Gamma-aminobutyric acid type B receptor subunit 1

NameGamma-aminobutyric acid type B receptor subunit 1
Synonyms
  • GABA-B receptor 1
  • GPRC3A
Gene NameGABBR1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000433|Gamma-aminobutyric acid type B receptor subunit 1
MLLLLLLAPLFLRPPGAGGAQTPNATSEGCQIIHPPWEGGIRYRGLTRDQVKAINFLPVD
YEIEYVCRGEREVVGPKVRKCLANGSWTDMDTPSRCVRICSKSYLTLENGKVFLTGGDLP
ALDGARVDFRCDPDFHLVGSSRSICSQGQWSTPKPHCQVNRTPHSERRAVYIGALFPMSG
GWPGGQACQPAVEMALEDVNSRRDILPDYELKLIHHDSKCDPGQATKYLYELLYNDPIKI
ILMPGCSSVSTLVAEAARMWNLIVLSYGSSSPALSNRQRFPTFFRTHPSATLHNPTRVKL
FEKWGWKKIATIQQTTEVFTSTLDDLEERVKEAGIEITFRQSFFSDPAVPVKNLKRQDAR
IIVGLFYETEARKVFCEVYKERLFGKKYVWFLIGWYADNWFKIYDPSINCTVDEMTEAVE
GHITTEIVMLNPANTRSISNMTSQEFVEKLTKRLKRHPEETGGFQEAPLAYDAIWALALA
LNKTSGGGGRSGVRLEDFNYNNQTITDQIYRAMNSSSFEGVSGHVVFDASGSRMAWTLIE
QLQGGSYKKIGYYDSTKDDLSWSKTDKWIGGSPPADQTLVIKTFRFLSQKLFISVSVLSS
LGIVLAVVCLSFNIYNSHVRYIQNSQPNLNNLTAVGCSLALAAVFPLGLDGYHIGRNQFP
FVCQARLWLLGLGFSLGYGSMFTKIWWVHTVFTKKEEKKEWRKTLEPWKLYATVGLLVGM
DVLTLAIWQIVDPLHRTIETFAKEEPKEDIDVSILPQLEHCSSRKMNTWLGIFYGYKGLL
LLLGIFLAYETKSVSTEKINDHRAVGMAIYNVAVLCLITAPVTMILSSQQDAAFAFASLA
IVFSSYITLVVLFVPKMRRLITRGEWQSEAQDTMKTGSSTNNNEEEKSRLLEKENRELEK
IIAEKEERVSELRHQLQSRQQLRSRRHPPTPPEPSGGLPRGPPEPPDRLSCDGSRVHLLY
K
Number of residues961
Molecular Weight108319.4
Theoretical pI8.3
GO Classification
Functions
  • G-protein coupled GABA receptor activity
Processes
  • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway
  • negative regulation of adenylate cyclase activity
  • gamma-aminobutyric acid signaling pathway
  • synaptic transmission
Components
  • integral component of plasma membrane
  • dendrite
  • G-protein coupled receptor heterodimeric complex
  • presynaptic membrane
  • cytoplasm
  • extracellular region
  • postsynaptic membrane
  • plasma membrane
  • cell junction
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. Calcium is required for high affinity binding to GABA. 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. Activated by (-)-baclofen, cgp27492 and blocked by phaclofen.Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.
Pfam Domain Function
Transmembrane Regions592-612 632-652 668-688 711-731 769-789 805-825 834-854
GenBank Protein ID3892594
UniProtKB IDQ9UBS5
UniProtKB Entry NameGABR1_HUMAN
Cellular LocationCell membrane
Gene sequence
>lcl|BSEQ0010206|Gamma-aminobutyric acid type B receptor subunit 1 (GABBR1)
ATGTTGCTGCTGCTGCTACTGGCGCCACTCTTCCTCCGCCCCCCGGGCGCGGGCGGGGCG
CAGACCCCCAACGCCACCTCAGAAGGTTGCCAGATCATACACCCGCCCTGGGAAGGGGGC
ATCAGGTACCGGGGCCTGACTCGGGACCAGGTGAAGGCTATCAACTTCCTGCCAGTGGAC
TATGAGATTGAGTATGTGTGCCGGGGGGAGCGCGAGGTGGTGGGGCCCAAGGTCCGCAAG
TGCCTGGCCAACGGCTCCTGGACAGATATGGACACACCCAGCCGCTGTGTCCGAATCTGC
TCCAAGTCTTATTTGACCCTGGAAAATGGGAAGGTTTTCCTGACGGGTGGGGACCTCCCA
GCTCTGGACGGAGCCCGGGTGGATTTCCGGTGTGACCCCGACTTCCATCTGGTGGGCAGC
TCCCGGAGCATCTGTAGTCAGGGCCAGTGGAGCACCCCCAAGCCCCACTGCCAGGTGAAT
CGAACGCCACACTCAGAACGGCGCGCAGTGTACATCGGGGCACTGTTTCCCATGAGCGGG
GGCTGGCCAGGGGGCCAGGCCTGCCAGCCCGCGGTGGAGATGGCGCTGGAGGACGTGAAT
AGCCGCAGGGACATCCTGCCGGACTATGAGCTCAAGCTCATCCACCACGACAGCAAGTGT
GATCCAGGCCAAGCCACCAAGTACCTATATGAGCTGCTCTACAACGACCCTATCAAGATC
ATCCTTATGCCTGGCTGCAGCTCTGTCTCCACGCTGGTGGCTGAGGCTGCTAGGATGTGG
AACCTCATTGTGCTTTCCTATGGCTCCAGCTCACCAGCCCTGTCAAACCGGCAGCGTTTC
CCCACTTTCTTCCGAACGCACCCATCAGCCACACTCCACAACCCTACCCGCGTGAAACTC
TTTGAAAAGTGGGGCTGGAAGAAGATTGCTACCATCCAGCAGACCACTGAGGTCTTCACT
TCGACTCTGGACGACCTGGAGGAACGAGTGAAGGAGGCTGGAATTGAGATTACTTTCCGC
CAGAGTTTCTTCTCAGATCCAGCTGTGCCCGTCAAAAACCTGAAGCGCCAGGATGCCCGA
ATCATCGTGGGACTTTTCTATGAGACTGAAGCCCGGAAAGTTTTTTGTGAGGTGTACAAG
GAGCGTCTCTTTGGGAAGAAGTACGTCTGGTTCCTCATTGGGTGGTATGCTGACAATTGG
TTCAAGATCTACGACCCTTCTATCAACTGCACAGTGGATGAGATGACTGAGGCGGTGGAG
GGCCACATCACAACTGAGATTGTCATGCTGAATCCTGCCAATACCCGCAGCATTTCCAAC
ATGACATCCCAGGAATTTGTGGAGAAACTAACCAAGCGACTGAAAAGACACCCTGAGGAG
ACAGGAGGCTTCCAGGAGGCACCGCTGGCCTATGATGCCATCTGGGCCTTGGCACTGGCC
CTGAACAAGACATCTGGAGGAGGCGGCCGTTCTGGTGTGCGCCTGGAGGACTTCAACTAC
AACAACCAGACCATTACCGACCAAATCTACCGGGCAATGAACTCTTCGTCCTTTGAGGGT
GTCTCTGGCCATGTGGTGTTTGATGCCAGCGGCTCTCGGATGGCATGGACGCTTATCGAG
CAGCTTCAGGGTGGCAGCTACAAGAAGATTGGCTACTATGACAGCACCAAGGATGATCTT
TCCTGGTCCAAAACAGATAAATGGATTGGAGGGTCCCCCCCAGCTGACCAGACCCTGGTC
ATCAAGACATTCCGCTTCCTGTCACAGAAACTCTTTATCTCCGTCTCAGTTCTCTCCAGC
CTGGGCATTGTCCTAGCTGTTGTCTGTCTGTCCTTTAACATCTACAACTCACATGTCCGT
TATATCCAGAACTCACAGCCCAACCTGAACAACCTGACTGCTGTGGGCTGCTCACTGGCT
TTAGCTGCTGTCTTCCCCCTGGGGCTCGATGGTTACCACATTGGGAGGAACCAGTTTCCT
TTCGTCTGCCAGGCCCGCCTCTGGCTCCTGGGCCTGGGCTTTAGTCTGGGCTACGGTTCC
ATGTTCACCAAGATTTGGTGGGTCCACACGGTCTTCACAAAGAAGGAAGAAAAGAAGGAG
TGGAGGAAGACTCTGGAACCCTGGAAGCTGTATGCCACAGTGGGCCTGCTGGTGGGCATG
GATGTCCTCACTCTCGCCATCTGGCAGATCGTGGACCCTCTGCACCGGACCATTGAGACA
TTTGCCAAGGAGGAACCTAAGGAAGATATTGACGTCTCTATTCTGCCCCAGCTGGAGCAT
TGCAGCTCCAGGAAGATGAATACATGGCTTGGCATTTTCTATGGTTACAAGGGGCTGCTG
CTGCTGCTGGGAATCTTCCTTGCTTATGAGACCAAGAGTGTGTCCACTGAGAAGATCAAT
GATCACCGGGCTGTGGGCATGGCTATCTACAATGTGGCAGTCCTGTGCCTCATCACTGCT
CCTGTCACCATGATTCTGTCCAGCCAGCAGGATGCAGCCTTTGCCTTTGCCTCTCTTGCC
ATAGTTTTCTCCTCCTATATCACTCTTGTTGTGCTCTTTGTGCCCAAGATGCGCAGGCTG
ATCACCCGAGGGGAATGGCAGTCGGAGGCGCAGGACACCATGAAGACAGGGTCATCGACC
AACAACAACGAGGAGGAGAAGTCCCGGCTGTTGGAGAAGGAGAACCGTGAACTGGAAAAG
ATCATTGCTGAGAAAGAGGAGCGTGTCTCTGAACTGCGCCATCAACTCCAGTCTCGGCAG
CAGCTCCGCTCCCGGCGCCACCCACCGACACCCCCAGAACCCTCTGGGGGCCTGCCCAGG
GGACCCCCTGAGCCCCCCGACCGGCTTAGCTGTGATGGGAGTCGAGTGCATTTGCTTTAT
AAGTGA
GenBank Gene IDAJ225028
GeneCard IDNot Available
GenAtlas IDGABBR1
HGNC IDHGNC:4070
Chromosome Location6
Locus6p21.31
References
  1. Kaupmann K, Schuler V, Mosbacher J, Bischoff S, Bittiger H, Heid J, Froestl W, Leonhard S, Pfaff T, Karschin A, Bettler B: Human gamma-aminobutyric acid type B receptors are differentially expressed and regulate inwardly rectifying K+ channels. Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14991-6. 9844003
  2. 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
  3. Grifa A, Totaro A, Rommens JM, Carella M, Roetto A, Borgato L, Zelante L, Gasparini P: GABA (gamma-amino-butyric acid) neurotransmission: identification and fine mapping of the human GABAB receptor gene. Biochem Biophys Res Commun. 1998 Sep 18;250(2):240-5. 9753614
  4. Goei VL, Choi J, Ahn J, Bowlus CL, Raha-Chowdhury R, Gruen JR: Human gamma-aminobutyric acid B receptor gene: complementary DNA cloning, expression, chromosomal location, and genomic organization. Biol Psychiatry. 1998 Oct 15;44(8):659-66. 9798068
  5. Peters HC, Kammer G, Volz A, Kaupmann K, Ziegler A, Bettler B, Epplen JT, Sander T, Riess O: Mapping, genomic structure, and polymorphisms of the human GABABR1 receptor gene: evaluation of its involvement in idiopathic generalized epilepsy. Neurogenetics. 1998 Dec;2(1):47-54. 9933300
  6. Makoff A: Molecular cloning of human GABABR1 and its tissue distribution. Brain Res Mol Brain Res. 1999 Jan 22;64(1):137-40. 9889352
  7. Schwarz DA, Barry G, Eliasof SD, Petroski RE, Conlon PJ, Maki RA: Characterization of gamma-aminobutyric acid receptor GABAB(1e), a GABAB(1) splice variant encoding a truncated receptor. J Biol Chem. 2000 Oct 13;275(41):32174-81. 10906333
  8. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. 14574404
  9. 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
  10. Hillman RT, Green RE, Brenner SE: An unappreciated role for RNA surveillance. Genome Biol. 2004;5(2):R8. Epub 2004 Feb 2. 14759258
  11. 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
  12. Kuner R, Kohr G, Grunewald S, Eisenhardt G, Bach A, Kornau HC: Role of heteromer formation in GABAB receptor function. Science. 1999 Jan 1;283(5398):74-7. 9872744
  13. Couve A, Restituito S, Brandon JM, Charles KJ, Bawagan H, Freeman KB, Pangalos MN, Calver AR, Moss SJ: Marlin-1, a novel RNA-binding protein associates with GABA receptors. J Biol Chem. 2004 Apr 2;279(14):13934-43. Epub 2004 Jan 12. 14718537
  14. 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
  15. 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
  16. 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
  17. 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
  18. Sander T, Peters C, Kammer G, Samochowiec J, Zirra M, Mischke D, Ziegler A, Kaupmann K, Bettler B, Epplen JT, Riess O: Association analysis of exonic variants of the gene encoding the GABAB receptor and idiopathic generalized epilepsy. Am J Med Genet. 1999 Aug 20;88(4):305-10. 10402495