GABRA5

Protein-coding gene in the species Homo sapiens
GABRA5
Identifiers
AliasesGABRA5, gamma-aminobutyric acid type A receptor alpha5 subunit, EIEE79, gamma-aminobutyric acid type A receptor subunit alpha5, DEE79
External IDsOMIM: 137142 MGI: 95617 HomoloGene: 20219 GeneCards: GABRA5
Gene location (Human)
Chromosome 15 (human)
Chr.Chromosome 15 (human)[1]
Chromosome 15 (human)
Genomic location for GABRA5
Genomic location for GABRA5
Band15q12Start26,866,911 bp[1]
End26,949,208 bp[1]
Gene location (Mouse)
Chromosome 7 (mouse)
Chr.Chromosome 7 (mouse)[2]
Chromosome 7 (mouse)
Genomic location for GABRA5
Genomic location for GABRA5
Band7 B5|7 33.52 cMStart57,057,420 bp[2]
End57,159,807 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • nucleus accumbens

  • prefrontal cortex

  • Brodmann area 10

  • cingulate gyrus

  • orbitofrontal cortex

  • dorsolateral prefrontal cortex

  • hippocampus proper

  • Region I of hippocampus proper

  • Brodmann area 9

  • frontal pole
Top expressed in
  • Region I of hippocampus proper

  • hippocampus proper

  • dentate gyrus

  • ventromedial nucleus

  • subiculum

  • arcuate nucleus

  • amygdala

  • olfactory bulb

  • visual cortex

  • superior colliculus
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
  • sensory perception of sound
  • 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
SpeciesHumanMouse
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 MbChr 7: 57.06 – 57.16 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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 GABAA receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABAA receptor. At least 16 distinct subunits of GABAA 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 GABAA 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

See also

  • GABAA receptor

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000186297 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b "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". 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.
  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.
  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.
  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.
  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.
  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.

Further reading

  • Delong R (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, et al. (2005). "The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder". Neurosci. Lett. 381 (1–2): 108–113. doi:10.1016/j.neulet.2005.02.010. PMID 15882799. S2CID 54309071.
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
  • Chou KC (2004). "Modelling extracellular domains of GABA-A receptors: subtypes 1, 2, 3, and 5". Biochem. Biophys. Res. Commun. 316 (3): 636–642. doi:10.1016/j.bbrc.2004.02.098. PMID 15033447.
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–16903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
  • Ritchie RJ, Mattei MG, Lalande M (1998). "A large polymorphic repeat in the pericentromeric region of human chromosome 15q contains three partial gene duplications". Hum. Mol. Genet. 7 (8): 1253–1260. doi:10.1093/hmg/7.8.1253. PMID 9668167.
  • Kim Y, Glatt H, Xie W, et al. (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 (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, et al. (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". Hum. Mol. Genet. 2 (2): 183–189. doi:10.1093/hmg/2.2.183. PMID 8388764.
  • Russek SJ, Farb DH (1995). "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 (1993). "Dinucleotide repeat polymorphism at the GABAA receptor alpha 5 (GABRA5) locus at chromosome 15q11-q13". Hum. Mol. Genet. 1 (5): 348. doi:10.1093/hmg/1.5.348. PMID 1338907.
  • Wingrove P, Hadingham K, Wafford K, et al. (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.

External links

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

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Cys-loop receptors
5-HT/serotonin
GABA
  • GABAA
    • α1
    • α2
    • α3
    • α4
    • α5
    • α6
    • β1
    • β2
    • β3
    • γ1
    • γ2
    • γ3
    • δ
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    • π
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  • GABAA-ρ
    • ρ1
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Glycine
  • α1
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  • β
Nicotinic acetylcholine
  • pentamers: (α3)2(β4)3
  • (α4)2(β2)3
  • (α7)5
  • (α1)2(β4)3 - Ganglion type
  • (α1)2β1δε - Muscle type
Zinc
Ionotropic glutamates
Ligand-gated only
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‘Orphan’
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ATP-gated channels
Purinergic receptors
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GABA receptor modulators
Ionotropic
GABAATooltip γ-Aminobutyric acid A receptor
GABAA-ρTooltip γ-Aminobutyric acid A-rho receptor
Metabotropic
GABABTooltip γ-Aminobutyric acid B receptor
See also
Receptor/signaling modulators
GABAA receptor positive modulators
GABA metabolism/transport modulators
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