Gamma-aminobutyric acid type B receptor subunit 2

Details

Name

Gamma-aminobutyric acid type B receptor subunit 2

Synonyms

• G-protein coupled receptor 51
• GABA-B receptor 2
• GABA-B-R2
• GABA-BR2
• GABABR2
• Gb2
• GPR51
• GPRC3B
• HG20

Gene Name

GABBR2

UniProtKB Entry

O75899Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

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 residues

941

Molecular Weight

105820.52

Theoretical pI

8.83

GO Classification

Functions

G protein-coupled GABA receptor activity / protein heterodimerization activity / transmembrane signaling receptor activity

Processes

adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / chemical synaptic transmission / G protein-coupled receptor signaling pathway / neuron-glial cell signaling / synaptic transmission, GABAergic

Components

G protein-coupled GABA receptor complex / G protein-coupled receptor heterodimeric complex / GABA receptor complex

General Function

Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054, PubMed:9872316, PubMed:9872744). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688). 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 (PubMed:10075644, PubMed:10773016, PubMed:24305054). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644, PubMed:10773016, PubMed:10906333, PubMed:9872744). Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:22660477, PubMed:9872744). 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 (PubMed:10075644, PubMed:22660477, PubMed:9872316, PubMed:9872744). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable)

Specific Function

G protein-coupled GABA receptor activity

Pfam Domain Function

• 7tm_3 (PF00003)
• ANF_receptor (PF01094)
• GBR2_CC (PF18455)

Signal Regions

1-41

Transmembrane Regions

484-504 523-543 552-572 598-618 655-675 692-712 721-741

Cellular Location

Cell 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

Chromosome Location

9

Locus

9q22.33

External Identifiers

Resource	Link
UniProtKB ID	O75899
UniProtKB Entry Name	GABR2_HUMAN
GenBank Protein ID	3776098
GenBank Gene ID	AJ012188
GeneCard ID	GABBR2
GenAtlas ID	GABBR2
HGNC ID	HGNC:4507
PDB ID(s)	4F11, 4F12, 4MQE, 4MQF, 4MR7, 4MR8, 4MR9, 4MRM, 4MS1, 4MS3, 4MS4, 4PAS, 6M8R, 6OCP, 6UO8, 6UO9, 6UOA, 6VJM, 6W2X, 6WIV, 7C7Q, 7C7S, 7CA3, 7CA5, 7CUM, 7EB2
KEGG ID	hsa:9568
IUPHAR/Guide To Pharmacology ID	241
NCBI Gene ID	9568

General 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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]
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. [Article]

Associated Data

Bio-Entities

Bio-Entity	Type
Gamma-aminobutyric acid type B receptor subunit 2 (Humans)	protein primary
GABA(B) Receptor	protein

Drug Relations

Drug	Drug group	Pharmacological action?	Type	Actions	Details
Baclofen	approved	yes	target	agonist	Details
SGS-742	investigational	yes	target	modulator	Details
Arbaclofen	investigational	yes	target	agonist	Details
Arbaclofen Placarbil	investigational	yes	target	agonist	Details
gamma-Aminobutyric acid	approved, investigational	yes	target	inhibitor	Details
Clozapine	approved	unknown	target	positive modulator	Details
Lesogaberan	investigational	yes	target	modulator	Details
Progabide	experimental	yes	target	agonist	Details
Gabapentin	approved, investigational	yes	target	antagonist	Details
gamma-Hydroxybutyric acid	approved, illicit, investigational	yes	target	modulator	Details
Sodium oxybate	approved	unknown	target	agonist	Details
gamma-Hydroxybutyric acid	approved, illicit, investigational	unknown	target	agonist	Details