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Protein

5-hydroxytryptamine receptor 3B

Gene

HTR3B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses. It is a cation-specific, but otherwise relatively nonselective, ion channel.1 Publication

GO - Molecular functioni

  • ion channel activity Source: ProtInc
  • serotonin-activated cation-selective channel activity Source: ProtInc
  • serotonin receptor activity Source: ProtInc

GO - Biological processi

  • ion transmembrane transport Source: Reactome
  • synaptic transmission Source: ProtInc
  • transmembrane transport Source: Reactome
  • transport Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Ion transport, Transport

Enzyme and pathway databases

ReactomeiREACT_25387. Ligand-gated ion channel transport.

Names & Taxonomyi

Protein namesi
Recommended name:
5-hydroxytryptamine receptor 3B
Short name:
5-HT3-B
Short name:
5-HT3B
Alternative name(s):
Serotonin receptor 3B
Gene namesi
Name:HTR3B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:5298. HTR3B.

Subcellular locationi

  • Cell membrane 1 Publication; Multi-pass membrane protein 1 Publication

  • Note: Presumably retained within the endoplasmic reticulum unless complexed with HTR3A.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 238217ExtracellularSequence AnalysisAdd
BLAST
Transmembranei239 – 25921Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini260 – 2689CytoplasmicSequence Analysis
Transmembranei269 – 28618Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini287 – 30317ExtracellularSequence AnalysisAdd
BLAST
Transmembranei304 – 32421Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini325 – 41490CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei415 – 43521Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini436 – 4416ExtracellularSequence Analysis

GO - Cellular componenti

  • cell surface Source: CACAO
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
  • postsynaptic membrane Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi52 – 521N → S: Reduced molecular weight. Very little expression in the cell membrane. 1 Publication
Mutagenesisi96 – 961N → S: Reduced molecular weight. Very little expression in the cell membrane. 1 Publication
Mutagenesisi138 – 1381N → S: Reduced molecular weight. Very little expression in the cell membrane. 1 Publication
Mutagenesisi168 – 1681N → S: Reduced molecular weight and cell membrane expression. 1 Publication
Mutagenesisi203 – 2031N → S: Reduced molecular weight. Very little expression in the cell membrane. 1 Publication

Organism-specific databases

PharmGKBiPA29556.

Chemistry

DrugBankiDB01049. Ergoloid mesylate.

Polymorphism and mutation databases

BioMutaiHTR3B.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Chaini22 – 4414205-hydroxytryptamine receptor 3BPRO_0000312289Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi52 – 521N-linked (GlcNAc...)1 Publication
Glycosylationi96 – 961N-linked (GlcNAc...)1 Publication
Glycosylationi138 – 1381N-linked (GlcNAc...)1 Publication
Disulfide bondi155 ↔ 169By similarity
Glycosylationi168 – 1681N-linked (GlcNAc...)1 Publication
Glycosylationi203 – 2031N-linked (GlcNAc...)1 Publication
Glycosylationi287 – 2871N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

N-glycosylation required for membrane localization.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiO95264.
PRIDEiO95264.

PTM databases

PhosphoSiteiO95264.

Expressioni

Tissue specificityi

Expressed in the brain cortex, in the caudate nucleus, the hyppocampus, the thalamus and the amygdala. Detected in the kidney and testis as well as in monocytes of the spleen, small and large intestine, uterus, prostate, ovary and placenta.2 Publications

Gene expression databases

BgeeiO95264.
CleanExiHS_HTR3B.
ExpressionAtlasiO95264. baseline and differential.
GenevisibleiO95264. HS.

Organism-specific databases

HPAiHPA039559.

Interactioni

Subunit structurei

Forms a pentaheteromeric complex with HTR3A. Not functional as a homomeric complex.2 Publications

Protein-protein interaction databases

STRINGi9606.ENSP00000260191.

Structurei

3D structure databases

ProteinModelPortaliO95264.
SMRiO95264. Positions 31-438.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni381 – 41333HA-stretchAdd
BLAST

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG260507.
GeneTreeiENSGT00790000122957.
HOGENOMiHOG000241519.
HOVERGENiHBG106638.
InParanoidiO95264.
KOiK04819.
OMAiSWNSSMF.
OrthoDBiEOG7FXZZK.
PhylomeDBiO95264.
TreeFamiTF315605.

Family and domain databases

Gene3Di1.20.120.370. 2 hits.
2.70.170.10. 1 hit.
InterProiIPR008132. 5HT3_rcpt.
IPR008134. 5HT3_rcpt_B.
IPR027361. Acetylcholine_rcpt_TM.
IPR006202. Neur_chan_lig-bd.
IPR006201. Neur_channel.
IPR006029. Neurotrans-gated_channel_TM.
[Graphical view]
PANTHERiPTHR18945. PTHR18945. 1 hit.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]
PRINTSiPR01710. 5HT3BRECEPTR.
PR01708. 5HT3RECEPTOR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsiTIGR00860. LIC. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O95264-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLSSVMAPLW ACILVAAGIL ATDTHHPQDS ALYHLSKQLL QKYHKEVRPV
60 70 80 90 100
YNWTKATTVY LDLFVHAILD VDAENQILKT SVWYQEVWND EFLSWNSSMF
110 120 130 140 150
DEIREISLPL SAIWAPDIII NEFVDIERYP DLPYVYVNSS GTIENYKPIQ
160 170 180 190 200
VVSACSLETY AFPFDVQNCS LTFKSILHTV EDVDLAFLRS PEDIQHDKKA
210 220 230 240 250
FLNDSEWELL SVSSTYSILQ SSAGGFAQIQ FNVVMRRHPL VYVVSLLIPS
260 270 280 290 300
IFLMLVDLGS FYLPPNCRAR IVFKTSVLVG YTVFRVNMSN QVPRSVGSTP
310 320 330 340 350
LIGHFFTICM AFLVLSLAKS IVLVKFLHDE QRGGQEQPFL CLRGDTDADR
360 370 380 390 400
PRVEPRAQRA VVTESSLYGE HLAQPGTLKE VWSQLQSISN YLQTQDQTDQ
410 420 430 440
QEAEWLVLLS RFDRLLFQSY LFMLGIYTIT LCSLWALWGG V
Length:441
Mass (Da):50,292
Last modified:May 1, 1999 - v1
Checksum:i2ED59E4E11400648
GO
Isoform 2 (identifier: O95264-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-17: MLSSVMAPLWACILVAA → MIVYFP

Show »
Length:430
Mass (Da):49,285
Checksum:i8C69BE27437D6D03
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti129 – 1291Y → S.4 Publications
Corresponds to variant rs1176744 [ dbSNP | Ensembl ].
VAR_037472
Natural varianti143 – 1431I → T.1 Publication
Corresponds to variant rs34550504 [ dbSNP | Ensembl ].
VAR_037473
Natural varianti156 – 1561S → R.3 Publications
Corresponds to variant rs72466469 [ dbSNP | Ensembl ].
VAR_037474
Natural varianti183 – 1831V → I.3 Publications
Corresponds to variant rs17116138 [ dbSNP | Ensembl ].
VAR_037475

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 1717MLSSV…ILVAA → MIVYFP in isoform 2. 1 PublicationVSP_029796Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169255 mRNA. Translation: AAF03691.1.
AF080582 mRNA. Translation: AAD12242.1.
AM293589 mRNA. Translation: CAL25321.1.
EF444985 Genomic DNA. Translation: ACA06001.1.
AK314268 mRNA. Translation: BAG36930.1.
CCDSiCCDS8364.1. [O95264-1]
RefSeqiNP_006019.1. NM_006028.4. [O95264-1]
UniGeneiHs.241377.

Genome annotation databases

EnsembliENST00000260191; ENSP00000260191; ENSG00000149305. [O95264-1]
ENST00000537778; ENSP00000443118; ENSG00000149305. [O95264-2]
GeneIDi9177.
KEGGihsa:9177.
UCSCiuc001pok.3. human. [O95264-1]
uc001pol.3. human. [O95264-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF169255 mRNA. Translation: AAF03691.1.
AF080582 mRNA. Translation: AAD12242.1.
AM293589 mRNA. Translation: CAL25321.1.
EF444985 Genomic DNA. Translation: ACA06001.1.
AK314268 mRNA. Translation: BAG36930.1.
CCDSiCCDS8364.1. [O95264-1]
RefSeqiNP_006019.1. NM_006028.4. [O95264-1]
UniGeneiHs.241377.

3D structure databases

ProteinModelPortaliO95264.
SMRiO95264. Positions 31-438.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000260191.

Chemistry

BindingDBiO95264.
ChEMBLiCHEMBL2096904.
DrugBankiDB01049. Ergoloid mesylate.
GuidetoPHARMACOLOGYi374.

PTM databases

PhosphoSiteiO95264.

Polymorphism and mutation databases

BioMutaiHTR3B.

Proteomic databases

PaxDbiO95264.
PRIDEiO95264.

Protocols and materials databases

DNASUi9177.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000260191; ENSP00000260191; ENSG00000149305. [O95264-1]
ENST00000537778; ENSP00000443118; ENSG00000149305. [O95264-2]
GeneIDi9177.
KEGGihsa:9177.
UCSCiuc001pok.3. human. [O95264-1]
uc001pol.3. human. [O95264-2]

Organism-specific databases

CTDi9177.
GeneCardsiGC11P113775.
HGNCiHGNC:5298. HTR3B.
HPAiHPA039559.
MIMi604654. gene.
neXtProtiNX_O95264.
PharmGKBiPA29556.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG260507.
GeneTreeiENSGT00790000122957.
HOGENOMiHOG000241519.
HOVERGENiHBG106638.
InParanoidiO95264.
KOiK04819.
OMAiSWNSSMF.
OrthoDBiEOG7FXZZK.
PhylomeDBiO95264.
TreeFamiTF315605.

Enzyme and pathway databases

ReactomeiREACT_25387. Ligand-gated ion channel transport.

Miscellaneous databases

GeneWikiiHTR3B.
GenomeRNAii9177.
NextBioi34409.
PROiO95264.
SOURCEiSearch...

Gene expression databases

BgeeiO95264.
CleanExiHS_HTR3B.
ExpressionAtlasiO95264. baseline and differential.
GenevisibleiO95264. HS.

Family and domain databases

Gene3Di1.20.120.370. 2 hits.
2.70.170.10. 1 hit.
InterProiIPR008132. 5HT3_rcpt.
IPR008134. 5HT3_rcpt_B.
IPR027361. Acetylcholine_rcpt_TM.
IPR006202. Neur_chan_lig-bd.
IPR006201. Neur_channel.
IPR006029. Neurotrans-gated_channel_TM.
[Graphical view]
PANTHERiPTHR18945. PTHR18945. 1 hit.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]
PRINTSiPR01710. 5HT3BRECEPTR.
PR01708. 5HT3RECEPTOR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsiTIGR00860. LIC. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The pharmacological and functional characteristics of the serotonin 5-HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit."
    Dubin A.E., Huvar R., D'Andrea M.R., Pyati J., Zhu J.Y., Joy K.C., Wilson S.J., Galindo J.E., Glass C.A., Luo L., Jackson M.R., Lovenberg T.W., Erlander M.G.
    J. Biol. Chem. 274:30799-30810(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Small intestine.
  2. "The 5-HT3B subunit is a major determinant of serotonin-receptor function."
    Davies P.A., Pistis M., Hanna M.C., Peters J.A., Lambert J.J., Hales T.G., Kirkness E.F.
    Nature 397:359-363(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBUNIT.
  3. "Tissue-specific alternative promoters of the serotonin receptor gene HTR3B in human brain and intestine."
    Tzvetkov M.V., Meineke C., Oetjen E., Hirsch-Ernst K., Brockmoller J.
    Gene 386:52-62(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT SER-129.
    Tissue: Brain.
  4. NHLBI resequencing and genotyping service (RS&G)
    Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  6. "A cytoplasmic region determines single-channel conductance in 5-HT3 receptors."
    Kelley S.P., Dunlop J.I., Kirkness E.F., Lambert J.J., Peters J.A.
    Nature 424:321-324(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, REGION.
  7. "Characterization of the novel human serotonin receptor subunits 5-HT3C, 5-HT3D, and 5-HT3E."
    Niesler B., Walstab J., Combrink S., Moeller D., Kapeller J., Rietdorf J., Boenisch H., Goethert M., Rappold G., Bruess M.
    Mol. Pharmacol. 72:8-17(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  8. "The identification of N-glycosylated residues of the human 5-HT3B receptor subunit: importance for cell membrane expression."
    Massoura A.N., Dover T.J., Newman A.S., Barnes N.M.
    J. Neurochem. 116:975-983(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-52; ASN-96; ASN-138; ASN-168 AND ASN-203, MUTAGENESIS OF ASN-52; ASN-96; ASN-138; ASN-168 AND ASN-203.
  9. "Investigation of the human serotonin receptor gene HTR3B in bipolar affective and schizophrenic patients."
    Frank B., Niesler B., Noethen M.M., Neidt H., Propping P., Bondy B., Rietschel M., Maier W., Albus M., Rappold G.
    Am. J. Med. Genet. B Neuropsychiatr. Genet. 131:1-5(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS SER-129; ARG-156 AND ILE-183.
  10. "Mutational analysis of serotonin receptor genes: HTR3A and HTR3B in fibromyalgia patients."
    Frank B., Niesler B., Bondy B., Spaeth M., Pongratz D.E., Ackenheil M., Fischer C., Rappold G.
    Clin. Rheumatol. 23:338-344(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS SER-129; ARG-156 AND ILE-183.
  11. "Distinguishable haplotype blocks in the HTR3A and HTR3B region in the Japanese reveal evidence of association of HTR3B with female major depression."
    Yamada K., Hattori E., Iwayama Y., Ohnishi T., Ohba H., Toyota T., Takao H., Minabe Y., Nakatani N., Higuchi T., Detera-Wadleigh S.D., Yoshikawa T.
    Biol. Psychiatry 60:192-201(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS SER-129; THR-143 AND ILE-183.
  12. Cited for: VARIANT ARG-156.

Entry informationi

Entry namei5HT3B_HUMAN
AccessioniPrimary (citable) accession number: O95264
Secondary accession number(s): B0YJ23, Q0VJC3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: May 1, 1999
Last modified: June 24, 2015
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

The HA-stretch region of HTR3B seems to confer increased conductance to HTR3A/HTR3B heteromers compared to that of HTR3A homomers.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.