Tmic
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Record Information
Version2.0
Creation Date2009-07-21 20:26:11 UTC
Update Date2014-12-24 20:25:49 UTC
Accession NumberT3D2700
Identification
Common NameAlpha-Tocopherol
ClassSmall Molecule
DescriptionA generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids.
Compound Type
  • Antioxidant
  • Dietary Supplement
  • Drug
  • Ether
  • Food Toxin
  • Household Toxin
  • Metabolite
  • Micronutrient
  • Natural Compound
  • Nutraceutical
  • Organic Compound
  • Supplement
  • Vitamin
Chemical Structure
Thumb
Synonyms
Synonym
(+)-a-Tocopherol
(+)-alpha-Tocopherol
(+)-α-tocopherol
(2R)-3,4-Dihydro-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-2H-1-benzopyran-6-ol
(2R,4'R,8'R)-a-Tocopherol
(2R,4'R,8'R)-alpha-Tocopherol
(R,R,R)-a-Tocopherol
(R,R,R)-alpha-Tocopherol
(R,R,R)-α-tocopherol
5,7,8-Trimethyltocol
a-D-Tocopherol
a-Tocopherol
alpha-delta-Tocopherol
alpha-Tocopherol
Amino-Opti-E
Aquasol E
D-alpha-Tocopherol
d-α-tocopherol
delta-alpha-Tocopherol
Denamone
Eprolin
Phytogermin
Phytogermine
RRR-alpha-tocopherol
RRR-alpha-tocopheryl
Vitamin E
Vitamin Ea
α-Tocopherol
Chemical FormulaC29H50O2
Average Molecular Mass430.706 g/mol
Monoisotopic Mass430.381 g/mol
CAS Registry Number59-02-9
IUPAC Name(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydro-2H-1-benzopyran-6-ol
Traditional NameVitaE
SMILES[H][C@@](C)(CCCC(C)C)CCC[C@@]([H])(C)CCC[C@]1(C)CCC2=C(C)C(O)=C(C)C(C)=C2O1
InChI IdentifierInChI=1S/C29H50O2/c1-20(2)12-9-13-21(3)14-10-15-22(4)16-11-18-29(8)19-17-26-25(7)27(30)23(5)24(6)28(26)31-29/h20-22,30H,9-19H2,1-8H3/t21-,22-,29-/m1/s1
InChI KeyInChIKey=GVJHHUAWPYXKBD-IEOSBIPESA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as tocopherols. These are vitamin E derivatives containing a saturated trimethyltridecyl chain attached to the carbon C6 atom of a benzopyran ring system. The differ from tocotrienols that contain an unsaturated trimethyltrideca-3,7,11-trien-1-yl chain.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassPrenol lipids
Sub ClassQuinone and hydroquinone lipids
Direct ParentTocopherols
Alternative Parents
Substituents
  • Tocopherol
  • Diterpenoid
  • 1-benzopyran
  • Benzopyran
  • Chromane
  • Alkyl aryl ether
  • Benzenoid
  • Oxacycle
  • Organoheterocyclic compound
  • Ether
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue Locations
  • Adipose Tissue
  • Bladder
  • Erythrocyte
  • Eye Lens
  • Fibroblasts
  • Intestine
  • Liver
  • Lymphocyte
  • Muscle
  • Nerve Cells
  • Nervous Tissues
  • Neuron
  • Pancreas
  • Placenta
  • Platelet
  • Prostate
  • Skeletal Muscle
  • Skin
  • Spleen
  • Stratum Corneum
  • Testes
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateLiquid
AppearanceNot Available
Experimental Properties
PropertyValue
Melting Point3°C
Boiling PointNot Available
SolubilityInsoluble in water, but water-dispersible.
LogP10
Predicted Properties
PropertyValueSource
Water Solubility7.0e-06 g/LALOGPS
logP8.84ALOGPS
logP10.51ChemAxon
logS-7.8ALOGPS
pKa (Strongest Acidic)10.8ChemAxon
pKa (Strongest Basic)-4.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.46 ŲChemAxon
Rotatable Bond Count12ChemAxon
Refractivity135.37 m³·mol⁻¹ChemAxon
Polarizability55.29 ųChemAxon
Number of Rings2ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)splash10-000i-1390000000-fc8c4f9b9405598ede7fView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies) (1 TMS)splash10-00dr-9150010000-c4abc0e689e9b2476b9dView in MoNA
GC-MSGC-MS Spectrum - GC-MS (1 TMS)splash10-0f79-1190040000-663296a69129a59be1a6View in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-000i-1390000000-fc8c4f9b9405598ede7fView in MoNA
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-00dr-9150010000-c4abc0e689e9b2476b9dView in MoNA
GC-MSGC-MS Spectrum - GC-MS (Non-derivatized)splash10-0f79-1190040000-663296a69129a59be1a6View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0aor-9886300000-b3225facac6ebdd8ddbdView in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-000l-7735900000-1585eb83c1211ebe95f2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-03di-9600100000-aaf885290800a10d3fb2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-01wr-9300000000-f0c814976a58a9d837caView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0f79-1494700000-6b5f8f817c5a5429ed70View in MoNA
LC-MS/MSLC-MS/MS Spectrum - EI-EBEB (JMS-HX/HX 110A, JEOL) , Positivesplash10-00lr-4910600000-1eda05dacf9642d7cea0View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-001i-0842900000-f51286676592fd184193View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-1920000000-1994f86bec2bb4a77b9cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-066r-3930000000-02190bf16d5d85d44bceView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-004i-0110900000-c3541294fc60a7a8cc7eView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01t9-0730900000-553c4898757f6876036cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03e9-0920200000-276273a531fed5b3a2b0View in MoNA
MSMass Spectrum (Electron Ionization)splash10-0159-2900500000-03e8a824731610752eb3View in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureOral, Topical, Intramuscular 50 to 80% absorbed from gastrointestinal tract.
Mechanism of ToxicityAlthough all forms of Vitamin E exhibit antioxidant activity, it is known that the antioxidant activity of vitamin E is not sufficient to explain the vitamin's biological activity.
Vitamin E's anti-atherogenic activity involves the inhibition of the oxidation of LDL and the accumulation of oxLDL in the arterial wall. It also appears to reduce oxLDL-induced apoptosis in human endothelial cells. Oxidation of LDL is a key early step in atherogenesis as it triggers a number of events which lead to the formation of atherosclerotic plaque. In addition, vitamin E inhibits protein kinase C (PKC) activity. PKC plays a role in smooth muscle cell proliferation, and, thus, the inhibition of PKC results in inhibition of smooth muscle cell proliferation, which is involved in atherogenesis.
Vitamin E's antithrombotic and anticoagulant activities involves the downregulation of the expression of intracellular cell adhesion molecule(ICAM)-1 and vascular cell adhesion molecule(VCAM)-1 which lowers the adhesion of blood components to the endothelium. In addition, vitamin E upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase (COX)-1 which in turn enhances the release of prostacyclin. Prostacyclin is a vasodilating factor and inhibitor of platelet aggregation and platelet release. It is also known that platelet aggregation is mediated by a mechanism involving the binding of fibrinogen to the glycoprotein IIb/IIIa (GPIIb/IIIa) complex of platelets. GPIIb/IIIa is the major membrane receptor protein that is key to the role of the platelet aggregation response. GPIIb is the alpha-subunit of this platelet membrane protein. Alpha-tocopherol downregulates GPIIb promoter activity which results in reduction of GPIIb protein expression and decreased platelet aggregation. Vitamin E has also been found in culture to decrease plasma production of thrombin, a protein which binds to platelets and induces aggregation. A metabolite of vitamin E called vitamin E quinone or alpha-tocopheryl quinone (TQ) is a potent anticoagulant. This metabolite inhibits vitamin K-dependent carboxylase, which is a major enzyme in the coagulation cascade.
The neuroprotective effects of vitamin E are explained by its antioxidant effects. Many disorders of the nervous system are caused by oxidative stress. Vitamin E protects against this stress, thereby protecting the nervouse system.
The immunomodulatory effects of Vitamin E have been demonstrated in vitro, where alpha-tocopherol increases mitogenic response of T lymphocytes from aged mice. The mechanism of this response by vitamin E is not well understood, however it has been suggested that vitamin E itself may have mitogenic activity independent of its antioxidant activity.
Lastly, the mechanism of action of vitamin E's antiviral effects (primarily against HIV-1) involves its antioxidant activity. Vitamin E reduces oxidative stress, which is thought to contribute to HIV-1 pathogenesis, as well as to the pathogenesis of other viral infections. Vitamin E also affects membrane integrity and fluidity and, since HIV-1 is a membraned virus, altering membrane fluidity of HIV-1 may interfere with its ability to bind to cell-receptor sites, thus decreasing its infectivity.
MetabolismHepatic.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesVitamin E, known for its antioxidant activities, is protective against cardiovascular disease and some forms of cancer and has also demonstrated immune-enhancing effects. It may be of limited benefit in some with asthma and rheumatoid arthritis. It may be helpful in some neurological diseases including Alzheimer's, some eye disorders including cataracts, and diabetes and premenstrual syndrome. It may also help protect skin from ultraviolet irradiation although claims that it reverses skin aging, enhances male fertility and exercise performance are poorly supported. It may help relieve some muscle cramps.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00163
HMDB IDHMDB01893
PubChem Compound ID14985
ChEMBL IDCHEMBL47
ChemSpider ID14265
KEGG IDC02477
UniProt IDNot Available
OMIM ID107730 , 200100 , 277460 , 606721 , 607692
ChEBI ID18145
BioCyc IDCPD-1125
CTD IDNot Available
Stitch IDVitamin E
PDB IDVIV
ACToR ID3248
Wikipedia LinkVitamin_E
References
Synthesis Reference

Ralph E. Close, William Oroshnik, “Synthesis of dehydrophytol and Vitamin E.” U.S. Patent US4039591, issued February, 1945.

MSDSLink
General References
  1. Iuliano L, Micheletta F, Maranghi M, Frati G, Diczfalusy U, Violi F: Bioavailability of vitamin E as function of food intake in healthy subjects: effects on plasma peroxide-scavenging activity and cholesterol-oxidation products. Arterioscler Thromb Vasc Biol. 2001 Oct;21(10):E34-7. [11597949 ]
  2. Miller ER 3rd, Pastor-Barriuso R, Dalal D, Riemersma RA, Appel LJ, Guallar E: Meta-analysis: high-dosage vitamin E supplementation may increase all-cause mortality. Ann Intern Med. 2005 Jan 4;142(1):37-46. Epub 2004 Nov 10. [15537682 ]
  3. Horwitt MK, Elliott WH, Kanjananggulpan P, Fitch CD: Serum concentrations of alpha-tocopherol after ingestion of various vitamin E preparations. Am J Clin Nutr. 1984 Aug;40(2):240-5. [6465056 ]
  4. Rumbold AR, Crowther CA, Haslam RR, Dekker GA, Robinson JS: Vitamins C and E and the risks of preeclampsia and perinatal complications. N Engl J Med. 2006 Apr 27;354(17):1796-806. [16641396 ]
  5. Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH: Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Lancet. 2006 Apr 8;367(9517):1145-54. [16616557 ]
  6. de Souza Junior O, Treitinger A, Baggio GL, Michelon C, Verdi JC, Cunha J, Ferreira SI, Spada C: alpha-Tocopherol as an antiretroviral therapy supplement for HIV-1-infected patients for increased lymphocyte viability. Clin Chem Lab Med. 2005;43(4):376-82. [15899652 ]
  7. Palan PR, Woodall AL, Anderson PS, Mikhail MS: Alpha-tocopherol and alpha-tocopheryl quinone levels in cervical intraepithelial neoplasia and cervical cancer. Am J Obstet Gynecol. 2004 May;190(5):1407-10. [15167851 ]
  8. Traber MG, Siddens LK, Leonard SW, Schock B, Gohil K, Krueger SK, Cross CE, Williams DE: Alpha-tocopherol modulates Cyp3a expression, increases gamma-CEHC production, and limits tissue gamma-tocopherol accumulation in mice fed high gamma-tocopherol diets. Free Radic Biol Med. 2005 Mar 15;38(6):773-85. [15721988 ]
  9. Hino K, Murakami Y, Nagai A, Kitase A, Hara Y, Furutani T, Ren F, Yamaguchi Y, Yutoku K, Yamashita S, Okuda M, Okita M, Okita K: Alpha-tocopherol [corrected] and ascorbic acid attenuates the ribavirin [corrected] induced decrease of eicosapentaenoic acid in erythrocyte membrane in chronic hepatitis C patients. J Gastroenterol Hepatol. 2006 Aug;21(8):1269-75. [16872308 ]
  10. Mardla V, Kobzar G, Samel N: Potentiation of antiaggregating effect of prostaglandins by alpha-tocopherol and quercetin. Platelets. 2004 Aug;15(5):319-24. [15370103 ]
  11. Pappert EJ, Tangney CC, Goetz CG, Ling ZD, Lipton JW, Stebbins GT, Carvey PM: Alpha-tocopherol in the ventricular cerebrospinal fluid of Parkinson's disease patients: dose-response study and correlations with plasma levels. Neurology. 1996 Oct;47(4):1037-42. [8857741 ]
  12. Rota C, Barella L, Minihane AM, Stocklin E, Rimbach G: Dietary alpha-tocopherol affects differential gene expression in rat testes. IUBMB Life. 2004 May;56(5):277-80. [15370891 ]
  13. Ble-Castillo JL, Carmona-Diaz E, Mendez JD, Larios-Medina FJ, Medina-Santillan R, Cleva-Villanueva G, Diaz-Zagoya JC: Effect of alpha-tocopherol on the metabolic control and oxidative stress in female type 2 diabetics. Biomed Pharmacother. 2005 Jul;59(6):290-5. [15932790 ]
  14. Jeanes YM, Hall WL, Proteggente AR, Lodge JK: Cigarette smokers have decreased lymphocyte and platelet alpha-tocopherol levels and increased excretion of the gamma-tocopherol metabolite gamma-carboxyethyl-hydroxychroman (gamma-CEHC). Free Radic Res. 2004 Aug;38(8):861-8. [15493460 ]
  15. Ekanayake-Mudiyanselage S, Tavakkol A, Polefka TG, Nabi Z, Elsner P, Thiele JJ: Vitamin E delivery to human skin by a rinse-off product: penetration of alpha-tocopherol versus wash-out effects of skin surface lipids. Skin Pharmacol Physiol. 2005 Jan-Feb;18(1):20-6. [15608499 ]
  16. Liu ZQ: The "unexpected role" of vitamin E in free radical-induced hemolysis of human erythrocytes: alpha-tocopherol-mediated peroxidation. Cell Biochem Biophys. 2006;44(2):233-9. [16456225 ]
  17. Kang MJ, Lin YC, Yeh WH, Pan WH: Vitamin E status and its dietary determinants in Taiwanese--results of the Nutrition and Health Survey in Taiwan 1993-1996. Eur J Nutr. 2004 Apr;43(2):86-92. Epub 2004 Jan 6. [15083315 ]
  18. Hozyasz K, Chelchowska M: [Vitamin E status in mothers of children with cleft lip]. Pol Merkur Lekarski. 2004 Jul;17(97):25-7. [15559605 ]
  19. Rose AT, McFadden DW: Alpha-tocopherol succinate inhibits growth of gastric cancer cells in vitro. J Surg Res. 2001 Jan;95(1):19-22. [11120630 ]
  20. Jeanes YM, Hall WL, Lodge JK: Comparative (2)H-labelled alpha-tocopherol biokinetics in plasma, lipoproteins, erythrocytes, platelets and lymphocytes in normolipidaemic males. Br J Nutr. 2005 Jul;94(1):92-9. [16115338 ]
  21. Murohara T, Ikeda H, Otsuka Y, Aoki M, Haramaki N, Katoh A, Takajo Y, Imaizumi T: Inhibition of platelet adherence to mononuclear cells by alpha-tocopherol: role of P-selectin. Circulation. 2004 Jul 13;110(2):141-8. Epub 2004 Jun 14. [15197142 ]
  22. Hozyasz KK, Chelchowska M, Laskowska-Klita T, Ruszkowska L, Milanowski A: [Low concentration of alpha-tocopherol in erythrocytes of atopic dermatitis patients]. Med Wieku Rozwoj. 2004 Oct-Dec;8(4 Pt 1):963-9. [15951615 ]
  23. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]
  24. Linus Pauling Institute: Micronutrient Information Center (2009). Vitamin E. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Zinc ion binding
Specific Function:
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription.
Gene Name:
PRKCA
Uniprot ID:
P17252
Molecular Weight:
76749.445 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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 ]
  3. Huang Y, Ishizuka T, Miura A, Kajita K, Ishizawa M, Kimura M, Yamamoto Y, Kawai Y, Morita H, Uno Y, Yasuda K: Effect of 1 alpha,25-dihydroxy vitamin D3 and vitamin E on insulin-induced glucose uptake in rat adipocytes. Diabetes Res Clin Pract. 2002 Mar;55(3):175-83. [11850093 ]
  4. Azzi A, Boscoboinik D, Clement S, Marilley D, Ozer NK, Ricciarelli R, Tasinato A: Alpha-tocopherol as a modulator of smooth muscle cell proliferation. Prostaglandins Leukot Essent Fatty Acids. 1997 Oct;57(4-5):507-14. [9430404 ]
  5. Sylvester PW, McIntyre BS, Gapor A, Briski KP: Vitamin E inhibition of normal mammary epithelial cell growth is associated with a reduction in protein kinase C(alpha) activation. Cell Prolif. 2001 Dec;34(6):347-57. [11736999 ]
General Function:
Zinc ion binding
Specific Function:
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. May participate in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription.
Gene Name:
PRKCB
Uniprot ID:
P05771
Molecular Weight:
76868.45 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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 ]
  3. Wigg SJ, Tare M, Forbes J, Cooper ME, Thomas MC, Coleman HA, Parkington HC, O'Brien RC: Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-beta in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats. Diabetologia. 2004 Jun;47(6):1038-46. Epub 2004 Jun 8. [15184978 ]
  4. Huang Y, Ishizuka T, Miura A, Kajita K, Ishizawa M, Kimura M, Yamamoto Y, Kawai Y, Morita H, Uno Y, Yasuda K: Effect of 1 alpha,25-dihydroxy vitamin D3 and vitamin E on insulin-induced glucose uptake in rat adipocytes. Diabetes Res Clin Pract. 2002 Mar;55(3):175-83. [11850093 ]
  5. Ganz MB, Seftel A: Glucose-induced changes in protein kinase C and nitric oxide are prevented by vitamin E. Am J Physiol Endocrinol Metab. 2000 Jan;278(1):E146-52. [10644549 ]
General Function:
Transporter activity
Specific Function:
Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids.
Gene Name:
SEC14L3
Uniprot ID:
Q9UDX4
Molecular Weight:
46047.835 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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 ]
  3. Ye X, Ji C, Yin G, Tang R, Zeng L, Gu S, Ying K, Xie Y, Zhao RC, Mao Y: Characterization of a human Sec14-like protein cDNA SEC14L3 highly homologous to human SPF/TAP. Mol Biol Rep. 2004 Mar;31(1):59-63. [15040456 ]
General Function:
Phospholipid binding
Specific Function:
Upon cell stimulation converts the second messenger diacylglycerol into phosphatidate, initiating the resynthesis of phosphatidylinositols and attenuating protein kinase C activity.
Gene Name:
DGKA
Uniprot ID:
P23743
Molecular Weight:
82629.55 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
References
  1. Rabovsky A, Cuomo J, Eich N: Measurement of plasma antioxidant reserve after supplementation with various antioxidants in healthy subjects. Clin Chim Acta. 2006 Sep;371(1-2):55-60. Epub 2006 Mar 6. [16603143 ]
  2. Meijerman I, Beijnen JH, Schellens JH: Herb-drug interactions in oncology: focus on mechanisms of induction. Oncologist. 2006 Jul-Aug;11(7):742-52. [16880233 ]
General Function:
Vitamin e binding
Specific Function:
Carrier protein. Binds to some hydrophobic molecules and promotes their transfer between the different cellular sites. Binds with high affinity to alpha-tocopherol. Also binds with a weaker affinity to other tocopherols and to tocotrienols. May have a transcriptional activatory activity via its association with alpha-tocopherol. Probably recognizes and binds some squalene structure, suggesting that it may regulate cholesterol biosynthesis by increasing the transfer of squalene to a metabolic active pool in the cell.
Gene Name:
SEC14L2
Uniprot ID:
O76054
Molecular Weight:
46144.9 Da
References
  1. Neuzil J, Dong LF, Wang XF, Zingg JM: Tocopherol-associated protein-1 accelerates apoptosis induced by alpha-tocopheryl succinate in mesothelioma cells. Biochem Biophys Res Commun. 2006 May 19;343(4):1113-7. Epub 2006 Mar 31. [16579965 ]
  2. Ni J, Pang ST, Yeh S: Differential retention of alpha-vitamin E is correlated with its transporter gene expression and growth inhibition efficacy in prostate cancer cells. Prostate. 2007 Apr 1;67(5):463-71. [17252538 ]
General Function:
Transporter activity
Specific Function:
Probable hydrophobic ligand-binding protein; may play a role in the transport of hydrophobic ligands like tocopherol, squalene and phospholipids.
Gene Name:
SEC14L4
Uniprot ID:
Q9UDX3
Molecular Weight:
46643.385 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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 ]
General Function:
PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'.
Specific Function:
Gaba receptor binding
Gene Name:
PPP2CA
Uniprot ID:
P67775
Molecular Weight:
35593.93 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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 ]
General Function:
Protein serine/threonine phosphatase activity
Specific Function:
PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase.
Gene Name:
PPP2CB
Uniprot ID:
P62714
Molecular Weight:
35574.85 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. 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 ]
General Function:
Iron ion binding
Specific Function:
Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes.
Gene Name:
ALOX5
Uniprot ID:
P09917
Molecular Weight:
77982.595 Da
References
  1. Taccone-Gallucci M, Manca-di-Villahermosa S, Battistini L, Stuffler RG, Tedesco M, Maccarrone M: N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity. Kidney Int. 2006 Apr;69(8):1450-4. [16531984 ]
General Function:
Vitamin e binding
Specific Function:
Binds alpha-tocopherol, enhances its transfer between separate membranes, and stimulates its release from liver cells (PubMed:7887897). Binds both phosphatidylinol 3,4-bisphosphate and phosphatidylinol 4,5-bisphosphate; the resulting conformation change is important for the release of the bound alpha-tocopherol (By similarity).
Gene Name:
TTPA
Uniprot ID:
P49638
Molecular Weight:
31749.305 Da