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Showing drug card for Topiramate (DB00273)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-04-16 16:47:34
Primary Accession Number DB00273
Secondary Accession Number
  • APRD00237
Name Topiramate
Drug Type
  • Approved
  • Investigational
  • Small Molecule
Description Topiramate (brand name Topamax) is an anticonvulsant drug produced by Ortho-McNeil Neurologics, a division of Johnson & Johnson. It is used to treat epilepsy in both children and adults. In children it is also indicated for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delays). It is also Food and Drug Administration (FDA) approved for, and now most frequently prescribed for, the prevention of migraines. [Wikipedia]
Synonyms
  1. Tipiramate [French]
  2. Tipiramato [Spanish]
  3. Topiramato [INN-Spanish]
  4. Topiramatum [INN-Latin]
  5. Topiramic acid
  6. topiramate tablet
Brand Names
  1. Topamax
  2. Topamax Sprinkle
Brand Mixtures Not Available
Chemical IUPAC Name 2,3:4,5-Bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate
Chemical Formula C12H21NO8S
Chemical Structure Structure
CAS Registry Number 97240-79-4
InChI Identifier InChI=1/C12H21NO8S/c1-10(2)18-7-5-16-12(6-17-22(13,14)15)9(8(7)19-10)20-11(3,4)21-12/h7-9H,5-6H2,1-4H3,(H2,13,14,15)/t7-,8-,9+,12+/m1/s1/f/h13H2
InChI Key KJADKKWYZYXHBB-OBCVYQOWDF
KEGG Drug D00537 Link Image
KEGG Compound C07502 Link Image
PubChem Compound 5284627 Link Image
PubChem Substance 194321 Link Image
ChEBI ID Not Available
PharmGKB ID PA451728 Link Image
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] 02239908 Link Image
RxList Link http://www.rxlist.com/cgi/generic2/topiram.htm Link Image
PDRhealth Link http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/top1541.shtml Link Image
Wikipedia Link http://en.wikipedia.org/wiki/Topiramate Link Image
FDA Label
Material Safety Data Sheet (MSDS)
Synthesis Reference Not Available
Average Molecular Weight 339.3620
Monoisotopic Molecular Weight 339.0988
State Solid
Melting Point Not Available
Experimental Water Solubility 9.8 mg/mL Source: PhysProp
Predicted Water Solubility 6.80e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -0.7 Source: PhysProp
Predicted LogP 1.29 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -1.70 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 CC1(C)O[C@@H]2CO[C@@]3(COS(N)(=O)=O)OC(C)(C)O[C@H]3[C@@H]2O1
Canonical SMILES CC1(C)OC2COC3(COS(N)(=O)=O)OC(C)(C)OC3C2O1
Drug Category
  • Anti-Obesity Agents
  • Anticonvulsants
  • Neuroprotective Agents
ATC Codes
AHFS Codes
  • 28:12.92
Indication Used for the treatment and control of partial seizures and severe tonic-clonic (grand mal) seizures and also for the prevention of migraine headaches. In children it is also used for treatment of Lennox-Gastaut syndrome.
Pharmacology Topiramate is an anticonvulsant indicated in the treatment of epilepsy and migraine. Topiramate enhances GABA-activated chloride channels. In addition, topiramate inhibits excitatory neurotransmission, through actions on kainate and AMPA receptors. There is evidence that topiramate has a specific effect on GluR5 kainate receptors. It is also an inhibitor of carbonic anhydrase, particular subtypes II and IV, but this action is weak and unlikely to be related to its anticonvulsant actions, but may account for the bad taste and the development of renal stones seen during treatment. Its possible effect as a mood stabilizer seems to occur before anticonvulsant qualities at lower dosages. Topiramate inhibits maximal electroshock and pentylenetetrazol-induced seizures as well as partial and secundarily generalized tonic-clonic seizures in the kindling model, findings predective of a broad spectrum of antiseizure activities clinically.
Mechanism of Action The precise mechanism of action of topiramate is not known. However, studies have shown that topiramate blocks the action potentials elicited repetitively by a sustained depolarization of the neurons in a time-dependent manner, suggesting a state-dependent sodium channel blocking action. Topiramate also augments the activity of the neurotransmitter gamma-aminobutyrate (GABA) at some subtypes of the GABAA receptor (controls an integral chloride channel), indicating a possible mechanism through potentiation of the activity of GABA. Topiramate also demonstrates antagonism of the AMPA/kainate subtype of the glutamat excitatory amino acid receptor. It also inhibits carbonic anhydrase (particularly isozymes II and IV), but this action is weak and unlikely to be related to its anticonvulsant actions.
Absorption Rapid with pleak plasma concentrations occurring after 2 hours and a bioavailability of 80%.
Toxicity Symptoms of overdose include abdominal pain, agitation, blurred vision, convulsions, depression, dizziness, double vision, drowsiness, impaired coordination, impaired mental activity, low blood pressure, reduced consciousness, severe diarrhea, sluggishness, and speech problems.
Protein Binding 15-41% (over the blood concentration range of 0.5 - 250 mg/mL).
Biotransformation Not extensively metabolized, 70% of the dose is eliminated unchanged in the urine. The other 30% is metabolized hepatically to six metabolites (formed by hydroxylation, hydrolysis, and glucuronidation), none of which constitute more than 5% of an administered dose.
Half Life 19 to 23 hours
Dosage Forms
Form Route
Capsule Oral
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Show Link Image
Drug Interactions
Drug Interaction
Acetazolamide Additive renal carbonic anhydrase inhibition may occur increasing the risk of crystaluria and renal calculi. Increased risk of nephrolithiasis. Consider altnerate therapy.
Carbamazepine Carbamazepine may decrease the effectiveness of Topiramate by increase its clearance. Monitor for changes in the therapeutic and adverse effects of Topiramate if Carbamazepine is initiated, discontinued or dose changed. Adverse effects related to CNS depression have also been observed during concomitant therapy.
Ethinyl Estradiol Topiramate may decrease the effect of the oral contraceptive, Ethinyl estradiol. An alternate form of contraception should be used during concomitant therapy.
Maraviroc Topiramate, a CYP3A4 inducer, may decrease the serum concentration of Maraviroc by increasing Maraviroc metabolism and clearance. A dose adjustment of Maraviroc may be required. Monitor for changes in Maraviroc therapeutic and adverse effects if Topiramate is initiated, discontinued or dose changed.
Mestranol Topiramate may decrease the effect of the oral contraceptive, Mestranol. An alternate form of contraception should be used during concomitant therapy.
Food Interactions Not Available
Pathways Not Available
General References
  1. Blum D, Meador K, Biton V, Fakhoury T, Shneker B, Chung S, Mills K, Hammer A, Isojarvi J: Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy. Neurology. 2006 Aug 8;67(3):400-6. [PubMed Link Image]
  2. Drugs.com Link Image
  3. Wikipedia Link Image
  4. RxList Link Image
  5. PDRhealth Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 2C19 (CYP2C19)
Targets
  1. Sodium channel protein type 1 subunit alpha
  2. Carbonic anhydrase 2
  3. Glutamate receptor, ionotropic kainate 1
  4. Carbonic anhydrase 4
  5. Gamma-aminobutyric-acid receptor subunit alpha-1
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 2C19 (CYP2C19)
Enzyme 1 Gene Name CYP2C19
Enzyme 1 SwissProt ID P33261 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P33261|CP2CJ_HUMAN Cytochrome P450 2C19 (EC 1.14.13.80) 
MDPFVVLVLCLSCLLLLSIWRQSSGRGKLPPGPTPLPVIGNILQIDIKDVSKSLTNLSKI
YGPVFTLYFGLERMVVLHGYEVVKEALIDLGEEFSGRGHFPLAERANRGFGIVFSNGKRW
KEIRRFSLMTLRNFGMGKRSIEDRVQEEARCLVEELRKTKASPCDPTFILGCAPCNVICS
IIFQKRFDYKDQQFLNLMEKLNENIRIVSTPWIQICNNFPTIIDYFPGTHNKLLKNLAFM
ESDILEKVKEHQESMDINNPRDFIDCFLIKMEKEKQNQQSEFTIENLVITAADLLGAGTE
TTSTTLRYALLLLLKHPEVTAKVQEEIERVVGRNRSPCMQDRGHMPYTDAVVHEVQRYID
LIPTSLPHAVTCDVKFRNYLIPKGTTILTSLTSVLHDNKEFPNPEMFDPRHFLDEGGNFK
KSNYFMPFSAGKRICVGEGLARMELFLFLTFILQNFNLKSLIDPKDLDTTPVVNGFASVP
PFYQLCFIPV
Drug Target 1 [top]
Target 1 ID 158
Target 1 Name Sodium channel protein type 1 subunit alpha
Target 1 Synonyms
  1. Sodium channel protein type I subunit alpha
  2. Sodium channel protein, brain I subunit alpha
  3. Voltage-gated sodium channel subunit alpha Nav1.1
Target 1 Gene Name SCN1A
Target 1 Protein Sequence >Sodium channel protein type 1 subunit alpha 
MEQTVLVPPGPDSFNFFTRESLAAIERRIAEEKAKNPKPDKKDDDENGPKPNSDLEAGKN
LPFIYGDIPPEMVSEPLEDLDPYYINKKTFIVLNKGKAIFRFSATSALYILTPFNPLRKI
AIKILVHSLFSMLIMCTILTNCVFMTMSNPPDWTKNVEYTFTGIYTFESLIKIIARGFCL
EDFTFLRDPWNWLDFTVITFAYVTEFVDLGNVSALRTFRVLRALKTISVIPGLKTIVGAL
IQSVKKLSDVMILTVFCLSVFALIGLQLFMGNLRNKCIQWPPTNASLEEHSIEKNITVNY
NGTLINETVFEFDWKSYIQDSRYHYFLEGFLDALLCGNSSDAGQCPEGYMCVKAGRNPNY
GYTSFDTFSWAFLSLFRLMTQDFWENLYQLTLRAAGKTYMIFFVLVIFLGSFYLINLILA
VVAMAYEEQNQATLEEAEQKEAEFQQMIEQLKKQQEAAQQAATATASEHSREPSAAGRLS
DSSSEASKLSSKSAKERRNRRKKRKQKEQSGGEEKDEDEFQKSESEDSIRRKGFRFSIEG
NRLTYEKRYSSPHQSLLSIRGSLFSPRRNSRTSLFSFRGRAKDVGSENDFADDEHSTFED
NESRRDSLFVPRRHGERRNSNLSQTSRSSRMLAVFPANGKMHSTVDCNGVVSLVGGPSVP
TSPVGQLLPEVIIDKPATDDNGTTTETEMRKRRSSSFHVSMDFLEDPSQRQRAMSIASIL
TNTVEELEESRQKCPPCWYKFSNIFLIWDCSPYWLKVKHVVNLVVMDPFVDLAITICIVL
NTLFMAMEHYPMTDHFNNVLTVGNLVFTGIFTAEMFLKIIAMDPYYYFQEGWNIFDGFIV
TLSLVELGLANVEGLSVLRSFRLLRVFKLAKSWPTLNMLIKIIGNSVGALGNLTLVLAII
VFIFAVVGMQLFGKSYKDCVCKIASDCQLPRWHMNDFFHSFLIVFRVLCGEWIETMWDCM
EVAGQAMCLTVFMMVMVIGNLVVLNLFLALLLSSFSADNLAATDDDNEMNNLQIAVDRMH
KGVAYVKRKIYEFIQQSFIRKQKILDEIKPLDDLNNKKDSCMSNHTAEIGKDLDYLKDVN
GTTSGIGTGSSVEKYIIDESDYMSFINNPSLTVTVPIAVGESDFENLNTEDFSSESDLEE
SKEKLNESSSSSEGSTVDIGAPVEEQPVVEPEETLEPEACFTEGCVQRFKCCQINVEEGR
GKQWWNLRRTCFRIVEHNWFETFIVFMILLSSGALAFEDIYIDQRKTIKTMLEYADKVFT
YIFILEMLLKWVAYGYQTYFTNAWCWLDFLIVDVSLVSLTANALGYSELGAIKSLRTLRA
LRPLRALSRFEGMRVVVNALLGAIPSIMNVLLVCLIFWLIFSIMGVNLFAGKFYHCINTT
TGDRFDIEDVNNHTDCLKLIERNETARWKNVKVNFDNVGFGYLSLLQVATFKGWMDIMYA
AVDSRNVELQPKYEESLYMYLYFVIFIIFGSFFTLNLFIGVIIDNFNQQKKKFGGQDIFM
TEEQKKYYNAMKKLGSKKPQKPIPRPGNKFQGMVFDFVTRQVFDISIMILICLNMVTMMV
ETDDQSEYVTTILSRINLVFIVLFTGECVLKLISLRHYYFTIGWNIFDFVVVILSIVGMF
LAELIEKYFVSPTLFRVIRLARIGRILRLIKGAKGIRTLLFALMMSLPALFNIGLLLFLV
MFIYAIFGMSNFAYVKREVGIDDMFNFETFGNSMICLFQITTSAGWDGLLAPILNSKPPD
CDPNKVNPGSSVKGDCGNPSVGIFFFVSYIIISFLVVVNMYIAVILENFSVATEESAEPL
SEDDFEMFYEVWEKFDPDATQFMEFEKLSQFAAALEPPLNLPQPNKLQLIAMDLPMVSGD
RIHCLDILFAFTKRVLGESGEMDALRIQMEERFMASNPSKVSYQPITTTLKRKQEEVSAV
IIQRAYRRHLLKRTVKQASFTYNKNKIKGGANLLIKEDMIIDRINENSITEKTDLTMSTA
ACPPSYDRVTKPIVEKHEQEGKDEKAKGK
Target 1 Number of Residues 2042
Target 1 Molecular Weight 228974
Target 1 Theoretical pI 5.53
Target 1 GO Classification
Function
voltage-gated ion channel activity
voltage-gated sodium channel activity
transporter activity
ion transporter activity
ion channel activity
binding
ion binding
cation binding
calcium ion binding
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 1 General Function Involved in ion channel activity
Target 1 Specific Function 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
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 124-147
  • 156-175
  • 189-207
  • 214-233
  • 250-273
  • 400-425
  • 763-787
  • 799-822
  • 831-850
  • 857-876
  • 893-913
  • 967-992
  • 1214-1237
  • 1251-1276
  • 1283-1304
  • 1309-1330
  • 1350-1377
  • 1457-1483
  • 1537-1560
  • 1572-1595
  • 1602-1625
  • 1636-1657
  • 1673-1695
  • 1762-1786
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 12642270 Link Image
Target 1 UniProtKB/Swiss-Prot ID P35498 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name SCN1A_HUMAN Link Image
Target 1 PDB ID 1BYY Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >6000 bp 
ATGGAGCAAACAGTGCTTGTACCACCAGGACCTGACAGCTTCAACTTCTTCACCAGAGAA
TCTCTTGCGGCTATTGAAAGACGCATTGCAGAAGAAAAGGCAAAGAATCCCAAACCAGAC
AAAAAAGATGACGACGAAAATGGCCCAAAGCCAAATAGTGACTTGGAAGCTGGAAAGAAC
CTTCCATTTATTTATGGAGACATTCCTCCAGAGATGGTGTCAGAGCCCCTGGAGGACCTG
GACCCCTACTATATCAATAAGAAAACTTTTATAGTATTGAATAAAGGGAAGGCCATCTTC
CGGTTCAGTGCCACCTCTGCCCTGTACATTTTAACTCCCTTCAATCCTCTTAGGAAAATA
GCTATTAAGATTTTGGTACATTCATTATTCAGCATGCTAATTATGTGCACTATTTTGACA
AACTGTGTGTTTATGACAATGAGTAACCCTCCTGATTGGACAAAGAATGTAGAATACACC
TTCACAGGAATATATACTTTTGAATCACTTATAAAAATTATTGCAAGGGGATTCTGTTTA
GAAGATTTTACTTTCCTTCGGGATCCATGGAACTGGCTCGATTTCACTGTCATTACATTT
GCGTACGTCACAGAGTTTGTGGACCTGGGCAATGTCTCGGCATTGAGAACATTCAGAGTT
CTCCGAGCATTGAAGACGATTTCAGTCATTCCAGGCCTGAAAACCATTGTGGGAGCCCTG
ATCCAGTCTGTGAAGAAGCTCTCAGATGTAATGATCCTGACTGTGTTCTGTCTGAGCGTA
TTTGCTCTAATTGGGCTGCAGCTGTTCATGGGCAACCTGAGGAATAAATGTATACAATGG
CCTCCCACCAATGCTTCCTTGGAGGAACATAGTATAGAAAAGAATATAACTGTGAATTAT
AATGGTACACTTATAAATGAAACTGTCTTTGAGTTTGACTGGAAGTCATATATTCAAGAT
TCAAGATATCATTATTTCCTGGAGGGTTTTTTAGATGCACTACTATGTGGAAATAGCTCT
GATGCAGGCCAATGTCCAGAGGGATATATGTGTGTGAAAGCTGGTAGAAATCCCAATTAT
GGCTACACAAGCTTTGATACCTTCAGTTGGGCTTTTCTGTCCTTGTTTCGACTAATGACT
CAGGACTTCTGGGAAAATCTTTATCAACTGACATTACGTGCTGCTGGGAAAACGTACATG
ATATTTTTTGTGTTGGTCATTTTCTTGGGCTCATTCTACCTAATAAATTTGATCCTGGCT
GTGGTGGCCATGGCCTACGAGGAACAGAATCAGGCCACCTTGGAAGAAGCAGAACAGAAA
GAGGCCGAATTTCAGCAGATGATTGAACAGCTTAAAAAGCAACAGGAGGCAGCTCAGCAG
GCAGCAACGGCAACTGCCTCAGAACATTCCAGAGAGCCCAGTGCAGCAGGCAGGCTCTCA
GACAGCTCATCTGAAGCCTCTAAGTTGAGTTCCAAGAGTGCTAAGGAAAGAAGAAATCGG
AGGAAGAAAAGAAAACAGAAAGAGCAGTCTGGTGGGGAAGAGAAAGATGAGGATGAATTC
CAAAAATCTGAATCTGAGGACAGCATCAGGAGGAAAGGTTTTCGCTTCTCCATTGAAGGG
AACCGATTGACATATGAAAAGAGGTACTCCTCCCCACACCAGTCTTTGTTGAGCATCCGT
GGCTCCCTATTTTCACCAAGGCGAAATAGCAGAACAAGCCTTTTCAGCTTTAGAGGGCGT
GCAAAGGATGTGGGATCTGAGAACGACTTCGCAGATGATGAGCACAGCACCTTTGAGGAT
AACGAGAGCCGTAGAGATTCCTTGTTTGTGCCCCGACGACACGGAGAGAGACGCAACAGC
AACCTGAGTCAGACCAGTAGGTCATCCCGGATGCTGGCAGTGTTTCCAGCGAATGGGAAG
ATGCACAGCACTGTGGATTGCAATGGTGTGGTTTCCTTGGTTGGTGGACCTTCAGTTCCT
ACATCGCCTGTTGGACAGCTTCTGCCAGGGGGAACAACCACTGAAACTGAAATGAGAAAG
AGAAGGTCAAGTTCTTTCCACGTTTCCATGGACTTTCTAGAAGATCCTTCCCAAAGGCAA
CGAGCAATGAGTATAGCCAGCATTCTAACAAATACAGTAGAAGAACTTGAAGAATCCAGG
CAGAAATGCCCACCCTGTTGGTATAAATTTTCCAACATATTCTCAATCTGGGACTGTTCT
CCATATTGGTTAAAAGTGAAACATGTTGTCAACCTGGTCGTGATGGACCCATTTGTTGAC
CTGGCCATCACCATCTGTATTGTCTTAAATACTCTTTTCATGGCCATGGAGCACTATCCA
ATGACGGACCATTTCAATAATGTGCTTACAGTAGGAAACTTGGTTTTCACTGGGATCTTT
ACAGCAGAAATGTTTCTGAAAATTATTGCCATGGATCCTTACTATTATTTCCAAGAAGGC
TGGAATATCTTTGACGGTTTTATTGTGACGCTTAGCCTGGTAGAACTTGGACTCGCCAAT
GTGGAAGGATTATCTGTTCTCCGTTCATTTCGATTGCTGCGAGTTTTCAAGTTGGCAAAA
TCTTGGCCAACGTTAAATATGCTAATAAAGATCATCGGCAATTCCGTGGGGGCTCTGGGA
AATTTAACCCTCGTCTTGGCCATCATCGTCTTCATTTTTGCCGTGGTCGGCATGCAGCTC
TTTGGTAAAAGCTACAAAGATTGTGTCTGCAAGATCGCCAGTGATTGTCAACTCCCACAA
CGCTGGCACATGAATGACTTCTTCCACTCCTTCCTGATTGTGTTCCGCGTGCTGTGTGGG
GAGTGGATAGAGACCATGTGGGACTGTATGGAGGTTGCTGGTCAAGCCATGTGCCTTACT
GTCTTCATGATGGTCATGGTGATTGGAAACCTAGTGGTCCTGAATCTCTTTCTGGCCTTG
CTTCTGAGCTCATTTAGTGCAGACAACCTTGCAGCCACTGATGATGATAATGAAATGAAT
AATCTCCAAATTGCTGTGGATAGGATGCACAAAGGAGTAGCTTATGTGAAAAGAAAAATA
TATGAATTTATTCAACAGTCCTTCATTAGGAAACAAAAGATTTTAGATGAAATTAAACCA
CTTGATGATCTAAACAACAAGAAAGACAGTTGTATGTCCAATCATACAACAGAAATTGGG
AAAGATCTTGACTATCTTAAAGATGTAAATGGAACTACAAGTGGTATAGGAACTGGCAGC
AGTGTTGAAAAATACATTATTGATGAAAGTGATTACATGTCATTCATAAACAACCCCAGT
CTTACTGTGACTGTACCAATTGCTGTAGGAGAATCTGACTTTGAAAATTTAAACACGGAA
GACTTTAGTAGTGAATCGGATCTGGAAGAAAGCAAAGAGAAACTGAATGAAAGCAGTAGC
TCATCAGAAGGTAGCACTGTGGGACATCGGCGCCCTGTAGAAGAACAGCCCGTAGTGGAA
CCTGAAGAAACTCTTGAACCAGAAGCTTGTTTCACTGAAGGCTGTGTACAAAGATTCAAG
TGTTGTCAAATCAATGTGGAAGAAGGCAGAGGAAAACAATGGTGGAACCTGAGAAGGACG
TGTTTCCGAATAGTTGAACATAACTGGTTTGAGACCTTCATTGTTTTCATGATTCTCCTT
AGTAGTGGTGCTCTGGCATTTGAAGATATATATATTGATCAGCGAAAGACGATTAAGACG
ATGTTGGAATATGCTGACAAGGTTTTCACTTACATTTTCATTCTGGAAATGCTTCTAAAA
TGGGTGGCATATGGCTATCAAACATATTTCACCAATGCCTGGTGTTGGCTGGACTTCTTA
ATTGTTGATGTTTCATTGGTCAGTTTAACAGCAAATGCCTTGGGTTACTCAGAACTTGGA
GCCATCAAATCTCTCAGGACACTAAGAGCTCTGAGACCTCTAAGAGCCTTATCTCGATTT
GAAGGGATGAGGGTGGTTGTGAATGCCCTTTTAGGAGCAATTCCATCCATCATGAATGTG
CTTCTGGTTTGTCTTATATTCTGGCTAATTTTCAGCATCATGGGCGTAAATTTGTTTGCT
GGCAAATTCTACCACTGTATTAACACCACAACTGGTGACAGGTTTGACATCGAAGACGTG
AATAATCATACTGATTGCCTAAAACTAATAGAAAGAAATGAGACTGCTCGATGGAAAAAT
GTGAAAGTAAACTTTGATAATGTAGGATTTGGGTATCTCTCTTTGCTTCAAGTTGCCACA
TTCAAAGGATGGATGGATATAATGTATGCAGCAGTTGATTCCAGAAATGTGGAACTCCAG
CCTAAGTATGAAGAAAGTCTGTACATGTATCTTTACTTTGTTATTTTCATCATCTTTGGG
TCCTTCTTCACCTTGAACCTGTTTATTGGTGTCATCATAGATAATTTCAACCAGCAGAAA
AAGAAGTTTGGAGGTCAAGACATCTTTATGACAGAAGAACAGAAGAAATACTATAATGCA
ATGAAAAAATTAGGATCGAAAAAACCGCAAAAGCCTATACCTCGACCAGGAAACAAATTT
CAAGGAATGGTCTTTGACTTCGTAACCAGACAAGTTTTTGACATAAGCATCATGATTCTC
ATCTGTCTTAACATGGTCACAATGATGGTGGAAACAGATGACCAGAGTGAATATGTGACT
ACCATTTTGTCACGCATCAATCTGGTGTTCATTGTGCTATTTACTGGAGAGTGTGTACTG
AAACTCATCTCTCTACGCCATTATTATTTTACCATTGGATGGAATATTTTTGATTTTGTG
GTTGTCATTCTCTCCATTGTAGGTATGTTTCTTGCCGAGCTGATAGAAAAGTATTTCGTG
TCCCCTACCCTGTTCCGAGTGATCCGTCTTGCTAGGATTGGCCGAATCCTACGTCTGATC
AAAGGAGCAAAGGGGATCCGCACGCTGCTCTTTGCTTTGATGATGTCCCTTCCTGCGTTG
TTTAACATCGGCCTCCTACTCTTCCTAGTCATGTTCATCTACGCCATCTTTGGGATGTCC
AACTTTGCCTATGTTAAGAGGGAAGTTGGGATCGATGACATGTTCAACTTTGAGACCTTT
GGCAACAGCATGATCTGCCTATTCCAAATTACAACCTCTGCTGGCTGGGATGGATTGCTA
GCACCCATTCTCAACAGTAAGCCACCCGACTGTGACCCTAATAAAGTTAACCCTGGAAGC
TCAGTTAAGGGAGACTGTGGGAACCCATCTGTTGGAATTTTCTTTTTTGTCAGTTACATC
ATCATATCCTTCCTGGTTGTGGTGAACATGTACATCGCGGTCATCCTGGAGAACTTCAGT
GTTGCTACTGAAGAAAGTGCAGAGCCTCTGAGTGAGGATGACTTTGAGATGTTCTATGAG
GTTTGGGAGAAGTTTGATCCCGATGCAACTCAGTTCATGGAATTTGAAAAATTATCTCAG
TTTGCAGCTGCGCTTGAACCGCCTCTCAATCTGCCACAACCAAACAAACTCCAGCTCATT
GCCATGGATTTGCCCATGGTGAGTGGTGACCGGATCCACTGTCTTGATATCTTATTTGCT
TTTACAAAGCGGGTTCTAGGAGAGAGTGGAGAGATGGATGCTCTACGAATACAGATGGAA
GAGCGATTCATGGCTTCCAATCCTTCCAAGGTCTCCTATCAGCCAATCACTACTACTTTA
AAACGAAAACAAGAGGAAGTATCTGCTGTCATTATTCAGCGTGCTTACAGACGCCACCTT
TTAAAGCGAACTGTAAAACAAGCTTCCTTTACGTACAATAAAAACAAAATCAAAGGTGGG
GCTAATCTTCTTATAAAAGAAGACATGATAATTGACAGAATAAATGAAAACTCTATTACA
GAAAAAACTGATCTGACCATGTCCACTGCAGCTTGTCCACCTTCCTATGACCGGGTGACA
AAGCCAATTGTGGAAAAACATGAGCAAGAAGGCAAAGATGAAAAAGCCAAAGGGAAATAA
Target 1 GenBank Gene ID
Target 1 GeneCard ID SCN1A Link Image
Target 1 GenAtlas ID SCN1A Link Image
Target 1 HGNC ID HGNC:10585 Link Image
Target 1 Chromosome Location 2
Target 1 Locus 2q24.3
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Escayg A, MacDonald BT, Meisler MH, Baulac S, Huberfeld G, An-Gourfinkel I, Brice A, LeGuern E, Moulard B, Chaigne D, Buresi C, Malafosse A: Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2. Nat Genet. 2000 Apr;24(4):343-5. [PubMed Link Image]
  2. Wallace RH, Scheffer IE, Barnett S, Richards M, Dibbens L, Desai RR, Lerman-Sagie T, Lev D, Mazarib A, Brand N, Ben-Zeev B, Goikhman I, Singh R, Kremmidiotis G, Gardner A, Sutherland GR, George AL Jr, Mulley JC, Berkovic SF: Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus. Am J Hum Genet. 2001 Apr;68(4):859-65. Epub 2001 Mar 13. [PubMed Link Image]
  3. Escayg A, Heils A, MacDonald BT, Haug K, Sander T, Meisler MH: A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus--and prevalence of variants in patients with epilepsy. Am J Hum Genet. 2001 Apr;68(4):866-73. Epub 2001 Mar 14. [PubMed Link Image]
  4. Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P: De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet. 2001 Jun;68(6):1327-32. Epub 2001 May 15. [PubMed Link Image]
  5. Abou-Khalil B, Ge Q, Desai R, Ryther R, Bazyk A, Bailey R, Haines JL, Sutcliffe JS, George AL Jr: Partial and generalized epilepsy with febrile seizures plus and a novel SCN1A mutation. Neurology. 2001 Dec 26;57(12):2265-72. [PubMed Link Image]
  6. Lu CM, Han J, Rado TA, Brown GB: Differential expression of two sodium channel subtypes in human brain. FEBS Lett. 1992 May 25;303(1):53-8. [PubMed Link Image]
  7. Malo MS, Blanchard BJ, Andresen JM, Srivastava K, Chen XN, Li X, Jabs EW, Korenberg JR, Ingram VM: Localization of a putative human brain sodium channel gene (SCN1A) to chromosome band 2q24. Cytogenet Cell Genet. 1994;67(3):178-86. [PubMed Link Image]
Target 1 Drug References
  1. Coppola G, Capovilla G, Montagnini A, Romeo A, Spano M, Tortorella G, Veggiotti P, Viri M, Pascotto A: Topiramate as add-on drug in severe myoclonic epilepsy in infancy: an Italian multicenter open trial. Epilepsy Res. 2002 Mar;49(1):45-8. [PubMed Link Image]
  2. Nieto Barrera M, Candau Fernandez Mensaque R, Nieto Jimenez M: [Severe myoclonic epilepsy in infancy (Dravet's syndrome). Its nosological characteristics and therapeutic aspects] Rev Neurol. 2003 Jul 1-15;37(1):64-8. [PubMed Link Image]
  3. Ceulemans B, Cras P: "Severe myoclonic epilepsy in infancy". Relevance for the clinician of severe epilepsy starting in infancy. Acta Neurol Belg. 2004 Sep;104(3):95-9. [PubMed Link Image]
  4. Ceulemans B, Boel M, Claes L, Dom L, Willekens H, Thiry P, Lagae L: Severe myoclonic epilepsy in infancy: toward an optimal treatment. J Child Neurol. 2004 Jul;19(7):516-21. [PubMed Link Image]
  5. Korff C, Laux L, Kelley K, Goldstein J, Koh S, Nordli D Jr: Dravet syndrome (severe myoclonic epilepsy in infancy): a retrospective study of 16 patients. J Child Neurol. 2007 Feb;22(2):185-94. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 357
Target 2 Name Carbonic anhydrase 2
Target 2 Synonyms
  1. CA-II
  2. Carbonate dehydratase II
  3. Carbonic anhydrase C
  4. Carbonic anhydrase II
  5. EC 4.2.1.1
Target 2 Gene Name CA2
Target 2 Protein Sequence >Carbonic anhydrase 2 
SHHWGYGKHNGPEHWHKDFPIAKGERQSPVDIDTHTAKYDPSLKPLSVSYDQATSLRILN
NGHAFNVEFDDSQDKAVLKGGPLDGTYRLIQFHFHWGSLDGQGSEHTVDKKKYAAELHLV
HWNTKYGDFGKAVQQPDGLAVLGIFLKVGSAKPGLQKVVDVLDSIKTKGKSADFTNFDPR
GLLPESLDYWTYPGSLTTPPLLECVTWIVLKEPISVSSEQVLKFRKLNFNGEGEPEELMV
DNWRPAQPLKNRQIKASFK
Target 2 Number of Residues 263
Target 2 Molecular Weight 29115
Target 2 Theoretical pI 7.47
Target 2 GO Classification
Function
binding
ion binding
cation binding
transition metal ion binding
zinc ion binding
catalytic activity
lyase activity
carbon-oxygen lyase activity
hydro-lyase activity
carbonate dehydratase activity
Process
physiological process
metabolism
cellular metabolism
one-carbon compound metabolism
Component
Not Available
Target 2 General Function Inorganic ion transport and metabolism
Target 2 Specific Function Reversible hydration of carbon dioxide
Target 2 Pathways
Name SMPDB Link KEGG Link
Nitrogen metabolism map00910 Link Image
Target 2 Reactions
  • H2CO3 = CO2 + H2O
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 179780 Link Image
Target 2 UniProtKB/Swiss-Prot ID P00918 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name CAH2_HUMAN Link Image
Target 2 PDB ID 1T9N Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location
  • Cytoplasm
Target 2 Gene Sequence >783 bp 
ATGTCCCATCACTGGGGGTACGGCAAACACAACGGACCTGAGCACTGGCATAAGGACTTC
CCCATTGCCAAGGGAGAGCGCCAGTCCCCTGTTGACATCGACACTCATACAGCCAAGTAT
GACCCTTCCCTGAAGCCCCTGTCTGTTTCCTATGATCAAGCAACTTCCCTGAGGATCCTC
AACAATGGTCATGCTTTCAACGTGGAGTTTGATGACTCTCAGGACAAAGCAGTGCTCAAG
GGAGGACCCCTGGATGGCACTTACAGATTGATTCAGTTTCACTTTCACTGGGGTTCACTT
GATGGACAAGGTTCAGAGCATACTGTGGATAAAAAGAAATATGCTGCAGAACTTCACTTG
GTTCACTGGAACACCAAATATGGGGATTTTGGGAAAGCTGTGCAGCAACCTGATGGACTG
GCCGTTCTAGGTATTTTTTTGAAGGTTGGCAGCGCTAAACCGGGCCTTCAGAAAGTTGTT
GATGTGCTGGATTCCATTAAAACAAAGGGCAAGAGTGCTGACTTCACTAACTTCGATCCT
CGTGGCCTCCTTCCTGAATCCTTGGATTACTGGACCTACCCAGGCTCACTGACCACCCCT
CCTCTTCTGGAATGTGTGACCTGGATTGTGCTCAAGGAACCCATCAGCGTCAGCAGCGAG
CAGGTGTTGAAATTCCGTAAACTTAACTTCAATGGGGAGGGTGAACCCGAAGAACTGATG
GTGGACAACTGGCGCCCAGCTCAGCCACTGAAGAACAGGCAAATCAAAGCTTCCTTCAAA
TAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID CA2 Link Image
Target 2 GenAtlas ID CA2 Link Image
Target 2 HGNC ID HGNC:1373 Link Image
Target 2 Chromosome Location 8
Target 2 Locus 8q22
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Cox JD, Hunt JA, Compher KM, Fierke CA, Christianson DW: Structural influence of hydrophobic core residues on metal binding and specificity in carbonic anhydrase II. Biochemistry. 2000 Nov 14;39(45):13687-94. [PubMed Link Image]
  2. Roth DE, Venta PJ, Tashian RE, Sly WS: Molecular basis of human carbonic anhydrase II deficiency. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1804-8. [PubMed Link Image]
  3. Venta PJ, Welty RJ, Johnson TM, Sly WS, Tashian RE: Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His----Tyr): complete structure of the normal human CA II gene. Am J Hum Genet. 1991 Nov;49(5):1082-90. [PubMed Link Image]
  4. Venta PJ, Montgomery JC, Hewett-Emmett D, Tashian RE: Comparison of the 5' regions of human and mouse carbonic anhydrase II genes and identification of possible regulatory elements. Biochim Biophys Acta. 1985 Dec 18;826(4):195-201. [PubMed Link Image]
  5. Montgomery JC, Venta PJ, Tashian RE, Hewett-Emmett D: Nucleotide sequence of human liver carbonic anhydrase II cDNA. Nucleic Acids Res. 1987 Jun 11;15(11):4687. [PubMed Link Image]
  6. Murakami H, Marelich GP, Grubb JH, Kyle JW, Sly WS: Cloning, expression, and sequence homologies of cDNA for human carbonic anhydrase II. Genomics. 1987 Oct;1(2):159-66. [PubMed Link Image]
  7. Eriksson AE, Jones TA, Liljas A: Refined structure of human carbonic anhydrase II at 2.0 A resolution. Proteins. 1988;4(4):274-82. [PubMed Link Image]
  8. Eriksson AE, Kylsten PM, Jones TA, Liljas A: Crystallographic studies of inhibitor binding sites in human carbonic anhydrase II: a pentacoordinated binding of the SCN- ion to the zinc at high pH. Proteins. 1988;4(4):283-93. [PubMed Link Image]
  9. Lin KT, Deutsch HF: Human carbonic anhydrases. XII. The complete primary structure of the C isozyme. J Biol Chem. 1974 Apr 25;249(8):2329-37. [PubMed Link Image]
  10. Liljas A, Kannan KK, Bergsten PC, Waara I, Fridborg K, Strandberg B, Carlbom U, Jarup L, Lovgren S, Petef M: Crystal structure of human carbonic anhydrase C. Nat New Biol. 1972 Feb 2;235(57):131-7. [PubMed Link Image]
  11. 6407977 Jones GL, Shaw DC: A chemical and enzymological comparison of the common major human erythrocyte carbonic anhydrase II, its minor component, and a new genetic variant, CA II Melbourne (237 Pro leads to His). Hum Genet. 1983;63(4):392-9.
  12. 6817747 Jones GL, Sofro AS, Shaw DC: Chemical and enzymological characterization of an Indonesian variant of human erythrocyte carbonic anhydrase II, CAII Jogjakarta (17 Lys leads to Glu). Biochem Genet. 1982 Oct;20(9-10):979-1000.
  13. 823150 Henderson LE, Henriksson D, Nyman PO: Primary structure of human carbonic anhydrase C. J Biol Chem. 1976 Sep 25;251(18):5457-63.
  14. 8834238 Soda H, Yukizane S, Yoshida I, Koga Y, Aramaki S, Kato H: A point mutation in exon 3 (His 107-->Tyr) in two unrelated Japanese patients with carbonic anhydrase II deficiency with central nervous system involvement. Hum Genet. 1996 Apr;97(4):435-7.
  15. 9143915 Hu PY, Lim EJ, Ciccolella J, Strisciuglio P, Sly WS: Seven novel mutations in carbonic anhydrase II deficiency syndrome identified by SSCP and direct sequencing analysis. Hum Mutat. 1997;9(5):383-7.
  16. 9541386 Stams T, Chen Y, Boriack-Sjodin PA, Hurt JD, Liao J, May JA, Dean T, Laipis P, Silverman DN, Christianson DW: Structures of murine carbonic anhydrase IV and human carbonic anhydrase II complexed with brinzolamide: molecular basis of isozyme-drug discrimination. Protein Sci. 1998 Mar;7(3):556-63.
Target 2 Drug References
  1. Casini A, Antel J, Abbate F, Scozzafava A, David S, Waldeck H, Schafer S, Supuran CT: Carbonic anhydrase inhibitors: SAR and X-ray crystallographic study for the interaction of sugar sulfamates/sulfamides with isozymes I, II and IV. Bioorg Med Chem Lett. 2003 Mar 10;13(5):841-5. [PubMed Link Image]
  2. Winum JY, Scozzafava A, Montero JL, Supuran CT: Sulfamates and their therapeutic potential. Med Res Rev. 2005 Mar;25(2):186-228. [PubMed Link Image]
  3. Maryanoff BE, McComsey DF, Costanzo MJ, Hochman C, Smith-Swintosky V, Shank RP: Comparison of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II by using topiramate as a structural platform. J Med Chem. 2005 Mar 24;48(6):1941-7. [PubMed Link Image]
  4. Di Fiore A, Scozzafava A, Winum JY, Montero JL, Pedone C, Supuran CT, De Simone G: Carbonic anhydrase inhibitors: binding of an antiglaucoma glycosyl-sulfanilamide derivative to human isoform II and its consequences for the drug design of enzyme inhibitors incorporating sugar moieties. Bioorg Med Chem Lett. 2007 Mar 15;17(6):1726-31. Epub 2007 Jan 8. [PubMed Link Image]
  5. Ma L, Huang YG, Deng YC, Tian JY, Rao ZR, Che HL, Zhang HF, Zhao G: Topiramate reduced sweat secretion and aquaporin-5 expression in sweat glands of mice. Life Sci. 2007 Jun 6;80(26):2461-8. Epub 2007 Apr 29. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 382
Target 3 Name Glutamate receptor, ionotropic kainate 1
Target 3 Synonyms
  1. EAA3
  2. Excitatory amino acid receptor 3
  3. GluR-5
  4. GluR5
  5. Glutamate receptor 5
  6. Glutamate receptor, ionotropic kainate 1 precursor
Target 3 Gene Name GRIK1
Target 3 Protein Sequence >Glutamate receptor, ionotropic kainate 1 precursor 
MEHGTLLAQPGLWTRDTSWALLYFLCYILPQTAPQVLRIGGIFETVENEPVNVEELAFKF
AVTSINRNRTLMPNTTLTYDIQRINLFDSFEASRRACDQLALGVAALFGPSHSSSVSAVQ
SICNALEVPHIQTRWKHPSVDNKDLFYINLYPDYAAISRAILDLVLYYNWKTVTVVYEDS
TGLIRLQELIKAPSRYNIKIKIRQLPSGNKDAKPLLKEMKKGKEFYVIFDCSHETAAEIL
KQILFMGMMTEYYHYFFTTLDLFALDLELYRYSGVNMTGFRLLNIDNPHVSSIIEKWSME
RLQAPPRPETGLLDGMMTTEAALMYDAVYMVAIASHRASQLTVSSLQCHRHKPWRLGPRF
MNLIKEARWDGLTGHITFNKTNGLRKDFDLDIISLKEEGTEKAAGEVSKHLYKVWKKIGI
WNSNSGLNMTDSNKDKSSNITDSLANRTLIVTTILEEPYVMYRKSDKPLYGNDRFEGYCL
DLLKELSNILGFIYDVKLVPDGKYGAQNDKGEWNGMVKELIDHRADLAVAPLTITYVREK
VIDFSKPFMTLGISILYRKPNGTNPGVFSFLNPLSPDIWMYVLLACLGVSCVLFVIARFT
PYEWYNPHPCNPDSDVVENNFTLLNSFWFGVGALMQQGSELMPKALSTRIVGGIWWFFTL
IIISSYTANLAAFLTVERMESPIDSADDLAKQTKIEYGAVRDGSTMTFFKKSKISTYEKM
WAFMSSRQQTALVRNSDEGIQRVLTTDYALLMESTSIEYVTQRNCNLTQIGGLIDSKGYG
VGTPIGSPYRDKITIAILQLQEEGKLHMMKEKWWRGNGCPEEDNKEASALGVENIGGIFI
VLAAGLVLSVFVAIGEFIYKSRKNNDIEQAFCFFYGLQCKQTHPTNSTSGTTLSTDLECG
KLIREERGIRKQSSVHTV
Target 3 Number of Residues 933
Target 3 Molecular Weight 103982
Target 3 Theoretical pI 7.09
Target 3 GO Classification
Function
transporter activity
ion transporter activity
ion channel activity
ligand-gated ion channel activity
extracellular ligand-gated ion channel activity
excitatory extracellular ligand-gated ion channel activity
glutamate-gated ion channel activity
signal transducer activity
receptor activity
transmembrane receptor activity
glutamate receptor activity
ionotropic glutamate receptor activity
Process
physiological process
cellular physiological process
transport
ion transport
Component
cell
membrane
Target 3 General Function Involved in ionotropic glutamate receptor activity
Target 3 Specific Function L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. May be involved in the transmission of light information from the retina to the hypothalamus. This receptor binds domoate > kainate > L-glutamate = quisqualate > CNQX = DNQX > AMPA > dihydrokainate > NMDA
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-30
Target 3 Transmembrane Regions
  • 577-597
  • 616-636
  • 654-674
  • 835-855
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 455448 Link Image
Target 3 UniProtKB/Swiss-Prot ID P39086 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name GRIK1_HUMAN Link Image
Target 3 PDB ID 1YAE Link Image
Target 3 PDB File Show
Target 3 3D Structure
Target 3 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 3 Gene Sequence >2757 bp 
ATGGAGCACGGCACACTCCTCGCCCAGCCCGGGCTCTGGACCAGGGACACCAGCTGGGCA
CTCCTCTATTTCCTCTGCTATATCCTCCCTCAGACCGCCCCGCAAGTACTCAGGATCGGA
GGGATTTTTGAAACAGTGGAAAATGAGCCTGTTAATGTTGAAGAATTAGCTTTCAAGTTT
GCAGTCACCAGCATTAACAGAAACCGAACCCTGATGCCTAACACCACATTAACCTATGAC
ATCCAGAGAATTAACCTTTTTGATAGTTTTGAAGCCTCGCGGAGAGCATGTGACCAGCTG
GCTCTTGGTGTGGCTGCTCTCTTTGGCCCTTCCCATAGCTCCTCCGTCAGTGCTGTGCAG
TCGATTTGCAATGCTCTCGAAGTTCCACACATACAGACCCGCTGGAAACACCCCTCGGTG
GACAACAAAGATTTGTTTTACATCAACCTTTACCCAGATTATGCAGCTATCAGCAGGGCG
ATCCTGGATCTGGTCCTCTATTACAACTGGAAAACAGTGACCGTGGTGTATGAAGACAGC
ACAGGTCTAATTCGTCTACAAGAGCTCATCAAAGCTCCCTCCAGATATAATATTAAAATC
AAAATCCGCCAGCTGCCCTCTGGGAATAAAGATGCCAAGCCTTTACTCAAGGAGATGAAG
AAAGGCAAGGAGTTCTATGTGATATTTGATTGTTCACATGAAACAGCCGCTGAAATCCTT
AAGCAGATTCTGTTCATGGGCATGATGACCGAGTACTATCACTACTTTTTCACAACCCTG
GACTTATTTGCTTTGGATCTGGAACTCTATAGGTACAGTGGCGTAAACATGACCGGGTTT
CGGCTGCTTAACATTGACAACCCTCACGTGTCATCCATCATTGAGAAGTGGTCCATGGAG
AGACTGCAGGCCCCACCCAGGCCCGAGACTGGCCTTTTGGATGGCATGATGACAACTGAA
GCGGCTCTGATGTACGATGCTGTGTACATGGTGGCCATTGCCTCGCACCGGGCATCCCAG
CTGACCGTCAGCTCCCTGCAGTGCCATAGACATAAGCCATGGCGCCTCGGACCCAGATTT
ATGAACCTGATCAAAGAGGCCCGGTGGGATGGCTTGACTGGGCATATCACCTTTAATAAA
ACCAATGGCTTGAGGAAGGATTTTGATCTGGACATTATTAGTCTCAAAGAGGAAGGAACT
GAAAAGGCTGCTGGCGAAGTGTCTAAACACTTGTATAAAGTGTGGAAGAAGATTGGGATT
TGGAATTCCAACAGTGGGCTTAACATGACGGACAGCAACAAAGACAAGTCCAGCAATATC
ACTGATTCATTGGCCAACAGAACACTCATTGTCACCACCATTCTGGAAGAACCCTATGTT
ATGTACAGGAAATCTGATAAGCCTCTATATGGAAATGACAGATTTGAAGGATATTGCCTA
GACCTGTTGAAAGAATTGTCAAACATCCTGGGTTTCATTTATGATGTTAAACTAGTTCCC
GATGGCAAATATGGGGCCCAGAATGACAAAGGGGAGTGGAACGGGATGGTTAAAGAACTC
ATAGATCACAGGGCTGACCTGGCAGTGGCTCCTCTTACCATCACCTACGTGCGGGAGAAA
GTCATTGACTTCTCCAAACCCTTCATGACCCTAGGCATCAGCATTCTCTACCGGAAGCCC
AATGGTACCAATCCAGGCGTTTTCTCCTTCCTCAACCCCCTGTCTCCAGATATTTGGATG
TATGTGCTCTTAGCCTGCTTGGGAGTCAGCTGTGTACTCTTTGTGATTGCAAGGTTTACA
CCCTACGAGTGGTATAACCCCCACCCATGCAACCCTGACTCAGACGTGGTGGAAAACAAT
TTTACTTTACTAAATAGTTTCTGGTTTGGAGTTGGAGCTCTCATGCAGCAAGGATCAGAG
CTGATGCCCAAAGCTCTATCGACCAGAATAGTTGGAGGGATATGGTGGTTTTTCACCCTA
ATCATCATTTCATCCTACACGGCCAATCTGGCTGCCTTCTTGACAGTAGAGAGAATGGAA
TCCCCCATAGATTCGGCAGATGATCTGGCAAAGCAAACCAAGATAGAATATGGGGCGGTT
AGAGATGGATCAACAATGACCTTCTTCAAGAAATCAAAAATCTCCACCTATGAGAAGATG
TGGGCTTTCATGAGCAGCAGGCAGCAGACCGCCCTGGTAAGAAACAGTGATGAGGGGATC
CAGAGAGTGCTCACCACAGACTACGCGCTGCTGATGGAGTCCACCAGCATTGAGTATGTG
ACGCAGAGAAACTGCAACCTCACTCAGATCGGGGGCCTCATTGACTCCAAAGGTTACGGA
GTGGGAACACCTATTGGTTCTCCTTACCGGGATAAAATTACTATTGCTATTCTTCAACTC
CAAGAAGAAGGGAAGCTGCATATGATGAAAGAGAAGTGGTGGCGTGGGAATGGCTGCCCC
GAGGAAGACAACAAAGAAGCCAGTGCCCTGGGAGTGGAAAATATTGGAGGCATCTTCATT
GTTCTGGCTGCCGGACTGGTCCTTTCTGTATTTGTAGCTATTGGAGAATTCATATACAAA
TCACGGAAGAATAATGATATTGAACAGGCTTTTTGTTTCTTTTATGGACTGCAATGTAAG
CAAACCCATCCAACCAACTCCACTTCTGGAACTACTTTATCTACGGATTTAGAATGTGGT
AAATTAATTCGAGAGGAGAGAGGGATTCGAAAACAGTCCTCAGTTCATACTGTGTAA
Target 3 GenBank Gene ID
Target 3 GeneCard ID GRIK1 Link Image
Target 3 GenAtlas ID GRIK1 Link Image
Target 3 HGNC ID HGNC:4579 Link Image
Target 3 Chromosome Location Not Available
Target 3 Locus Not Available
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Shibata H, Joo A, Fujii Y, Tani A, Makino C, Hirata N, Kikuta R, Ninomiya H, Tashiro N, Fukumaki Y: Association study of polymorphisms in the GluR5 kainate receptor gene (GRIK1) with schizophrenia. Psychiatr Genet. 2001 Sep;11(3):139-44. [PubMed Link Image]
  2. Nutt SL, Kamboj RK: RNA editing of human kainate receptor subunits. Neuroreport. 1994 Dec 20;5(18):2625-9. [PubMed Link Image]
  3. Gregor P, O'Hara BF, Yang X, Uhl GR: Expression and novel subunit isoforms of glutamate receptor genes GluR5 and GluR6. Neuroreport. 1993 Sep 30;4(12):1343-6. [PubMed Link Image]
  4. Korczak B, Nutt SL, Fletcher EJ, Hoo KH, Elliott CE, Rampersad V, McWhinnie EA, Kamboj RK: cDNA cloning and functional properties of human glutamate receptor EAA3 (GluR5) in homomeric and heteromeric configuration. Receptors Channels. 1995;3(1):41-9. [PubMed Link Image]
Target 3 Drug References
  1. Rogawski MA, Gryder D, Castaneda D, Yonekawa W, Banks MK, Lia H: GluR5 kainate receptors, seizures, and the amygdala. Ann N Y Acad Sci. 2003 Apr;985:150-62. [PubMed Link Image]
  2. Gryder DS, Rogawski MA: Selective antagonism of GluR5 kainate-receptor-mediated synaptic currents by topiramate in rat basolateral amygdala neurons. J Neurosci. 2003 Aug 6;23(18):7069-74. [PubMed Link Image]
  3. Kaminski RM, Banerjee M, Rogawski MA: Topiramate selectively protects against seizures induced by ATPA, a GluR5 kainate receptor agonist. Neuropharmacology. 2004 Jun;46(8):1097-104. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 592
Target 4 Name Carbonic anhydrase 4
Target 4 Synonyms
  1. CA-IV
  2. Carbonate dehydratase IV
  3. Carbonic anhydrase 4 precursor
  4. Carbonic anhydrase IV
  5. EC 4.2.1.1
Target 4 Gene Name CA4
Target 4 Protein Sequence >Carbonic anhydrase 4 precursor 
MRMLLALLALSAARPSASAESHWCYEVQAESSNYPCLVPVKWGGNCQKDRQSPINIVTTK
AKVDKKLGRFFFSGYDKKQTWTVQNNGHSVMMLLENKASISGGGLPAPYQAKQLHLHWSD
LPYKGSEHSLDGEHFAMEMHIVHEKEKGTSRNVKEAQDPEDEIAVLAFLVEAGTQVNEGF
QPLVEALSNIPKPEMSTTMAESSLLDLLPKEEKLRHYFRYLGSLTTPTCDEKVVWTVFRE
PIQLHREQILAFSQKLYYDKEQTVSMKDNVRPLQQLGQRTVIKSGAPGRPLPWALPALLG
PMLACLLAGFLR
Target 4 Number of Residues 317
Target 4 Molecular Weight 35033
Target 4 Theoretical pI 7.94
Target 4 GO Classification
Function
binding
ion binding
cation binding
transition metal ion binding
zinc ion binding
catalytic activity
lyase activity
carbon-oxygen lyase activity
hydro-lyase activity
carbonate dehydratase activity
Process
physiological process
metabolism
cellular metabolism
one-carbon compound metabolism
Component
Not Available
Target 4 General Function Inorganic ion transport and metabolism
Target 4 Specific Function Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4
Target 4 Pathways
Name SMPDB Link KEGG Link
Nitrogen metabolism map00910 Link Image
Target 4 Reactions
  • H2CO3 = CO2 + H2O
Target 4 Pfam Domain Function
Target 4 Signals
  • 1-18
Target 4 Transmembrane Regions
  • 292-311
Target 4 Essentiality Non-Essential
Target 4 GenBank ID Protein 179791 Link Image
Target 4 UniProtKB/Swiss-Prot ID P22748 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name CAH4_HUMAN Link Image
Target 4 PDB ID 1ZNC Link Image
Target 4 PDB File Show
Target 4 3D Structure
Target 4 Cellular Location
  • Cell membrane
  • GPI-anchor
  • lipid-anchor
Target 4 Gene Sequence >939 bp 
ATGCGGATGCTGCTGGCGCTCCTGGCCCTCTCCGCGGCGCGGCCATCGGCCAGTGCAGAG
TCACACTGGTGCTACGAGGTTCAAGCCGAGTCCTCCAACTACCCCTGCTTGGTGCCAGTC
AAGTGGGGTGGAAACTGCCAGAAGGACCGCCAGTCCCCCATCAACATCGTCACCACCAAG
GCAAAGGTGGACAAAAAACTGGGACGCTTCTTCTTCTCTGGCTACGATAAGAAGCAAACG
TGGACTGTCCAAAATAACGGGCACTCAGTGATGATGTTGCTGGAGAACAAGGCCAGCATT
TCTGGAGGAGGACTGCCTGCCCCATACCAGGCCAAACAGTTGCACCTGCACTGGTCCGAC
TTGCCATATAAGGGCTCGGAGCACAGCCTCGATGGGGAGCACTTTGCCATGGAGATGCAC
ATAGTACATGAGAAAGAGAAGGGGACATCGAGGAATGTGAAAGAGGCCCAGGACCCTGAA
GACGAAATTGCGGTGCTGGCCTTTCTGGTGGAGGCTGGAACCCAGGTGAACGAGGGCTTC
CAGCCACTGGTGGAGGCACTGTCTAATATCCCCAAACCTGAGATGAGCACTACGATGGCA
GAGAGCAGCCTGTTGGACCTGCTCCCCAAGGAGGAGAAACTGAGGCACTACTTCCGCTAC
CTGGGCTCACTCACCACACCGACCTGCGATGAGAAGGTCGTCTGGACTGTGTTCCGGGAG
CCCATTCAGCTTCACAGAGAACAGATCCTGGCATTCTCTCAGAAGCTGTACTACGACAAG
GAACAGACAGTGAGCATGAAGGACAATGTCAGGCCCCTGCAGCAGCTGGGGCAGCGCACG
GTGATAAAGTCCGGGGCCCCGGGTCGGCCGCTGCCCTGGGCCCTGCCTGCCCTGCTGGGC
CCCATGCTGGCCTGCCTGCTGGCCGGCTTCCTGCGATGA
Target 4 GenBank Gene ID
Target 4 GeneCard ID CA4 Link Image
Target 4 GenAtlas ID CA4 Link Image
Target 4 HGNC ID HGNC:1375 Link Image
Target 4 Chromosome Location 17
Target 4 Locus 17q23
Target 4 SNPs SNPJam Report Link Image
Target 4 General References
  1. Okuyama T, Sato S, Zhu XL, Waheed A, Sly WS: Human carbonic anhydrase IV: cDNA cloning, sequence comparison, and expression in COS cell membranes. Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1315-9. [PubMed Link Image]
  2. Zhu XL, Sly WS: Carbonic anhydrase IV from human lung. Purification, characterization, and comparison with membrane carbonic anhydrase from human kidney. J Biol Chem. 1990 May 25;265(15):8795-801. [PubMed Link Image]
  3. Okuyama T, Waheed A, Kusumoto W, Zhu XL, Sly WS: Carbonic anhydrase IV: role of removal of C-terminal domain in glycosylphosphatidylinositol anchoring and realization of enzyme activity. Arch Biochem Biophys. 1995 Jul 10;320(2):315-22. [PubMed Link Image]
  4. Okuyama T, Batanian JR, Sly WS: Genomic organization and localization of gene for human carbonic anhydrase IV to chromosome 17q. Genomics. 1993 Jun;16(3):678-84. [PubMed Link Image]
  5. Waheed A, Okuyama T, Heyduk T, Sly WS: Carbonic anhydrase IV: purification of a secretory form of the recombinant human enzyme and identification of the positions and importance of its disulfide bonds. Arch Biochem Biophys. 1996 Sep 15;333(2):432-8. [PubMed Link Image]
  6. Stams T, Nair SK, Okuyama T, Waheed A, Sly WS, Christianson DW: Crystal structure of the secretory form of membrane-associated human carbonic anhydrase IV at 2.8-A resolution. Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13589-94. [PubMed Link Image]
Target 4 Drug References
  1. Dodgson SJ, Shank RP, Maryanoff BE: Topiramate as an inhibitor of carbonic anhydrase isoenzymes. Epilepsia. 2000;41 Suppl 1:S35-9. [PubMed Link Image]
  2. Masereel B, Rolin S, Abbate F, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: anticonvulsant sulfonamides incorporating valproyl and other lipophilic moieties. J Med Chem. 2002 Jan 17;45(2):312-20. [PubMed Link Image]
  3. Abbate F, Casini A, Owa T, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: E7070, a sulfonamide anticancer agent, potently inhibits cytosolic isozymes I and II, and transmembrane, tumor-associated isozyme IX. Bioorg Med Chem Lett. 2004 Jan 5;14(1):217-23. [PubMed Link Image]
  4. Vullo D, Franchi M, Gallori E, Antel J, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides. J Med Chem. 2004 Feb 26;47(5):1272-9. [PubMed Link Image]
Drug Target 5 [top]
Target 5 ID 872
Target 5 Name Gamma-aminobutyric-acid receptor subunit alpha-1
Target 5 Synonyms
  1. Gamma-aminobutyric-acid receptor subunit alpha-1 precursor
Target 5 Gene Name GABRA1
Target 5 Protein Sequence >Gamma-aminobutyric-acid receptor subunit alpha-1 precursor 
MRKSPGLSDCLWAWILLLSTLTGRSYGQPSLQDELKDNTTVFTRILDRLLDGYDNRLRPG
LGERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASK
IWTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHAC
PLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVM
TTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISA
RNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDP
LIKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKID
RLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ
Target 5 Number of Residues 463
Target 5 Molecular Weight 51802
Target 5 Theoretical pI 9.61
Target 5 GO Classification
Function
neurotransmitter receptor activity
transporter activity
ion transporter activity
ion channel activity
ligand-gated ion channel activity
extracellular ligand-gated ion channel activity
signal transducer activity
receptor activity
transmembrane receptor activity
GABA receptor activity
GABA-A receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
gamma-aminobutyric acid signaling pathway
anion transport
inorganic anion transport
chloride transport
physiological process
cellular physiological process
transport
ion transport
Component
postsynaptic membrane
cell
membrane
intrinsic to membrane
integral to membrane
Target 5 General Function Involved in GABA-A receptor activity
Target 5 Specific Function GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel
Target 5 Pathways Not Available
Target 5 Reactions Not Available
Target 5 Pfam Domain Function
Target 5 Signals
  • 1-27
Target 5 Transmembrane Regions
  • 252-273
  • 279-300
  • 313-334
  • 422-443
Target 5 Essentiality Non-Essential
Target 5 GenBank ID Protein 31631 Link Image
Target 5 UniProtKB/Swiss-Prot ID P14867 Link Image
Target 5 UniProtKB/Swiss-Prot Entry Name GBRA1_HUMAN Link Image
Target 5 PDB ID Not Available
Target 5 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 5 Gene Sequence >1371 bp 
ATGAGGAAAAGTCCAGGTCTGTCTGACTGTCTTTGGGCCTGGATCCTCCTTCTGAGCACA
CTGACTGGAAGAAGCTATGGACAGCCGTCATTACAAGATGAACTTAAAGACAATACCACT
GTCTTCACCAGGATTTTGGACAGACTCCTAGATGGTTATGACAATCGCCTGAGACCAGGA
TTGGGAGAGCGTGTAACCGAAGTGAAGACTGATATCTTCGTCACCAGTTTCGGACCCGTT
TCAGACCATGATATGGAATATACAATAGATGTATTTTTCCGTCAAAGCTGGAAGGATGAA
AGGTTAAAATTTAAAGGACCTATGACAGTCCTCCGGTTAAATAACCTAATGGCAAGTAAA
ATCTGGACTCCGGACACATTTTTCCACAATGGAAAGAAGTCAGTGGCCCACAACATGACC
ATGCCCAACAAACTCCTGCGGATCACAGAGGATGGCACCTTGCTGTACACCATGAGGCTG
ACAGTGAGAGCTGAATGTCCGATGCATTTGGAGGACTTCCCTATGGATGCCCATGCTTGC
CCACTAAAATTTGGAAGTTATGCTTATACAAGAGCAGAAGTTGTTTATGAATGGACCAGA
GAGCCAGCACGCTCAGTGGTTGTAGCAGAAGATGGATCACGTCTAAACCAGTATGACCTT
CTTGGACAAACAGTAGACTCTGGAATTGTCCAGTCAAGTACAGGAGAATATGTTGTTATG
ACCACTCATTTCCACTTGAAGAGAAAGATTGGCTACTTTGTTATTCAAACATACCTGCCA
TGCATAATGACAGTGATTCTCTCACAAGTCTCCTTCTGGCTCAACAGAGAGTCTGTACCA
GCAAGAACTGTCTTTGGAGTAACAACTGTGCTCACCATGACAACATTGAGCATCAGTGCC
AGAAACTCCCTCCCTAAGGTGGCTTATGCAACAGCTATGGATTGGTTTATTGCCGTGTGC
TATGCCTTTGTGTTCTCAGCTCTGATTGAGTTTGCCACAGTAAACTATTTCACTAAGAGA
GGTTATGCATGGGATGGCAAAAGTGTGGTTCCAGAAAAGCCAAAGAAAGTAAAGGATCCT
CTTATTAAGAAAAACAACACTTACGCTCCAACAGCAACCAGCTACACCCCTAATTTGGCC
AGGGGCGACCCGGGCTTAGCCACCATTGCTAAAAGTGCAACCATAGAACCTAAAGAGGTC
AAGCCCGAAACAAAACCACCAGAACCCAAGAAAACCTTTAACAGTGTCAGCAAAATTGAC
CGACTGTCAAGAATAGCCTTCCCGCTGCTATTTGGAATCTTTAACTTAGTCTACTGGGCT
ACGTATTTAAACAGAGAGCCTCAGCTAAAAGCCCCCACACCACATCAATAG
Target 5 GenBank Gene ID
Target 5 GeneCard ID GABRA1 Link Image
Target 5 GenAtlas ID GABRA1 Link Image
Target 5 HGNC ID HGNC:4075 Link Image
Target 5 Chromosome Location 5
Target 5 Locus 5q34-q35
Target 5 SNPs SNPJam Report Link Image
Target 5 General References
  1. Cossette P, Liu L, Brisebois K, Dong H, Lortie A, Vanasse M, Saint-Hilaire JM, Carmant L, Verner A, Lu WY, Wang YT, Rouleau GA: Mutation of GABRA1 in an autosomal dominant form of juvenile myoclonic epilepsy. Nat Genet. 2002 Jun;31(2):184-9. Epub 2002 May 6. [PubMed Link Image]
  2. Schofield PR, Pritchett DB, Sontheimer H, Kettenmann H, Seeburg PH: Sequence and expression of human GABAA receptor alpha 1 and beta 1 subunits. FEBS Lett. 1989 Feb 27;244(2):361-4. [PubMed Link Image]
  3. Garrett KM, Duman RS, Saito N, Blume AJ, Vitek MP, Tallman JF: Isolation of a cDNA clone for the alpha subunit of the human GABA-A receptor. Biochem Biophys Res Commun. 1988 Oct 31;156(2):1039-45. [PubMed Link Image]
Target 5 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]

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.