, exhibits high sensitivity to GABA and is insensitive to benzodiazepines. What’s more, research has shown that variations in the GABRA6 gene are associated with risk for pathology, including anxiety, drug and alcohol dependence, and schizophrenia.

Structure of ionotropic GABA receptors based on the consensus in multiple literature reviews. Fig.1 Structure of ionotropic GABA receptors based on the consensus in multiple literature reviews. (Gong, 2015)

Application GABRA6 of Membrane Protein in Literature

  1. Gonda X., et al. A new stress sensor and risk factor for suicide: the T allele of the functional genetic variant in the GABRA6 gene. Scientific reports. 2017, 7(1):12887. PubMed ID: 29018204

    This article suggests that stress-associated suicide risk is elevated in carriers of the GABRA6 rs3219151 T allele with several independent markers and predictors of suicidal behaviors converging to this increased risk.

  2. Liao Y.H., et al. Hispidulin alleviated methamphetamine-induced hyperlocomotion by acting at α6 subunit-containing GABAA receptors in the cerebellum. Psychopharmacology. 2016, 233(17):3187-99. PubMed ID: 27385415

    This article suggests that hispidulin could alleviate MIH via acting as a PAM of cerebellar α6GABAARs, but not through COMT inhibition or affecting dopamine receptor responsiveness. Therefore, selective α6GABAAR PAMs may be used as a potential therapeutic target for hyperdopaminergic disorders.

  3. Leggio G.M., et al. Dopamine D3 receptor-dependent changes in alpha6 GABAA subunit expression in striatum modulate anxiety-like behavior: responsiveness and tolerance to diazepam. European Neuropsychopharmacology. 2015, 25(9):1427-36. PubMed ID: 25482686

    This article suggests that genetic deletion or pharmacological blockade of D3R could accelerate the development of tolerance to repeated administrations of diazepam and increase GABRA6 expression. Furthermore, modulation of GABAA receptor by DA transmission may be involved in the mechanisms of anxiety and, if occurring in humans, may have therapeutic relevance following repeated use of drugs targeting D3R.

  4. Inoue A., et al. Association of TMEM132D, COMT, and GABRA6 genotypes with cingulate, frontal cortex and hippocampal emotional processing in panic and major depressive disorder. International journal of psychiatry in clinical practice. 2015, 19(3):192-200. PubMed ID: 25974322

    The aim of this study is to evaluate the association of transmembrane protein 132D (TMEM132D), catechol-O-methyltransferase (COMT), and gamma-aminobutyric acid (GABA) receptor alpha 6 subunit (GABRA6) genotypes with cingulate, frontal cortex and hippocampal emotional processing in panic disorder (PD) and major depressive disorder (MDD). It suggests that TMEM132D, GABRA6, and COMT variants may increase vulnerability to panic.

  5. Prasad D.K., et al. Association of GABRA6 1519 T> C (rs3219151) and Synapsin II (rs37733634) gene polymorphisms with the development of idiopathic generalized epilepsy. Epilepsy research. 2014, 108(8):1267-73. PubMed ID: 25088614

    This article aims to investigate the association of GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G gene polymorphisms with IGE. It indicates that both GABRA6 (rs3219151) T>C and Syn II (rs37733634) A>G polymorphisms are important risk factors for the development of IGE in the South Indian population from Andhra Pradesh.

GABRA6 Preparation Options

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Reference

  1. Gong P, et al. (2015). Ionotropic GABA receptor antagonism-induced adverse outcome pathways for potential neurotoxicity biomarkers. Biomarkers in Medicine. 9(11), 1225-39.

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