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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:07:48
Primary Accession Number DB00604
Secondary Accession Number
  • APRD00454
Name Cisapride
Drug Type
  • Approved
  • Investigational
  • Small Molecule
  • Withdrawn
Description In many countries (including Canada) cisapride has been either withdrawn or has had its indications limited due to reports about long QT syndrome due to cisapride, which predisposes to arrhythmias. The FDA issued a warning letter regarding this risk to health care professionals and patients.
Synonyms
  1. cisapride
Brand Names
  1. Acenalin
  2. Alimix
  3. Cipril
  4. Enteropride
  5. Kinestase
  6. Prepulsid
  7. Pridesia
  8. Propulsid
  9. Propulsid Quicksolv
  10. Propulsin
  11. Risamal
  12. Syspride
Brand Mixtures Not Available
Chemical IUPAC Name 4-amino-5-chloro-N-[1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl]-2-methoxybenzamide
Chemical Formula C23H29ClFN3O4
Chemical Structure Structure
CAS Registry Number 81098-60-4
InChI Identifier InChI=1/C23H29ClFN3O4/c1-30-21-13-19(26)18(24)12-17(21)23(29)27-20-8-10-28(14-22(20)31-2)9-3-11-32-16-6-4-15(25)5-7-16/h4-7,12-13,20,22H,3,8-11,14,26H2,1-2H3,(H,27,29)/f/h27H
InChI Key DCSUBABJRXZOMT-LELJVTLKCZ
KEGG Drug D00274 Link Image
KEGG Compound C06910 Link Image
PubChem Compound 2769 Link Image
PubChem Substance 192212 Link Image
ChEBI ID Not Available
PharmGKB ID PA449011 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02054817 Link Image
RxList Link http://www.rxlist.com/cgi/generic/cisap.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Cisapride Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 465.9450
Monoisotopic Molecular Weight 465.1831
State Solid
Melting Point 110 oC
Experimental Water Solubility 2.71 mg/L Source: PhysProp
Predicted Water Solubility 1.20e-02 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.3 Source: PhysProp
Predicted LogP 2.95 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.59 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point Not Available
Mass Spectrum Not Available
MOL File Show Link Image | Download Link Image
SDF File Show Link Image | Download Link Image
PDB File Show Link Image | Download Link Image
2D Structure
3D Structure
Experimental PDB ID Not Available
Isomeric SMILES CO[C@H]1CN(CCCOC2=CC=C(F)C=C2)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)C=C1OC
Canonical SMILES COC1CN(CCCOC2=CC=C(F)C=C2)CCC1NC(=O)C1=CC(Cl)=C(N)C=C1OC
Drug Category
  • Anti-Ulcer Agents
  • Gastrointestinal Agents
  • Prokinetic Agents
  • Serotonin Agonists
ATC Codes
AHFS Codes Not Available
Indication For the symptomatic treatment of adult patients with nocturnal heartburn due to gastroesophageal reflux disease.
Pharmacology Cisapride is a parasympathomimetic which acts as a serotonin 5-HT4 agonist. Stimulation of the serotonin receptors increases acetylcholine release in the enteric nervous system. Cisapride stimulates motility of the upper gastrointestinal tract without stimulating gastric, biliary, or pancreatic secretions. Cisapride increases the tone and amplitude of gastric (especially antral) contractions, relaxes the pyloric sphincter and the duodenal bulb, and increases peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit. It increases the resting tone of the lower esophageal sphincter. It has little, if any, effect on the motility of the colon or gallbladder. Cisapride does not induce muscarinic or nicotinic receptor stimulation, nor does it inhibit acetylcholinesterase activity.
Mechanism of Action Cisapride acts through the stimulation of the serotonin 5-HT4 receptors which increases acetylcholine release in the enteric nervous system (specifically the myenteric plexus). This results in increased tone and amplitude of gastric (especially antral) contractions, relaxation of the pyloric sphincter and the duodenal bulb, and increased peristalsis of the duodenum and jejunum resulting in accelerated gastric emptying and intestinal transit.
Absorption Cisapride is rapidly absorbed after oral administration, with an absolute bioavailability of 35-40%.
Toxicity Not Available
Protein Binding 97.5%
Biotransformation Hepatic. Extensively metabolized via cytochrome P450 3A4 enzyme.
Half Life 6-12 hours
Dosage Forms
Form Route
Suspension Oral
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol Increases the anticoagulant effect
Acetophenazine Increased risk of cardiotoxicity and arrhythmias
Amiodarone Increased risk of cardiotoxicity and arrhythmias
Amitriptyline Increased risk of cardiotoxicity and arrhythmias
Amoxapine Increased risk of cardiotoxicity and arrhythmias
Amprenavir Amprenavir increases the effect and toxicity of cisapride
Anisindione Increases the anticoagulant effect
Aprepitant Increased risk of cardiotoxicity and arrhythmias
Astemizole Increased risk of cardiotoxicity and arrhythmias
Atazanavir Increased risk of cardiotoxicity and arrhythmias
Bepridil Increased risk of cardiotoxicity and arrhythmias
Bretylium Increased risk of cardiotoxicity and arrhythmias
Chlorpromazine Increased risk of cardiotoxicity and arrhythmias
Clarithromycin Increased risk of cardiotoxicity and arrhythmias
Clomipramine Increased risk of cardiotoxicity and arrhythmias
Delavirdine Increased risk of cardiotoxicity and arrhythmias
Desipramine Increased risk of cardiotoxicity and arrhythmias
Dicumarol Increases the anticoagulant effect
Dihydroquinidine barbiturate Increased risk of cardiotoxicity and arrhythmias
Diltiazem Diltiazem increases the levels of cisapride
Disopyramide Increased risk of cardiotoxicity and arrhythmias
Doxepin Increased risk of cardiotoxicity and arrhythmias
Efavirenz Increased risk of cardiotoxicity and arrhythmias
Encainide Increased risk of cardiotoxicity and arrhythmias
Erythromycin Increased risk of cardiotoxicity and arrhythmias
Ethopropazine Increased risk of cardiotoxicity and arrhythmias
Fexofenadine Increased risk of cardiotoxicity and arrhythmias
Flecainide Increased risk of cardiotoxicity and arrhythmias
Fluconazole Increased risk of cardiotoxicity and arrhythmias
Fluphenazine Increased risk of cardiotoxicity and arrhythmias
Fosamprenavir Amprenavir increases the effect and toxicity of cisapride
Ibutilide Increased risk of cardiotoxicity and arrhythmias
Imipramine Increased risk of cardiotoxicity and arrhythmias
Indinavir Increased risk of cardiotoxicity and arrhythmias
Itraconazole Increased risk of cardiotoxicity and arrhythmias
Josamycin Increased risk of cardiotoxicity and arrhythmias
Ketoconazole Increased risk of cardiotoxicity and arrhythmias
Maprotiline Increased risk of cardiotoxicity and arrhythmias
Mesoridazine Increased risk of cardiotoxicity and arrhythmias
Methdilazine Increased risk of cardiotoxicity and arrhythmias
Methotrimeprazine Increased risk of cardiotoxicity and arrhythmias
Mibefradil Mibefradil increases levels of cisapride
Nefazodone Nefazodone increases serum levels of cisapride
Nelfinavir Increased risk of cardiotoxicity and arrhythmias
Nifedipine Increases the effect and toxicity of nifedipine
Nortriptyline Increased risk of cardiotoxicity and arrhythmias
Perphenazine Increased risk of cardiotoxicity and arrhythmias
Posaconazole Contraindicated co-administration
Procainamide Increased risk of cardiotoxicity and arrhythmias
Prochlorperazine Increased risk of cardiotoxicity and arrhythmias
Promazine Increased risk of cardiotoxicity and arrhythmias
Promethazine Increased risk of cardiotoxicity and arrhythmias
Propafenone Increased risk of cardiotoxicity and arrhythmias
Propiomazine Increased risk of cardiotoxicity and arrhythmias
Protriptyline Increased risk of cardiotoxicity and arrhythmias
Quinidine Increased risk of cardiotoxicity and arrhythmias
Quinidine barbiturate Increased risk of cardiotoxicity and arrhythmias
Quinupristin This combination presents an increased risk of toxicity
Ritonavir Increased risk of cardiotoxicity and arrhythmias
Saquinavir Increased risk of cardiotoxicity and arrhythmias
Sotalol Increased risk of cardiotoxicity and arrhythmias
Telithromycin Increased risk of cardiotoxicity and arrhythmias
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thiethylperazine Increased risk of cardiotoxicity and arrhythmias
Thioridazine Increased risk of cardiotoxicity and arrhythmias
Trifluoperazine Increased risk of cardiotoxicity and arrhythmias
Triflupromazine Increased risk of cardiotoxicity and arrhythmias
Trimeprazine Increased risk of cardiotoxicity and arrhythmias
Trimipramine Increased risk of cardiotoxicity and arrhythmias
Troleandomycin Increased risk of cardiotoxicity and arrhythmias
Voriconazole Increased risk of cardiotoxicity and arrhythmias
Warfarin Increases the anticoagulant effect
Zafirlukast Increased risk of cardiotoxicity and arrhythmias
Ziprasidone Increased risk of cardiotoxicity and arrhythmias
Food Interactions
  • Grapefruit and grapefruit juice should be avoided throughout treatment, grapefruit can significantly increase serum levels of this product.
  • Increases absorption, take 30 minutes before a meal.
Pathways Not Available
General References
  1. Pearce RE, Gotschall RR, Kearns GL, Leeder JS: Cytochrome P450 Involvement in the biotransformation of cisapride and racemic norcisapride in vitro: differential activity of individual human CYP3A isoforms. Drug Metab Dispos. 2001 Dec;29(12):1548-54. [PubMed Link Image]
  2. Drugs.com Link Image
  3. Wikipedia Link Image
  4. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 3A4 (CYP3A4)
Targets
  1. 5-hydroxytryptamine 4 receptor
  2. Potassium voltage-gated channel subfamily H member 2
  3. 5-hydroxytryptamine 3 receptor
  4. 5-hydroxytryptamine 2A receptor
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 3A4 (CYP3A4)
Enzyme 1 Gene Name CYP3A4
Enzyme 1 SwissProt ID P08684 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P08684|CP3A4_HUMAN Cytochrome P450 3A4 (EC 1.14.13.67) 
ALIPDLAMETWLLLAVSLVLLYLYGTHSHGLFKKLGIPGPTPLPFLGNILSYHKGFCMFD
MECHKKYGKVWGFYDGQQPVLAITDPDMIKTVLVKECYSVFTNRRPFGPVGFMKSAISIA
EDEEWKRLRSLLSPTFTSGKLKEMVPIIAQYGDVLVRNLRREAETGKPVTLKDVFGAYSM
DVITSTSFGVNIDSLNNPQDPFVENTKKLLRFDFLDPFFLSITVFPFLIPILEVLNICVF
PREVTNFLRKSVKRMKESRLEDTQKHRVDFLQLMIDSQNSKETESHKALSDLELVAQSII
FIFAGYETTSSVLSFIMYELATHPDVQQKLQEEIDAVLPNKAPPTYDTVLQMEYLDMVVN
ETLRLFPIAMRLERVCKKDVEINGMFIPKGWVVMIPSYALHRDPKYWTEPEKFLPERFSK
KNKDNIDPYIYTPFGSGPRNCIGMRFALMNMKLALIRVLQNFSFKPCKETQIPLKLSLGG
LLQPEKPVVLKVESRDGTVSGA
Drug Target 1 [top]
Target 1 ID 94
Target 1 Name 5-hydroxytryptamine 4 receptor
Target 1 Synonyms
  1. 5- HT4
  2. 5-HT-4
  3. Serotonin receptor 4
Target 1 Gene Name HTR4
Target 1 Protein Sequence >5-hydroxytryptamine 4 receptor 
MDKLDANVSSEEGFGSVEKVVLLTFLSTVILMAILGNLLVMVAVCWDRQLRKIKTNYFIV
SLAFADLLVSVLVMPFGAIELVQDIWIYGEVFCLVRTSLDVLLTTASIFHLCCISLDRYY
AICCQPLVYRNKMTPLRIALMLGGCWVIPTFISFLPIMQGWNNIGIIDLIEKRKFNQNSN
STYCVFMVNKPYAITCSVVAFYIPFLLMVLAYYRIYVTAKEHAHQIQMLQRAGASSESRP
QSADQHSTHRMRTETKAAKTLCIIMGCFCLCWAPFFVTNIVDPFIDYTVPGQVWTAFLWL
GYINSGLNPFLYAFLNKSFRRAFLIILCCDDERYRRPSILGQTVPCSTTTINGSTHVLRD
AVECGGQWESQCHPPATSPLVAAQPSDT
Target 1 Number of Residues 394
Target 1 Molecular Weight 43762
Target 1 Theoretical pI 7.82
Target 1 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
adrenoceptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in adrenoceptor activity
Target 1 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
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 20-40
  • 59-79
  • 94-116
  • 138-158
  • 193-213
  • 261-281
  • 295-315
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 2661757 Link Image
Target 1 UniProtKB/Swiss-Prot ID Q13639 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name 5HT4R_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >1167 bp 
ATGGACAAACTTGATGCTAATGTGAGTTCTGAGGAGGGTTTCGGGTCAGTGGAGAAGGTG
GTGCTGCTCACGTTTCTCTCGACGGTTATCCTGATGGCCATCTTGGGGAACCTGCTGGTG
ATGGTGGCTGTGTGCTGGGACAGGCAGCTCAGGAAAATAAAAACAAATTATTTCATTGTA
TCTCTTGCTTTTGCGGATCTGCTGGTTTCGGTGCTGGTGATGCCCTTTGGTGCCATTGAG
CTGGTTCAAGACATCTGGATTTATGGGGAGGTGTTTTGTCTTGTTCGGACATCTCTGGAC
GTCCTGCTCACAACGGCATCGATTTTTCACCTGTGCTGCATTTCTCTGGATAGGTATTAC
GCCATCTGCTGCCAGCCTTTGGTCTATAGGAACAAGATGACCCCTCTGCGCATCGCATTA
ATGCTGGGAGGCTGCTGGGTCATCCCCACGTTTATTTCTTTTCTCCCTATAATGCAAGGC
TGGAATAACATTGGCATAATTGATTTGATAGAAAAGAGGAAGTTCAACCAGAACTCTAAC
TCTACGTACTGTGTCTTCATGGTCAACAAGCCCTACGCCATCACCTGCTCTGTGGTGGCC
TTCTACATCCCATTTCTCCTCATGGTGCTGGCCTATTACCGCATCTATGTCACAGCTAAG
GAGCATGCCCATCAGATCCAGATGTTACAACGGGCAGGAGCCTCCTCCGAGAGCAGGCCT
CAGTCGGCAGACCAGCATAGCACTCATCGCATGAGGACAGAGACCAAAGCAGCCAAGACC
CTGTGCATCATCATGGGTTGCTTCTGCCTCTGCTGGGCACCATTCTTTGTCACCAATATT
GTGGATCCTTTCATAGACTACACTGTCCCTGGGCAGGTGTGGACTGCTTTCCTCTGGCTC
GGCTATATCAATTCCGGGTTGAACCCTTTTCTCTACGCCTTCTTGAATAAGTCTTTTAGA
CGTGCCTTCCTCATCATCCTCTGCTGTGATGATGAGCGCTACCGAAGACCTTCCATTCTG
GGCCAGACTGTCCCTTGTTCAACCACAACCATTAATGGATCCACACATGTACTAAGGGAT
GCAGTGGAGTGTGGTGGCCAGTGGGAGAGTCAGTGTCACCCGCCAGCAACTTCTCCTTTG
GTGGCTGCTCAGCCCAGTGACACTTAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID HTR4 Link Image
Target 1 GenAtlas ID HTR4 Link Image
Target 1 HGNC ID HGNC:5299 Link Image
Target 1 Chromosome Location 5
Target 1 Locus 5q31-q33
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. 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 Link Image]
  2. 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 Link Image]
  3. 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 Link Image]
  4. 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 Link Image]
  5. 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 Link Image]
Target 1 Drug References
  1. Crema F, Modini C, Croci T, Langlois M, de Ponti F: Intestinal prokinesia by two esters of 4-amino-5-chloro-2- methoxybenzoic acid: involvement of 5-hydroxytryptamine-4 receptors and dissociation from cardiac effects in vivo. J Pharmacol Exp Ther. 1999 Mar;288(3):1045-52. [PubMed Link Image]
  2. Nagakura Y, Akuzawa S, Miyata K, Kamato T, Suzuki T, Ito H, Yamaguchi T: Pharmacological properties of a novel gastrointestinal prokinetic benzamide selective for human 5-HT4 receptor versus human 5-HT3 receptor. Pharmacol Res. 1999 May;39(5):375-82. [PubMed Link Image]
  3. Rahme MM, Cotter B, Leistad E, Wadhwa MK, Mohabir R, Ford AP, Eglen RM, Feld GK: Electrophysiological and antiarrhythmic effects of the atrial selective 5-HT(4) receptor antagonist RS-100302 in experimental atrial flutter and fibrillation. Circulation. 1999 Nov 9;100(19):2010-7. [PubMed Link Image]
  4. Bharucha AE, Camilleri M, Haydock S, Ferber I, Burton D, Cooper S, Tompson D, Fitzpatrick K, Higgins R, Zinsmeister AR: Effects of a serotonin 5-HT(4) receptor antagonist SB-207266 on gastrointestinal motor and sensory function in humans. Gut. 2000 Nov;47(5):667-74. [PubMed Link Image]
  5. Bach T, Syversveen T, Kvingedal AM, Krobert KA, Brattelid T, Kaumann AJ, Levy FO: 5HT4(a) and 5-HT4(b) receptors have nearly identical pharmacology and are both expressed in human atrium and ventricle. Naunyn Schmiedebergs Arch Pharmacol. 2001 Feb;363(2):146-60. [PubMed Link Image]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 101
Target 2 Name Potassium voltage-gated channel subfamily H member 2
Target 2 Synonyms
  1. Eag-related protein 1
  2. Erg1
  3. Ether-a-go-go-related gene potassium channel 1
  4. Ether-a-go-go-related protein 1
  5. H-ERG
  6. Voltage-gated potassium channel subunit Kv11.1
  7. eag homolog
Target 2 Gene Name KCNH2
Target 2 Protein Sequence >Potassium voltage-gated channel subfamily H member 2 
MPVRRGHVAPQNTFLDTIIRKFEGQSRKFIIANARVENCAVIYCNDGFCELCGYSRAEVM
QRPCTCDFLHGPRTQRRAAAQIAQALLGAEERKVEIAFYRKDGSCFLCLVDVVPVKNEDG
AVIMFILNFEVVMEKDMVGSPAHDTNHRGPPTSWLAPGRAKTFRLKLPALLALTARESSV
RSGGAGGAGAPGAVVVDVDLTPAAPSSESLALDEVTAMDNHVAGLGPAEERRALVGPGSP
PRSAPGQLPSPRAHSLNPDASGSSCSLARTRSRESCASVRRASSADDIEAMRAGVLPPPP
RHASTGAMHPLRSGLLNSTSDSDLVRYRTISKIPQITLNFVDLKGDPFLASPTSDREIIA
PKIKERTHNVTEKVTQVLSLGADVLPEYKLQAPRIHRWTILHYSPFKAVWDWLILLLVIY
TAVFTPYSAAFLLKETEEGPPATECGYACQPLAVVDLIVDIMFIVDILINFRTTYVNANE
EVVSHPGRIAVHYFKGWFLIDMVAAIPFDLLIFGSGSEELIGLLKTARLLRLVRVARKLD
RYSEYGAAVLFLLMCTFALIAHWLACIWYAIGNMEQPHMDSRIGWLHNLGDQIGKPYNSS
GLGGPSIKDKYVTALYFTFSSLTSVGFGNVSPNTNSEKIFSICVMLIGSLMYASIFGNVS
AIIQRLYSGTARYHTQMLRVREFIRFHQIPNPLRQRLEEYFQHAWSYTNGIDMNAVLKGF
PECLQADICLHLNRSLLQHCKPFRGATKGCLRALAMKFKTTHAPPGDTLVHAGDLLTALY
FISRGSIEILRGDVVVAILGKNDIFGEPLNLYARPGKSNGDVRALTYCDLHKIHRDDLLE
VLDMYPEFSDHFWSSLEITFNLRDTNMIPGSPGSTELEGGFSRQRKRKLSFRRRTDKDTE
QPGEVSALGPGRAGAGPSSRGRPGGPWGESPSSGPSSPESSEDEGPGRSSSPLRLVPFSS
PRPPGEPPGGEPLMEDCEKSSDTCNPLSGAFSGVSNIFSFWGDSRGRQYQELPRCPAPTP
SLLNIPLSSPGRRPRGDVESRLDALQRQLNRLETRLSADMATVLQLLQRQMTLVPPAYSA
VTTPGPGPTSTSPLLPVSPLPTLTLDSLSQVSQFMACEELPPGAPELPQEGPTRRLSLPG
QLGALTSQPLHRHGSDPGS
Target 2 Number of Residues 1178
Target 2 Molecular Weight 126656
Target 2 Theoretical pI 7.97
Target 2 GO Classification
Function
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
protein kinase activity
protein histidine kinase activity
two-component sensor molecule activity
signal transducer activity
transporter activity
ion transporter activity
ion channel activity
voltage-gated ion channel activity
voltage-gated potassium channel activity
Process
two-component signal transduction system (phosphorelay)
cellular process
cell communication
signal transduction
regulation of biological process
regulation of physiological process
regulation of metabolism
regulation of cellular metabolism
regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism
regulation of transcription
regulation of transcription, DNA-dependent
physiological process
cellular physiological process
transport
ion transport
cation transport
monovalent inorganic cation transport
potassium ion transport
Component
cell
membrane
Target 2 General Function Voltage-gated signal transduction
Target 2 Specific Function Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 404-424
  • 451-471
  • 496-516
  • 521-541
  • 548-568
  • 639-659
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 487738 Link Image
Target 2 UniProtKB/Swiss-Prot ID Q12809 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name KCNH2_HUMAN Link Image
Target 2 PDB ID 1BYW Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >3480 bp 
ATGCCGGTGCGGAGGGGCCACGTCGCGCCGCAGAACACCTTCCTGGACACCATCATCCGC
AAGTTTGAGGGCCAGAGCCGTAAGTTCATCATCGCCAACGCTCGGGTGGAGAACTGCGCC
GTCATCTACTGCAACGACGGCTTCTGCGAGCTGTGCGGCTACTCGCGGGCCGAGGTGATG
CAGCGACCCTGCACCTGCGACTTCCTGCACGGGCCGCGCACGCAGCGCCGCGCTGCCGCG
CAGATCGCGCAGGCACTGCTGGGCGCCGAGGAGCGCAAAGTGGAAATCGCCTTCTACCGG
AAAGATGGGAGCTGCTTCCTATGTCTGGTGGATGTGGTGCCCGTGAAGAACGAGGATGGG
GCTGTCATCATGTTCATCCTCAATTTCGAGGTGGTGATGGAGAAGGACATGGTGGGGTCC
CCGGCTCATGACACCAACCACCGGGGCCCCCCCACCAGCTGGCTGGCCCCAGGCCGCGCC
AAGACCTTCCGCCTGAAGCTGCCCGCGCTGCTGGCGCTGACGGCCCGGGAGTCGTCGGTG
CGGTCGGGCGGCGCGGGCGGCGCGGGCGCCCCGGGGGCCGTGGTGGTGGACGTGGACCTG
ACGCCCGCGGCACCCAGCAGCGAGTCGCTGGCCCTGGACGAAGTGACAGCCATGGACAAC
CACGTGGCAGGGCTCGGGCCCGCGGAGGAGCGGCGTGCGCTGGTGGGTCCCGGCTCTCCG
CCCCGCAGCGCGCCCGGCCAGCTCCCATCGCCCCGGGCGCACAGCCTCAACCCCGACGCC
TCGGGCTCCAGCTGCAGCCTGGCCCGGACGCGCTCCCGAGAAAGCTGCGCCAGCGTGCGC
CGCGCCTCGTCGGCCGACGACATCGAGGCCATGCGCGCCGGGGTGCTGCCCCCGCCACCG
CGCCACGCCAGCACCGGGGCCATGCACCCACTGCGCAGCGGCTTGCTCAACTCCACCTCG
GACTCCGACCTCGTGCGCTACCGCACCATTAGCAAGATTCCCCAAATCACCCTCAACTTT
GTGGACCTCAAGGGCGACCCCTTCTTGGCTTCGCCCACCAGTGACCGTGAGATCATAGCA
CCTAAGATAAAGGAGCGAACCCACAATGTCACTGAGAAGGTCACCCAGGTCCTGTCCCTG
GGCGCCGACGTGCTGCCTGAGTACAAGCTGCAGGCACCGCGCATCCACCGCTGGACCATC
CTGCATTACAGCCCCTTCAAGGCCGTGTGGGACTGGCTCATCCTGCTGCTGGTCATCTAC
ACGGCTGTCTTCACACCCTACTCGGCTGCCTTCCTGCTGAAGGAGACGGAAGAAGGCCCG
CCTGCTACCGAGTGTGGCTACGCCTGCCAGCCGCTGGCTGTGGTGGACCTCATCGTGGAC
ATCATGTTCATTGTGGACATCCTCATCAACTTCCGCACCACCTACGTCAATGCCAACGAG
GAGGTGGTCAGCCACCCCGGCCGCATCGCCGTCCACTACTTCAAGGGCTGGTTCCTCATC
GACATGGTGGCCGCCATCCCCTTCGACCTGCTCATCTTCGGCTCTGGCTCTGAGGAGCTG
ATCGGGCTGCTGAAGACTGCGCGGCTGCTGCGGCTGGTGCGCGTGGCGCGGAAGCTGGAT
CGCTACTCAGAGTACGGCGCGGCCGTGCTGTTCTTGCTCATGTGCACCTTTGCGCTCATC
GCGCACTGGCTAGCCTGCATCTGGTACGCCATCGGCAACATGGAGCAGCCACACATGGAC
TCACGCATCGGCTGGCTGCACAACCTGGGCGACCAGATAGGCAAACCCTACAACAGCAGC
GGCCTGGGCGGCCCCTCCATCAAGGACAAGTATGTGACGGCGCTCTACTTCACCTTCAGC
AGCCTCACCAGTGTGGGCTTCGGCAACGTCTCTCCCAACACCAACTCAGAGAAGATCTTC
TCCATCTGCGTCATGCTCATTGGCTCCCTCATGTATGCTAGCATCTTCGGCAACGTGTCG
GCCATCATCCAGCGGCTGTACTCGGGCACAGCCCGCTACCACACACAGATGCTGCGGGTG
CGGGAGTTCATCCGCTTCCACCAGATCCCCAATCCCCTGCGCCAGCGCCTCGAGGAGTAC
TTCCAGCACGCCTGGTCCTACACCAACGGCATCGACATGAACGCGGTGCTGAAGGGCTTC
CCTGAGTGCCTGCAGGCTGACATCTGCCTGCACCTGAACCGCTCACTGCTGCAGCACTGC
AAACCCTTCCGAGGGGCCACCAAGGGCTGCCTTCGGGCCCTGGCCATGAAGTTCAAGACC
ACACATGCACCGCCAGGGGACACACTGGTGCATGCTGGGGACCTGCTCACCGCCCTGTAC
TTCATCTCCCGGGGCTCCATCGAGATCCTGCGGGGCGACGTCGTCGTGGCCATCCTGGGG
AAGAATGACATCTTTGGGGAGCCTCTGAACCTGTATGCAAGGCCTGGCAAGTCGAACGGG
GATGTGCGGGCCCTCACCTACTGTGACCTACACAAGATCCATCGGGACGACCTGCTGGAG
GTGCTGGACATGTACCCTGAGTTCTCCGACCACTTCTGGTCCAGCCTGGAGATCACCTTC
AACCTGCGAGATACCAACATGATCCCGGGCTCCCCCGGCAGTACGGAGTTAGAGGGTGGC
TTCAGTCGGCAACGCAAGCGCAAGTTGTCCTTCCGCAGGCGCACGGACAAGGACACGGAG
CAGCCAGGGGAGGTGTCGGCCTTGGGGCCGGGCCGGGCGGGGGCAGGGCCGAGTAGCCGG
GGCCGGCCGGGGGGGCCGTGGGGGGAGAGCCCGTCCAGTGGCCCCTCCAGCCCTGAGAGC
AGTGAGGATGAGGGCCCAGGCCGCAGCTCCAGCCCCCTCCGCCTGGTGCCCTTCTCCAGC
CCCAGGCCCCCCGGAGAGCCGCCGGGTGGGGAGCCCCTGATGGAGGACTGCGAGAAGAGC
AGCGACACTTGCAACCCCCTGTCAGGCGCCTTCTCAGGAGTGTCCAACATTTTCAGCTTC
TGGGGGGACAGTCGGGGCCGCCAGTACCAGGAGCTCCCTCGATGCCCCGCCCCCACCCCC
AGCCTCCTCAACATCCCCCTCTCCAGCCCGGGTCGGCGGCCCCGGGGCGACGTGGAGAGC
AGGCTGGATGCCCTCCAGCGCCAGCTCAACAGGCTGGAGACCCGGCTGAGTGCAGACATG
GCCACTGTCCTGCAGCTGCTACAGAGGCAGATGACGCTGGTCCCGCCCGCCTACAGTGCT
GTGACCACCCCGGGGCCTGGCCCCACTTCCACATCCCCGCTGTTGCCCGTCAGCCCCCTC
CCCACCCTCACCTTGGACTCGCTTTCTCAGGTTTCCCAGTTCATGGCGTGTGAGGAGCTG
CCCCCGGGGGCCCCAGAGCTTCCCCAAGAAGGCCCCACACGACGCCTCTCCCTACCGGGC
CAGCTGGGGGCCCTCACCTCCCAGCCCCTGCACAGACACGGCTCGGACCCGGGCAGTTAG
Target 2 GenBank Gene ID
Target 2 GeneCard ID KCNH2 Link Image
Target 2 GenAtlas ID KCNH2 Link Image
Target 2 HGNC ID HGNC:6251 Link Image
Target 2 Chromosome Location 7
Target 2 Locus 7q35-q36
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Berthet M, Denjoy I, Donger C, Demay L, Hammoude H, Klug D, Schulze-Bahr E, Richard P, Funke H, Schwartz K, Coumel P, Hainque B, Guicheney P: C-terminal HERG mutations: the role of hypokalemia and a KCNQ1-associated mutation in cardiac event occurrence. Circulation. 1999 Mar 23;99(11):1464-70. [PubMed Link Image]
  2. Chen J, Zou A, Splawski I, Keating MT, Sanguinetti MC: Long QT syndrome-associated mutations in the Per-Arnt-Sim (PAS) domain of HERG potassium channels accelerate channel deactivation. J Biol Chem. 1999 Apr 9;274(15):10113-8. [PubMed Link Image]
  3. Abbott GW, Sesti F, Splawski I, Buck ME, Lehmann MH, Timothy KW, Keating MT, Goldstein SA: MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell. 1999 Apr 16;97(2):175-87. [PubMed Link Image]
  4. Jongbloed RJ, Wilde AA, Geelen JL, Doevendans P, Schaap C, Van Langen I, van Tintelen JP, Cobben JM, Beaufort-Krol GC, Geraedts JP, Smeets HJ: Novel KCNQ1 and HERG missense mutations in Dutch long-QT families. Hum Mutat. 1999;13(4):301-10. [PubMed Link Image]
  5. Yoshida H, Horie M, Otani H, Takano M, Tsuji K, Kubota T, Fukunami M, Sasayama S: Characterization of a novel missense mutation in the pore of HERG in a patient with long QT syndrome. J Cardiovasc Electrophysiol. 1999 Sep;10(9):1262-70. [PubMed Link Image]
  6. Larsen LA, Svendsen IH, Jensen AM, Kanters JK, Andersen PS, Moller M, Sorensen SA, Sandoe E, Jacobsen JR, Vuust J, Christiansen M: Long QT syndrome with a high mortality rate caused by a novel G572R missense mutation in KCNH2. Clin Genet. 2000 Feb;57(2):125-30. [PubMed Link Image]
  7. Paulussen A, Yang P, Pangalos M, Verhasselt P, Marrannes R, Verfaille C, Vandenberk I, Crabbe R, Konings F, Luyten W, Armstrong M: Analysis of the human KCNH2(HERG) gene: identification and characterization of a novel mutation Y667X associated with long QT syndrome and a non-pathological 9 bp insertion. Hum Mutat. 2000 May;15(5):483. [PubMed Link Image]
  8. Cui J, Melman Y, Palma E, Fishman GI, McDonald TV: Cyclic AMP regulates the HERG K(+) channel by dual pathways. Curr Biol. 2000 Jun 1;10(11):671-4. [PubMed Link Image]
  9. Laitinen P, Fodstad H, Piippo K, Swan H, Toivonen L, Viitasalo M, Kaprio J, Kontula K: Survey of the coding region of the HERG gene in long QT syndrome reveals six novel mutations and an amino acid polymorphism with possible phenotypic effects. Hum Mutat. 2000 Jun;15(6):580-1. [PubMed Link Image]
  10. Splawski I, Shen J, Timothy KW, Lehmann MH, Priori S, Robinson JL, Moss AJ, Schwartz PJ, Towbin JA, Vincent GM, Keating MT: Spectrum of mutations in long-QT syndrome genes. KVLQT1, HERG, SCN5A, KCNE1, and KCNE2. Circulation. 2000 Sep 5;102(10):1178-85. [PubMed Link Image]
  11. 11374908 Soejima H, Kawamoto S, Akai J, Miyoshi O, Arai Y, Morohka T, Matsuo S, Niikawa N, Kimura A, Okubo K, Mukai T: Isolation of novel heart-specific genes using the BodyMap database. Genomics. 2001 May 15;74(1):115-20.
  12. 12062363 Hayashi K, Shimizu M, Ino H, Yamaguchi M, Mabuchi H, Hoshi N, Higashida H: Characterization of a novel missense mutation E637K in the pore-S6 loop of HERG in a patient with long QT syndrome. Cardiovasc Res. 2002 Apr;54(1):67-76.
  13. 12063277 Gong Q, Anderson CL, January CT, Zhou Z: Role of glycosylation in cell surface expression and stability of HERG potassium channels. Am J Physiol Heart Circ Physiol. 2002 Jul;283(1):H77-84.
  14. 7889573 Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT: A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell. 1995 Mar 10;80(5):795-803.
  15. 8159766 Warmke JW, Ganetzky B: A family of potassium channel genes related to eag in Drosophila and mammals. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3438-42.
  16. 8635257 Benson DW, MacRae CA, Vesely MR, Walsh EP, Seidman JG, Seidman CE, Satler CA: Missense mutation in the pore region of HERG causes familial long QT syndrome. Circulation. 1996 May 15;93(10):1791-5.
  17. 8877771 Dausse E, Berthet M, Denjoy I, Andre-Fouet X, Cruaud C, Bennaceur M, Faure S, Coumel P, Schwartz K, Guicheney P: A mutation in HERG associated with notched T waves in long QT syndrome. J Mol Cell Cardiol. 1996 Aug;28(8):1609-15.
  18. 8914737 Satler CA, Walsh EP, Vesely MR, Plummer MH, Ginsburg GS, Jacob HJ: Novel missense mutation in the cyclic nucleotide-binding domain of HERG causes long QT syndrome. Am J Med Genet. 1996 Oct 2;65(1):27-35.
  19. 9024139 Tanaka T, Nagai R, Tomoike H, Takata S, Yano K, Yabuta K, Haneda N, Nakano O, Shibata A, Sawayama T, Kasai H, Yazaki Y, Nakamura Y: Four novel KVLQT1 and four novel HERG mutations in familial long-QT syndrome. Circulation. 1997 Feb 4;95(3):565-7.
  20. 9230439 McDonald TV, Yu Z, Ming Z, Palma E, Meyers MB, Wang KW, Goldstein SA, Fishman GI: A minK-HERG complex regulates the cardiac potassium current I(Kr). Nature. 1997 Jul 17;388(6639):289-92.
  21. 9351446 Lees-Miller JP, Kondo C, Wang L, Duff HJ: Electrophysiological characterization of an alternatively processed ERG K+ channel in mouse and human hearts. Circ Res. 1997 Nov;81(5):719-26.
  22. 9351462 London B, Trudeau MC, Newton KP, Beyer AK, Copeland NG, Gilbert DJ, Jenkins NA, Satler CA, Robertson GA: Two isoforms of the mouse ether-a-go-go-related gene coassemble to form channels with properties similar to the rapidly activating component of the cardiac delayed rectifier K+ current. Circ Res. 1997 Nov;81(5):870-8.
  23. 9452080 Akimoto K, Furutani M, Imamura S, Furutani Y, Kasanuki H, Takao A, Momma K, Matsuoka R: Novel missense mutation (G601S) of HERG in a Japanese long QT syndrome family. Hum Mutat. 1998;Suppl 1:S184-6.
  24. 9544837 Satler CA, Vesely MR, Duggal P, Ginsburg GS, Beggs AH: Multiple different missense mutations in the pore region of HERG in patients with long QT syndrome. Hum Genet. 1998 Mar;102(3):265-72.
  25. 9600240 Itoh T, Tanaka T, Nagai R, Kamiya T, Sawayama T, Nakayama T, Tomoike H, Sakurada H, Yazaki Y, Nakamura Y: Genomic organization and mutational analysis of HERG, a gene responsible for familial long QT syndrome. Hum Genet. 1998 Apr;102(4):435-9.
  26. 9693036 Splawski I, Shen J, Timothy KW, Vincent GM, Lehmann MH, Keating MT: Genomic structure of three long QT syndrome genes: KVLQT1, HERG, and KCNE1. Genomics. 1998 Jul 1;51(1):86-97.
  27. 9765245 Kupershmidt S, Snyders DJ, Raes A, Roden DM: A K+ channel splice variant common in human heart lacks a C-terminal domain required for expression of rapidly activating delayed rectifier current. J Biol Chem. 1998 Oct 16;273(42):27231-5.
  28. 9845367 Morais Cabral JH, Lee A, Cohen SL, Chait BT, Li M, Mackinnon R: Crystal structure and functional analysis of the HERG potassium channel N terminus: a eukaryotic PAS domain. Cell. 1998 Nov 25;95(5):649-55.
Target 2 Drug References
  1. Walker BD, Singleton CB, Bursill JA, Wyse KR, Valenzuela SM, Qiu MR, Breit SN, Campbell TJ: Inhibition of the human ether-a-go-go-related gene (HERG) potassium channel by cisapride: affinity for open and inactivated states. Br J Pharmacol. 1999 Sep;128(2):444-50. [PubMed Link Image]
  2. Chen J, Seebohm G, Sanguinetti MC: Position of aromatic residues in the S6 domain, not inactivation, dictates cisapride sensitivity of HERG and eag potassium channels. Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12461-6. Epub 2002 Sep 3. [PubMed Link Image]
  3. Lin J, Guo J, Gang H, Wojciechowski P, Wigle JT, Zhang S: Intracellular K+ is required for the inactivation-induced high-affinity binding of cisapride to HERG channels. Mol Pharmacol. 2005 Sep;68(3):855-65. Epub 2005 Jun 20. [PubMed Link Image]
  4. Perrio M, Voss S, Shakir SA: Application of the bradford hill criteria to assess the causality of cisapride-induced arrhythmia: a model for assessing causal association in pharmacovigilance. Drug Saf. 2007;30(4):333-46. [PubMed Link Image]
  5. Mohammad S, Zhou Z, Gong Q, January CT: Blockage of the HERG human cardiac K+ channel by the gastrointestinal prokinetic agent cisapride. Am J Physiol. 1997 Nov;273(5 Pt 2):H2534-8. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 341
Target 3 Name 5-hydroxytryptamine 3 receptor
Target 3 Synonyms
  1. 5-HT-3
  2. 5-HT3R
  3. 5-hydroxytryptamine 3 receptor precursor
  4. Serotonin-gated ion channel receptor
Target 3 Gene Name HTR3A
Target 3 Protein Sequence >5-hydroxytryptamine 3 receptor precursor 
MLLWVQQALLALLLPTLLAQGEARRSRNTTRPALLRLSDYLLTNYRKGVRPVRDWRKPTT
VSIDVIVYAILNVDEKNQVLTTYIWYRQYWTDEFLQWNPEDFDNITKLSIPTDSIWVPDI
LINEFVDVGKSPNIPYVYIRHQGEVQNYKPLQVVTACSLDIYNFPFDVQNCSLTFTSWLH
TIQDINISLWRLPEKVKSDRSVFMNQGEWELLGVLPYFREFSMESSNYYAEMKFYVVIRR
RPLFYVVSLLLPSIFLMVMDIVGFYLPPNSGERVSFKITLLLGYSVFLIIVSDTLPATAI
GTPLIGVYFVVCMALLVISLAETIFIVRLVHKQDLQQPVPAWLRHLVLERIAWLLCLREQ
STSQRPPATSQATKTDDCSAMGNHCSHMGGPQDFEKSPRDRCSPPPPPREASLAVCGLLQ
ELSSIRQFLEKRDEIREVARDWLRVGSVLDKLLFHIYLLAVLAYSITLVMLWSIWQYA
Target 3 Number of Residues 485
Target 3 Molecular Weight 55281
Target 3 Theoretical pI 7.43
Target 3 GO Classification
Function
signal transducer activity
receptor activity
neurotransmitter receptor activity
transporter activity
ion transporter activity
ion channel activity
ligand-gated ion channel activity
extracellular ligand-gated ion channel activity
Process
physiological process
cellular physiological process
transport
ion transport
Component
postsynaptic membrane
cell
membrane
intrinsic to membrane
integral to membrane
Target 3 General Function Involved in extracellular ligand-gated ion channel activity
Target 3 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. This receptor is a ligand-gated ion channel, which when activated causes fast, depolarizing responses in neurons. It is a cation-specific, but otherwise relatively nonselective, ion channel
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-23
Target 3 Transmembrane Regions
  • 242-268
  • 274-292
  • 303-321
  • 456-475
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 681914 Link Image
Target 3 UniProtKB/Swiss-Prot ID P46098 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name 5HT3R_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 3 Gene Sequence >1437 bp 
ATGCTGCTGTGGGTCCAGCAGGCGCTGCTCGCCTTGCTCCTCCCCACACTCCTGGCACAG
GGAGAAGCCAGGAGGAGCCGAAACACCACCAGGCCCGCTCTGCTGAGGCTGTCGGATTAC
CTTTTGACCAACTACAGGAAGGGTGTGCGCCCCGTGAGGGACTGGAGGAAGCCAACCACC
GTATCCATTGACGTCATTGTCTATGCCATCCTCAACGTGGATGAGAAGAATCAGGTGCTG
ACCACCTACATCTGGTACCGGCAGTACTGGACTGATGAGTTTCTCCAGTGGAACCCTGAG
GACTTTGACAACATCACCAAGTTGTCCATCCCCACGGACAGCATCTGGGTCCCGGACATT
CTCATCAATGAGTTCGTGGATGTGGGGAAGTCTCCAAATATCCCGTACGTGTATATTCGG
CATCAAGGCGAAGTTCAGAACTACAAGCCCCTTCAGGTGGTGACTGCCTGTAGCCTCGAC
ATCTACAACTTCCCCTTCGATGTCCAGAACTGCTCGCTGACCTTCACCAGTTGGCTGCAC
ACCATCCAGGACATCAACATCTCTTTGTGGCGCTTGCCAGAAAAGGTGAAATCCGACAGG
AGTGTCTTCATGAACCAGGGAGAGTGGGAGTTGCTGGGGGTGCTGCCCTACTTTCGGGAG
TTCAGCATGGAAAGCAGTAACTACTATGCAGAAATGAAGTTCTATGTGGTCATCCGCCGG
CGGCCCCTCTTCTATGTGGTCAGCCTGCTACTGCCCAGCATCTTCCTCATGGTCATGGAC
ATCGTGGGCTTCTACCTGCCCCCCAACAGTGGCGAGAGGGTCTCTTTCAAGATTACACTC
CTCCTGGGCTACTCGGTCTTCCTGATCATCGTTTCTGACACGCTGCCGGCCACTGCCATC
GGCACTCCTCTCATTGGTGTCTACTTTGTGGTGTGCATGGCTCTGCTGGTGATAAGTTTG
GCCGAGACCATCTTCATTGTGCGGCTGGTGCACAAGCAAGACCTGCAGCAGCCCGTGCCT
GCTTGGCTGCGTCACCTGGTTCTGGAGAGAATCGCCTGGCTACTTTGCCTGAGGGAGCAG
TCAACTTCCCAGAGGCCCCCAGCCACCTCCCAAGCCACCAAGACTGATGACTGCTCAGCC
ATGGGAAACCACTGCAGCCACATGGGAGGACCCCAGGACTTCGAGAAGAGCCCGAGGGAC
AGATGTAGCCCTCCCCCACCACCTCGGGAGGCCTCGCTGGCGGTGTGTGGGCTGCTGCAG
GAGCTGTCCTCCATCCGGCAATTCCTGGAAAAGCGGGATGAGATCCGAGAGGTGGCCCGA
GACTGGCTGCGCGTGGGCTCCGTGCTGGACAAGCTGCTATTCCACATTTACCTGCTAGCG
GTGCTGGCCTACAGCATCACCCTGGTTATGCTCTGGTCCATCTGGCAGTACGCTTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID HTR3A Link Image
Target 3 GenAtlas ID HTR3A Link Image
Target 3 HGNC ID HGNC:5297 Link Image
Target 3 Chromosome Location 11
Target 3 Locus 11q23.1
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Bruss M, Eucker T, Gothert M, Bonisch H: Exon-intron organization of the human 5-HT3A receptor gene. Neuropharmacology. 2000 Jan 4;39(2):308-15. [PubMed Link Image]
  2. Miyake A, Mochizuki S, Takemoto Y, Akuzawa S: Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species. Mol Pharmacol. 1995 Sep;48(3):407-16. [PubMed Link Image]
  3. Belelli D, Balcarek JM, Hope AG, Peters JA, Lambert JJ, Blackburn TP: Cloning and functional expression of a human 5-hydroxytryptamine type 3AS receptor subunit. Mol Pharmacol. 1995 Dec;48(6):1054-62. [PubMed Link Image]
  4. Bruss M, Gothert M, Hayer M, Bonisch H: Molecular cloning of alternatively spliced human 5-HT3 receptor cDNAs. Ann N Y Acad Sci. 1998 Dec 15;861:234-5. [PubMed Link Image]
Target 3 Drug References
  1. Nagakura Y, Akuzawa S, Miyata K, Kamato T, Suzuki T, Ito H, Yamaguchi T: Pharmacological properties of a novel gastrointestinal prokinetic benzamide selective for human 5-HT4 receptor versus human 5-HT3 receptor. Pharmacol Res. 1999 May;39(5):375-82. [PubMed Link Image]
  2. Talley NJ: Review article: 5-hydroxytryptamine agonists and antagonists in the modulation of gastrointestinal motility and sensation: clinical implications. Aliment Pharmacol Ther. 1992 Jun;6(3):273-89. [PubMed Link Image]
  3. de Ridder WJ, Schuurkes JA: Cisapride and 5-hydroxytryptamine enhance motility in the canine antrum via separate pathways, not involving 5-hydroxytryptamine1,2,3,4 receptors. J Pharmacol Exp Ther. 1993 Jan;264(1):79-88. [PubMed Link Image]
  4. Haga N, Suzuki H, Shiba Y, Mochiki E, Mizumoto A, Itoh Z: Effect of TKS159, a novel 5-hydroxytryptamine4 agonist, on gastric contractile activity in conscious dogs. Neurogastroenterol Motil. 1998 Aug;10(4):295-303. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 502
Target 4 Name 5-hydroxytryptamine 2A receptor
Target 4 Synonyms
  1. 5- HT-2
  2. 5-HT-2A
  3. Serotonin receptor 2A
Target 4 Gene Name HTR2A
Target 4 Protein Sequence >5-hydroxytryptamine 2A receptor 
MDILCEENTSLSSTTNSLMQLNDDTRLYSNDFNSGEANTSDAFNWTVDSENRTNLSCEGC
LSPSCLSLLHLQEKNWSALLTAVVIILTIAGNILVIMAVSLEKKLQNATNYFLMSLAIAD
MLLGFLVMPVSMLTILYGYRWPLPSKLCAVWIYLDVLFSTASIMHLCAISLDRYVAIQNP
IHHSRFNSRTKAFLKIIAVWTISVGISMPIPVFGLQDDSKVFKEGSCLLADDNFVLIGSF
VSFFIPLTIMVITYFLTIKSLQKEATLCVSDLGTRAKLASFSFLPQSSLSSEKLFQRSIH
REPGSYTGRRTMQSISNEQKACKVLGIVFFLFVVMWCPFFITNIMAVICKESCNEDVIGA
LLNVFVWIGYLSSAVNPLVYTLFNKTYRSAFSRYIQCQYKENKKPLQLILVNTIPALAYK
SSQLQMGQKKNSKQDAKTTDNDCSMVALGKQHSEEASKDNSDGVNEKVSCV
Target 4 Number of Residues 478
Target 4 Molecular Weight 52604
Target 4 Theoretical pI 7.72
Target 4 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 4 General Function Involved in rhodopsin-like receptor activity
Target 4 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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • 76-99
  • 111-132
  • 148-171
  • 192-215
  • 234-254
  • 325-346
  • 363-384
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 36431 Link Image
Target 4 UniProtKB/Swiss-Prot ID P28223 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name 5HT2A_HUMAN Link Image
Target 4 PDB ID Not Available
Target 4 Cellular Location
  • Cell membrane
  • multi-pass membrane protein. Localizes to the post-synaptic thickening of axo-dendrit
Target 4 Gene Sequence >1416 bp 
ATGGATATTCTTTGTGAAGAAAATACTTCTTTGAGCTCAACTACGAACTCCCTAATGCAA
TTAAATGATGACACCAGGCTCTACAGTAATGACTTTAACTCTGGAGAAGCTAACACTTCT
GATGCATTTAACTGGACAGTCGACTCTGAAAATCGAACCAACCTTTCCTGTGAAGGGTGC
CTCTCACCGTCGTGTCTCTCCTTACTTCATCTCCAGGAAAAAAACTGGTCTGCTTTACTG
ACAGCCGTAGTGATTATTCTAACTATTGCTGGAAACATACTCGTCATCATGGCAGTGTCC
CTAGAGAAAAAGCTGCAGAATGCCACCAACTATTTCCTGATGTCACTTGCCATAGCTGAT
ATGCTGCTGGGTTTCCTTGTCATGCCCGTGTCCATGTTAACCATCCTGTATGGGTACCGG
TGGCCTCTGCCGAGCAAGCTTTGTGCAGTCTGGATTTACCTGGACGTGCTCTTCTCCACG
GCCTCCATCATGCACCTCTGCGCCATCTCGCTGGACCGCTACGTCGCCATCCAGAATCCC
ATCCACCACAGCCGCTTCAACTCCAGAACTAAGGCATTTCTGAAAATCATTGCTGTTTGG
ACCATATCAGTAGGTATATCCATGCCAATACCAGTCTTTGGGCTACAGGACGATTCGAAG
GTCTTTAAGGAGGGGAGTTGCTTACTCGCCGATGATAACTTTGTCCTGATCGGCTCTTTT
GTGTCATTTTTCATTCCCTTAACCATCATGGTGATCACCTACTTTCTAACTATCAAGTCA
CTCCAGAAAGAAGCTACTTTGTGTGTAAGTGATCTTGGCACACGGGCCAAATTAGCTTCT
TTCAGCTTCCTCCCTCAGAGTTCTTTGTCTTCAGAAAAGCTCTTCCAGCGGTCGATCCAT
AGGGAGCCAGGGTCCTACACAGGCAGGAGGACTATGCAGTCCATCAGCAATGAGCAAAAG
GCATGCAAGGTGCTGGGCATCGTCTTCTTCCTGTTTGTGGTGATGTGGTGCCCTTTCTTC
ATCACAAACATCATGGCCGTCATCTGCAAAGAGTCCTGCAATGAGGATGTCATTGGGGCC
CTGCTCAATGTGTTTGTTTGGATCGGTTATCTCTCTTCAGCAGTCAACCCACTAGTCTAC
ACACTGTTCAACAAGACCTATAGGTCAGCCTTTTCACGGTATATTCAGTGTCAGTACAAG
GAAAACAAAAAACCATTGCAGTTAATTTTAGTGAACACAATACCGGCTTTGGCCTACAAG
TCTAGCCAACTTCAAATGGGACAAAAAAAGAATTCAAAGCAAGATGCCAAGACAACAGAT
AATGACTGCTCAATGGTTGCTCTAGGAAAGCAGCATTCTGAAGAGGCTTCTAAAGACAAT
AGCGACGGAGTGAATGAAAAGGTGAGCTGTGTGTGA
Target 4 GenBank Gene ID
Target 4 GeneCard ID HTR2A Link Image
Target 4 GenAtlas ID HTR2A Link Image
Target 4 HGNC ID HGNC:5293 Link Image
Target 4 Chromosome Location 13
Target 4 Locus 13q14-q21
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Marshall SE, Bird TG, Hart K, Welsh KI: Unified approach to the analysis of genetic variation in serotonergic pathways. Am J Med Genet. 1999 Dec 15;88(6):621-7. [PubMed Link Image]
  3. Becamel C, Figge A, Poliak S, Dumuis A, Peles E, Bockaert J, Lubbert H, Ullmer C: Interaction of serotonin 5-hydroxytryptamine type 2C receptors with PDZ10 of the multi-PDZ domain protein MUPP1. J Biol Chem. 2001 Apr 20;276(16):12974-82. Epub 2001 Jan 9. [PubMed Link Image]
  4. Chen K, Yang W, Grimsby J, Shih JC: The human 5-HT2 receptor is encoded by a multiple intron-exon gene. Brain Res Mol Brain Res. 1992 Jun;14(1-2):20-6. [PubMed Link Image]
  5. Stam NJ, Van Huizen F, Van Alebeek C, Brands J, Dijkema R, Tonnaer JA, Olijve W: Genomic organization, coding sequence and functional expression of human 5-HT2 and 5-HT1A receptor genes. Eur J Pharmacol. 1992 Oct 1;227(2):153-62. [PubMed Link Image]
  6. Saltzman AG, Morse B, Whitman MM, Ivanshchenko Y, Jaye M, Felder S: Cloning of the human serotonin 5-HT2 and 5-HT1C receptor subtypes. Biochem Biophys Res Commun. 1991 Dec 31;181(3):1469-78. [PubMed Link Image]
  7. Cook EH Jr, Fletcher KE, Wainwright M, Marks N, Yan SY, Leventhal BL: Primary structure of the human platelet serotonin 5-HT2A receptor: identify with frontal cortex serotonin 5-HT2A receptor. J Neurochem. 1994 Aug;63(2):465-9. [PubMed Link Image]
  8. Erdmann J, Shimron-Abarbanell D, Rietschel M, Albus M, Maier W, Korner J, Bondy B, Chen K, Shih JC, Knapp M, Propping P, Nothen MM: Systematic screening for mutations in the human serotonin-2A (5-HT2A) receptor gene: identification of two naturally occurring receptor variants and association analysis in schizophrenia. Hum Genet. 1996 May;97(5):614-9. [PubMed Link Image]
Target 4 Drug References
  1. Nieto JE, Snyder JR, Kollias-Baker C, Stanley S: In vitro effects of 5-hydroxytryptamine and cisapride on the circular smooth muscle of the jejunum of horses. Am J Vet Res. 2000 Dec;61(12):1561-5. [PubMed Link Image]
  2. Beubler E, Coupar IM, Hardcastle J, Hardcastle PT: Stimulatory effects of 5-hydroxytryptamine on fluid secretion and transmural potential difference in rat small intestine are mediated by different receptor subtypes. J Pharm Pharmacol. 1990 Jan;42(1):35-9. [PubMed Link Image]
  3. Cushing DJ, Cohen ML: Serotonin-induced contraction in porcine coronary artery: use of ergolines to support vascular 5-hydroxytryptamine2-receptor heterogeneity. J Pharmacol Exp Ther. 1993 Jan;264(1):193-200. [PubMed Link Image]

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.