MOD1_CAEEL
ID MOD1_CAEEL Reviewed; 489 AA.
AC Q9GQ00; H2L0B8; Q8MPU3; Q9GYH1;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Serotonin-gated chloride channel mod-1 {ECO:0000303|PubMed:11100728};
DE AltName: Full=Modulation Of locomotion defective protein 1 {ECO:0000312|WormBase:K06C4.6a};
DE Flags: Precursor;
GN Name=mod-1 {ECO:0000312|WormBase:K06C4.6a};
GN ORFNames=K06C4.6 {ECO:0000312|WormBase:K06C4.6a};
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:AAG36975.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF ALA-281.
RX PubMed=11100728; DOI=10.1038/35044083;
RA Ranganathan R., Cannon S.C., Horvitz H.R.;
RT "MOD-1 is a serotonin-gated chloride channel that modulates locomotory
RT behaviour in C. elegans.";
RL Nature 408:470-475(2000).
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.
RX PubMed=12783521; DOI=10.1021/ja0348086;
RA Mu T.W., Lester H.A., Dougherty D.A.;
RT "Different binding orientations for the same agonist at homologous
RT receptors: a lock and key or a simple wedge?";
RL J. Am. Chem. Soc. 125:6850-6851(2003).
RN [4] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF 266-LYS--ALA-267; 266-LYS--THR-272 AND
RP ALA-270.
RX PubMed=15878844; DOI=10.1074/jbc.m501624200;
RA Menard C., Horvitz H.R., Cannon S.;
RT "Chimeric mutations in the M2 segment of the 5-hydroxytryptamine-gated
RT chloride channel MOD-1 define a minimal determinant of anion/cation
RT permeability.";
RL J. Biol. Chem. 280:27502-27507(2005).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=16291940; DOI=10.1523/jneurosci.3399-05.2005;
RA Carnell L., Illi J., Hong S.W., McIntire S.L.;
RT "The G-protein-coupled serotonin receptor SER-1 regulates egg laying and
RT male mating behaviors in Caenorhabditis elegans.";
RL J. Neurosci. 25:10671-10681(2005).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=16281027; DOI=10.1038/nature04216;
RA Zhang Y., Lu H., Bargmann C.I.;
RT "Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis
RT elegans.";
RL Nature 438:179-184(2005).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=19193891; DOI=10.1523/jneurosci.4585-08.2009;
RA Harris G.P., Hapiak V.M., Wragg R.T., Miller S.B., Hughes L.J.,
RA Hobson R.J., Steven R., Bamber B., Komuniecki R.W.;
RT "Three distinct amine receptors operating at different levels within the
RT locomotory circuit are each essential for the serotonergic modulation of
RT chemosensation in Caenorhabditis elegans.";
RL J. Neurosci. 29:1446-1456(2009).
RN [8] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=23023001; DOI=10.1534/genetics.112.142125;
RA Guerel G., Gustafson M.A., Pepper J.S., Horvitz H.R., Koelle M.R.;
RT "Receptors and other signaling proteins required for serotonin control of
RT locomotion in Caenorhabditis elegans.";
RL Genetics 192:1359-1371(2012).
RN [9] {ECO:0000305}
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23972393; DOI=10.1016/j.cell.2013.08.001;
RA Flavell S.W., Pokala N., Macosko E.Z., Albrecht D.R., Larsch J.,
RA Bargmann C.I.;
RT "Serotonin and the neuropeptide PDF initiate and extend opposing behavioral
RT states in C. elegans.";
RL Cell 154:1023-1035(2013).
RN [10] {ECO:0000305}
RP FUNCTION.
RX PubMed=24120942; DOI=10.1016/j.cmet.2013.09.007;
RA Noble T., Stieglitz J., Srinivasan S.;
RT "An integrated serotonin and octopamine neuronal circuit directs the
RT release of an endocrine signal to control C. elegans body fat.";
RL Cell Metab. 18:672-684(2013).
CC -!- FUNCTION: Functions as a 5-hydroxytryptamine (serotonin) receptor
CC (PubMed:11100728, PubMed:12783521, PubMed:23023001). This receptor is a
CC ligand-gated anion-specific ion channel, selective for chloride ions
CC (PubMed:11100728, PubMed:15878844). Relays a long-range endocrine
CC signal from the body cavity neurons to modulate distal adipose
CC triglyceride lipase atgl-1 function, via the nuclear receptor nhr-76
CC (PubMed:24120942). Together with the G-protein coupled serotonin
CC receptor ser-1 involved in male mating behavior (PubMed:16291940). May
CC mediate an inhibitory effect of serotonin on egg laying
CC (PubMed:16291940). Involved in regulating locomotory behavior, perhaps
CC by modulating interneuronal signaling, acting in concert with G-protein
CC coupled serotonin receptor ser-4 (PubMed:19193891, PubMed:23023001). In
CC the presence of food, plays a role in initiating and extending dwelling
CC behavior, perhaps acting in AIY, RIF and ASI neurons, in opposition to
CC neuropeptide PDF-mediated signaling (PubMed:23972393). Plays a role in
CC aversive learning upon exposure to pathogens such as Gram-negative
CC bacterium P.aeruginosa strain PA14; perhaps acting in interneurons in
CC response to serotonin released by the serotonergic ADF neurons
CC (PubMed:16281027). {ECO:0000269|PubMed:11100728,
CC ECO:0000269|PubMed:12783521, ECO:0000269|PubMed:15878844,
CC ECO:0000269|PubMed:16281027, ECO:0000269|PubMed:16291940,
CC ECO:0000269|PubMed:19193891, ECO:0000269|PubMed:23023001,
CC ECO:0000269|PubMed:23972393, ECO:0000269|PubMed:24120942}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:12783521}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:K06C4.6a};
CC IsoId=Q9GQ00-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:K06C4.6b};
CC IsoId=Q9GQ00-2; Sequence=VSP_061451;
CC Name=c {ECO:0000312|WormBase:K06C4.6c};
CC IsoId=Q9GQ00-3; Sequence=VSP_061452, VSP_061453;
CC -!- TISSUE SPECIFICITY: Expressed in a subset of muscles, and head and tail
CC neurons, including RME and GABAergic ventral nerve cord neurons
CC (PubMed:23023001). Expressed in AIY, RME, RID, RIF, ASI, DD1-6, and PVN
CC neurons (PubMed:23972393). {ECO:0000269|PubMed:23023001,
CC ECO:0000269|PubMed:23972393}.
CC -!- DEVELOPMENTAL STAGE: Expressed in all body-wall muscles in L3 stage
CC larvae, and at a lower level in L4 stage larvae and adults.
CC {ECO:0000269|PubMed:23023001}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC {ECO:0000255|RuleBase:RU000687}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF303088; AAG36975.1; -; mRNA.
DR EMBL; BX284605; CCD72364.1; -; Genomic_DNA.
DR EMBL; BX284605; CCD72365.1; -; Genomic_DNA.
DR EMBL; BX284605; CCD72366.1; -; Genomic_DNA.
DR RefSeq; NP_741580.1; NM_171495.4.
DR AlphaFoldDB; Q9GQ00; -.
DR SMR; Q9GQ00; -.
DR STRING; 6239.K06C4.6a; -.
DR TCDB; 1.A.9.6.1; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR PaxDb; Q9GQ00; -.
DR EnsemblMetazoa; K06C4.6a.1; K06C4.6a.1; WBGene00003386. [Q9GQ00-1]
DR EnsemblMetazoa; K06C4.6b.1; K06C4.6b.1; WBGene00003386. [Q9GQ00-2]
DR EnsemblMetazoa; K06C4.6c.1; K06C4.6c.1; WBGene00003386. [Q9GQ00-3]
DR GeneID; 179269; -.
DR UCSC; K06C4.6a; c. elegans. [Q9GQ00-1]
DR CTD; 179269; -.
DR WormBase; K06C4.6a; CE28590; WBGene00003386; mod-1.
DR WormBase; K06C4.6b; CE30814; WBGene00003386; mod-1.
DR WormBase; K06C4.6c; CE38391; WBGene00003386; mod-1.
DR eggNOG; KOG3644; Eukaryota.
DR HOGENOM; CLU_010920_1_3_1; -.
DR InParanoid; Q9GQ00; -.
DR OMA; DFDMVHY; -.
DR OrthoDB; 459332at2759; -.
DR PhylomeDB; Q9GQ00; -.
DR Reactome; R-CEL-977443; GABA receptor activation.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00003386; Expressed in larva and 2 other tissues.
DR ExpressionAtlas; Q9GQ00; baseline and differential.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:WormBase.
DR GO; GO:0043005; C:neuron projection; IBA:GO_Central.
DR GO; GO:0043025; C:neuronal cell body; IDA:WormBase.
DR GO; GO:0045202; C:synapse; IBA:GO_Central.
DR GO; GO:0005254; F:chloride channel activity; IDA:WormBase.
DR GO; GO:0005231; F:excitatory extracellular ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0005230; F:extracellular ligand-gated ion channel activity; IDA:WormBase.
DR GO; GO:0004993; F:G protein-coupled serotonin receptor activity; IDA:WormBase.
DR GO; GO:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:1904315; F:transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential; IBA:GO_Central.
DR GO; GO:0042595; P:behavioral response to starvation; IMP:WormBase.
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:0006821; P:chloride transport; IDA:WormBase.
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:1904123; P:positive regulation of fatty acid beta-oxidation by serotonin receptor signaling pathway; IMP:WormBase.
DR GO; GO:0042391; P:regulation of membrane potential; IBA:GO_Central.
DR GO; GO:0007210; P:serotonin receptor signaling pathway; IDA:WormBase.
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 TIGRFAMs; TIGR00860; LIC; 1.
DR PROSITE; PS00236; NEUROTR_ION_CHANNEL; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Coiled coil; Glycoprotein;
KW Ion channel; Ion transport; Membrane; Plasmid; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..489
FT /note="Serotonin-gated chloride channel mod-1"
FT /evidence="ECO:0000255"
FT /id="PRO_5015099770"
FT TOPO_DOM 21..240
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:12783521"
FT TRANSMEM 241..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 274..294
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 304..324
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 325..458
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:12783521"
FT TRANSMEM 459..479
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 365..399
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 180
FT /ligand="serotonin"
FT /ligand_id="ChEBI:CHEBI:350546"
FT /ligand_note="agonist"
FT /evidence="ECO:0000305|PubMed:12783521"
FT BINDING 226
FT /ligand="serotonin"
FT /ligand_id="ChEBI:CHEBI:350546"
FT /ligand_note="agonist"
FT /evidence="ECO:0000305|PubMed:12783521"
FT CARBOHYD 44
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 103
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 422..435
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_061451"
FT VAR_SEQ 436..442
FT /note="MRSTSPP -> VTVKVVN (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_061452"
FT VAR_SEQ 443..489
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_061453"
FT MUTAGEN 266..272
FT /note="KALPART->ELPARV: Converts the channel ion
FT selectivity from anionic to cationic; most selective for
FT potassium ions."
FT /evidence="ECO:0000269|PubMed:15878844"
FT MUTAGEN 266..267
FT /note="KA->E: Converts the channel ion selectivity from
FT anionic to cationic."
FT /evidence="ECO:0000269|PubMed:15878844"
FT MUTAGEN 270
FT /note="A->E: Converts the channel ion selectivity from
FT anionic to cationic."
FT /evidence="ECO:0000269|PubMed:15878844"
FT MUTAGEN 281
FT /note="A->V: In n3034; locomotory rate of food-deprived
FT animals is significantly faster than that of the wild type;
FT resistant to exogenous serotonin treatment, unlike wild-
FT type animals."
FT /evidence="ECO:0000269|PubMed:11100728"
SQ SEQUENCE 489 AA; 56143 MW; 2500DD8F1136387F CRC64;
MKFIPEITLL LLLFVHSTQA KGKRRKCPEG AWSEGKIMNT IMSNYTKMLP DAEDSVQVNI
EIHVQDMGSL NEISSDFEID ILFTQLWHDS ALSFAHLPAC KRNITMETRL LPKIWSPNTC
MINSKRTTVH ASPSENVMVI LYENGTVWIN HRLSVKSPCN LDLRQFPFDT QTCILIFESY
SHNSEEVELH WMEEAVTLMK PIQLPDFDMV HYSTKKETLL YPNGYWDQLQ VTFTFKRRYG
FYIIQAYVPT YLTIIVSWVS FCMEPKALPA RTTVGISSLL ALTFQFGNIL KNLPRVSYVK
AMDVWMLGCI SFVFGTMVEL AFVCYISRCQ NSVRNAERRR ERMRNSQVWA NGSCRTRSNG
YANGGSVISH YHPTSNGNGN NNRHDTPQVT GRGSLHRNGP PSPLNLQMTT FDSEIPLTFD
QLPVSMESDR PLIEEMRSTS PPPPSGCLAR FHPEAVDKFS IVAFPLAFTM FNLVYWWHYL
SQTFDQNYQ
