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Record Information
Version2.0
Creation Date2014-09-11 05:16:33 UTC
Update Date2014-12-24 20:26:57 UTC
Accession NumberT3D4787
Identification
Common NameLovastatin
ClassSmall Molecule
DescriptionLovastatin is a cholesterol-lowering agent that belongs to the class of medications called statins. It was the second agent of this class discovered. It was discovered by Alfred Alberts and his team at Merck in 1978 after screening only 18 compounds over 2 weeks. The agent, also known as mevinolin, was isolated from the fungi Aspergillus terreus. Research on this compound was suddenly shut down in 1980 and the drug was not approved until 1987. Interesting, Akira Endo at Sankyo Co. (Japan) patented lovastatin isolated from Monascus ruber four months before Merck. Lovastatin was found to be 2 times more potent than its predecessor, mevastatin, the first discovered statin. Like mevastatin, lovastatin is structurally similar to hydroxymethylglutarate (HMG), a substituent of HMG-Coenzyme A (HMG-CoA), a substrate of the cholesterol biosynthesis pathway via the mevalonic acid pathway. Lovastatin is a competitive inhibitor of HMG-CoA reductase with a binding affinity 20,000 times greater than HMG-CoA. Lovastatin differs structurally from mevastatin by a single methyl group at the 6' position. Lovastatin is a prodrug that is activated by in vivo hydrolysis of the lactone ring. It, along with mevastatin, has served as one of the lead compounds for the development of the synthetic compounds used today.
Compound Type
  • Anticholesteremic Agent
  • Drug
  • Ester
  • Ether
  • Hydroxymethylglutaryl-CoA Reductase Inhibitor
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(1S,3R,7S,8S,8AR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(2R,4R)-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl (S)-2-methyl-butyrate
2beta,6alpha-Dimethyl-8alpha-(2-methyl-1-oxobutoxy)-mevinic acid lactone
6 alpha-Methylcompactin
6-alpha-methylcompactin
6alpha-Methylcompactin
6α-methylcompactin
Altocor
Altoprev
LOVASTATIN
Lovastatina
Lovastatine
Lovastatinum
Mevacor
Mevinolin
MK-803
ML-530b
Chemical FormulaC24H36O5
Average Molecular Mass404.540 g/mol
Monoisotopic Mass404.256 g/mol
CAS Registry Number75330-75-5
IUPAC Name(1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (2S)-2-methylbutanoate
Traditional Namelovastatin
SMILES[H][C@](C)(CC)C(=O)O[C@@]1([H])C[C@@]([H])(C)C=C2C=C[C@]([H])(C)[C@]([H])(CC[C@]3([H])C[C@@]([H])(O)CC(=O)O3)[C@@]12[H]
InChI IdentifierInChI=1S/C24H36O5/c1-5-15(3)24(27)29-21-11-14(2)10-17-7-6-16(4)20(23(17)21)9-8-19-12-18(25)13-22(26)28-19/h6-7,10,14-16,18-21,23,25H,5,8-9,11-13H2,1-4H3/t14-,15-,16-,18+,19+,20-,21-,23-/m0/s1
InChI KeyInChIKey=PCZOHLXUXFIOCF-BXMDZJJMSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as delta valerolactones. These are cyclic organic compounds containing an oxan-2- one moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassLactones
Sub ClassDelta valerolactones
Direct ParentDelta valerolactones
Alternative Parents
Substituents
  • Delta valerolactone
  • Fatty acid ester
  • Delta_valerolactone
  • Dicarboxylic acid or derivatives
  • Oxane
  • Fatty acyl
  • Carboxylic acid ester
  • Secondary alcohol
  • Carboxylic acid derivative
  • Oxacycle
  • Organooxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Alcohol
  • Organic oxygen compound
  • Carbonyl group
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Lovastatin PathwayNot AvailableNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point174.5°C
Boiling PointNot Available
Solubility0.0004 mg/mL
LogP4.26
Predicted Properties
PropertyValueSource
Water Solubility0.024 g/LALOGPS
logP4.11ALOGPS
logP3.9ChemAxon
logS-4.2ALOGPS
pKa (Strongest Acidic)14.91ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area72.83 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity113.18 m³·mol⁻¹ChemAxon
Polarizability46.11 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4i-2910000000-dc8caf3905a76d1dc259JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4j-1910000000-8aeacab386a420581150JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4i-2910000000-dc8caf3905a76d1dc259JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0a4j-1910000000-8aeacab386a420581150JSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4r-9155000000-825da9f6a87f5a59c1c2JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-03di-9137500000-a125220abcd76ffa9a89JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000i-0049000000-86650e3e374df663aa35JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-000i-0049000000-86650e3e374df663aa35JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-017j-3981000000-8a9df18d5a3d8401a040JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0k9j-0392200000-046f8ecdd9105ec8f133JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0fg2-0590000000-79f2e6dc3b230361fea3JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0092-0970000000-029f3798d63ab95ed321JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0592-0930000000-85de8f33dd78ba45de36JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-05fv-0910000000-7a730b8fcd91e3df5b8fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-000e-0590000000-2206c97b74e146b3218dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0092-1960000000-6b3a14df210273b89f18JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0592-1910000000-38bd634327305fe325cfJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0abd-1900000000-e7dab133ffe03d435831JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0536-2900000000-12e639483c7d1a83da05JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-002f-2900000000-ed64daa9de830f1f3cb0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-0092-0960000000-cb24a6eb72478d051b37JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0k9j-0392200000-046f8ecdd9105ec8f133JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-0597-0910000000-87327bc487bcb23a89f1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-000b-0590000000-c8c50c20a62e59420cf2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 50V, Positivesplash10-05fv-0910000000-d4c442d499341c3a56f4JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-052r-2019200000-72562315d7aa45f51111JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0f79-9176000000-32a60aba487dd125aab1JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-052r-9130000000-effc5ee7a79a5469060cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0009500000-03828e23d026b9da8a74JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-100r-5219100000-bd7b9834593ecb989122JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9132000000-6ad0a599a6d123e8d3bbJSpectraViewer
Toxicity Profile
Route of ExposureStudies suggest that <5% of the oral dose reaches the general circulation as active inhibitors. Time to peak serum concentration is 2-4 hours. Lovastatin undergoes extensive first-pass metabolism so the availability of the drug in the system is low and variable.
Mechanism of ToxicityLovastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Lovastatin is a prodrug that is activated in vivo via hydrolysis of the lactone ring to form the ‘_-hydroxyacid. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind to HMG-CoA reductase with 20,000 times greater affinity than its natural substrate. The bicyclic portion of lovastatin binds to the coenzyme A portion of the active site.
MetabolismLovastatin is hepatically metabolized in which the major active metabolites are the beta-hydroxyacid of lovastatin, the 6'-hydroxy derivative, and two additional metabolites. Route of Elimination: Lovastatin undergoes extensive first-pass extraction in the liver, its primary site of action, with subsequent excretion of drug equivalents in the bile. 83% of the orally administered dose is excreted in bile and 10% is excreted in urine. Half Life: 5.3 hours
Toxicity ValuesLD50>1000 mg/kg (orally in mice)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia. For primary prevention of coronary heart disease and to slow progression of coronary atherosclerosis in patients with coronary heart disease.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00227
HMDB IDHMDB14372
PubChem Compound ID53232
ChEMBL IDCHEMBL503
ChemSpider ID48085
KEGG IDC07074
UniProt IDNot Available
OMIM ID
ChEBI ID40303
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB ID803
ACToR IDNot Available
Wikipedia LinkLovastatin
References
Synthesis Reference

Donald F. Gerson, Xinfa Xiao, “Process for the production of lovastatin using Coniothyrium fuckelii.” U.S. Patent US5409820, issued January, 1984.

MSDSLink
General References
  1. Bobek P, Ozdin L, Galbavy S: Dose- and time-dependent hypocholesterolemic effect of oyster mushroom (Pleurotus ostreatus) in rats. Nutrition. 1998 Mar;14(3):282-6. [9583372 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Nadph binding
Specific Function:
Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.
Gene Name:
HMGCR
Uniprot ID:
P04035
Molecular Weight:
97475.155 Da
References
  1. Abe Y, Suzuki T, Ono C, Iwamoto K, Hosobuchi M, Yoshikawa H: Molecular cloning and characterization of an ML-236B (compactin) biosynthetic gene cluster in Penicillium citrinum. Mol Genet Genomics. 2002 Jul;267(5):636-46. Epub 2002 Jun 28. [12172803 ]
  2. Miyazaki A, Koieyama T, Shimada Y, Kikuchi T, Nezu H, Ito K, Kasanuki N, Koga T: Effects of pravastatin sodium on mevalonate metabolism in common marmosets. J Biochem. 2002 Sep;132(3):395-400. [12204108 ]
  3. Buxbaum JD, Geoghagen NS, Friedhoff LT: Cholesterol depletion with physiological concentrations of a statin decreases the formation of the Alzheimer amyloid Abeta peptide. J Alzheimers Dis. 2001 Apr;3(2):221-229. [12214063 ]
  4. Baranova NA, Kreier VG, Egorov NS: [Concentration on Diapak C 16 capsules of lovastatin, mevinolinic acid and other inhibitors of biosynthesis of sterins produced by Penicillium citrinum 89]. Antibiot Khimioter. 2002;47(4):3-6. [12369143 ]
  5. Farina HG, Bublik DR, Alonso DF, Gomez DE: Lovastatin alters cytoskeleton organization and inhibits experimental metastasis of mammary carcinoma cells. Clin Exp Metastasis. 2002;19(6):551-9. [12405293 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  7. Podar K, Tai YT, Hideshima T, Vallet S, Richardson PG, Anderson KC: Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127. doi: 10.1517/14728210802676278 . [19249983 ]
  8. Dimitroulakos J, Marhin WH, Tokunaga J, Irish J, Gullane P, Penn LZ, Kamel-Reid S: Microarray and biochemical analysis of lovastatin-induced apoptosis of squamous cell carcinomas. Neoplasia. 2002 Jul-Aug;4(4):337-46. [12082550 ]
General Function:
Transcription factor binding
Specific Function:
Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Forms transcriptional repressor complexes by associating with MAD, SIN3, YY1 and N-COR. Interacts in the late S-phase of DNA-replication with DNMT1 in the other transcriptional repressor complex composed of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Component of a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. May be involved in the transcriptional repression of circadian target genes, such as PER1, mediated by CRY1 through histone deacetylation. Involved in MTA1-mediated transcriptional corepression of TFF1 and CDKN1A.
Gene Name:
HDAC2
Uniprot ID:
Q92769
Molecular Weight:
55363.855 Da
References
  1. Lin YC, Lin JH, Chou CW, Chang YF, Yeh SH, Chen CC: Statins increase p21 through inhibition of histone deacetylase activity and release of promoter-associated HDAC1/2. Cancer Res. 2008 Apr 1;68(7):2375-83. doi: 10.1158/0008-5472.CAN-07-5807. [18381445 ]
General Function:
Metal ion binding
Specific Function:
Integrin alpha-L/beta-2 is a receptor for ICAM1, ICAM2, ICAM3 and ICAM4. It is involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell mediated killing, and antibody dependent killing by granulocytes and monocytes.
Gene Name:
ITGAL
Uniprot ID:
P20701
Molecular Weight:
128768.495 Da
References
  1. Kallen J, Welzenbach K, Ramage P, Geyl D, Kriwacki R, Legge G, Cottens S, Weitz-Schmidt G, Hommel U: Structural basis for LFA-1 inhibition upon lovastatin binding to the CD11a I-domain. J Mol Biol. 1999 Sep 10;292(1):1-9. [10493852 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.57 uMATG_PXR_TRANSAttagene
AC504 uMATG_PXRE_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Oxygen binding
Specific Function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular Weight:
57882.48 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.64 uMTox21_Aromatase_InhibitionTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.79 uMATG_LXRa_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.2 uMTox21_AR_BLA_Antagonist_ratioTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
TP53
Uniprot ID:
P04637
Molecular Weight:
43652.79 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.16836009 uMAPR_p53Act_72h_upApredica
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Recruited to promoters via its interaction with BAZ1B/WSTF which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.
Gene Name:
VDR
Uniprot ID:
P11473
Molecular Weight:
48288.64 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.06 uMATG_VDRE_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.21 uMATG_ERa_TRANSAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]