ID 5HT3A_HUMAN Reviewed; 478 AA. AC P46098; B4DSY6; G5E986; O60854; Q7KZM7; Q99918; Q9BSZ9; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 27-MAR-2024, entry version 221. DE RecName: Full=5-hydroxytryptamine receptor 3A {ECO:0000305|PubMed:7565620}; DE Short=5-HT3-A; DE Short=5-HT3A; DE AltName: Full=5-hydroxytryptamine receptor 3; DE Short=5-HT-3; DE Short=5-HT3R; DE AltName: Full=Serotonin receptor 3A; DE AltName: Full=Serotonin-gated ion channel receptor; DE Flags: Precursor; GN Name=HTR3A {ECO:0000312|HGNC:HGNC:5297}; Synonyms=5HT3R, HTR3; 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 1). RC TISSUE=Hippocampus; RX PubMed=7565620; RA Miyake A., Mochizuki S., Takemoto Y., Akuzawa S.; RT "Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in RT distribution and function among species."; RL Mol. Pharmacol. 48:407-416(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Amygdala; RX PubMed=8848005; RA Belelli D., Balcarek J.M., Hope A.G., Peters J.A., Lambert J.J., RA Blackburn T.P.; RT "Cloning and functional expression of a human 5-hydroxytryptamine type 3AS RT receptor subunit."; RL Mol. Pharmacol. 48:1054-1062(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Amygdala, and Hippocampus; RX PubMed=9928262; DOI=10.1111/j.1749-6632.1998.tb10196.x; RA Bruess M., Goethert M., Hayer M., Bonisch H.; RT "Molecular cloning of alternatively spliced human 5HT3 receptor cDNAs."; RL Ann. N. Y. Acad. Sci. 861:234-235(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Blood; RX PubMed=10670426; DOI=10.1016/s0028-3908(99)00116-1; RA Bruess M., Eucker T., Goethert M., Bonisch H.; RT "Exon-intron organization of the human 5-HT3A receptor gene."; RL Neuropharmacology 39:308-315(2000). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.; RT "cDNA clones of human proteins involved in signal transduction sequenced by RT the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RX PubMed=15028279; DOI=10.1016/j.ygeno.2003.09.023; RA Jin P., Fu G.K., Wilson A.D., Yang J., Chien D., Hawkins P.R., Au-Young J., RA Stuve L.L.; RT "PCR isolation and cloning of novel splice variant mRNAs from known drug RT target genes."; RL Genomics 83:566-571(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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). RN [12] RP FUNCTION, TRANSPORTER ACTIVITY, SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=9950429; DOI=10.1038/16941; RA Davies P.A., Pistis M., Hanna M.C., Peters J.A., Lambert J.J., Hales T.G., RA Kirkness E.F.; RT "The 5-HT3B subunit is a major determinant of serotonin-receptor RT function."; RL Nature 397:359-363(1999). RN [13] RP FUNCTION, TRANSPORTER ACTIVITY, SUBUNIT, AND TISSUE SPECIFICITY. RC TISSUE=Small intestine; RX PubMed=10521471; DOI=10.1074/jbc.274.43.30799; RA Dubin A.E., Huvar R., D'Andrea M.R., Pyati J., Zhu J.Y., Joy K.C., RA Wilson S.J., Galindo J.E., Glass C.A., Luo L., Jackson M.R., RA Lovenberg T.W., Erlander M.G.; RT "The pharmacological and functional characteristics of the serotonin 5- RT HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit."; RL J. Biol. Chem. 274:30799-30810(1999). RN [14] RP FUNCTION, DOMAIN, REGION, AND MUTAGENESIS OF ARG-432; ARG-436 AND ARG-440. RX PubMed=12867984; DOI=10.1038/nature01788; RA Kelley S.P., Dunlop J.I., Kirkness E.F., Lambert J.J., Peters J.A.; RT "A cytoplasmic region determines single-channel conductance in 5-HT3 RT receptors."; RL Nature 424:321-324(2003). RN [15] RP INTERACTION WITH RIC3. RX PubMed=15809299; DOI=10.1074/jbc.m414341200; RA Cheng A., McDonald N.A., Connolly C.N.; RT "Cell surface expression of 5-hydroxytryptamine type 3 receptors is RT promoted by RIC-3."; RL J. Biol. Chem. 280:22502-22507(2005). RN [16] RP FUNCTION, TRANSPORTER ACTIVITY, SUBUNIT, AND MUTAGENESIS OF TRP-178. 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 [17] RP VARIANT THR-33. RX PubMed=15293096; DOI=10.1007/s10067-004-0927-2; RA Frank B., Niesler B., Bondy B., Spaeth M., Pongratz D.E., Ackenheil M., RA Fischer C., Rappold G.; RT "Mutational analysis of serotonin receptor genes: HTR3A and HTR3B in RT fibromyalgia patients."; RL Clin. Rheumatol. 23:338-344(2004). RN [18] RP VARIANTS HIS-344; ARG-391 AND GLN-409. RX PubMed=16487942; DOI=10.1016/j.biopsych.2005.11.008; RA Yamada K., Hattori E., Iwayama Y., Ohnishi T., Ohba H., Toyota T., RA Takao H., Minabe Y., Nakatani N., Higuchi T., Detera-Wadleigh S.D., RA Yoshikawa T.; RT "Distinguishable haplotype blocks in the HTR3A and HTR3B region in the RT Japanese reveal evidence of association of HTR3B with female major RT depression."; RL Biol. Psychiatry 60:192-201(2006). 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:10521471, CC ECO:0000269|PubMed:12867984, ECO:0000269|PubMed:17392525, CC ECO:0000269|PubMed:9950429}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Na(+)(in) = Na(+)(out); Xref=Rhea:RHEA:34963, CC ChEBI:CHEBI:29101; Evidence={ECO:0000269|PubMed:9950429}; CC -!- CATALYTIC ACTIVITY: CC Reaction=K(+)(in) = K(+)(out); Xref=Rhea:RHEA:29463, ChEBI:CHEBI:29103; CC Evidence={ECO:0000269|PubMed:9950429}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Ca(2+)(in) = Ca(2+)(out); Xref=Rhea:RHEA:29671, CC ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:10521471, CC ECO:0000269|PubMed:17392525, ECO:0000269|PubMed:9950429}; CC -!- CATALYTIC ACTIVITY: CC Reaction=Mg(2+)(in) = Mg(2+)(out); Xref=Rhea:RHEA:29827, CC ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:9950429}; CC -!- SUBUNIT: Forms homopentameric as well as heteropentameric serotonin- CC activated cation-selective channel complexes with HTR3B or HTR3C or CC HTR3D or HTR3E. The homomeric complex is functional but exhibits low CC conductance with modified voltage dependence, and decreased agonist and CC antagonist affinity. Heteropentameric complexes display properties CC which resemble that of neuronal serotonin-activated channels in vivo CC (PubMed:15809299, PubMed:10521471, PubMed:17392525, PubMed:9950429). CC Interacts with RIC3 (PubMed:15809299). {ECO:0000269|PubMed:10521471, CC ECO:0000269|PubMed:15809299, ECO:0000269|PubMed:17392525, CC ECO:0000269|PubMed:9950429}. CC -!- INTERACTION: CC P46098; Q8WXA8: HTR3C; NbExp=5; IntAct=EBI-9008743, EBI-9008753; CC P46098; Q70Z44: HTR3D; NbExp=5; IntAct=EBI-9008743, EBI-9008717; CC P46098; A5X5Y0-1: HTR3E; NbExp=5; IntAct=EBI-9008743, EBI-11174612; CC P46098; A5X5Y0-3: HTR3E; NbExp=3; IntAct=EBI-9008743, EBI-11163690; CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane CC {ECO:0000305|PubMed:9950429}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P23979}. Cell membrane CC {ECO:0000305|PubMed:9950429}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P23979}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; Synonyms=5-HT3R-AS; CC IsoId=P46098-1; Sequence=Displayed; CC Name=2; Synonyms=5-HT3R-AL; CC IsoId=P46098-2; Sequence=VSP_000078; CC Name=3; CC IsoId=P46098-3; Sequence=VSP_042214; CC Name=4; CC IsoId=P46098-4; Sequence=VSP_043484; CC Name=5; CC IsoId=P46098-5; Sequence=VSP_043484, VSP_000078; CC -!- TISSUE SPECIFICITY: Expressed in cerebral cortex, amygdala, CC hippocampus, and testis. Detected in monocytes of the spleen and CC tonsil, in small and large intestine, uterus, prostate, ovary and CC placenta. {ECO:0000269|PubMed:10521471}. CC -!- DOMAIN: The HA-stretch region of HTR3A seems to be responsible for the CC low conductance of HTR3A homomers compared to that of HTR3A/HTR3B CC heteromers. {ECO:0000269|PubMed:12867984}. CC -!- SIMILARITY: Belongs to the ligand-gated ion channel (TC 1.A.9) family. CC 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3A 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; D49394; BAA08387.1; -; mRNA. DR EMBL; S82612; AAB37533.2; -; mRNA. DR EMBL; AJ003078; CAA05851.1; -; mRNA. DR EMBL; AJ003079; CAA05852.1; -; mRNA. DR EMBL; AJ005205; CAA06442.3; -; Genomic_DNA. DR EMBL; AF498984; AAM21131.1; -; mRNA. DR EMBL; BT007204; AAP35868.1; -; mRNA. DR EMBL; CD014118; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AK299973; BAG61798.1; -; mRNA. DR EMBL; AP000908; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471065; EAW67238.1; -; Genomic_DNA. DR EMBL; CH471065; EAW67240.1; -; Genomic_DNA. DR EMBL; BC002354; AAH02354.1; -; mRNA. DR EMBL; BC004453; AAH04453.2; -; mRNA. DR CCDS; CCDS53710.1; -. [P46098-3] DR CCDS; CCDS8365.3; -. [P46098-1] DR CCDS; CCDS8366.3; -. [P46098-2] DR RefSeq; NP_000860.2; NM_000869.5. [P46098-1] DR RefSeq; NP_001155244.1; NM_001161772.2. [P46098-3] DR RefSeq; NP_998786.2; NM_213621.3. [P46098-2] DR AlphaFoldDB; P46098; -. DR SMR; P46098; -. DR BioGRID; 109591; 118. DR ComplexPortal; CPX-2175; 5-hydroxytryptamine-3A receptor complex. DR ComplexPortal; CPX-271; 5-hydroxytryptamine-3A/B receptor complex. DR ComplexPortal; CPX-272; 5-hydroxytryptamine-3A/D receptor complex. DR ComplexPortal; CPX-273; 5-hydroxytryptamine-3A/E receptor complex. DR ComplexPortal; CPX-276; 5-hydroxytryptamine-3A/C receptor complex. DR IntAct; P46098; 101. DR STRING; 9606.ENSP00000347754; -. DR BindingDB; P46098; -. DR ChEMBL; CHEMBL1899; -. DR DrugBank; DB00969; Alosetron. DR DrugBank; DB00543; Amoxapine. DR DrugBank; DB01238; Aripiprazole. DR DrugBank; DB14185; Aripiprazole lauroxil. DR DrugBank; DB01156; Bupropion. DR DrugBank; DB09061; Cannabidiol. DR DrugBank; DB01239; Chlorprothixene. DR DrugBank; DB04885; Cilansetron. DR DrugBank; DB00604; Cisapride. DR DrugBank; DB00363; Clozapine. DR DrugBank; DB05642; DDP-225. DR DrugBank; DB05049; DDP733. DR DrugBank; DB11273; Dihydroergocornine. DR DrugBank; DB13345; Dihydroergocristine. DR DrugBank; DB00757; Dolasetron. DR DrugBank; DB00988; Dopamine. DR DrugBank; DB01049; Ergoloid mesylate. DR DrugBank; DB00898; Ethanol. DR DrugBank; DB12141; Gilteritinib. DR DrugBank; DB00889; Granisetron. DR DrugBank; DB01221; Ketamine. DR DrugBank; DB00555; Lamotrigine. DR DrugBank; DB00408; Loxapine. DR DrugBank; DB01043; Memantine. DR DrugBank; DB00333; Methadone. DR DrugBank; DB01233; Metoclopramide. DR DrugBank; DB00334; Olanzapine. DR DrugBank; DB00904; Ondansetron. DR DrugBank; DB00377; Palonosetron. DR DrugBank; DB00715; Paroxetine. DR DrugBank; DB00721; Procaine. DR DrugBank; DB01224; Quetiapine. DR DrugBank; DB09290; Ramosetron. DR DrugBank; DB04917; Renzapride. DR DrugBank; DB00728; Rocuronium. DR DrugBank; DB08839; Serotonin. DR DrugBank; DB09304; Setiptiline. DR DrugBank; DB06204; Tapentadol. DR DrugBank; DB13025; Tiapride. DR DrugBank; DB06422; Ticalopride. DR DrugBank; DB00726; Trimipramine. DR DrugBank; DB11699; Tropisetron. DR DrugBank; DB01199; Tubocurarine. DR DrugBank; DB09068; Vortioxetine. DR DrugBank; DB00246; Ziprasidone. DR DrugCentral; P46098; -. DR GuidetoPHARMACOLOGY; 373; -. DR TCDB; 1.A.9.2.1; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family. DR GlyCosmos; P46098; 4 sites, No reported glycans. DR GlyGen; P46098; 6 sites. DR iPTMnet; P46098; -. DR PhosphoSitePlus; P46098; -. DR BioMuta; HTR3A; -. DR DMDM; 1168222; -. DR MassIVE; P46098; -. DR PaxDb; 9606-ENSP00000347754; -. DR PeptideAtlas; P46098; -. DR Antibodypedia; 18364; 476 antibodies from 36 providers. DR DNASU; 3359; -. DR Ensembl; ENST00000299961.5; ENSP00000299961.4; ENSG00000166736.12. [P46098-3] DR Ensembl; ENST00000355556.6; ENSP00000347754.2; ENSG00000166736.12. [P46098-5] DR Ensembl; ENST00000375498.6; ENSP00000364648.2; ENSG00000166736.12. [P46098-4] DR Ensembl; ENST00000504030.7; ENSP00000424189.2; ENSG00000166736.12. [P46098-1] DR Ensembl; ENST00000506841.6; ENSP00000424776.2; ENSG00000166736.12. [P46098-2] DR GeneID; 3359; -. DR KEGG; hsa:3359; -. DR MANE-Select; ENST00000504030.7; ENSP00000424189.2; NM_000869.6; NP_000860.3. DR UCSC; uc010rxa.3; human. [P46098-1] DR AGR; HGNC:5297; -. DR CTD; 3359; -. DR DisGeNET; 3359; -. DR GeneCards; HTR3A; -. DR HGNC; HGNC:5297; HTR3A. DR HPA; ENSG00000166736; Group enriched (brain, intestine, lymphoid tissue, pancreas, salivary gland). DR MIM; 182139; gene. DR neXtProt; NX_P46098; -. DR OpenTargets; ENSG00000166736; -. DR PharmGKB; PA29555; -. DR VEuPathDB; HostDB:ENSG00000166736; -. DR eggNOG; KOG3645; Eukaryota. DR GeneTree; ENSGT00940000157705; -. DR HOGENOM; CLU_018074_5_0_1; -. DR InParanoid; P46098; -. DR OMA; VGNHCSH; -. DR OrthoDB; 5489962at2759; -. DR PhylomeDB; P46098; -. DR TreeFam; TF315605; -. DR PathwayCommons; P46098; -. DR Reactome; R-HSA-112314; Neurotransmitter receptors and postsynaptic signal transmission. DR SignaLink; P46098; -. DR SIGNOR; P46098; -. DR BioGRID-ORCS; 3359; 7 hits in 1155 CRISPR screens. DR GeneWiki; HTR3A; -. DR GenomeRNAi; 3359; -. DR Pharos; P46098; Tclin. DR PRO; PR:P46098; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P46098; Protein. DR Bgee; ENSG00000166736; Expressed in dorsal root ganglion and 94 other cell types or tissues. DR ExpressionAtlas; P46098; baseline and differential. DR GO; GO:0032154; C:cleavage furrow; IDA:HGNC. 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; IDA:GO_Central. 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:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0099507; F:ligand-gated monoatomic ion channel activity involved in regulation of presynaptic membrane potential; IEA:Ensembl. DR GO; GO:0051378; F:serotonin binding; IDA:MGI. DR GO; GO:0022850; F:serotonin-gated monoatomic cation channel activity; IDA:MGI. DR GO; GO:0098662; P:inorganic cation transmembrane transport; IDA:ComplexPortal. DR GO; GO:0007210; P:serotonin receptor signaling pathway; IDA:ComplexPortal. DR CDD; cd19011; LGIC_ECD_5-HT3A; 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; IPR008132; 5HT3_rcpt. DR InterPro; IPR008133; 5HT3_rcpt_A. 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 NCBIfam; TIGR00860; LIC; 1. DR PANTHER; PTHR18945:SF52; 5-HYDROXYTRYPTAMINE RECEPTOR 3A; 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; PR01709; 5HT3ARECEPTR. DR PRINTS; PR01708; 5HT3RECEPTOR. 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. DR Genevisible; P46098; HS. 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..23 FT /evidence="ECO:0000255" FT CHAIN 24..478 FT /note="5-hydroxytryptamine receptor 3A" FT /id="PRO_0000000408" FT TOPO_DOM 24..241 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P23979" FT TRANSMEM 242..268 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 269..273 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P23979" FT TRANSMEM 274..292 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 293..302 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P23979" FT TRANSMEM 303..321 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 322..455 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:P23979" FT TRANSMEM 456..475 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 476..478 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:P23979" FT REGION 389..408 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 414..450 FT /note="HA-stretch; determines single-channel conductance in FT 5-HT3 receptors" FT /evidence="ECO:0000269|PubMed:12867984" FT CARBOHYD 28 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 104 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 170 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 186 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 157..171 FT /evidence="ECO:0000250|UniProtKB:P23979" FT VAR_SEQ 1..22 FT /note="MLLWVQQALLALLLPTLLAQGE -> MHRSFLQ (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042214" FT VAR_SEQ 1 FT /note="M -> MLGKLAM (in isoform 4 and isoform 5)" FT /evidence="ECO:0000303|PubMed:15028279, ECO:0000303|Ref.6" FT /id="VSP_043484" FT VAR_SEQ 306 FT /note="G -> GKAPPGSRAQSGEKPAPSHLLHVSLASALGCTG (in isoform 2 FT and isoform 5)" FT /evidence="ECO:0000303|PubMed:15028279, FT ECO:0000303|PubMed:9928262" FT /id="VSP_000078" FT VARIANT 33 FT /note="A -> T (in dbSNP:rs117793058)" FT /evidence="ECO:0000269|PubMed:15293096" FT /id="VAR_037398" FT VARIANT 253 FT /note="S -> N (in dbSNP:rs4938063)" FT /id="VAR_037399" FT VARIANT 344 FT /note="R -> H (in dbSNP:rs35815285)" FT /evidence="ECO:0000269|PubMed:16487942" FT /id="VAR_037400" FT VARIANT 391 FT /note="P -> R" FT /evidence="ECO:0000269|PubMed:16487942" FT /id="VAR_037401" FT VARIANT 409 FT /note="R -> Q (in dbSNP:rs183698487)" FT /evidence="ECO:0000269|PubMed:16487942" FT /id="VAR_037402" FT MUTAGEN 178 FT /note="W->S: Abolished 5-hydroxytryptamine (serotonin) FT binding to the heteromeric receptor." FT /evidence="ECO:0000269|PubMed:17392525" FT MUTAGEN 432 FT /note="R->Q: Little effect on conductance. Massive increase FT of conductance; when associated with D-436 and A-440." FT /evidence="ECO:0000269|PubMed:12867984" FT MUTAGEN 436 FT /note="R->D: Increased conductance. Massive increase of FT conductance; when associated with Q-432 and A-440." FT /evidence="ECO:0000269|PubMed:12867984" FT MUTAGEN 440 FT /note="R->A: Increased conductance. Massive increase of FT conductance; when associated with Q-432 and D-436." FT /evidence="ECO:0000269|PubMed:12867984" FT CONFLICT 46 FT /note="R -> T (in Ref. 2; AAB37533)" FT /evidence="ECO:0000305" FT CONFLICT 125 FT /note="F -> L (in Ref. 2; AAB37533)" FT /evidence="ECO:0000305" FT CONFLICT 321 FT /note="A -> T (in Ref. 2; AAB37533)" FT /evidence="ECO:0000305" FT CONFLICT 386 FT /note="S -> T (in Ref. 2; AAB37533)" FT /evidence="ECO:0000305" FT CONFLICT P46098-5:342 FT /note="C -> W (in Ref. 7; CD014118)" FT /evidence="ECO:0000305" SQ SEQUENCE 478 AA; 55280 MW; 24CA9A232286FBC9 CRC64; MLLWVQQALL ALLLPTLLAQ GEARRSRNTT RPALLRLSDY LLTNYRKGVR PVRDWRKPTT VSIDVIVYAI LNVDEKNQVL TTYIWYRQYW TDEFLQWNPE DFDNITKLSI PTDSIWVPDI LINEFVDVGK SPNIPYVYIR HQGEVQNYKP LQVVTACSLD IYNFPFDVQN CSLTFTSWLH TIQDINISLW RLPEKVKSDR SVFMNQGEWE LLGVLPYFRE FSMESSNYYA EMKFYVVIRR RPLFYVVSLL LPSIFLMVMD IVGFYLPPNS GERVSFKITL LLGYSVFLII VSDTLPATAI GTPLIGVYFV VCMALLVISL AETIFIVRLV HKQDLQQPVP AWLRHLVLER IAWLLCLREQ STSQRPPATS QATKTDDCSA MGNHCSHMGG PQDFEKSPRD RCSPPPPPRE ASLAVCGLLQ ELSSIRQFLE KRDEIREVAR DWLRVGSVLD KLLFHIYLLA VLAYSITLVM LWSIWQYA //