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Showing drug card for Levodopa (DB01235)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-06-23 18:05:54
Primary Accession Number DB01235
Secondary Accession Number
  • APRD00309
  • EXPT01107
Name Levodopa
Drug Type
  • Approved
  • Small Molecule
Description The naturally occurring form of dihydroxyphenylalanine and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonian disorders and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [PubChem]
Synonyms
  1. 3,4-dihydroxyphenylalanine
  2. DOPA
  3. L-DOPA
  4. L-Dihydroxyphenylalanine
Brand Names
  1. Bendopa
  2. Brocadopa
  3. Cidandopa
  4. Deadopa
  5. Dopaflex
  6. Dopaidan
  7. Dopal
  8. Dopal-Fher
  9. Dopalina
  10. Dopar
  11. Doparkine
  12. Doparl
  13. Dopasol
  14. Dopaston
  15. Dopastral
  16. Doprin
  17. Eldopal
  18. Eldopar
  19. Eldopatec
  20. Eurodopa
  21. Helfo-Dopa
  22. Insulamina
  23. Laradopa
  24. Larodopa
  25. Ledopa
  26. Levedopa
  27. Levopa
  28. Maipedopa
  29. Parda
  30. Pardopa
  31. Prodopa
  32. Syndopa
  33. Veldopa
  34. Weldopa
Brand Mixtures
  1. Apo-Levocarb CR Controlled-Release Tablets (carbidopa + levodopa)
  2. Dom-Levo-Carbidopa (carbidopa + levodopa)
  3. Novo-Levocarbidopa (carbidopa + levodopa)
  4. Pro-Lecarb-100/10 - Tab (carbidopa + levodopa)
  5. Pro-Lecarb-100/25 - Tab (carbidopa + levodopa)
  6. Prolopa Cap 50-12.5 (Benserazide + Levodopa)
  7. Ratio-Levodopa/Carbidopa (carbidopa + levodopa)
  8. Sinemet (carbidopa + levodopa)
  9. Sinemet CR (carbidopa + levodopa)
Chemical IUPAC Name (2S)-2-amino-3-(3,4-dihydroxyphenyl)propanoic acid
Chemical Formula C9H11NO4
Chemical Structure Structure
CAS Registry Number 59-92-7
InChI Identifier InChI=1/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1/f/h13H
InChI Key WTDRDQBEARUVNC-UDXUTFKQDG
KEGG Drug D00059 Link Image
KEGG Compound C00355 Link Image
PubChem Compound 6047 Link Image
PubChem Substance 7847127 Link Image
ChEBI ID 15765 Link Image
PharmGKB ID PA450213 Link Image
HET ID DAH Link Image
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link http://www.rxlist.com/cgi/generic3/stalevo.htm Link Image
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Levodopa Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS)
Synthesis Reference Wasser, Lewandowski, Helv. Chem. Acta 4, 657(1921)
Average Molecular Weight 197.1879
Monoisotopic Molecular Weight 197.0688
State Solid
Melting Point 276-278 oC
Experimental Water Solubility 5000 mg/L Source: PhysProp
Predicted Water Solubility 3.30e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -1.8 Source: PhysProp
Predicted LogP -2.31 Calculated using ALOGPS
Experimental LogS -1.6 [ADME Research, USCD]
Predicted LogS -1.78 Calculated using ALOGPS
Experimental Caco2 Permeability Not Available
pKa/Isoelectric Point 2.32
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 6PAH Link Image
Experimental PDB File Show
Experimental PDB Structure
Isomeric SMILES N[C@@H](CC1=CC(O)=C(O)C=C1)C(O)=O
Canonical SMILES NC(CC1=CC(O)=C(O)C=C1)C(O)=O
Drug Category
  • Antidyskinetics
  • Antiparkinson Agents
  • Dopamine Agents
ATC Codes
AHFS Codes Not Available
Indication For the treatment of idiopathic Parkinson's disease (Paralysis Agitans), postencephalitic parkinsonism, symptomatic parkinsonism which may follow injury to the nervous system by carbon monoxide intoxication, and manganese intoxication.
Pharmacology Levodopa (L-dopa) is used to replace dopamine lost in Parkinson's disease because dopamine itself cannot cross the blood-brain barrier where its precursor can. However, L-DOPA is converted to dopamine in the periphery as well as in the CNS, so it is administered with a peripheral DDC (dopamine decarboxylase) inhibitor such as carbidopa, without which 90% is metabolised in the gut wall, and with a COMT inhibitor if possible; this prevents about a 5% loss. The form given therapeutically is therefore a prodrug which avoids decarboxylation in the stomach and periphery, can cross the blood-brain barrier, and once in the brain is converted to the neurotransmitter dopamine by the enzyme aromatic-L-amino-acid decarboxylase.
Mechanism of Action Striatal dopamine levels in symptomatic Parkinson's disease are decreased by 60 to 80%, striatal dopaminergic neurotransmission may be enhanced by exogenous supplementation of dopamine through administration of dopamine's precursor, levodopa. A small percentage of each levodopa dose crosses the blood-brain barrier and is decarboxylated to dopamine. This newly formed dopamine then is available to stimulate dopaminergic receptors, thus compensating for the depleted supply of endogenous dopamine.
Absorption Levodopa is rapidly absorbed from the proximal small intestine by the large neutral amino acid (LNAA) transport carrier system.
Toxicity Oral, mouse: LD50 = 2363 mg/kg; Oral, rabbit: LD50 = 609 mg/kg; Oral, rat: LD50 = 1780 mg/kg.
Protein Binding High
Biotransformation 95% of an administered oral dose of levodopa is pre-systemically decarboxylated to dopamine by the L-aromatic amino acid decarboxylase (AAAD) enzyme in the stomach, lumen of the intestine, kidney, and liver. Levodopa also may be methoxylated by the hepatic catechol-O-methyltransferase (COMT) enzyme system to 3-O-methyldopa (3-OMD), which cannot be converted to central dopamine.
Half Life 50 to 90 minutes
Dosage Forms
Form Route
Tablet Oral
Patient Information Show Link Image
Contraindications Show Link Image
Interactions Not Available
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Drugs.com Link Image
  2. Wikipedia Link Image
  3. RxList Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Monoamine oxidase type A (MAO-A)
  2. Monoamine oxidase type B (MAO-B)
  3. Aromatic-L-amino-acid decarboxylase (AADC)
Targets
  1. D(1A) dopamine receptor
  2. Phenylalanine-4-hydroxylase
  3. D(2) dopamine receptor
  4. Phenylethylamine oxidase
  5. Catechol O-methyltransferase
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Monoamine oxidase type A (MAO-A)
Enzyme 1 Gene Name MAOA
Enzyme 1 SwissProt ID P21397 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P21397|AOFA_HUMAN Amine oxidase [flavin-containing] 
MENQEKASIAGHMFDVVVIGGGISGLSAAKLLTEYGVSVLVLEARDRVGGRTYTIRNEHV
DYVDVGGAYVGPTQNRILRLSKELGIETYKVNVSERLVQYVKGKTYPFRGAFPPVWNPIA
YLDYNNLWRTIDNMGKEIPTDAPWEAQHADKWDKMTMKELIDKICWTKTARRFAYLFVNI
NVTSEPHEVSALWFLWYVKQCGGTTRIFSVTNGGQERKFVGGSGQVSERIMDLLGDQVKL
NHPVTHVDQSSDNIIIETLNHEHYECKYVINAIPPTLTAKIHFRPELPAERNQLIQRLPM
GAVIKCMMYYKEAFWKKKDYCGCMIIEDEDAPISITLDDTKPDGSLPAIMGFILARKADR
LAKLHKEIRKKKICELYAKVLGSQEALHPVHYEEKNWCEEQYSGGCYTAYFPPGIMTQYG
RVIRQPVGRIFFAGTETATKWSGYMEGAVEAGERAAREVLNGLGKVTEKDIWVQEPESKD
VPAVEITHTFWERNLPSVSGLLKIIGFSTSVTALGFVLYKYKLLPRS
Phase 1 Metabolizing Enzyme 2 [top]
Enzyme 2 Name Monoamine oxidase type B (MAO-B)
Enzyme 2 Gene Name MAOB
Enzyme 2 SwissProt ID P27338 Link Image
Enzyme 2 SNPs SNPJam Report Link Image
Enzyme 2 Protein Sequence >sp|P27338|AOFB_HUMAN Amine oxidase B 
SNKCDVVVVGGGISGMAAAKLLHDSGLNVVVLEARDRVGGRTYTLRNQKVKYVDLGGSYV
GPTQNRILRLAKELGLETYKVNEVERLIHHVKGKSYPFRGPFPPVWNPITYLDHNNFWRT
MDDMGREIPSDAPWKAPLAEEWDNMTMKELLDKLCWTESAKQLATLFVNLCVTAETHEVS
ALWFLWYVKQCGGTTRIISTTNGGQERKFVGGSGQVSERIMDLLGDRVKLERPVIYIDQT
RENVLVETLNHEMYEAKYVISAIPPTLGMKIHFNPPLPMMRNQMITRVPLGSVIKCIVYY
KEPFWRKKDYCGTMIIDGEEAPVAYTLDDTKPEGNYAAIMGFILAHKARKLARLTKEERL
KKLCELYAKVLGSLEALEPVHYEEKNWCEEQYSGGCYTTYFPPGILTQYGRVLRQPVDRI
YFAGTETATHWSGYMEGAVEAGERAAREILHAMGKIPEDEIWQSEPESVDVPAQPITTTF
LERHLPSVPGLLRLIGLTTIFSATALGFLAHKRGLLVRV
Phase 1 Metabolizing Enzyme 3 [top]
Enzyme 3 Name Aromatic-L-amino-acid decarboxylase (AADC)
Enzyme 3 Gene Name DDC
Enzyme 3 SwissProt ID P20711 Link Image
Enzyme 3 SNPs SNPJam Report Link Image
Enzyme 3 Protein Sequence >sp|P20711|DDC_HUMAN Aromatic-L-amino-acid decarboxylase 
MNASEFRRRGKEMVDYVANYMEGIEGRQVYPDVEPGYLRPLIPAAAPQEPDTFEDIINDV
EKIIMPGVTHWHSPYFFAYFPTASSYPAMLADMLCGAIGCIGFSWAASPACTELETVMMD
WLGKMLELPKAFLNEKAGEGGGVIQGSASEATLVALLAARTKVIHRLQAASPELTQAAIM
EKLVAYSSDQAHSSVERAGLIGGVKLKAIPSDGNFAMRASALQEALERDKAAGLIPFFMV
ATLGTTTCCSFDNLLEVGPICNKEDIWLHVDAAYAGSAFICPEFRHLLNGVEFADSFNFN
PHKWLLVNFDCSAMWVKKRTDLTGAFRLDPTYLKHSHQDSGLITDYRHWQIPLGRRFRSL
KMWFVFRMYGVKGLQAYIRKHVQLSHEFESLVRQDPRFEICVEVILGLVCFRLKGSNKVN
EALLQRINSAKKIHLVPCHLRDKFVLRFAICSRTVESAHVQRAWEHIKELAADVLRAERE
Drug Target 1 [top]
Target 1 ID 23
Target 1 Name D(1A) dopamine receptor
Target 1 Synonyms Not Available
Target 1 Gene Name DRD1
Target 1 Protein Sequence >D(1A) dopamine receptor 
MRTLNTSAMDGTGLVVERDFSVRILTACFLSLLILSTLLGNTLVCAAVIRFRHLRSKVTN
FFVISLAVSDLLVAVLVMPWKAVAEIAGFWPFGSFCNIWVAFDIMCSTASILNLCVISVD
RYWAISSPFRYERKMTPKAAFILISVAWTLSVLISFIPVQLSWHKAKPTSPSDGNATSLA
ETIDNCDSSLSRTYAISSSVISFYIPVAIMIVTYTRIYRIAQKQIRRIAALERAAVHAKN
CQTTTGNGKPVECSQPESSFKMSFKRETKVLKTLSVIMGVFVCCWLPFFILNCILPFCGS
GETQPFCIDSNTFDVFVWFGWANSSLNPIIYAFNADFRKAFSTLLGCYRLCPATNNAIET
VSINNNGAAMFSSHHEPRGSISKECNLVYLIPHAVGSSEDLKKEEAAGIARPLEKLSPAL
SVILDYDTDVSLEKIQPITQNGQHPT
Target 1 Number of Residues 453
Target 1 Molecular Weight 49294
Target 1 Theoretical pI 8.34
Target 1 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
dopamine receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in dopamine receptor activity
Target 1 Specific Function This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 24-49
  • 61-87
  • 97-119
  • 139-163
  • 193-218
  • 273-299
  • 313-337
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 30397 Link Image
Target 1 UniProtKB/Swiss-Prot ID P21728 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name DRD1_HUMAN Link Image
Target 1 PDB ID Not Available
Target 1 Cellular Location
  • Cell membrane
  • endoplasmic reticulum membrane
  • m
  • multi-pass membrane protein. Endoplasmic reticulum
Target 1 Gene Sequence >1341 bp 
ATGAGGACTCTGAACACCTCTGCCATGGACGGGACTGGGCTGGTGGTGGAGAGGGACTTC
TCTGTTCGTATCCTCACTGCCTGTTTCCTGTCGCTGCTCATCCTGTCCACGCTCCTGGGG
AACACGCTGGTCTGTGCTGCCGTTATCAGGTTCCGACACCTGCGGTCCAAGGTGACCAAC
TTCTTTGTCATCTCCTTGGCTGTGTCAGATCTCTTGGTGGCCGTCCTGGTCATGCCCTGG
AAGGCAGTGGCTGAGATTGCTGGCTTCTGGCCCTTTGGGTCCTTCTGTAACATCTGGGTG
GCCTTTGACATCATGTGCTCCACTGCATCCATCCTCAACCTCTGTGTGATCAGCGTGGAC
AGGTATTGGGCTATCTCCAGCCCTTTCCGGTATGAGAGAAAGATGACCCCCAAGGCAGCC
TTCATCCTGATCAGTGTGGCATGGACCTTGTCTGTACTCATCTCCTTCATCCCAGTGCAG
CTCAGCTGGCACAAGGCAAAACCCACAAGCCCCTCTGATGGAAATGCCACTTCCCTGGCT
GAGACCATAGACAACTGTGACTCCAGCCTCAGCAGGACATATGCCATCTCATCCTCTGTA
ATAAGCTTTTACATCCCTGTGGCCATCATGATTGTCACCTACACCAGGATCTACAGGATT
GCTCAGAAACAAATACGGCGCATTGCGGCCTTGGAGAGGGCAGCAGTCCACGCCAAGAAT
TGCCAGACCACCACAGGTAATGGAAAGCCTGTCGAATGTTCTCAACCGGAAAGTTCTTTT
AAGATGTCCTTCAAAAGAGAAACTAAAGTCCTGAAGACTCTGTCGGTGATCATGGGTGTG
TTTGTGTGCTGTTGGCTACCTTTCTTCATCTTGAACTGCATTTTGCCCTTCTGTGGGTCT
GGGGAGACGCAGCCCTTCTGCATTGATTCCAACACCTTTGACGTGTTTGTGTGGTTTGGG
TGGGCTAATTCATCCTTGAACCCCATCATTTATGCCTTTAATGCTGATTTTCGGAAGGCA
TTTTCAACCCTCTTAGGATGCTACAGACTTTGCCCTGCGACGAATAATGCCATAGAGACG
GTGAGTATCAATAACAATGGGGCCGCGATGTTTTCCAGCCATCATGAGCCACGAGGCTCC
ATCTCCAAGGAGTGCAATCTGGTTTACCTGATCCCACATGCTGTGGGCTCCTCTGAGGAC
CTGAAAAAGGAGGAGGCAGCTGGCATCGCCAGACCCTTGGAGAAGCTGTCCCCAGCCCTA
TCGGTCATATTGGACTATGACACTGACGTCTCTCTGGAGAAGATCCAACCCATCACACAA
AACGGTCAGCACCCAACCTGA
Target 1 GenBank Gene ID
Target 1 GeneCard ID DRD1 Link Image
Target 1 GenAtlas ID DRD1 Link Image
Target 1 HGNC ID HGNC:3020 Link Image
Target 1 Chromosome Location 5
Target 1 Locus 5q35.1
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Jin H, Xie Z, George SR, O'Dowd BF: Palmitoylation occurs at cysteine 347 and cysteine 351 of the dopamine D(1) receptor. Eur J Pharmacol. 1999 Dec 15;386(2-3):305-12. [PubMed Link Image]
  2. Sunahara RK, Niznik HB, Weiner DM, Stormann TM, Brann MR, Kennedy JL, Gelernter JE, Rozmahel R, Yang YL, Israel Y, et al.: Human dopamine D1 receptor encoded by an intronless gene on chromosome 5. Nature. 1990 Sep 6;347(6288):80-3. [PubMed Link Image]
  3. Dearry A, Gingrich JA, Falardeau P, Fremeau RT Jr, Bates MD, Caron MG: Molecular cloning and expression of the gene for a human D1 dopamine receptor. Nature. 1990 Sep 6;347(6288):72-6. [PubMed Link Image]
  4. Zhou QY, Grandy DK, Thambi L, Kushner JA, Van Tol HH, Cone R, Pribnow D, Salon J, Bunzow JR, Civelli O: Cloning and expression of human and rat D1 dopamine receptors. Nature. 1990 Sep 6;347(6288):76-80. [PubMed Link Image]
  5. Ohara K, Ulpian C, Seeman P, Sunahara RK, Van Tol HH, Niznik HB: Schizophrenia: dopamine D1 receptor sequence is normal, but has DNA polymorphisms. Neuropsychopharmacology. 1993 Feb;8(2):131-5. [PubMed Link Image]
Target 1 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 2 [top]
Target 2 ID 828
Target 2 Name Phenylalanine-4-hydroxylase
Target 2 Synonyms
  1. EC 1.14.16.1
  2. PAH
  3. Phe-4- monooxygenase
Target 2 Gene Name PAH
Target 2 Protein Sequence >Phenylalanine-4-hydroxylase 
MSTAVLENPGLGRKLSDFGQETSYIEDNCNQNGAISLIFSLKEEVGALAKVLRLFEENDV
NLTHIESRPSRLKKDEYEFFTHLDKRSLPALTNIIKILRHDIGATVHELSRDKKKDTVPW
FPRTIQELDRFANQILSYGAELDADHPGFKDPVYRARRKQFADIAYNYRHGQPIPRVEYM
EEEKKTWGTVFKTLKSLYKTHACYEYNHIFPLLEKYCGFHEDNIPQLEDVSQFLQTCTGF
RLRPVAGLLSSRDFLGGLAFRVFHCTQYIRHGSKPMYTPEPDICHELLGHVPLFSDRSFA
QFSQEIGLASLGAPDEYIEKLATIYWFTVEFGLCKQGDSIKAYGAGLLSSFGELQYCLSE
KPKLLPLELEKTAIQNYTVTEFQPLYYVAESFNDAKEKVRNFAATIPRPFSVRYDPYTQR
IEVLDNTQQLKILADSINSEIGILCSALQKIK
Target 2 Number of Residues 459
Target 2 Molecular Weight 51863
Target 2 Theoretical pI 6.57
Target 2 GO Classification
Function
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen
phenylalanine 4-monooxygenase activity
amine binding
amino acid binding
binding
ion binding
cation binding
transition metal ion binding
iron ion binding
catalytic activity
oxidoreductase activity
monooxygenase activity
Process
L-phenylalanine metabolism
L-phenylalanine catabolism
physiological process
metabolism
cellular metabolism
amino acid and derivative metabolism
amino acid metabolism
aromatic amino acid family metabolism
Component
Not Available
Target 2 General Function Amino acid transport and metabolism
Target 2 Specific Function Not Available
Target 2 Pathways
Name SMPDB Link KEGG Link
Phenylalanine, tyrosine and tryptophan biosynthesis map00400 Link Image
Target 2 Reactions
  • L-phenylalanine + tetrahydrobiopterin + O2 = L-tyrosine + 4a-hydroxytetrahydrobiopterin
Target 2 Pfam Domain Function
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 189937 Link Image
Target 2 UniProtKB/Swiss-Prot ID P00439 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name PH4H_HUMAN Link Image
Target 2 PDB ID 2PHM Link Image
Target 2 PDB File Show
Target 2 3D Structure
Target 2 Cellular Location Not Available
Target 2 Gene Sequence >1359 bp 
ATGTCCACTGCGGTCCTGGAAAACCCAGGCTTGGGCAGGAAACTCTCTGACTTTGGACAG
GAAACAAGCTATATTGAAGACAACTGCAATCAAAATGGTGCCATATCACTGATCTTCTCA
CTCAAAGAAGAAGTTGGTGCATTGGCCAAAGTATTGCGCTTATTTGAGGAGAATGATGTA
AACCTGACCCACATTGAATCTAGACCTTCTCGTTTAAAGAAAGATGAGTATGAATTTTTC
ACCCATTTGGATAAACGTAGCCTGCCTGCTCTGACAAACATCATCAAGATCTTGAGGCAT
GACATTGGTGCCACTGTCCATGAGCTTTCACGAGATAAGAAGAAAGACACAGTGCCCTGG
TTCCCAAGAACCATTCAAGAGCTGGACAGATTTGCCAATCAGATTCTCAGCTATGGAGCG
GAACTGGATGCTGACCACCCTGGTTTTAAAGATCCTGTGTACCGTGCAAGACGGAAGCAG
TTTGCTGACATTGCCTACAACTACCGCCATGGGCAGCCCATCCCTCGAGTGGAATACATG
GAGGAAGAAAAGAAAACATGGGGCACAGTGTTCAAGACTCTGAAGTCCTTGTATAAAACC
CATGCTTGCTATGAGTACAATCACATTTTTCCACTTCTTGAAAAGTACTGTGGCTTCCAT
GAAGATAACATTCCCCAGCTGGAAGACGTTTCTCAATTCCTGCAGACTTGCACTGGTTTC
CGCCTCCGACCTGTGGCTGGCCTGCTTTCCTCTCGGGATTTCTTGGGTGGCCTGGCCTTC
CGAGTCTTCCACTGCACACAGTACATCAGACATGGATCCAAGCCCATGTATACCCCCGAA
CCTGACATCTGCCATGAGCTGTTGGGACATGTGCCCTTGTTTTCAGATCGCAGCTTTGCC
CAGTTTTCCCAGGAAATTGGCCTTGCCTCTCTGGGTGCACCTGATGAATACATTGAAAAG
CTCGCCACAATTTACTGGTTTACTGTGGAGTTTGGGCTCTGCAAACAAGGAGACTCCATA
AAGGCATATGGTGCTGGGCTCCTGTCATCCTTTGGTGAATTACAGTACTGCTTATCAGAG
AAGCCAAAGCTTCTCCCCCTGGAGCTGGAGAAGACAGCCATCCAAAATTACACTGTCACG
GAGTTCCAGCCCCTGTATTACGTGGCAGAGAGTTTTAATGATGCCAAGGAGAAAGTAAGG
AACTTTGCTGCCACAATACCTCGGCCCTTCTCAGTTCGCTACGACCCATACACCCAAAGG
ATTGAGGTCTTGGACAATACCCAGCAGCTTAAGATTTTGGCTGATTCCATTAACAGTGAA
ATTGGAATCCTTTGCAGTGCCCTCCAGAAAATAAAGTAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID PAH Link Image
Target 2 GenAtlas ID PAH Link Image
Target 2 HGNC ID HGNC:8582 Link Image
Target 2 Chromosome Location 12
Target 2 Locus 12q22-q24.2
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Hennermann JB, Vetter B, Wolf C, Windt E, Buhrdel P, Seidel J, Monch E, Kulozik AE: Phenylketonuria and hyperphenylalaninemia in eastern Germany: a characteristic molecular profile and 15 novel mutations. Hum Mutat. 2000;15(3):254-60. [PubMed Link Image]
  2. Erlandsen H, Bjorgo E, Flatmark T, Stevens RC: Crystal structure and site-specific mutagenesis of pterin-bound human phenylalanine hydroxylase. Biochemistry. 2000 Mar 7;39(9):2208-17. [PubMed Link Image]
  3. Acosta A, Silva W Jr, Carvalho T, Gomes M, Zago M: Mutations of the phenylalanine hydroxylase (PAH) gene in Brazilian patients with phenylketonuria. Hum Mutat. 2001 Feb;17(2):122-30. [PubMed Link Image]
  4. Gjetting T, Petersen M, Guldberg P, Guttler F: Missense mutations in the N-terminal domain of human phenylalanine hydroxylase interfere with binding of regulatory phenylalanine. Am J Hum Genet. 2001 Jun;68(6):1353-60. Epub 2001 Apr 20. [PubMed Link Image]
  5. Yang Y, Drummond-Borg M, Garcia-Heras J: Molecular analysis of phenylketonuria (PKU) in newborns from Texas. Hum Mutat. 2001 Jun;17(6):523. [PubMed Link Image]
  6. Gjetting T, Romstad A, Haavik J, Knappskog PM, Acosta AX, Silva WA Jr, Zago MA, Guldberg P, Guttler F: A phenylalanine hydroxylase amino acid polymorphism with implications for molecular diagnostics. Mol Genet Metab. 2001 Jul;73(3):280-4. [PubMed Link Image]
  7. Andersen OA, Flatmark T, Hough E: High resolution crystal structures of the catalytic domain of human phenylalanine hydroxylase in its catalytically active Fe(II) form and binary complex with tetrahydrobiopterin. J Mol Biol. 2001 Nov 23;314(2):279-91. [PubMed Link Image]
  8. Eisensmith RC, Woo SL: Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene. Hum Mutat. 1992;1(1):13-23. [PubMed Link Image]
  9. Lin CH, Hsiao KJ, Tsai TF, Chao HK, Su TS: Identification of a missense phenylketonuria mutation at codon 408 in Chinese. Hum Genet. 1992 Aug;89(6):593-6. [PubMed Link Image]
  10. Economou-Petersen E, Henriksen KF, Guldberg P, Guttler F: Molecular basis for nonphenylketonuria hyperphenylalaninemia. Genomics. 1992 Sep;14(1):1-5. [PubMed Link Image]
  11. 1363837 Jaruzelska J, Melle D, Matuszak R, Borski K, Munnich A: A new 15 bp deletion in exon 11 of the phenylalanine hydroxylase gene in phenylketonuria. Hum Mol Genet. 1992 Dec;1(9):763-4.
  12. 1363838 Desviat LR, Perez B, Ugarte M: A new PKU mutation associated with haplotype 12. Hum Mol Genet. 1992 Dec;1(9):765-6.
  13. 1671810 Dianzani I, Forrest SM, Camaschella C, Saglio G, Ponzone A, Cotton RG: Screening for mutations in the phenylalanine hydroxylase gene from Italian patients with phenylketonuria by using the chemical cleavage method: a new splice mutation. Am J Hum Genet. 1991 Mar;48(3):631-5.
  14. 1672290 Dworniczak B, Grudda K, Stumper J, Bartholome K, Aulehla-Scholz C, Horst J: Phenylalanine hydroxylase gene: novel missense mutation in exon 7 causing severe phenylketonuria. Genomics. 1991 Jan;9(1):193-9.
  15. 1672294 Okano Y, Wang T, Eisensmith RC, Longhi R, Riva E, Giovannini M, Cerone R, Romano C, Woo SL: Phenylketonuria missense mutations in the Mediterranean. Genomics. 1991 Jan;9(1):96-103.
  16. 1679029 Konecki DS, Lichter-Konecki U: The phenylketonuria locus: current knowledge about alleles and mutations of the phenylalanine hydroxylase gene in various populations. Hum Genet. 1991 Aug;87(4):377-88.
  17. 1679030 Konecki DS, Schlotter M, Trefz FK, Lichter-Konecki U: The identification of two mis-sense mutations at the PAH gene locus in a Turkish patient with phenylketonuria. Hum Genet. 1991 Aug;87(4):389-93.
  18. 1709636 Caillaud C, Lyonnet S, Rey F, Melle D, Frebourg T, Berthelon M, Vilarinho L, Vaz Osorio R, Rey J, Munnich A: A 3-base pair in-frame deletion of the phenylalanine hydroxylase gene results in a kinetic variant of phenylketonuria. J Biol Chem. 1991 May 25;266(15):9351-4.
  19. 1975559 Svensson E, Andersson B, Hagenfeldt L: Two mutations within the coding sequence of the phenylalanine hydroxylase gene. Hum Genet. 1990 Aug;85(3):300-4.
  20. 2014802 Hofman KJ, Steel G, Kazazian HH, Valle D: Phenylketonuria in U.S. blacks: molecular analysis of the phenylalanine hydroxylase gene. Am J Hum Genet. 1991 Apr;48(4):791-8.
  21. 2246858 Cotton RG: Heterogeneity of phenylketonuria at the clinical, protein and DNA levels. J Inherit Metab Dis. 1990;13(5):739-50.
  22. 2461704 Cotton RG, McAdam W, Jennings I, Morgan FJ: A monoclonal antibody to aromatic amino acid hydroxylases. Identification of the epitope. Biochem J. 1988 Oct 1;255(1):193-6.
  23. 2564729 Lyonnet S, Caillaud C, Rey F, Berthelon M, Frezal J, Rey J, Munnich A: Molecular genetics of phenylketonuria in Mediterranean countries: a mutation associated with partial phenylalanine hydroxylase deficiency. Am J Hum Genet. 1989 Apr;44(4):511-7.
  24. 2615649 Hofman KJ, Antonarakis SE, Missiou-Tsangaraki S, Boehm CD, Valle D: Phenylketonuria in the Greek population. Haplotype analysis of the phenylalanine hydroxylase gene and identification of a PKU mutation. Mol Biol Med. 1989 Jun;6(3):245-50.
  25. 2840952 Lichter-Konecki U, Konecki DS, DiLella AG, Brayton K, Marvit J, Hahn TM, Trefz FK, Woo SL: Phenylalanine hydroxylase deficiency caused by a single base substitution in an exon of the human phenylalanine hydroxylase gene. Biochemistry. 1988 Apr 19;27(8):2881-5.
  26. 2986678 Kwok SC, Ledley FD, DiLella AG, Robson KJ, Woo SL: Nucleotide sequence of a full-length complementary DNA clone and amino acid sequence of human phenylalanine hydroxylase. Biochemistry. 1985 Jan 29;24(3):556-61.
  27. 7833954 Benit P, Rey F, Melle D, Munnich A, Rey J: Five novel missense mutations of the phenylalanine hydroxylase gene in phenylketonuria. Hum Mutat. 1994;4(3):229-31.
  28. 8068076 Goebel-Schreiner B, Schreiner R: Identification of a new missense mutation in Japanese phenylketonuric patients. J Inherit Metab Dis. 1993;16(6):950-6.
  29. 8088845 Guldberg P, Henriksen KF, Thony B, Blau N, Guttler F: Molecular heterogeneity of nonphenylketonuria hyperphenylalaninemia in 25 Danish patients. Genomics. 1994 May 15;21(2):453-5.
  30. 8098245 Abadie V, Jaruzelska J, Lyonnet S, Millasseau P, Berthelon M, Rey F, Munnich A, Rey J: Illegitimate transcription of the phenylalanine hydroxylase gene in lymphocytes for identification of mutations in phenylketonuria. Hum Mol Genet. 1993 Jan;2(1):31-4.
  31. 8406445 Guldberg P, Henriksen KF, Guttler F: Molecular analysis of phenylketonuria in Denmark: 99% of the mutations detected by denaturing gradient gel electrophoresis. Genomics. 1993 Jul;17(1):141-6.
  32. 8594560 Hoang L, Byck S, Prevost L, Scriver CR: PAH Mutation Analysis Consortium Database: a database for disease-producing and other allelic variation at the human PAH locus. Nucleic Acids Res. 1996 Jan 1;24(1):127-31.
  33. 8889583 Knappskog PM, Eiken HG, Martinez A, Bruland O, Apold J, Flatmark T: PKU mutation (D143G) associated with an apparent high residual enzyme activity: expression of a kinetic variant form of phenylalanine hydroxylase in three different systems. Hum Mutat. 1996;8(3):236-46.
  34. 8889590 Guldberg P, Mallmann R, Henriksen KF, Guttler F: Phenylalanine hydroxylase deficiency in a population in Germany: mutational profile and nine novel mutations. Hum Mutat. 1996;8(3):276-9.
  35. 9048935 Argiolas A, Bosco P, Cali F, Ceratto N, Anello G, Riva E, Biasucci G, Carducci C, Romano V: Two novel PAH gene mutations detected in Italian phenylketonuric patients. Hum Genet. 1997 Feb;99(2):275-8.
  36. 9101291 Byck S, Tyfield L, Carter K, Scriver CR: Prediction of multiple hypermutable codons in the human PAH gene: codon 280 contains recurrent mutations in Quebec and other populations. Hum Mutat. 1997;9(4):316-21.
  37. 9406548 Erlandsen H, Fusetti F, Martinez A, Hough E, Flatmark T, Stevens RC: Crystal structure of the catalytic domain of human phenylalanine hydroxylase reveals the structural basis for phenylketonuria. Nat Struct Biol. 1997 Dec;4(12):995-1000.
  38. 9450897 Waters PJ, Parniak MA, Nowacki P, Scriver CR: In vitro expression analysis of mutations in phenylalanine hydroxylase: linking genotype to phenotype and structure to function. Hum Mutat. 1998;11(1):4-17.
  39. 9452061 Park YS, Seoung CS, Lee SW, Oh KH, Lee DH, Yim J: Identification of three novel mutations in Korean phenylketonuria patients: R53H, N207D, and Y325X. Hum Mutat. 1998;Suppl 1:S121-2.
  40. 9452062 Michiels L, Francois B, Raus J, Vandevyver C: Identification of seven new mutations in the phenylalanine hydroxylase gene, associated with hyperphenylalaninemia in the Belgian population. Hum Mutat. 1998;Suppl 1:S123-4.
  41. 9521426 Bosco P, Cali F, Meli C, Mollica F, Zammarchi E, Cerone R, Vanni C, Palillo L, Greco D, Romano V: Eight new mutations of the phenylalanine hydroxylase gene in Italian patients with hyperphenylalaninemia. Hum Mutat. 1998;11(3):240-3.
  42. 9600453 De Lucca M, Perez B, Desviat LR, Ugarte M: Molecular basis of phenylketonuria in Venezuela: presence of two novel null mutations. Hum Mutat. 1998;11(5):354-9.
  43. 9642259 Fusetti F, Erlandsen H, Flatmark T, Stevens RC: Structure of tetrameric human phenylalanine hydroxylase and its implications for phenylketonuria. J Biol Chem. 1998 Jul 3;273(27):16962-7.
  44. 9792407 Popescu T, Blazkova M, Kozak L, Jebeleanu G, Popescu A: Mutation spectrum and phenylalanine hydroxylase RFLP/VNTR background in 44 Romanian phenylketonuric alleles. Hum Mutat. 1998;12(5):314-9.
  45. 9792411 Waters PJ, Parniak MA, Hewson AS, Scriver CR: Alterations in protein aggregation and degradation due to mild and severe missense mutations (A104D, R157N) in the human phenylalanine hydroxylase gene (PAH). Hum Mutat. 1998;12(5):344-54.
  46. 9843368 Erlandsen H, Flatmark T, Stevens RC, Hough E: Crystallographic analysis of the human phenylalanine hydroxylase catalytic domain with bound catechol inhibitors at 2.0 A resolution. Biochemistry. 1998 Nov 10;37(45):15638-46.
  47. 9852673 Kibayashi M, Nagao M, Chiba S: Mutation analysis of the phenylalanine hydroxylase gene and its clinical implications in two Japanese patients with non-phenylketonuria hyperphenylalaninemia. J Hum Genet. 1998;43(4):231-6.
Target 2 Drug References
  1. Erlandsen H, Flatmark T, Stevens RC, Hough E: Crystallographic analysis of the human phenylalanine hydroxylase catalytic domain with bound catechol inhibitors at 2.0 A resolution. Biochemistry. 1998 Nov 10;37(45):15638-46. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 831
Target 3 Name D(2) dopamine receptor
Target 3 Synonyms
  1. Dopamine D2 receptor
Target 3 Gene Name DRD2
Target 3 Protein Sequence >D(2) dopamine receptor 
MDPLNLSWYDDDLERQNWSRPFNGSDGKADRPHYNYYATLLTLLIAVIVFGNVLVCMAVS
REKALQTTTNYLIVSLAVADLLVATLVMPWVVYLEVVGEWKFSRIHCDIFVTLDVMMCTA
SILNLCAISIDRYTAVAMPMLYNTRYSSKRRVTVMISIVWVLSFTISCPLLFGLNNADQN
ECIIANPAFVVYSSIVSFYVPFIVTLLVYIKIYIVLRRRRKRVNTKRSSRAFRAHLRAPL
KGNCTHPEDMKLCTVIMKSNGSFPVNRRRVEAARRAQELEMEMLSSTSPPERTRYSPIPP
SHHQLTLPDPSHHGLHSTPDSPAKPEKNGHAKDHPKIAKIFEIQTMPNGKTRTSLKTMSR
RKLSQQKEKKATQMLAIVLGVFIICWLPFFITHILNIHCDCNIPPVLYSAFTWLGYVNSA
VNPIIYTTFNIEFRKAFLKILHC
Target 3 Number of Residues 450
Target 3 Molecular Weight 50620
Target 3 Theoretical pI 9.85
Target 3 GO Classification
Function
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
amine receptor activity
dopamine receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 3 General Function Involved in dopamine receptor activity
Target 3 Specific Function This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 38-60
  • 72-97
  • 109-130
  • 152-174
  • 187-210
  • 374-397
  • 406-429
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 181432 Link Image
Target 3 UniProtKB/Swiss-Prot ID P14416 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name DRD2_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 3 Gene Sequence >1332 bp 
ATGGATCCACTGAATCTGTCCTGGTATGATGATGATCTGGAGAGGCAGAACTGGAGCCGG
CCCTTCAACGGGTCAGACGGGAAGGCGGACAGACCCCACTACAACTACTATGCCACACTG
CTCACCCTGCTCATCGCTGTCATCGTCTTCGGCAACGTGCTGGTGTGCATGGCTGTGTCC
CGCGAGAAGGCGCTGCAGACCACCACCAACTACCTGATCGTCAGCCTCGCAGTGGCCGAC
CTCCTCGTCGCCACACTGGTCATGCCATGGGTTGTCTACCTGGAGGTGGTAGGTGAGTGG
AAATTCAGCAGGATTCACTGTGACATCTTCGTCACTCTGGACGTCATGATGTGCACGGCG
AGCATCCTGAACTTGTGTGCCATCAGCATCGACAGGTACACAGCTGTGGCCATGCCCATG
CTGTACAATACGCGCTACAGCTCCAAGCGCCGGGTCACCGTCATGATCTCCATCGTCTGG
GTCCTGTCCTTCACCATCTCCTGCCCACTCCTCTTCGGACTCAATAACGCAGACCAGAAC
GAGTGCATCATTGCCAACCCGGCCTTCGTGGTCTACTCCTCCATCGTCTCCTTCTACGTG
CCCTTCATTGTCACCCTGCTGGTCTACATCAAGATCTACATTGTCCTCCGCAGACGCCGC
AAGCGAGTCAACACCAAACGCAGCAGCCGAGCTTTCAGGGCCCACCTGAGGGCTCCACTA
AAGGGCAACTGTACTCACCCCGAGGACATGAAACTCTGCACCGTTATCATGAAGTCTAAT
GGGAGTTTCCCAGTGAACAGGCGGAGAGTGGAGGCTGCCCGGCGAGCCCAGGAGCTGGAG
ATGGAGATGCTCTCCAGCACCAGCCCACCCGAGAGGACCCGGTACAGCCCCATCCCACCC
AGCCACCACCAGCTGACTCTCCCCGACCCGTCCCACCACGGTCTCCACAGCACTCCTGAC
AGCCCCGCCAAACCAGAGAAGAATGGGCATGCCAAAGACCACCCCAAGATTGCCAAGATC
TTTGAGATCCAGACCATGCCCAATGGCAAAACCCGGACCTCCCTCAAGACCATGAGCCGT
AGAAAGCTCTCCCAGCAGAAGGAGAAGAAAGCCACTCAGATGCTCGCCATTGTTCTCGGC
GTGTTCATCATCTGCTGGCTGCCCTTCTTCATCACACACATCCTGAACATACACTGTGAC
TGCAACATCCCGCCTGTCCTGTACAGCGCCTTCACGTGGCTGGGCTATGTCAACAGCGCC
GTGAACCCCATCATCTACACCACCTTCAACATTGAGTTCCGCAAGGCCTTCCTGAAGATC
CTTCACTGCTGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID DRD2 Link Image
Target 3 GenAtlas ID DRD2 Link Image
Target 3 HGNC ID HGNC:3023 Link Image
Target 3 Chromosome Location 11
Target 3 Locus 11q23
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Klein C, Brin MF, Kramer P, Sena-Esteves M, de Leon D, Doheny D, Bressman S, Fahn S, Breakefield XO, Ozelius LJ: Association of a missense change in the D2 dopamine receptor with myoclonus dystonia. Proc Natl Acad Sci U S A. 1999 Apr 27;96(9):5173-6. [PubMed Link Image]
  2. Seeman P, Nam D, Ulpian C, Liu IS, Tallerico T: New dopamine receptor, D2(Longer), with unique TG splice site, in human brain. Brain Res Mol Brain Res. 2000 Mar 10;76(1):132-41. [PubMed Link Image]
  3. Araki K, Kuwano R, Morii K, Hayashi S, Minoshima S, Shimizu N, Katagiri T, Usui H, Kumanishi T, Takahashi Y: Structure and expression of human and rat D2 dopamine receptor genes. Neurochem Int. 1992 Jul;21(1):91-8. [PubMed Link Image]
  4. Dearry A, Falardeau P, Shores C, Caron MG: D2 dopamine receptors in the human retina: cloning of cDNA and localization of mRNA. Cell Mol Neurobiol. 1991 Oct;11(5):437-53. [PubMed Link Image]
  5. Stormann TM, Gdula DC, Weiner DM, Brann MR: Molecular cloning and expression of a dopamine D2 receptor from human retina. Mol Pharmacol. 1990 Jan;37(1):1-6. [PubMed Link Image]
  6. Robakis NK, Mohamadi M, Fu DY, Sambamurti K, Refolo LM: Human retina D2 receptor cDNAs have multiple polyadenylation sites and differ from a pituitary clone at the 5' non-coding region. Nucleic Acids Res. 1990 Mar 11;18(5):1299. [PubMed Link Image]
  7. Selbie LA, Hayes G, Shine J: DNA homology screening: isolation and characterization of the human D2A dopamine receptor subtype. Adv Second Messenger Phosphoprotein Res. 1990;24:9-14. [PubMed Link Image]
  8. Dal Toso R, Sommer B, Ewert M, Herb A, Pritchett DB, Bach A, Shivers BD, Seeburg PH: The dopamine D2 receptor: two molecular forms generated by alternative splicing. EMBO J. 1989 Dec 20;8(13):4025-34. [PubMed Link Image]
  9. Grandy DK, Marchionni MA, Makam H, Stofko RE, Alfano M, Frothingham L, Fischer JB, Burke-Howie KJ, Bunzow JR, Server AC, et al.: Cloning of the cDNA and gene for a human D2 dopamine receptor. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9762-6. [PubMed Link Image]
  10. Selbie LA, Hayes G, Shine J: The major dopamine D2 receptor: molecular analysis of the human D2A subtype. DNA. 1989 Nov;8(9):683-9. [PubMed Link Image]
  11. 7902708 Itokawa M, Arinami T, Futamura N, Hamaguchi H, Toru M: A structural polymorphism of human dopamine D2 receptor, D2(Ser311-->Cys). Biochem Biophys Res Commun. 1993 Nov 15;196(3):1369-75.
  12. 8471125 Seeman P, Ohara K, Ulpian C, Seeman MV, Jellinger K, Van Tol HH, Niznik HB: Schizophrenia: normal sequence in the dopamine D2 receptor region that couples to G-proteins. DNA polymorphisms in D2. Neuropsychopharmacology. 1993 Feb;8(2):137-42.
Target 3 Drug References
  1. Mori A, Ohashi S, Nakai M, Moriizumi T, Mitsumoto Y: Neural mechanisms underlying motor dysfunction as detected by the tail suspension test in MPTP-treated C57BL/6 mice. Neurosci Res. 2005 Mar;51(3):265-74. Epub 2005 Jan 8. [PubMed Link Image]
  2. Kovoor A, Seyffarth P, Ebert J, Barghshoon S, Chen CK, Schwarz S, Axelrod JD, Cheyette BN, Simon MI, Lester HA, Schwarz J: D2 dopamine receptors colocalize regulator of G-protein signaling 9-2 (RGS9-2) via the RGS9 DEP domain, and RGS9 knock-out mice develop dyskinesias associated with dopamine pathways. J Neurosci. 2005 Feb 23;25(8):2157-65. [PubMed Link Image]
  3. Zappia M, Annesi G, Nicoletti G, Arabia G, Annesi F, Messina D, Pugliese P, Spadafora P, Tarantino P, Carrideo S, Civitelli D, De Marco EV, Ciro-Candiano IC, Gambardella A, Quattrone A: Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study. Arch Neurol. 2005 Apr;62(4):601-5. [PubMed Link Image]
  4. Chang CC, Shiah IS, Chang HA, Mao WC: Does domperidone potentiate mirtazapine-associated restless legs syndrome? Prog Neuropsychopharmacol Biol Psychiatry. 2006 Mar;30(2):316-8. Epub 2005 Nov 23. [PubMed Link Image]
  5. Dupre KB, Eskow KL, Negron G, Bishop C: The differential effects of 5-HT(1A) receptor stimulation on dopamine receptor-mediated abnormal involuntary movements and rotations in the primed hemiparkinsonian rat. Brain Res. 2007 Jul 16;1158:135-43. Epub 2007 May 8. [PubMed Link Image]
Drug Target 4 [top]
Target 4 ID 3330
Target 4 Name Phenylethylamine oxidase
Target 4 Synonyms
  1. Amine oxidase
  2. EC 1.4.3.6
  3. Phenylethylamine oxidase precursor
Target 4 Gene Name Not Available
Target 4 Protein Sequence >Phenylethylamine oxidase precursor 
MTPSTIQTASPFRLASAGEISEVQGILRTAGLLGPEKRIAYLGVLDPARGAGSEAEDRRF
RVFIHDVSGARPQEVTVSVTNGTVISAVELDTAATGELPVLEEEFEVVEQLLATDERWLK
ALAARNLDVSKVRVAPLSAGVFEYAEERGRRILRGLAFVQDFPEDSAWAHPVDGLVAYVD
VVSKEVTRVIDTGVFPVPAEHGNYTDPELTGPLRTTQKPISITQPEGPSFTVTGGNHIEW
EKWSLDVGFDVREGVVLHNIAFRDGDRLRPIINRASIAEMVVPYGDPSPIRSWQNYFDTG
EYLVGQYANSLELGCDCLGDITYLSPVISDAFGNPREIRNGICMHEEDWGILAKHSDLWS
GINYTRRNRRMVISFFTTIGNYDYGFYWYLYLDGTIEFEAKATGVVFTSAFPEGGSDNIS
QLAPGLGAPFHQHIFSARLDMAIDGFTNRVEEEDVVRQTMGPGNERGNAFSRKRTVLTRE
SEAVREADARTGRTWIISNPESKNRLNEPVGYKLHAHNQPTLLADPGSSIARRAAFATKD
LWVTRYADDERYPTGDFVNQHSGGAGLPSYIAQDRDIDGQDIVVWHTFGLTHFPRVEDWP
IMPVDTVGFKLRPEGFFDRSPVLDVPANPSQSGSHCHG
Target 4 Number of Residues 648
Target 4 Molecular Weight 70647
Target 4 Theoretical pI 4.81
Target 4 GO Classification
Function
binding
ion binding
cation binding
transition metal ion binding
copper ion binding
Process
Not Available
Component
Not Available
Target 4 General Function Secondary metabolites biosynthesis, transport and catabolism
Target 4 Specific Function RCH(2)NH(2) + H(2)O + O(2) = RCHO + NH(3) + H(2)O(2)
Target 4 Pathways
Name SMPDB Link KEGG Link
Glycine, serine and threonine metabolism SMP00004 Link Image map00260 Link Image
Target 4 Reactions
  • RCH2NH2 + H2O + O2 = RCHO + NH3 + H2O2
Target 4 Pfam Domain Function
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • None
Target 4 Essentiality Essential
Target 4 GenBank ID Protein Not Available
Target 4 UniProtKB/Swiss-Prot ID P46881 Link Image
Target 4 UniProtKB/Swiss-Prot Entry Name PAOX_ARTGO Link Image
Target 4 PDB ID 1IVU Link Image
Target 4 PDB File Show
Target 4 3D Structure
Target 4 Cellular Location Not Available
Target 4 Gene Sequence >1917 bp 
ATGACGCCCTCCACTATCCAAACAGCCAGCCCCTTCCGCCTTGCCTCAGCTGGGGAAATC
AGTGAGGTGCAGGGCATTCTTCGGACCGCGGGCCTCCTTGGCCCGGAGAAGCGCATTGCC
TACCTGGGCGTCCTTGACCCGGCCCGCGGCGCCGGCAGTGAAGCGGAAGACCGGCGCTTC
CGGGTTTTCATCCACGACGTCTCCGGCGCCCGGCCCCAGGAAGTCACTGTCTCGGTCACC
AACGGCACTGTGATCTCCGCCGTCGAACTCGATACCGCGGCCACCGGCGAACTGCCGGTC
CTGGAAGAGGAGTTCGAGGTTGTGGAGCAACTGCTGGCCACCGACGAACGGTGGCTGAAG
GCCCTGGCCGCCCGGAACCTTGACGTCAGCAAGGTGCGCGTTGCTCCGCTGTCCGCGGGT
GTCTTCGAGTATGCGGAGGAGAGGGGCCGCCGGATCCTCCGCGGGCTTGCCTTCGTACAG
GATTTTCCGGAGGACAGCGCTTGGGCTCATCCGGTTGACGGGCTGGTGGCCTACGTGGAC
GTGGTCAGCAAGGAAGTCACCCGGGTGATCGACACCGGCGTCTTCCCCGTCCCGGCAGAG
CACGGCAATTACACCGATCCCGAACTCACGGGTCCACTCCGCACCACCCAGAAACCCATC
AGCATCACCCAGCCCGAAGGCCCCAGCTTCACGGTGACCGGCGGCAACCACATCGAATGG
GAAAAATGGAGCCTGGACGTCGGCTTTGACGTCCGCGAGGGCGTGGTGCTGCACAACATT
GCCTTCCGGGACGGGGACCGGCTCCGGCCCATCATCAACCGCGCGTCGATCGCCGAGATG
GTGGTGCCGTACGGCGATCCGTCCCCGATCAGGTCCTGGCAGAACTACTTCGACACGGGG
GAGTACCTGGTGGGCCAGTACGCCAACTCCCTCGAACTGGGCTGCGACTGCCTCGGCGAC
ATCACCTACCTCAGCCCGGTCATCAGCGACGCCTTCGGCAACCCCCGCGAGATCCGCAAC
GGCATCTGCATGCACGAGGAGGACTGGGGCATCCTGGCCAAGCACAGCGACCTTTGGTCC
GGCATCAACTACACCCGCCGGAACCGCCGCATGGTGATCTCCTTCTTCACCACTATCGGC
AACTACGACTACGGCTTCTACTGGTACCTCTACCTCGACGGCACCATCGAATTCGAAGCG
AAAGCCACCGGCGTCGTCTTCACGTCCGCATTCCCGGAAGGCGGCTCGGACAACATTTCC
CAGCTGGCACCGGGCCTGGGAGCGCCGTTCCACCAGCACATCTTCAGCGCCCGCCTGGAC
ATGGCCATCGACGGCTTCACCAACAGGGTGGAGGAAGAGGACGTGGTCCGGCAAACCATG
GGCCCGGGCAACGAGCGCGGCAACGCGTTCTCCCGAAAGCGCACCGTGCTGACCCGTGAG
TCGGAGGCTGTCCGCGAGGCCGATGCCCGCACCGGCCGGACCTGGATCATCTCCAACCCC
GAATCCAAGAACCGTCTCAACGAGCCGGTGGGCTACAAGCTGCACGCCCACAACCAGCCC
ACCCTGCTGGCCGATCCCGGGTCCTCCATTGCGCGGCGGGCCGCCTTTGCCACCAAGGAC
CTGTGGGTCACCCGCTACGCCGACGACGAGCGCTACCCCACCGGCGACTTCGTCAACCAG
CACTCCGGCGGCGCGGGCCTGCCCTCCTACATCGCCCAGGACCGCGACATCGACGGCCAG
GACATCGTCGTGTGGCACACCTTCGGACTGACCCACTTCCCGCGCGTGGAGGACTGGCCC
ATCATGCCGGTGGACACCGTCGGCTTCAAGCTCCGTCCCGAGGGCTTCTTCGACCGCAGC
CCGGTCCTCGATGTCCCGGCCAACCCCAGCCAGTCCGGCTCCCACTGCCACGGCTAG
Target 4 GenBank Gene ID
Target 4 GeneCard ID Not Available
Target 4 GenAtlas ID Not Available
Target 4 HGNC ID Not Available
Target 4 Chromosome Location Not Available
Target 4 Locus Not Available
Target 4 SNPs Not Available
Target 4 General References
  1. Tanizawa K, Matsuzaki R, Shimizu E, Yorifuji T, Fukui T: Cloning and sequencing of phenylethylamine oxidase from Arthrobacter globiformis and implication of Tyr-382 as the precursor to its covalently bound quinone cofactor. Biochem Biophys Res Commun. 1994 Mar 30;199(3):1096-102. [PubMed Link Image]
  2. Wilce MC, Dooley DM, Freeman HC, Guss JM, Matsunami H, McIntire WS, Ruggiero CE, Tanizawa K, Yamaguchi H: Crystal structures of the copper-containing amine oxidase from Arthrobacter globiformis in the holo and apo forms: implications for the biogenesis of topaquinone. Biochemistry. 1997 Dec 23;36(51):16116-33. [PubMed Link Image]
Target 4 Drug References Not Available
Drug Target 5 [top]
Target 5 ID 3810
Target 5 Name Catechol O-methyltransferase
Target 5 Synonyms
  1. EC 2.1.1.6
Target 5 Gene Name COMT
Target 5 Protein Sequence >Catechol O-methyltransferase 
MPEAPPLLLAAVLLGLVLLVVLLLLLRHWGWGLCLIGWNEFILQPIHNLLMGDTKEQRIL
NHVLQHAEPGNAQSVLEAIDTYCEQKEWAMNVGDKKGKIVDAVIQEHQPSVLLELGAYCG
YSAVRMARLLSPGARLITIEINPDCAAITQRMVDFAGVKDKVTLVVGASQDIIPQLKKKY
DVDTLDMVFLDHWKDRYLPDTLLLEECGLLRKGTVLLADNVICPGAPDFLAHVRGSSCFE
CTHYQSFLEYREVVDGLEKAIYKGPGSEAGP
Target 5 Number of Residues 275
Target 5 Molecular Weight 30037
Target 5 Theoretical pI 5.15
Target 5 GO Classification
Function
catalytic activity
transferase activity
transferase activity, transferring one-carbon groups
methyltransferase activity
O-methyltransferase activity
Process
Not Available
Component
Not Available
Target 5 General Function Involved in O-methyltransferase activity
Target 5 Specific Function Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol
Target 5 Pathways
Name SMPDB Link KEGG Link
Tyrosine metabolism SMP00006 Link Image map00350 Link Image
Target 5 Reactions
  • S-adenosyl-L-methionine + a catechol = S-adenosyl-L-homocysteine + a guaiacol
Target 5 Pfam Domain Function
Target 5 Signals
  • None
Target 5 Transmembrane Regions
  • 7-26
Target 5 Essentiality Non-Essential
Target 5 GenBank ID Protein 180920 Link Image
Target 5 UniProtKB/Swiss-Prot ID P21964 Link Image
Target 5 UniProtKB/Swiss-Prot Entry Name COMT_HUMAN Link Image
Target 5 PDB ID Not Available
Target 5 Cellular Location
  • Isoform S-COMT:Cytoplasm. Isoform MB-COMT:Cell membrane
  • extra
  • single-pass type II membrane protein
Target 5 Gene Sequence >816 bp 
ATGCCGGAGGCCCCGCCTCTGCTGTTGGCAGCTGTGTTGCTGGGCCTGGTGCTGCTGGTG
GTGCTGCTGCTGCTTCTGAGGCACTGGGGCTGGGGCCTGTGCCTTATCGGCTGGAACGAG
TTCATCCTGCAGCCCATCCACAACCTGCTCATGGGTGACACCAAGGAGCAGCGCATCCTG
AACCACGTGCTGCAGCATGCGGAGCCCGGGAACGCACAGAGCGTGCTGGAGGCCATTGAC
ACCTACTGCGAGCAGAAGGAGTGGGCCATGAACGTGGGCGACAAGAAAGGCAAGATCGTG
GACGCCGTGATTCAGGAGCACCAGCCCTCCGTGCTGCTGGAGCTGGGGGCCTACTGTGGC
TACTCAGCTGTGCGCATGGCCCGCCTGCTGTCACCAGGGGCGAGGCTCATCACCATCGAG
ATCAACCCCGACTGTGCCGCCATCACCCAGCGGATGGTGGATTTCGCTGGCGTGAAGGAC
AAGGTCACCCTTGTGGTTGGAGCGTCCCAGGACATCATCCCCCAGCTGAAGAAGAAGTAT
GATGTGGACACACTGGACATGGTCTTCCTCGACCACTGGAAGGACCGGTACCTGCCGGAC
ACGCTTCTCTTGGAGGAATGTGGCCTGCTGCGGAAGGGGACAGTGCTACTGGCTGACAAC
GTGATCTGCCCAGGTGCGCCAGACTTCCTAGCACACGTGCGCGGGAGCAGCTGCTTTGAG
TGCACACACTACCAATCGTTCCTGGAATACAGGGAGGTGGTGGACGGCCTGGAGAAGGCC
ATCTACAAGGGCCCAGGCAGCGAAGCAGGGCCCTGA
Target 5 GenBank Gene ID
Target 5 GeneCard ID COMT Link Image
Target 5 GenAtlas ID COMT Link Image
Target 5 HGNC ID HGNC:2228 Link Image
Target 5 Chromosome Location 22
Target 5 Locus 22q11.21-q11.23|22q11.21
Target 5 SNPs SNPJam Report Link Image
Target 5 General References
  1. Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES: Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet. 1999 Jul;22(3):231-8. [PubMed Link Image]
  2. Lundstrom K, Salminen M, Jalanko A, Savolainen R, Ulmanen I: Cloning and characterization of human placental catechol-O-methyltransferase cDNA. DNA Cell Biol. 1991 Apr;10(3):181-9. [PubMed Link Image]
  3. Ulmanen I, Lundstrom K: Cell-free synthesis of rat and human catechol O-methyltransferase. Insertion of the membrane-bound form into microsomal membranes in vitro. Eur J Biochem. 1991 Dec 18;202(3):1013-20. [PubMed Link Image]
  4. Bertocci B, Miggiano V, Da Prada M, Dembic Z, Lahm HW, Malherbe P: Human catechol-O-methyltransferase: cloning and expression of the membrane-associated form. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1416-20. [PubMed Link Image]
  5. Tilgmann C, Kalkkinen N: Purification and partial sequence analysis of the soluble catechol-O-methyltransferase from human placenta: comparison to the rat liver enzyme. Biochem Biophys Res Commun. 1991 Jan 31;174(2):995-1002. [PubMed Link Image]
  6. Tenhunen J, Salminen M, Lundstrom K, Kiviluoto T, Savolainen R, Ulmanen I: Genomic organization of the human catechol O-methyltransferase gene and its expression from two distinct promoters. Eur J Biochem. 1994 Aug 1;223(3):1049-59. [PubMed Link Image]
  7. Lachman HM, Papolos DF, Saito T, Yu YM, Szumlanski CL, Weinshilboum RM: Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics. 1996 Jun;6(3):243-50. [PubMed Link Image]
Target 5 Drug References Not Available

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.