GABR2_CAEEL
ID GABR2_CAEEL Reviewed; 842 AA.
AC G5ECB2; B7WN65;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Gamma-aminobutyric acid type B receptor subunit 2 {ECO:0000305};
DE Flags: Precursor;
GN Name=gbb-2 {ECO:0000303|PubMed:18614679, ECO:0000312|WormBase:ZK180.1};
GN ORFNames=ZK180.1 {ECO:0000312|WormBase:ZK180.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:ACE63491.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND DISRUPTION PHENOTYPE.
RX PubMed=18614679; DOI=10.1523/jneurosci.0378-08.2008;
RA Dittman J.S., Kaplan J.M.;
RT "Behavioral impact of neurotransmitter-activated G-protein-coupled
RT receptors: muscarinic and GABAB receptors regulate Caenorhabditis elegans
RT locomotion.";
RL J. Neurosci. 28:7104-7112(2008).
RN [2] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3] {ECO:0000305}
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ALA-484 AND VAL-572.
RX PubMed=21613582; DOI=10.1152/jn.00578.2010;
RA Schultheis C., Brauner M., Liewald J.F., Gottschalk A.;
RT "Optogenetic analysis of GABAB receptor signaling in Caenorhabditis elegans
RT motor neurons.";
RL J. Neurophysiol. 106:817-827(2011).
CC -!- FUNCTION: Component of a heterodimeric G-protein coupled receptor for
CC GABA, formed by gbb-1 and gbb-2 (By similarity). Within the
CC heterodimeric GABA receptor, only gbb-1 seems to bind agonists, while
CC gbb-2 mediates coupling to G proteins (By similarity). Ligand binding
CC causes a conformation change that triggers signaling via guanine
CC nucleotide-binding proteins (G proteins) and modulates the activity of
CC down-stream effectors, such as adenylate cyclase (By similarity).
CC Signaling inhibits adenylate cyclase, stimulates phospholipase A2,
CC activates potassium channels, inactivates voltage-dependent calcium-
CC channels and modulates inositol phospholipid hydrolysis (By
CC similarity). Plays a critical role in the fine-tuning of inhibitory
CC synaptic transmission (By similarity). Pre-synaptic GABA receptor
CC inhibits neurotransmitter release by down-regulating high-voltage
CC activated calcium channels, whereas postsynaptic GABA receptor
CC decreases neuronal excitability by activating a prominent inwardly
CC rectifying potassium (Kir) conductance that underlies the late
CC inhibitory postsynaptic potentials (By similarity). Along with gbb-1,
CC may couple to the G(o)-alpha G-protein goa-1 to negatively regulate
CC cholinergic receptor activity in the presence of high levels of
CC acetylcholine in ventral cord motor neurons (PubMed:18614679). As
CC acetylcholine depolarizes body wall muscles, modulation of
CC acetylcholine levels most likely results in the control of locomotory
CC behavior (PubMed:18614679). Regulates locomotory behavior in response
CC to GABA release by GABAergic motor neurons (PubMed:18614679,
CC PubMed:21613582). {ECO:0000250|UniProtKB:O88871,
CC ECO:0000269|PubMed:18614679, ECO:0000269|PubMed:21613582}.
CC -!- SUBUNIT: May form a heterodimer with gbb-1.
CC {ECO:0000305|PubMed:18614679}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O75899};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in cholinergic motor neurons.
CC {ECO:0000269|PubMed:21613582}.
CC -!- DOMAIN: Alpha-helical parts of the C-terminal intracellular region may
CC mediate heterodimeric interaction with gbb-1.
CC {ECO:0000250|UniProtKB:O75899}.
CC -!- DISRUPTION PHENOTYPE: Increased sensitivity to the acetylcholine
CC esterase inhibitor Aldicarb, which results in accelerated paralysis
CC likely due to enhanced acetylcholine release by ventral cord neurons
CC and enhanced depolarization of muscles on one side of the body
CC (PubMed:18614679). Increased locomotion and body curvature (deeper
CC bends) in response to induced GABA release of GABAergic motor neurons,
CC which in wild-type animals results in acute body relaxation
CC (PubMed:21613582). Double knockout with gbb-1 also results in increased
CC sensitivity to Aldicarb and accelerated paralysis, but in addition
CC results in irregular locomotory behavior characterized by increased
CC speed of locomotion, decreased turning frequency, reduced rate of
CC reversals, and an increased maximal distance covered in a 40 second
CC interval (PubMed:18614679). Double knockout with the muscarinic
CC acetylcholine receptor gar-2 results in a slight increase in
CC sensitivity to Aldicarb and accelerated paralysis 50 minutes following
CC exposure to Aldicarb as compared to the gar-2 and gbb-2 single mutants
CC (PubMed:18614679). Double knockout with the GABA(A) receptor unc-49
CC results in body elongation defects in response to induced GABA release
CC of GABAergic motor neurons (PubMed:21613582).
CC {ECO:0000269|PubMed:18614679, ECO:0000269|PubMed:21613582}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family.
CC {ECO:0000305}.
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DR EMBL; EU729335; ACE63491.1; -; mRNA.
DR EMBL; BX284604; CCD73081.1; -; Genomic_DNA.
DR RefSeq; NP_500579.3; NM_068178.3.
DR AlphaFoldDB; G5ECB2; -.
DR SMR; G5ECB2; -.
DR ComplexPortal; CPX-1158; GABA-B receptor complex.
DR STRING; 6239.ZK180.1; -.
DR EPD; G5ECB2; -.
DR PaxDb; G5ECB2; -.
DR EnsemblMetazoa; ZK180.1.1; ZK180.1.1; WBGene00022675.
DR GeneID; 191240; -.
DR KEGG; cel:CELE_ZK180.1; -.
DR CTD; 191240; -.
DR WormBase; ZK180.1; CE43384; WBGene00022675; gbb-2.
DR eggNOG; KOG1055; Eukaryota.
DR GeneTree; ENSGT00940000171994; -.
DR HOGENOM; CLU_005240_1_1_1; -.
DR InParanoid; G5ECB2; -.
DR OMA; LLKHYHW; -.
DR OrthoDB; 590810at2759; -.
DR PhylomeDB; G5ECB2; -.
DR Reactome; R-CEL-1296041; Activation of G protein gated Potassium channels.
DR Reactome; R-CEL-418594; G alpha (i) signalling events.
DR Reactome; R-CEL-420499; Class C/3 (Metabotropic glutamate/pheromone receptors).
DR Reactome; R-CEL-977444; GABA B receptor activation.
DR Reactome; R-CEL-997272; Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits.
DR PRO; PR:G5ECB2; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00022675; Expressed in larva and 3 other tissues.
DR GO; GO:1902712; C:G protein-coupled GABA receptor complex; TAS:UniProtKB.
DR GO; GO:0038039; C:G protein-coupled receptor heterodimeric complex; IBA:GO_Central.
DR GO; GO:0004965; F:G protein-coupled GABA receptor activity; IMP:UniProtKB.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IBA:GO_Central.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0007214; P:gamma-aminobutyric acid signaling pathway; IBA:GO_Central.
DR GO; GO:0032223; P:negative regulation of synaptic transmission, cholinergic; IMP:UniProtKB.
DR GO; GO:0040012; P:regulation of locomotion; IMP:ComplexPortal.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:UniProtKB.
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; IPR028082; Peripla_BP_I.
DR PANTHER; PTHR10519; PTHR10519; 1.
DR Pfam; PF00003; 7tm_3; 1.
DR Pfam; PF01094; ANF_receptor; 1.
DR PRINTS; PR00248; GPCRMGR.
DR SUPFAM; SSF53822; SSF53822; 1.
DR PROSITE; PS00196; COPPER_BLUE; 1.
DR PROSITE; PS50259; G_PROTEIN_RECEP_F3_4; 1.
PE 1: Evidence at protein level;
KW Cell membrane; G-protein coupled receptor; Glycoprotein; Membrane;
KW Receptor; Reference proteome; Signal; Transducer; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..842
FT /note="Gamma-aminobutyric acid type B receptor subunit 2"
FT /evidence="ECO:0000305"
FT /id="PRO_5010674398"
FT TOPO_DOM 18..438
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 439..459
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 460..477
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 478..498
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 499..506
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 507..527
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 528..556
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 557..577
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 578..610
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 611..631
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 632..647
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 648..668
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 669..676
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 677..697
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 698..842
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 725..744
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 791..842
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 725..739
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 791..823
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 274
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 279
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 366
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 605
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT MUTAGEN 484
FT /note="A->V: No change in protein function; when associated
FT with A-572."
FT /evidence="ECO:0000269|PubMed:21613582"
FT MUTAGEN 572
FT /note="V->A: No change in protein function; when associated
FT with V-484."
FT /evidence="ECO:0000269|PubMed:21613582"
SQ SEQUENCE 842 AA; 94861 MW; 2AE45E919FED1B39 CRC64;
MSRWLSLLLF AVQAVGGYEA GEELSCKRRH GGIPLPLGVF TVQKEGFPDA LPAIRTALSH
VHSRSCILQG YRLEMIVKDT HCKTSQGMKA LFDLIASRPR PVAILGGQCT EVNEPIAMAL
KYWQIVQLSY AETHAKFASS DSHELFTTFF RVVPGSRNTN MAKCKFVNHF GWKRVGTVKQ
NDQPRYALPH EALTTRLEHG FGVKIVHTAG VNWEQIETVG GELDELKERD VRIILVDVDE
EMAATVLCAG YHRGMYGDNY VWILPGYHSD KWLNQTHDNC TVEEMREAAK NHFSVEFALT
RRDVDTKIVG NTRAGDVWNE ITQLDPNNTW RGYLYDGLWT LAIALSHSMG DNAEFSHHKM
MEAIDNSSFQ GLTGKVKFAN NERLGLVDIK QWSDGQYVPF AVYDGADDEF KIIDSTTKGW
SPPLDSTITE RRREHISSIL FLAMSLLALI GIFLALIFLL INFRYRNHRF IKMSSPNLNN
IIIAGSICTF ASVIMLGLDT RIVSPDVFVW LCYTKTWTLC IGFTLSFGAM FSKTWRVHSI
FTNIRMDRKA IKDSKLFIIL GILLFIDICV LVTWAFVSPF SYTVTELPHI PEDNIVIIPE
VEKCNSSHSG VFQAVLYAVK GVLMILGCFL AWETRHVNVP ALNDSKYIGT SVYCCVVMSV
LGLSTSVILQ ERVNEMFSLA SFFVIFSTTL TLCLVFVPKV IELARNPVGN EPRAYRRGLM
KSVVAKTSQP MSPQPRSDSS GDLIGKAESE NKLRRRYLHQ KSTQLWDLVE KLRAQGDTRF
LQQEWCLSSA SPSSQERETS LLLRQPSSSN NREETSLTAA GPNGERSSDW PWVDPDEPST
KL
