GABR1_CAEEL
ID GABR1_CAEEL Reviewed; 899 AA.
AC H2L0Q3; A0A0K3AVQ1; B3VBI8; B7CED7; Q9N502;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 11-NOV-2015, sequence version 2.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=Gamma-aminobutyric acid type B receptor subunit 1 {ECO:0000305};
DE Flags: Precursor;
GN Name=gbb-1 {ECO:0000312|WormBase:Y41G9A.4b};
GN ORFNames=Y41G9A.4 {ECO:0000312|WormBase:Y41G9A.4b};
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:ACE63490.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM C), FUNCTION, SUBUNIT, TISSUE
RP SPECIFICITY, 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 DISRUPTION PHENOTYPE.
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).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26537867; DOI=10.1038/ncomms9828;
RA Chun L., Gong J., Yuan F., Zhang B., Liu H., Zheng T., Yu T., Xu X.Z.,
RA Liu J.;
RT "Metabotropic GABA signalling modulates longevity in C. elegans.";
RL Nat. Commun. 6:8828-8828(2015).
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). Calcium is required for high affinity binding to GABA (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-2,
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). Acts in neurons to regulate lifespan, and
CC this may be through G-protein-egl-8/PLC-beta signaling to the
CC transcription factor daf-16/FOXO (PubMed:26537867).
CC {ECO:0000250|UniProtKB:Q9UBS5, ECO:0000250|UniProtKB:Q9Z0U4,
CC ECO:0000269|PubMed:18614679, ECO:0000269|PubMed:26537867}.
CC -!- SUBUNIT: May form a heterodimer with gbb-2.
CC {ECO:0000305|PubMed:18614679}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9UBS5};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=b {ECO:0000312|WormBase:Y41G9A.4b};
CC IsoId=H2L0Q3-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:Y41G9A.4a};
CC IsoId=H2L0Q3-2; Sequence=VSP_059101, VSP_059102;
CC Name=c {ECO:0000312|WormBase:Y41G9A.4c};
CC IsoId=H2L0Q3-3; Sequence=VSP_059103;
CC Name=e {ECO:0000312|WormBase:Y41G9A.4e};
CC IsoId=H2L0Q3-4; Sequence=VSP_059100;
CC -!- TISSUE SPECIFICITY: Expressed in the nervous system, including
CC cholinergic motor neurons, but not in GABAergic motor neurons or
CC muscle. {ECO:0000269|PubMed:18614679}.
CC -!- DOMAIN: Alpha-helical parts of the C-terminal intracellular region may
CC mediate heterodimeric interaction with gbb-2.
CC {ECO:0000250|UniProtKB:Q9UBS5}.
CC -!- DISRUPTION PHENOTYPE: Increased lifespan (PubMed:26537867). Increased
CC sensitivity to the acetylcholine esterase inhibitor Aldicarb, which
CC results in accelerated paralysis likely due to enhanced acetylcholine
CC release by ventral cord neurons and enhanced depolarization of muscles
CC on one side of the body (PubMed:18614679). Double knockout with gbb-2
CC also results in increased sensitivity to Aldicarb and accelerated
CC paralysis, but in addition results in irregular locomotory behavior
CC characterized by increased speed of locomotion, decreased turning
CC frequency, reduced rate of reversals, and an increased maximal distance
CC covered in a 40 second interval (PubMed:18614679). Double knockout with
CC the GABA(A) receptor unc-49 results in body elongation defects in
CC response to induced GABA release of GABAergic motor neurons
CC (PubMed:21613582). {ECO:0000269|PubMed:18614679,
CC ECO:0000269|PubMed:21613582, ECO:0000269|PubMed:26537867}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 3 family.
CC {ECO:0000305}.
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DR EMBL; EU729334; ACE63490.1; -; mRNA.
DR EMBL; BX284606; CCD74420.2; -; Genomic_DNA.
DR EMBL; BX284606; CCD74424.2; -; Genomic_DNA.
DR EMBL; BX284606; CCD74425.2; -; Genomic_DNA.
DR EMBL; BX284606; CTQ87097.1; -; Genomic_DNA.
DR RefSeq; NP_001256997.2; NM_001270068.2. [H2L0Q3-3]
DR RefSeq; NP_001300386.1; NM_001313457.1. [H2L0Q3-4]
DR RefSeq; NP_741740.3; NM_171645.4. [H2L0Q3-1]
DR RefSeq; NP_741741.2; NM_171646.4. [H2L0Q3-2]
DR AlphaFoldDB; H2L0Q3; -.
DR SMR; H2L0Q3; -.
DR ComplexPortal; CPX-1158; GABA-B receptor complex.
DR STRING; 6239.Y41G9A.4b; -.
DR PaxDb; H2L0Q3; -.
DR EnsemblMetazoa; Y41G9A.4a.1; Y41G9A.4a.1; WBGene00021528. [H2L0Q3-2]
DR EnsemblMetazoa; Y41G9A.4b.1; Y41G9A.4b.1; WBGene00021528. [H2L0Q3-1]
DR EnsemblMetazoa; Y41G9A.4c.1; Y41G9A.4c.1; WBGene00021528. [H2L0Q3-3]
DR EnsemblMetazoa; Y41G9A.4e.1; Y41G9A.4e.1; WBGene00021528. [H2L0Q3-4]
DR GeneID; 189837; -.
DR UCSC; Y41G9A.4a; c. elegans.
DR CTD; 189837; -.
DR WormBase; Y41G9A.4a; CE50190; WBGene00021528; gbb-1. [H2L0Q3-2]
DR WormBase; Y41G9A.4b; CE50147; WBGene00021528; gbb-1. [H2L0Q3-1]
DR WormBase; Y41G9A.4c; CE50293; WBGene00021528; gbb-1. [H2L0Q3-3]
DR WormBase; Y41G9A.4e; CE50186; WBGene00021528; gbb-1. [H2L0Q3-4]
DR eggNOG; KOG1055; Eukaryota.
DR GeneTree; ENSGT00940000157642; -.
DR InParanoid; H2L0Q3; -.
DR OMA; WAGGEAC; -.
DR OrthoDB; 590810at2759; -.
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:H2L0Q3; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00021528; Expressed in larva and 3 other tissues.
DR ExpressionAtlas; H2L0Q3; baseline.
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 CDD; cd15291; 7tmC_GABA-B-R1; 1.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR002455; GPCR3_GABA-B.
DR InterPro; IPR017978; GPCR_3_C.
DR InterPro; IPR002456; GPCR_3_GABA_rcpt_B1.
DR InterPro; IPR028082; Peripla_BP_I.
DR PANTHER; PTHR10519; PTHR10519; 1.
DR Pfam; PF00003; 7tm_3; 1.
DR Pfam; PF01094; ANF_receptor; 1.
DR SUPFAM; SSF53822; SSF53822; 1.
DR PROSITE; PS50259; G_PROTEIN_RECEP_F3_4; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Coiled coil;
KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..899
FT /note="Gamma-aminobutyric acid type B receptor subunit 1"
FT /evidence="ECO:0000305"
FT /id="PRO_5005682875"
FT TOPO_DOM 20..447
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 448..468
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 469..487
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 488..508
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 509..525
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 526..546
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 547..616
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 617..637
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 638..674
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 675..695
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 696..713
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 714..734
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 735..741
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 742..762
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 763..899
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 870..899
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 791..842
FT /evidence="ECO:0000255"
FT CARBOHYD 69
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 339
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 371
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 1..680
FT /note="Missing (in isoform e)"
FT /evidence="ECO:0000305"
FT /id="VSP_059100"
FT VAR_SEQ 524..529
FT /note="ARVTIL -> VSQTFR (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_059101"
FT VAR_SEQ 530..899
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_059102"
FT VAR_SEQ 566..609
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_059103"
SQ SEQUENCE 899 AA; 101531 MW; 1F4F987E3B2F1489 CRC64;
MFVRSSWLLL WGTIVWASAE PVTLHIGGTF PMESGSGGWA GGEACLPAVE MALKDVNSRL
DILPGYVLNM TNHNSQCQPG LAMQQLYDFL YKPPTKLMLL TGCSPVTTVI AEAAPVWKLV
VLSYGGSSPA LSNRNRFPTL FRTHPSANMQ NPTRIHIMEK FKWKRFTILM SVEEVFVTTA
KDLEAIARKK GIKVDRQSFY GDPTDAMKTL QRQDARIIVG LFYVTEARKV LCQAYHHGLY
GRRYVWFFIG WYADTWYIPP PEEHLNCTAE QMTEAAEYHF TTESVMLSRD NIPAISEMTG
MQFQQRLTQY FQKDTANVGG FPEAPLAYDA VWALALAFNC TRNNLPSHIR LENFTYDNKV
IADTLFQCVK NTSFRGVSGK VMFSDSGDRI ARTQIEQMQG GKYKIMGYYD TTSGDLEWYN
KEQWLNGKGP PPDSTVIKKH AMTVSNEFYY PTILFAVLGI AACVFIYLFT QKHHERLIIF
QSQPECNNIL LIGCSLCLFS LFLIGLPSDD ISISESLFPL LCHARVTILL FGFTFAYGSM
FAKVWIVHRM GATENQQLAS RQKDEEENTP WEGIRTLIST MVGRQALMRK SSGQAYGALL
EKRNTVLNQP ISSSKFYVIV AALTAVDVFV CFVWVLIDPL HLTEQKFPLF TPADSEEDEM
IMPVLQQCQS NQQEVWIGII MGFKCLLLVF GTFLSYETRN LKLRFINDSR FVGLAIYNVA
VMTLVTAPVV TLLIHGKVDA NFAFISLTVL ICTYISVGLI YGPKIRHIIK VPPSADEIQL
NGNVGPGVMS KVDQKRYDML KKENETLQIQ IEEKERKIHE CKERLEELTK NSETEDMNAQ
LLCENDKQIA DENLTYSTAT TLTTTIPLID LQNGNHPGQI YENDNDDDGS STSSDEILL
