Gamma-aminobutyric acid type B receptor subunit 1

Details

Name
Gamma-aminobutyric acid type B receptor subunit 1
Synonyms
  • GABA-B receptor 1
  • GPRC3A
Gene Name
GABBR1
Organism
Humans
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 residues
961
Molecular Weight
108319.4
Theoretical pI
8.3
GO Classification
Functions
G-protein coupled GABA receptor activity
Processes
adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway / gamma-aminobutyric acid signaling pathway / negative regulation of adenylate cyclase activity / synaptic transmission
Components
cell junction / cytoplasm / dendrite / extracellular region / G-protein coupled receptor heterodimeric complex / integral component of plasma membrane / plasma membrane / postsynaptic membrane / presynaptic membrane
General Function
G-protein coupled gaba receptor activity
Specific Function
Component 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 Regions
592-612 632-652 668-688 711-731 769-789 805-825 834-854
Cellular Location
Cell 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
Chromosome Location
6
Locus
6p21.31
External Identifiers
ResourceLink
UniProtKB IDQ9UBS5
UniProtKB Entry NameGABR1_HUMAN
GenBank Protein ID3892594
GenBank Gene IDAJ225028
GenAtlas IDGABBR1
HGNC IDHGNC:4070
General References
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  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:9889352]
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  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. [PubMed:15489334]
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  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. [PubMed: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. [PubMed:14718537]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00181BaclofenapprovedunknownagonistDetails
DB00837ProgabideexperimentalyesagonistDetails
DB05010SGS-742investigationalunknownDetails
DB06354TezampanelinvestigationalunknownDetails
DB01080VigabatrinapprovedyesagonistDetails
DB08891ArbaclofeninvestigationalyesagonistDetails
DB08892Arbaclofen PlacarbilinvestigationalyesagonistDetails
DB00996Gabapentinapproved, investigationalunknownDetails
DB02530gamma-Aminobutyric acidapproved, investigationalunknownDetails
DB01956Taurineapproved, nutraceuticalyesagonistDetails