Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

5-hydroxytryptamine receptor 4

Gene

HTR4

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. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.

GO - Molecular functioni

  • G-protein coupled serotonin receptor activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-390666 Serotonin receptors
R-HSA-418555 G alpha (s) signalling events

Names & Taxonomyi

Protein namesi
Recommended name:
5-hydroxytryptamine receptor 4
Short name:
5-HT-4
Short name:
5-HT4
Alternative name(s):
Serotonin receptor 4
Gene namesi
Name:HTR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000164270.17
HGNCiHGNC:5299 HTR4
MIMi602164 gene
neXtProtiNX_Q13639

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 domaini1 – 19ExtracellularBy similarityAdd BLAST19
Transmembranei20 – 40Helical; Name=1By similarityAdd BLAST21
Topological domaini41 – 58CytoplasmicBy similarityAdd BLAST18
Transmembranei59 – 79Helical; Name=2By similarityAdd BLAST21
Topological domaini80 – 93ExtracellularBy similarityAdd BLAST14
Transmembranei94 – 116Helical; Name=3By similarityAdd BLAST23
Topological domaini117 – 137CytoplasmicBy similarityAdd BLAST21
Transmembranei138 – 158Helical; Name=4By similarityAdd BLAST21
Topological domaini159 – 192ExtracellularBy similarityAdd BLAST34
Transmembranei193 – 213Helical; Name=5By similarityAdd BLAST21
Topological domaini214 – 260CytoplasmicBy similarityAdd BLAST47
Transmembranei261 – 281Helical; Name=6By similarityAdd BLAST21
Topological domaini282 – 294ExtracellularBy similarityAdd BLAST13
Transmembranei295 – 315Helical; Name=7By similarityAdd BLAST21
Topological domaini316 – 388CytoplasmicBy similarityAdd BLAST73

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi3360
OpenTargetsiENSG00000164270
PharmGKBiPA29557

Chemistry databases

ChEMBLiCHEMBL1875
DrugBankiDB08810 Cinitapride
DB00604 Cisapride
DB01049 Ergoloid mesylate
DB01233 Metoclopramide
DB00904 Ondansetron
DB04873 Piboserod
DB06480 Prucalopride
DB04917 Renzapride
DB05905 TD-2749
DB05655 TD-5108
DB01079 Tegaserod
DB13025 Tiapride
GuidetoPHARMACOLOGYi9

Polymorphism and mutation databases

BioMutaiHTR4
DMDMi12644029

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000689651 – 3885-hydroxytryptamine receptor 4Add BLAST388

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi7N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi93 ↔ 184PROSITE-ProRule annotation
Lipidationi329S-palmitoyl cysteineBy similarity1

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PeptideAtlasiQ13639
PRIDEiQ13639

PTM databases

iPTMnetiQ13639
PhosphoSitePlusiQ13639
SwissPalmiQ13639

Expressioni

Tissue specificityi

Isoform 5-HT4(A) is expressed in ileum, brain, and atrium, but not in the ventricle.1 Publication

Gene expression databases

BgeeiENSG00000164270
ExpressionAtlasiQ13639 baseline and differential
GenevisibleiQ13639 HS

Organism-specific databases

HPAiHPA040591

Interactioni

Subunit structurei

Isoform 5-HT4(A) interacts with MAGI2, MPP3, SLC9A3R1 and SNX27 isoforms 1 and 2. Isoform 5-HT4(E) interacts with PATJ, NOS1 and SEC23A. Isoform 5-HT4(A) forms a complex including SLC9A3R1 and EZR (By similarity). Interacts (via C-terminus 330-346 AA) with GRK5; this interaction is promoted by 5-HT (serotonin).By similarity1 Publication

Protein-protein interaction databases

MINTiQ13639

Chemistry databases

BindingDBiQ13639

Structurei

Secondary structure

1388
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi264 – 268Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5EM9X-ray1.60B264-268[»]
ProteinModelPortaliQ13639
SMRiQ13639
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

GeneTreeiENSGT00890000139340
HOGENOMiHOG000239242
HOVERGENiHBG106962
InParanoidiQ13639
KOiK04160
OMAiYRIYITA
OrthoDBiEOG091G06VI
PhylomeDBiQ13639
TreeFamiTF316350

Family and domain databases

CDDicd15056 7tmA_5-HT4, 1 hit
InterProiView protein in InterPro
IPR001520 5HT4_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR01059 5HT4RECEPTR
PR00237 GPCRRHODOPSN
SMARTiView protein in SMART
SM01381 7TM_GPCR_Srsx, 1 hit
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequences (9)i

Sequence statusi: Complete.

This entry describes 9 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 5-HT4(B) (identifier: Q13639-1) [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
MDKLDANVSS EEGFGSVEKV VLLTFLSTVI LMAILGNLLV MVAVCWDRQL
60 70 80 90 100
RKIKTNYFIV SLAFADLLVS VLVMPFGAIE LVQDIWIYGE VFCLVRTSLD
110 120 130 140 150
VLLTTASIFH LCCISLDRYY AICCQPLVYR NKMTPLRIAL MLGGCWVIPT
160 170 180 190 200
FISFLPIMQG WNNIGIIDLI EKRKFNQNSN STYCVFMVNK PYAITCSVVA
210 220 230 240 250
FYIPFLLMVL AYYRIYVTAK EHAHQIQMLQ RAGASSESRP QSADQHSTHR
260 270 280 290 300
MRTETKAAKT LCIIMGCFCL CWAPFFVTNI VDPFIDYTVP GQVWTAFLWL
310 320 330 340 350
GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYRRPSIL GQTVPCSTTT
360 370 380
INGSTHVLRD AVECGGQWES QCHPPATSPL VAAQPSDT
Length:388
Mass (Da):43,761
Last modified:January 11, 2001 - v2
Checksum:i7FCFEC60E7BDF560
GO
Isoform 5-HT4(A) (identifier: Q13639-2) [UniParc]FASTAAdd to basket
Also known as: 5-HT4S

The sequence of this isoform differs from the canonical sequence as follows:
     360-388: DAVECGGQWESQCHPPATSPLVAAQPSDT → YTVLHRGHHQELEKLPIHNDPESLESCF

Show »
Length:387
Mass (Da):44,109
Checksum:i43019BED75AC9D0F
GO
Isoform 5-HT4(C) (identifier: Q13639-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     360-388: DAVECGGQWESQCHPPATSPLVAAQPSDT → F

Show »
Length:360
Mass (Da):40,944
Checksum:iF2BE6033F518178A
GO
Isoform 5-HT4(D) (identifier: Q13639-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     359-388: RDAVECGGQWESQCHPPATSPLVAAQPSDT → SSGTETDRRNFGIRKRRLTKPS

Show »
Length:380
Mass (Da):43,186
Checksum:iC7591BFE6A9C1D62
GO
Isoform 5-HT4(E) (identifier: Q13639-5) [UniParc]FASTAAdd to basket
Also known as: H5-HT4(g)

The sequence of this isoform differs from the canonical sequence as follows:
     359-388: RDAVECGGQWESQCHPPATSPLVAAQPSDT → SGCSPVSSFLLLFCNRPVPV

Note: Mainly expressed in atria and cardiac ventricle.
Show »
Length:378
Mass (Da):42,746
Checksum:iE45038FEF832270D
GO
Isoform 5-HT4(F) (identifier: Q13639-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     169-169: L → LERSLNQGLGQDFHA

Show »
Length:402
Mass (Da):45,315
Checksum:i243F4AE87A6F77FA
GO
Isoform 5-HT4(G) (identifier: Q13639-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     360-388: Missing.

Show »
Length:359
Mass (Da):40,797
Checksum:iCE6033F518178AF3
GO
Isoform 5-HT4(I) (identifier: Q13639-8) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     359-359: R → RTDFLFDRDILARYWTKPARAGPFSGTLSIRCLTARKPVLG

Note: Expressed in all cardiovascular tissues analyzed.
Show »
Length:428
Mass (Da):48,255
Checksum:i463644AFC1C7D882
GO
Isoform 5-HT4c1 (identifier: Q13639-9) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     359-388: RDAVECGGQWESQCHPPATSPLVAAQPSDT → SSGTETDRKK...GRKSCFREGK

Show »
Length:411
Mass (Da):46,907
Checksum:i7A842A2702C855D3
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06741227S → L in a patient with diffuse leukoencephalopathy with spheroids; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs199508638Ensembl.1
Natural variantiVAR_049364372C → Y. Corresponds to variant dbSNP:rs34826744Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001845169L → LERSLNQGLGQDFHA in isoform 5-HT4(F). Curated1
Alternative sequenceiVSP_001847359 – 388RDAVE…QPSDT → SSGTETDRRNFGIRKRRLTK PS in isoform 5-HT4(D). CuratedAdd BLAST30
Alternative sequenceiVSP_001846359 – 388RDAVE…QPSDT → SGCSPVSSFLLLFCNRPVPV in isoform 5-HT4(E). CuratedAdd BLAST30
Alternative sequenceiVSP_047862359 – 388RDAVE…QPSDT → SSGTETDRKKLWNKEEKIDQ TIQMPKRKRKKKASLSYEDL ILLGRKSCFREGK in isoform 5-HT4c1. 1 PublicationAdd BLAST30
Alternative sequenceiVSP_043316359R → RTDFLFDRDILARYWTKPAR AGPFSGTLSIRCLTARKPVL G in isoform 5-HT4(I). Curated1
Alternative sequenceiVSP_001849360 – 388DAVEC…QPSDT → YTVLHRGHHQELEKLPIHND PESLESCF in isoform 5-HT4(A). CuratedAdd BLAST29
Alternative sequenceiVSP_001848360 – 388DAVEC…QPSDT → F in isoform 5-HT4(C). CuratedAdd BLAST29
Alternative sequenceiVSP_001850360 – 388Missing in isoform 5-HT4(G). CuratedAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y08756 mRNA Translation: CAA70002.1
Y12505 mRNA Translation: CAA73107.1
Y12506 mRNA Translation: CAA73108.1
Y12507 mRNA Translation: CAA73109.1
Y10437 mRNA Translation: CAA71462.1
Y13584 mRNA Translation: CAA73911.1
Y09586 mRNA Translation: CAA70774.1
AJ131724 mRNA Translation: CAC20411.1
AJ011371 mRNA Translation: CAA09600.1
AJ278979 mRNA Translation: CAC22248.1
AJ278980 mRNA Translation: CAC22249.1
AJ278981 mRNA Translation: CAC22250.1
AJ278982 mRNA Translation: CAC22251.1
AJ131725 mRNA Translation: CAC79533.1
AJ131726 mRNA Translation: CAC79538.1
AJ633645 mRNA Translation: CAG17627.1
AM712912 mRNA Translation: CAN84676.1
AC008627 Genomic DNA No translation available.
AC011390 Genomic DNA No translation available.
AC091971 Genomic DNA No translation available.
AC114939 Genomic DNA No translation available.
CH471062 Genomic DNA Translation: EAW61800.1
CH471062 Genomic DNA Translation: EAW61801.1
CH471062 Genomic DNA Translation: EAW61804.1
BC074755 mRNA Translation: AAH74755.1
BC095497 mRNA Translation: AAH95497.1
AJ243213 Genomic DNA Translation: CAB71316.1
Z48150 mRNA Translation: CAA88167.1
CCDSiCCDS34270.1 [Q13639-2]
CCDS34271.1 [Q13639-5]
CCDS34272.1 [Q13639-8]
CCDS34273.2 [Q13639-3]
CCDS4291.1 [Q13639-1]
CCDS75353.1 [Q13639-9]
PIRiS66493
RefSeqiNP_000861.1, NM_000870.6 [Q13639-1]
NP_001035259.1, NM_001040169.2 [Q13639-2]
NP_001035262.2, NM_001040172.2 [Q13639-3]
NP_001035263.1, NM_001040173.2 [Q13639-8]
NP_001273339.1, NM_001286410.1 [Q13639-9]
NP_955525.1, NM_199453.3 [Q13639-5]
UniGeneiHs.483773

Genome annotation databases

EnsembliENST00000360693; ENSP00000353915; ENSG00000164270 [Q13639-8]
ENST00000362016; ENSP00000355037; ENSG00000164270 [Q13639-8]
ENST00000377888; ENSP00000367120; ENSG00000164270 [Q13639-1]
ENST00000517929; ENSP00000435904; ENSG00000164270 [Q13639-3]
ENST00000520514; ENSP00000427913; ENSG00000164270 [Q13639-9]
ENST00000521530; ENSP00000428320; ENSG00000164270 [Q13639-2]
ENST00000521735; ENSP00000430979; ENSG00000164270 [Q13639-5]
ENST00000522588; ENSP00000430874; ENSG00000164270 [Q13639-5]
ENST00000631296; ENSP00000485747; ENSG00000164270 [Q13639-1]
GeneIDi3360
KEGGihsa:3360
UCSCiuc003lpn.5 human [Q13639-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry namei5HT4R_HUMAN
AccessioniPrimary (citable) accession number: Q13639
Secondary accession number(s): C4WYH4
, Q546Q1, Q684M0, Q712M9, Q96KH9, Q96KI0, Q9H199, Q9NY73, Q9UBM6, Q9UBT4, Q9UE22, Q9UE23, Q9UQR6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: January 11, 2001
Last modified: May 23, 2018
This is version 172 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  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
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health