5-hydroxytryptamine receptor 4

Details

Name
5-hydroxytryptamine receptor 4
Synonyms
  • 5-HT-4
  • Serotonin receptor 4
Gene Name
HTR4
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000168|5-hydroxytryptamine receptor 4
MDKLDANVSSEEGFGSVEKVVLLTFLSTVILMAILGNLLVMVAVCWDRQLRKIKTNYFIV
SLAFADLLVSVLVMPFGAIELVQDIWIYGEVFCLVRTSLDVLLTTASIFHLCCISLDRYY
AICCQPLVYRNKMTPLRIALMLGGCWVIPTFISFLPIMQGWNNIGIIDLIEKRKFNQNSN
STYCVFMVNKPYAITCSVVAFYIPFLLMVLAYYRIYVTAKEHAHQIQMLQRAGASSESRP
QSADQHSTHRMRTETKAAKTLCIIMGCFCLCWAPFFVTNIVDPFIDYTVPGQVWTAFLWL
GYINSGLNPFLYAFLNKSFRRAFLIILCCDDERYRRPSILGQTVPCSTTTINGSTHVLRD
AVECGGQWESQCHPPATSPLVAAQPSDT
Number of residues
388
Molecular Weight
43760.975
Theoretical pI
7.82
GO Classification
Functions
serotonin receptor activity
Processes
G-protein coupled receptor signaling pathway / G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / gamma-aminobutyric acid signaling pathway / positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway / regulation of appetite / sensory perception of chemical stimulus / serotonin receptor signaling pathway / synaptic transmission
Components
cytoplasm / endosome / integral component of plasma membrane / membrane / plasma membrane
General Function
Serotonin receptor activity
Specific 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.
Pfam Domain Function
Transmembrane Regions
20-40 59-79 94-116 138-158 193-213 261-281 295-315
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0009924|5-hydroxytryptamine receptor 4 (HTR4)
ATGGACAAACTTGATGCTAATGTGAGTTCTGAGGAGGGTTTCGGGTCAGTGGAGAAGGTG
GTGCTGCTCACGTTTCTCTCGACGGTTATCCTGATGGCCATCTTGGGGAACCTGCTGGTG
ATGGTGGCTGTGTGCTGGGACAGGCAGCTCAGGAAAATAAAAACAAATTATTTCATTGTA
TCTCTTGCTTTTGCGGATCTGCTGGTTTCGGTGCTGGTGATGCCCTTTGGTGCCATTGAG
CTGGTTCAAGACATCTGGATTTATGGGGAGGTGTTTTGTCTTGTTCGGACATCTCTGGAC
GTCCTGCTCACAACGGCATCGATTTTTCACCTGTGCTGCATTTCTCTGGATAGGTATTAC
GCCATCTGCTGCCAGCCTTTGGTCTATAGGAACAAGATGACCCCTCTGCGCATCGCATTA
ATGCTGGGAGGCTGCTGGGTCATCCCCACGTTTATTTCTTTTCTCCCTATAATGCAAGGC
TGGAATAACATTGGCATAATTGATTTGATAGAAAAGAGGAAGTTCAACCAGAACTCTAAC
TCTACGTACTGTGTCTTCATGGTCAACAAGCCCTACGCCATCACCTGCTCTGTGGTGGCC
TTCTACATCCCATTTCTCCTCATGGTGCTGGCCTATTACCGCATCTATGTCACAGCTAAG
GAGCATGCCCATCAGATCCAGATGTTACAACGGGCAGGAGCCTCCTCCGAGAGCAGGCCT
CAGTCGGCAGACCAGCATAGCACTCATCGCATGAGGACAGAGACCAAAGCAGCCAAGACC
CTGTGCATCATCATGGGTTGCTTCTGCCTCTGCTGGGCACCATTCTTTGTCACCAATATT
GTGGATCCTTTCATAGACTACACTGTCCCTGGGCAGGTGTGGACTGCTTTCCTCTGGCTC
GGCTATATCAATTCCGGGTTGAACCCTTTTCTCTACGCCTTCTTGAATAAGTCTTTTAGA
CGTGCCTTCCTCATCATCCTCTGCTGTGATGATGAGCGCTACCGAAGACCTTCCATTCTG
GGCCAGACTGTCCCTTGTTCAACCACAACCATTAATGGATCCACACATGTACTAAGGGAT
GCAGTGGAGTGTGGTGGCCAGTGGGAGAGTCAGTGTCACCCGCCAGCAACTTCTCCTTTG
GTGGCTGCTCAGCCCAGTGACACTTAG
Chromosome Location
5
Locus
5q31-q33
External Identifiers
ResourceLink
UniProtKB IDQ13639
UniProtKB Entry Name5HT4R_HUMAN
GenBank Protein ID2661757
GenBank Gene IDY12505
GenAtlas IDHTR4
HGNC IDHGNC:5299
General References
  1. Blondel O, Gastineau M, Dahmoune Y, Langlois M, Fischmeister R: Cloning, expression, and pharmacology of four human 5-hydroxytryptamine 4 receptor isoforms produced by alternative splicing in the carboxyl terminus. J Neurochem. 1998 Jun;70(6):2252-61. [PubMed:9603189]
  2. Claeysen S, Faye P, Sebben M, Lemaire S, Bockaert J, Dumuis A: Cloning and expression of human 5-HT4S receptors. Effect of receptor density on their coupling to adenylyl cyclase. Neuroreport. 1997 Oct 20;8(15):3189-96. [PubMed:9351641]
  3. Claeysen S, Sebben M, Becamel C, Bockaert J, Dumuis A: Novel brain-specific 5-HT4 receptor splice variants show marked constitutive activity: role of the C-terminal intracellular domain. Mol Pharmacol. 1999 May;55(5):910-20. [PubMed:10220570]
  4. Vilaro MT, Domenech T, Palacios JM, Mengod G: Cloning and characterization of a novel human 5-HT4 receptor variant that lacks the alternatively spliced carboxy terminal exon. RT-PCR distribution in human brain and periphery of multiple 5-HT4 receptor variants. Neuropharmacology. 2002 Jan;42(1):60-73. [PubMed:11750916]
  5. Brattelid T, Kvingedal AM, Krobert KA, Andressen KW, Bach T, Hystad ME, Kaumann AJ, Levy FO: Cloning, pharmacological characterisation and tissue distribution of a novel 5-HT4 receptor splice variant, 5-HT4(i). Naunyn Schmiedebergs Arch Pharmacol. 2004 Jun;369(6):616-28. Epub 2004 Apr 30. [PubMed:15118808]
  6. Schmutz J, Martin J, Terry A, Couronne O, Grimwood J, Lowry S, Gordon LA, Scott D, Xie G, Huang W, Hellsten U, Tran-Gyamfi M, She X, Prabhakar S, Aerts A, Altherr M, Bajorek E, Black S, Branscomb E, Caoile C, Challacombe JF, Chan YM, Denys M, Detter JC, Escobar J, Flowers D, Fotopulos D, Glavina T, Gomez M, Gonzales E, Goodstein D, Grigoriev I, Groza M, Hammon N, Hawkins T, Haydu L, Israni S, Jett J, Kadner K, Kimball H, Kobayashi A, Lopez F, Lou Y, Martinez D, Medina C, Morgan J, Nandkeshwar R, Noonan JP, Pitluck S, Pollard M, Predki P, Priest J, Ramirez L, Retterer J, Rodriguez A, Rogers S, Salamov A, Salazar A, Thayer N, Tice H, Tsai M, Ustaszewska A, Vo N, Wheeler J, Wu K, Yang J, Dickson M, Cheng JF, Eichler EE, Olsen A, Pennacchio LA, Rokhsar DS, Richardson P, Lucas SM, Myers RM, Rubin EM: The DNA sequence and comparative analysis of human chromosome 5. Nature. 2004 Sep 16;431(7006):268-74. [PubMed:15372022]
  7. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  8. Bender E, Pindon A, van Oers I, Zhang YB, Gommeren W, Verhasselt P, Jurzak M, Leysen J, Luyten W: Structure of the human serotonin 5-HT4 receptor gene and cloning of a novel 5-HT4 splice variant. J Neurochem. 2000 Feb;74(2):478-89. [PubMed:10646498]
  9. Ullmer C, Schmuck K, Kalkman HO, Lubbert H: Expression of serotonin receptor mRNAs in blood vessels. FEBS Lett. 1995 Aug 21;370(3):215-21. [PubMed:7656980]
  10. Barthet G, Carrat G, Cassier E, Barker B, Gaven F, Pillot M, Framery B, Pellissier LP, Augier J, Kang DS, Claeysen S, Reiter E, Baneres JL, Benovic JL, Marin P, Bockaert J, Dumuis A: Beta-arrestin1 phosphorylation by GRK5 regulates G protein-independent 5-HT4 receptor signalling. EMBO J. 2009 Sep 16;28(18):2706-18. doi: 10.1038/emboj.2009.215. Epub 2009 Aug 6. [PubMed:19661922]
  11. Rademakers R, Baker M, Nicholson AM, Rutherford NJ, Finch N, Soto-Ortolaza A, Lash J, Wider C, Wojtas A, DeJesus-Hernandez M, Adamson J, Kouri N, Sundal C, Shuster EA, Aasly J, MacKenzie J, Roeber S, Kretzschmar HA, Boeve BF, Knopman DS, Petersen RC, Cairns NJ, Ghetti B, Spina S, Garbern J, Tselis AC, Uitti R, Das P, Van Gerpen JA, Meschia JF, Levy S, Broderick DF, Graff-Radford N, Ross OA, Miller BB, Swerdlow RH, Dickson DW, Wszolek ZK: Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat Genet. 2011 Dec 25;44(2):200-5. doi: 10.1038/ng.1027. [PubMed:22197934]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00604Cisaprideapproved, investigational, withdrawnyesagonistDetails
DB01079Tegaserodapproved, investigational, withdrawnyesantagonistpartial agonistDetails
DB04873PiboserodinvestigationalunknownDetails
DB04917RenzaprideinvestigationalunknownDetails
DB12702VelusetraginvestigationalunknownDetails
DB05905TD-2749investigationalunknownDetails
DB06422TicaloprideinvestigationalunknownDetails
DB06480PrucaloprideapprovedyesagonistDetails
DB05542NaronaprideinvestigationalunknownagonistDetails
DB01233Metoclopramideapproved, investigationalyesagonistDetails
DB00904OndansetronapprovedunknownagonistDetails
DB08810CinitaprideinvestigationalunknownagonistDetails
DB13025TiaprideinvestigationalyesantagonistDetails
DB09304SetiptilineexperimentalunknownantagonistDetails
DB13345Dihydroergocristineapproved, experimentalyesantagonistDetails
DB01049Ergoloid mesylateapprovedyesantagonistagonistDetails
DB11273DihydroergocornineapprovedyesantagonistagonistDetails
DB12141Gilteritinibapproved, investigationalnoinhibitorDetails
DB00715Paroxetineapproved, investigationalunknownDetails