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Protein

5-hydroxytryptamine receptor 4

Gene

Htr4

Organism
Mus musculus (Mouse)
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. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_313192. G alpha (s) signalling events.
REACT_332615. Serotonin receptors.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:109246. 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.

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 – 38873CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 3883885-hydroxytryptamine receptor 4PRO_0000068966Add
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

PRIDEiP97288.

PTM databases

PhosphoSiteiP97288.

Expressioni

Gene expression databases

BgeeiP97288.
CleanExiMM_HTR4.
GenevisibleiP97288. MM.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
GRK5P349478EBI-7149283,EBI-7149314From a different organism.
SRCP129312EBI-7149283,EBI-621482From a different organism.

Protein-protein interaction databases

IntActiP97288. 5 interactions.
STRINGi10090.ENSMUSP00000027560.

Structurei

3D structure databases

ProteinModelPortaliP97288.
SMRiP97288. Positions 25-328.
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.
GeneTreeiENSGT00760000118774.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP97288.
KOiK04160.
OMAiYRIYITA.
OrthoDBiEOG7CG707.
TreeFamiTF316350.

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 (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P97288-1) [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 NEGFRSVEKV VLLTFLAVVI LMAILGNLLV MVAVCRDRQL
60 70 80 90 100
RKIKTNYFIV SLAFADLLVS VLVMPFGAIE LVQDIWAYGE MFCLVRTSLD
110 120 130 140 150
VLLTTASIFH LCCISLDRYY AICCQPLVYR NKMTPLRIAL MLGGCWVLPM
160 170 180 190 200
FISFLPIMQG WNNIGIVDVI EKRKFSHNSN STWCVFMVNK PYAITCSVVA
210 220 230 240 250
FYIPFLLMVL AYYRIYVTAK EHAQQIQMLQ RAGATSESRP QPADQHSTHR
260 270 280 290 300
MRTETKAAKT LCVIMGCFCF CWAPFFVTNI VDPFIDYTVP EQVWTAFLWL
310 320 330 340 350
GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYKRPPIL GQTVPCSTTT
360 370 380
INGSTHVLRD TVECGGQWES RCHLTATSPL VAAQPSDT
Length:388
Mass (Da):43,962
Last modified:July 27, 2011 - v3
Checksum:iF84163E7CAE415B0
GO
Isoform 5-HT4(A) (identifier: P97288-2) [UniParc]FASTAAdd to basket

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

Show »
Length:387
Mass (Da):44,162
Checksum:i2EE398916C432032
GO
Isoform 5-HT4(E) (identifier: P97288-3) [UniParc]FASTAAdd to basket

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

Show »
Length:371
Mass (Da):42,287
Checksum:iD1AD0ACD3D1C8129
GO
Isoform 5-HT4(F) (identifier: P97288-4) [UniParc]FASTAAdd to basket

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

Show »
Length:363
Mass (Da):41,312
Checksum:i2C8C6F05B22CF91C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti361 – 3611T → A in CAA70773 (PubMed:8946946).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei359 – 38830RDTVE…QPSDT → SFPLLFRNRPVPV in isoform 5-HT4(E). CuratedVSP_001852Add
BLAST
Alternative sequencei360 – 38829DTVEC…QPSDT → YTVLHSGHHQELEKLPIHND PESLESCF in isoform 5-HT4(A). CuratedVSP_001851Add
BLAST
Alternative sequencei360 – 38829DTVEC…QPSDT → PVPV in isoform 5-HT4(F). CuratedVSP_001853Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y09585 mRNA. Translation: CAA70773.1.
Y09587 mRNA. Translation: CAA70775.1.
Y09588 mRNA. Translation: CAA70776.1.
AJ011369 mRNA. Translation: CAA09598.1.
AK141587 mRNA. Translation: BAE24750.1.
AK141625 mRNA. Translation: BAE24773.1.
CH466528 Genomic DNA. Translation: EDL09743.1.
CCDSiCCDS29291.1. [P97288-1]
RefSeqiNP_032339.2. NM_008313.4. [P97288-1]
XP_006525738.1. XM_006525675.2. [P97288-1]
XP_006525739.1. XM_006525676.2. [P97288-1]
XP_006525741.1. XM_006525678.2. [P97288-1]
XP_006525743.1. XM_006525680.2. [P97288-2]
XP_006525746.1. XM_006525683.2. [P97288-3]
UniGeneiMm.20440.

Genome annotation databases

EnsembliENSMUST00000027560; ENSMUSP00000027560; ENSMUSG00000026322. [P97288-1]
GeneIDi15562.
KEGGimmu:15562.
UCSCiuc008fda.1. mouse. [P97288-1]
uc008fdb.1. mouse. [P97288-2]
uc008fdc.1. mouse. [P97288-4]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Y09585 mRNA. Translation: CAA70773.1.
Y09587 mRNA. Translation: CAA70775.1.
Y09588 mRNA. Translation: CAA70776.1.
AJ011369 mRNA. Translation: CAA09598.1.
AK141587 mRNA. Translation: BAE24750.1.
AK141625 mRNA. Translation: BAE24773.1.
CH466528 Genomic DNA. Translation: EDL09743.1.
CCDSiCCDS29291.1. [P97288-1]
RefSeqiNP_032339.2. NM_008313.4. [P97288-1]
XP_006525738.1. XM_006525675.2. [P97288-1]
XP_006525739.1. XM_006525676.2. [P97288-1]
XP_006525741.1. XM_006525678.2. [P97288-1]
XP_006525743.1. XM_006525680.2. [P97288-2]
XP_006525746.1. XM_006525683.2. [P97288-3]
UniGeneiMm.20440.

3D structure databases

ProteinModelPortaliP97288.
SMRiP97288. Positions 25-328.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP97288. 5 interactions.
STRINGi10090.ENSMUSP00000027560.

Chemistry

BindingDBiP97288.
ChEMBLiCHEMBL2183.
GuidetoPHARMACOLOGYi9.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiP97288.

Proteomic databases

PRIDEiP97288.

Protocols and materials databases

DNASUi15562.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000027560; ENSMUSP00000027560; ENSMUSG00000026322. [P97288-1]
GeneIDi15562.
KEGGimmu:15562.
UCSCiuc008fda.1. mouse. [P97288-1]
uc008fdb.1. mouse. [P97288-2]
uc008fdc.1. mouse. [P97288-4]

Organism-specific databases

CTDi3360.
MGIiMGI:109246. Htr4.

Phylogenomic databases

eggNOGiNOG262978.
GeneTreeiENSGT00760000118774.
HOGENOMiHOG000239242.
HOVERGENiHBG106962.
InParanoidiP97288.
KOiK04160.
OMAiYRIYITA.
OrthoDBiEOG7CG707.
TreeFamiTF316350.

Enzyme and pathway databases

ReactomeiREACT_313192. G alpha (s) signalling events.
REACT_332615. Serotonin receptors.

Miscellaneous databases

NextBioi288518.
PROiP97288.
SOURCEiSearch...

Gene expression databases

BgeeiP97288.
CleanExiMM_HTR4.
GenevisibleiP97288. MM.

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

« Hide 'large scale' publications
  1. "Cloning, expression and pharmacology of the mouse 5-HT(4L) receptor."
    Claeysen S., Sebben M., Journot L., Bockaert J., Dumuis A.
    FEBS Lett. 398:19-25(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Swiss.
    Tissue: Brain.
  2. Dumuis A.
    Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: SEQUENCE REVISION TO C-TERMINUS.
  3. "5-HT4 receptors: cloning and expression of new splice variants."
    Claeysen S., Faye P., Sebben M., Taviaux S., Bockaert J., Dumuis A.
    Ann. N. Y. Acad. Sci. 861:49-56(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5-HT4(A) AND 5-HT4(E)).
    Strain: Swiss.
    Tissue: Brain.
  4. "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(F)).
    Tissue: Brain.
  5. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  6. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a receptor splice variant: roles in receptor targeting."
    Joubert L., Hanson B., Barthet G., Sebben M., Claeysen S., Hong W., Marin P., Dumuis A., Bockaert J.
    J. Cell Sci. 117:5367-5379(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH INADL; MAGI2; MPP3; NOS1; SEC23A; SLC9A3R1 AND SNX27.

Entry informationi

Entry namei5HT4R_MOUSE
AccessioniPrimary (citable) accession number: P97288
Secondary accession number(s): O89003
, O89004, Q3URB5, Q9R2A4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 27, 2011
Last modified: June 24, 2015
This is version 134 of the entry and version 3 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. 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.