5HT3E_HUMAN
ID 5HT3E_HUMAN Reviewed; 456 AA.
AC A5X5Y0; A8IKD7; E9PGF1; Q495G1; Q495G3; Q6V706; Q6V707; Q7Z6B2;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 10-JUL-2007, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=5-hydroxytryptamine receptor 3E;
DE Short=5-HT3-E;
DE Short=5-HT3E;
DE AltName: Full=Serotonin receptor 3E;
DE Flags: Precursor;
GN Name=HTR3E;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND TISSUE SPECIFICITY.
RX PubMed=12801637; DOI=10.1016/s0378-1119(03)00503-1;
RA Niesler B., Frank B., Kapeller J., Rappold G.A.;
RT "Cloning, physical mapping and expression analysis of the human 5-HT3
RT serotonin receptor-like genes HTR3C, HTR3D and HTR3E.";
RL Gene 310:101-111(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4), AND TISSUE SPECIFICITY.
RX PubMed=14597179; DOI=10.1016/s0378-1119(03)00803-5;
RA Karnovsky A.M., Gotow L.F., McKinley D.D., Piechan J.L., Ruble C.L.,
RA Mills C.J., Schellin K.A.B., Slightom J.L., Fitzgerald L.R., Benjamin C.W.,
RA Roberds S.L.;
RT "A cluster of novel serotonin receptor 3-like genes on human chromosome
RT 3.";
RL Gene 319:137-148(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), SUBUNIT, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17392525; DOI=10.1124/mol.106.032144;
RA Niesler B., Walstab J., Combrink S., Moeller D., Kapeller J., Rietdorf J.,
RA Boenisch H., Goethert M., Rappold G., Bruess M.;
RT "Characterization of the novel human serotonin receptor subunits 5-HT3C, 5-
RT HT3D, and 5-HT3E.";
RL Mol. Pharmacol. 72:8-17(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), ALTERNATIVE SPLICING, SUBCELLULAR
RP LOCATION, AND VARIANT THR-71.
RX PubMed=19012743; DOI=10.1111/j.1471-4159.2008.05775.x;
RA Holbrook J.D., Gill C.H., Zebda N., Spencer J.P., Leyland R., Rance K.H.,
RA Trinh H., Balmer G., Kelly F.M., Yusaf S.P., Courtenay N., Luck J.,
RA Rhodes A., Modha S., Moore S.E., Sanger G.J., Gunthorpe M.J.;
RT "Characterisation of 5-HT3C, 5-HT3D and 5-HT3E receptor subunits:
RT evolution, distribution and function.";
RL J. Neurochem. 108:384-396(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: This is one of the several different receptors for 5-
CC hydroxytryptamine (serotonin), a biogenic hormone that functions as a
CC neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-
CC gated ion channel, which when activated causes fast, depolarizing
CC responses. It is a cation-specific, but otherwise relatively
CC nonselective, ion channel.
CC -!- SUBUNIT: Forms a pentaheteromeric complex with HTR3A. Not functional as
CC a homomeric complex. {ECO:0000269|PubMed:17392525}.
CC -!- INTERACTION:
CC A5X5Y0-1; P46098: HTR3A; NbExp=5; IntAct=EBI-11174612, EBI-9008743;
CC A5X5Y0-3; P46098: HTR3A; NbExp=3; IntAct=EBI-11163690, EBI-9008743;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17392525,
CC ECO:0000269|PubMed:19012743}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:17392525, ECO:0000269|PubMed:19012743}.
CC Note=Presumably retained within the endoplasmic reticulum unless
CC complexed with HTR3A.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=A5X5Y0-1; Sequence=Displayed;
CC Name=2; Synonyms=5-HT3c1;
CC IsoId=A5X5Y0-2; Sequence=VSP_029804;
CC Name=3;
CC IsoId=A5X5Y0-3; Sequence=VSP_029803;
CC Name=4; Synonyms=5-HT3c1 long;
CC IsoId=A5X5Y0-4; Sequence=VSP_029803, VSP_029804;
CC Name=5; Synonyms=HTR3E_V3;
CC IsoId=A5X5Y0-6; Sequence=VSP_029803, VSP_029804, VSP_045573;
CC -!- TISSUE SPECIFICITY: Expressed in adult colon and intestine.
CC {ECO:0000269|PubMed:12801637, ECO:0000269|PubMed:14597179}.
CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
CC 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3E sub-
CC subfamily. {ECO:0000305}.
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DR EMBL; AY349352; AAQ93476.1; -; mRNA.
DR EMBL; AY349353; AAQ93477.1; -; mRNA.
DR EMBL; AY159813; AAO38167.2; -; mRNA.
DR EMBL; DQ644022; ABG35128.1; -; mRNA.
DR EMBL; EU165354; ABW05298.1; -; mRNA.
DR EMBL; AC131235; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC101182; AAI01183.1; -; mRNA.
DR EMBL; BC101183; AAI01184.1; -; mRNA.
DR EMBL; BC101185; AAI01186.1; -; mRNA.
DR CCDS; CCDS3251.1; -. [A5X5Y0-3]
DR CCDS; CCDS58868.1; -. [A5X5Y0-1]
DR CCDS; CCDS58869.1; -. [A5X5Y0-2]
DR CCDS; CCDS58870.1; -. [A5X5Y0-4]
DR CCDS; CCDS58871.1; -. [A5X5Y0-6]
DR RefSeq; NP_001243542.1; NM_001256613.1. [A5X5Y0-1]
DR RefSeq; NP_001243543.1; NM_001256614.1. [A5X5Y0-6]
DR RefSeq; NP_872395.2; NM_182589.2. [A5X5Y0-3]
DR RefSeq; NP_938055.1; NM_198313.2. [A5X5Y0-2]
DR RefSeq; NP_938056.1; NM_198314.2. [A5X5Y0-4]
DR AlphaFoldDB; A5X5Y0; -.
DR SMR; A5X5Y0; -.
DR BioGRID; 130056; 10.
DR ComplexPortal; CPX-273; 5-hydroxytryptamine-3A/E receptor complex.
DR IntAct; A5X5Y0; 4.
DR STRING; 9606.ENSP00000406050; -.
DR BindingDB; A5X5Y0; -.
DR ChEMBL; CHEMBL4296087; -.
DR DrugBank; DB01239; Chlorprothixene.
DR DrugBank; DB11273; Dihydroergocornine.
DR DrugBank; DB13345; Dihydroergocristine.
DR DrugBank; DB01049; Ergoloid mesylate.
DR DrugBank; DB00898; Ethanol.
DR DrugBank; DB12141; Gilteritinib.
DR DrugBank; DB00715; Paroxetine.
DR DrugBank; DB09304; Setiptiline.
DR DrugBank; DB13025; Tiapride.
DR DrugBank; DB00246; Ziprasidone.
DR DrugCentral; A5X5Y0; -.
DR GlyGen; A5X5Y0; 1 site.
DR iPTMnet; A5X5Y0; -.
DR PhosphoSitePlus; A5X5Y0; -.
DR BioMuta; HTR3E; -.
DR PaxDb; A5X5Y0; -.
DR PeptideAtlas; A5X5Y0; -.
DR PRIDE; A5X5Y0; -.
DR Antibodypedia; 33787; 125 antibodies from 18 providers.
DR DNASU; 285242; -.
DR Ensembl; ENST00000335304.6; ENSP00000335511.2; ENSG00000186038.9. [A5X5Y0-3]
DR Ensembl; ENST00000415389.6; ENSP00000401444.2; ENSG00000186038.9. [A5X5Y0-1]
DR Ensembl; ENST00000425359.6; ENSP00000401900.2; ENSG00000186038.9. [A5X5Y0-2]
DR Ensembl; ENST00000436361.6; ENSP00000395833.2; ENSG00000186038.9. [A5X5Y0-4]
DR Ensembl; ENST00000440596.2; ENSP00000406050.2; ENSG00000186038.9. [A5X5Y0-6]
DR GeneID; 285242; -.
DR KEGG; hsa:285242; -.
DR MANE-Select; ENST00000415389.6; ENSP00000401444.2; NM_001256613.2; NP_001243542.1.
DR UCSC; uc003fml.5; human. [A5X5Y0-1]
DR CTD; 285242; -.
DR DisGeNET; 285242; -.
DR GeneCards; HTR3E; -.
DR HGNC; HGNC:24005; HTR3E.
DR HPA; ENSG00000186038; Tissue enhanced (intestine).
DR MIM; 610123; gene.
DR neXtProt; NX_A5X5Y0; -.
DR OpenTargets; ENSG00000186038; -.
DR PharmGKB; PA134900226; -.
DR VEuPathDB; HostDB:ENSG00000186038; -.
DR eggNOG; KOG3645; Eukaryota.
DR GeneTree; ENSGT00940000163899; -.
DR HOGENOM; CLU_018074_5_2_1; -.
DR InParanoid; A5X5Y0; -.
DR OMA; SYMHTRD; -.
DR OrthoDB; 123230at2759; -.
DR PhylomeDB; A5X5Y0; -.
DR TreeFam; TF315605; -.
DR PathwayCommons; A5X5Y0; -.
DR Reactome; R-HSA-112314; Neurotransmitter receptors and postsynaptic signal transmission.
DR SignaLink; A5X5Y0; -.
DR SIGNOR; A5X5Y0; -.
DR BioGRID-ORCS; 285242; 8 hits in 1061 CRISPR screens.
DR GeneWiki; HTR3E; -.
DR GenomeRNAi; 285242; -.
DR Pharos; A5X5Y0; Tchem.
DR PRO; PR:A5X5Y0; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; A5X5Y0; protein.
DR Bgee; ENSG00000186038; Expressed in mucosa of transverse colon and 16 other tissues.
DR ExpressionAtlas; A5X5Y0; baseline and differential.
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:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:1904602; C:serotonin-activated cation-selective channel complex; IPI:ComplexPortal.
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:0030594; F:neurotransmitter receptor activity; IBA:GO_Central.
DR GO; GO:0022850; F:serotonin-gated cation-selective channel activity; IDA:CACAO.
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:0098662; P:inorganic cation transmembrane transport; IDA:ComplexPortal.
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:0007210; P:serotonin receptor signaling pathway; IDA:ComplexPortal.
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; 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; 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 Alternative splicing; Cell membrane; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Ligand-gated ion channel; Membrane; Receptor;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix; Transport.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..456
FT /note="5-hydroxytryptamine receptor 3E"
FT /id="PRO_0000312294"
FT TOPO_DOM 26..248
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 249..269
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 270..282
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 283..303
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 304..307
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 308..328
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 329..433
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 434..454
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 455..456
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 162..176
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..22
FT /note="MEGSWFHRKRFSFYLLLGFLLQ -> MLAFILSRATPRPALGPLSYREHRVA
FT LLHLTHSMSTT (in isoform 3, isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:12801637,
FT ECO:0000303|PubMed:14597179, ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:17392525, ECO:0000303|PubMed:19012743"
FT /id="VSP_029803"
FT VAR_SEQ 79..93
FT /note="Missing (in isoform 2, isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14597179,
FT ECO:0000303|PubMed:19012743"
FT /id="VSP_029804"
FT VAR_SEQ 129
FT /note="E -> ELCVSRAGQREVPSPGSHRDHSLPLGP (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:19012743"
FT /id="VSP_045573"
FT VARIANT 71
FT /note="A -> T (in dbSNP:rs7627615)"
FT /evidence="ECO:0000269|PubMed:19012743"
FT /id="VAR_037481"
FT VARIANT 430
FT /note="A -> T (in dbSNP:rs13324468)"
FT /id="VAR_037482"
FT CONFLICT 44
FT /note="A -> T (in Ref. 6; AAI01183/AAI01184)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 456 AA; 51438 MW; 4BFA6561BA309E83 CRC64;
MEGSWFHRKR FSFYLLLGFL LQGRGVTFTI NCSGFGQHGA DPTALNSVFN RKPFRPVTNI
SVPTQVNISF AMSAILDVNE QLHLLSSFLW LEMVWDNPFI SWNPEECEGI TKMSMAAKNL
WLPDIFIIEL MDVDKTPKGL TAYVSNEGRI RYKKPMKVDS ICNLDIFYFP FDQQNCTLTF
SSFLYTVDSM LLDMEKEVWE ITDASRNILQ THGEWELLGL SKATAKLSRG GNLYDQIVFY
VAIRRRPSLY VINLLVPSGF LVAIDALSFY LPVKSGNRVP FKITLLLGYN VFLLMMSDLL
PTSGTPLIGV YFALCLSLMV GSLLETIFIT HLLHVATTQP PPLPRWLHSL LLHCNSPGRC
CPTAPQKENK GPGLTPTHLP GVKEPEVSAG QMPGPAEAEL TGGSEWTRAQ REHEAQKQHS
VELWLQFSHA MDAMLFRLYL LFMASSIITV ICLWNT
