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Showing drug card for Ouabain (DB01092)

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Version 2.5
Creation Date 2005-06-13 13:24:05
Update Date 2009-02-19 16:04:34
Primary Accession Number DB01092
Secondary Accession Number
  • APRD00135
Name Ouabain
Drug Type
  • Approved
  • Small Molecule
Description A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like digitalis. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-exchanging ATPase. [PubChem]
Synonyms
  1. G-Strophanthin
  2. Ouabagenin L-Rhamnoside
  3. Ouabain Octahydrate
  4. Ouabain, Octahydrate
  5. Ouabaine
  6. Strophanthin G
  7. Strophanthin-G
Brand Names
  1. Acocantherin
  2. Astrobain
  3. G-Strophicor
  4. Gratibain
  5. Gratus Strophanthin
  6. Kombetin
  7. Purostrophan
  8. Rectobaina
  9. Solufantina
  10. Strodival
  11. Strophalen
  12. Strophoperm
  13. Strophosan
  14. Uabaina
  15. Uabanin
Brand Mixtures Not Available
Chemical IUPAC Name 4-[(1R,3S,5S,8R,9S,10R,11R,13R,14S,17R)-1,5,11,14-tetrahydroxy-10-(hydroxymethyl)-13-methyl-3-[(2R,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy-2,3,4,6,7,8,9,11,12,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-5H-furan-2-one
Chemical Formula C29H44O12
Chemical Structure Structure
CAS Registry Number 630-60-4
InChI Identifier InChI=1/C29H44O12/c1-13-22(34)23(35)24(36)25(40-13)41-15-8-19(32)28(12-30)21-17(3-5-27(28,37)9-15)29(38)6-4-16(14-7-20(33)39-11-14)26(29,2)10-18(21)31/h7,13,15-19,21-25,30-32,34-38H,3-6,8-12H2,1-2H3/t13-,15-,16+,17+,18+,19+,21+,22-,23+,24+,25-,26+,27-,28+,29-/m0/s1
InChI Key LPMXVESGRSUGHW-HBYQJFLCBJ
KEGG Drug D00112 Link Image
KEGG Compound C01443 Link Image
PubChem Compound 439501 Link Image
PubChem Substance 4621 Link Image
ChEBI ID Not Available
PharmGKB ID Not Available
HET ID Not Available
GenBank ID Not Available
Drug ID Number [DIN] Not Available
RxList Link Not Available
PDRhealth Link Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Ouabain Link Image
FDA Label Not Available
Material Safety Data Sheet (MSDS) Not Available
Synthesis Reference Not Available
Average Molecular Weight 584.6525
Monoisotopic Molecular Weight 584.2833
State Solid
Melting Point 200 oC
Experimental Water Solubility 1.03E+004 mg/L Source: PhysProp
Predicted Water Solubility 4.61e+00 mg/mL Calculated using ALOGPS
Experimental LogP/Hydrophobicity -1.2 Source: PhysProp
Predicted LogP -1.02 Calculated using ALOGPS
Experimental LogS Not Available
Predicted LogS -2.10 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 C[C@@H]1O[C@@H](O[C@H]2C[C@@H](O)[C@]3(CO)[C@H]4[C@H](O)C[C@]5(C)[C@H](CC[C@]5(O)[C@@H]4CC[C@]3(O)C2)C2=CC(=O)OC2)[C@H](O)[C@H](O)[C@H]1O
Canonical SMILES CC1OC(OC2CC(O)C3(CO)C4C(O)CC5(C)C(CCC5(O)C4CCC3(O)C2)C2=CC(=O)OC2)C(O)C(O)C1O
Drug Category
  • Cardiotonic Agents
  • Enzyme Inhibitors
ATC Codes Not Available
AHFS Codes Not Available
Indication For the treatment of atrial fibrillation and flutter and heart failure
Pharmacology Ouabain, a cardiac glycoside similar to digitoxin, is used to treat congestive heart failure and supraventricular arrhythmias due to reentry mechanisms, and to control ventricular rate in the treatment of chronic atrial fibrillation.
Mechanism of Action Ouabain inhibits the Na-K-ATPase membrane pump, resulting in an increase in intracellular sodium and calcium concentrations. Increased intracellular concentrations of calcium may promote activation of contractile proteins (e.g., actin, myosin). Ouabain also acts on the electrical activity of the heart, increasing the slope of phase 4 depolarization, shortening the action potential duration, and decreasing the maximal diastolic potential.
Absorption Not Available
Toxicity Not Available
Protein Binding 60%
Biotransformation Not Available
Half Life Not Available
Dosage Forms Not Available
Patient Information Not Available
Contraindications Not Available
Interactions Not Available
Drug Interactions Not Available
Food Interactions Not Available
Pathways Not Available
General References
  1. Gao J, Wymore RS, Wang Y, Gaudette GR, Krukenkamp IB, Cohen IS, Mathias RT: Isoform-specific stimulation of cardiac Na/K pumps by nanomolar concentrations of glycosides. J Gen Physiol. 2002 Apr;119(4):297-312. [PubMed Link Image]
  2. Hamlyn JM, Laredo J, Shah JR, Lu ZR, Hamilton BP: 11-hydroxylation in the biosynthesis of endogenous ouabain: multiple implications. Ann N Y Acad Sci. 2003 Apr;986:685-93. [PubMed Link Image]
  3. Saunders R, Scheiner-Bobis G: Ouabain stimulates endothelin release and expression in human endothelial cells without inhibiting the sodium pump. Eur J Biochem. 2004 Mar;271(5):1054-62. [PubMed Link Image]
  4. Hamlyn JM, Blaustein MP, Bova S, DuCharme DW, Harris DW, Mandel F, Mathews WR, Ludens JH: Identification and characterization of a ouabain-like compound from human plasma. Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6259-63. [PubMed Link Image]
  5. Laredo J, Hamilton BP, Hamlyn JM: Ouabain is secreted by bovine adrenocortical cells. Endocrinology. 1994 Aug;135(2):794-7. [PubMed Link Image]
  6. Wikipedia Link Image
Organisms Affected
  • Humans and other mammals
Phase 1 Metabolizing Enzymes
  1. Cytochrome P450 11A1 (CYP11A1)
Targets
  1. Sodium/potassium-transporting ATPase alpha-1 chain
  2. Kininogen-1
  3. Angiotensinogen
Phase 1 Metabolizing Enzyme 1 [top]
Enzyme 1 Name Cytochrome P450 11A1 (CYP11A1)
Enzyme 1 Gene Name CYP11A1
Enzyme 1 SwissProt ID P05108 Link Image
Enzyme 1 SNPs SNPJam Report Link Image
Enzyme 1 Protein Sequence >sp|P05108|C11A_HUMAN Cytochrome P450 11A1 
MLAKGLPPRSVLVKGYQTFLSAPREGLGRLRVPTGEGAGISTRSPRPFNEIPSPGDNGWL
NLYHFWRETGTHKVHLHHVQNFQKYGPIYREKLGNVESVYVIDPEDVALLFKSEGPNPER
FLIPPWVAYHQYYQRPIGVLLKKSAAWKKDRVALNQEVMAPEATKNFLPLLDAVSRDFVS
VLHRRIKKAGSGNYSGDISDDLFRFAFESITNVIFGERQGMLEEVVNPEAQRFIDAIYQM
FHTSVPMLNLPPDLFRLFRTKTWKDHVAAWDVIFSKADIYTQNFYWELRQKGSVHHDYRG
MLYRLLGDSKMSFEDIKANVTEMLAGGVDTTSMTLQWHLYEMARNLKVQDMLRAEVLAAR
HQAQGDMATMLQLVPLLKASIKETLRLHPISVTLQRYLVNDLVLRDYMIPAKTLVQVAIY
ALGREPTFFFDPENFDPTRWLSKDKNITYFRNLGFGWGVRQCLGRRIAELEMTIFLINML
ENFRVEIQHLSDVGTTFNLILMPEKPISFTFWPFNQEATQQ
Drug Target 1 [top]
Target 1 ID 806
Target 1 Name Sodium/potassium-transporting ATPase alpha-1 chain
Target 1 Synonyms
  1. EC 3.6.3.9
  2. Na(+)/K(+) ATPase alpha-1 subunit
  3. Sodium pump subunit alpha 1
  4. Sodium/potassium-transporting ATPase alpha-1 chain precursor
Target 1 Gene Name ATP1A1
Target 1 Protein Sequence >Sodium/potassium-transporting ATPase alpha-1 chain precursor 
MGKGVGRDKYEPAAVSEQGDKKGKKGKKDRDMDELKKEVSMDDHKLSLDELHRKYGTDLS
RGLTSARAAEILARDGPNALTPPPTTPEWIKFCRQLFGGFSMLLWIGAILCFLAYSIQAA
TEEEPQNDNLYLGVVLSAVVIITGCFSYYQEAKSSKIMESFKNMVPQQALVIRNGEKMSI
NAEEVVVGDLVEVKGGDRIPADLRIISANGCKVDNSSLTGESEPQTRSPDFTNENPLETR
NIAFFSTNCVEGTARGIVVYTGDRTVMGRIATLASGLEGGQTPIAAEIEHFIHIITGVAV
FLGVSFFILSLILEYTWLEAVIFLIGIIVANVPEGLLATVTVCLTLTAKRMARKNCLVKN
LEAVETLGSTSTICSDKTGTLTQNRMTVAHMWFDNQIHEADTTENQSGVSFDKTSATWLA
LSRIAGLCNRAVFQANQENLPILKRAVAGDASESALLKCIELCCGSVKEMRERYAKIVEI
PFNSTNKYQLSIHKNPNTSEPQHLLVMKGAPERILDRCSSILLHGKEQPLDEELKDAFQN
AYLELGGLGERVLGFCHLFLPDEQFPEGFQFDTDDVNFPIDNLCFVGLISMIDPPRAAVP
DAVGKCRSAGIKVIMVTGDHPITAKAIAKGVGIISEGNETVEDIAARLNIPVSQVNPRDA
KACVVHGSDLKDMTSEQLDDILKYHTEIVFARTSPQQKLIIVEGCQRQGAIVAVTGDGVN
DSPALKKADIGVAMGIAGSDVSKQAADMILLDDNFASIVTGVEEGRLIFDNLKKSIAYTL
TSNIPEITPFLIFIIANIPLPLGTVTILCIDLGTDMVPAISLAYEQAESDIMKRQPRNPK
TDKLVNERLISMAYGQIGMIQALGGFFTYFVILAENGFLPIHLLGLRVDWDDRWINDVED
SYGQQWTYEQRKIVEFTCHTAFFVSIVVVQWADLVICKTRRNSVFQQGMKNKILIFGLFE
ETALAAFLSYCPGMGVALRMYPLKPTWWFCAFPYSLLIFVYDEVRKLIIRRRPGGWVEKE
TYY
Target 1 Number of Residues 1040
Target 1 Molecular Weight 112897
Target 1 Theoretical pI 5.15
Target 1 GO Classification
Function
hydrolase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, catalyzing transmembrane movement of substances
catalytic activity
binding
nucleotide binding
purine nucleotide binding
adenyl nucleotide binding
ATP binding
monovalent inorganic cation transporter activity
transporter activity
ion transporter activity
cation transporter activity
ATPase activity, coupled to transmembrane movement of ions, phosphorylative mechanism
Process
metabolism
monovalent inorganic cation transport
physiological process
cellular physiological process
transport
ion transport
cation transport
Component
intrinsic to membrane
integral to membrane
cell
membrane
Target 1 General Function Inorganic ion transport and metabolism
Target 1 Specific Function This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients
Target 1 Pathways Not Available
Target 1 Reactions
  • ATP + H2O + Na+in + K+out = ADP + phosphate + Na+out + K+in
Target 1 Pfam Domain Function
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 88-108
  • 132-152
  • 289-308
  • 321-338
  • 773-792
  • 803-823
  • 844-866
  • 919-938
  • 952-970
  • 986-1006
Target 1 Essentiality Non-Essential
Target 1 GenBank ID Protein 219942 Link Image
Target 1 UniProtKB/Swiss-Prot ID P05023 Link Image
Target 1 UniProtKB/Swiss-Prot Entry Name AT1A1_HUMAN Link Image
Target 1 PDB ID 1MO8 Link Image
Target 1 PDB File Show
Target 1 3D Structure
Target 1 Cellular Location
  • Membrane
  • multi-pass membrane protein
Target 1 Gene Sequence >3072 bp 
ATGGGGAAGGGGGTTGGACGTGATAAGTATGAGCCTGCAGCTGTTTCAGAACAAGGTGAT
AAAAAGGGCAAAAAGGGCAAAAAAGACAGGGACATGGATGAACTGAAGAAAGAAGTTTCT
ATGGATGATCATAAACTTAGCCTTGATGAACTTCATCGTAAATATGGAACAGACTTGAGC
CGGGGATTAACATCTGCTCGTGCAGCTGAGATCCTGGCGCGAGATGGTCCCAACGCCCTC
ACTCCCCCTCCCACTACTCCTGAATGGATCAAGTTTTGTCGGCAGCTCTTTGGGGGGTTC
TCAATGTTACTGTGGATTGGAGCGATTCTTTGTTTCTTGGCTTATAGCATCCAAGCTGCT
ACAGAAGAGGAACCTCAAAACGATAATCTGTACCTGGGTGTGGTGCTATCAGCCGTTGTA
ATCATAACTGGTTGCTTCTCCTACTATCAAGAAGCTAAAAGTTCAAAGATCATGGAATCC
TTCAAAAACATGGTCCCTCAGCAAGCCCTTGTGATTCGAAATGGTGAGAAAATGAGCATA
AATGCGGAGGAAGTTGTGGTTGGGGATCTGGTGGAAGTAAAAGGAGGAGACCGAATTCCT
GCTGACCTCAGAATCATATCTGCAAATGGCTGCAAGGTGGATAACTCCTCGCTCACTGGT
GAATCAGAACCCCAGACTAGGTCTCCAGATTTCACAAATGAAAACCCCCTGGAGACGAGG
AACATTGCCTTCTTTTCAACAAATTGTGTTGAAGGCACCGCACGTGGTATTGTTGTCTAC
ACTGGGGATCGCACTGTGATGGGAAGAATTGCCACACTTGCTTCTGGGCTGGAAGGAGGC
CAGACCCCCATTGCTGCAGAAATTGAACATTTTATCCACATCATCACGGGTGTGGCTGTG
TTCCTGGGTGTGTCTTTCTTCATCCTTTCTCTCATCCTTGAGTACACCTGGCTTGAGGCT
GTCATCTTCCTCATCGGTATCATCGTAGCCAATGTGCCGGAAGGTTTGCTGGCCACTGTC
ACGGTCTGTCTGACACTTACTGCCAAACGCATGGCAAGGAAAAACTGCTTAGTGAAGAAC
TTAGAAGCTGTGGAGACCTTGGGGTCCACGTCCACCATCTGCTCTGATAAAACTGGAACT
CTGACTCAGAACCGGATGACAGTGGCCCACATGTGGTTTGACAATCAAATCCATGAAGCT
GATACGACAGAGAATCAGAGTGGTGTCTCTTTTGACAAGACTTCAGCTACCTGGCTTGCT
CTGTCCAGAATTGCAGGTCTTTGTAACAGGGCAGTGTTTCAGGCTAACCAGGAAAACCTA
CCTATTCTTAAGCGGGCAGTTGCAGGAGATGCCTCTGAGTCAGCACTCTTAAAGTGCATA
GAGCTGTGCTGTGGTTCCGTGAAGGAGATGAGAGAAAGATACGCCAAAATCGTCGAGATA
CCCTTCAACTCCACCAACAAGTACCAGTTGTCTATTCATAAGAACCCCAACACATCGGAG
CCCCAACACCTGTTGGTGATGAAGGGCGCCCCAGAAAGGATCCTAGACCGTTGCAGCTCT
ATCCTCCTCCACGGCAAGGAGCAGCCCCTGGATGAGGAGCTGAAAGACGCCTTTCAGAAC
GCCTATTTGGAGCTGGGGGGCCTCGGAGAACGAGTCCTAGGTTTCTGCCACCTCTTTCTG
CCAGATGAACAGTTTCCTGAAGGGTTCCAGTTTGACACTGACGATGTGAATTTCCCTATC
GATAATCTGTGCTTTGTTGGGCTCATCTCCATGATTGACCCTCCACGGGCGGCCGTTCCT
GATGCCGTGGGCAAATGTCGAAGTGCTGGAATTAAGGTCATCATGGTCACAGGAGACCAT
CCAATCACAGCTAAAGCTATTGCCAAAGGTGTGGGCATCATCTCAGAAGGCAATGAGACC
GTGGAAGACATTGCTGCCCGCCTCAACATCCCAGTCAGCCAGGTGAACCCCAGGGATGCC
AAGGCCTGCGTAGTACACGGCAGTGATCTAAAGGACATGACCTCCGAGCAGCTGGATGAC
ATTTTGAAGTACCACACTGAGATAGTGTTTGCCAGGACCTCCCCTCAGCAGAAGCTCATC
ATTGTGGAAGGCTGCCAAAGACAGGGTGCTATCGTGGCTGTGACTGGTGACGGTGTGAAT
GACTCTCCAGCTTTGAAGAAAGCAGACATTGGGGTTGCTATGGGGATTGCTGGCTCAGAT
GTGTCCAAGCAAGCTGCTGACATGATTCTTCTGGATGACAACTTTGCCTCAATTGTGACT
GGAGTAGAGGAAGGTCGTCTGATCTTTGATAACTTGAAGAAATCCATTGCTTATACCTTA
ACCAGTAACATTCCCGAGATCACCCCGTTCCTGATATTTATTATTGCAAACATTCCACTA
CCACTGGGGACTGTCACCATCCTCTGCATTGACTTGGGCACTGACATGGTTCCTGCCATC
TCCCTGGCTTATGAGCAGGCTGAGAGTGACATCATGAAGAGACAGCCCAGAAATCCCAAA
ACAGACAAACTTGTGAATGAGCGGCTGATCAGCATGGCCTATGGGCAGATTGGAATGATC
CAGGCCCTGGGAGGCTTCTTTACTTACTTTGTGATTCTGGCTGAGAACGGCTTCCTCCCA
ATTCACCTGTTGGGCCTCCGAGTGGACTGGGATGACCGCTGGATCAACGATGTGGAAGAC
AGCTACGGGCAGCAGTGGACCTATGAGCAGAGGAAAATCGTGGAGTTCACCTGCCACACA
GCCTTCTTCGTCAGTATCGTGGTGGTGCAGTGGGCCGACTTGGTCATCTGTAAGACCAGG
AGGAATTCGGTCTTCCAGCAGGGGATGAAGAACAAGATCTTGATATTTGGCCTCTTTGAA
GAGACAGCCCTGGCTGCTTTCCTTTCCTACTGCCCTGGAATGGGTGTTGCTCTTAGGATG
TATCCCCTCAAACCTACCTGGTGGTTCTGTGCCTTCCCCTACTCTCTTCTCATCTTCGTA
TATGACGAAGTCAGAAAACTCATCATCAGGCGACGCCCTGGCGGCTGGGTGGAGAAGGAA
ACCTACTATTAG
Target 1 GenBank Gene ID
Target 1 GeneCard ID ATP1A1 Link Image
Target 1 GenAtlas ID ATP1A1 Link Image
Target 1 HGNC ID HGNC:799 Link Image
Target 1 Chromosome Location 1
Target 1 Locus 1p21
Target 1 SNPs SNPJam Report Link Image
Target 1 General References
  1. Shull MM, Pugh DG, Lingrel JB: The human Na, K-ATPase alpha 1 gene: characterization of the 5'-flanking region and identification of a restriction fragment length polymorphism. Genomics. 1990 Mar;6(3):451-60. [PubMed Link Image]
  2. Kawakami K, Ohta T, Nojima H, Nagano K: Primary structure of the alpha-subunit of human Na,K-ATPase deduced from cDNA sequence. J Biochem (Tokyo). 1986 Aug;100(2):389-97. [PubMed Link Image]
  3. Chehab FF, Kan YW, Law ML, Hartz J, Kao FT, Blostein R: Human placental Na+,K+-ATPase alpha subunit: cDNA cloning, tissue expression, DNA polymorphism, and chromosomal localization. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7901-5. [PubMed Link Image]
  4. Shull MM, Lingrel JB: Multiple genes encode the human Na+,K+-ATPase catalytic subunit. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4039-43. [PubMed Link Image]
  5. Sverdlov ED, Monastyrskaya GS, Broude NE, Ushkaryov YuA, Allikmets RL, Melkov AM, Smirnov YuV, Malyshev IV, Dulobova IE, Petrukhin KE, et al.: The family of human Na+,K+-ATPase genes. No less than five genes and/or pseudogenes related to the alpha-subunit. FEBS Lett. 1987 Jun 15;217(2):275-8. [PubMed Link Image]
  6. Ruiz A, Bhat SP, Bok D: Characterization and quantification of full-length and truncated Na,K-ATPase alpha 1 and beta 1 RNA transcripts expressed in human retinal pigment epithelium. Gene. 1995 Apr 3;155(2):179-84. [PubMed Link Image]
Target 1 Drug References
  1. Mentre P, Debey P: An unexpected effect of an ouabain-sensitive ATPase activity on the amount of antigen-antibody complexes formed in situ. Cell Mol Biol (Noisy-le-grand). 1999 Sep;45(6):781-91. [PubMed Link Image]
  2. Qazzaz HM, El-Masri MA, Stolowich NJ, Valdes R Jr: Two biologically active isomers of dihydroouabain isolated from a commercial preparation. Biochim Biophys Acta. 1999 Nov 16;1472(3):486-97. [PubMed Link Image]
  3. Tao QF, Hollenberg NK, Graves SW: Sodium pump inhibition and regional expression of sodium pump alpha-isoforms in lens. Hypertension. 1999 Nov;34(5):1168-74. [PubMed Link Image]
  4. Hawke TJ, Willmets RG, Lindinger MI: K+ transport in resting rat hind-limb skeletal muscle in response to paraxanthine, a caffeine metabolite. Can J Physiol Pharmacol. 1999 Nov;77(11):835-43. [PubMed Link Image]
  5. Almotrefi AA, Basco C, Moorji A, Dzimiri N: Class I antiarrhythmic drug effects on ouabain binding to guinea pig cardiac Na+ -K+ ATPase. Can J Physiol Pharmacol. 1999 Nov;77(11):866-70. [PubMed Link Image]
Drug Target 2 [top]
Target 2 ID 1536
Target 2 Name Kininogen-1
Target 2 Synonyms
  1. Alpha-2-thiol proteinase inhibitor
  2. Kininogen-1 precursor
Target 2 Gene Name KNG1
Target 2 Protein Sequence >Kininogen-1 precursor 
MKLITILFLCSRLLLSLTQESQSEEIDCNDKDLFKAVDAALKKYNSQNQSNNQFVLYRIT
EATKTVGSDTFYSFKYEIKEGDCPVQSGKTWQDCEYKDAAKAATGECTATVGKRSSTKFS
VATQTCQITPAEGPVVTAQYDCLGCVHPISTQSPDLEPILRHGIQYFNNNTQHSSLFMLN
EVKRAQRQVVAGLNFRITYSIVQTNCSKENFLFLTPDCKSLWNGDTGECTDNAYIDIQLR
IASFSQNCDIYPGKDFVQPPTKICVGCPRDIPTNSPELEETLTHTITKLNAENNATFYFK
IDNVKKARVQVVAGKKYFIDFVARETTCSKESNEELTESCETKKLGQSLDCNAEVYVVPW
EKKIYPTVNCQPLGMISLMKRPPGFSPFRSSRIGEIKEETTVSPPHTSMAPAQDEERDSG
KEQGHTRRHDWGHEKQRKHNLGHGHKHERDQGHGHQRGHGLGHGHEQQHGLGHGHKFKLD
DDLEHQGGHVLDHGHKHKHGHGHGKHKNKGKKNGKHNGWKTEHLASSSEDSTTPSAQTQE
KTEGPTPIPSLAKPGVTVTFSDFQDSDLIATMMPPISPAPIQSDDDWIPDIQIDPNGLSF
NPISDFPDTTSPKCPGRPWKSVSEINPTTQMKESYYFDLTDGLS
Target 2 Number of Residues 654
Target 2 Molecular Weight 71958
Target 2 Theoretical pI 6.80
Target 2 GO Classification
Function
enzyme regulator activity
enzyme inhibitor activity
protease inhibitor activity
endopeptidase inhibitor activity
cysteine protease inhibitor activity
Process
Not Available
Component
Not Available
Target 2 General Function Inorganic ion transport and metabolism
Target 2 Specific Function (1) Kininogens are inhibitors of thiol proteases; (2) HMW-kininogen plays an important role in blood coagulation by helping to position optimally prekallikrein and factor XI next to factor XII; (3) HMW-kininogen inhibits the thrombin- and plasmin- induced aggregation of thrombocytes; (4) the active peptide bradykinin that is released from HMW-kininogen shows a variety of physiological effects:(4A) influence in smooth muscle contraction, (4B) induction of hypotension, (4C) natriuresis and diuresis, (4D) decrease in blood glucose level, (4E) it is a mediator of inflammation and causes (4E1) increase in vascular permeability, (4E2) stimulation of nociceptors (4E3) release of other mediators of inflammation (e.g. prostaglandins), (4F) it has a cardioprotective effect (directly via bradykinin action, indirectly via endothelium-derived relaxing factor action); (5) LMW-kininogen inhibits the aggregation of thrombocytes; (6) LMW- kininogen is in contrast to HMW-kininogen not involved in blood clotting
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Pfam Domain Function
Target 2 Signals
  • 1-18
Target 2 Transmembrane Regions
  • None
Target 2 Essentiality Non-Essential
Target 2 GenBank ID Protein 177890 Link Image
Target 2 UniProtKB/Swiss-Prot ID P01042 Link Image
Target 2 UniProtKB/Swiss-Prot Entry Name KNG1_HUMAN Link Image
Target 2 PDB ID Not Available
Target 2 Cellular Location
  • Secreted protein
  • extracellular space
Target 2 Gene Sequence >1935 bp 
ATGAAACTAATTACCATCCTTTTCCTCTGCTCCAGGCTGCTACTAAGTTTAACCCAGGAA
TCACAGTCCGAGGAAATTGACTGCAATGACAAGGATTTATTTAAAGCTGTGGATGCTGCT
CTGAAGAAATATAACAGTCAAAACCAAAGTAACAACCAGTTTGTATTGTACCGCATAACT
GAAGCCACTAAGACGGTTGGCTCTGACACGTTTTATTCCTTCAAGTACGAAATCAAGGAG
GGGGATTGTCCTGTTCAAAGTGGCAAAACCTGGCAGGACTGTGAGTACAAGGATGCTGCA
AAAGCAGCCACTGGAGAATGCACGGCAACCGTGGGGAAGAGGAGCAGTACGAAATTCTCC
GTGGCTACCCAGACCTGCCAGATTACTCCAGCCGAGGGCCCTGTGGTGACAGCCCAGTAC
GACTGCCTCGGCTGTGTGCATCCTATATCCACGCAGAGCCCAGACCTGGAGCCCATTCTG
AGACACGGCATTCAGTACTTTAACAACAACACTCAACATTCCTCCCTCTTCATGCTTAAT
GAAGTAAAACGGGCCCAAAGACAGGTGGTGGCTGGATTGAACTTTCGAATTACCTACTCA
ATTGTGCAAACGAATTGTTCCAAAGAGAATTTTCTGTTCTTAACTCCAGACTGCAAGTCC
CTTTGGAATGGTGATACCGGTGAATGTACAGATAATGCATACATCGATATTCAGCTACGA
ATTGCTTCCTTCTCACAGAACTGTGACATTTATCCAGGGAAGGATTTTGTACAACCACCT
ACCAAGATTTGCGTGGGCTGCCCCAGAGATATACCCACCAACAGCCCAGAGCTGGAGGAG
ACACTGACTCACACCATCACAAAGCTTAATGCAGAGAATAACGCAACTTTCTATTTCAAG
ATTGACAATGTGAAAAAAGCAAGAGTACAGGTGGTGGCTGGCAAGAAATATTTTATTGAC
TTCGTGGCCAGGGAAACCACATGTTCCAAGGAAAGTAATGAAGAGTTGACCGAAAGCTGT
GAGACCAAAAAACTTGGCCAAAGCCTAGATTGCAACGCTGAAGTTTATGTGGTACCCTGG
GAGAAAAAAATTTACCCTACTGTCAACTGTCAACCACTGGGAATGATCTCACTGATGAAA
AGGCCTCCAGGTTTTTCACCTTTCCGATCATCACGAATAGGGGAAATAAAAGAAGAAACA
ACTGTAAGTCCACCCCACACTTCCATGGCACCTGCACAAGATGAAGAGCGGGATTCAGGA
AAAGAACAAGGGCATACTCGTAGACATGACTGGGGCCATGAAAAACAAAGAAAACATAAT
CTTGGCCATGGCCATAAACATGAACGTGACCAAGGGCATGGGCACCAAAGAGGACATGGC
CTTGGCCATGGACACGAACAACAGCATGGTCTTGGTCATGGACATAAGTTCAAACTTGAT
GATGATCTTGAACACCAAGGGGGCCATGTCCTTGACCATGGACATAAGCATAAGCATGGT
CATGGCCACGGAAAACATAAAAATAAAGGCAAAAAGAATGGAAAGCACAATGGTTGGAAA
ACAGAGCATTTGGCAAGCTCTTCTGAAGACAGTACTACACCTTCTGCACAGACACAAGAG
AAGACAGAAGGGCCAACACCCATCCCTTCCCTAGCCAAGCCAGGTGTAACAGTTACCTTT
TCTGACTTTCAGGACTCTGATCTCATTGCAACTATGATGCCTCCTATATCACCAGCTCCC
ATACAGAGTGATGACGATTGGATCCCTGATATCCAGATAGACCCAAATGGCCTTTCATTT
AACCCAATATCAGATTTTCCAGACACGACCTCCCCAAAATGTCCTGGACGCCCCTGGAAG
TCAGTTAGTGAAATTAATCCAACCACACAAATGAAAGAATCTTATTATTTCGATCTCACT
GATGGCCTTTCTTAA
Target 2 GenBank Gene ID
Target 2 GeneCard ID KNG1 Link Image
Target 2 GenAtlas ID KNG1 Link Image
Target 2 HGNC ID HGNC:6383 Link Image
Target 2 Chromosome Location 3
Target 2 Locus 3q27
Target 2 SNPs SNPJam Report Link Image
Target 2 General References
  1. Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. Nat Biotechnol. 2003 Jun;21(6):660-6. Epub 2003 May 18. [PubMed Link Image]
  2. Takagaki Y, Kitamura N, Nakanishi S: Cloning and sequence analysis of cDNAs for human high molecular weight and low molecular weight prekininogens. Primary structures of two human prekininogens. J Biol Chem. 1985 Jul 15;260(14):8601-9. [PubMed Link Image]
  3. Kitamura N, Kitagawa H, Fukushima D, Takagaki Y, Miyata T, Nakanishi S: Structural organization of the human kininogen gene and a model for its evolution. J Biol Chem. 1985 Jul 15;260(14):8610-7. [PubMed Link Image]
  4. Maeda H, Matsumura Y, Kato H: Purification and identification of [hydroxyprolyl3]bradykinin in ascitic fluid from a patient with gastric cancer. J Biol Chem. 1988 Nov 5;263(31):16051-4. [PubMed Link Image]
  5. Kato H, Matsumura Y, Maeda H: Isolation and identification of hydroxyproline analogues of bradykinin in human urine. FEBS Lett. 1988 May 9;232(1):252-4. [PubMed Link Image]
  6. Kellermann J, Lottspeich F, Henschen A, Muller-Esterl W: Completion of the primary structure of human high-molecular-mass kininogen. The amino acid sequence of the entire heavy chain and evidence for its evolution by gene triplication. Eur J Biochem. 1986 Jan 15;154(2):471-8. [PubMed Link Image]
  7. Lottspeich F, Kellermann J, Henschen A, Foertsch B, Muller-Esterl W: The amino acid sequence of the light chain of human high-molecular-mass kininogen. Eur J Biochem. 1985 Oct 15;152(2):307-14. [PubMed Link Image]
  8. Pierce JV: Structural features of plasma kinins and kininogens. Fed Proc. 1968 Jan-Feb;27(1):52-7. [PubMed Link Image]
  9. Ohkubo I, Kurachi K, Takasawa T, Shiokawa H, Sasaki M: Isolation of a human cDNA for alpha 2-thiol proteinase inhibitor and its identity with low molecular weight kininogen. Biochemistry. 1984 Nov 20;23(24):5691-7. [PubMed Link Image]
  10. Straczek J, Maachi F, Le Nguyen D, Becchi M, Heulin MH, Nabet P, Belleville F: Purification from human plasma of a tetrapeptide that potentiates insulin-like growth factor-I activity in chick embryo cartilage. FEBS Lett. 1995 Oct 16;373(3):207-11. [PubMed Link Image]
Target 2 Drug References
  1. Pratt PF, Li P, Hillard CJ, Kurian J, Campbell WB: Endothelium-independent, ouabain-sensitive relaxation of bovine coronary arteries by EETs. Am J Physiol Heart Circ Physiol. 2001 Mar;280(3):H1113-21. [PubMed Link Image]
  2. Dodson AM, Rhoden KJ: Bradykinin increases Na(+)-K(+) pump activity in cultured guinea-pig tracheal smooth muscle cells. Br J Pharmacol. 2001 Aug;133(8):1339-45. [PubMed Link Image]
  3. Bussemaker E, Wallner C, Fisslthaler B, Fleming I: The Na-K-ATPase is a target for an EDHF displaying characteristics similar to potassium ions in the porcine renal interlobar artery. Br J Pharmacol. 2002 Nov;137(5):647-54. [PubMed Link Image]
  4. Taddei S, Virdis A, Ghiadoni L, Versari D, Salvetti G, Magagna A, Salvetti A: Calcium antagonist treatment by lercanidipine prevents hyperpolarization in essential hypertension. Hypertension. 2003 Apr;41(4):950-5. Epub 2003 Mar 17. [PubMed Link Image]
  5. Nelli S, Wilson WS, Laidlaw H, Llano A, Middleton S, Price AG, Martin W: Evaluation of potassium ion as the endothelium-derived hyperpolarizing factor (EDHF) in the bovine coronary artery. Br J Pharmacol. 2003 Jul;139(5):982-8. [PubMed Link Image]
Drug Target 3 [top]
Target 3 ID 1694
Target 3 Name Angiotensinogen
Target 3 Synonyms
  1. Angiotensinogen precursor
  2. Serpin A8
Target 3 Gene Name AGT
Target 3 Protein Sequence >Angiotensinogen precursor 
MRKRAPQSEMAPAGVSLRATILCLLAWAGLAAGDRVYIHPFHLVIHNESTCEQLAKANAG
KPKDPTFIPAPIQAKTSPVDEKALQDQLVLVAAKLDTEDKLRAAMVGMLANFLGFRIYGM
HSELWGVVHGATVLSPTAVFGTLASLYLGALDHTADRLQAILGVPWKDKNCTSRLDAHKV
LSALQAVQGLLVAQGRADSQAQLLLSTVVGVFTAPGLHLKQPFVQGLALYTPVVLPRSLD
FTELDVAAEKIDRFMQAVTGWKTGCSLMGASVDSTLAFNTYVHFQGKMKGFSLLAEPQEF
WVDNSTSVSVPMLSGMGTFQHWSDIQDNFSVTQVPFTESACLLLIQPHYASDLDKVEGLT
FQQNSLNWMKKLSPRTIHLTMPQLVLQGSYDLQDLLAQAELPAILHTELNLQKLSNDRIR
VGEVLNSIFFELEADEREPTESTQQLNKPEVLEVTLNRPFLFAVYDQSATALHFLGRVAN
PLSTA
Target 3 Number of Residues 493
Target 3 Molecular Weight 53155
Target 3 Theoretical pI 6.27
Target 3 GO Classification
Function
enzyme regulator activity
enzyme inhibitor activity
protease inhibitor activity
endopeptidase inhibitor activity
serine-type endopeptidase inhibitor activity
Process
Not Available
Component
Not Available
Target 3 General Function Involved in serine-type endopeptidase inhibitor activity
Target 3 Specific Function Angiotensin-3 stimulates aldosterone release
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Pfam Domain Function
Target 3 Signals
  • 1-33
Target 3 Transmembrane Regions
  • None
Target 3 Essentiality Non-Essential
Target 3 GenBank ID Protein 178640 Link Image
Target 3 UniProtKB/Swiss-Prot ID P01019 Link Image
Target 3 UniProtKB/Swiss-Prot Entry Name ANGT_HUMAN Link Image
Target 3 PDB ID Not Available
Target 3 Cellular Location
  • Secreted protein
Target 3 Gene Sequence >1458 bp 
ATGCGGAAGCGAGCACCCCAGTCTGAGATGGCTCCTGCCGGTGTGAGCCTGAGGGCCACC
ATCCTCTGCCTCCTGGCCTGGGCTGGCCTGGCTGCAGGTGACCGGGTGTACATACACCCC
TTCCACCTCGTCATCCACAATGAGAGTACCTGTGAGCAGCTGGCAAAGGCCAATGCCGGG
AAGCCCAAAGACCCCACCTTCATACCTGCTCCAATTCAGGCCAAGACATCCCCTGTGGAT
GAAAAGGCCCTACAGGACCAGCTGGTGCTAGTCGCTGCAAAACTTGACACCGAAGACAAG
TTGAGGGCCGCAATGGTCGGGATGCTGGCCAACTTCTTGGGCTTCCGTATATATGGCATG
CACAGTGAGCTATGGGGCGTGGTCCATGGGGCCACCGTCCTCTCCCCAACGGCTGTCTTT
GGCACCCTGGCCTCTCTCTATCTGGGAGCCTTGGACCACACAGCTGACAGGCTACAGGCA
ATCCTGGGTGTTCCTTGGAAGGACAAGAACTGCACCTCCCGGCTGGATGCGCACAAGGTC
CTGTCTGCCCTGCAGGCTGTACAGGGCCTGCTAGTGGCCCAGGGCAGGGCTGATAGCCAG
GCCCAGCTGCTGCTGTCCACGGTGGTGGGCGTGTTCACAGCCCCAGGCCTGCACCTGAAG
CAGCCGTTTGTGCAGGGCCTGGCTCTCTATACCCCTGTGGTCCTCCCACGCTCTCTGGAC
TTCACAGAACTGGATGTTGCTGCTGAGAAGATTGACAGGTTCATGCAGGCTGTGACAGGA
TGGAAGACTGGCTGCTCCCTGATGGGAGCCAGTGTGGACAGCACCCTGGCTTTCAACACC
TACGTCCACTTCCAAGGGAAGATGAAGGGCTTCTCCCTGCTGGCCGAGCCCCAGGAGTTC
TGGGTGGACAACAGCACCTCAGTGTCTGTTCCCATGCTCTCTGGCATGGGCACCTTCCAG
CACTGGAGTGACATCCAGGACAACTTCTCGGTGACTCAAGTGCCCTTCACTGAGAGCGCC
TGCCTGCTGCTGATCCAGCCTCACTATGCCTCTGACCTGGACAAGGTGGAGGGTCTCACT
TTCCAGCAAAACTCCCTCAACTGGATGAAGAAACTGTCTCCCCGGACCATCCACCTGACC
ATGCCCCAACTGGTGCTGCAAGGATCTTATGACCTGCAGGACCTGCTCGCCCAGGCTGAG
CTGCCCGCCATTCTGCACACCGAGCTGAACCTGCAAAAATTGAGCAATGACCGCATCAGG
GTGGGGGAGGTGCTGAACAGCATTTTTTTTGAGCTTGAAGCGGATGAGAGAGAGCCCACA
GAGTCTACCCAACAGCTTAACAAGCCTGAGGTCTTGGAGGTGACCCTGAACCGCCCATTC
CTGTTTGCTGTGTATGATCAAAGCGCCACTGCCCTGCACTTCCTGGGCCGCGTGGCCAAC
CCGCTGAGCACAGCATGA
Target 3 GenBank Gene ID
Target 3 GeneCard ID AGT Link Image
Target 3 GenAtlas ID AGT Link Image
Target 3 HGNC ID HGNC:333 Link Image
Target 3 Chromosome Location 1
Target 3 Locus 1q42-q43
Target 3 SNPs SNPJam Report Link Image
Target 3 General References
  1. Goodfriend TL, Peach MJ: Angiotensin III: (DES-Aspartic Acid-1)-Angiotensin II. Evidence and speculation for its role as an important agonist in the renin - angiotensin system. Circ Res. 1975 Jun;36(6 Suppl 1):38-48. [PubMed Link Image]
  2. Jeunemaitre X, Soubrier F, Kotelevtsev YV, Lifton RP, Williams CS, Charru A, Hunt SC, Hopkins PN, Williams RR, Lalouel JM, et al.: Molecular basis of human hypertension: role of angiotensinogen. Cell. 1992 Oct 2;71(1):169-80. [PubMed Link Image]
  3. Fukamizu A, Takahashi S, Seo MS, Tada M, Tanimoto K, Uehara S, Murakami K: Structure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter. J Biol Chem. 1990 May 5;265(13):7576-82. [PubMed Link Image]
  4. Kunapuli SP, Kumar A: Molecular cloning of human angiotensinogen cDNA and evidence for the presence of its mRNA in rat heart. Circ Res. 1987 May;60(5):786-90. [PubMed Link Image]
  5. Gaillard I, Clauser E, Corvol P: Structure of human angiotensinogen gene. DNA. 1989 Mar;8(2):87-99. [PubMed Link Image]
  6. Kunapuli SP, Benedict CR, Kumar A: Tissue specific hormonal regulation of the rat angiotensinogen gene expression. Arch Biochem Biophys. 1987 May 1;254(2):642-6. [PubMed Link Image]
  7. Campbell DJ, Bouhnik J, Coezy E, Menard J, Corvol P: Processing of rat and human angiotensinogen precursors by microsomal membranes. Mol Cell Endocrinol. 1985 Nov;43(1):31-40. [PubMed Link Image]
  8. Arakawa K, Minohara A, Yamada J, Nakamura M: Enzymatic degradation and electrophoresis of human angiotensin I. Biochim Biophys Acta. 1968 Sep 10;168(1):106-12. [PubMed Link Image]
  9. Kageyama R, Ohkubo H, Nakanishi S: Primary structure of human preangiotensinogen deduced from the cloned cDNA sequence. Biochemistry. 1984 Jul 31;23(16):3603-9. [PubMed Link Image]
  10. Tewksbury DA, Dart RA, Travis J: The amino terminal amino acid sequence of human angiotensinogen. Biochem Biophys Res Commun. 1981 Apr 30;99(4):1311-5. [PubMed Link Image]
  11. 7539791 Oxvig C, Haaning J, Kristensen L, Wagner JM, Rubin I, Stigbrand T, Gleich GJ, Sottrup-Jensen L: Identification of angiotensinogen and complement C3dg as novel proteins binding the proform of eosinophil major basic protein in human pregnancy serum and plasma. J Biol Chem. 1995 Jun 9;270(23):13645-51.
  12. 7607642 Hixson JE, Powers PK: Detection and characterization of new mutations in the human angiotensinogen gene (AGT). Hum Genet. 1995 Jul;96(1):110-2.
  13. 7744780 Inoue I, Rohrwasser A, Helin C, Jeunemaitre X, Crain P, Bohlender J, Lifton RP, Corvol P, Ward K, Lalouel JM: A mutation of angiotensinogen in a patient with preeclampsia leads to altered kinetics of the renin-angiotensin system. J Biol Chem. 1995 May 12;270(19):11430-6.
  14. 8513325 Ward K, Hata A, Jeunemaitre X, Helin C, Nelson L, Namikawa C, Farrington PF, Ogasawara M, Suzumori K, Tomoda S, et al.: A molecular variant of angiotensinogen associated with preeclampsia. Nat Genet. 1993 May;4(1):59-61.
  15. 8621667 Gimenez-Roqueplo AP, Leconte I, Cohen P, Simon D, Guyene TT, Celerier J, Pau B, Corvol P, Clauser E, Jeunemaitre X: The natural mutation Y248C of human angiotensinogen leads to abnormal glycosylation and altered immunological recognition of the protein. J Biol Chem. 1996 Apr 19;271(16):9838-44.
  16. 9492317 Carpenter KA, Wilkes BC, Schiller PW: The octapeptide angiotensin II adopts a well-defined structure in a phospholipid environment. Eur J Biochem. 1998 Jan 15;251(1-2):448-53.
Target 3 Drug References
  1. Huang BS, Ganten D, Leenen FH: Responses to central Na(+) and ouabain are attenuated in transgenic rats deficient in brain angiotensinogen. Hypertension. 2001 Feb;37(2 Part 2):683-6. [PubMed Link Image]
  2. Budzikowski AS, Leenen FH: ANG II in median preoptic nucleus and pressor responses to CSF sodium and high sodium intake in SHR. Am J Physiol Heart Circ Physiol. 2001 Sep;281(3):H1210-6. [PubMed Link Image]
  3. Hou Y, Delamere NA: Influence of ANG II on cytoplasmic sodium in cultured rabbit nonpigmented ciliary epithelium. Am J Physiol Cell Physiol. 2002 Aug;283(2):C552-9. [PubMed Link Image]
  4. Schoner W, Bauer N, Muller-Ehmsen J, Kramer U, Hambarchian N, Schwinger R, Moeller H, Kost H, Weitkamp C, Schweitzer T, Kirch U, Neu H, Grunbaum EG: Ouabain as a mammalian hormone. Ann N Y Acad Sci. 2003 Apr;986:678-84. [PubMed Link Image]
  5. Yingst DR, Massey KJ, Rossi NF, Mohanty MJ, Mattingly RR: Angiotensin II directly stimulates activity and alters the phosphorylation of Na-K-ATPase in rat proximal tubule with a rapid time course. Am J Physiol Renal Physiol. 2004 Oct;287(4):F713-21. Epub 2004 May 25. [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.