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 27-MAR-2024, entry version 141. DE RecName: Full=5-hydroxytryptamine receptor 3E {ECO:0000305|PubMed:17392525}; DE Short=5-HT3-E; DE Short=5-HT3E; DE AltName: Full=Serotonin receptor 3E; DE Flags: Precursor; GN Name=HTR3E {ECO:0000312|HGNC:HGNC:24005}; 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), FUNCTION, TRANSPORTER RP ACTIVITY, SUBUNIT, AND SUBCELLULAR 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: Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation- CC selective channel complexes, which when activated cause fast, CC depolarizing responses in neurons. {ECO:0000269|PubMed:17392525}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963, CC ChEBI:CHEBI:29101; Evidence={ECO:0000250|UniProtKB:P46098}; CC -!- CATALYTIC ACTIVITY: CC Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103; CC Evidence={ECO:0000250|UniProtKB:P46098}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, CC ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:17392525}; CC -!- SUBUNIT: Forms homopentameric as well as heteropentameric serotonin- CC activated cation-selective channel complexes with HTR3A. The homomeric CC complex is not functional. Heteropentameric complexes display CC properties which resemble that of neuronal serotonin-activated channels CC in vivo. {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: Postsynaptic cell membrane CC {ECO:0000305|PubMed:17392525}; Multi-pass membrane protein CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:17392525, CC ECO:0000269|PubMed:19012743}; Multi-pass membrane protein CC {ECO:0000255}. Note=Presumably retained within the endoplasmic CC reticulum unless complexed with HTR3A. {ECO:0000269|PubMed:17392525}. 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 -!- DOMAIN: The HA-stretch region of HTR3E seems to confer increased CC conductance to HTR3A/HTR3E heteropentamers compared to that of HTR3A CC homopentamers. {ECO:0000250|UniProtKB:O95264}. 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}. 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; 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 GlyCosmos; A5X5Y0; 1 site, No reported glycans. DR GlyGen; A5X5Y0; 1 site. DR iPTMnet; A5X5Y0; -. DR PhosphoSitePlus; A5X5Y0; -. DR BioMuta; HTR3E; -. DR MassIVE; A5X5Y0; -. DR PaxDb; 9606-ENSP00000406050; -. DR PeptideAtlas; A5X5Y0; -. DR Antibodypedia; 33787; 132 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 AGR; HGNC:24005; -. DR CTD; 285242; -. DR DisGeNET; 285242; -. DR GeneCards; HTR3E; -. DR HGNC; HGNC:24005; HTR3E. DR HPA; ENSG00000186038; Not detected. 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; 5489962at2759; -. 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; 10 hits in 1140 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 cell types or tissues. DR ExpressionAtlas; A5X5Y0; baseline and differential. DR GO; GO:0043005; C:neuron projection; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell. 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:0022848; F:acetylcholine-gated monoatomic cation-selective channel activity; IBA:GO_Central. DR GO; GO:0022850; F:serotonin-gated monoatomic cation channel activity; IDA:CACAO. DR GO; GO:0098662; P:inorganic cation transmembrane transport; IDA:ComplexPortal. DR GO; GO:0007210; P:serotonin receptor signaling pathway; IDA:ComplexPortal. DR CDD; cd19013; LGIC_ECD_5-HT3C_E; 1. DR CDD; cd19063; LGIC_TM_5-HT3; 1. DR Gene3D; 2.70.170.10; Neurotransmitter-gated ion-channel ligand-binding domain; 1. DR Gene3D; 1.20.58.390; Neurotransmitter-gated ion-channel transmembrane domain; 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:SF764; 5-HYDROXYTRYPTAMINE RECEPTOR 3E; 1. DR PANTHER; PTHR18945; NEUROTRANSMITTER GATED ION CHANNEL; 1. DR Pfam; PF02931; Neur_chan_LBD; 1. DR Pfam; PF02932; Neur_chan_memb; 1. DR PRINTS; PR00252; NRIONCHANNEL. DR SUPFAM; SSF90112; Neurotransmitter-gated ion-channel transmembrane pore; 1. DR SUPFAM; SSF63712; Nicotinic receptor ligand binding domain-like; 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; KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse; KW 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 REGION 401..432 FT /note="HA-stretch; determines single-channel conductance in FT 5-HT3 receptors" FT /evidence="ECO:0000250|UniProtKB:P46098" 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 //