| 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 |
|
| Name |
Ouabain |
| Drug Type |
|
| 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 |
- G-Strophanthin
- Ouabagenin L-Rhamnoside
- Ouabain Octahydrate
- Ouabain, Octahydrate
- Ouabaine
- Strophanthin G
- Strophanthin-G
|
| Brand Names |
- Acocantherin
- Astrobain
- G-Strophicor
- Gratibain
- Gratus Strophanthin
- Kombetin
- Purostrophan
- Rectobaina
- Solufantina
- Strodival
- Strophalen
- Strophoperm
- Strophosan
- Uabaina
- 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 |
 |
| 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  |
| KEGG Compound |
C01443  |
| PubChem Compound |
439501  |
| PubChem Substance |
4621  |
| 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  |
| 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 | Download  |
| SDF File |
Show | Download  |
| PDB File |
Show | Download  |
| 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 |
- 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
]
- 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
]
- 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
]
- 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
]
- Laredo J, Hamilton BP, Hamlyn JM: Ouabain is secreted by bovine adrenocortical cells. Endocrinology. 1994 Aug;135(2):794-7. [PubMed
]
- Wikipedia

|
| Organisms Affected |
|
| Phase 1 Metabolizing Enzymes |
- Cytochrome P450 11A1 (CYP11A1)
|
| Targets |
- Sodium/potassium-transporting ATPase alpha-1 chain
- Kininogen-1
- Angiotensinogen
|
|
Drug Target 1
[top]
|
| Target 1 ID |
806 |
| Target 1 Name |
Sodium/potassium-transporting ATPase alpha-1 chain |
| Target 1 Synonyms |
- EC 3.6.3.9
- Na(+)/K(+) ATPase alpha-1 subunit
- Sodium pump subunit alpha 1
- 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 |
|
| 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  |
| Target 1 UniProtKB/Swiss-Prot ID |
P05023  |
| Target 1 UniProtKB/Swiss-Prot Entry Name |
AT1A1_HUMAN  |
| Target 1 PDB ID |
1MO8  |
| 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  |
| Target 1 GenAtlas ID |
ATP1A1  |
| Target 1 HGNC ID |
HGNC:799  |
| Target 1 Chromosome Location |
1 |
| Target 1 Locus |
1p21 |
| Target 1 SNPs |
SNPJam Report  |
| Target 1 General References |
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
|
| Target 1 Drug References |
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
|
|
Drug Target 2
[top]
|
| Target 2 ID |
1536 |
| Target 2 Name |
Kininogen-1 |
| Target 2 Synonyms |
- Alpha-2-thiol proteinase inhibitor
- 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 |
|
| Target 2 Transmembrane Regions |
|
| Target 2 Essentiality |
Non-Essential |
| Target 2 GenBank ID Protein |
177890  |
| Target 2 UniProtKB/Swiss-Prot ID |
P01042  |
| Target 2 UniProtKB/Swiss-Prot Entry Name |
KNG1_HUMAN  |
| 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  |
| Target 2 GenAtlas ID |
KNG1  |
| Target 2 HGNC ID |
HGNC:6383  |
| Target 2 Chromosome Location |
3 |
| Target 2 Locus |
3q27 |
| Target 2 SNPs |
SNPJam Report  |
| Target 2 General References |
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- Pierce JV: Structural features of plasma kinins and kininogens. Fed Proc. 1968 Jan-Feb;27(1):52-7. [PubMed
]
- 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
]
- 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
]
|
| Target 2 Drug References |
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
|
|
Drug Target 3
[top]
|
| Target 3 ID |
1694 |
| Target 3 Name |
Angiotensinogen |
| Target 3 Synonyms |
- Angiotensinogen precursor
- 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 |
|
| Target 3 Transmembrane Regions |
|
| Target 3 Essentiality |
Non-Essential |
| Target 3 GenBank ID Protein |
178640  |
| Target 3 UniProtKB/Swiss-Prot ID |
P01019  |
| Target 3 UniProtKB/Swiss-Prot Entry Name |
ANGT_HUMAN  |
| Target 3 PDB ID |
Not Available |
| Target 3 Cellular Location |
|
| 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  |
| Target 3 GenAtlas ID |
AGT  |
| Target 3 HGNC ID |
HGNC:333  |
| Target 3 Chromosome Location |
1 |
| Target 3 Locus |
1q42-q43 |
| Target 3 SNPs |
SNPJam Report  |
| Target 3 General References |
- 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
]
- 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
]
- 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
]
- 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
]
- Gaillard I, Clauser E, Corvol P: Structure of human angiotensinogen gene. DNA. 1989 Mar;8(2):87-99. [PubMed
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
- 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.
- 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.
- 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.
- 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.
- 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.
- 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 |
- 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
]
- 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
]
- 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
]
- 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
]
- 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
]
|