GLUCL_CAEEL
ID GLUCL_CAEEL Reviewed; 461 AA.
AC G5EBR3;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 72.
DE RecName: Full=Glutamate-gated chloride channel alpha {ECO:0000305};
DE AltName: Full=Avermectin-sensitive glutamate-gated chloride channel GluCl alpha {ECO:0000303|PubMed:7935817};
DE AltName: Full=GluCl alpha {ECO:0000305};
DE Flags: Precursor;
GN Name=glc-1 {ECO:0000312|WormBase:F11A5.10};
GN ORFNames=F11A5.10 {ECO:0000312|WormBase:F11A5.10};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|EMBL:CAB07361.2};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND
RP INTERACTION WITH GLC-2.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAA50785.1};
RX PubMed=7935817; DOI=10.1038/371707a0;
RA Cully D.F., Vassilatis D.K., Liu K.K., Paress P.S., Van der Ploeg L.H.T.,
RA Schaeffer J.M., Arena J.P.;
RT "Cloning of an avermectin-sensitive glutamate-gated chloride channel from
RT Caenorhabditis elegans.";
RL Nature 371:707-711(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16527366; DOI=10.1016/j.molbiopara.2006.02.003;
RA Cook A., Aptel N., Portillo V., Siney E., Sihota R., Holden-Dye L.,
RA Wolstenholme A.;
RT "Caenorhabditis elegans ivermectin receptors regulate locomotor behaviour
RT and are functional orthologues of Haemonchus contortus receptors.";
RL Mol. Biochem. Parasitol. 147:118-125(2006).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (3.26 ANGSTROMS) OF 62-454 IN COMPLEXES WITH
RP IVERMECTIN; GLUTAMATE AND PICROTOXIN, FUNCTION, SUBUNIT, DOMAIN,
RP SUBCELLULAR LOCATION, TOPOLOGY, DISULFIDE BOND, AND GLYCOSYLATION AT
RP ASN-246.
RX PubMed=21572436; DOI=10.1038/nature10139;
RA Hibbs R.E., Gouaux E.;
RT "Principles of activation and permeation in an anion-selective Cys-loop
RT receptor.";
RL Nature 474:54-60(2011).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (3.20 ANGSTROMS) OF 62-363 AND 422-455, SUBUNIT,
RP SUBCELLULAR LOCATION, TOPOLOGY, DISULFIDE BOND, AND GLYCOSYLATION AT
RP ASN-246.
RX PubMed=25143115; DOI=10.1038/nature13669;
RA Althoff T., Hibbs R.E., Banerjee S., Gouaux E.;
RT "X-ray structures of GluCl in apo states reveal a gating mechanism of Cys-
RT loop receptors.";
RL Nature 512:333-337(2014).
CC -!- FUNCTION: Glutamate-gated chloride channel subunit; channel properties
CC depend on the subunit composition. Glutamate binding triggers a rapidly
CC reversible current in heteromeric channels formed by glc-1 and glc-2,
CC while the anti-helmintic drug ivermectin and other avermectins trigger
CC a permanently open channel configuration. Channels containing only glc-
CC 1 are activated by ivermectin, but not by glutamate alone (in vitro).
CC The heteromeric channel formed by glc-1 and glc-2 is also activated by
CC ibotenate, and it is blocked by picrotoxin and flufenamic acid
CC (PubMed:7935817). Plays a role in the regulation of locomotor behavior
CC (PubMed:16527366). {ECO:0000269|PubMed:16527366,
CC ECO:0000269|PubMed:21572436, ECO:0000269|PubMed:7935817}.
CC -!- SUBUNIT: Pentamer (PubMed:21572436 and PubMed:25143115). Homooligomer,
CC forms functional heterooligomers with glc-2 (PubMed:7935817).
CC {ECO:0000269|PubMed:21572436, ECO:0000269|PubMed:25143115,
CC ECO:0000269|PubMed:7935817}.
CC -!- INTERACTION:
CC G5EBR3; G5EBR3: glc-1; NbExp=2; IntAct=EBI-16006417, EBI-16006417;
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000250|UniProtKB:Q94900}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q94900}. Cell membrane {ECO:0000255,
CC ECO:0000269|PubMed:21572436, ECO:0000269|PubMed:25143115,
CC ECO:0000269|PubMed:7935817}; Multi-pass membrane protein {ECO:0000255,
CC ECO:0000269|PubMed:21572436, ECO:0000269|PubMed:25143115,
CC ECO:0000303|PubMed:7935817}.
CC -!- DOMAIN: Glutamate binding is mediated by the extracellular domain. In
CC contrast, the allosteric modulator ivermectin binds between subunits at
CC the periphery of the transmembrane domain, proximal to the
CC extracellular side. {ECO:0000269|PubMed:21572436}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a decrease in the
CC duration of forward locomotion in the absence of food, and an increase
CC in the frequency of turns. {ECO:0000269|PubMed:16527366}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC Glutamate-gated chloride channel (TC 1.A.9.4) subfamily. {ECO:0000305}.
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DR EMBL; U14524; AAA50785.1; -; mRNA.
DR EMBL; Z92830; CAB07361.2; -; Genomic_DNA.
DR PIR; S50864; S50864.
DR PIR; T20754; T20754.
DR RefSeq; NP_507090.1; NM_074689.5.
DR PDB; 3RHW; X-ray; 3.26 A; A/B/C/D/E=62-454.
DR PDB; 3RI5; X-ray; 3.40 A; A/B/C/D/E=62-454.
DR PDB; 3RIA; X-ray; 3.80 A; A/B/C/D/E=62-454.
DR PDB; 3RIF; X-ray; 3.35 A; A/B/C/D/E=62-454.
DR PDB; 4TNV; X-ray; 3.60 A; A/B/C/D/E/P/Q/R/S/T=62-363, A/B/C/D/E/P/Q/R/S/T=422-455.
DR PDB; 4TNW; X-ray; 3.20 A; A/B/C/D/E/P/Q/R/S/T=62-363, A/B/C/D/E/P/Q/R/S/T=422-455.
DR PDBsum; 3RHW; -.
DR PDBsum; 3RI5; -.
DR PDBsum; 3RIA; -.
DR PDBsum; 3RIF; -.
DR PDBsum; 4TNV; -.
DR PDBsum; 4TNW; -.
DR AlphaFoldDB; G5EBR3; -.
DR SMR; G5EBR3; -.
DR BioGRID; 45076; 1.
DR STRING; 6239.F11A5.10; -.
DR iPTMnet; G5EBR3; -.
DR EPD; G5EBR3; -.
DR PaxDb; G5EBR3; -.
DR PeptideAtlas; G5EBR3; -.
DR ABCD; G5EBR3; 1 sequenced antibody.
DR EnsemblMetazoa; F11A5.10.1; F11A5.10.1; WBGene00001591.
DR GeneID; 180086; -.
DR KEGG; cel:CELE_F11A5.10; -.
DR CTD; 180086; -.
DR WormBase; F11A5.10; CE24896; WBGene00001591; glc-1.
DR eggNOG; KOG3644; Eukaryota.
DR GeneTree; ENSGT00940000173436; -.
DR HOGENOM; CLU_010920_1_4_1; -.
DR InParanoid; G5EBR3; -.
DR OMA; YSCLRTT; -.
DR OrthoDB; 614790at2759; -.
DR PhylomeDB; G5EBR3; -.
DR Reactome; R-CEL-112314; Neurotransmitter receptors and postsynaptic signal transmission.
DR PRO; PR:G5EBR3; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00001591; Expressed in larva and 2 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0008068; F:extracellularly glutamate-gated chloride channel activity; IDA:UniProtKB.
DR GO; GO:0016595; F:glutamate binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:1902476; P:chloride transmembrane transport; IDA:UniProtKB.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0031987; P:locomotion involved in locomotory behavior; IMP:WormBase.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd19062; LGIC_TM_GluCl; 1.
DR Gene3D; 1.20.58.390; -; 1.
DR Gene3D; 2.70.170.10; -; 1.
DR InterPro; IPR006028; GABAA/Glycine_rcpt.
DR InterPro; IPR015680; Glu_Cl_Channel.
DR InterPro; IPR044721; GluCl_TM.
DR InterPro; IPR006202; Neur_chan_lig-bd.
DR InterPro; IPR036734; Neur_chan_lig-bd_sf.
DR InterPro; IPR006201; Neur_channel.
DR InterPro; IPR036719; Neuro-gated_channel_TM_sf.
DR InterPro; IPR038050; Neuro_actylchol_rec.
DR InterPro; IPR006029; Neurotrans-gated_channel_TM.
DR InterPro; IPR018000; Neurotransmitter_ion_chnl_CS.
DR PANTHER; PTHR18945; PTHR18945; 1.
DR PANTHER; PTHR18945:SF754; PTHR18945:SF754; 1.
DR Pfam; PF02931; Neur_chan_LBD; 1.
DR Pfam; PF02932; Neur_chan_memb; 1.
DR PRINTS; PR00253; GABAARECEPTR.
DR PRINTS; PR00252; NRIONCHANNEL.
DR SUPFAM; SSF63712; SSF63712; 1.
DR SUPFAM; SSF90112; SSF90112; 1.
DR TIGRFAMs; TIGR00860; LIC; 1.
DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Chloride; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Postsynaptic cell membrane;
KW Reference proteome; Signal; Synapse; Transmembrane; Transmembrane helix;
KW Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..461
FT /note="Glutamate-gated chloride channel alpha"
FT /evidence="ECO:0000255"
FT /id="PRO_0000430674"
FT TOPO_DOM 21..275
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT TRANSMEM 276..298
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT TOPO_DOM 299..303
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT TRANSMEM 304..325
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT TOPO_DOM 326..332
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT TRANSMEM 333..353
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT TOPO_DOM 354..432
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT TRANSMEM 433..454
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT TOPO_DOM 455..461
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT BINDING 98
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000269|PubMed:21572436"
FT BINDING 117
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000269|PubMed:21572436"
FT BINDING 182
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000269|PubMed:21572436"
FT BINDING 211
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000269|PubMed:21572436"
FT CARBOHYD 246
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT DISULFID 191..205
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT DISULFID 252..263
FT /evidence="ECO:0000269|PubMed:21572436,
FT ECO:0000269|PubMed:25143115"
FT HELIX 63..70
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 89..104
FT /evidence="ECO:0007829|PDB:4TNW"
FT TURN 105..108
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 109..121
FT /evidence="ECO:0007829|PDB:4TNW"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 136..139
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 156..161
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 168..174
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 177..190
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 202..213
FT /evidence="ECO:0007829|PDB:4TNW"
FT TURN 216..218
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 219..223
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:4TNW"
FT TURN 236..238
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 240..251
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 263..272
FT /evidence="ECO:0007829|PDB:4TNW"
FT HELIX 274..280
FT /evidence="ECO:0007829|PDB:4TNW"
FT HELIX 282..293
FT /evidence="ECO:0007829|PDB:4TNW"
FT STRAND 296..298
FT /evidence="ECO:0007829|PDB:4TNW"
FT HELIX 303..327
FT /evidence="ECO:0007829|PDB:4TNW"
FT HELIX 336..363
FT /evidence="ECO:0007829|PDB:4TNW"
FT HELIX 422..453
FT /evidence="ECO:0007829|PDB:4TNW"
SQ SEQUENCE 461 AA; 52553 MW; 0F2388D1FAC0309F CRC64;
MATWIVGKLI IASLILGIQA QQARTKSQDI FEDDNDNGTT TLESLARLTS PIHIPIEQPQ
TSDSKILAHL FTSGYDFRVR PPTDNGGPVV VSVNMLLRTI SKIDVVNMEY SAQLTLRESW
IDKRLSYGVK GDGQPDFVIL TVGHQIWMPD TFFPNEKQAY KHTIDKPNVL IRIHNDGTVL
YSVRISLVLS CPMYLQYYPM DVQQCSIDLA SYAYTTKDIE YLWKEHSPLQ LKVGLSSSLP
SFQLTNTSTT YCTSVTNTGI YSCLRTTIQL KREFSFYLLQ LYIPSCMLVI VSWVSFWFDR
TAIPARVTLG VTTLLTMTAQ SAGINSQLPP VSYIKAIDVW IGACMTFIFC ALLEFALVNH
IANKQGVERK ARTEREKAEI PLLQNLHNDV PTKVFNQEEK VRTVPLNRRQ MNSFLNLLET
KTEWNDISKR VDLISRALFP VLFFVFNILY WSRFGQQNVL F
