5HT3D_HUMAN
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 03-AUG-2022, entry version 156.
DE RecName: Full=5-hydroxytryptamine receptor 3D;
DE Short=5-HT3-D;
DE Short=5-HT3D;
DE AltName: Full=Serotonin receptor 3D;
DE Flags: Precursor;
GN Name=HTR3D;
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), SUBUNIT, SUBCELLULAR LOCATION, AND
RP 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: 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 Q70Z44; P46098: HTR3A; NbExp=5; IntAct=EBI-9008717, EBI-9008743;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17392525};
CC Multi-pass membrane protein {ECO:0000269|PubMed:17392525}.
CC Note=Presumably retained within the endoplasmic reticulum unless
CC complexed with HTR3A.
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 -!- 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 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. [Q70Z44-3]
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 GlyGen; Q70Z44; 1 site.
DR iPTMnet; Q70Z44; -.
DR PhosphoSitePlus; Q70Z44; -.
DR BioMuta; HTR3D; -.
DR DMDM; 338817899; -.
DR jPOST; Q70Z44; -.
DR MassIVE; Q70Z44; -.
DR PaxDb; Q70Z44; -.
DR PeptideAtlas; Q70Z44; -.
DR PRIDE; Q70Z44; -.
DR Antibodypedia; 56799; 55 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 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; MRVVSIC; -.
DR OrthoDB; 123230at2759; -.
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 1060 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 olfactory segment of nasal mucosa and 4 other tissues.
DR ExpressionAtlas; Q70Z44; 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 PANTHER; PTHR18945; PTHR18945; 1.
DR Pfam; PF02931; Neur_chan_LBD; 1.
DR Pfam; PF02932; Neur_chan_memb; 1.
DR SUPFAM; SSF63712; SSF63712; 1.
DR SUPFAM; SSF90112; SSF90112; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Glycoprotein; Ion channel;
KW Ion transport; Ligand-gated ion channel; Membrane; Receptor;
KW Reference proteome; Signal; 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 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
