ID   5HT3D_HUMAN             Reviewed;         454 AA.
AC   Q70Z44; C9J2I6; J3QT78; Q495N5; Q495N6; Q7Z6B3;
DT   04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT   28-JUN-2011, sequence version 3.
DT   27-MAR-2024, entry version 165.
DE   RecName: Full=5-hydroxytryptamine receptor 3D {ECO:0000305|PubMed:17392525};
DE            Short=5-HT3-D;
DE            Short=5-HT3D;
DE   AltName: Full=Serotonin receptor 3D;
DE   Flags: Precursor;
GN   Name=HTR3D {ECO:0000312|HGNC:HGNC:24004};
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), 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] (ISOFORM 2), FUNCTION, TRANSPORTER ACTIVITY,
RP   SUBUNIT, SUBCELLULAR LOCATION, AND VARIANT GLY-171.
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   [3]
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3), AND VARIANTS
RP   HIS-225 AND HIS-435.
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       Q70Z44; P46098: HTR3A; NbExp=5; IntAct=EBI-9008717, 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}; Multi-pass
CC       membrane protein {ECO:0000255}. Note=Presumably retained within the
CC       endoplasmic reticulum unless complexed with HTR3A.
CC       {ECO:0000269|PubMed:17392525}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=1;
CC         IsoId=Q70Z44-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q70Z44-2; Sequence=VSP_029798, VSP_029799, VSP_029801;
CC       Name=3;
CC         IsoId=Q70Z44-3; Sequence=VSP_029797, VSP_029800, VSP_029801;
CC       Name=4;
CC         IsoId=Q70Z44-4; Sequence=VSP_044828, VSP_044829, VSP_044830,
CC                                  VSP_029801;
CC   -!- TISSUE SPECIFICITY: Expressed in liver, as well as fetal and adult
CC       colon and kidney. {ECO:0000269|PubMed:12801637}.
CC   -!- DOMAIN: The HA-stretch region of HTR3D seems to confer increased
CC       conductance to HTR3A/HTR3D 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. HTR3D sub-
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AJ437318; CAD24817.1; -; mRNA.
DR   EMBL; AY159812; AAO38166.2; -; mRNA.
DR   EMBL; AC068644; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC131235; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC101090; AAI01091.1; -; mRNA.
DR   EMBL; BC101091; AAI01092.1; -; mRNA.
DR   CCDS; CCDS3249.1; -. [Q70Z44-2]
DR   CCDS; CCDS46966.1; -. [Q70Z44-4]
DR   CCDS; CCDS54685.1; -. [Q70Z44-1]
DR   CCDS; CCDS93429.1; -. [Q70Z44-3]
DR   RefSeq; NP_001138615.1; NM_001145143.1. [Q70Z44-4]
DR   RefSeq; NP_001157118.1; NM_001163646.1. [Q70Z44-1]
DR   RefSeq; NP_872343.2; NM_182537.2.
DR   RefSeq; XP_016861343.1; XM_017005854.1.
DR   AlphaFoldDB; Q70Z44; -.
DR   BioGRID; 128355; 11.
DR   ComplexPortal; CPX-272; 5-hydroxytryptamine-3A/D receptor complex.
DR   IntAct; Q70Z44; 4.
DR   STRING; 9606.ENSP00000371929; -.
DR   BindingDB; Q70Z44; -.
DR   ChEMBL; CHEMBL2094132; -.
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; Q70Z44; -.
DR   TCDB; 1.A.9.2.3; the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.
DR   GlyCosmos; Q70Z44; 1 site, No reported glycans.
DR   GlyGen; Q70Z44; 1 site.
DR   iPTMnet; Q70Z44; -.
DR   PhosphoSitePlus; Q70Z44; -.
DR   BioMuta; HTR3D; -.
DR   DMDM; 338817899; -.
DR   jPOST; Q70Z44; -.
DR   MassIVE; Q70Z44; -.
DR   PaxDb; 9606-ENSP00000371929; -.
DR   PeptideAtlas; Q70Z44; -.
DR   ProteomicsDB; 68580; -. [Q70Z44-1]
DR   Antibodypedia; 56799; 68 antibodies from 14 providers.
DR   DNASU; 200909; -.
DR   Ensembl; ENST00000382489.3; ENSP00000371929.3; ENSG00000186090.11. [Q70Z44-1]
DR   Ensembl; ENST00000428798.7; ENSP00000405409.2; ENSG00000186090.11. [Q70Z44-4]
DR   Ensembl; ENST00000453435.1; ENSP00000389268.1; ENSG00000186090.11. [Q70Z44-3]
DR   GeneID; 200909; -.
DR   KEGG; hsa:200909; -.
DR   MANE-Select; ENST00000428798.7; ENSP00000405409.2; NM_001145143.1; NP_001138615.1. [Q70Z44-4]
DR   UCSC; uc010hxp.4; human. [Q70Z44-1]
DR   AGR; HGNC:24004; -.
DR   CTD; 200909; -.
DR   DisGeNET; 200909; -.
DR   GeneCards; HTR3D; -.
DR   HGNC; HGNC:24004; HTR3D.
DR   HPA; ENSG00000186090; Not detected.
DR   MIM; 610122; gene.
DR   neXtProt; NX_Q70Z44; -.
DR   OpenTargets; ENSG00000186090; -.
DR   PharmGKB; PA134866755; -.
DR   VEuPathDB; HostDB:ENSG00000186090; -.
DR   eggNOG; KOG3645; Eukaryota.
DR   GeneTree; ENSGT00940000156739; -.
DR   HOGENOM; CLU_018074_5_2_1; -.
DR   InParanoid; Q70Z44; -.
DR   OMA; WKCAGIT; -.
DR   OrthoDB; 5489962at2759; -.
DR   PhylomeDB; Q70Z44; -.
DR   TreeFam; TF315605; -.
DR   PathwayCommons; Q70Z44; -.
DR   Reactome; R-HSA-112314; Neurotransmitter receptors and postsynaptic signal transmission.
DR   SignaLink; Q70Z44; -.
DR   SIGNOR; Q70Z44; -.
DR   BioGRID-ORCS; 200909; 15 hits in 1140 CRISPR screens.
DR   ChiTaRS; HTR3D; human.
DR   GeneWiki; HTR3D; -.
DR   GenomeRNAi; 200909; -.
DR   Pharos; Q70Z44; Tchem.
DR   PRO; PR:Q70Z44; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q70Z44; Protein.
DR   Bgee; ENSG00000186090; Expressed in primordial germ cell in gonad and 2 other cell types or tissues.
DR   ExpressionAtlas; Q70Z44; 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; 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   PANTHER; PTHR18945:SF409; 5-HYDROXYTRYPTAMINE RECEPTOR 3D; 1.
DR   PANTHER; PTHR18945; NEUROTRANSMITTER GATED ION CHANNEL; 1.
DR   Pfam; PF02931; Neur_chan_LBD; 1.
DR   Pfam; PF02932; Neur_chan_memb; 1.
DR   SUPFAM; SSF90112; Neurotransmitter-gated ion-channel transmembrane pore; 1.
DR   SUPFAM; SSF63712; Nicotinic receptor ligand binding domain-like; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Glycoprotein; Ion channel;
KW   Ion transport; Ligand-gated ion channel; Membrane;
KW   Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse;
KW   Transmembrane; Transmembrane helix; Transport.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..454
FT                   /note="5-hydroxytryptamine receptor 3D"
FT                   /id="PRO_0000312293"
FT   TOPO_DOM        25..232
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        233..253
FT                   /note="Helical; Name=1"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        254..264
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        265..285
FT                   /note="Helical; Name=2"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        286..306
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        307..327
FT                   /note="Helical; Name=3"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        328..431
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        432..452
FT                   /note="Helical; Name=4"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        453..454
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   REGION          363..410
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          399..430
FT                   /note="HA-stretch; determines single-channel conductance in
FT                   5-HT3 receptors"
FT                   /evidence="ECO:0000250|UniProtKB:P46098"
FT   CARBOHYD        66
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..219
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_029797"
FT   VAR_SEQ         1..135
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:17392525"
FT                   /id="VSP_029798"
FT   VAR_SEQ         1..37
FT                   /note="MQKHSPGPPALALLSQSLLTTGNGDTLIINCPGFGQH -> MERGWFHGKGF
FT                   LLGFILHLLLQDSHLQLVTSFLWLNM (in isoform 4)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_044828"
FT   VAR_SEQ         38..98
FT                   /note="Missing (in isoform 4)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_044829"
FT   VAR_SEQ         171
FT                   /note="A -> GERSPSALSPTQVT (in isoform 4)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_044830"
FT   VAR_SEQ         172..220
FT                   /note="RAWRRMSRSFQIHHRTSFRTRREWVLLGIQKRTIKVTVATNQYEQAIFH ->
FT                   ERSPSALSPTQ (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:17392525"
FT                   /id="VSP_029799"
FT   VAR_SEQ         220
FT                   /note="H -> M (in isoform 3)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_029800"
FT   VAR_SEQ         295..306
FT                   /note="APLALMQTPLPA -> RPHPSRDQKR (in isoform 2, isoform 3
FT                   and isoform 4)"
FT                   /evidence="ECO:0000303|PubMed:15489334,
FT                   ECO:0000303|PubMed:17392525"
FT                   /id="VSP_029801"
FT   VARIANT         171
FT                   /note="A -> G (in dbSNP:rs6443930)"
FT                   /evidence="ECO:0000269|PubMed:17392525"
FT                   /id="VAR_037478"
FT   VARIANT         225
FT                   /note="R -> H (in dbSNP:rs1000952)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_037479"
FT   VARIANT         435
FT                   /note="R -> H (in dbSNP:rs6789754)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_037480"
FT   CONFLICT        155
FT                   /note="S -> P (in Ref. 4; AAI01092)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        368
FT                   /note="K -> R (in Ref. 2; AAO38166)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   454 AA;  50191 MW;  8B12F6CC31C4446C CRC64;
     MQKHSPGPPA LALLSQSLLT TGNGDTLIIN CPGFGQHRVD PAAFQAVFDR KAIGPVTNYS
     VATHVNISFT LSAIWNCYSR IHTFNCHHAR PWHNQFVQWN PDECGGIKKS GMATENLWLS
     DVFIEESVDQ TPAGLMASMS IVKATSNTIS QCGWSASANW TPSISPSMDR ARAWRRMSRS
     FQIHHRTSFR TRREWVLLGI QKRTIKVTVA TNQYEQAIFH VAIRRRCRPS PYVVNFLVPS
     GILIAIDALS FYLPLESGNC APFKMTVLLG YSVFLLMMND LLPATSTSSH ASLVAPLALM
     QTPLPAGVYF ALCLSLMVGS LLETIFITHL LHVATTQPLP LPRWLHSLLL HCTGQGRCCP
     TAPQKGNKGP GLTPTHLPGV KEPEVSAGQM PGPGEAELTG GSEWTRAQRE HEAQKQHSVE
     LWVQFSHAMD ALLFRLYLLF MASSIITVIC LWNT
//