Gamma-aminobutyric acid receptor subunit alpha-2

Details

Name
Gamma-aminobutyric acid receptor subunit alpha-2
Kind
protein
Synonyms
  • GABA(A) receptor subunit alpha-2
  • GABAAR subunit alpha-2
Gene Name
GABRA2
UniProtKB Entry
P47869Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0037005|Gamma-aminobutyric acid receptor subunit alpha-2
MKTKLNIYNMQFLLFVFLVWDPARLVLANIQEDEAKNNITIFTRILDRLLDGYDNRLRPG
LGDSITEVFTNIYVTSFGPVSDTDMEYTIDVFFRQKWKDERLKFKGPMNILRLNNLMASK
IWTPDTFFHNGKKSVAHNMTMPNKLLRIQDDGTLLYTMRLTVQAECPMHLEDFPMDAHSC
PLKFGSYAYTTSEVTYIWTYNASDSVQVAPDGSRLNQYDLLGQSIGKETIKSSTGEYTVM
TAHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISA
RNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGWAWDGKSVVNDKKKEKASV
MIQNNAYAVAVANYAPNLSKDPVLSTISKSATTPEPNKKPENKPAEAKKTFNSVSKIDRM
SRIVFPVLFGTFNLVYWATYLNREPVLGVSP
Number of residues
451
Molecular Weight
51325.85
Theoretical pI
9.41
GO Classification
Functions
GABA-gated chloride ion channel activity / ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
Processes
inhibitory synapse assembly / regulation of postsynaptic membrane potential / synaptic transmission, GABAergic
Components
dendrite membrane / GABA-ergic synapse / inhibitory synapse / neuronal cell body / postsynapse / postsynaptic specialization membrane / synapse / synaptic vesicle membrane / transmembrane transporter complex
General Function
Alpha subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:10449790, PubMed:29961870, PubMed:31032849). GABA-gated chloride channels, also named GABA(A) receptors (GABAAR), consist of five subunits arranged around a central pore and contain GABA active binding site(s) located at the alpha and beta subunit interfaces (By similarity). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (PubMed:10449790). Chloride influx into the postsynaptic neuron following GABAAR opening decreases the neuron ability to generate a new action potential, thereby reducing nerve transmission (By similarity). The alpha-2 subunit exhibits synaptogenic activity together with beta-2 and very little to no activity together with beta-3, the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (By similarity)
Specific Function
benzodiazepine receptor activity
Pfam Domain Function
Signal Regions
1-28
Transmembrane Regions
250-270 281-300 312-332 421-441
Cellular Location
Postsynaptic cell membrane
Gene sequence
>lcl|BSEQ0010268|Gamma-aminobutyric acid receptor subunit alpha-2 (GABRA2)
ATGAAGACAAAATTGAACATCTACAACATGCAGTTCCTGCTTTTTGTTTTCTTGGTGTGG
GACCCTGCCAGGTTGGTGCTGGCTAACATCCAAGAAGATGAGGCTAAAAATAACATTACC
ATCTTTACGAGAATTCTTGACAGACTTCTGGATGGTTACGATAATCGGCTTAGACCAGGA
CTGGGAGACAGTATTACTGAAGTCTTCACTAACATCTACGTGACCAGTTTTGGCCCTGTC
TCAGATACAGATATGGAATATACAATTGATGTTTTCTTTCGACAAAAATGGAAAGATGAA
CGTTTAAAATTTAAAGGTCCTATGAATATCCTTCGACTAAACAATTTAATGGCTAGCAAA
ATCTGGACTCCAGATACCTTTTTTCACAATGGGAAAAAATCAGTAGCTCATAATATGACA
ATGCCAAATAAGTTGCTTCGAATTCAGGATGATGGGACTCTGCTGTATACCATGAGGCTT
ACAGTTCAAGCTGAATGCCCAATGCACTTGGAGGATTTCCCAATGGATGCTCATTCATGT
CCTCTGAAATTTGGCAGCTATGCATATACAACTTCAGAGGTCACTTATATTTGGACTTAC
AATGCATCTGATTCAGTACAGGTTGCTCCTGATGGCTCTAGGTTAAATCAATATGACCTG
CTGGGCCAATCAATCGGAAAGGAGACAATTAAATCCAGTACAGGTGAATATACTGTAATG
ACAGCTCATTTCCACCTGAAAAGAAAAATTGGGTATTTTGTGATTCAAACCTATCTGCCT
TGCATCATGACTGTCATTCTCTCCCAAGTTTCATTCTGGCTTAACAGAGAATCTGTGCCT
GCAAGAACTGTGTTTGGAGTAACAACTGTCCTAACAATGACAACTCTAAGCATCAGTGCT
CGGAATTCTCTCCCCAAAGTGGCTTATGCAACTGCCATGGACTGGTTTATTGCTGTTTGT
TATGCATTTGTGTTCTCTGCCCTAATTGAATTTGCAACTGTTAATTACTTCACCAAAAGA
GGATGGGCTTGGGATGGGAAGAGTGTAGTAAATGACAAGAAAAAAGAAAAGGCTTCCGTT
ATGATACAGAACAACGCTTATGCAGTGGCTGTTGCCAATTATGCCCCGAATCTTTCAAAA
GATCCAGTTCTCTCCACCATCTCCAAGAGTGCAACCACGCCAGAACCCAACAAGAAGCCA
GAAAACAAGCCAGCTGAAGCAAAGAAAACTTTCAACAGTGTTAGCAAAATTGACAGAATG
TCCAGAATAGTTTTTCCAGTTTTGTTTGGTACCTTTAATTTAGTTTACTGGGCTACATAT
TTAAACAGAGAACCTGTATTAGGGGTCAGTCCTTGA
Chromosome Location
4
Locus
4p12
External Identifiers
ResourceLink
UniProtKB IDP47869
UniProtKB Entry NameGBRA2_HUMAN
GenBank Protein ID386422
GenBank Gene IDS62907
GeneCard IDGABRA2
GenAtlas IDGABRA2
HGNC IDHGNC:4076
KEGG IDhsa:2555
IUPHAR/Guide To Pharmacology ID405
NCBI Gene ID2555
General References
  1. Hadingham KL, Wingrove P, Le Bourdelles B, Palmer KJ, Ragan CI, Whiting PJ: Cloning of cDNA sequences encoding human alpha 2 and alpha 3 gamma-aminobutyric acidA receptor subunits and characterization of the benzodiazepine pharmacology of recombinant alpha 1-, alpha 2-, alpha 3-, and alpha 5-containing human gamma-aminobutyric acidA receptors. Mol Pharmacol. 1993 Jun;43(6):970-5. [Article]
  2. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. Edenberg HJ, Dick DM, Xuei X, Tian H, Almasy L, Bauer LO, Crowe RR, Goate A, Hesselbrock V, Jones K, Kwon J, Li TK, Nurnberger JI Jr, O'Connor SJ, Reich T, Rice J, Schuckit MA, Porjesz B, Foroud T, Begleiter H: Variations in GABRA2, encoding the alpha 2 subunit of the GABA(A) receptor, are associated with alcohol dependence and with brain oscillations. Am J Hum Genet. 2004 Apr;74(4):705-14. Epub 2004 Mar 12. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Fludiazepamexperimental, illicityestargetpotentiatorDetails
Meprobamateapproved, illicityestargetagonistDetails
PagocloneinvestigationalunknowntargetDetails
ZolpidemapprovedunknowntargetagonistDetails
Eszopicloneapproved, investigationalunknowntargetagonistDetails
ZopicloneapprovedyestargetpotentiatorDetails
Amobarbitalapproved, illicityestargetpotentiatorDetails
Pentobarbitalapproved, investigational, vet_approvedyestargetpotentiatorDetails
Butalbitalapproved, illicityestargetpotentiatorDetails
Talbutalapproved, illicityestargetpotentiatorDetails
Secobarbitalapproved, vet_approvedyestargetpotentiatorDetails
MetharbitalwithdrawnyestargetpotentiatorDetails
Thiopentalapproved, vet_approvedyestargetpotentiatorDetails
Primidoneapproved, vet_approvedyestargetpotentiatorDetails
MethylphenobarbitalapprovedyestargetpotentiatorDetails
Aprobarbitalexperimental, illicityestargetpotentiatorDetails
Butobarbitalapproved, illicityestargetpotentiatorDetails
HeptabarbitalexperimentalyestargetpotentiatorDetails
HexobarbitalexperimentalyestargetpotentiatorDetails
BarbitalillicityestargetpotentiatorDetails
Dihydro-2-thioxo-5-((5-(2-(trifluoromethyl)phenyl)-2-furanyl)methyl)-4,6(1H,5H)-pyrimidinedioneexperimental, illicityestargetpotentiatorDetails
Quinidine barbiturateapprovedyestargetpotentiatorDetails
EthanolapprovedunknowntargetDetails
AZD-7325investigationalyestargetpositive allosteric modulatorDetails
MRK-409experimentalyestargetmodulatorDetails
gamma-Aminobutyric acidapproved, investigationalyestargetinhibitorDetails
Flumazenilapprovedyestargetallosteric modulatorDetails