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)
End	26,949,208 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	57,159,807 bp
RNA expression pattern
	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
	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
	2558
	110886
	ENSG00000186297
	ENSMUSG00000055078
	P31644
	Q8BHJ7
	NM_000810; NM_001165037
	NM_176942; NM_001362161; NM_001362162
	NP_000801; NP_001158509
	NP_795916; NP_001349090; NP_001349091
	Wikidata
View/Edit Human	View/Edit Mouse

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

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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000186297 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000055078 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: GABRA5 gamma-aminobutyric acid (GABA) A receptor, alpha 5".
^ 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". Biochem. Soc. Trans. 20 (1): 18S. doi:10.1042/bst020018s. PMID 1321750.
^ McCabe, L. L.; McCabe, E. R. B. (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.
^ Savić MM, Clayton T, Furtmüller R, et al. (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 Res. 1208: 150–159. doi:10.1016/j.brainres.2008.02.020. PMC 2577822. PMID 18394590.
^ van Niel MB, Wilson K, Adkins CH, et al. (2005). "A new pyridazine series of GABAA alpha5 ligands". J. Med. Chem. 48 (19): 6004–6011. doi:10.1021/jm050249x. PMID 16162003.
^ Ballard TM, Knoflach F, Prinssen E, et al. (2008). "RO4938581, a novel cognitive enhancer acting at GABA(A) alpha5 subunit-containing receptors". Psychopharmacology. 202 (1–3): 207–223. doi:10.1007/s00213-008-1357-7. PMID 18936916. S2CID 22011375.
^ Chambers MS, Atack JR, Bromidge FA, et al. (2002). "6,7-Dihydro-2-benzothiophen-4(5H)-ones: a novel class of GABA-A alpha5 receptor inverse agonists". J. Med. Chem. 45 (6): 1176–1179. doi:10.1021/jm010471b. PMID 11881985.
^ Chambers MS, Atack JR, Broughton HB, et al. (2003). "Identification of a novel, selective GABA(A) alpha5 receptor inverse agonist which enhances cognition". J. Med. Chem. 46 (11): 2227–2240. doi:10.1021/jm020582q. PMID 12747794.

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.

This membrane protein–related article is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000186297 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[entrez-5] "Entrez Gene: GABRA5 gamma-aminobutyric acid (GABA) A receptor, alpha 5".

[pmid1321750-6] 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". Biochem. Soc. Trans. 20 (1): 18S. doi:10.1042/bst020018s. PMID 1321750.

[7] McCabe, L. L.; McCabe, E. R. B. (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.

[pmid18394590-8] Savić MM, Clayton T, Furtmüller R, et al. (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 Res. 1208: 150–159. doi:10.1016/j.brainres.2008.02.020. PMC 2577822. PMID 18394590.

[pmid16162003-9] van Niel MB, Wilson K, Adkins CH, et al. (2005). "A new pyridazine series of GABAA alpha5 ligands". J. Med. Chem. 48 (19): 6004–6011. doi:10.1021/jm050249x. PMID 16162003.

[pmid18936916-10] Ballard TM, Knoflach F, Prinssen E, et al. (2008). "RO4938581, a novel cognitive enhancer acting at GABA(A) alpha5 subunit-containing receptors". Psychopharmacology. 202 (1–3): 207–223. doi:10.1007/s00213-008-1357-7. PMID 18936916. S2CID 22011375.

[pmid11881985-11] Chambers MS, Atack JR, Bromidge FA, et al. (2002). "6,7-Dihydro-2-benzothiophen-4(5H)-ones: a novel class of GABA-A alpha5 receptor inverse agonists". J. Med. Chem. 45 (6): 1176–1179. doi:10.1021/jm010471b. PMID 11881985.

[pmid12747794-12] Chambers MS, Atack JR, Broughton HB, et al. (2003). "Identification of a novel, selective GABA(A) alpha5 receptor inverse agonist which enhances cognition". J. Med. Chem. 46 (11): 2227–2240. doi:10.1021/jm020582q. PMID 12747794.

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