Gamma-aminobutyric acid receptor subunit beta-2

Details

Name
Gamma-aminobutyric acid receptor subunit beta-2
Synonyms
  • GABA(A) receptor subunit beta-2
  • GABAAR subunit beta-2
Gene Name
GABRB2
UniProtKB Entry
P47870Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0037195|Gamma-aminobutyric acid receptor subunit beta-2
MWRVRKRGYFGIWSFPLIIAAVCAQSVNDPSNMSLVKETVDRLLKGYDIRLRPDFGGPPV
AVGMNIDIASIDMVSEVNMDYTLTMYFQQAWRDKRLSYNVIPLNLTLDNRVADQLWVPDT
YFLNDKKSFVHGVTVKNRMIRLHPDGTVLYGLRITTTAACMMDLRRYPLDEQNCTLEIES
YGYTTDDIEFYWRGDDNAVTGVTKIELPQFSIVDYKLITKKVVFSTGSYPRLSLSFKLKR
NIGYFILQTYMPSILITILSWVSFWINYDASAARVALGITTVLTMTTINTHLRETLPKIP
YVKAIDMYLMGCFVFVFMALLEYALVNYIFFGRGPQRQKKAAEKAASANNEKMRLDVNKI
FYKDIKQNGTQYRSLWDPTGNLSPTRRTTNYDFSLYTMDPHENILLSTLEIKNEMATSEA
VMGLGDPRSTMLAYDASSIQYRKAGLPRHSFGRNALERHVAQKKSRLRRRASQLKITIPD
LTDVNAIDRWSRIFFPVVFSFFNIVYWLYYVN
Number of residues
512
Molecular Weight
59149.895
Theoretical pI
9.66
GO Classification
Functions
GABA-gated chloride ion channel activity / neurotransmitter receptor activity / transmitter-gated monoatomic ion channel activity involved in regulation of postsynaptic membrane potential
Processes
chemical synaptic transmission / inhibitory synapse assembly
Components
cytoplasmic vesicle membrane / GABA-ergic synapse / postsynaptic specialization membrane / transmembrane transporter complex
General Function
Beta subunit of the heteropentameric ligand-gated chloride channel gated by gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in the brain (PubMed:19763268, PubMed:27789573, PubMed:29950725, PubMed:8264558). 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 interface(s) (PubMed:29950725). When activated by GABA, GABAARs selectively allow the flow of chloride anions across the cell membrane down their electrochemical gradient (By similarity). 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). GABAARs containing alpha-1 and beta-2 or -3 subunits exhibit synaptogenic activity; the gamma-2 subunit being necessary but not sufficient to induce rapid synaptic contacts formation (PubMed:23909897, PubMed:25489750). Extrasynaptic beta-2 receptors contribute to the tonic GABAergic inhibition (By similarity). Beta-containing GABAARs can simultaneously bind GABA and histamine where histamine binds at the interface of two neighboring beta subunits, which may be involved in the regulation of sleep and wakefulness (By similarity)
Specific Function
Chloride channel activity
Pfam Domain Function
Signal Regions
1-25
Transmembrane Regions
242-262 273-292 311-331 491-511
Cellular Location
Postsynaptic cell membrane
Gene sequence
>lcl|BSEQ0011685|Gamma-aminobutyric acid receptor subunit beta-2 (GABRB2)
ATGTGGAGAGTGCGGAAAAGGGGCTACTTTGGGATTTGGTCCTTCCCCTTAATAATCGCC
GCTGTCTGTGCGCAGAGTGTCAATGACCCTAGTAATATGTCGCTGGTTAAAGAGACGGTG
GATAGACTCCTGAAAGGCTATGACATTCGTCTGAGACCAGATTTTGGAGGTCCCCCCGTG
GCTGTGGGGATGAACATTGACATTGCCAGCATCGATATGGTTTCTGAAGTCAATATGGAT
TATACCTTGACAATGTACTTTCAACAAGCCTGGAGAGATAAGAGGCTGTCCTATAATGTA
ATACCTTTAAACTTGACTCTGGACAACAGAGTGGCAGACCAGCTCTGGGTGCCTGATACC
TATTTCCTGAACGATAAGAAGTCATTTGTGCACGGAGTGACTGTTAAGAACCGCATGATT
CGCCTGCATCCTGATGGCACCGTCCTTTATGGACTCAGAATCACAACCACAGCTGCCTGC
ATGATGGACCTAAGGAGGTACCCACTGGATGAACAAAACTGCACCTTGGAAATTGAGAGC
TATGGATACACAACTGATGACATTGAGTTTTACTGGCGTGGCGATGATAATGCAGTAACA
GGAGTAACGAAAATTGAACTTCCACAGTTCTCTATTGTAGATTACAAACTTATCACCAAG
AAGGTTGTTTTTTCCACAGGTTCCTATCCCAGGTTATCCCTCAGCTTTAAGCTTAAGAGA
AACATTGGCTACTTTATCCTGCAAACATACATGCCTTCCATCCTGATTACCATCCTCTCC
TGGGTCTCCTTCTGGATTAATTACGATGCTTCAGCTGCAAGGGTGGCATTAGGAATCACA
ACTGTCCTCACAATGACCACAATCAACACCCACCTCCGGGAAACTCTCCCTAAAATCCCC
TATGTGAAGGCCATTGACATGTACCTGATGGGGTGCTTTGTCTTCGTTTTCATGGCCCTT
CTGGAATATGCCCTAGTCAACTACATCTTCTTTGGGAGGGGGCCCCAACGCCAAAAGAAA
GCAGCTGAGAAGGCTGCCAGTGCCAACAATGAGAAGATGCGCCTGGATGTCAACAAGATG
GACCCCCATGAGAACATCTTACTGAGCACTCTCGAGATAAAAAATGAAATGGCCACATCT
GAGGCTGTGATGGGACTTGGAGACCCCAGAAGCACAATGCTAGCCTATGATGCCTCCAGC
ATCCAGTATCGGAAAGCTGGGTTGCCCAGGCATAGTTTTGGCCGAAATGCTCTGGAACGA
CATGTGGCGCAAAAGAAAAGTCGCCTGAGGAGACGCGCCTCCCAACTGAAAATCACCATC
CCTGACTTGACTGATGTGAATGCCATAGATCGGTGGTCCCGCATATTCTTCCCAGTGGTT
TTTTCCTTCTTCAACATCGTCTATTGGCTTTATTATGTGAACTAA
Chromosome Location
5
Locus
5q34
External Identifiers
ResourceLink
UniProtKB IDP47870
UniProtKB Entry NameGBRB2_HUMAN
GenBank Protein ID455946
GenBank Gene IDS67368
GeneCard IDGABRB2
GenAtlas IDGABRB2
HGNC IDHGNC:4082
PDB ID(s)6D6T, 6D6U, 6X3S, 6X3T, 6X3U, 6X3V, 6X3W, 6X3X, 6X3Z, 6X40, 7T0W, 7T0Z, 8DD2, 8DD3, 8SGO, 8SI9, 8SID
KEGG IDhsa:2561
NCBI Gene ID2561
General References
  1. Hadingham KL, Wingrove PB, Wafford KA, Bain C, Kemp JA, Palmer KJ, Wilson AW, Wilcox AS, Sikela JM, Ragan CI, et al.: Role of the beta subunit in determining the pharmacology of human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1993 Dec;44(6):1211-8. [Article]
  2. McKinley DD, Lennon DJ, Carter DB: Cloning, sequence analysis and expression of two forms of mRNA coding for the human beta 2 subunit of the GABAA receptor. Brain Res Mol Brain Res. 1995 Jan;28(1):175-9. [Article]
  3. Zhao C, Xu Z, Wang F, Chen J, Ng SK, Wong PW, Yu Z, Pun FW, Ren L, Lo WS, Tsang SY, Xue H: Alternative-splicing in the exon-10 region of GABA(A) receptor beta(2) subunit gene: relationships between novel isoforms and psychotic disorders. PLoS One. 2009 Sep 18;4(9):e6977. doi: 10.1371/journal.pone.0006977. [Article]
  4. 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]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Zhao C, Xu Z, Chen J, Yu Z, Tong KL, Lo WS, Pun FW, Ng SK, Tsang SY, Xue H: Two isoforms of GABA(A) receptor beta2 subunit with different electrophysiological properties: Differential expression and genotypical correlations in schizophrenia. Mol Psychiatry. 2006 Dec;11(12):1092-105. Epub 2006 Sep 19. [Article]
  7. Denis NJ, Vasilescu J, Lambert JP, Smith JC, Figeys D: Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry. Proteomics. 2007 Mar;7(6):868-74. [Article]

Associated Data

Bio-Entities
Bio-EntityType
Gamma-aminobutyric acid receptor subunit beta-2 (Humans)protein
primary
GABA(A) Receptor (Humans)protein
Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
Propofolapproved, investigational, vet_approvedyestargetpotentiatorDetails
Ginkgo bilobaapproved, investigational, nutraceuticalunknowntargetnegative modulatorDetails
Fludiazepamexperimental, illicityestargetpotentiatorDetails
Fospropofolapproved, illicit, investigationalyestargetpotentiatorDetails
EthanolapprovedunknowntargetDetails
CarisoprodolapprovedunknowntargetmodulatorDetails
EltanoloneinvestigationalyestargetinhibitorDetails
gamma-Aminobutyric acidapproved, investigationalyestargetinhibitorDetails
ZK-93423investigationalyestargetinhibitorDetails
Ethchlorvynolapproved, illicit, withdrawnyestargetantagonistDetails
ThiocolchicosideexperimentalyestargetinhibitorDetails
Brexanoloneapproved, investigationalyestargetinhibitorDetails
Desfluraneapprovedyestargetpositive allosteric modulatorDetails
Alprazolamapproved, illicit, investigationalyestargetpositive allosteric modulatorDetails
Butabarbitalapproved, illicityestargetpositive allosteric modulatorDetails
Chlordiazepoxideapproved, illicit, investigationalyestargetpositive allosteric modulatorDetails
Clobazamapproved, illicityestargetpositive allosteric modulatorDetails
Clonazepamapproved, illicityestargetpositive allosteric modulatorDetails
Clorazepic acidapproved, illicityestargetpositive allosteric modulatorDetails
Lorazepamapprovedyestargetpositive allosteric modulatorDetails
Ethchlorvynolapproved, illicit, withdrawnyestargetpositive allosteric modulatorDetails
Enfluraneapproved, investigational, vet_approvedyestargetpotentiatorDetails
Temazepamapproved, investigationalyestargetpositive allosteric modulatorDetails
Butalbitalapproved, illicityestargetpositive allosteric modulatorDetails
Etomidateapprovedyestargetpositive allosteric modulatorDetails
Talbutalapproved, illicityestargetpositive allosteric modulatorDetails
Pentobarbitalapproved, investigational, vet_approvedyestargetpositive allosteric modulatorDetails
Meprobamateapproved, illicityestargetpositive allosteric modulatorDetails
Eszopicloneapproved, investigationalyestargetpositive allosteric modulatorDetails
Metharbitalwithdrawnyestargetpositive allosteric modulatorDetails
Isofluraneapproved, vet_approvedyestargetpositive allosteric modulatorDetails
Primidoneapproved, vet_approvedyestargetpositive allosteric modulatorDetails
Halazepamapproved, illicit, withdrawnyestargetpositive allosteric modulatorDetails
Propofolapproved, investigational, vet_approvedyestargetpositive allosteric modulatorDetails
Diazepamapproved, illicit, investigational, vet_approvedyestargetpositive allosteric modulatorDetails
Oxazepamapprovedyestargetpositive allosteric modulatorDetails
Methoxyfluraneapproved, investigational, vet_approved, withdrawnyestargetpositive allosteric modulatorDetails
Methyprylonapproved, illicit, withdrawnyestargetpositive allosteric modulatorDetails
Halothaneapproved, vet_approvedyestargetpositive allosteric modulatorDetails
Flumazenilapprovedyestargetpositive allosteric modulatorDetails
Estazolamapproved, illicityestargetpositive allosteric modulatorDetails
Sevofluraneapproved, vet_approvedyestargetagonistDetails
Glutethimideapproved, illicityestargetpositive allosteric modulatorDetails
Prazepamapproved, illicityestargetpositive allosteric modulatorDetails
Quazepamapproved, illicityestargetpositive allosteric modulatorDetails
AmoxapineapprovedunknowntargetbinderDetails
Prasteroneapproved, investigational, nutraceuticalunknowntargetantagonistDetails
ThiocolchicosideexperimentalyestargetantagonistDetails
Stiripentolapprovedyestargetagonistpositive allosteric modulatorDetails
Taurineapproved, nutraceuticalyestargetagonistDetails
Lamotrigineapproved, investigationalunknowntargetantagonistinducerDetails
Apalutamideapproved, investigationalnotargetantagonistDetails
Brexanoloneapproved, investigationalyestargetpositive allosteric modulatorDetails
Memantineapproved, investigationalunknowntargetbinderDetails
Medroxyprogesterone acetateapproved, investigationalunknowntargetinhibitorDetails
Phenytoinapproved, vet_approvedunknowntargetDetails
Midazolamapproved, illicityestargetpositive allosteric modulatorDetails
Flurazepamapproved, illicit, investigationalyestargetpositive allosteric modulatorDetails
Triazolamapproved, investigationalyestargetpositive allosteric modulatorDetails
Bromazepamapproved, illicit, investigationalyestargetpositive allosteric modulatorDetails
Nitrazepamapprovedyestargetpositive allosteric modulatorDetails
Camazepamexperimental, illicityestargetpositive allosteric modulatorDetails
Delorazepamexperimental, illicityestargetpositive allosteric modulatorDetails
Flunitrazepamapproved, illicityestargetpositive allosteric modulatorDetails
Etizolamexperimentalyestargetpositive allosteric modulatorDetails
Medazepamexperimentalyestargetpositive allosteric modulatorDetails
Doxefazepamexperimentalyestargetpositive allosteric modulatorDetails
Lormetazepamapprovedyestargetpositive allosteric modulatorDetails
Nordazepamexperimentalyestargetpositive allosteric modulatorDetails
Adinazolamexperimentalyestargetpositive allosteric modulatorDetails
Ethyl loflazepateexperimental, illicityestargetpositive allosteric modulatorDetails
Cloxazolamexperimentalyestargetpositive allosteric modulatorDetails
Clotiazepamapproved, illicityestargetpositive allosteric modulatorDetails
Ketazolamapprovedyestargetpositive allosteric modulatorDetails
Cinolazepamexperimentalyestargetpositive allosteric modulatorDetails
Brotizolaminvestigational, withdrawnyestargetpositive allosteric modulatorDetails
Pinazepamexperimentalyestargetpositive allosteric modulatorDetails
Loprazolamexperimentalyestargetpositive allosteric modulatorDetails
Oxazepam acetateexperimentalyestargetpositive allosteric modulatorDetails
1,2-Benzodiazepineapproved, investigationalunknowntargetpositive allosteric modulatorDetails
Cinazepamexperimentalyestargetpositive allosteric modulatorDetails
Bentazepamexperimentalyestargetpositive allosteric modulatorDetails
Mexazolamexperimentalyestargetpositive allosteric modulatorDetails
Remimazolamapproved, investigationalyestargetpositive allosteric modulatorDetails
Ganaxoloneapproved, investigationalyestargetpositive allosteric modulatorDetails
Zuranoloneapproved, experimentalyestargetpositive allosteric modulatorDetails