Gamma-aminobutyric acid type B receptor subunit 2

NameGamma-aminobutyric acid type B receptor subunit 2
Synonyms
  • G-protein coupled receptor 51
  • GABA-B receptor 2
  • GPR51
  • GPRC3B
  • HG20
Gene NameGABBR2
OrganismHuman
Amino acid sequence
>lcl|BSEQ0004595|Gamma-aminobutyric acid type B receptor subunit 2
MASPRSSGQPGPPPPPPPPPARLLLLLLLPLLLPLAPGAWGWARGAPRPPPSSPPLSIMG
LMPLTKEVAKGSIGRGVLPAVELAIEQIRNESLLRPYFLDLRLYDTECDNAKGLKAFYDA
IKYGPNHLMVFGGVCPSVTSIIAESLQGWNLVQLSFAATTPVLADKKKYPYFFRTVPSDN
AVNPAILKLLKHYQWKRVGTLTQDVQRFSEVRNDLTGVLYGEDIEISDTESFSNDPCTSV
KKLKGNDVRIILGQFDQNMAAKVFCCAYEENMYGSKYQWIIPGWYEPSWWEQVHTEANSS
RCLRKNLLAAMEGYIGVDFEPLSSKQIKTISGKTPQQYEREYNNKRSGVGPSKFHGYAYD
GIWVIAKTLQRAMETLHASSRHQRIQDFNYTDHTLGRIILNAMNETNFFGVTGQVVFRNG
ERMGTIKFTQFQDSREVKVGEYNAVADTLEIINDTIRFQGSEPPKDKTIILEQLRKISLP
LYSILSALTILGMIMASAFLFFNIKNRNQKLIKMSSPYMNNLIILGGMLSYASIFLFGLD
GSFVSEKTFETLCTVRTWILTVGYTTAFGAMFAKTWRVHAIFKNVKMKKKIIKDQKLLVI
VGGMLLIDLCILICWQAVDPLRRTVEKYSMEPDPAGRDISIRPLLEHCENTHMTIWLGIV
YAYKGLLMLFGCFLAWETRNVSIPALNDSKYIGMSVYNVGIMCIIGAAVSFLTRDQPNVQ
FCIVALVIIFCSTITLCLVFVPKLITLRTNPDAATQNRRFQFTQNQKKEDSKTSTSVTSV
NQASTSRLEGLQSENHRLRMKITELDKDLEEVTMQLQDTPEKTTYIKQNHYQELNDILNL
GNFTESTDGGKAILKNHLDQNPQLQWNTTEPSRTCKDPIEDINSPEHIQRRLSLQLPILH
HAYLPSIGGVDASCVSPCVSPTASPRHRHVPPSFRVMVSGL
Number of residues941
Molecular Weight105820.52
Theoretical pI8.83
GO Classification
Functions
  • G-protein coupled GABA receptor activity
Processes
  • synaptic transmission
  • G-protein coupled receptor signaling pathway
  • negative regulation of adenylate cyclase activity
  • gamma-aminobutyric acid signaling pathway
Components
  • plasma membrane
  • cell junction
  • integral component of plasma membrane
  • neuron projection
  • G-protein coupled receptor heterodimeric complex
  • cytoplasm
  • postsynaptic membrane
General FunctionG-protein coupled gaba receptor activity
Specific FunctionComponent of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception.
Pfam Domain Function
Transmembrane Regions484-504 523-543 552-572 598-618 655-675 692-712 721-741
GenBank Protein ID3776098
UniProtKB IDO75899
UniProtKB Entry NameGABR2_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0016760|Gamma-aminobutyric acid type B receptor subunit 2 (GABBR2)
ATGGCTTCCCCGCGGAGCTCCGGGCAGCCCGGGCCGCCGCCGCCGCCGCCACCGCCGCCC
GCGCGCCTGCTACTGCTACTGCTGCTGCCGCTGCTGCTGCCTCTGGCGCCCGGGGCCTGG
GGCTGGGCGCGGGGCGCCCCCCGGCCGCCGCCCAGCAGCCCGCCGCTCTCCATCATGGGC
CTCATGCCGCTCACCAAGGAGGTGGCCAAGGGCAGCATCGGGCGCGGTGTGCTCCCCGCC
GTGGAACTGGCCATCGAGCAGATCCGCAACGAGTCACTCCTGCGCCCCTACTTCCTCGAC
CTGCGGCTCTATGACACGGAGTGCGACAACGCAAAAGGGTTGAAAGCCTTCTACGATGCA
ATAAAATACGGGCCTAACCACTTGATGGTGTTTGGAGGCGTCTGTCCATCCGTCACATCC
ATCATTGCAGAGTCCCTCCAAGGCTGGAATCTGGTGCAGCTTTCTTTTGCTGCAACCACG
CCTGTTCTAGCCGATAAGAAAAAATACCCTTATTTCTTTCGGACCGTCCCATCAGACAAT
GCGGTGAATCCAGCCATTCTGAAGTTGCTCAAGCACTACCAGTGGAAGCGCGTGGGCACG
CTGACGCAAGACGTTCAGAGGTTCTCTGAGGTGCGGAATGACCTGACTGGAGTTCTGTAT
GGCGAGGACATTGAGATTTCAGACACCGAGAGCTTCTCCAACGATCCCTGTACCAGTGTC
AAAAAGCTGAAGGGGAATGATGTGCGGATCATCCTTGGCCAGTTTGACCAGAATATGGCA
GCAAAAGTGTTCTGTTGTGCATACGAGGAGAACATGTATGGTAGTAAATATCAGTGGATC
ATTCCGGGCTGGTACGAGCCTTCTTGGTGGGAGCAGGTGCACACGGAAGCCAACTCATCC
CGCTGCCTCCGGAAGAATCTGCTTGCTGCCATGGAGGGCTACATTGGCGTGGATTTCGAG
CCCCTGAGCTCCAAGCAGATCAAGACCATCTCAGGAAAGACTCCACAGCAGTATGAGAGA
GAGTACAACAACAAGCGGTCAGGCGTGGGGCCCAGCAAGTTCCACGGGTACGCCTACGAT
GGCATCTGGGTCATCGCCAAGACACTGCAGAGGGCCATGGAGACACTGCATGCCAGCAGC
CGGCACCAGCGGATCCAGGACTTCAACTACACGGACCACACGCTGGGCAGGATCATCCTC
AATGCCATGAACGAGACCAACTTCTTCGGGGTCACGGGTCAAGTTGTATTCCGGAATGGG
GAGAGAATGGGGACCATTAAATTTACTCAATTTCAAGACAGCAGGGAGGTGAAGGTGGGA
GAGTACAACGCTGTGGCCGACACACTGGAGATCATCAATGACACCATCAGGTTCCAAGGA
TCCGAACCACCAAAAGACAAGACCATCATCCTGGAGCAGCTGCGGAAGATCTCCCTACCT
CTCTACAGCATCCTCTCTGCCCTCACCATCCTCGGGATGATCATGGCCAGTGCTTTTCTC
TTCTTCAACATCAAGAACCGGAATCAGAAGCTCATAAAGATGTCGAGTCCATACATGAAC
AACCTTATCATCCTTGGAGGGATGCTCTCCTATGCTTCCATATTTCTCTTTGGCCTTGAT
GGATCCTTTGTCTCTGAAAAGACCTTTGAAACACTTTGCACCGTCAGGACCTGGATTCTC
ACCGTGGGCTACACGACCGCTTTTGGGGCCATGTTTGCAAAGACCTGGAGAGTCCACGCC
ATCTTCAAAAATGTGAAAATGAAGAAGAAGATCATCAAGGACCAGAAACTGCTTGTGATC
GTGGGGGGCATGCTGCTGATCGACCTGTGTATCCTGATCTGCTGGCAGGCTGTGGACCCC
CTGCGAAGGACAGTGGAGAAGTACAGCATGGAGCCGGACCCAGCAGGACGGGATATCTCC
ATCCGCCCTCTCCTGGAGCACTGTGAGAACACCCATATGACCATCTGGCTTGGCATCGTC
TATGCCTACAAGGGACTTCTCATGTTGTTCGGTTGTTTCTTAGCTTGGGAGACCCGCAAC
GTCAGCATCCCCGCACTCAACGACAGCAAGTACATCGGGATGAGTGTCTACAACGTGGGG
ATCATGTGCATCATCGGGGCCGCTGTCTCCTTCCTGACCCGGGACCAGCCCAATGTGCAG
TTCTGCATCGTGGCTCTGGTCATCATCTTCTGCAGCACCATCACCCTCTGCCTGGTATTC
GTGCCGAAGCTCATCACCCTGAGAACAAACCCAGATGCAGCAACGCAGAACAGGCGATTC
CAGTTCACTCAGAATCAGAAGAAAGAAGATTCTAAAACGTCCACCTCGGTCACCAGTGTG
AACCAAGCCAGCACATCCCGCCTGGAGGGCCTACAGTCAGAAAACCATCGCCTGCGAATG
AAGATCACAGAGCTGGATAAAGACTTGGAAGAGGTCACCATGCAGCTGCAGGACACACCA
GAAAAGACCACCTACATTAAACAGAACCACTACCAAGAGCTCAATGACATCCTCAACCTG
GGAAACTTCACTGAGAGCACAGATGGAGGAAAGGCCATTTTAAAAAATCACCTCGATCAA
AATCCCCAGCTACAGTGGAACACAACAGAGCCCTCTCGAACATGCAAAGATCCTATAGAA
GATATAAACTCTCCAGAACACATCCAGCGTCGGCTGTCCCTCCAGCTCCCCATCCTCCAC
CACGCCTACCTCCCATCCATCGGAGGCGTGGACGCCAGCTGTGTCAGCCCCTGCGTCAGC
CCCACCGCCAGCCCCCGCCACAGACATGTGCCACCCTCCTTCCGAGTCATGGTCTCGGGC
CTGTAA
GenBank Gene IDAJ012188
GeneCard IDNot Available
GenAtlas IDGABBR2
HGNC IDHGNC:4507
Chromosome Location9
Locus9q22.1-q22.3
References
  1. White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, Marshall FH: Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature. 1998 Dec 17;396(6712):679-82. 9872316
  2. Ng GY, McDonald T, Bonnert T, Rigby M, Heavens R, Whiting P, Chateauneuf A, Coulombe N, Kargman S, Caskey T, Evans J, O'neill GP, Liu Q: Cloning of a novel G-protein-coupled receptor GPR 51 resembling GABAB receptors expressed predominantly in nervous tissues and mapped proximal to the hereditary sensory neuropathy type 1 locus on chromosome 9. Genomics. 1999 Mar 15;56(3):288-95. 10087195
  3. Martin SC, Russek SJ, Farb DH: Molecular identification of the human GABABR2: cell surface expression and coupling to adenylyl cyclase in the absence of GABABR1. Mol Cell Neurosci. 1999 Mar;13(3):180-91. 10328880
  4. Clark JA, Mezey E, Lam AS, Bonner TI: Distribution of the GABA(B) receptor subunit gb2 in rat CNS. Brain Res. 2000 Mar 31;860(1-2):41-52. 10727622
  5. Humphray SJ, Oliver K, Hunt AR, Plumb RW, Loveland JE, Howe KL, Andrews TD, Searle S, Hunt SE, Scott CE, Jones MC, Ainscough R, Almeida JP, Ambrose KD, Ashwell RI, Babbage AK, Babbage S, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beasley H, Beasley O, Bird CP, Bray-Allen S, Brown AJ, Brown JY, Burford D, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Chen Y, Clarke G, Clark SY, Clee CM, Clegg S, Collier RE, Corby N, Crosier M, Cummings AT, Davies J, Dhami P, Dunn M, Dutta I, Dyer LW, Earthrowl ME, Faulkner L, Fleming CJ, Frankish A, Frankland JA, French L, Fricker DG, Garner P, Garnett J, Ghori J, Gilbert JG, Glison C, Grafham DV, Gribble S, Griffiths C, Griffiths-Jones S, Grocock R, Guy J, Hall RE, Hammond S, Harley JL, Harrison ES, Hart EA, Heath PD, Henderson CD, Hopkins BL, Howard PJ, Howden PJ, Huckle E, Johnson C, Johnson D, Joy AA, Kay M, Keenan S, Kershaw JK, Kimberley AM, King A, Knights A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd C, Lloyd DM, Lovell J, Martin S, Mashreghi-Mohammadi M, Matthews L, McLaren S, McLay KE, McMurray A, Milne S, Nickerson T, Nisbett J, Nordsiek G, Pearce AV, Peck AI, Porter KM, Pandian R, Pelan S, Phillimore B, Povey S, Ramsey Y, Rand V, Scharfe M, Sehra HK, Shownkeen R, Sims SK, Skuce CD, Smith M, Steward CA, Swarbreck D, Sycamore N, Tester J, Thorpe A, Tracey A, Tromans A, Thomas DW, Wall M, Wallis JM, West AP, Whitehead SL, Willey DL, Williams SA, Wilming L, Wray PW, Young L, Ashurst JL, Coulson A, Blocker H, Durbin R, Sulston JE, Hubbard T, Jackson MJ, Bentley DR, Beck S, Rogers J, Dunham I: DNA sequence and analysis of human chromosome 9. Nature. 2004 May 27;429(6990):369-74. 15164053
  6. 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. 15489334
  7. Ng GY, Clark J, Coulombe N, Ethier N, Hebert TE, Sullivan R, Kargman S, Chateauneuf A, Tsukamoto N, McDonald T, Whiting P, Mezey E, Johnson MP, Liu Q, Kolakowski LF Jr, Evans JF, Bonner TI, O'Neill GP: Identification of a GABAB receptor subunit, gb2, required for functional GABAB receptor activity. J Biol Chem. 1999 Mar 19;274(12):7607-10. 10075644
  8. Sullivan R, Chateauneuf A, Coulombe N, Kolakowski LF Jr, Johnson MP, Hebert TE, Ethier N, Belley M, Metters K, Abramovitz M, O'Neill GP, Ng GY: Coexpression of full-length gamma-aminobutyric acid(B) (GABA(B)) receptors with truncated receptors and metabotropic glutamate receptor 4 supports the GABA(B) heterodimer as the functional receptor. J Pharmacol Exp Ther. 2000 May;293(2):460-7. 10773016
  9. Villemure JF, Adam L, Bevan NJ, Gearing K, Chenier S, Bouvier M: Subcellular distribution of GABA(B) receptor homo- and hetero-dimers. Biochem J. 2005 May 15;388(Pt 1):47-55. 15617512
  10. Nomura R, Suzuki Y, Kakizuka A, Jingami H: Direct detection of the interaction between recombinant soluble extracellular regions in the heterodimeric metabotropic gamma-aminobutyric acid receptor. J Biol Chem. 2008 Feb 22;283(8):4665-73. doi: 10.1074/jbc.M705202200. Epub 2007 Dec 28. 18165688
  11. Geng Y, Xiong D, Mosyak L, Malito DL, Kniazeff J, Chen Y, Burmakina S, Quick M, Bush M, Javitch JA, Pin JP, Fan QR: Structure and functional interaction of the extracellular domain of human GABA(B) receptor GBR2. Nat Neurosci. 2012 Jun 3;15(7):970-8. doi: 10.1038/nn.3133. 22660477
  12. Geng Y, Bush M, Mosyak L, Wang F, Fan QR: Structural mechanism of ligand activation in human GABA(B) receptor. Nature. 2013 Dec 12;504(7479):254-9. doi: 10.1038/nature12725. Epub 2013 Dec 4. 24305054