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Q62758

- 5HT4R_RAT

UniProt

Q62758 - 5HT4R_RAT

Protein

5-hydroxytryptamine receptor 4

Gene

Htr4

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 118 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    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

    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

    GO - Cellular componenti

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

    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...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 1919ExtracellularBy similarityAdd
    BLAST
    Topological domaini41 – 5818CytoplasmicBy similarityAdd
    BLAST
    Topological domaini80 – 9314ExtracellularBy similarityAdd
    BLAST
    Topological domaini117 – 13721CytoplasmicBy similarityAdd
    BLAST
    Topological domaini159 – 19234ExtracellularBy similarityAdd
    BLAST
    Topological domaini214 – 26047CytoplasmicBy similarityAdd
    BLAST
    Topological domaini282 – 29413ExtracellularBy similarityAdd
    BLAST
    Topological domaini316 – 40691CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei20 – 4021Helical; Name=1By similarityAdd
    BLAST
    Transmembranei59 – 7921Helical; Name=2By similarityAdd
    BLAST
    Transmembranei94 – 11623Helical; Name=3By similarityAdd
    BLAST
    Transmembranei138 – 15821Helical; Name=4By similarityAdd
    BLAST
    Transmembranei193 – 21321Helical; Name=5By similarityAdd
    BLAST
    Transmembranei261 – 28121Helical; Name=6By similarityAdd
    BLAST
    Transmembranei295 – 31521Helical; Name=7By similarityAdd
    BLAST

    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

    Gene3Di1.20.1070.10. 1 hit.
    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. Align

    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

    MDRLDANVSS NEGFGSVEKV VLLTFFAMVI LMAILGNLLV MVAVCRDRQL    50
    RKIKTNYFIV SLAFADLLVS VLVNAFGAIE LVQDIWFYGE MFCLVRTSLD 100
    VLLTTASIFH LCCISLDRYY AICCQPLVYR NKMTPLRIAL MLGGCWVIPM 150
    FISFLPIMQG WNNIGIVDVI EKRKFNHNSN STFCVFMVNK PYAITCSVVA 200
    FYIPFLLMVL AYYRIYVTAK EHAQQIQMLQ RAGATSESRP QTADQHSTHR 250
    MRTETKAAKT LCVIMGCFCF CWAPFFVTNI VDPFIDYTVP EKVWTAFLWL 300
    GYINSGLNPF LYAFLNKSFR RAFLIILCCD DERYKRPPIL GQTVPCSTTT 350
    INGSTHVLRD TVECGGQWES RCHLTATSPL VAAQPVIRRP QDNDLEDSCS 400
    LKRSQS 406
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U20907 mRNA. Translation: AAC52233.1 .
    U20906 mRNA. Translation: AAC52232.1 .
    Z48153 mRNA. Translation: CAA88170.1 .
    AJ011370 mRNA. Translation: CAA09599.1 .
    PIRi S55549.
    S55550.
    RefSeqi NP_036985.1. NM_012853.1. [Q62758-1 ]
    UniGenei Rn.10094.

    3D structure databases

    ProteinModelPortali Q62758.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi Q62758.
    ChEMBLi CHEMBL4317.
    GuidetoPHARMACOLOGYi 9.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei Q62758.

    Proteomic databases

    PaxDbi Q62758.
    PRIDEi Q62758.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 25324.
    KEGGi rno:25324.
    UCSCi RGD:2850. rat. [Q62758-1 ]

    Organism-specific databases

    CTDi 3360.
    RGDi 2850. Htr4.

    Phylogenomic databases

    eggNOGi NOG262978.
    HOGENOMi HOG000239242.
    HOVERGENi HBG106962.
    InParanoidi Q62758.
    KOi K04160.
    PhylomeDBi Q62758.

    Miscellaneous databases

    NextBioi 606177.
    PROi Q62758.

    Gene expression databases

    Genevestigatori Q62758.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR001520. 5HT4_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    PANTHERi PTHR24249:SF33. PTHR24249:SF33. 1 hit.
    Pfami PF00001. 7tm_1. 1 hit.
    [Graphical view ]
    PRINTSi PR01059. 5HT4RECEPTR.
    PR00237. GPCRRHODOPSN.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    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: October 1, 2014
    This is version 118 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