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Q62758 (5HT4R_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
5-hydroxytryptamine receptor 4

Short name=5-HT-4
Short name=5-HT4
Alternative name(s):
Serotonin receptor 4
Gene names
Name:Htr4
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length406 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Subunit structure

May interact with INADL, MAGI2, MPP3, NOS1, SLC9A3R1, SEC23A and SNX27. May form 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 similarity.

Subcellular location

Cell membrane; Multi-pass membrane protein. Endosome. Note: Interaction with SNX27 mediates recruitment to early endosomes, while interaction with SLC9A3R1 and EZR might target the protein to specialized subcellular regions, such as microvilli By similarity.

Tissue specificity

In brain, isoform 5-HT4S is restricted to the striatum, but isoform 5-HT4L is expressed throughout the brain, except in the cerebellum. In peripheral tissues, differential expression is also observed in the atrium of the heart where only isoform 5-HT4S is detectable.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 5-HT4L (identifier: Q62758-1)

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.
Isoform 5-HT4S (identifier: Q62758-2)

The sequence of this isoform differs from the canonical sequence as follows:
     360-406: DTVECGGQWESRCHLTATSPLVAAQPVIRRPQDNDLEDSCSLKRSQS → YTVLHSGQHQELEKLPIHNDPESLESCF
Isoform 5-HT4(E) (identifier: Q62758-3)

The sequence of this isoform differs from the canonical sequence as follows:
     359-406: RDTVECGGQWESRCHLTATSPLVAAQPVIRRPQDNDLEDSCSLKRSQS → SFPLLFCNRPVPV

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 4064065-hydroxytryptamine receptor 4
PRO_0000068968

Regions

Topological domain1 – 1919Extracellular By similarity
Transmembrane20 – 4021Helical; Name=1; By similarity
Topological domain41 – 5818Cytoplasmic By similarity
Transmembrane59 – 7921Helical; Name=2; By similarity
Topological domain80 – 9314Extracellular By similarity
Transmembrane94 – 11623Helical; Name=3; By similarity
Topological domain117 – 13721Cytoplasmic By similarity
Transmembrane138 – 15821Helical; Name=4; By similarity
Topological domain159 – 19234Extracellular By similarity
Transmembrane193 – 21321Helical; Name=5; By similarity
Topological domain214 – 26047Cytoplasmic By similarity
Transmembrane261 – 28121Helical; Name=6; By similarity
Topological domain282 – 29413Extracellular By similarity
Transmembrane295 – 31521Helical; Name=7; By similarity
Topological domain316 – 40691Cytoplasmic By similarity

Amino acid modifications

Lipidation3291S-palmitoyl cysteine By similarity
Glycosylation71N-linked (GlcNAc...) Potential
Disulfide bond93 ↔ 184 By similarity

Natural variations

Alternative sequence359 – 40648RDTVE…KRSQS → SFPLLFCNRPVPV in isoform 5-HT4(E).
VSP_001855
Alternative sequence360 – 40647DTVEC…KRSQS → YTVLHSGQHQELEKLPIHND PESLESCF in isoform 5-HT4S.
VSP_001854

Experimental info

Sequence conflict74 – 752NA → MP in CAA09599. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 5-HT4L [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: A1889155A08930B4

FASTA40646,107
        10         20         30         40         50         60 
MDRLDANVSS NEGFGSVEKV VLLTFFAMVI LMAILGNLLV MVAVCRDRQL RKIKTNYFIV 

        70         80         90        100        110        120 
SLAFADLLVS VLVNAFGAIE LVQDIWFYGE MFCLVRTSLD VLLTTASIFH LCCISLDRYY 

       130        140        150        160        170        180 
AICCQPLVYR NKMTPLRIAL MLGGCWVIPM FISFLPIMQG WNNIGIVDVI EKRKFNHNSN 

       190        200        210        220        230        240 
STFCVFMVNK PYAITCSVVA FYIPFLLMVL AYYRIYVTAK EHAQQIQMLQ RAGATSESRP 

       250        260        270        280        290        300 
QTADQHSTHR MRTETKAAKT LCVIMGCFCF CWAPFFVTNI VDPFIDYTVP EKVWTAFLWL 

       310        320        330        340        350        360 
GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYKRPPIL GQTVPCSTTT INGSTHVLRD 

       370        380        390        400 
TVECGGQWES RCHLTATSPL VAAQPVIRRP QDNDLEDSCS LKRSQS 

« Hide

Isoform 5-HT4S [UniParc].

Checksum: 09B2236DF4978D3A
Show »

FASTA38744,173
Isoform 5-HT4(E) [UniParc].

Checksum: 7D5F0B514486BDA1
Show »

FASTA37142,254

References

[1]"The 5-HT4 receptor: molecular cloning and pharmacological characterization of two splice variants."
Gerald C., Adham N., Kao H.T., Olsen M.A., Laz T.M., Schechter L.E., Bard J.A., Vaysse P., Hartig P.R., Branchek T.A., Weinshank R.L.
EMBO J. 14:2806-2815(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"Expression of serotonin receptor mRNAs in blood vessels."
Ullmer C., Schmuck K., Kalkman H.O., Luebbert H.
FEBS Lett. 370:215-221(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 165-259.
Tissue: Brain.
[3]"Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain."
Claeysen S., Sebben M., Becamel C., Bockaert J., Dumuis A.
Mol. Pharmacol. 55:910-920(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5-HT4(E)).
Tissue: Brain.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U20907 mRNA. Translation: AAC52233.1.
U20906 mRNA. Translation: AAC52232.1.
Z48153 mRNA. Translation: CAA88170.1.
AJ011370 mRNA. Translation: CAA09599.1.
PIRS55549.
S55550.
RefSeqNP_036985.1. NM_012853.1.
UniGeneRn.10094.

3D structure databases

ProteinModelPortalQ62758.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBQ62758.
ChEMBLCHEMBL2094123.
GuidetoPHARMACOLOGY9.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteQ62758.

Proteomic databases

PaxDbQ62758.
PRIDEQ62758.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID25324.
KEGGrno:25324.
UCSCRGD:2850. rat. [Q62758-1]

Organism-specific databases

CTD3360.
RGD2850. Htr4.

Phylogenomic databases

eggNOGNOG262978.
HOGENOMHOG000239242.
HOVERGENHBG106962.
InParanoidQ62758.
KOK04160.
PhylomeDBQ62758.

Gene expression databases

GenevestigatorQ62758.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR001520. 5HT4_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24249:SF33. PTHR24249:SF33. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR01059. 5HT4RECEPTR.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio606177.
PROQ62758.

Entry information

Entry name5HT4R_RAT
AccessionPrimary (citable) accession number: Q62758
Secondary accession number(s): O89034, Q62757, Q63006
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries