ID GABR2_HUMAN Reviewed; 941 AA. AC O75899; O75974; O75975; Q5VXZ2; Q8WX04; Q9P1R2; Q9UNR1; Q9UNS9; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 13-FEB-2019, entry version 182. DE RecName: Full=Gamma-aminobutyric acid type B receptor subunit 2; DE Short=GABA-B receptor 2; DE Short=GABA-B-R2; DE Short=GABA-BR2; DE Short=GABABR2; DE Short=Gb2; DE AltName: Full=G-protein coupled receptor 51; DE AltName: Full=HG20; DE Flags: Precursor; GN Name=GABBR2; Synonyms=GPR51, GPRC3B; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, INTERACTION WITH RP GABBR1, AND SUBCELLULAR LOCATION. RC TISSUE=Cerebellum {ECO:0000303|PubMed:9872316}; RX PubMed=9872316; DOI=10.1038/25354; RA White J.H., Wise A., Main M.J., Green A., Fraser N.J., Disney G.H., RA Barnes A.A., Emson P., Foord S.M., Marshall F.H.; RT "Heterodimerization is required for the formation of a functional RT GABA(B) receptor."; RL Nature 396:679-682(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Fetal brain {ECO:0000303|PubMed:10087195}; RX PubMed=10087195; DOI=10.1006/geno.1998.5706; RA Ng G.Y.K., McDonald T., Bonnert T., Rigby M., Heavens R., Whiting P., RA Chateauneuf A., Coulombe N., Kargman S., Caskey T., Evans J.F., RA O'Neill G.P., Liu Q.; RT "Cloning of a novel G-protein-coupled receptor GPR 51 resembling GABAB RT receptors expressed predominantly in nervous tissues and mapped RT proximal to the hereditary sensory neuropathy type 1 locus on RT chromosome 9."; RL Genomics 56:288-295(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND VARIANTS PHE-628 AND ALA-869. RC TISSUE=Brain {ECO:0000303|PubMed:10328880}; RX PubMed=10328880; DOI=10.1006/mcne.1999.0741; RA Martin S.C., Russek S.J., Farb D.H.; RT "Molecular identification of the human GABABR2: cell surface RT expression and coupling to adenylyl cyclase in the absence of RT GABABR1."; RL Mol. Cell. Neurosci. 13:180-191(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Brain {ECO:0000303|PubMed:10727622}; RX PubMed=10727622; DOI=10.1016/S0006-8993(00)01958-2; RA Clark J.A., Mezey E., Lam A.S., Bonner T.I.; RT "Distribution of the GABA(B) receptor subunit gb2 in rat CNS."; RL Brain Res. 860:41-52(2000). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Liu M., Parker R., McCrea K., Watson J., Baker E., Sutherland G., RA Herzog H.; RT "Cloning and characterization of a novel human GABA-B receptor subtype RT with high affinity for GABA and low affinity for baclofen."; RL Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Hippocampus {ECO:0000303|Ref.6}; RA Borowsky B., Laz T., Gerald C.; RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., RA Rogers J., Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-941. RC TISSUE=Hippocampus {ECO:0000303|PubMed:15489334}; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP FUNCTION. RX PubMed=10075644; DOI=10.1074/jbc.274.12.7607; RA Ng G.Y.K., Clark J., Coulombe N., Ethier N., Hebert T.E., Sullivan R., RA Kargman S., Chateauneuf A., Tsukamoto N., McDonald T., Whiting P., RA Mezey E., Johnson M.P., Liu Q., Kolakowski L.F. Jr., Evans J.F., RA Bonner T.I., O'Neill G.P.; RT "Identification of a GABAB receptor subunit, gb2, required for RT functional GABAB receptor activity."; RL J. Biol. Chem. 274:7607-7610(1999). RN [10] RP FUNCTION, INTERACTION WITH GABBR1, TISSUE SPECIFICITY, AND DOMAIN. RX PubMed=9872744; DOI=10.1126/science.283.5398.74; RA Kuner R., Koehr G., Gruenewald S., Eisenhardt G., Bach A., RA Kornau H.-C.; RT "Role of heteromer formation in GABAB receptor function."; RL Science 283:74-77(1999). RN [11] RP FUNCTION, AND INTERACTION WITH GABBR1. RX PubMed=10906333; DOI=10.1074/jbc.M005333200; RA Schwarz D.A., Barry G., Eliasof S.D., Petroski R.E., Conlon P.J., RA Maki R.A.; RT "Characterization of gamma-aminobutyric acid receptor GABAB(1e), a RT GABAB(1) splice variant encoding a truncated receptor."; RL J. Biol. Chem. 275:32174-32181(2000). RN [12] RP FUNCTION, AND INTERACTION WITH GABBR1. RX PubMed=10773016; RA Sullivan R., Chateauneuf A., Coulombe N., Kolakowski L.F. Jr., RA Johnson M.P., Hebert T.E., Ethier N., Belley M., Metters K., RA Abramovitz M., O'Neill G.P., Ng G.Y.K.; RT "Coexpression of full-length gamma-aminobutyric acid(B) (GABA(B)) RT receptors with truncated receptors and metabotropic glutamate receptor RT 4 supports the GABA(B) heterodimer as the functional receptor."; RL J. Pharmacol. Exp. Ther. 293:460-467(2000). RN [13] RP VARIANT NDPLHS THR-567. RX PubMed=26740508; DOI=10.1136/jmedgenet-2015-103568; RA Lopes F., Barbosa M., Ameur A., Soares G., de Sa J., Dias A.I., RA Oliveira G., Cabral P., Temudo T., Calado E., Cruz I.F., Vieira J.P., RA Oliveira R., Esteves S., Sauer S., Jonasson I., Syvaenen A.C., RA Gyllensten U., Pinto D., Maciel P.; RT "Identification of novel genetic causes of Rett syndrome-like RT phenotypes."; RL J. Med. Genet. 53:190-199(2016). RN [14] RP FUNCTION, INTERACTION WITH GABBR1, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=15617512; DOI=10.1042/BJ20041435; RA Villemure J.F., Adam L., Bevan N.J., Gearing K., Chenier S., RA Bouvier M.; RT "Subcellular distribution of GABA(B) receptor homo- and hetero- RT dimers."; RL Biochem. J. 388:47-55(2005). RN [15] RP FUNCTION, SUBUNIT, AND INTERACTION WITH GABBR1. RX PubMed=18165688; DOI=10.1074/jbc.M705202200; RA Nomura R., Suzuki Y., Kakizuka A., Jingami H.; RT "Direct detection of the interaction between recombinant soluble RT extracellular regions in the heterodimeric metabotropic gamma- RT aminobutyric acid receptor."; RL J. Biol. Chem. 283:4665-4673(2008). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 42-466, PARTIAL PROTEIN RP SEQUENCE, FUNCTION, INTERACTION WITH GABBR1, MUTAGENESIS OF TYR-118, RP GLYCOSYLATION AT ASN-90; ASN-389; ASN-404 AND ASN-453, AND DISULFIDE RP BONDS. RX PubMed=22660477; DOI=10.1038/nn.3133; RA Geng Y., Xiong D., Mosyak L., Malito D.L., Kniazeff J., Chen Y., RA Burmakina S., Quick M., Bush M., Javitch J.A., Pin J.P., Fan Q.R.; RT "Structure and functional interaction of the extracellular domain of RT human GABA(B) receptor GBR2."; RL Nat. Neurosci. 15:970-978(2012). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 42-466 IN COMPLEXES WITH RP GABBR1; AGONISTS AND ANTAGONISTS, FUNCTION, SUBUNIT, GLYCOSYLATION AT RP ASN-404, AND DISULFIDE BOND. RX PubMed=24305054; DOI=10.1038/nature12725; RA Geng Y., Bush M., Mosyak L., Wang F., Fan Q.R.; RT "Structural mechanism of ligand activation in human GABA(B) RT receptor."; RL Nature 504:254-259(2013). RN [18] RP INVOLVEMENT IN EIEE59, AND VARIANT EIEE59 TRP-693. RX PubMed=29100083; DOI=10.1016/j.ajhg.2017.09.008; RG Deciphering Developmental Disorders Study; RA Hamdan F.F., Myers C.T., Cossette P., Lemay P., Spiegelman D., RA Laporte A.D., Nassif C., Diallo O., Monlong J., Cadieux-Dion M., RA Dobrzeniecka S., Meloche C., Retterer K., Cho M.T., Rosenfeld J.A., RA Bi W., Massicotte C., Miguet M., Brunga L., Regan B.M., Mo K., Tam C., RA Schneider A., Hollingsworth G., FitzPatrick D.R., Donaldson A., RA Canham N., Blair E., Kerr B., Fry A.E., Thomas R.H., Shelagh J., RA Hurst J.A., Brittain H., Blyth M., Lebel R.R., Gerkes E.H., RA Davis-Keppen L., Stein Q., Chung W.K., Dorison S.J., Benke P.J., RA Fassi E., Corsten-Janssen N., Kamsteeg E.J., Mau-Them F.T., RA Bruel A.L., Verloes A., Ounap K., Wojcik M.H., Albert D.V.F., RA Venkateswaran S., Ware T., Jones D., Liu Y.C., Mohammad S.S., RA Bizargity P., Bacino C.A., Leuzzi V., Martinelli S., Dallapiccola B., RA Tartaglia M., Blumkin L., Wierenga K.J., Purcarin G., O'Byrne J.J., RA Stockler S., Lehman A., Keren B., Nougues M.C., Mignot C., Auvin S., RA Nava C., Hiatt S.M., Bebin M., Shao Y., Scaglia F., Lalani S.R., RA Frye R.E., Jarjour I.T., Jacques S., Boucher R.M., Riou E., Srour M., RA Carmant L., Lortie A., Major P., Diadori P., Dubeau F., D'Anjou G., RA Bourque G., Berkovic S.F., Sadleir L.G., Campeau P.M., Kibar Z., RA Lafreniere R.G., Girard S.L., Mercimek-Mahmutoglu S., Boelman C., RA Rouleau G.A., Scheffer I.E., Mefford H.C., Andrade D.M., Rossignol E., RA Minassian B.A., Michaud J.L.; RT "High rate of recurrent de novo mutations in developmental and RT epileptic encephalopathies."; RL Am. J. Hum. Genet. 101:664-685(2017). RN [19] RP INVOLVEMENT IN NDPLHS, INVOLVEMENT IN EIEE59, VARIANT NDPLHS THR-567, RP VARIANTS EIEE59 ILE-695 AND ASN-705, CHARACTERIZATION OF VARIANT RP NDPLHS THR-567, AND CHARACTERIZATION OF VARIANTS EIEE59 ILE-695 AND RP ASN-705. RX PubMed=28856709; DOI=10.1002/ana.25032; RA Yoo Y., Jung J., Lee Y.N., Lee Y., Cho H., Na E., Hong J., Kim E., RA Lee J.S., Lee J.S., Hong C., Park S.Y., Wie J., Miller K., Shur N., RA Clow C., Ebel R.S., DeBrosse S.D., Henderson L.B., Willaert R., RA Castaldi C., Tikhonova I., Bilguevar K., Mane S., Kim K.J., RA Hwang Y.S., Lee S.G., So I., Lim B.C., Choi H.J., Seong J.Y., RA Shin Y.B., Jung H., Chae J.H., Choi M.; RT "GABBR2 mutations determine phenotype in rett syndrome and epileptic RT encephalopathy."; RL Ann. Neurol. 82:466-478(2017). RN [20] RP INVOLVEMENT IN NDPLHS, VARIANT NDPLHS THR-707, CHARACTERIZATION OF RP VARIANTS NDPLHS THR-567 AND THR-707, AND CHARACTERIZATION OF VARIANTS RP EIEE59 ILE-695 AND ASN-705. RX PubMed=29369404; DOI=10.1002/ana.25155; RA Vuillaume M.L., Jeanne M., Xue L., Blesson S., Denomme-Pichon A.S., RA Alirol S., Brulard C., Colin E., Isidor B., Gilbert-Dussardier B., RA Odent S., Parent P., Donnart A., Redon R., Bezieau S., Rondard P., RA Laumonnier F., Toutain A.; RT "A novel mutation in the transmembrane 6 domain of GABBR2 leads to a RT Rett-like phenotype."; RL Ann. Neurol. 83:437-439(2018). CC -!- FUNCTION: Component of a heterodimeric G-protein coupled receptor CC for GABA, formed by GABBR1 and GABBR2 (PubMed:9872316, CC PubMed:9872744, PubMed:15617512, PubMed:18165688, PubMed:22660477, CC PubMed:24305054). Within the heterodimeric GABA receptor, only CC GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G CC proteins (PubMed:18165688). Ligand binding causes a conformation CC change that triggers signaling via guanine nucleotide-binding CC proteins (G proteins) and modulates the activity of down-stream CC effectors, such as adenylate cyclase (PubMed:10075644, CC PubMed:10773016, PubMed:24305054). Signaling inhibits adenylate CC cyclase, stimulates phospholipase A2, activates potassium CC channels, inactivates voltage-dependent calcium-channels and CC modulates inositol phospholipid hydrolysis (PubMed:10075644, CC PubMed:9872744, PubMed:10906333, PubMed:10773016). Plays a CC critical role in the fine-tuning of inhibitory synaptic CC transmission (PubMed:9872744, PubMed:22660477). Pre-synaptic GABA CC receptor inhibits neurotransmitter release by down-regulating CC high-voltage activated calcium channels, whereas postsynaptic GABA CC receptor decreases neuronal excitability by activating a prominent CC inwardly rectifying potassium (Kir) conductance that underlies the CC late inhibitory postsynaptic potentials (PubMed:9872316, CC PubMed:10075644, PubMed:9872744, PubMed:22660477). Not only CC implicated in synaptic inhibition but also in hippocampal long- CC term potentiation, slow wave sleep, muscle relaxation and CC antinociception (Probable). {ECO:0000269|PubMed:10075644, CC ECO:0000269|PubMed:10328880, ECO:0000269|PubMed:15617512, CC ECO:0000269|PubMed:18165688, ECO:0000269|PubMed:22660477, CC ECO:0000269|PubMed:24305054, ECO:0000269|PubMed:9872316, CC ECO:0000269|PubMed:9872744, ECO:0000305}. CC -!- SUBUNIT: Heterodimer of GABBR1 and GABBR2 (PubMed:9872316, CC PubMed:9872744, PubMed:10906333, PubMed:10773016, PubMed:15617512, CC PubMed:18165688, PubMed:22660477, PubMed:24305054). Homodimers may CC form, but are inactive (PubMed:15617512). Interacts (via C- CC terminus) with ATF4 (via leucine zipper domain) (By similarity). CC {ECO:0000250|UniProtKB:Q9Z0U4, ECO:0000269|PubMed:10773016, CC ECO:0000269|PubMed:15617512, ECO:0000269|PubMed:18165688, CC ECO:0000269|PubMed:22660477, ECO:0000269|PubMed:24305054, CC ECO:0000269|PubMed:9872316, ECO:0000269|PubMed:9872744}. CC -!- INTERACTION: CC Q9UBS5:GABBR1; NbExp=2; IntAct=EBI-715469, EBI-724156; CC Q9UBS5-2:GABBR1; NbExp=3; IntAct=EBI-715469, EBI-16084001; CC P46459:NSF; NbExp=4; IntAct=EBI-715469, EBI-712251; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10328880, CC ECO:0000269|PubMed:15617512, ECO:0000269|PubMed:9872316}; Multi- CC pass membrane protein {ECO:0000305}. Cell junction, synapse, CC postsynaptic cell membrane {ECO:0000250|UniProtKB:O88871}; Multi- CC pass membrane protein {ECO:0000305}. Note=Coexpression of GABBR1 CC and GABBR2 is required for GABBR1 maturation and transport to the CC plasma membrane. In contrast, GABBR2 does not depend on GABBR1 for CC transport to the cell membrane. {ECO:0000269|PubMed:15617512}. CC -!- TISSUE SPECIFICITY: Highly expressed in brain, especially in CC cerebral cortex, thalamus, hippocampus, frontal, occipital and CC temporal lobe, occipital pole and cerebellum, followed by corpus CC callosum, caudate nucleus, spinal cord, amygdala and medulla CC (PubMed:10087195, PubMed:10328880, PubMed:10727622, CC PubMed:9872744). Weakly expressed in heart, testis and skeletal CC muscle (PubMed:10087195, PubMed:10727622). CC {ECO:0000269|PubMed:10087195, ECO:0000269|PubMed:10328880, CC ECO:0000269|PubMed:10727622, ECO:0000269|PubMed:9872744}. CC -!- DOMAIN: Alpha-helical parts of the C-terminal intracellular region CC mediate heterodimeric interaction with GABBR1. CC {ECO:0000305|PubMed:9872744}. CC -!- DISEASE: Neurodevelopmental disorder with poor language and loss CC of hand skills (NDPLHS) [MIM:617903]: An autosomal dominant CC disorder characterized by psychomotor developmental stagnation or CC regression. NDPLHS manifest in the first years of life as loss of CC purposeful hand movements, loss of language, and intellectual CC disability. {ECO:0000269|PubMed:26740508, CC ECO:0000269|PubMed:28856709, ECO:0000269|PubMed:29369404}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Epileptic encephalopathy, early infantile, 59 (EIEE59) CC [MIM:617904]: A form of epileptic encephalopathy, a heterogeneous CC group of severe childhood onset epilepsies characterized by CC refractory seizures, neurodevelopmental impairment, and poor CC prognosis. Development is normal prior to seizure onset, after CC which cognitive and motor delays become apparent. EIEE59 is an CC autosomal dominant condition characterized by onset of refractory CC seizures in early infancy. {ECO:0000269|PubMed:28856709, CC ECO:0000269|PubMed:29100083, ECO:0000269|PubMed:29369404}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family. CC GABA-B receptor subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH35071.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AJ012188; CAA09942.1; -; mRNA. DR EMBL; AF069755; AAC99345.1; -; mRNA. DR EMBL; AF099033; AAD45867.1; -; mRNA. DR EMBL; AF056085; AAC63228.1; -; mRNA. DR EMBL; AF095784; AAD30389.1; -; mRNA. DR EMBL; AF074483; AAD03336.1; -; mRNA. DR EMBL; AL445495; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL353782; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL356282; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL591502; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC035071; AAH35071.2; ALT_INIT; mRNA. DR CCDS; CCDS6736.1; -. DR RefSeq; NP_005449.5; NM_005458.7. DR UniGene; Hs.198612; -. DR PDB; 4F11; X-ray; 2.38 A; A=42-466. DR PDB; 4F12; X-ray; 3.02 A; A=42-466. DR PDB; 4MQE; X-ray; 2.35 A; B=42-466. DR PDB; 4MQF; X-ray; 2.22 A; B=42-466. DR PDB; 4MR7; X-ray; 2.15 A; B=42-466. DR PDB; 4MR8; X-ray; 2.15 A; B=42-466. DR PDB; 4MR9; X-ray; 2.35 A; B=42-466. DR PDB; 4MRM; X-ray; 2.86 A; B=42-466. DR PDB; 4MS1; X-ray; 2.25 A; B=42-466. DR PDB; 4MS3; X-ray; 2.50 A; B=42-466. DR PDB; 4MS4; X-ray; 1.90 A; B=42-466. DR PDB; 4PAS; X-ray; 1.62 A; B=779-819. DR PDBsum; 4F11; -. DR PDBsum; 4F12; -. DR PDBsum; 4MQE; -. DR PDBsum; 4MQF; -. DR PDBsum; 4MR7; -. DR PDBsum; 4MR8; -. DR PDBsum; 4MR9; -. DR PDBsum; 4MRM; -. DR PDBsum; 4MS1; -. DR PDBsum; 4MS3; -. DR PDBsum; 4MS4; -. DR PDBsum; 4PAS; -. DR ProteinModelPortal; O75899; -. DR SMR; O75899; -. DR BioGrid; 114938; 7. DR ComplexPortal; CPX-2955; GABA-B receptor complex. DR CORUM; O75899; -. DR DIP; DIP-42851N; -. DR IntAct; O75899; 7. DR MINT; O75899; -. DR STRING; 9606.ENSP00000259455; -. DR BindingDB; O75899; -. DR ChEMBL; CHEMBL5034; -. DR DrugBank; DB08891; Arbaclofen. DR DrugBank; DB08892; Arbaclofen Placarbil. DR DrugBank; DB00181; Baclofen. DR DrugBank; DB05010; SGS742. DR GuidetoPHARMACOLOGY; 241; -. DR TCDB; 9.A.14.15.1; the g-protein-coupled receptor (gpcr) family. DR iPTMnet; O75899; -. DR PhosphoSitePlus; O75899; -. DR BioMuta; GABBR2; -. DR EPD; O75899; -. DR jPOST; O75899; -. DR PaxDb; O75899; -. DR PeptideAtlas; O75899; -. DR PRIDE; O75899; -. DR ProteomicsDB; 50252; -. DR DNASU; 9568; -. DR Ensembl; ENST00000259455; ENSP00000259455; ENSG00000136928. DR GeneID; 9568; -. DR KEGG; hsa:9568; -. DR UCSC; uc004ays.4; human. DR CTD; 9568; -. DR DisGeNET; 9568; -. DR EuPathDB; HostDB:ENSG00000136928.5; -. DR GeneCards; GABBR2; -. DR HGNC; HGNC:4507; GABBR2. DR HPA; CAB079065; -. DR HPA; HPA013820; -. DR HPA; HPA031684; -. DR MalaCards; GABBR2; -. DR MIM; 607340; gene. DR MIM; 617903; phenotype. DR MIM; 617904; phenotype. DR neXtProt; NX_O75899; -. DR OpenTargets; ENSG00000136928; -. DR Orphanet; 3095; Atypical Rett syndrome. DR PharmGKB; PA28896; -. DR eggNOG; KOG1055; Eukaryota. DR eggNOG; ENOG410XNN1; LUCA. DR GeneTree; ENSGT00940000155783; -. DR HOVERGEN; HBG080355; -. DR InParanoid; O75899; -. DR KO; K04615; -. DR OMA; VEASKFH; -. DR OrthoDB; 590810at2759; -. DR PhylomeDB; O75899; -. DR TreeFam; TF313965; -. DR Reactome; R-HSA-1296041; Activation of G protein gated Potassium channels. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR Reactome; R-HSA-420499; Class C/3 (Metabotropic glutamate/pheromone receptors). DR Reactome; R-HSA-977444; GABA B receptor activation. DR Reactome; R-HSA-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits. DR ChiTaRS; GABBR2; human. DR GeneWiki; GABBR2; -. DR GenomeRNAi; 9568; -. DR PRO; PR:O75899; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; ENSG00000136928; Expressed in 149 organ(s), highest expression level in primary visual cortex. DR ExpressionAtlas; O75899; baseline and differential. DR Genevisible; O75899; HS. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0038039; C:G protein-coupled receptor heterodimeric complex; IPI:UniProtKB. DR GO; GO:1902710; C:GABA receptor complex; IDA:CAFA. DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB. DR GO; GO:0043005; C:neuron projection; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell. DR GO; GO:0004965; F:G protein-coupled GABA receptor activity; IBA:GO_Central. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:CAFA. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:Reactome. DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IDA:UniProtKB. DR GO; GO:0007194; P:negative regulation of adenylate cyclase activity; TAS:ProtInc. DR CDD; cd15294; 7tmC_GABA-B-R2; 1. DR InterPro; IPR001828; ANF_lig-bd_rcpt. DR InterPro; IPR002455; GPCR3_GABA-B. DR InterPro; IPR000337; GPCR_3. DR InterPro; IPR017978; GPCR_3_C. DR InterPro; IPR017979; GPCR_3_CS. DR InterPro; IPR002457; GPCR_3_GABA_rcpt_B2. DR InterPro; IPR028082; Peripla_BP_I. DR PANTHER; PTHR10519; PTHR10519; 1. DR PANTHER; PTHR10519:SF62; PTHR10519:SF62; 1. DR Pfam; PF00003; 7tm_3; 1. DR Pfam; PF01094; ANF_receptor; 1. DR PRINTS; PR01178; GABAB2RECPTR. DR PRINTS; PR00248; GPCRMGR. DR SUPFAM; SSF53822; SSF53822; 1. DR PROSITE; PS00981; G_PROTEIN_RECEP_F3_3; 1. DR PROSITE; PS50259; G_PROTEIN_RECEP_F3_4; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell junction; Cell membrane; Coiled coil; KW Complete proteome; Direct protein sequencing; Disease mutation; KW Disulfide bond; Epilepsy; G-protein coupled receptor; Glycoprotein; KW Membrane; Mental retardation; Phosphoprotein; Polymorphism; KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal; KW Synapse; Transducer; Transmembrane; Transmembrane helix. FT SIGNAL 1 41 {ECO:0000255}. FT CHAIN 42 941 Gamma-aminobutyric acid type B receptor FT subunit 2. FT /FTId=PRO_0000012952. FT TOPO_DOM 42 483 Extracellular. {ECO:0000255}. FT TRANSMEM 484 504 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 505 522 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 523 543 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 544 551 Extracellular. {ECO:0000255}. FT TRANSMEM 552 572 Helical; Name=3. {ECO:0000255}. FT TOPO_DOM 573 597 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 598 618 Helical; Name=4. {ECO:0000255}. FT TOPO_DOM 619 654 Extracellular. {ECO:0000255}. FT TRANSMEM 655 675 Helical; Name=5. {ECO:0000255}. FT TOPO_DOM 676 691 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 692 712 Helical; Name=6. {ECO:0000255}. FT TOPO_DOM 713 720 Extracellular. {ECO:0000255}. FT TRANSMEM 721 741 Helical; Name=7. {ECO:0000255}. FT TOPO_DOM 742 941 Cytoplasmic. {ECO:0000255}. FT COILED 781 819 {ECO:0000255}. FT MOD_RES 776 776 Phosphoserine. FT {ECO:0000250|UniProtKB:Q80T41}. FT MOD_RES 779 779 Phosphoserine. FT {ECO:0000250|UniProtKB:Q80T41}. FT MOD_RES 819 819 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q80T41}. FT MOD_RES 884 884 Phosphoserine. FT {ECO:0000250|UniProtKB:Q80T41}. FT MOD_RES 893 893 Phosphoserine. FT {ECO:0000250|UniProtKB:Q80T41}. FT MOD_RES 913 913 Phosphoserine. FT {ECO:0000250|UniProtKB:Q80T41}. FT MOD_RES 916 916 Phosphoserine. FT {ECO:0000250|UniProtKB:Q80T41}. FT MOD_RES 920 920 Phosphoserine. FT {ECO:0000250|UniProtKB:Q80T41}. FT MOD_RES 924 924 Phosphoserine. FT {ECO:0000250|UniProtKB:Q80T41}. FT CARBOHYD 90 90 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22660477}. FT CARBOHYD 298 298 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 389 389 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22660477}. FT CARBOHYD 404 404 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22660477, FT ECO:0000269|PubMed:24305054}. FT CARBOHYD 453 453 N-linked (GlcNAc...) asparagine. FT {ECO:0000269|PubMed:22660477}. FT DISULFID 108 135 FT DISULFID 237 266 FT DISULFID 265 302 FT VARIANT 163 163 L -> P (in dbSNP:rs35449008). FT /FTId=VAR_049280. FT VARIANT 567 567 A -> T (in NDPLHS; increased basal FT signaling activity and only weak FT stimulation by GABA agonist; when FT injected into Xenopus tadpoles, causes FT abnormal swimming patterns and increased FT frequencies of seizure-like behavior FT compared to wild-type-injected animals; FT no effect on cell surface expression; FT dbSNP:rs922847767). FT {ECO:0000269|PubMed:26740508, FT ECO:0000269|PubMed:28856709, FT ECO:0000269|PubMed:29369404}. FT /FTId=VAR_079029. FT VARIANT 628 628 Y -> F. {ECO:0000269|PubMed:10328880}. FT /FTId=VAR_010148. FT VARIANT 693 693 G -> W (in EIEE59; unknown pathological FT significance). FT {ECO:0000269|PubMed:29100083}. FT /FTId=VAR_080569. FT VARIANT 695 695 S -> I (in EIEE59; full signaling FT activity in the absence of GABA agonist; FT when injected into Xenopus tadpoles, FT causes abnormal swimming patterns and FT increased frequencies of seizure-like FT behavior compared to wild-type-injected FT animals; no effect on cell surface FT expression). FT {ECO:0000269|PubMed:28856709, FT ECO:0000269|PubMed:29369404}. FT /FTId=VAR_080570. FT VARIANT 705 705 I -> N (in EIEE59; increased basal FT signaling activity and no stimulation by FT GABA agonist; when injected into Xenopus FT tadpoles, causes abnormal swimming FT patterns and increased frequencies of FT seizure-like behavior compared to wild- FT type-injected animals; no effect on cell FT surface expression). FT {ECO:0000269|PubMed:28856709, FT ECO:0000269|PubMed:29369404}. FT /FTId=VAR_080571. FT VARIANT 707 707 A -> T (in NDPLHS; increased basal FT signaling activity and only weak FT stimulation by GABA agonist; no effect on FT cell surface expression). FT {ECO:0000269|PubMed:29369404}. FT /FTId=VAR_080572. FT VARIANT 869 869 T -> A (in dbSNP:rs10985765). FT {ECO:0000269|PubMed:10328880}. FT /FTId=VAR_010149. FT MUTAGEN 118 118 Y->A: Impairs interaction with GABBR1. FT Decreases signaling via G-proteins. FT {ECO:0000269|PubMed:22660477}. FT CONFLICT 6 6 S -> R (in Ref. 2; AAC99345). FT {ECO:0000305}. FT CONFLICT 12 12 P -> R (in Ref. 2; AAC99345). FT {ECO:0000305}. FT CONFLICT 424 424 G -> E (in Ref. 5; AAD30389). FT {ECO:0000305}. FT CONFLICT 797 797 R -> H (in Ref. 8; AAH35071). FT {ECO:0000305}. FT STRAND 55 62 {ECO:0000244|PDB:4MS4}. FT STRAND 66 68 {ECO:0000244|PDB:4MQE}. FT HELIX 71 90 {ECO:0000244|PDB:4MS4}. FT TURN 91 96 {ECO:0000244|PDB:4MS4}. FT STRAND 98 105 {ECO:0000244|PDB:4MS4}. FT HELIX 110 123 {ECO:0000244|PDB:4MS4}. FT STRAND 128 132 {ECO:0000244|PDB:4MS4}. FT HELIX 136 145 {ECO:0000244|PDB:4MS4}. FT HELIX 146 149 {ECO:0000244|PDB:4MS4}. FT STRAND 152 157 {ECO:0000244|PDB:4MS4}. FT HELIX 161 164 {ECO:0000244|PDB:4MS4}. FT TURN 166 168 {ECO:0000244|PDB:4MS4}. FT STRAND 172 176 {ECO:0000244|PDB:4MS4}. FT HELIX 179 181 {ECO:0000244|PDB:4MS4}. FT HELIX 182 192 {ECO:0000244|PDB:4MS4}. FT STRAND 197 205 {ECO:0000244|PDB:4MS4}. FT HELIX 206 219 {ECO:0000244|PDB:4MS4}. FT TURN 220 223 {ECO:0000244|PDB:4MS4}. FT STRAND 225 234 {ECO:0000244|PDB:4MS4}. FT HELIX 237 245 {ECO:0000244|PDB:4MS4}. FT STRAND 250 254 {ECO:0000244|PDB:4MS4}. FT HELIX 257 269 {ECO:0000244|PDB:4MS4}. FT STRAND 278 283 {ECO:0000244|PDB:4MS4}. FT TURN 287 290 {ECO:0000244|PDB:4MS4}. FT HELIX 304 311 {ECO:0000244|PDB:4MS4}. FT STRAND 315 319 {ECO:0000244|PDB:4MS4}. FT HELIX 335 345 {ECO:0000244|PDB:4MS4}. FT TURN 346 348 {ECO:0000244|PDB:4MR7}. FT HELIX 355 372 {ECO:0000244|PDB:4MS4}. FT HELIX 378 387 {ECO:0000244|PDB:4MS4}. FT HELIX 393 404 {ECO:0000244|PDB:4MS4}. FT STRAND 407 410 {ECO:0000244|PDB:4MS4}. FT STRAND 413 418 {ECO:0000244|PDB:4MS4}. FT STRAND 421 423 {ECO:0000244|PDB:4MS4}. FT STRAND 425 431 {ECO:0000244|PDB:4MS4}. FT STRAND 436 443 {ECO:0000244|PDB:4MS4}. FT TURN 444 447 {ECO:0000244|PDB:4MS4}. FT STRAND 448 451 {ECO:0000244|PDB:4MS4}. FT TURN 453 455 {ECO:0000244|PDB:4MS4}. FT STRAND 459 462 {ECO:0000244|PDB:4MS4}. FT HELIX 780 816 {ECO:0000244|PDB:4PAS}. SQ SEQUENCE 941 AA; 105821 MW; 09F1773DB0673C5D CRC64; MASPRSSGQP GPPPPPPPPP ARLLLLLLLP LLLPLAPGAW GWARGAPRPP PSSPPLSIMG LMPLTKEVAK GSIGRGVLPA VELAIEQIRN ESLLRPYFLD LRLYDTECDN AKGLKAFYDA IKYGPNHLMV FGGVCPSVTS IIAESLQGWN LVQLSFAATT PVLADKKKYP YFFRTVPSDN AVNPAILKLL KHYQWKRVGT LTQDVQRFSE VRNDLTGVLY GEDIEISDTE SFSNDPCTSV KKLKGNDVRI ILGQFDQNMA AKVFCCAYEE NMYGSKYQWI IPGWYEPSWW EQVHTEANSS RCLRKNLLAA MEGYIGVDFE PLSSKQIKTI SGKTPQQYER EYNNKRSGVG PSKFHGYAYD GIWVIAKTLQ RAMETLHASS RHQRIQDFNY TDHTLGRIIL NAMNETNFFG VTGQVVFRNG ERMGTIKFTQ FQDSREVKVG EYNAVADTLE IINDTIRFQG SEPPKDKTII LEQLRKISLP LYSILSALTI LGMIMASAFL FFNIKNRNQK LIKMSSPYMN NLIILGGMLS YASIFLFGLD GSFVSEKTFE TLCTVRTWIL TVGYTTAFGA MFAKTWRVHA IFKNVKMKKK IIKDQKLLVI VGGMLLIDLC ILICWQAVDP LRRTVEKYSM EPDPAGRDIS IRPLLEHCEN THMTIWLGIV YAYKGLLMLF GCFLAWETRN VSIPALNDSK YIGMSVYNVG IMCIIGAAVS FLTRDQPNVQ FCIVALVIIF CSTITLCLVF VPKLITLRTN PDAATQNRRF QFTQNQKKED SKTSTSVTSV NQASTSRLEG LQSENHRLRM KITELDKDLE EVTMQLQDTP EKTTYIKQNH YQELNDILNL GNFTESTDGG KAILKNHLDQ NPQLQWNTTE PSRTCKDPIE DINSPEHIQR RLSLQLPILH HAYLPSIGGV DASCVSPCVS PTASPRHRHV PPSFRVMVSG L //