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Showing drug card for Propafenone (DB01182)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:48:18
Primary Accession Number DB01182
Secondary Accession Number
  • APRD00261
Name Propafenone
Drug Type
  • Approved
  • Small Molecule
Description An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity. The drug is generally well tolerated. [PubChem]
Synonyms
  1. Propafenona [INN-Spanish]
  2. Propafenone HCl
  3. Propafenone hydrochloride
  4. Propafenone-HCl
  5. Propafenonum [INN-Latin]
Brand Names
  1. Rythmol
  2. Rythmol SR
Brand Mixtures Not Available
Chemical IUPAC Name 1-[2-(2-hydroxy-3-propylaminopropoxy)phenyl]-3-phenylpropan-1-one
Chemical Formula C21H27NO3
Chemical Structure Structure
CAS Registry Number 54063-53-5
InChI Identifier InChI=1/C21H27NO3/c1-2-14-22-15-18(23)16-25-21-11-7-6-10-19(21)20(24)13-12-17-8-4-3-5-9-17/h3-11,18,22-23H,2,12-16H2,1H3
InChI Key JWHAUXFOSRPERK-UHFFFAOYAI
KEGG Drug Not Available
KEGG Compound C07381 Link Image
PubChem Compound 4932 Link Image
PubChem Substance 181774 Link Image
ChEBI ID Not Available
PharmGKB ID PA451131 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02243728 Link Image
RxList Link http://www.rxlist.com/cgi/generic3/propafen.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ryt1392.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Propafenone Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 341.4440
Monoisotopic Molecular Weight 341.1991
State Solid
Melting Point Not Available
Experimental Water Solubility Slightly soluble Source: PhysProp
Predicted Water Solubility 7.58e-03 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity 3.2 Source: PhysProp
Predicted LogP 3.10 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -4.65 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 CCCNC[C@@H](O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1
Canonical SMILES CCCNCC(O)COC1=CC=CC=C1C(=O)CCC1=CC=CC=C1
Drug Category
  • Anti-Arrhythmia Agents
ATC Codes
AHFS Codes
  • 24:04.04.12
Indication Used to prolong the time to recurrence of paroxysmal atrial fibrillation/flutter (PAF) associated with disabling symptoms in patients without structural heart disease. Also used for the treatment of life-threatening documented ventricular arrhythmias, such as sustained ventricular tachycardia.
Pharmacology Propafenone is a Class 1C antiarrhythmic drug with local anesthetic effects, and a direct stabilizing action on myocardial membranes. It is used in the treatment of atrial and ventricular arrhythmias. It works by slowing the influx of sodium ions into the cardiac muscle cells, causing a decrease in excitablity of the cells. Propafenone has local anesthetic activity approximately equal to procaine.
Mechanism of Action The electrophysiological effect of propafenone manifests itself in a reduction of upstroke velocity (Phase 0) of the monophasic action potential. In Purkinje fibers, and to a lesser extent myocardial fibers, propafenone reduces the fast inward current carried by sodium ions, which is responsible for the drugs antiarrhythmic actions. Diastolic excitability threshold is increased and effective refractory period prolonged. Propafenone reduces spontaneous automaticity and depresses triggered activity. At very high concentrations in vitro, propafenone can inhibit the slow inward current carried by calcium but this calcium antagonist effect probably does not contribute to antiarrhythmic efficacy.
Absorption Nearly completely absorbed following oral administration (90%). Systemic bioavailability ranges from 5 to 50%, due to significant first-pass metabolism. This wide range in systemic bioavailability is related to two factors: presence of food (food increases bioavailability) and dosage (bioavailability is 3.4% for a 150-mg tablet compared to 10.6% for a 300-mg tablet).
Toxicity Symptoms of propafenone overdose (usually most severe within the first 3 hours) may include convulsions (rarely), heartbeat irregularities, low blood pressure, and sleepiness.
Protein Binding 97%
Biotransformation Metabolized primarily in the liver where it is rapidly and extensively metabolized to two active metabolites, 5-hydroxypropafenone and N-depropylpropafenone. These metabolites have antiarrhythmic activity comparable to propafenone but are present in concentrations less than 25% of propafenone concentrations.
Half Life 2-10 hours
Dosage Forms
Form Route
Tablet Oral
Patient Information Not Available
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acenocoumarol The agent increases the effect of anticoagulant
Aminophylline Propafenone increases the effect of theophylline
Anisindione The agent increases the effect of anticoagulant
Atomoxetine Tje CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
Cisapride Increased risk of cardiotoxicity and arrhytmias
Cyclosporine Propafenone increases the effect and toxicity of cyclosporine
Dicumarol The agent increases the effect of anticoagulant
Digoxin Propafenone increases the effect of digoxin
Dihydroquinidine barbiturate Quinidine increases the effect of propafenone
Duloxetine Possible increase in the levels of this agent when used with duloxetine
Dyphylline Propafenone increases the effect of theophylline
Fluoxetine Fluoxetine increases the effect and toxicity of propafenone
Mesoridazine Increased risk of cardiotoxicity and arrhytmias
Metoprolol Propafenone increases the effect of the beta-blocker
Mexiletine Propafenone increases the effect and toxicity of mexilitine
Oxtriphylline Propafenone increases the effect of theophylline
Paroxetine Fluoxetine increases the effect and toxicity of propafenone
Propranolol Propafenone increases the effect of the beta-blocker
Quinidine Quinidine increases the effect of propafenone
Quinidine barbiturate Quinidine increases the effect of propafenone
Rifabutin Rifampin decreases the effect of propafenone
Rifampin Rifampin decreases the effect of propafenone
Ritonavir Ritonavir increases the effect and toxicity of propafenone
Sertraline Fluoxetine increases the effect and toxicity of propafenone
Terfenadine Increased risk of cardiotoxicity and arrhytmias
Theophylline Propafenone increases the effect of theophylline
Thioridazine Increased risk of cardiotoxicity and arrhytmias
Venlafaxine Propafenone increases the effect and toxicity of venlafaxine
Warfarin The agent increases the effect of anticoagulant
Food Interactions
  • Always take at the same time in regard to meals.
  • Grapefruit and grapefruit juice should be avoided throughout treatment. Grapefruit can increase serum levels of this product.
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
  4. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 1A2 (CYP1A2)
  2. Cytochrome P450 2D6 (CYP2D6)
Targets
  1. Potassium voltage-gated channel subfamily H member 2
  2. Sodium channel protein type 5 subunit alpha
  3. Multidrug resistance protein 1
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 1A2 (CYP1A2)
Enzyme 1 Gene Name CYP1A2
Enzyme 1 SwissProt ID P05177 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >P05177|CP1A2_HUMAN Cytochrome P450 1A2 - Homo sapiens (Human). 
MALSQSVPFSATELLLASAIFCLVFWVLKGLRPRVPKGLKSPPEPWGWPLLGHVLTLGKN
PHLALSRMSQRYGDVLQIRIGSTPVLVLSRLDTIRQALVRQGDDFKGRPDLYTSTLITDG
QSLTFSTDSGPVWAARRRLAQNALNTFSIASDPASSSSCYLEEHVSKEAKALISRLQELM
AGPGHFDPYNQVVVSVANVIGAMCFGQHFPESSDEMLSLVKNTHEFVETASSGNPLDFFP
ILRYLPNPALQRFKAFNQRFLWFLQKTVQEHYQDFDKNSVRDITGALFKHSKKGPRASGN
LIPQEKIVNLVNDIFGAGFDTVTTAISWSLMYLVTKPEIQRKIQKELDTVIGRERRPRLS
DRPQLPYLEAFILETFRHSSFLPFTIPHSTTRDTTLNGFYIPKKCCVFVNQWQVNHDPEL
WEDPSEFRPERFLTADGTAINKPLSEKMMLFGMGKRRCIGEVLAKWEIFLFLAILLQQLE
FSVPPGVKVDLTPIYGLTMKHARCEHVQARRFSIN
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Cytochrome P450 2D6 (CYP2D6)
Enzyme 2 Gene Name CYP2D6
Enzyme 2 SwissProt ID P10635 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P10635|CP2D6_HUMAN Cytochrome P450 2D6 (EC 1.14.14.1) 
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGMTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
Drug Target 1 [top]
Target 1 ID 101
Target 1 Name Potassium voltage-gated channel subfamily H member 2
Target 1 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 1 Gene Name KCNH2
Target 1 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 1 Number of Residues 1178
Target 1 Molecular Weight 126656
Target 1 Theoretical pI 7.97
Target 1 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 1 General Function Voltage-gated signal transduction
Target 1 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 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 404-424
  • 451-471
  • 496-516
  • 521-541
  • 548-568
  • 639-659
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 487738 Link Image
Target 1 UniProtKB/Swiss-Prot ID Q12809 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name KCNH2_HUMAN Link Image
Target 1 PDB ID 1BYW Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 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 1 GenBank Gene ID
Target 1 GeneCard ID KCNH2 Link Image
Target 1 GenAtlas ID KCNH2 Link Image
Target 1 HGNC ID HGNC:6251 Link Image
Target 1 Chromosome Location 7
Target 1 Locus 7q35-q36
Target 1 SNPs SNPJam Report Link Image
Target 1 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 1 Drug References
  1. Mergenthaler J, Haverkamp W, Huttenhofer A, Skryabin BV, Musshoff U, Borggrefe M, Speckmann EJ, Breithardt G, Madeja M: Blocking effects of the antiarrhythmic drug propafenone on the HERG potassium channel. Naunyn Schmiedebergs Arch Pharmacol. 2001 Apr;363(4):472-80. [PubMed Link Image]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
  3. Arias C, Gonzalez T, Moreno I, Caballero R, Delpon E, Tamargo J, Valenzuela C: Effects of propafenone and its main metabolite, 5-hydroxypropafenone, on HERG channels. Cardiovasc Res. 2003 Mar;57(3):660-9. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 220
Target 2 Name Sodium channel protein type 5 subunit alpha
Target 2 Synonyms
  1. HH1
  2. Sodium channel protein type V subunit alpha
  3. Sodium channel protein, cardiac muscle alpha-subunit
  4. Voltage-gated sodium channel subunit alpha Nav1.5
Target 2 Gene Name SCN5A
Target 2 Protein Sequence >Sodium channel protein type 5 subunit alpha 
MANFLLPRGTSSFRRFTRESLAAIEKRMAEKQARGSTTLQESREGLPEEEAPRPQLDLQA
SKKLPDLYGNPPQELIGEPLEDLDPFYSTQKTFIVLNKGKTIFRFSATNALYVLSPFHPV
RRAAVKILVHSLFNMLIMCTILTNCVFMAQHDPPPWTKYVEYTFTAIYTFESLVKILARA
FCLHAFTFLRDPWNWLDFSVIIMAYTTEFVDLGNVSALRTFRVLRALKTISVISGLKTIV
GALIQSVKKLADVMVLTVFCLSVFALIGLQLFMGNLRHKCVRNFTALNGTNGSVEADGLV
WESLDLYLSDPENYLLKNGTSDVLLCGNSSDAGTCPEGYRCLKAGENPDHGYTSFDSFAW
AFLALFRLMTQDCWERLYQQTLRSAGKIYMIFFMLVIFLGSFYLVNLILAVVAMAYEEQN
QATIAETEEKEKRFQEAMEMLKKEHEALTIRGVDTVSRSSLEMSPLAPVNSHERRSKRRK
RMSSGTEECGEDRLPKSDSEDGPRAMNHLSLTRGLSRTSMKPRSSRGSIFTFRRRDLGSE
ADFADDENSTARESESHHTSLLVPWPLRRTSAQGQPSPGTSAPGHALHGKKNSTVDCNGV
VSLLGAGDPEATSPGSHLLRPVMLEHPPDTTTPSEEPGGPQMLTSQAPCVDGFEEPGARQ
RALSAVSVLTSALEELEESRHKCPPCWNRLAQRYLIWECCPLWMSIKQGVKLVVMDPFTD
LTITMCIVLNTLFMALEHYNMTSEFEEMLQVGNLVFTGIFTAEMTFKIIALDPYYYFQQG
WNIFDSIIVILSLMELGLSRMSNLSVLRSFRLLRVFKLAKSWPTLNTLIKIIGNSVGALG
NLTLVLAIIVFIFAVVGMQLFGKNYSELRDSDSGLLPRWHMMDFFHAFLIIFRILCGEWI
ETMWDCMEVSGQSLCLLVFLLVMVIGNLVVLNLFLALLLSSFSADNLTAPDEDREMNNLQ
LALARIQRGLRFVKRTTWDFCCGLLRHRPQKPAALAAQGQLPSCIATPYSPPPPETEKVP
PTRKETQFEEGEQPGQGTPGDPEPVCVPIAVAESDTDDQEEDEENSLGTEEESSKQQESQ
PVSGWPRGPPDSRTWSQVSATASSEAEASASQADWRQQWKAEPQAPGCGETPEDSCSEGS
TADMTNTAELLEQIPDLGQDVKDPEDCFTEGCVRRCPCCAVDTTQAPGKVWWRLRKTCYH
IVEHSWFETFIIFMILLSSGALAFEDIYLEERKTIKVLLEYADKMFTYVFVLEMLLKWVA
YGFKKYFTNAWCWLDFLIVDVSLVSLVANTLGFAEMGPIKSLRTLRALRPLRALSRFEGM
RVVVNALVGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFGRCINQTEGDLPLNYTIVNN
KSQCESLNLTGELYWTKVKVNFDNVGAGYLALLQVATFKGWMDIMYAAVDSRGYEEQPQW
EYNLYMYIYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKLGGQDIFMTEEQKKYYNAMKK
LGSKKPQKPIPRPLNKYQGFIFDIVTKQAFDVTIMFLICLNMVTMMVETDDQSPEKINIL
AKINLLFVAIFTGECIVKLAALRHYYFTNSWNIFDFVVVILSIVGTVLSDIIQKYFFSPT
LFRVIRLARIGRILRLIRGAKGIRTLLFALMMSLPALFNIGLLLFLVMFIYSIFGMANFA
YVKWEAGIDDMFNFQTFANSMLCLFQITTSAGWDGLLSPILNTGPPYCDPTLPNSNGSRG
DCGSPAVGILFFTTYIIISFLIVVNMYIAIILENFSVATEESTEPLSEDDFDMFYEIWEK
FDPEATQFIEYSVLSDFADALSEPLRIAKPNQISLINMDLPMVSGDRIHCMDILFAFTKR
VLGESGEMDALKIQMEEKFMAANPSKISYEPITTTLRRKHEEVSAMVIQRAFRRHLLQRS
LKHASFLFRQQAGSGLSEEDAPEREGLIAYVMSENFSRPLGPPSSSSISSTSFPPSYDSV
TRATSDNLQVRGSDYSHSEDLADFPPSPDRDRESIV
Target 2 Number of Residues 2049
Target 2 Molecular Weight 227165
Target 2 Theoretical pI 5.23
Target 2 GO Classification
Function
voltage-gated ion channel activity
voltage-gated sodium channel activity
transporter activity
ion transporter activity
ion channel activity
Process
cation transport
monovalent inorganic cation transport
sodium ion transport
physiological process
cellular physiological process
transport
ion transport
Component
protein complex
voltage-gated sodium channel complex
cell
membrane
Target 2 General Function Involved in ion channel activity
Target 2 Specific Function This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential in the electrocardiogram
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 127-150
  • 159-178
  • 192-210
  • 217-236
  • 253-276
  • 390-415
  • 712-736
  • 748-771
  • 780-799
  • 806-825
  • 842-862
  • 914-939
  • 1201-1224
  • 1238-1263
  • 1270-1291
  • 1296-1317
  • 1337-1359
  • 1444-1470
  • 1524-1547
  • 1559-1582
  • 1589-1612
  • 1623-1644
  • 1660-1682
  • 1748-1772
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 184039 Link Image
Target 2 UniProtKB/Swiss-Prot ID Q14524 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name SCN5A_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 2 Gene Sequence >6051 bp 
ATGGCAAACTTCCTATTACCTCGGGGCACCAGCAGCTTCCGCAGGTTCACACGGGAGTCC
CTGGCAGCCATCGAGAAGCGCATGGCGGAGAAGCAAGCCCGCGGCTCAACCACCTTGCAG
GAGAGCCGAGAGGGGCTGCCCGAGGAGGAGGCTCCCCGGCCCCAGCTGGACCTGCAGGCC
TCCAAAAAGCTGCCAGATCTCTATGGCAATCCACCCCAAGAGCTCATCGGAGAGCCCCTG
GAGGACCTGGACCCCTTCTATAGCACCCAAAAGACTTTCATCGTACTGAATAAAGGCAAG
ACCATCTTCCGGTTCAGTGCCACCAACGCCTTGTATGTCCTCAGTCCCTTCCACCCAGTT
CGGAGAGCGGCTGTGAAGATTCTGGTTCACTCGCTCTTCAACATGCTCATCATGTGCACC
ATCCTCACCAACTGCGTGTTCATGGCCCAGCACGACCCTCCACCCTGGACCAAGTATGTC
GAGTACACCTTCACCGCCATTTACACCTTTGAGTCTCTGGTCAAGATTCTGGCTCGAGCT
TTCTGCCTGCACGCGTTCACTTTCCTTCGGGACCCATGGAACTGGCTGGACTTTAGTGTG
ATTATCATGGCATACACAACTGAATTTGTGGACCTGGGCAATGTCTCAGCCTTACGCACC
TTCCGAGTCCTCCGGGCCCTGAAAACTATATCAGTCATTTCAGGGCTGAAGACCATCGTG
GGGGCCCTGATCCAGTCTGTGAAGAAGCTGGCTGATGTGATGGTCCTCACAGTCTTCTGC
CTCAGCGTCTTTGCCCTCATCGGCCTGCAGCTCTTCATGGGCAACCTAAGGCACAAGTGT
GTGCGCAACTTCACAGCGCTCAACGGCACCAACGGCTCCGTGGAGGCCGACGGCTTGGTC
TGGGAATCCCTGGACCTTTACCTCAGTGATCCAGAAAATTACCTGCTCAAGAACGGCACC
TCTGATGTGTTACTGTGTGGGAACAGCTCTGACGCTGGGACATGTCCGGAGGGCTACCGG
TGCCTAAAGGCAGGCGAGAACCCCGACCACGGCTACACCAGCTTCGATTCCTTTGCCTGG
GCCTTTCTTGCACTCTTCCGCCTGATGACGCAGGACTGCTGGGAGCGCCTCTATCAGCAG
ACCCTCAGGTCCGCAGGGAAGATCTACATGATCTTCTTCATGCTTGTCATCTTCCTGGGG
TCCTTCTACCTGGTGAACCTGATCCTGGCCGTGGTCGCAATGGCCTATGAGGAGCAAAAC
CAAGCCACCATCGCTGAGACCGAGGAGAAGGAAAAGCGCTTCCAGGAGGCCATGGAAATG
CTCAAGAAAGAACACGAGGCCCTCACCATCAGGGGTGTGGATACCGTGTCCCGTAGCTCC
TTGGAGATGTCCCCTTTGGCCCCAGTAAACAGCCATGAGAGAAGAAGCAAGAGGAGAAAA
CGGATGTCTTCAGGAACTGAGGAGTGTGGGGAGGACAGGCTCCCCAAGTCTGACTCAGAA
GATGGTCCCAGAGCAATGAATCATCTCAGCCTCACCCGTGGCCTCAGCAGGACTTCTATG
AAGCCACGTTCCAGCCGCGGGAGCATTTTCACCTTTCGCAGGCGAGACCTGGGTTCTGAA
GCAGATTTTGCAGATGATGAAAACAGCACAGCGCGGGAGAGCGAGAGCCACCACACATCA
CTGCTGGTGCCCTGGCCCCTGCGCCGGACCAGTGCCCAGGGACAGCCCAGTCCCGGAACC
TCGGCTCCTGGCCACGCCCTCCATGGCAAAAAGAACAGCACTGTGGACTGCAATGGGGTG
GTCTCATTACTGGGGGCAGGCGACCCAGAGGCCACATCCCCAGGAAGCCACCTCCTCCGC
CCTGTGATGCTAGAGCACCCGCCAGACACGACCACGCCATCGGAGGAGCCAGGCGGCCCC
CAGATGCTGACCTCCCAGGCTCCGTGTGTAGATGGCTTCGAGGAGCCAGGAGCACGGCAG
CGGGCCCTCAGCGCAGTCAGCGTCCTCACAAGCGCACTGGAAGAGTTAGAGGAGTCTCGC
CACAAGTGTCCACCATGCTGGAACCGTCTCGCCCAGCGCTACCTGATCTGGGAGTGCTGC
CCGCTGTGGATGTCCATCAAGCAGGGAGTGAAGTTGGTGGTCATGGACCCGTTTACTGAC
CTCACCATCACTATGTGCATCGTACTCAACACACTCTTCATGGCGCTGGAGCACTACAAC
ATGACAAGTGAATTCGAGGAGATGCTGCAGGTCGGAAACCTGGTCTTCACAGGGATTTTC
ACAGCAGAGATGACCTTCAAGATCATTGCCCTCGACCCCTACTACTACTTCCAACAGGGC
TGGAACATCTTCGACAGCATCATCGTCATCCTTAGCCTCATGGAGCTGGGCCTGTCCCGC
ATGAGCAACTTGTCGGTGCTGCGCTCCTTCCGCCTGCTGCGGGTCTTCAAGCTGGCCAAA
TCATGGCCCACCCTGAACACACTCATCAAGATCATCGGGAACTCAGTGGGGGCACTGGGG
AACCTGACACTGGTGCTAGCCATCATCGTGTTCATCTTTGCTGTGGTGGGCATGCAGCTC
TTTGGCAAGAACTACTCGGAGCTGAGGGACAGCGACTCAGGCCTGCTGCCTCGCTGGCAC
ATGATGGACTTCTTTCATGCCTTCCTAATCATCTTCCGCATCCTCTGTGGAGAGTGGATC
GAGACCATGTGGGACTGCATGGAGGTGTCGGGGCAGTCATTATGCCTGCTGGTCTTCTTG
CTTGTTATGGTCATTGGCAACCTTGTGGTCCTGAATCTCTTCCTGGCCTTGCTGCTCAGC
TCCTTCAGTGCAGACAACCTCACAGCCCCTGATGAGGACAGAGAGATGAACAACCTCCAG
CTGGCCCTGGCCCGCATCCAGAGGGGCCTGCGCTTTGTCAAGCGGACCACCTGGGATTTC
TGCTGTGGTCTCCTGCGGCACCGGCCTCAGAAGCCCGCAGCCCTTGCCGCCCAGGGCCAG
CTGCCCAGCTGCATTGCCACCCCCTACTCCCCGCCACCCCCAGAGACGGAGAAGGTGCCT
CCCACCCGCAAGGAAACACAGTTTGAGGAAGGCGAGCAACCAGGCCAGGGCACCCCCGGG
GATCCAGAGCCCGTGTGTGTGCCCATCGCTGTGGCCGAGTCAGACACAGATGACCAAGAA
GAGGATGAGGAGAACAGCCTGGGCACGGAGGAGGAGTCCAGCAAGCAGCAGGAATCCCAG
CCTGTGTCCGGCTGGCCCAGAGGCCCTCCGGATTCCAGGACCTGGAGCCAGGTGTCAGCG
ACTGCCTCCTCTGAGGCCGAGGCCAGTGCATCTCAGGCCGACTGGCGGCAGCAGTGGAAA
GCGGAACCCCAGGCCCCAGGGTGCGGTGAGACCCCAGAGGACAGTTGCTCCGAGGGCAGC
ACAGCAGACATGACCAACACCGCTGAGCTCCTGGAGCAGATCCCTGACCTCGGCCAGGAT
GTCAAGGACCCAGAGGACTGCTTCACTGAAGGCTGTGTCCGGCGCTGTCCCTGCTGTGCG
GTGGACACCACACAGGCCCCAGGGAAGGTCTGGTGGCGGTTGCGCAAGACCTGCTACCAC
ATCGTGGAGCACAGCTGGTTCGAGACATTCATCATCTTCATGATCCTACTCAGCAGTGGA
GCGCTGGCCTTCGAGGACATCTACCTAGAGGAGCGGAAGACCATCAAGGTTCTGCTTGAG
TATGCCGACAAGATGTTCACATATGTCTTCGTGCTGGAGATGCTGCTCAAGTGGGTGGCC
TACGGCTTCAAGAAGTACTTCACCAATGCCTGGTGCTGGCTCGACTTCCTCATCGTAGAC
GTCTCTCTGGTCAGCCTGGTGGCCAACACCCTGGGCTTTGCCGAGATGGGCCCCATCAAG
TCACTGCGGACGCTGCGTGCACTCCGTCCTCTGAGAGCTCTGTCACGATTTGAGGGCATG
AGGGTGGTGGTCAATGCCCTGGTGGGCGCCATCCCGTCCATCATGAACGTCCTCCTCGTC
TGCCTCATCTTCTGGCTCATCTTCAGCATCATGGGCGTGAACCTCTTTGCGGGGAAGTTT
GGGAGGTGCATCAACCAGACAGAGGGAGACTTGCCTTTGAACTACACCATCGTGAACAAC
AAGAGCCAGTGTGAGTCCTTGAACTTGACCGGAGAATTGTACTGGACCAAGGTGAAAGTC
AACTTTGACAACGTGGGGGCCGGGTACCTGGCCCTTCTGCAGGTGGCAACATTTAAAGGC
TGGATGGACATTATGTATGCAGCTGTGGACTCCAGGGGGTATGAAGAGCAGCCTCAGTGG
GAATACAACCTCTACATGTACATCTATTTTGTCATTTTCATCATCTTTGGGTCTTTCTTC
ACCCTGAACCTCTTTATTGGTGTCATCATTGACAACTTCAACCAACAGAAGAAAAAGTTA
GGGGGCCAGGACATCTTCATGACAGAGGAGCAGAAGAAGTACTACAATGCCATGAAGAAG
CTGGGCTCCAAGAAGCCCCAGAAGCCCATCCCACGGCCCCTGAACAAGTACCAGGGCTTC
ATATTCGACATTGTGACCAAGCAGGCCTTTGACGTCACCATCATGTTTCTGATCTGCTTG
AATATGGTGACCATGATGGTGGAGACAGATGACCAAAGTCCTGAGAAAATCAACATCTTG
GCCAAGATCAACCTGCTCTTTGTGGCCATCTTCACAGGCGAGTGTATTGTCAAGCTGGCT
GCCCTGCGCCACTACTACTTCACCAACAGCTGGAATATCTTCGACTTCGTGGTTGTCATC
CTCTCCATCGTGGGCACTGTGCTCTCGGACATCATCCAGAAGTACTTCTTCTCCCCGACG
CTCTTCCGAGTCATCCGCCTGGCCCGAATAGGCCGCATCCTCAGACTGATCCGAGGGGCC
AAGGGGATCCGCACGCTGCTCTTTGCCCTCATGATGTCCCTGCCTGCCCTCTTCAACATC
GGGCTGCTGCTCTTCCTCGTCATGTTCATCTACTCCATCTTTGGCATGGCCAACTTCGCT
TATGTCAAGTGGGAGGCTGGCATCGACGACATGTTCAACTTCCAGACCTTCGCCAACAGC
ATGCTGTGCCTCTTCCAGATCACCACGTCGGCCGGCTGGGATGGCCTCCTCAGCCCCATC
CTCAACACTGGGCCGCCCTACTGCGACCCCACTCTGCCCAACAGCAATGGCTCTCGGGGG
GACTGCGGGAGCCCAGCCGTGGGCATCCTCTTCTTCACCACCTACATCATCATCTCCTTC
CTCATCGTGGTCAACATGTACATTGCCATCATCCTGGAGAACTTCAGCGTGGCCACGGAG
GAGAGCACCGAGCCCCTGAGTGAGGACGACTTCGATATGTTCTATGAGATCTGGGAGAAA
TTTGACCCAGAGGCCACTCAGTTTATTGAGTATTCGGTCCTGTCTGACTTTGCCGACGCC
CTGTCTGAGCCACTCCGTATCGCCAAGCCCAACCAGATAAGCCTCATCAACATGGACCTG
CCCATGGTGAGTGGGGACCGCATCCATTGCATGGACATTCTCTTTGCCTTCACCAAAAGG
GTCCTGGGGGAGTCTGGGGAGATGGACGCCCTGAAGATCCAGATGGAGGAGAAGTTCATG
GCAGCCAACCCATCCAAGATCTCCTACGAGCCCATCACCACCACACTCCGGCGCAAGCAC
GAAGAGGTGTCGGCCATGGTTATCCAGAGAGCCTTCCGCAGGCACCTGCTGCAACGCTCT
TTGAAGCATGCCTCCTTCCTCTTCCGTCAGCAGGCGGGCAGCGGCCTCTCCGAAGAGGAT
GCCCCTGAGCGAGAGGGCCTCATCGCCTACGTGATGAGTGAGAACTTCTCCCGACCCCTT
GGCCCACCCTCCAGCTCCTCCATCTCCTCCACTTCCTTCCCACCCTCCTATGACAGTGTC
ACTAGAGCCACCAGCGATAACCTCCAGGTGCGGGGGTCTGACTACAGCCACAGTGAAGAT
CTCGCCGACTTCCCCCCTTCTCCGGACAGGGACCGTGAGTCCATCGTGTGA
Target 2 GenBank Gene ID
Target 2 GeneCard ID SCN5A Link Image
Target 2 GenAtlas ID SCN5A Link Image
Target 2 HGNC ID HGNC:10593 Link Image
Target 2 Chromosome Location 3
Target 2 Locus 3p21
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Wei J, Wang DW, Alings M, Fish F, Wathen M, Roden DM, George AL Jr: Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel. Circulation. 1999 Jun 22;99(24):3165-71. [PubMed Link Image]
  2. Wattanasirichaigoon D, Vesely MR, Duggal P, Levine JC, Blume ED, Wolff GS, Edwards SB, Beggs AH: Sodium channel abnormalities are infrequent in patients with long QT syndrome: identification of two novel SCN5A mutations. Am J Med Genet. 1999 Oct 29;86(5):470-6. [PubMed Link Image]
  3. 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]
  4. Wehrens XH, Rossenbacker T, Jongbloed RJ, Gewillig M, Heidbuchel H, Doevendans PA, Vos MA, Wellens HJ, Kass RS: A novel mutation L619F in the cardiac Na+ channel SCN5A associated with long-QT syndrome (LQT3): a role for the I-II linker in inactivation gating. Hum Mutat. 2003 May;21(5):552. [PubMed Link Image]
  5. Gellens ME, George AL Jr, Chen LQ, Chahine M, Horn R, Barchi RL, Kallen RG: Primary structure and functional expression of the human cardiac tetrodotoxin-insensitive voltage-dependent sodium channel. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):554-8. [PubMed Link Image]
  6. Bennett PB, Yazawa K, Makita N, George AL Jr: Molecular mechanism for an inherited cardiac arrhythmia. Nature. 1995 Aug 24;376(6542):683-5. [PubMed Link Image]
  7. Wang Q, Shen J, Splawski I, Atkinson D, Li Z, Robinson JL, Moss AJ, Towbin JA, Keating MT: SCN5A mutations associated with an inherited cardiac arrhythmia, long QT syndrome. Cell. 1995 Mar 10;80(5):805-11. [PubMed Link Image]
  8. Wang Q, Shen J, Li Z, Timothy K, Vincent GM, Priori SG, Schwartz PJ, Keating MT: Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia. Hum Mol Genet. 1995 Sep;4(9):1603-7. [PubMed Link Image]
  9. Makita N, Shirai N, Nagashima M, Matsuoka R, Yamada Y, Tohse N, Kitabatake A: A de novo missense mutation of human cardiac Na+ channel exhibiting novel molecular mechanisms of long QT syndrome. FEBS Lett. 1998 Feb 13;423(1):5-9. [PubMed Link Image]
  10. An RH, Wang XL, Kerem B, Benhorin J, Medina A, Goldmit M, Kass RS: Novel LQT-3 mutation affects Na+ channel activity through interactions between alpha- and beta1-subunits. Circ Res. 1998 Jul 27;83(2):141-6. [PubMed Link Image]
Target 2 Drug References
  1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed Link Image]
  2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 1588
Target 3 Name Multidrug resistance protein 1
Target 3 Synonyms
  1. ATP-binding cassette sub-family B member 1
  2. CD243 antigen
  3. EC 3.6.3.44
  4. P-glycoprotein 1
Target 3 Gene Name ABCB1
Target 3 Protein Sequence >Multidrug resistance protein 1 
MDLEGDRNGGAKKKNFFKLNNKSEKDKKEKKPTVSVFSMFRYSNWLDKLYMVVGTLAAII
HGAGLPLMMLVFGEMTDIFANAGNLEDLMSNITNRSDINDTGFFMNLEEDMTRYAYYYSG
IGAGVLVAAYIQVSFWCLAAGRQIHKIRKQFFHAIMRQEIGWFDVHDVGELNTRLTDDVS
KINEGIGDKIGMFFQSMATFFTGFIVGFTRGWKLTLVILAISPVLGLSAAVWAKILSSFT
DKELLAYAKAGAVAEEVLAAIRTVIAFGGQKKELERYNKNLEEAKRIGIKKAITANISIG
AAFLLIYASYALAFWYGTTLVLSGEYSIGQVLTVFFSVLIGAFSVGQASPSIEAFANARG
AAYEIFKIIDNKPSIDSYSKSGHKPDNIKGNLEFRNVHFSYPSRKEVKILKGLNLKVQSG
QTVALVGNSGCGKSTTVQLMQRLYDPTEGMVSVDGQDIRTINVRFLREIIGVVSQEPVLF
ATTIAENIRYGRENVTMDEIEKAVKEANAYDFIMKLPHKFDTLVGERGAQLSGGQKQRIA
IARALVRNPKILLLDEATSALDTESEAVVQVALDKARKGRTTIVIAHRLSTVRNADVIAG
FDDGVIVEKGNHDELMKEKGIYFKLVTMQTAGNEVELENAADESKSEIDALEMSSNDSRS
SLIRKRSTRRSVRGSQAQDRKLSTKEALDESIPPVSFWRIMKLNLTEWPYFVVGVFCAII
NGGLQPAFAIIFSKIIGVFTRIDDPETKRQNSNLFSLLFLALGIISFITFFLQGFTFGKA
GEILTKRLRYMVFRSMLRQDVSWFDDPKNTTGALTTRLANDAAQVKGAIGSRLAVITQNI
ANLGTGIIISFIYGWQLTLLLLAIVPIIAIAGVVEMKMLSGQALKDKKELEGAGKIATEA
IENFRTVVSLTQEQKFEHMYAQSLQVPYRNSLRKAHIFGITFSFTQAMMYFSYAGCFRFG
AYLVAHKLMSFEDVLLVFSAVVFGAMAVGQVSSFAPDYAKAKISAAHIIMIIEKTPLIDS
YSTEGLMPNTLEGNVTFGEVVFNYPTRPDIPVLQGLSLEVKKGQTLALVGSSGCGKSTVV
QLLERFYDPLAGKVLLDGKEIKRLNVQWLRAHLGIVSQEPILFDCSIAENIAYGDNSRVV
SQEEIVRAAKEANIHAFIESLPNKYSTKVGDKGTQLSGGQKQRIAIARALVRQPHILLLD
EATSALDTESEKVVQEALDKAREGRTCIVIAHRLSTIQNADLIVVFQNGRVKEHGTHQQL
LAQKGIYFSMVSVQAGTKRQ
Target 3 Number of Residues 1301
Target 3 Molecular Weight 141464
Target 3 Theoretical pI 9.44
Target 3 GO Classification
Function
ATPase activity
hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances
ATPase activity, coupled to transmembrane movement of substances
purine nucleotide binding
adenyl nucleotide binding
ATP binding
catalytic activity
hydrolase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
nucleoside-triphosphatase activity
binding
nucleotide binding
Process
physiological process
cellular physiological process
transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 3 General Function Defense mechanisms and drug export
Target 3 Specific Function Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Target 3 Pathways Not Available
Target 3 Reactions
  • ATP + H2O + xenobioticin = ADP + phosphate + xenobioticout
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 52-72
  • 120-140
  • 189-209
  • 216-236
  • 297-317
  • 326-346
  • 711-731
  • 757-777
  • 833-853
  • 854-874
  • 937-957
  • 974-994
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 307180 Link Image
Target 3 UniProtKB/Swiss-Prot ID P08183 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name MDR1_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 3 Gene Sequence >3843 bp 
ATGGATCTTGAAGGGGACCGCAATGGAGGAGCAAAGAAGAAGAACTTTTTTAAACTGAAC
AATAAAAGTGAAAAAGATAAGAAGGAAAAGAAACCAACTGTCAGTGTATTTTCAATGTTT
CGCTATTCAAATTGGCTTGACAAGTTGTATATGGTGGTGGGAACTTTGGCTGCCATCATC
CATGGGGCTGGACTTCCTCTCATGATGCTGGTGTTTGGAGAAATGACAGATATCTTTGCA
AATGCAGGAAATTTAGAAGATCTGATGTCAAACATCACTAATAGAAGTGATATCAATGAT
ACAGGGTTCTTCATGAATCTGGAGGAAGACATGACCAGGTATGCCTATTATTACAGTGGA
ATTGGTGCTGGGGTGCTGGTTGCTGCTTACATTCAGGTTTCATTTTGGTGCCTGGCAGCT
GGAAGACAAATACACAAAATTAGAAAACAGTTTTTTCATGCTATAATGCGACAGGAGATA
GGCTGGTTTGATGTGCACGATGTTGGGGAGCTTAACACCCGACTTACAGATGATGTCTCT
AAGATTAATGAAGTTATTGGTGACAAAATTGGAATGTTCTTTCAGTCAATGGCAACATTT
TTCACTGGGTTTATAGTAGGATTTACACGTGGTTGGAAGCTAACCCTTGTGATTTTGGCC
ATCAGTCCTGTTCTTGGACTGTCAGCTGCTGTCTGGGCAAAGATACTATCTTCATTTACT
GATAAAGAACTCTTAGCGTATGCAAAAGCTGGAGCAGTAGCTGAAGAGGTCTTGGCAGCA
ATTAGAACTGTGATTGCATTTGGAGGACAAAAGAAAGAACTTGAAAGGTACAACAAAAAT
TTAGAAGAAGCTAAAAGAATTGGGATAAAGAAAGCTATTACAGCCAATATTTCTATAGGT
GCTGCTTTCCTGCTGATCTATGCATCTTATGCTCTGGCCTTCTGGTATGGGACCACCTTG
GTCCTCTCAGGGGAATATTCTATTGGACAAGTACTCACTGTATTCTTTTCTGTATTAATT
GGGGCTTTTAGTGTTGGACAGGCATCTCCAAGCATTGAAGCATTTGCAAATGCAAGAGGA
GCAGCTTATGAAATCTTCAAGATAATTGATAATAAGCCAAGTATTGACAGCTATTCGAAG
AGTGGGCACAAACCAGATAATATTAAGGGAAATTTGGAATTCAGAAATGTTCACTTCAGT
TACCCATCTCGAAAAGAAGTTAAGATCTTGAAGGGCCTGAACCTGAAGGTGCAGAGTGGG
CAGACGGTGGCCCTGGTTGGAAACAGTGGCTGTGGGAAGAGCACAACAGTCCAGCTGATG
CAGAGGCTCTATGACCCCACAGAGGGGATGGTCAGTGTTGATGGACAGGATATTAGGACC
ATAAATGTAAGGTTTCTACGGGAAATCATTGGTGTGGTGAGTCAGGAACCTGTATTGTTT
GCCACCACGATAGCTGAAAACATTCGCTATGGCCGTGAAAATGTCACCATGGATGAGATT
GAGAAAGCTGTCAAGGAAGCCAATGCCTATGACTTTATCATGAAACTGCCTCATAAATTT
GACACCCTGGTTGGAGAGAGAGGGGCCCAGTTGAGTGGTGGGCAGAAGCAGAGGATCGCC
ATTGCACGTGCCCTGGTTCGCAACCCCAAGATCCTCCTGCTGGATGAGGCCACGTCAGCC
TTGGACACAGAAAGCGAAGCAGTGGTTCAGGTGGCTCTGGATAAGGCCAGAAAAGGTCGG
ACCACCATTGTGATAGCTCATCGTTTGTCTACAGTTCGTAATGCTGACGTCATCGCTGGT
TTCGATGATGGAGTCATTGTGGAGAAAGGAAATCATGATGAACTCATGAAAGAGAAAGGC
ATTTACTTCAAACTTGTCACAATGCAGACAGCAGGAAATGAAGTTGAATTAGAAAATGCA
GCTGATGAATCCAAAAGTGAAATTGATGCCTTGGAAATGTCTTCAAATGATTCAAGATCC
AGTCTAATAAGAAAAAGATCAACTCGTAGGAGTGTCCGTGGATCACAAGCCCAAGACAGA
AAGCTTAGTACCAAAGAGGCTCTGGATGAAAGTATACCTCCAGTTTCCTTTTGGAGGATT
ATGAAGCTAAATTTAACTGAATGGCCTTATTTTGTTGTTGGTGTATTTTGTGCCATTATA
AATGGAGGCCTGCAACCAGCATTTGCAATAATATTTTCAAAGATTATAGGGGTTTTTACA
AGAATTGATGATCCTGAAACAAAACGACAGAATAGTAACTTGTTTTCACTATTGTTTCTA
GCCCTTGGAATTATTTCTTTTATTACATTTTTCCTTCAGGGTTTCACATTTGGCAAAGCT
GGAGAGATCCTCACCAAGCGGCTCCGATACATGGTTTTCCGATCCATGCTCAGACAGGAT
GTGAGTTGGTTTGATGACCCTAAAAACACCACTGGAGCATTGACTACCAGGCTCGCCAAT
GATGCTGCTCAAGTTAAAGGGGCTATAGGTTCCAGGCTTGCTGTAATTACCCAGAATATA
GCAAATCTTGGGACAGGAATAATTATATCCTTCATCTATGGTTGGCAACTAACACTGTTA
CTCTTAGCAATTGTACCCATCATTGCAATAGCAGGAGTTGTTGAAATGAAAATGTTGTCT
GGACAAGCACTGAAAGATAAGAAAGAACTAGAAGGTGCTGGGAAGATCGCTACTGAAGCA
ATAGAAAACTTCCGAACCGTTGTTTCTTTGACTCAGGAGCAGAAGTTTGAACATATGTAT
GCTCAGAGTTTGCAGGTACCATACAGAAACTCTTTGAGGAAAGCACACATCTTTGGAATT
ACATTTTCCTTCACCCAGGCAATGATGTATTTTTCCTATGCTGGATGTTTCCGGTTTGGA
GCCTACTTGGTGGCACATAAACTCATGAGCTTTGAGGATGTTCTGTTAGTATTTTCAGCT
GTTGTCTTTGGTGCCATGGCCGTGGGGCAAGTCAGTTCATTTGCTCCTGACTATGCCAAA
GCCAAAATATCAGCAGCCCACATCATCATGATCATTGAAAAAACCCCTTTGATTGACAGC
TACAGCACGGAAGGCCTAATGCCGAACACATTGGAAGGAAATGTCACATTTGGTGAAGTT
GTATTCAACTATCCCACCCGACCGGACATCCCAGTGCTTCAGGGACTGAGCCTGGAGGTG
AAGAAGGGCCAGACGCTGGCTCTGGTGGGCAGCAGTGGCTGTGGGAAGAGCACAGTGGTC
CAGCTCCTGGAGCGGTTCTACGACCCCTTGGCAGGGAAAGTGCTGCTTGATGGCAAAGAA
ATAAAGCGACTGAATGTTCAGTGGCTCCGAGCACACCTGGGCATCGTGTCCCAGGAGCCC
ATCCTGTTTGACTGCAGCATTGCTGAGAACATTGCCTATGGAGACAACAGCCGGGTGGTG
TCACAGGAAGAGATCGTGAGGGCAGCAAAGGAGGCCAACATACATGCCTTCATCGAGTCA
CTGCCTAATAAATATAGCACTAAAGTAGGAGACAAAGGAACTCAGCTCTCTGGTGGCCAG
AAACAACGCATTGCCATAGCTCGTGCCCTTGTTAGACAGCCTCATATTTTGCTTTTGGAT
GAAGCCACGTCAGCTCTGGATACAGAAAGTGAAAAGGTTGTCCAAGAAGCCCTGGACAAA
GCCAGAGAAGGCCGCACCTGCATTGTGATTGCTCACCGCCTGTCCACCATCCAGAATGCA
GACTTAATAGTGGTGTTTCAGAATGGCAGAGTCAAGGAGCATGGCACGCATCAGCAGCTG
CTGGCACAGAAAGGCATCTATTTTTCAATGGTCAGTGTCCAGGCTGGAACAAAGCGCCAG
TGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID ABCB1 Link Image
Target 3 GenAtlas ID ABCB1 Link Image
Target 3 HGNC ID HGNC:40 Link Image
Target 3 Chromosome Location 7
Target 3 Locus 7q21.1
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U: Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3473-8. [PubMed Link Image]
  2. Decleves X, Chevillard S, Charpentier C, Vielh P, Laplanche JL: A new polymorphism (N21D) in the exon 2 of the human MDR1 gene encoding the P-glycoprotein. Hum Mutat. 2000 May;15(5):486. [PubMed Link Image]
  3. Cascorbi I, Gerloff T, Johne A, Meisel C, Hoffmeyer S, Schwab M, Schaeffeler E, Eichelbaum M, Brinkmann U, Roots I: Frequency of single nucleotide polymorphisms in the P-glycoprotein drug transporter MDR1 gene in white subjects. Clin Pharmacol Ther. 2001 Mar;69(3):169-74. [PubMed Link Image]
  4. Kerb R, Hoffmeyer S, Brinkmann U: ABC drug transporters: hereditary polymorphisms and pharmacological impact in MDR1, MRP1 and MRP2. Pharmacogenomics. 2001 Feb;2(1):51-64. [PubMed Link Image]
  5. Saito S, Iida A, Sekine A, Miura Y, Ogawa C, Kawauchi S, Higuchi S, Nakamura Y: Three hundred twenty-six genetic variations in genes encoding nine members of ATP-binding cassette, subfamily B (ABCB/MDR/TAP), in the Japanese population. J Hum Genet. 2002;47(1):38-50. [PubMed Link Image]
  6. Hillier LW, Fulton RS, Fulton LA, Graves TA, Pepin KH, Wagner-McPherson C, Layman D, Maas J, Jaeger S, Walker R, Wylie K, Sekhon M, Becker MC, O'Laughlin MD, Schaller ME, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Cordes M, Du H, Sun H, Edwards J, Bradshaw-Cordum H, Ali J, Andrews S, Isak A, Vanbrunt A, Nguyen C, Du F, Lamar B, Courtney L, Kalicki J, Ozersky P, Bielicki L, Scott K, Holmes A, Harkins R, Harris A, Strong CM, Hou S, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Leonard S, Rohlfing T, Rock SM, Tin-Wollam AM, Abbott A, Minx P, Maupin R, Strowmatt C, Latreille P, Miller N, Johnson D, Murray J, Woessner JP, Wendl MC, Yang SP, Schultz BR, Wallis JW, Spieth J, Bieri TA, Nelson JO, Berkowicz N, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Bedell JA, Mardis ER, Clifton SW, Chissoe SL, Marra MA, Raymond C, Haugen E, Gillett W, Zhou Y, James R, Phelps K, Iadanoto S, Bubb K, Simms E, Levy R, Clendenning J, Kaul R, Kent WJ, Furey TS, Baertsch RA, Brent MR, Keibler E, Flicek P, Bork P, Suyama M, Bailey JA, Portnoy ME, Torrents D, Chinwalla AT, Gish WR, Eddy SR, McPherson JD, Olson MV, Eichler EE, Green ED, Waterston RH, Wilson RK: The DNA sequence of human chromosome 7. Nature. 2003 Jul 10;424(6945):157-64. [PubMed Link Image]
  7. Chen CJ, Clark D, Ueda K, Pastan I, Gottesman MM, Roninson IB: Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins. J Biol Chem. 1990 Jan 5;265(1):506-14. [PubMed Link Image]
  8. Gekeler V, Weger S, Probst H: mdr1/P-glycoprotein gene segments analyzed from various human leukemic cell lines exhibiting different multidrug resistance profiles. Biochem Biophys Res Commun. 1990 Jun 15;169(2):796-802. [PubMed Link Image]
  9. Kioka N, Tsubota J, Kakehi Y, Komano T, Gottesman MM, Pastan I, Ueda K: P-glycoprotein gene (MDR1) cDNA from human adrenal: normal P-glycoprotein carries Gly185 with an altered pattern of multidrug resistance. Biochem Biophys Res Commun. 1989 Jul 14;162(1):224-31. [PubMed Link Image]
  10. Chen CJ, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, Roninson IB: Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell. 1986 Nov 7;47(3):381-9. [PubMed Link Image]
  11. 2897240 Choi KH, Chen CJ, Kriegler M, Roninson IB: An altered pattern of cross-resistance in multidrug-resistant human cells results from spontaneous mutations in the mdr1 (P-glycoprotein) gene. Cell. 1988 May 20;53(4):519-29.
  12. 9038218 Chen G, Duran GE, Steger KA, Lacayo NJ, Jaffrezou JP, Dumontet C, Sikic BI: Multidrug-resistant human sarcoma cells with a mutant P-glycoprotein, altered phenotype, and resistance to cyclosporins. J Biol Chem. 1997 Feb 28;272(9):5974-82.
  13. 9473242 Mickley LA, Lee JS, Weng Z, Zhan Z, Alvarez M, Wilson W, Bates SE, Fojo T: Genetic polymorphism in MDR-1: a tool for examining allelic expression in normal cells, unselected and drug-selected cell lines, and human tumors. Blood. 1998 Mar 1;91(5):1749-56.
Target 3 Drug References
  1. Schmid D, Ecker G, Kopp S, Hitzler M, Chiba P: Structure-activity relationship studies of propafenone analogs based on P-glycoprotein ATPase activity measurements. Biochem Pharmacol. 1999 Nov 1;58(9):1447-56. [PubMed Link Image]
  2. Bachmakov I, Rekersbrink S, Hofmann U, Eichelbaum M, Fromm MF: Characterisation of (R/S)-propafenone and its metabolites as substrates and inhibitors of P-glycoprotein. Naunyn Schmiedebergs Arch Pharmacol. 2005 Mar;371(3):195-201. Epub 2005 Apr 15. [PubMed Link Image]
  3. Singh P, Paul K: Studies of interactions between uracil-based hybrid molecules and P-glycoprotein--search for multidrug resistance modulators. Bioorg Med Chem. 2006 Nov 1;14(21):7183-6. Epub 2006 Jul 14. [PubMed Link Image]
  4. Woodland C, Verjee Z, Giesbrecht E, Koren G, Ito S: The digoxin-propafenone interaction: characterization of a mechanism using renal tubular cell monolayers. J Pharmacol Exp Ther. 1997 Oct;283(1):39-45. [PubMed Link Image]
  5. Tmej C, Chiba P, Huber M, Richter E, Hitzler M, Schaper KJ, Ecker G: A combined Hansch/Free-Wilson approach as predictive tool in QSAR studies on propafenone-type modulators of multidrug resistance. Arch Pharm (Weinheim). 1998 Jul-Aug;331(7-8):233-40. [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.