GABRA5

GABRA5
Identifiers
Aliases	GABRA5, gamma-aminobutyric acid type A receptor alpha5 subunit, EIEE79, gamma-aminobutyric acid type A receptor subunit alpha5, DEE79
External IDs	OMIM: 137142; MGI: 95617; HomoloGene: 20219; GeneCards: GABRA5; OMA:GABRA5 - orthologs
Gene location (Human) Chr. Chromosome 15 (human)[1] Band 15q12 Start 26,866,911 bp[1] End 26,949,208 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 B5|7 33.52 cM Start 57,057,420 bp[2] End 57,159,807 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in nucleus accumbens prefrontal cortex Brodmann area 10 cingulate gyrus anterior cingulate cortex orbitofrontal cortex dorsolateral prefrontal cortex hippocampus proper Region I of hippocampus proper Brodmann area 9 Top expressed in subdivision of hippocampus Region I of hippocampus proper hippocampus proper Subplate dentate gyrus dentate gyrus of hippocampal formation granule cell ventromedial nucleus lumbar subsegment of spinal cord subiculum arcuate nucleus More reference expression data BioGPS n/a
Gene ontology Molecular function GABA-A receptor activity transporter activity ion channel activity chloride channel activity extracellular ligand-gated ion channel activity transmembrane signaling receptor activity signaling receptor activity GABA receptor binding inhibitory extracellular ligand-gated ion channel activity benzodiazepine receptor activity GABA-gated chloride ion channel activity transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential Cellular component integral component of membrane cell body GABA-A receptor complex postsynaptic membrane membrane receptor complex synapse integral component of plasma membrane chloride channel complex neuronal cell body membrane dendrite nucleoplasm cytosol plasma membrane cell junction GABA-ergic synapse integral component of postsynaptic membrane integral component of presynaptic membrane integral component of postsynaptic specialization membrane dendrite membrane neuron projection postsynapse Biological process gamma-aminobutyric acid signaling pathway negative regulation of neuron apoptotic process cochlea development associative learning regulation of neuron apoptotic process neuron development chloride transmembrane transport hearing ion transport behavioral fear response brain development inner ear receptor cell development chloride transport innervation signal transduction chemical synaptic transmission ion transmembrane transport regulation of membrane potential nervous system process synaptic transmission, GABAergic regulation of postsynaptic membrane potential Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2558 110886 Ensembl ENSG00000186297 ENSMUSG00000055078 UniProt P31644 Q8BHJ7 RefSeq (mRNA) NM_000810 NM_001165037 NM_176942 NM_001362161 NM_001362162 RefSeq (protein) NP_000801 NP_001158509 NP_795916 NP_001349090 NP_001349091 Location (UCSC) Chr 15: 26.87 – 26.95 Mb Chr 7: 57.06 – 57.16 Mb PubMed search [3] [4]
Wikidata
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Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the GABRA5 gene.^[5][6]

Function

GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA_A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA_A receptor. At least 16 distinct subunits of GABA_A receptors have been identified. Transcript variants utilizing three different alternative non-coding first exons have been described.^[5]

Subunit selective ligands

Recent research has produced several ligands which are moderately selective for GABA_A receptors containing the α₅ subunit. These have proved to be useful in investigating some of the side effects of benzodiazepine and nonbenzodiazepine drugs, particularly the effects on learning and memory such as anterograde amnesia. Inverse agonists at this subunit have nootropic effects and may be useful for the treatment of cognitive disorders such as Alzheimer's disease.

Agonists

• QH-ii-066
• SH-053-R-CH3-2′F

Antagonists

• α₅IA
• Basmisanil (RG-1662, RO5186582): derivative of Ro4938581, negative allosteric modulator at GABA_A α₅, in human trials for treating cognitive deficit in Down syndrome.^[7]
• L-655,708
• MRK-016
• PWZ-029: moderate inverse agonist^[8]
• Pyridazines^[9]
• Ro4938581^[10]
• TB-21007^[11][12]

See also

• GABA_A receptor

References

1. GRCh38: Ensembl release 89: ENSG00000186297 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000055078 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: GABRA5 gamma-aminobutyric acid (GABA) A receptor, alpha 5".
6. Wingrove P, Hadingham K, Wafford K, Kemp JA, Ragan CI, Whiting P (February 1992). "Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit". Biochemical Society Transactions. 20 (1): 18S. doi:10.1042/bst020018s. PMID 1321750.
7. McCabe LL, McCabe ER (March 2013). "Down syndrome and personalized medicine: changing paradigms from genotype to phenotype to treatment". Congenital Anomalies. 53 (1): 1–2. doi:10.1111/cga.12000. PMID 23480351. S2CID 28096008.
8. Savić MM, Clayton T, Furtmüller R, Gavrilović I, Samardzić J, Savić S, et al. (May 2008). "PWZ-029, a compound with moderate inverse agonist functional selectivity at GABA(A) receptors containing alpha5 subunits, improves passive, but not active, avoidance learning in rats". Brain Research. 1208: 150–159. doi:10.1016/j.brainres.2008.02.020. PMC 2577822. PMID 18394590.
9. van Niel MB, Wilson K, Adkins CH, Atack JR, Castro JL, Clarke DE, et al. (September 2005). "A new pyridazine series of GABAA alpha5 ligands". Journal of Medicinal Chemistry. 48 (19): 6004–6011. doi:10.1021/jm050249x. PMID 16162003.
10. Ballard TM, Knoflach F, Prinssen E, Borroni E, Vivian JA, Basile J, et al. (January 2009). "RO4938581, a novel cognitive enhancer acting at GABAA alpha5 subunit-containing receptors". Psychopharmacology. 202 (1–3): 207–223. doi:10.1007/s00213-008-1357-7. PMID 18936916. S2CID 22011375.
11. Chambers MS, Atack JR, Bromidge FA, Broughton HB, Cook S, Dawson GR, et al. (March 2002). "6,7-Dihydro-2-benzothiophen-4(5H)-ones: a novel class of GABA-A alpha5 receptor inverse agonists". Journal of Medicinal Chemistry. 45 (6): 1176–1179. doi:10.1021/jm010471b. PMID 11881985.
12. Chambers MS, Atack JR, Broughton HB, Collinson N, Cook S, Dawson GR, et al. (May 2003). "Identification of a novel, selective GABA(A) alpha5 receptor inverse agonist which enhances cognition". Journal of Medicinal Chemistry. 46 (11): 2227–2240. doi:10.1021/jm020582q. PMID 12747794.

Further reading

• Delong R (March 2007). "GABA(A) receptor alpha5 subunit as a candidate gene for autism and bipolar disorder: a proposed endophenotype with parent-of-origin and gain-of-function features,with or without oculocutaneous albinism". Autism. 11 (2): 135–147. doi:10.1177/1362361307075705. PMID 17353214. S2CID 44688865.
• Otani K, Ujike H, Tanaka Y, Morita Y, Katsu T, Nomura A, et al. (2005). "The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder". Neuroscience Letters. 381 (1–2): 108–113. doi:10.1016/j.neulet.2005.02.010. PMID 15882799. S2CID 54309071.
• Chou KC (April 2004). "Modelling extracellular domains of GABA-A receptors: subtypes 1, 2, 3, and 5". Biochemical and Biophysical Research Communications. 316 (3): 636–642. Bibcode:2004BBRC..316..636C. doi:10.1016/j.bbrc.2004.02.098. PMID 15033447.
• Ritchie RJ, Mattei MG, Lalande M (August 1998). "A large polymorphic repeat in the pericentromeric region of human chromosome 15q contains three partial gene duplications". Human Molecular Genetics. 7 (8): 1253–1260. doi:10.1093/hmg/7.8.1253. PMID 9668167.
• Kim Y, Glatt H, Xie W, Sinnett D, Lalande M (June 1997). "Human gamma-aminobutyric acid-type A receptor alpha5 subunit gene (GABRA5): characterization and structural organization of the 5' flanking region". Genomics. 42 (3): 378–387. doi:10.1006/geno.1997.4770. PMID 9205108.
• Glatt K, Glatt H, Lalande M (April 1997). "Structure and organization of GABRB3 and GABRA5". Genomics. 41 (1): 63–69. doi:10.1006/geno.1997.4639. PMID 9126483.
• Knoll JH, Sinnett D, Wagstaff J, Glatt K, Wilcox AS, Whiting PM, et al. (February 1993). "FISH ordering of reference markers and of the gene for the alpha 5 subunit of the gamma-aminobutyric acid receptor (GABRA5) within the Angelman and Prader-Willi syndrome chromosomal regions". Human Molecular Genetics. 2 (2): 183–189. doi:10.1093/hmg/2.2.183. PMID 8388764.
• Russek SJ, Farb DH (October 1994). "Mapping of the beta 2 subunit gene (GABRB2) to microdissected human chromosome 5q34-q35 defines a gene cluster for the most abundant GABAA receptor isoform". Genomics. 23 (3): 528–533. doi:10.1006/geno.1994.1539. PMID 7851879.
• Glatt KA, Sinnett D, Lalande M (August 1992). "Dinucleotide repeat polymorphism at the GABAA receptor alpha 5 (GABRA5) locus at chromosome 15q11-q13". Human Molecular Genetics. 1 (5): 348. doi:10.1093/hmg/1.5.348. PMID 1338907.
• Wingrove P, Hadingham K, Wafford K, Kemp JA, Ragan CI, Whiting P (February 1992). "Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit". Biochemical Society Transactions. 20 (1): 18S. doi:10.1042/bst020018s. PMID 1321750.

External links

• GABRA5+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.