Acetaminophen (T3D2571)

General Function:

Prostaglandin-endoperoxide synthase activity

Specific Function:

Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis.

Gene Name:

PTGS2

Uniprot ID:

P35354

Molecular Weight:

68995.625 Da

References

1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
2. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
3. 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. [17016423 ]
4. Lee YS, Kim H, Brahim JS, Rowan J, Lee G, Dionne RA: Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation. Pain. 2007 Jun;129(3):279-86. Epub 2006 Dec 18. [17175104 ]
5. Hinz B, Cheremina O, Brune K: Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J. 2008 Feb;22(2):383-90. Epub 2007 Sep 20. [17884974 ]
6. Weinheimer EM, Jemiolo B, Carroll CC, Harber MP, Haus JM, Burd NA, LeMoine JK, Trappe SW, Trappe TA: Resistance exercise and cyclooxygenase (COX) expression in human skeletal muscle: implications for COX-inhibiting drugs and protein synthesis. Am J Physiol Regul Integr Comp Physiol. 2007 Jun;292(6):R2241-8. Epub 2007 Feb 22. [17322116 ]
7. Sinning C, Watzer B, Coste O, Nusing RM, Ott I, Ligresti A, Di Marzo V, Imming P: New analgesics synthetically derived from the paracetamol metabolite N-(4-hydroxyphenyl)-(5Z,8Z,11Z,14Z)-icosatetra-5,8,11,14-enamide. J Med Chem. 2008 Dec 25;51(24):7800-5. doi: 10.1021/jm800807k. [19053765 ]
8. Cryer B, Feldman M: Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med. 1998 May;104(5):413-21. [9626023 ]

General Function:

Zinc ion binding

Specific Function:

Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.

Gene Name:

CA1

Uniprot ID:

P00915

Molecular Weight:

28870.0 Da

References

1. Innocenti A, Hilvo M, Scozzafava A, Parkkila S, Supuran CT: Carbonic anhydrase inhibitors: Inhibition of the new membrane-associated isoform XV with phenols. Bioorg Med Chem Lett. 2008 Jun 15;18(12):3593-6. doi: 10.1016/j.bmcl.2008.04.077. Epub 2008 May 4. [18501600 ]
2. Innocenti A, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. doi: 10.1016/j.bmc.2008.06.013. Epub 2008 Jun 13. [18579385 ]

General Function:

Zinc ion binding

Specific Function:

Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.

Gene Name:

CA2

Uniprot ID:

P00918

Molecular Weight:

29245.895 Da

References

1. Innocenti A, Hilvo M, Scozzafava A, Parkkila S, Supuran CT: Carbonic anhydrase inhibitors: Inhibition of the new membrane-associated isoform XV with phenols. Bioorg Med Chem Lett. 2008 Jun 15;18(12):3593-6. doi: 10.1016/j.bmcl.2008.04.077. Epub 2008 May 4. [18501600 ]
2. Innocenti A, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. doi: 10.1016/j.bmc.2008.06.013. Epub 2008 Jun 13. [18579385 ]

General Function:

Prostaglandin-endoperoxide synthase activity

Specific Function:

Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells.

Gene Name:

PTGS1

Uniprot ID:

P23219

Molecular Weight:

68685.82 Da

References

1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]

General Function:

Protein n-terminus binding

Specific Function:

Required for leukotriene biosynthesis by ALOX5 (5-lipoxygenase). Anchors ALOX5 to the membrane. Binds arachidonic acid, and could play an essential role in the transfer of arachidonic acid to ALOX5. Binds to MK-886, a compound that blocks the biosynthesis of leukotrienes.

Gene Name:

ALOX5AP

Uniprot ID:

P20292

Molecular Weight:

18156.96 Da

References

1. Friesen RW, Mancini JA: Microsomal prostaglandin E2 synthase-1 (mPGES-1): a novel anti-inflammatory therapeutic target. J Med Chem. 2008 Jul 24;51(14):4059-67. doi: 10.1021/jm800197b. Epub 2008 May 7. [18459759 ]

General Function:

Zinc ion binding

Specific Function:

Reversible hydration of carbon dioxide.

Gene Name:

CA12

Uniprot ID:

O43570

Molecular Weight:

39450.615 Da

References

1. Innocenti A, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. doi: 10.1016/j.bmc.2008.06.013. Epub 2008 Jun 13. [18579385 ]

General Function:

Metal ion binding

Specific Function:

Reversible hydration of carbon dioxide.

Gene Name:

CA14

Uniprot ID:

Q9ULX7

Molecular Weight:

37667.37 Da

References

1. Innocenti A, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. doi: 10.1016/j.bmc.2008.06.013. Epub 2008 Jun 13. [18579385 ]

General Function:

Zinc ion binding

Specific Function:

Reversible hydration of carbon dioxide.

Gene Name:

CA3

Uniprot ID:

P07451

Molecular Weight:

29557.215 Da

References

1. Innocenti A, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. doi: 10.1016/j.bmc.2008.06.013. Epub 2008 Jun 13. [18579385 ]

General Function:

Zinc ion binding

Specific Function:

Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.

Gene Name:

CA4

Uniprot ID:

P22748

Molecular Weight:

35032.075 Da

References

1. Innocenti A, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. doi: 10.1016/j.bmc.2008.06.013. Epub 2008 Jun 13. [18579385 ]

General Function:

Zinc ion binding

Specific Function:

Reversible hydration of carbon dioxide. Low activity.

Gene Name:

CA5A

Uniprot ID:

P35218

Molecular Weight:

34750.21 Da

References

1. Innocenti A, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. doi: 10.1016/j.bmc.2008.06.013. Epub 2008 Jun 13. [18579385 ]

General Function:

Zinc ion binding

Specific Function:

Reversible hydration of carbon dioxide.

Gene Name:

CA5B

Uniprot ID:

Q9Y2D0

Molecular Weight:

36433.43 Da

References

1. Innocenti A, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. doi: 10.1016/j.bmc.2008.06.013. Epub 2008 Jun 13. [18579385 ]

General Function:

Zinc ion binding

Specific Function:

Reversible hydration of carbon dioxide. Its role in saliva is unknown.

Gene Name:

CA6

Uniprot ID:

P23280

Molecular Weight:

35366.615 Da

References

1. Innocenti A, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. doi: 10.1016/j.bmc.2008.06.013. Epub 2008 Jun 13. [18579385 ]

General Function:

Zinc ion binding

Specific Function:

Reversible hydration of carbon dioxide.

Gene Name:

CA7

Uniprot ID:

P43166

Molecular Weight:

29658.235 Da

References

1. Innocenti A, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. doi: 10.1016/j.bmc.2008.06.013. Epub 2008 Jun 13. [18579385 ]

General Function:

Zinc ion binding

Specific Function:

Reversible hydration of carbon dioxide. Participates in pH regulation. May be involved in the control of cell proliferation and transformation. Appears to be a novel specific biomarker for a cervical neoplasia.

Gene Name:

CA9

Uniprot ID:

Q16790

Molecular Weight:

49697.36 Da

References

1. Innocenti A, Vullo D, Scozzafava A, Supuran CT: Carbonic anhydrase inhibitors: inhibition of mammalian isoforms I-XIV with a series of substituted phenols including paracetamol and salicylic acid. Bioorg Med Chem. 2008 Aug 1;16(15):7424-8. doi: 10.1016/j.bmc.2008.06.013. Epub 2008 Jun 13. [18579385 ]

General Function:

Vitamin d 24-hydroxylase activity

Specific Function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.

Gene Name:

CYP1A1

Uniprot ID:

P04798

Molecular Weight:

58164.815 Da

References

1. Rosales-Hernandez MC, Mendieta-Wejebe JE, Trujillo-Ferrara JG, Correa-Basurto J: Homology modeling and molecular dynamics of CYP1A1 and CYP2B1 to explore the metabolism of aryl derivatives by docking and experimental assays. Eur J Med Chem. 2010 Nov;45(11):4845-55. doi: 10.1016/j.ejmech.2010.07.055. Epub 2010 Aug 14. [20813430 ]

General Function:

Oxygen transporter activity

Specific Function:

Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles.

Gene Name:

MB

Uniprot ID:

P02144

Molecular Weight:

17183.725 Da

References

1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]

General Function:

Electron carrier activity

Specific Function:

Not Available

Gene Name:

ALDH2

Uniprot ID:

P05091

Molecular Weight:

56380.93 Da

General Function:

Steroid hydroxylase activity

Specific Function:

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.

Gene Name:

CYP2E1

Uniprot ID:

P05181

Molecular Weight:

56848.42 Da

General Function:

Vitamin d3 25-hydroxylase activity

Specific Function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide (PubMed:11159812). Catalyzes 4-beta-hydroxylation of cholesterol. May catalyze 25-hydroxylation of cholesterol in vitro (PubMed:21576599).

Gene Name:

CYP3A4

Uniprot ID:

P08684

Molecular Weight:

57342.67 Da

General Function:

Methyltransferase activity

Specific Function:

Not Available

Gene Name:

ALDH1L1

Uniprot ID:

O75891

Molecular Weight:

98828.505 Da

General Function:

Nad+ binding

Specific Function:

Mitochondrial glutamate dehydrogenase that converts L-glutamate into alpha-ketoglutarate. Plays a key role in glutamine anaplerosis by producing alpha-ketoglutarate, an important intermediate in the tricarboxylic acid cycle. May be involved in learning and memory reactions by increasing the turnover of the excitatory neurotransmitter glutamate (By similarity).

Gene Name:

GLUD1

Uniprot ID:

P00367

Molecular Weight:

61397.315 Da

General Function:

Manganese ion binding

Specific Function:

This enzyme has 2 functions: it catalyzes the production of glutamine and 4-aminobutanoate (gamma-aminobutyric acid, GABA), the latter in a pyridoxal phosphate-independent manner (By similarity). Essential for proliferation of fetal skin fibroblasts.

Gene Name:

GLUL

Uniprot ID:

P15104

Molecular Weight:

42064.15 Da

General Function:

Sh3 domain binding

Specific Function:

Protects the hemoglobin in erythrocytes from oxidative breakdown.

Gene Name:

GPX1

Uniprot ID:

P07203

Molecular Weight:

22087.94 Da

General Function:

Nad binding

Specific Function:

Not Available

Gene Name:

GPD1

Uniprot ID:

P21695

Molecular Weight:

37567.4 Da

General Function:

Sn-glycerol-3-phosphate:ubiquinone-8 oxidoreductase activity

Specific Function:

Not Available

Gene Name:

GPD2

Uniprot ID:

P43304

Molecular Weight:

80851.99 Da

General Function:

Thioether s-methyltransferase activity

Specific Function:

Functions as thioether S-methyltransferase and is active with a variety of thioethers and the corresponding selenium and tellurium compounds, including 3-methylthiopropionaldehyde, dimethyl selenide, dimethyl telluride, 2-methylthioethylamine, 2-methylthioethanol, methyl-n-propyl sulfide and diethyl sulfide. Plays an important role in the detoxification of selenium compounds (By similarity). Catalyzes the N-methylation of tryptamine and structurally related compounds.

Gene Name:

INMT

Uniprot ID:

O95050

Molecular Weight:

28890.75 Da

General Function:

Toxic substance binding

Specific Function:

Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.

Gene Name:

ALB

Uniprot ID:

P02768

Molecular Weight:

69365.94 Da

General Function:

Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of phenolic monoamines (neurotransmitters such as dopamine, norepinephrine and serotonin) and phenolic and catechol drugs.

Specific Function:

Amine sulfotransferase activity

Gene Name:

SULT1A3

Uniprot ID:

P0DMM9

Molecular Weight:

34195.96 Da

General Function:

Thioredoxin-disulfide reductase activity

Specific Function:

Isoform 1 may possess glutaredoxin activity as well as thioredoxin reductase activity and induces actin and tubulin polymerization, leading to formation of cell membrane protrusions. Isoform 4 enhances the transcriptional activity of estrogen receptors alpha and beta while isoform 5 enhances the transcriptional activity of the beta receptor only. Isoform 5 also mediates cell death induced by a combination of interferon-beta and retinoic acid.

Gene Name:

TXNRD1

Uniprot ID:

Q16881

Molecular Weight:

70905.58 Da

General Function:

Thioredoxin-disulfide reductase activity

Specific Function:

Maintains thioredoxin in a reduced state. Implicated in the defenses against oxidative stress. May play a role in redox-regulated cell signaling.

Gene Name:

TXNRD2

Uniprot ID:

Q9NNW7

Molecular Weight:

56506.275 Da

General Function:

Thioredoxin-disulfide reductase activity

Specific Function:

Displays thioredoxin reductase, glutaredoxin and glutathione reductase activities. Catalyzes disulfide bond isomerization. Promotes disulfide bond formation between GPX4 and various sperm proteins and may play a role in sperm maturation by promoting formation of sperm structural components (By similarity).

Gene Name:

TXNRD3

Uniprot ID:

Q86VQ6

Molecular Weight:

70682.52 Da