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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
 
 
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