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Protein

5-hydroxytryptamine receptor 4

Gene

Htr4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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

  1. serotonin receptor activity Source: RGD

GO - Biological processi

  1. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: RGD
  2. cognition Source: RGD
  3. gamma-aminobutyric acid signaling pathway Source: RGD
  4. regulation of appetite Source: InterPro
  5. serotonin receptor signaling pathway Source: GOC
  6. synaptic transmission Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi2850. Htr4.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 1919ExtracellularBy similarityAdd
BLAST
Transmembranei20 – 4021Helical; Name=1By similarityAdd
BLAST
Topological domaini41 – 5818CytoplasmicBy similarityAdd
BLAST
Transmembranei59 – 7921Helical; Name=2By similarityAdd
BLAST
Topological domaini80 – 9314ExtracellularBy similarityAdd
BLAST
Transmembranei94 – 11623Helical; Name=3By similarityAdd
BLAST
Topological domaini117 – 13721CytoplasmicBy similarityAdd
BLAST
Transmembranei138 – 15821Helical; Name=4By similarityAdd
BLAST
Topological domaini159 – 19234ExtracellularBy similarityAdd
BLAST
Transmembranei193 – 21321Helical; Name=5By similarityAdd
BLAST
Topological domaini214 – 26047CytoplasmicBy similarityAdd
BLAST
Transmembranei261 – 28121Helical; Name=6By similarityAdd
BLAST
Topological domaini282 – 29413ExtracellularBy similarityAdd
BLAST
Transmembranei295 – 31521Helical; Name=7By similarityAdd
BLAST
Topological domaini316 – 40691CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

  1. endosome Source: UniProtKB-SubCell
  2. integral component of plasma membrane Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 4064065-hydroxytryptamine receptor 4PRO_0000068968Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi7 – 71N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi93 ↔ 184PROSITE-ProRule annotation
Lipidationi329 – 3291S-palmitoyl cysteineBy similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Proteomic databases

PaxDbiQ62758.
PRIDEiQ62758.

PTM databases

PhosphoSiteiQ62758.

Expressioni

Tissue specificityi

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.

Gene expression databases

GenevestigatoriQ62758.

Interactioni

Subunit structurei

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).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ62758.
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

eggNOGiNOG262978.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiQ62758.
KOiK04160.
PhylomeDBiQ62758.

Family and domain databases

InterProiIPR001520. 5HT4_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24249:SF33. PTHR24249:SF33. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01059. 5HT4RECEPTR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.

Isoform 5-HT4L (identifier: Q62758-1) [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
MDRLDANVSS NEGFGSVEKV VLLTFFAMVI LMAILGNLLV MVAVCRDRQL
60 70 80 90 100
RKIKTNYFIV SLAFADLLVS VLVNAFGAIE LVQDIWFYGE MFCLVRTSLD
110 120 130 140 150
VLLTTASIFH LCCISLDRYY AICCQPLVYR NKMTPLRIAL MLGGCWVIPM
160 170 180 190 200
FISFLPIMQG WNNIGIVDVI EKRKFNHNSN STFCVFMVNK PYAITCSVVA
210 220 230 240 250
FYIPFLLMVL AYYRIYVTAK EHAQQIQMLQ RAGATSESRP QTADQHSTHR
260 270 280 290 300
MRTETKAAKT LCVIMGCFCF CWAPFFVTNI VDPFIDYTVP EKVWTAFLWL
310 320 330 340 350
GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYKRPPIL GQTVPCSTTT
360 370 380 390 400
INGSTHVLRD TVECGGQWES RCHLTATSPL VAAQPVIRRP QDNDLEDSCS

LKRSQS
Length:406
Mass (Da):46,107
Last modified:November 1, 1996 - v1
Checksum:iA1889155A08930B4
GO
Isoform 5-HT4S (identifier: Q62758-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     360-406: DTVECGGQWESRCHLTATSPLVAAQPVIRRPQDNDLEDSCSLKRSQS → YTVLHSGQHQELEKLPIHNDPESLESCF

Show »
Length:387
Mass (Da):44,173
Checksum:i09B2236DF4978D3A
GO
Isoform 5-HT4(E) (identifier: Q62758-3) [UniParc]FASTAAdd to basket

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

Show »
Length:371
Mass (Da):42,254
Checksum:i7D5F0B514486BDA1
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti74 – 752NA → MP in CAA09599 (PubMed:10220570).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei359 – 40648RDTVE…KRSQS → SFPLLFCNRPVPV in isoform 5-HT4(E). CuratedVSP_001855Add
BLAST
Alternative sequencei360 – 40647DTVEC…KRSQS → YTVLHSGQHQELEKLPIHND PESLESCF in isoform 5-HT4S. CuratedVSP_001854Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20907 mRNA. Translation: AAC52233.1.
U20906 mRNA. Translation: AAC52232.1.
Z48153 mRNA. Translation: CAA88170.1.
AJ011370 mRNA. Translation: CAA09599.1.
PIRiS55549.
S55550.
RefSeqiNP_036985.1. NM_012853.1. [Q62758-1]
UniGeneiRn.10094.

Genome annotation databases

GeneIDi25324.
KEGGirno:25324.
UCSCiRGD:2850. rat. [Q62758-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20907 mRNA. Translation: AAC52233.1.
U20906 mRNA. Translation: AAC52232.1.
Z48153 mRNA. Translation: CAA88170.1.
AJ011370 mRNA. Translation: CAA09599.1.
PIRiS55549.
S55550.
RefSeqiNP_036985.1. NM_012853.1. [Q62758-1]
UniGeneiRn.10094.

3D structure databases

ProteinModelPortaliQ62758.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

BindingDBiQ62758.
ChEMBLiCHEMBL2094123.
GuidetoPHARMACOLOGYi9.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiQ62758.

Proteomic databases

PaxDbiQ62758.
PRIDEiQ62758.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi25324.
KEGGirno:25324.
UCSCiRGD:2850. rat. [Q62758-1]

Organism-specific databases

CTDi3360.
RGDi2850. Htr4.

Phylogenomic databases

eggNOGiNOG262978.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiQ62758.
KOiK04160.
PhylomeDBiQ62758.

Miscellaneous databases

NextBioi606177.
PROiQ62758.

Gene expression databases

GenevestigatoriQ62758.

Family and domain databases

InterProiIPR001520. 5HT4_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24249:SF33. PTHR24249:SF33. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR01059. 5HT4RECEPTR.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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.

Entry informationi

Entry namei5HT4R_RAT
AccessioniPrimary (citable) accession number: Q62758
Secondary accession number(s): O89034, Q62757, Q63006
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: January 7, 2015
This is version 120 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. 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.