GABRA5: Difference between revisions

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{{Infobox_gene}}
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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]].<ref name="entrez">{{cite web | title = Entrez Gene: GABRA5 gamma-aminobutyric acid (GABA) A receptor, alpha 5| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2558| accessdate = }}</ref><ref name="pmid1321750">{{cite journal |vauthors=Wingrove P, Hadingham K, Wafford K, Kemp JA, Ragan CI, Whiting P | title = Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit | journal = Biochem. Soc. Trans. | volume = 20 | issue = 1 | pages = 18S |date=February 1992 | pmid = 1321750 | doi = | url = | issn = }}</ref>
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==Function==
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[[gamma-aminobutyric acid|GABA]] is the major inhibitory neurotransmitter in the mammalian brain where it acts at [[GABAA receptor|GABA<sub>A</sub> receptor]]s, which are [[ligand-gated ion channel|ligand-gated]] [[chloride channel]]s. Chloride conductance of these channels can be modulated by agents such as [[benzodiazepine]]s that bind to the GABA<sub>A</sub> receptor. At least 16 distinct subunits of GABA<sub>A</sub> receptors have been identified. Transcript variants utilizing three different alternative non-coding first [[exon]]s have been described.<ref name="entrez"/>
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==Subunit selective ligands==
}}
Recent research has produced several ligands which are moderately selective for GABA<sub>A</sub> receptors containing the α<sub>5</sub> 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]].


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===Agonists===
{{GNF_Protein_box
* [[QH-ii-066]]
| image =
* [[SH-053-R-CH3-2′F]]
| image_source =
| PDB =  
| Name = Gamma-aminobutyric acid (GABA) A receptor, alpha 5
| HGNCid = 4079
| Symbol = GABRA5
| AltSymbols =; MGC138184
| OMIM = 137142
| ECnumber = 
| Homologene = 20219
| MGIid = 95617
| Function = {{GNF_GO|id=GO:0004890 |text = GABA-A receptor activity}} {{GNF_GO|id=GO:0005215 |text = transporter activity}} {{GNF_GO|id=GO:0005216 |text = ion channel activity}} {{GNF_GO|id=GO:0005230 |text = extracellular ligand-gated ion channel activity}} {{GNF_GO|id=GO:0005254 |text = chloride channel activity}} {{GNF_GO|id=GO:0030594 |text = neurotransmitter receptor activity}} {{GNF_GO|id=GO:0031404 |text = chloride ion binding}}
| Component = {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0045211 |text = postsynaptic membrane}}
| Process = {{GNF_GO|id=GO:0001662 |text = behavioral fear response}} {{GNF_GO|id=GO:0006811 |text = ion transport}} {{GNF_GO|id=GO:0006821 |text = chloride transport}} {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007214 |text = gamma-aminobutyric acid signaling pathway}} {{GNF_GO|id=GO:0008306 |text = associative learning}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 2558
    | Hs_Ensembl = 
    | Hs_RefseqProtein = NP_000801
    | Hs_RefseqmRNA = NM_000810
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 
    | Hs_GenLoc_start = 
    | Hs_GenLoc_end = 
    | Hs_Uniprot = 
    | Mm_EntrezGene = 110886
    | Mm_Ensembl = ENSMUSG00000055078
    | Mm_RefseqmRNA = NM_176942
    | Mm_RefseqProtein = NP_795916
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 7
    | Mm_GenLoc_start = 57275688
    | Mm_GenLoc_end = 57377873
    | Mm_Uniprot = O88964
  }}
}}
'''Gamma-aminobutyric acid (GABA) A receptor, alpha 5''', also known as '''GABRA5''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: GABRA5 gamma-aminobutyric acid (GABA) A receptor, alpha 5| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2558| accessdate = }}</ref>


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===Inverse agonists===
{{PBB_Summary
* [[α5IA|α<sub>5</sub>IA]]
| section_title =  
* [[Basmisanil]] (RG-1662, RO5186582): derivative of Ro4938581, negative allosteric modulator at GABA<sub>A</sub> α<sub>5</sub>, in human trials for treating cognitive deficit in [[Down syndrome]].<ref>{{Cite journal | last1 = McCabe | first1 = L. L. | last2 = McCabe | first2 = E. R. B. | doi = 10.1111/cga.12000 | title = Down syndrome and personalized medicine: Changing paradigms from genotype to phenotype to treatment | journal = Congenital Anomalies | volume = 53 | issue = 1 | pages = 1–2 | year = 2013 | pmid =  23480351| pmc = }}</ref>
| summary_text = 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.<ref name="entrez">{{cite web | title = Entrez Gene: GABRA5 gamma-aminobutyric acid (GABA) A receptor, alpha 5| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2558| accessdate = }}</ref>
* [[L-655,708]]
}}
* [[MRK-016]]
* [[PWZ-029]]: moderate inverse agonist<ref name="pmid18394590">{{cite journal |vauthors=Savić MM, Clayton T, Furtmüller R |title=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 |journal=Brain Res. |volume=1208 |issue= |pages=150–9 |year=2008 |pmid=18394590 |pmc=2577822 |doi=10.1016/j.brainres.2008.02.020 |url=|display-authors=etal}}</ref>
* [[Pyridazine]]s<ref name="pmid16162003">{{cite journal |vauthors=van Niel MB, Wilson K, Adkins CH |title=A new pyridazine series of GABAA alpha5 ligands |journal=J. Med. Chem. |volume=48 |issue=19 |pages=6004–11 |year=2005 |pmid=16162003 |doi=10.1021/jm050249x |url=|display-authors=etal}}</ref>
* [[Ro4938581]]<ref name="pmid18936916">{{cite journal |vauthors=Ballard TM, Knoflach F, Prinssen E |title=RO4938581, a novel cognitive enhancer acting at GABA(A) alpha5 subunit-containing receptors |journal=Psychopharmacology |volume= 202|issue= 1–3|pages= 207–23|year=2008 |pmid=18936916 |doi=10.1007/s00213-008-1357-7 |url=|display-authors=etal}}</ref>
* [[TB-21007]]<ref name="pmid11881985">{{cite journal |vauthors=Chambers MS, Atack JR, Bromidge FA |title=6,7-Dihydro-2-benzothiophen-4(5H)-ones: a novel class of GABA-A alpha5 receptor inverse agonists |journal=J. Med. Chem. |volume=45 |issue=6 |pages=1176–9 |year=2002 |pmid=11881985|doi=10.1021/jm010471b|display-authors=etal}}</ref><ref name="pmid12747794">{{cite journal |vauthors=Chambers MS, Atack JR, Broughton HB |title=Identification of a novel, selective GABA(A) alpha5 receptor inverse agonist which enhances cognition |journal=J. Med. Chem. |volume=46 |issue=11 |pages=2227–40 |year=2003 |pmid=12747794 |doi=10.1021/jm020582q |url=|display-authors=etal}}</ref>


==See also==
==See also==
* [[GABAA receptor]]
* [[GABAA receptor|GABA<sub>A</sub> receptor]]
 


==References==
==References==
{{reflist|2}}
{{Reflist|2}}


==Further reading==
==Further reading==
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{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal  | author=Delong R |title=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. |journal=Autism : the international journal of research and practice |volume=11 |issue= 2 |pages= 135-47 |year= 2007 |pmid= 17353214 |doi= 10.1177/1362361307075705 }}
*{{cite journal  | author=Delong R |title=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 |journal=Autism |volume=11 |issue= 2 |pages= 135–47 |year= 2007 |pmid= 17353214 |doi= 10.1177/1362361307075705 }}
*{{cite journal  | author=Otani K, Ujike H, Tanaka Y, ''et al.'' |title=The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder. |journal=Neurosci. Lett. |volume=381 |issue= 1-2 |pages= 108-13 |year= 2005 |pmid= 15882799 |doi= 10.1016/j.neulet.2005.02.010 }}
*{{cite journal  |vauthors=Otani K, Ujike H, Tanaka Y |title=The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder |journal=Neurosci. Lett. |volume=381 |issue= 1–2 |pages= 108–13 |year= 2005 |pmid= 15882799 |doi= 10.1016/j.neulet.2005.02.010 |display-authors=etal}}
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
*{{cite journal  |vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |display-authors=etal}}
*{{cite journal  | author=Chou KC |title=Modelling extracellular domains of GABA-A receptors: subtypes 1, 2, 3, and 5. |journal=Biochem. Biophys. Res. Commun. |volume=316 |issue= 3 |pages= 636-42 |year= 2004 |pmid= 15033447 |doi= 10.1016/j.bbrc.2004.02.098 }}
*{{cite journal  | author=Chou KC |title=Modelling extracellular domains of GABA-A receptors: subtypes 1, 2, 3, and 5 |journal=Biochem. Biophys. Res. Commun. |volume=316 |issue= 3 |pages= 636–42 |year= 2004 |pmid= 15033447 |doi= 10.1016/j.bbrc.2004.02.098 }}
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  |vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |display-authors=etal}}
*{{cite journal  | author=Ritchie RJ, Mattei MG, Lalande M |title=A large polymorphic repeat in the pericentromeric region of human chromosome 15q contains three partial gene duplications. |journal=Hum. Mol. Genet. |volume=7 |issue= 8 |pages= 1253-60 |year= 1998 |pmid= 9668167 |doi=  }}
*{{cite journal  |vauthors=Ritchie RJ, Mattei MG, Lalande M |title=A large polymorphic repeat in the pericentromeric region of human chromosome 15q contains three partial gene duplications |journal=Hum. Mol. Genet. |volume=7 |issue= 8 |pages= 1253–60 |year= 1998 |pmid= 9668167 |doi=10.1093/hmg/7.8.1253 }}
*{{cite journal  | author=Kim Y, Glatt H, Xie W, ''et al.'' |title=Human gamma-aminobutyric acid-type A receptor alpha5 subunit gene (GABRA5): characterization and structural organization of the 5' flanking region. |journal=Genomics |volume=42 |issue= 3 |pages= 378-87 |year= 1997 |pmid= 9205108 |doi= 10.1006/geno.1997.4770 }}
*{{cite journal  |vauthors=Kim Y, Glatt H, Xie W |title=Human gamma-aminobutyric acid-type A receptor alpha5 subunit gene (GABRA5): characterization and structural organization of the 5' flanking region |journal=Genomics |volume=42 |issue= 3 |pages= 378–87 |year= 1997 |pmid= 9205108 |doi= 10.1006/geno.1997.4770 |display-authors=etal}}
*{{cite journal  | author=Glatt K, Glatt H, Lalande M |title=Structure and organization of GABRB3 and GABRA5. |journal=Genomics |volume=41 |issue= 1 |pages= 63-9 |year= 1997 |pmid= 9126483 |doi= 10.1006/geno.1997.4639 }}
*{{cite journal  |vauthors=Glatt K, Glatt H, Lalande M |title=Structure and organization of GABRB3 and GABRA5 |journal=Genomics |volume=41 |issue= 1 |pages= 63–9 |year= 1997 |pmid= 9126483 |doi= 10.1006/geno.1997.4639 }}
*{{cite journal  | author=Knoll JH, Sinnett D, Wagstaff J, ''et al.'' |title=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. |journal=Hum. Mol. Genet. |volume=2 |issue= 2 |pages= 183-9 |year= 1993 |pmid= 8388764 |doi=  }}
*{{cite journal  |vauthors=Knoll JH, Sinnett D, Wagstaff J |title=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 |journal=Hum. Mol. Genet. |volume=2 |issue= 2 |pages= 183–9 |year= 1993 |pmid= 8388764 |doi=10.1093/hmg/2.2.183 |display-authors=etal}}
*{{cite journal  | author=Russek SJ, Farb DH |title=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. |journal=Genomics |volume=23 |issue= 3 |pages= 528-33 |year= 1995 |pmid= 7851879 |doi= 10.1006/geno.1994.1539 }}
*{{cite journal  |vauthors=Russek SJ, Farb DH |title=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 |journal=Genomics |volume=23 |issue= 3 |pages= 528–33 |year= 1995 |pmid= 7851879 |doi= 10.1006/geno.1994.1539 }}
*{{cite journal  | author=Glatt KA, Sinnett D, Lalande M |title=Dinucleotide repeat polymorphism at the GABAA receptor alpha 5 (GABRA5) locus at chromosome 15q11-q13. |journal=Hum. Mol. Genet. |volume=1 |issue= 5 |pages= 348 |year= 1993 |pmid= 1338907 |doi=  }}
*{{cite journal  |vauthors=Glatt KA, Sinnett D, Lalande M |title=Dinucleotide repeat polymorphism at the GABAA receptor alpha 5 (GABRA5) locus at chromosome 15q11-q13 |journal=Hum. Mol. Genet. |volume=1 |issue= 5 |pages= 348 |year= 1993 |pmid= 1338907 |doi=10.1093/hmg/1.5.348 }}
*{{cite journal  | author=Wingrove P, Hadingham K, Wafford K, ''et al.'' |title=Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit. |journal=Biochem. Soc. Trans. |volume=20 |issue= 1 |pages= 18S |year= 1992 |pmid= 1321750 |doi=  }}
*{{cite journal  |vauthors=Wingrove P, Hadingham K, Wafford K |title=Cloning and expression of a cDNA encoding the human GABA-A receptor alpha 5 subunit |journal=Biochem. Soc. Trans. |volume=20 |issue= 1 |pages= 18S |year= 1992 |pmid= 1321750 |doi=  |display-authors=etal}}
}}
}}
{{refend}}
{{refend}}


== External links ==
==External links==
* {{MeshName|GABRA5+protein,+human}}
* {{MeshName|GABRA5+protein,+human}}


{{membrane-protein-stub}}
{{NLM content}}
{{NLM content}}
{{Ligand-gated ion channels}}
{{Ligand-gated ion channels}}
{{GABAergics}}
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[[Category:Ion channels]]
[[Category:Ion channels]]
{{WikiDoc Sources}}
[[Category:Biology of bipolar disorder]]
 
 
{{membrane-protein-stub}}

Latest revision as of 00:32, 24 September 2017

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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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Wikidata
View/Edit Human

Gamma-aminobutyric acid (GABA) A receptor, alpha 5, also known as GABRA5, is a protein which in humans is encoded by the GABRA5 gene.[1][2]

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.[1]

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

Inverse agonists

See also

References

  1. ↑ 1.0 1.1 "Entrez Gene: GABRA5 gamma-aminobutyric acid (GABA) A receptor, alpha 5".
  2. ↑ 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. PMID 1321750.
  3. ↑ 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.
  4. ↑ 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: 150–9. doi:10.1016/j.brainres.2008.02.020. PMC 2577822. PMID 18394590.
  5. ↑ van Niel MB, Wilson K, Adkins CH, et al. (2005). "A new pyridazine series of GABAA alpha5 ligands". J. Med. Chem. 48 (19): 6004–11. doi:10.1021/jm050249x. PMID 16162003.
  6. ↑ 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): 207–23. doi:10.1007/s00213-008-1357-7. PMID 18936916.
  7. ↑ 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): 1176–9. doi:10.1021/jm010471b. PMID 11881985.
  8. ↑ 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): 2227–40. doi:10.1021/jm020582q. PMID 12747794.

Further reading

External links

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


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