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Protein

5-hydroxytryptamine receptor 3A

Gene

HTR3A

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 in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel.2 Publications

GO - Molecular functioni

  • serotonin-activated cation-selective channel activity Source: GO_Central
  • serotonin binding Source: MGI
  • serotonin-gated cation channel activity Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ion channel, Ligand-gated ion channel, Receptor

Keywords - Biological processi

Ion transport, Transport

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166736-MONOMER.
ReactomeiR-HSA-975298. Ligand-gated ion channel transport.

Protein family/group databases

TCDBi1.A.9.2.1. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

Names & Taxonomyi

Protein namesi
Recommended name:
5-hydroxytryptamine receptor 3A
Short name:
5-HT3-A
Short name:
5-HT3A
Alternative name(s):
5-hydroxytryptamine receptor 3
Short name:
5-HT-3
Short name:
5-HT3R
Serotonin receptor 3A
Serotonin-gated ion channel receptor
Gene namesi
Name:HTR3A
Synonyms:5HT3R, HTR3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:5297. HTR3A.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 241ExtracellularSequence analysisAdd BLAST218
Transmembranei242 – 268Helical; Name=1Sequence analysisAdd BLAST27
Topological domaini269 – 273CytoplasmicSequence analysis5
Transmembranei274 – 292Helical; Name=2Sequence analysisAdd BLAST19
Topological domaini293 – 302ExtracellularSequence analysis10
Transmembranei303 – 321Helical; Name=3Sequence analysisAdd BLAST19
Topological domaini322 – 455CytoplasmicSequence analysisAdd BLAST134
Transmembranei456 – 475Helical; Name=4Sequence analysisAdd BLAST20
Topological domaini476 – 478ExtracellularSequence analysis3

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi178W → S: Abolished ligand binding to the heteromeric receptor. 1 Publication1
Mutagenesisi432R → Q: Little effect on conductance. Massive increase of conductance; when associated with D-436 and A-440. 1 Publication1
Mutagenesisi436R → D: Increased conductance. Massive increase of conductance; when associated with Q-432 and A-440. 1 Publication1
Mutagenesisi440R → A: Increased conductance. Massive increase of conductance; when associated with Q-432 and D-436. 1 Publication1

Organism-specific databases

DisGeNETi3359.
OpenTargetsiENSG00000166736.
PharmGKBiPA29555.

Chemistry databases

ChEMBLiCHEMBL1899.
DrugBankiDB00969. Alosetron.
DB00543. Amoxapine.
DB01238. Aripiprazole.
DB01161. Chloroprocaine.
DB00604. Cisapride.
DB00363. Clozapine.
DB00757. Dolasetron.
DB01049. Ergoloid mesylate.
DB00898. Ethanol.
DB00889. Granisetron.
DB00408. Loxapine.
DB01043. Memantine.
DB00333. Methadone.
DB01233. Metoclopramide.
DB00370. Mirtazapine.
DB00334. Olanzapine.
DB00904. Ondansetron.
DB00377. Palonosetron.
DB00721. Procaine.
DB01224. Quetiapine.
DB00728. Rocuronium.
DB06204. Tapentadol.
DB00726. Trimipramine.
DB01199. Tubocurarine.
DB09068. Vortioxetine.
DB00246. Ziprasidone.

Polymorphism and mutation databases

BioMutaiHTR3A.
DMDMi1168222.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000000040824 – 4785-hydroxytryptamine receptor 3AAdd BLAST455

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi28N-linked (GlcNAc...)Sequence analysis1
Glycosylationi104N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi157 ↔ 171By similarity
Glycosylationi170N-linked (GlcNAc...)Sequence analysis1
Glycosylationi186N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiP46098.

PTM databases

iPTMnetiP46098.
PhosphoSitePlusiP46098.

Expressioni

Tissue specificityi

Expressed in cerebral cortex, amygdala, hippocampus, and testis. Detected in monocytes of the spleen and tonsil, in small and large intestine, uterus, prostate, ovary and placenta.1 Publication

Gene expression databases

BgeeiENSG00000166736.
CleanExiHS_HTR3A.
ExpressionAtlasiP46098. baseline and differential.
GenevisibleiP46098. HS.

Interactioni

Subunit structurei

Forms pentahomomeric complex as well as pentaheteromeric complex with HTR3B or HTR3C or HTR3D or HTR3E; homomeric complex is functional but exhibits low conductance with modified voltage dependence, and decreased agonist and antagonist affinity. Interacts with RIC3.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
HTR3CQ8WXA85EBI-9008743,EBI-9008753
HTR3DQ70Z445EBI-9008743,EBI-9008717
HTR3EA5X5Y0-15EBI-9008743,EBI-11174612
HTR3EA5X5Y0-33EBI-9008743,EBI-11163690

Protein-protein interaction databases

BioGridi109591. 97 interactors.
IntActiP46098. 4 interactors.

Chemistry databases

BindingDBiP46098.

Structurei

3D structure databases

ProteinModelPortaliP46098.
SMRiP46098.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni414 – 450HA-stretchAdd BLAST37

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00790000122957.
HOGENOMiHOG000241519.
HOVERGENiHBG106638.
InParanoidiP46098.
KOiK04819.
OMAiHGEVQNY.
OrthoDBiEOG091G06Q8.
PhylomeDBiP46098.
TreeFamiTF315605.

Family and domain databases

Gene3Di1.20.120.370. 2 hits.
2.70.170.10. 1 hit.
InterProiIPR008132. 5HT3_rcpt.
IPR008133. 5HT3_rcpt_A.
IPR027361. Acetylcholine_rcpt_TM.
IPR006202. Neur_chan_lig-bd.
IPR006201. Neur_channel.
IPR006029. Neurotrans-gated_channel_TM.
IPR018000. Neurotransmitter_ion_chnl_CS.
[Graphical view]
PANTHERiPTHR18945. PTHR18945. 1 hit.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]
PRINTSiPR01709. 5HT3ARECEPTR.
PR01708. 5HT3RECEPTOR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsiTIGR00860. LIC. 1 hit.
PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

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

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P46098-1) [UniParc]FASTAAdd to basket
Also known as: 5-HT3R-AS

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
MLLWVQQALL ALLLPTLLAQ GEARRSRNTT RPALLRLSDY LLTNYRKGVR
60 70 80 90 100
PVRDWRKPTT VSIDVIVYAI LNVDEKNQVL TTYIWYRQYW TDEFLQWNPE
110 120 130 140 150
DFDNITKLSI PTDSIWVPDI LINEFVDVGK SPNIPYVYIR HQGEVQNYKP
160 170 180 190 200
LQVVTACSLD IYNFPFDVQN CSLTFTSWLH TIQDINISLW RLPEKVKSDR
210 220 230 240 250
SVFMNQGEWE LLGVLPYFRE FSMESSNYYA EMKFYVVIRR RPLFYVVSLL
260 270 280 290 300
LPSIFLMVMD IVGFYLPPNS GERVSFKITL LLGYSVFLII VSDTLPATAI
310 320 330 340 350
GTPLIGVYFV VCMALLVISL AETIFIVRLV HKQDLQQPVP AWLRHLVLER
360 370 380 390 400
IAWLLCLREQ STSQRPPATS QATKTDDCSA MGNHCSHMGG PQDFEKSPRD
410 420 430 440 450
RCSPPPPPRE ASLAVCGLLQ ELSSIRQFLE KRDEIREVAR DWLRVGSVLD
460 470
KLLFHIYLLA VLAYSITLVM LWSIWQYA
Length:478
Mass (Da):55,280
Last modified:November 1, 1995 - v1
Checksum:i24CA9A232286FBC9
GO
Isoform 2 (identifier: P46098-2) [UniParc]FASTAAdd to basket
Also known as: 5-HT3R-AL

The sequence of this isoform differs from the canonical sequence as follows:
     306-306: G → GKAPPGSRAQSGEKPAPSHLLHVSLASALGCTG

Show »
Length:510
Mass (Da):58,388
Checksum:i3DF54EB0BF54C519
GO
Isoform 3 (identifier: P46098-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: MLLWVQQALLALLLPTLLAQGE → MHRSFLQ

Show »
Length:463
Mass (Da):53,763
Checksum:iFA630E3384245F9C
GO
Isoform 4 (identifier: P46098-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLGKLAM

Note: No experimental confirmation available.
Show »
Length:484
Mass (Da):55,894
Checksum:i74F70567007BCB51
GO
Isoform 5 (identifier: P46098-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MLGKLAM
     306-306: G → GKAPPGSRAQSGEKPAPSHLLHVSLASALGCTG

Note: No experimental confirmation available.Curated
Show »
Length:516
Mass (Da):59,002
Checksum:i91E8DBE4B4802BA6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti46R → T in AAB37533 (PubMed:8848005).Curated1
Sequence conflicti125F → L in AAB37533 (PubMed:8848005).Curated1
Sequence conflicti321A → T in AAB37533 (PubMed:8848005).Curated1
Sequence conflicti386S → T in AAB37533 (PubMed:8848005).Curated1
Isoform 5 (identifier: P46098-5)
Sequence conflicti342C → W in CD014118 (PubMed:15028279).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03739833A → T.1 PublicationCorresponds to variant rs117793058dbSNPEnsembl.1
Natural variantiVAR_037399253S → N.Corresponds to variant rs4938063dbSNPEnsembl.1
Natural variantiVAR_037400344R → H.1 PublicationCorresponds to variant rs35815285dbSNPEnsembl.1
Natural variantiVAR_037401391P → R.1 Publication1
Natural variantiVAR_037402409R → Q.1 PublicationCorresponds to variant rs183698487dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0422141 – 22MLLWV…LAQGE → MHRSFLQ in isoform 3. 1 PublicationAdd BLAST22
Alternative sequenceiVSP_0434841M → MLGKLAM in isoform 4 and isoform 5. 2 Publications1
Alternative sequenceiVSP_000078306G → GKAPPGSRAQSGEKPAPSHL LHVSLASALGCTG in isoform 2 and isoform 5. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D49394 mRNA. Translation: BAA08387.1.
S82612 mRNA. Translation: AAB37533.2.
AJ003078 mRNA. Translation: CAA05851.1.
AJ003079 mRNA. Translation: CAA05852.1.
AJ005205 Genomic DNA. Translation: CAA06442.3.
AF498984 mRNA. Translation: AAM21131.1.
BT007204 mRNA. Translation: AAP35868.1.
CD014118 mRNA. No translation available.
AK299973 mRNA. Translation: BAG61798.1.
AP000908 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67238.1.
CH471065 Genomic DNA. Translation: EAW67240.1.
BC002354 mRNA. Translation: AAH02354.1.
BC004453 mRNA. Translation: AAH04453.2.
CCDSiCCDS53710.1. [P46098-3]
CCDS8365.2. [P46098-4]
CCDS8366.2. [P46098-5]
RefSeqiNP_000860.2. NM_000869.5. [P46098-4]
NP_001155244.1. NM_001161772.2. [P46098-3]
NP_998786.2. NM_213621.3. [P46098-5]
UniGeneiHs.413899.

Genome annotation databases

EnsembliENST00000299961; ENSP00000299961; ENSG00000166736. [P46098-3]
ENST00000355556; ENSP00000347754; ENSG00000166736. [P46098-5]
ENST00000375498; ENSP00000364648; ENSG00000166736. [P46098-4]
ENST00000504030; ENSP00000424189; ENSG00000166736. [P46098-1]
ENST00000506841; ENSP00000424776; ENSG00000166736. [P46098-2]
GeneIDi3359.
KEGGihsa:3359.
UCSCiuc010rxa.3. human. [P46098-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D49394 mRNA. Translation: BAA08387.1.
S82612 mRNA. Translation: AAB37533.2.
AJ003078 mRNA. Translation: CAA05851.1.
AJ003079 mRNA. Translation: CAA05852.1.
AJ005205 Genomic DNA. Translation: CAA06442.3.
AF498984 mRNA. Translation: AAM21131.1.
BT007204 mRNA. Translation: AAP35868.1.
CD014118 mRNA. No translation available.
AK299973 mRNA. Translation: BAG61798.1.
AP000908 Genomic DNA. No translation available.
CH471065 Genomic DNA. Translation: EAW67238.1.
CH471065 Genomic DNA. Translation: EAW67240.1.
BC002354 mRNA. Translation: AAH02354.1.
BC004453 mRNA. Translation: AAH04453.2.
CCDSiCCDS53710.1. [P46098-3]
CCDS8365.2. [P46098-4]
CCDS8366.2. [P46098-5]
RefSeqiNP_000860.2. NM_000869.5. [P46098-4]
NP_001155244.1. NM_001161772.2. [P46098-3]
NP_998786.2. NM_213621.3. [P46098-5]
UniGeneiHs.413899.

3D structure databases

ProteinModelPortaliP46098.
SMRiP46098.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109591. 97 interactors.
IntActiP46098. 4 interactors.

Chemistry databases

BindingDBiP46098.
ChEMBLiCHEMBL1899.
DrugBankiDB00969. Alosetron.
DB00543. Amoxapine.
DB01238. Aripiprazole.
DB01161. Chloroprocaine.
DB00604. Cisapride.
DB00363. Clozapine.
DB00757. Dolasetron.
DB01049. Ergoloid mesylate.
DB00898. Ethanol.
DB00889. Granisetron.
DB00408. Loxapine.
DB01043. Memantine.
DB00333. Methadone.
DB01233. Metoclopramide.
DB00370. Mirtazapine.
DB00334. Olanzapine.
DB00904. Ondansetron.
DB00377. Palonosetron.
DB00721. Procaine.
DB01224. Quetiapine.
DB00728. Rocuronium.
DB06204. Tapentadol.
DB00726. Trimipramine.
DB01199. Tubocurarine.
DB09068. Vortioxetine.
DB00246. Ziprasidone.

Protein family/group databases

TCDBi1.A.9.2.1. the neurotransmitter receptor, cys loop, ligand-gated ion channel (lic) family.

PTM databases

iPTMnetiP46098.
PhosphoSitePlusiP46098.

Polymorphism and mutation databases

BioMutaiHTR3A.
DMDMi1168222.

Proteomic databases

PRIDEiP46098.

Protocols and materials databases

DNASUi3359.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000299961; ENSP00000299961; ENSG00000166736. [P46098-3]
ENST00000355556; ENSP00000347754; ENSG00000166736. [P46098-5]
ENST00000375498; ENSP00000364648; ENSG00000166736. [P46098-4]
ENST00000504030; ENSP00000424189; ENSG00000166736. [P46098-1]
ENST00000506841; ENSP00000424776; ENSG00000166736. [P46098-2]
GeneIDi3359.
KEGGihsa:3359.
UCSCiuc010rxa.3. human. [P46098-1]

Organism-specific databases

CTDi3359.
DisGeNETi3359.
GeneCardsiHTR3A.
HGNCiHGNC:5297. HTR3A.
MIMi182139. gene.
neXtProtiNX_P46098.
OpenTargetsiENSG00000166736.
PharmGKBiPA29555.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00790000122957.
HOGENOMiHOG000241519.
HOVERGENiHBG106638.
InParanoidiP46098.
KOiK04819.
OMAiHGEVQNY.
OrthoDBiEOG091G06Q8.
PhylomeDBiP46098.
TreeFamiTF315605.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000166736-MONOMER.
ReactomeiR-HSA-975298. Ligand-gated ion channel transport.

Miscellaneous databases

GeneWikiiHTR3A.
GenomeRNAii3359.
PROiP46098.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166736.
CleanExiHS_HTR3A.
ExpressionAtlasiP46098. baseline and differential.
GenevisibleiP46098. HS.

Family and domain databases

Gene3Di1.20.120.370. 2 hits.
2.70.170.10. 1 hit.
InterProiIPR008132. 5HT3_rcpt.
IPR008133. 5HT3_rcpt_A.
IPR027361. Acetylcholine_rcpt_TM.
IPR006202. Neur_chan_lig-bd.
IPR006201. Neur_channel.
IPR006029. Neurotrans-gated_channel_TM.
IPR018000. Neurotransmitter_ion_chnl_CS.
[Graphical view]
PANTHERiPTHR18945. PTHR18945. 1 hit.
PfamiPF02931. Neur_chan_LBD. 1 hit.
PF02932. Neur_chan_memb. 1 hit.
[Graphical view]
PRINTSiPR01709. 5HT3ARECEPTR.
PR01708. 5HT3RECEPTOR.
PR00252. NRIONCHANNEL.
SUPFAMiSSF63712. SSF63712. 1 hit.
SSF90112. SSF90112. 1 hit.
TIGRFAMsiTIGR00860. LIC. 1 hit.
PROSITEiPS00236. NEUROTR_ION_CHANNEL. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry namei5HT3A_HUMAN
AccessioniPrimary (citable) accession number: P46098
Secondary accession number(s): B4DSY6
, G5E986, O60854, Q7KZM7, Q99918, Q9BSZ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 2, 2016
This is version 171 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 HTR3A seems to be responsible for the low conductance of HTR3A homomers compared to that of HTR3A/HTR3B heteromers.

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

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 one 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.