LGC46_CAEEL
ID LGC46_CAEEL Reviewed; 508 AA.
AC Q95Y52;
DT 22-NOV-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Probable ligand-gated ion channel 46 {ECO:0000312|WormBase:Y71D11A.5};
DE Flags: Precursor;
GN Name=lgc-46 {ECO:0000312|WormBase:Y71D11A.5};
GN ORFNames=Y71D11A.5 {ECO:0000312|WormBase:Y71D11A.5};
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|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 [2] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 301-PRO--ALA-302 AND MET-314.
RX PubMed=27782882; DOI=10.7554/elife.21734;
RA Takayanagi-Kiya S., Zhou K., Jin Y.;
RT "Release-dependent feedback inhibition by a presynaptically localized
RT ligand-gated anion channel.";
RL Elife 5:21734-21749(2016).
CC -!- FUNCTION: Probable component of a ligand-gated anion channel.
CC Negatively regulates synaptic transmission and synaptic vesicle release
CC in response to acetylcholine in cholinergic motor neurons. Role in
CC synaptic vesicle release kinetics may be in association with the
CC ligand-gated ion channel protein acc-4. {ECO:0000269|PubMed:27782882}.
CC -!- SUBCELLULAR LOCATION: Presynaptic cell membrane
CC {ECO:0000269|PubMed:27782882}; Multi-pass membrane protein
CC {ECO:0000255}. Cell projection, axon {ECO:0000269|PubMed:27782882}.
CC Cytoplasmic vesicle, secretory vesicle, synaptic vesicle
CC {ECO:0000269|PubMed:27782882}.
CC -!- TISSUE SPECIFICITY: Expressed in the nervous system, with high
CC expression in cholinergic motor neurons and weak expression in
CC GABAergic motor neurons. {ECO:0000269|PubMed:27782882}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the dorsal nerve cord of L1 larva and
CC on the dorsal side only of L4 larva and adults.
CC {ECO:0000269|PubMed:27782882}.
CC -!- DISRUPTION PHENOTYPE: Viable, with normal growth, reproduction and
CC locomotion. Increased sensitivity to the acetylcholine esterase
CC inhibitor aldicarb, but normal sensitivity to levamisole, an agonist
CC for postsynaptic acetylcholine receptors on muscles. In response to
CC induced acetylcholine release, the amplitude and rise phase of
CC excitatory postsynaptic currents (eEPSCs) during synaptic transmission
CC is as wild-type, but there is prolonged and slow decay of eEPSCs during
CC the late phase of synaptic transmission, which results in increased
CC release of synaptic vesicles in cholinergic motor neurons.
CC {ECO:0000269|PubMed:27782882}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC {ECO:0000305}.
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DR EMBL; BX284603; CCD72054.1; -; Genomic_DNA.
DR RefSeq; NP_497338.2; NM_064937.5.
DR AlphaFoldDB; Q95Y52; -.
DR SMR; Q95Y52; -.
DR STRING; 6239.Y71D11A.5; -.
DR PaxDb; Q95Y52; -.
DR EnsemblMetazoa; Y71D11A.5.1; Y71D11A.5.1; WBGene00022106.
DR GeneID; 175279; -.
DR KEGG; cel:CELE_Y71D11A.5; -.
DR UCSC; Y71D11A.5; c. elegans.
DR CTD; 175279; -.
DR WormBase; Y71D11A.5; CE29908; WBGene00022106; lgc-46.
DR eggNOG; KOG3644; Eukaryota.
DR HOGENOM; CLU_010920_1_3_1; -.
DR InParanoid; Q95Y52; -.
DR OMA; FNIAYWQ; -.
DR OrthoDB; 466513at2759; -.
DR PhylomeDB; Q95Y52; -.
DR Reactome; R-CEL-977443; GABA receptor activation.
DR PRO; PR:Q95Y52; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00022106; Expressed in larva and 3 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0008021; C:synaptic vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0050877; P:nervous system process; IBA:GO_Central.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR Gene3D; 1.20.58.390; -; 1.
DR Gene3D; 2.70.170.10; -; 1.
DR InterPro; IPR006028; GABAA/Glycine_rcpt.
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 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 PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell projection; Cytoplasmic vesicle; Disulfide bond;
KW Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel;
KW Membrane; Reference proteome; Signal; Synapse; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..508
FT /note="Probable ligand-gated ion channel 46"
FT /evidence="ECO:0000305"
FT /id="PRO_5004322281"
FT TOPO_DOM 19..274
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 275..295
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 296..301
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 302..321
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 322..335
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 336..356
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 357..480
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 481..501
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 502..508
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT REGION 374..407
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 65
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 201
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 190..204
FT /evidence="ECO:0000250|UniProtKB:P02712"
FT MUTAGEN 301..302
FT /note="PA->E: Does not suppress the increased number of
FT convulsions in the acr-2 (acetylcholine-gated cation
FT channel) gain of function mutant; when associated with I-
FT 314."
FT /evidence="ECO:0000269|PubMed:27782882"
FT MUTAGEN 314
FT /note="M->I: In ju825; gain of function mutation. Irregular
FT 'curly' body posture and slow locomotion. Slow locomotion
FT defect suppressed in an acc-4 null background. Reduces the
FT amplitude and suppresses synaptic vesicle release from the
FT presynaptic membrane of cholinergic motor neurons during
FT the late phase of synaptic transmission. Fully suppresses
FT sensitivity to the acetylcholine esterase inhibitor
FT aldicarb in lgc-46 null mutants. Suppresses the increased
FT number of convulsions in the double acr-2 gain of function
FT and acc-4 null mutant background. Does not suppress the
FT increased number of convulsions in the acr-2 gain of
FT function mutant; when associated with E-301."
FT /evidence="ECO:0000269|PubMed:27782882"
SQ SEQUENCE 508 AA; 58461 MW; FD9CE28A3E6D8F88 CRC64;
MQYLQFLSLV VLLLMCHARK SVYRRNSPSL RRLTRNYDWE VDEHGGLKPI INPAKVERAT
KNCANDSFIL GTIMSNYNRH KIPGGQVDVE VEVWVQEITT ISDITSDFQL DIYIYETWYD
PALNYAFMNP CKYNLSLNSV LLEKLWTPNS CFINSKTADI HKSPFPNIFL MIYANGTVWT
NYRLKLQGPC IMDLTKFPFD NVTCSLTFES FNYNTDEVKM DWSVNGVQKM RDKMELADYE
LVDIHKIRTT EEYPAGYWHE LTMSFEFKRR AGWYILQAYL PTYLTICISW ISFALGSKAI
PARTMLGVNS LLAMTFQFGN IIRNLPRVSY VKAIDVWMLS CMTFVFCSLL ELAWVGYLSR
EEEPTSAKCL QPSAQVAPKP CHPPPVQQNA NNSSVHRRQK QPKNEEESAL LSLRDNDYGY
IPPGFGLNGN VANAMKSFSS SCSCEPTNVV NLMLDEAETI PTSTSSSLSR KQRREILAHK
IDSVSVFMFP FLFVLFNIAY WQHYLRGY