You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Toxin, Toxin Target Database.
Record Information
Version2.0
Creation Date2014-08-29 06:19:27 UTC
Update Date2018-03-21 17:46:20 UTC
Accession NumberT3D4314
Identification
Common NameCholesterol
ClassSmall Molecule
DescriptionCholesterol is a sterol (a combination steroid and alcohol) and a lipid found in the cell membranes of all body tissues and transported in the blood plasma of all animals. The name originates from the Greek chole- (bile) and stereos (solid), and the chemical suffix -ol for an alcohol. This is because researchers first identified cholesterol in solid form in gallstones in 1784. In the body, cholesterol can exist in either the free form or as an ester with a single fatty acid (of 10-20 carbons in length) covalently attached to the hydroxyl group at position 3 of the cholesterol ring. Due to the mechanism of synthesis, plasma cholesterol esters tend to contain relatively high proportions of polyunsaturated fatty acids. Most of the cholesterol consumed as a dietary lipid exists as cholesterol esters. Cholesterol esters have a lower solubility in water than cholesterol and are more hydrophobic. They are hydrolyzed by the pancreatic enzyme cholesterol esterase to produce cholesterol and free fatty acids. Cholesterol has vital structural roles in membranes and in lipid metabolism in general. It is a biosynthetic precursor of bile acids, vitamin D, and steroid hormones (glucocorticoids, estrogens, progesterones, androgens and aldosterone). In addition, it contributes to the development and functioning of the central nervous system, and it has major functions in signal transduction and sperm development. Cholesterol is a ubiquitous component of all animal tissues where much of it is located in the membranes, although it is not evenly distributed. The highest proportion of unesterified cholesterol is in the plasma membrane (roughly 30-50% of the lipid in the membrane or 60-80% of the cholesterol in the cell), while mitochondria and the endoplasmic reticulum have very low cholesterol contents. Cholesterol is also enriched in early and recycling endosomes, but not in late endosomes. The brain contains more cholesterol than any other organ where it comprises roughly a quarter of the total free cholesterol in the human body. Of all the organic constituents of blood, only glucose is present in a higher molar concentration than cholesterol. Cholesterol esters appear to be the preferred form for transport in plasma and as a biologically inert storage (de-toxified) form. They do not contribute to membranes but are packed into intracellular lipid particles. Cholesterol molecules (i.e. cholesterol esters) are transported throughout the body via lipoprotein particles. The largest lipoproteins, which primarily transport fats from the intestinal mucosa to the liver, are called chylomicrons. They carry mostly triglyceride fats and cholesterol that are from food, especially internal cholesterol secreted by the liver into the bile. In the liver, chylomicron particles give up triglycerides and some cholesterol. They are then converted into low-density lipoprotein (LDL) particles, which carry triglycerides and cholesterol on to other body cells. In healthy individuals, the LDL particles are large and relatively few in number. In contrast, large numbers of small LDL particles are strongly associated with promoting atheromatous disease within the arteries. (Lack of information on LDL particle number and size is one of the major problems of conventional lipid tests.). In conditions with elevated concentrations of oxidized LDL particles, especially small LDL particles, cholesterol promotes atheroma plaque deposits in the walls of arteries, a condition known as atherosclerosis, which is a major contributor to coronary heart disease and other forms of cardiovascular disease. There is a worldwide trend to believe that lower total cholesterol levels tend to correlate with lower atherosclerosis event rates (though some studies refute this idea). As a result, cholesterol has become a very large focus for the scientific community trying to determine the proper amount of cholesterol needed in a healthy diet. However, the primary association of atherosclerosis with cholesterol has always been specifically with cholesterol transport patterns, not total cholesterol per se. For example, total cholesterol can be low, yet made up primarily of small LDL and small HDL particles and atheroma growth rates are high. In contrast, however, if LDL particle number is low (mostly large particles) and a large percentage of the HDL particles are large (HDL is actively reverse transporting cholesterol), then atheroma growth rates are usually low, even negative, for any given total cholesterol concentration. These effects are further complicated by the relative concentration of asymmetric dimethylarginine (ADMA) in the endothelium since ADMA down-regulates production of nitric oxide, a relaxant of the endothelium. Thus, high levels of ADMA, associated with highly oxidized levels of LDL, pose a heightened risk factor for vascular disease. Chronically high levels of cholesterol are associated with at least five inborn errors of metabolism, including cerebrotendinous xanthomatosis, cholesteryl ester storage disease, congenital lipoid adrenal hyperplasia, hypercholesterolemia, and Zellweger syndrome. In chronically high levels, cholesterol can function as an atherogen (causes atherosclerosis and cardiovascular disease). Specifically, chronically high levels (from diet or from genetic predisposition or from diseases such as hyperlipidemia) of cholesterol and cholesterol esters lead to an excess of low-density lipoprotein (LDL) particles. In healthy individuals, the LDL particles are large and relatively few in number. In contrast, large numbers of small LDL particles are strongly associated with promoting atheromatous disease within the arteries. In conditions with elevated concentrations of oxidized LDL particles, especially small LDL particles, cholesterol promotes atheroma plaque deposits in the walls of arteries, a condition known as atherosclerosis, which is a major contributor to coronary heart disease and other forms of cardiovascular disease. Resistin, a protein secreted by fat tissue, has been shown to increase the production of LDL in human liver cells and also degrades LDL receptors in the liver. As a result, the liver is less able to clear cholesterol from the bloodstream. Resistin accelerates the accumulation of LDL in arteries, increasing the risk of heart disease.
Compound Type
  • Animal Toxin
  • Food Toxin
  • Household Toxin
  • Industrial/Workplace Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(+)-ent-Cholesterol
(-)-Cholesterol
(20bFH)-cholest-5-en-3b-ol
(3b)-cholest-5-en-3-ol
(3beta)-Cholest-5-en-3-ol
20-Epi-cholesterol
20-Iso-cholesterol
20bFH-cholest-5-en-3b-ol
3beta-Hydroxycholest-5-ene
5-Cholesten-3B-ol
5-Cholesten-3beta-ol
5:6-Cholesten-3-ol
5:6-Cholesten-3beta-ol
Cholest-5-en-3-ol
Cholest-5-en-3b-ol
Cholest-5-en-3beta-ol
Cholesterin
Cholesterine
Cholesterol base H
Cholesteryl alcohol
Cholestrin
Cholestrol
Cordulan
Dastar
Dusoline
Dusoran
Dythol
Epicholesterin
Epicholesterol
Fancol CH
Hydrocerin
Kathro
Lanol
Liquid crystal CN/9
Nimco cholesterol base H
Nimco cholesterol base No. 712
Super hartolan
Tegolan
Chemical FormulaC27H46O
Average Molecular Mass386.654 g/mol
Monoisotopic Mass386.355 g/mol
CAS Registry Number57-88-5
IUPAC Name(1S,2R,10S,11S,14R,15R)-2,15-dimethyl-14-[(2R)-6-methylheptan-2-yl]tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-7-en-5-ol
Traditional Namecholest-5-en-3-ol
SMILES[H][C@@](C)(CCCC(C)C)[C@@]1([H])CC[C@@]2([H])[C@]3([H])CC=C4CC([H])(O)CC[C@]4(C)[C@@]3([H])CC[C@]12C
InChI IdentifierInChI=1S/C27H46O/c1-18(2)7-6-8-19(3)23-11-12-24-22-10-9-20-17-21(28)13-15-26(20,4)25(22)14-16-27(23,24)5/h9,18-19,21-25,28H,6-8,10-17H2,1-5H3/t19-,21?,22+,23-,24+,25+,26+,27-/m1/s1
InChI KeyInChIKey=HVYWMOMLDIMFJA-FNOPAARDSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as cholesterols and derivatives. Cholesterols and derivatives are compounds containing a 3-hydroxylated cholestane core.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassCholestane steroids
Direct ParentCholesterols and derivatives
Alternative Parents
Substituents
  • Cholesterol-skeleton
  • Cholesterol
  • Hydroxysteroid
  • 3-hydroxysteroid
  • 3-hydroxy-delta-5-steroid
  • Delta-5-steroid
  • Cyclic alcohol
  • Secondary alcohol
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Endoplasmic reticulum
  • Extracellular
  • Golgi apparatus
  • Lysosome
  • Membrane
  • Mitochondria
Biofluid LocationsNot Available
Tissue Locations
  • All Tissues
Pathways
NameSMPDB LinkKEGG Link
Bile Acid BiosynthesisSMP00035 Not Available
Steroid BiosynthesisSMP00023 map00100
SteroidogenesisSMP00130 map00140
Cerebrotendinous Xanthomatosis (CTX)SMP00315 Not Available
Cholesteryl ester storage diseaseSMP00508 Not Available
Congenital Lipoid Adrenal Hyperplasia (CLAH) or Lipoid CAHSMP00371 Not Available
HypercholesterolemiaSMP00209 Not Available
Zellweger SyndromeSMP00316 Not Available
ApplicationsNot Available
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point148°C
Boiling Point360°C (680°F)
Solubility9.5e-05 mg/mL
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility2.8e-05 g/LALOGPS
logP7.02ALOGPS
logP7.11ChemAxon
logS-7.1ALOGPS
pKa (Strongest Acidic)18.2ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area20.23 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity120.62 m³·mol⁻¹ChemAxon
Polarizability50.7 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-05fr-1109000000-3cc42021add80e72c319JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0006-3104900000-698223f49da0b0c1cf81JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014r-0009000000-dccd68f70545aeac4fabJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-05p9-3149000000-7f25daf2b709c7e0d177JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0c00-6269000000-5333d0216e01a3e43367JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0009000000-dc853b29b9e884bbb03bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-0009000000-09d9608700564a6fef78JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0ldi-1009000000-96f6e67651380e1c959eJSpectraViewer
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
2D NMR[1H,13C] 2D NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureIngestion, endogenous production.
Mechanism of ToxicityCholesterol is essential for life. However, chronically high levels (from diet or from genetic predisposition or from diseases such as hyperlipidemia) of cholesterol and cholesterol esters lead to an excess of low-density lipoprotein (LDL) particles. In healthy individuals the LDL particles are large and relatively few in number. In contrast, large numbers of small LDL particles are strongly associated with promoting atheromatous disease within the arteries. In conditions with elevated concentrations of oxidized LDL particles, especially small LDL particles, cholesterol promotes atheroma plaque deposits in the walls of arteries, a condition known as atherosclerosis, which is a major contributor to coronary heart disease and other forms of cardiovascular disease. Resistin, a protein secreted by fat tissue, has been shown to increase the production of LDL in human liver cells and also degrades LDL receptors in the liver. As a result, the liver is less able to clear cholesterol from the bloodstream. Resistin accelerates the accumulation of LDL in arteries, increasing the risk of heart disease.
MetabolismCholesterol is not readily biodegradable and is primarily eliminated in the feces as bile acids. Only the liver possesses the enzymes to degrade significant amounts. Cholesterol and its oxidized metabolites (oxysterols) are transferred back from peripheral tissues in lipoprotein complexes to the liver for catabolism by conversion to oxysterols and bile acids. The latter are exported into the intestines to aid digestion. Until recently, it was believed that approximately 90% of cholesterol elimination from the body occurred via bile acids in humans. However, experiments with animal models now suggest that a significant amount is secreted directly into the intestines by a process known as trans-intestinal cholesterol efflux.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (21)
Uses/SourcesFound in many foods (meats, eggs, milk, cheese, fish, shellfish) derived from animal products. Essential for membrane integrity. Used in steroid hormone synthesis.
Minimum Risk LevelIdeal plasma cholesterol (total free plust cholesterol ester) levels for adults should be <5200 uM or about <200 mg/dL. Chronically high values of >6200 uM (>240 mg/dL) are considered high risk and can lead to heart disease, atherosclerosis and stroke. The desirable LDL level is considered to be less than 100 mg/dL (2.6 mM)
Health EffectsHigh plasma levels lead to hyperlipidemia or hypercholesterolemia which over a long period of time can lead to athersoclerosis, heart disease, stroke, poor kidney function. Extremely low levels of cholesterol (hypocholesterolemia) can lead to depression, cancer and cerebral hemorrhage. Chronically high levels of cholesterol are associated with at least 5 inborn errors of metabolism including: Cerebrotendinous Xanthomatosis, Cholesteryl ester storage disease, Congenital Lipoid Adrenal Hyperplasia, Hypercholesterolemia and Zellweger syndrome.
SymptomsThere are no visible symptoms of high serum cholesterol. The following are symptoms of cardiovascular diseases: shortness of breath, chest pain, pain or weakness in legs or arms, pain in the neck, jaw, throat, upper abdomen, poor exercise tolerance, atherosclerotic plaques.
TreatmentCardiologists recommend that individuals 20 or older should be screened for high cholesterol at least once every five years, with more frequent screenings for anyone deemed to be at high risk for heart disease. The USDA recommends that those wishing to reduce their cholesterol through a change in diet should aim to consume less than 7% of their daily energy needs from saturated fat and fewer than 200 mg of cholesterol per day. Statin drugs (which are HMG-CoA reductase inhibitors) are effective at reducing the amount of cholesterol produced in the liver. The National Institute for Health and Clinical Excellence (NICE) recommends statin treatment for adults with an estimated 10-year risk of developing cardiovascular disease that is greater than 20%. Several types of cholesterol-lowering medication are available, including niacin, bile acid resins, dietary fiber, psyllium and fibrates. But statins are the treatment of choice for most individuals.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB04540
HMDB IDHMDB00067
PubChem Compound ID11025495
ChEMBL IDCHEMBL1867358
ChemSpider ID9200676
KEGG IDC00187
UniProt IDNot Available
OMIM ID
ChEBI ID1307929
BioCyc IDCHOLESTEROL
CTD IDNot Available
Stitch IDNot Available
PDB IDCLR
ACToR IDNot Available
Wikipedia LinkCholesterol
References
Synthesis Reference

Tatu Miettenen, Ingmar Wester, Hannu Vanhanen, “Substance for lowering high cholesterol level in serum and methods for preparing and using the same.” U.S. Patent US6174560, issued February, 1944.

MSDSLink
General References
  1. Bjorkhem I, Heverin M, Leoni V, Meaney S, Diczfalusy U: Oxysterols and Alzheimer's disease. Acta Neurol Scand Suppl. 2006;185:43-9. [16866910 ]
  2. Ellis D, Lloyd C, Becker DJ, Forrest KY, Orchard TJ: The changing course of diabetic nephropathy: low-density lipoprotein cholesterol and blood pressure correlate with regression of proteinuria. Am J Kidney Dis. 1996 Jun;27(6):809-18. [8651245 ]
  3. Gil'miiarova FN, Pervova IuV, Radomskaia VM, Gergel' NI, Tarasova SV: [Levels of unified metabolites and thyroid hormones in blood and oral fluid of children with minimal brain dysfunction]. Biomed Khim. 2004 Mar-Apr;50(2):204-10. [15179829 ]
  4. Thelen KM, Falkai P, Bayer TA, Lutjohann D: Cholesterol synthesis rate in human hippocampus declines with aging. Neurosci Lett. 2006 Jul 31;403(1-2):15-9. Epub 2006 May 15. [16701946 ]
  5. Schillaci G, Pirro M, Ronti T, Gemelli F, Pucci G, Innocente S, Porcellati C, Mannarino E: Prognostic impact of prolonged ventricular repolarization in hypertension. Arch Intern Med. 2006 Apr 24;166(8):909-13. [16636218 ]
  6. Higashijima H, Ichimiya H, Nakano T, Yamashita H, Kuroki S, Satoh H, Chijiiwa K, Tanaka M: Deconjugation of bilirubin accelerates coprecipitation of cholesterol, fatty acids, and mucin in human bile--in vitro study. J Gastroenterol. 1996 Dec;31(6):828-35. [9027647 ]
  7. Proksch GJ, Bonderman DP: Use of a cholesterol-rich bovine lipoprotein to enhance cholesterol concentrations in the preparation of serum control materials. Clin Chem. 1976 Aug;22(8):1302-5. [985740 ]
  8. van Rooij A, Nijenhuis AA, Wijburg FA, Schutgens RB: Highly increased CSF concentrations of cholesterol precursors in Smith-Lemli-Opitz syndrome. J Inherit Metab Dis. 1997 Aug;20(4):578-80. [9266395 ]
  9. Sanchez E, Fernandez-D'Pool J: [Liver function in patients exposed to a toluene in a hydrocarbon processing plant]. Invest Clin. 1996 Dec;37(4):255-70. [9004852 ]
  10. Mizuno S, Tazuma S, Kajiyama G: Stabilization of biliary lipid particles by ursodeoxycholic acid. Prolonged nucleation time in human gallbladder bile. Dig Dis Sci. 1993 Apr;38(4):684-93. [8462368 ]
  11. Bookman ID, Pham J, Guindi M, Heathcote EJ: Distinguishing nonalcoholic steatohepatitis from fatty liver: serum-free fatty acids, insulin resistance, and serum lipoproteins. Liver Int. 2006 Jun;26(5):566-71. [16762001 ]
  12. Nigg C, Gutzwiller F: [Cholesterol: blood level and control by Swiss physicians]. Schweiz Med Wochenschr. 1995 Feb 25;125(8):355-60. [7709184 ]
  13. Winocour PH, Durrington PN, Bhatnagar D, Ishola M, Mackness M, Arrol S: Influence of early diabetic nephropathy on very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) composition. Atherosclerosis. 1991 Jul;89(1):49-57. [1772471 ]
  14. Hoffmann G, Gibson KM, Brandt IK, Bader PI, Wappner RS, Sweetman L: Mevalonic aciduria--an inborn error of cholesterol and nonsterol isoprene biosynthesis. N Engl J Med. 1986 Jun 19;314(25):1610-4. [3012338 ]
  15. Markuszewski L, Rosiak M, Golanski J, Rysz J, Spychalska M, Watala C: Reduced blood platelet sensitivity to aspirin in coronary artery disease: are dyslipidaemia and inflammatory states possible factors predisposing to sub-optimal platelet response to aspirin? Basic Clin Pharmacol Toxicol. 2006 May;98(5):503-9. [16635110 ]
  16. Miettinen TE, Kesaniemi YA, Gylling H, Jarvinen H, Silvennoinen E, Miettinen TA: Noncholesterol sterols in bile and stones of patients with cholesterol and pigment stones. Hepatology. 1996 Feb;23(2):274-80. [8591852 ]
  17. Leoni V, Lutjohann D, Masterman T: Levels of 7-oxocholesterol in cerebrospinal fluid are more than one thousand times lower than reported in multiple sclerosis. J Lipid Res. 2005 Feb;46(2):191-5. Epub 2004 Dec 1. [15576852 ]
  18. D'Amico G, Gentile MG: Effect of dietary manipulation on the lipid abnormalities and urinary protein loss in nephrotic patients. Miner Electrolyte Metab. 1992;18(2-5):203-6. [1465059 ]
  19. Pak CH, Oleneva VA, Agadzhanov SA: [Dietetic aspects of preventing urolithiasis in patients with gout and uric acid diathesis]. Vopr Pitan. 1985 Jan-Feb;(1):21-4. [3885567 ]
  20. 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 ]
  21. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Key regulator of embryonic development, cellular differentiation, immunity, circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. Considered to have intrinsic transcriptional activity, have some natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing the transcriptional activity, respectively. Recruits distinct combinations of cofactors to target genes regulatory regions to modulate their transcriptional expression, depending on the tissue, time and promoter contexts. Regulates genes involved in photoreceptor development including OPN1SW, OPN1SM and ARR3 and skeletal muscle development with MYOD1. Required for proper cerebellum development, regulates SHH gene expression, among others, to induce granule cells proliferation as well as expression of genes involved in calcium-mediated signal transduction. Regulates the circadian expression of several clock genes, including CLOCK, ARNTL/BMAL1, NPAS2 and CRY1. Competes with NR1D1 for binding to their shared DNA response element on some clock genes such as ARNTL/BMAL1, CRY1 and NR1D1 itself, resulting in NR1D1-mediated repression or RORA-mediated activation of clock genes expression, leading to the circadian pattern of clock genes expression. Therefore influences the period length and stability of the clock. Regulates genes involved in lipid metabolism such as apolipoproteins APOA1, APOA5, APOC3 and PPARG. In liver, has specific and redundant functions with RORC as positive or negative modulator of expression of genes encoding phase I and phase II proteins involved in the metabolism of lipids, steroids and xenobiotics, such as CYP7B1 and SULT2A1. Induces a rhythmic expression of some of these genes. In addition, interplays functionally with NR1H2 and NR1H3 for the regulation of genes involved in cholesterol metabolism. Also involved in the regulation of hepatic glucose metabolism through the modulation of G6PC and PCK1. In adipose tissue, plays a role as negative regulator of adipocyte differentiation, probably acting through dual mechanisms. May suppress CEBPB-dependent adipogenesis through direct interaction and PPARG-dependent adipogenesis through competition for DNA-binding. Downstream of IL6 and TGFB and synergistically with RORC isoform 2, is implicated in the lineage specification of uncommitted CD4(+) T-helper (T(H)) cells into T(H)17 cells, antagonizing the T(H)1 program. Probably regulates IL17 and IL17F expression on T(H) by binding to the essential enhancer conserved non-coding sequence 2 (CNS2) in the IL17-IL17F locus. Involved in hypoxia signaling by interacting with and activating the transcriptional activity of HIF1A. May inhibit cell growth in response to cellular stress. May exert an anti-inflammatory role by inducing CHUK expression and inhibiting NF-kappa-B signaling.
Gene Name:
RORA
Uniprot ID:
P35398
Molecular Weight:
58974.35 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. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [10592235 ]
General Function:
Protein kinase binding
Specific Function:
Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes.
Gene Name:
POLA1
Uniprot ID:
P09884
Molecular Weight:
165911.405 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>500 uMNot AvailableBindingDB 20192
References
  1. Oshige M, Kuramochi K, Ohta K, Ogawa A, Kuriyama H, Sugawara F, Kobayashi S, Sakaguchi K: Molecular design of cholesterols as inhibitors of DNA polymerase alpha. J Med Chem. 2004 Sep 23;47(20):4971-4. [15369402 ]
General Function:
Sterol 14-demethylase activity
Specific Function:
Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol.
Gene Name:
CYP51A1
Uniprot ID:
Q16850
Molecular Weight:
56805.26 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>200 uMNot AvailableBindingDB 20192
References
  1. Ekins S, Mankowski DC, Hoover DJ, Lawton MP, Treadway JL, Harwood HJ Jr: Three-dimensional quantitative structure-activity relationship analysis of human CYP51 inhibitors. Drug Metab Dispos. 2007 Mar;35(3):493-500. Epub 2006 Dec 28. [17194716 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC508.2 uMNot AvailableBindingDB 20192
References
  1. Wang E, Casciano CN, Clement RP, Johnson WW: Cholesterol interaction with the daunorubicin binding site of P-glycoprotein. Biochem Biophys Res Commun. 2000 Oct 5;276(3):909-16. [11027568 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor. Interaction with RXR shifts RXR from its role as a silent DNA-binding partner to an active ligand-binding subunit in mediating retinoid responses through target genes defined by LXRES. LXRES are DR4-type response elements characterized by direct repeats of two similar hexanuclotide half-sites spaced by four nucleotides. Plays an important role in the regulation of cholesterol homeostasis, regulating cholesterol uptake through MYLIP-dependent ubiquitination of LDLR, VLDLR and LRP8. Interplays functionally with RORA for the regulation of genes involved in liver metabolism (By similarity). Exhibits a ligand-dependent transcriptional activation activity (PubMed:25661920).
Gene Name:
NR1H3
Uniprot ID:
Q13133
Molecular Weight:
50395.34 Da
References
  1. Ruan XZ, Moorhead JF, Fernando R, Wheeler DC, Powis SH, Varghese Z: PPAR agonists protect mesangial cells from interleukin 1beta-induced intracellular lipid accumulation by activating the ABCA1 cholesterol efflux pathway. J Am Soc Nephrol. 2003 Mar;14(3):593-600. [12595494 ]
General Function:
Phospholipid binding
Specific Function:
Apolipoprotein B is a major protein constituent of chylomicrons (apo B-48), LDL (apo B-100) and VLDL (apo B-100). Apo B-100 functions as a recognition signal for the cellular binding and internalization of LDL particles by the apoB/E receptor.
Gene Name:
APOB
Uniprot ID:
P04114
Molecular Weight:
515600.06 Da
7. Apolipoprotein C (Protein Group)
General Function:
Phospholipase inhibitor activity
Specific Function:
Inhibitor of lipoprotein binding to the low density lipoprotein (LDL) receptor, LDL receptor-related protein, and very low density lipoprotein (VLDL) receptor. Associates with high density lipoproteins (HDL) and the triacylglycerol-rich lipoproteins in the plasma and makes up about 10% of the protein of the VLDL and 2% of that of HDL. Appears to interfere directly with fatty acid uptake and is also the major plasma inhibitor of cholesteryl ester transfer protein (CETP). Binds free fatty acids and reduces their intracellular esterification. Modulates the interaction of APOE with beta-migrating VLDL and inhibits binding of beta-VLDL to the LDL receptor-related protein.
Included Proteins:
P02654 , P02655 , P02656 , P55056
General Function:
Very-low-density lipoprotein particle receptor binding
Specific Function:
Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues.
Gene Name:
APOE
Uniprot ID:
P02649
Molecular Weight:
36153.83 Da
General Function:
Virus receptor activity
Specific Function:
Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits.(Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins (PubMed:10535997, PubMed:12615904). Acts as a receptor for vesicular stomatitis virus (PubMed:23589850). In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells (PubMed:11100124).
Gene Name:
LDLR
Uniprot ID:
P01130
Molecular Weight:
95375.105 Da
General Function:
Not Available
Specific Function:
Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells. Potentially links obesity to diabetes.
Gene Name:
RETN
Uniprot ID:
Q9HD89
Molecular Weight:
11419.195 Da
General Function:
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function:
Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the fatty acid and to a lesser degree the cholesterol synthesis pathway (By similarity). Binds to the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3'). Has dual sequence specificity binding to both an E-box motif (5'-ATCACGTGA-3') and to SRE-1 (5'-ATCACCCCAC-3').
Gene Name:
SREBF1
Uniprot ID:
P36956
Molecular Weight:
121673.6 Da
General Function:
Transcriptional repressor activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function:
Transcriptional activator required for lipid homeostasis. Regulates transcription of the LDL receptor gene as well as the cholesterol and to a lesser degree the fatty acid synthesis pathway (By similarity). Binds the sterol regulatory element 1 (SRE-1) (5'-ATCACCCCAC-3') found in the flanking region of the LDRL and HMG-CoA synthase genes.
Gene Name:
SREBF2
Uniprot ID:
Q12772
Molecular Weight:
123686.44 Da