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Protein

5-hydroxytryptamine receptor 3A

Gene

HTR3A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionIon channel, Ligand-gated ion channel, Receptor
Biological processIon transport, Transport

Enzyme and pathway databases

ReactomeiR-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission

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

EuPathDBiHostDB:ENSG00000166736.11
HGNCiHGNC:5297 HTR3A
MIMi182139 gene
neXtProtiNX_P46098

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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
DB04885 Cilansetron
DB00604 Cisapride
DB00363 Clozapine
DB05049 DDP733
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
DB04917 Renzapride
DB00728 Rocuronium
DB06204 Tapentadol
DB13025 Tiapride
DB00726 Trimipramine
DB11699 Tropisetron
DB01199 Tubocurarine
DB09068 Vortioxetine
DB00246 Ziprasidone
GuidetoPHARMACOLOGYi373

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...) asparagineSequence analysis1
Glycosylationi104N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi157 ↔ 171By similarity
Glycosylationi170N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi186N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiP46098
ProteomicsDBi55722
55723 [P46098-2]
55724 [P46098-3]
55725 [P46098-4]

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 Expressed in 73 organ(s), highest expression level in islet of Langerhans
CleanExiHS_HTR3A
ExpressionAtlasiP46098 baseline and differential
GenevisibleiP46098 HS

Organism-specific databases

HPAiHPA069442

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

Protein-protein interaction databases

BioGridi109591, 112 interactors
ComplexPortaliCPX-2175 5-hydroxytryptamine-3A receptor complex
CPX-271 5-hydroxytryptamine-3A/B receptor complex
CPX-272 5-hydroxytryptamine-3A/D receptor complex
CPX-273 5-hydroxytryptamine-3A/E receptor complex
CPX-276 5-hydroxytryptamine-3A/C receptor complex
IntActiP46098, 4 interactors

Chemistry databases

BindingDBiP46098

Structurei

3D structure databases

ProteinModelPortaliP46098
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

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

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00910000144023
HOGENOMiHOG000241519
HOVERGENiHBG106638
InParanoidiP46098
KOiK04819
OMAiLWSIWQY
OrthoDBiEOG091G06Q8
PhylomeDBiP46098
TreeFamiTF315605

Family and domain databases

Gene3Di2.70.170.10, 1 hit
InterProiView protein in InterPro
IPR008132 5HT3_rcpt
IPR008133 5HT3_rcpt_A
IPR006202 Neur_chan_lig-bd
IPR036734 Neur_chan_lig-bd_sf
IPR006201 Neur_channel
IPR036719 Neuro-gated_channel_TM_sf
IPR006029 Neurotrans-gated_channel_TM
IPR018000 Neurotransmitter_ion_chnl_CS
PANTHERiPTHR18945 PTHR18945, 1 hit
PfamiView protein in Pfam
PF02931 Neur_chan_LBD, 1 hit
PF02932 Neur_chan_memb, 1 hit
PRINTSiPR01709 5HT3ARECEPTR
PR01708 5HT3RECEPTOR
PR00252 NRIONCHANNEL
SUPFAMiSSF63712 SSF63712, 1 hit
SSF90112 SSF90112, 1 hit
TIGRFAMsiTIGR00860 LIC, 1 hit
PROSITEiView protein in PROSITE
PS00236 NEUROTR_ION_CHANNEL, 1 hit

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

This entry has 5 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0B4J205A0A0B4J205_HUMAN
5-hydroxytryptamine receptor 3A
HTR3A
238Annotation score:

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 → T1 PublicationCorresponds to variant dbSNP:rs117793058Ensembl.1
Natural variantiVAR_037399253S → N. Corresponds to variant dbSNP:rs4938063Ensembl.1
Natural variantiVAR_037400344R → H1 PublicationCorresponds to variant dbSNP:rs35815285Ensembl.1
Natural variantiVAR_037401391P → R1 Publication1
Natural variantiVAR_037402409R → Q1 PublicationCorresponds to variant dbSNP:rs183698487Ensembl.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]
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

Similar proteinsi

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]
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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109591, 112 interactors
ComplexPortaliCPX-2175 5-hydroxytryptamine-3A receptor complex
CPX-271 5-hydroxytryptamine-3A/B receptor complex
CPX-272 5-hydroxytryptamine-3A/D receptor complex
CPX-273 5-hydroxytryptamine-3A/E receptor complex
CPX-276 5-hydroxytryptamine-3A/C receptor complex
IntActiP46098, 4 interactors

Chemistry databases

BindingDBiP46098
ChEMBLiCHEMBL1899
DrugBankiDB00969 Alosetron
DB00543 Amoxapine
DB01238 Aripiprazole
DB01161 Chloroprocaine
DB04885 Cilansetron
DB00604 Cisapride
DB00363 Clozapine
DB05049 DDP733
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
DB04917 Renzapride
DB00728 Rocuronium
DB06204 Tapentadol
DB13025 Tiapride
DB00726 Trimipramine
DB11699 Tropisetron
DB01199 Tubocurarine
DB09068 Vortioxetine
DB00246 Ziprasidone
GuidetoPHARMACOLOGYi373

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
ProteomicsDBi55722
55723 [P46098-2]
55724 [P46098-3]
55725 [P46098-4]

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
EuPathDBiHostDB:ENSG00000166736.11
GeneCardsiHTR3A
HGNCiHGNC:5297 HTR3A
HPAiHPA069442
MIMi182139 gene
neXtProtiNX_P46098
OpenTargetsiENSG00000166736
PharmGKBiPA29555
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00910000144023
HOGENOMiHOG000241519
HOVERGENiHBG106638
InParanoidiP46098
KOiK04819
OMAiLWSIWQY
OrthoDBiEOG091G06Q8
PhylomeDBiP46098
TreeFamiTF315605

Enzyme and pathway databases

ReactomeiR-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission

Miscellaneous databases

GeneWikiiHTR3A
GenomeRNAii3359
PROiPR:P46098
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000166736 Expressed in 73 organ(s), highest expression level in islet of Langerhans
CleanExiHS_HTR3A
ExpressionAtlasiP46098 baseline and differential
GenevisibleiP46098 HS

Family and domain databases

Gene3Di2.70.170.10, 1 hit
InterProiView protein in InterPro
IPR008132 5HT3_rcpt
IPR008133 5HT3_rcpt_A
IPR006202 Neur_chan_lig-bd
IPR036734 Neur_chan_lig-bd_sf
IPR006201 Neur_channel
IPR036719 Neuro-gated_channel_TM_sf
IPR006029 Neurotrans-gated_channel_TM
IPR018000 Neurotransmitter_ion_chnl_CS
PANTHERiPTHR18945 PTHR18945, 1 hit
PfamiView protein in Pfam
PF02931 Neur_chan_LBD, 1 hit
PF02932 Neur_chan_memb, 1 hit
PRINTSiPR01709 5HT3ARECEPTR
PR01708 5HT3RECEPTOR
PR00252 NRIONCHANNEL
SUPFAMiSSF63712 SSF63712, 1 hit
SSF90112 SSF90112, 1 hit
TIGRFAMsiTIGR00860 LIC, 1 hit
PROSITEiView protein in PROSITE
PS00236 NEUROTR_ION_CHANNEL, 1 hit
ProtoNetiSearch...

Entry informationi

Entry namei5HT3A_HUMAN
AccessioniPrimary (citable) accession number: P46098
Secondary accession number(s): B4DSY6
, G5E986, O60854, Q7KZM7, Q99918, Q9BSZ9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: October 10, 2018
This is version 188 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

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