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
- FunctionsGABA-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 potentialProcessesinhibitory synapse assembly / regulation of postsynaptic membrane potential / synaptic transmission, GABAergicComponentsdendrite 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
Resource Link UniProtKB ID P47869 UniProtKB Entry Name GBRA2_HUMAN GenBank Protein ID 386422 GenBank Gene ID S62907 GeneCard ID GABRA2 GenAtlas ID GABRA2 HGNC ID HGNC:4076 KEGG ID hsa:2555 IUPHAR/Guide To Pharmacology ID 405 NCBI Gene ID 2555 - General References
- 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]
- 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]
- 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]
- 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
Drug Drug group Pharmacological action? Type Actions Details Fludiazepam experimental, illicit yes target potentiator Details Meprobamate approved, illicit yes target agonist Details Pagoclone investigational unknown target Details Zolpidem approved unknown target agonist Details Eszopiclone approved, investigational unknown target agonist Details Zopiclone approved yes target potentiator Details Amobarbital approved, illicit yes target potentiator Details Pentobarbital approved, investigational, vet_approved yes target potentiator Details Butalbital approved, illicit yes target potentiator Details Talbutal approved, illicit yes target potentiator Details Secobarbital approved, vet_approved yes target potentiator Details Metharbital withdrawn yes target potentiator Details Thiopental approved, vet_approved yes target potentiator Details Primidone approved, vet_approved yes target potentiator Details Methylphenobarbital approved yes target potentiator Details Aprobarbital experimental, illicit yes target potentiator Details Butobarbital approved, illicit yes target potentiator Details Heptabarbital experimental yes target potentiator Details Hexobarbital experimental yes target potentiator Details Barbital illicit yes target potentiator Details Dihydro-2-thioxo-5-((5-(2-(trifluoromethyl)phenyl)-2-furanyl)methyl)-4,6(1H,5H)-pyrimidinedione experimental, illicit yes target potentiator Details Quinidine barbiturate approved yes target potentiator Details Ethanol approved unknown target Details AZD-7325 investigational yes target positive allosteric modulator Details MRK-409 experimental yes target modulator Details gamma-Aminobutyric acid approved, investigational yes target inhibitor Details Flumazenil approved yes target allosteric modulator Details