Thiabendazole
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Basic Info
| Common Name | Thiabendazole(F05144) |
| 2D Structure | |
| Description | Thiabendazole is a fungicide and parasiticide. It is used primarily to control mold, blight, and other fungally caused diseases in fruits (e.g. oranges) and vegetables; it is also used as a prophylactic treatment for Dutch elm disease. As an antiparasitic, it is able to control roundworms (such as those causing strongyloidiasis), hookworms, and other helminth species which attack wild animals, livestock and humans. |
| FRCD ID | F05144 |
| CAS Number | 148-79-8 |
| PubChem CID | 5430 |
| Formula | C10H7N3S |
| IUPAC Name | 4-(1H-benzimidazol-2-yl)-1,3-thiazole |
| InChI Key | WJCNZQLZVWNLKY-UHFFFAOYSA-N |
| InChI | InChI=1S/C10H7N3S/c1-2-4-8-7(3-1)12-10(13-8)9-5-14-6-11-9/h1-6H,(H,12,13) |
| Canonical SMILES | C1=CC=C2C(=C1)NC(=N2)C3=CSC=N3 |
| Isomeric SMILES | C1=CC=C2C(=C1)NC(=N2)C3=CSC=N3 |
| Wikipedia | Thiabendazole |
| Synonyms |
thiabendazole
148-79-8
Tiabendazole
Mintezol
Equizole
Tiabendazol
Mintesol
Omnizole
Thibenzole
Thiabendazol
|
| Classifies |
Veterinary Drug
Pesticide
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organoheterocyclic compounds |
| Class | Benzimidazoles |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Benzimidazoles |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Benzimidazole - Benzenoid - Heteroaromatic compound - Thiazole - Imidazole - Azole - Azacycle - Organic nitrogen compound - Organopnictogen compound - Hydrocarbon derivative - Organonitrogen compound - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as benzimidazoles. These are organic compounds containing a benzene ring fused to an imidazole ring (five member ring containing a nitrogen atom, 4 carbon atoms, and two double bonds). |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 201.247 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 1 |
| Complexity | 212 |
| Monoisotopic Mass | 201.036 |
| Exact Mass | 201.036 |
| XLogP | 2.5 |
| Formal Charge | 0 |
| Heavy Atom Count | 14 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9473 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2- | 0.6733 |
| P-glycoprotein Substrate | Non-substrate | 0.7174 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.9299 |
| Non-inhibitor | 0.9317 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8624 |
| Distribution | ||
| Subcellular localization | Nucleus | 0.3844 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8768 |
| CYP450 2D6 Substrate | Non-substrate | 0.9116 |
| CYP450 3A4 Substrate | Non-substrate | 0.8103 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.9106 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.9071 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.5658 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.8994 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.8216 |
| CYP Inhibitory Promiscuity | High CYP Inhibitory Promiscuity | 0.6773 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9838 |
| Non-inhibitor | 0.9321 | |
| AMES Toxicity | AMES toxic | 0.9107 |
| Carcinogens | Non-carcinogens | 0.9331 |
| Fish Toxicity | High FHMT | 0.7982 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9480 |
| Honey Bee Toxicity | Low HBT | 0.5375 |
| Biodegradation | Not ready biodegradable | 0.9814 |
| Acute Oral Toxicity | III | 0.8024 |
| Carcinogenicity (Three-class) | Non-required | 0.7007 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.1274 | LogS |
| Caco-2 Permeability | 1.1163 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.0170 | LD50, mol/kg |
| Fish Toxicity | 1.2714 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.8784 | pIGC50, ug/L |
MRLs
| Food | Product Code | Country | MRLs | Application Date | Notes |
|---|---|---|---|---|---|
| Wheat (Durum wheat, Einkorn wheat/small spelt/one-grain wheat, Emmer wheat, Khorasan wheat, Spelt, Triticale, Other species of genus Triticum, not elsewhere mentioned,) | 0500090 | European Union | 0.01* | 21/01/2018 | |
| Rose (Almond, Bee balm, Bitter orange/sour orange, Black locust, Cat’s foot, Chrysanthemum, Cinnamon, Clary sage, Cornflower, Cowslip/primrose, Daisy, Dyer’s broom, Elder, Field poppy, Great mullei... | 0631030 | European Union | 0.05* | 21/01/2018 | |
| Strawberry (Absinth/common wormwood, Agrimony, Alfalfa/lucerne, Aloe (leaf gel), Alpine ladies mantle, Bearberry, Bilberry/European blueberry/whortleberry, Birch, Bitter orange/sour orange, Blackbe... | 0632010 | European Union | 0.05* | 21/01/2018 | |
| Edible offals (other than liver and kidney) | 1011050 | European Union | 0.3 | 21/01/2018 | |
| Amphibians and Reptiles (Crocodiles, Frog legs, Snakes, Turtles, Other Amphibians and Reptiles, Other frog legs from frogs not belonging to the genus Rana,) | 1050000 | European Union | 0.01* | 21/01/2018 | |
| Citrus Fruits | New Zealand | 3mg/kg | |||
| Bananas | New Zealand | 3mg/kg | |||
| Peas (Without Pods) | Britain | 0.05mg/kg | |||
| Other Pome Fruit | Britain | 0.05mg/kg | |||
| Shiitake Mushroom | Japan | 2ppm | |||
| Celery | Japan | 2ppm | |||
| Parsley | Japan | 2ppm | |||
| Parsnip | Japan | 2ppm | |||
| Carrot | Japan | 2ppm | |||
| Milk | CAC | 0. 2mg/kg | |||
| Cashew nuts | 0120030 | European Union | 0.02* | 21/01/2018 | |
| Citrus fruits | 0110000 | European Union | 7 | 21/01/2018 | |
| Grapefruits (Natsudaidais, Shaddocks/pomelos, Sweeties/oroblancos, Tangelolos, Tangelos (except minneolas)/Ugli®, Other hybrids of Citrus paradisi, not elsewhere mentioned,) | 0110010 | European Union | 7 | 21/01/2018 | |
| Oranges (Bergamots, Bitter oranges/sour oranges, Blood oranges, Cara caras, Chinottos, Trifoliate oranges, Other hybrids of Citrus sinensis, not elsewhere mentioned,) | 0110020 | European Union | 7 | 21/01/2018 | |
| Lemons (Buddha's hands/Buddha's fingers, Citrons,) | 0110030 | European Union | 7 | 21/01/2018 |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Simple and fast spectrophotometric determination of low levels of thiabendazoleresidues in fruit and vegetables after pre-concentration with ionic liquid phase microextraction. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2018Jun | 29470140 |
| Rapid determination of thiabendazole in juice by SERS coupled with novel goldnanosubstrates. | Food Chem | 2018 Sep 1 | 29680047 |
| Target vs non-target analysis to determine pesticide residues in fruits fromSaudi Arabia and influence in potential risk associated with exposure. | Food Chem Toxicol | 2018 Jan | 29109044 |
| Quantitative Determination of Thiabendazole in Soil Extracts by Surface-Enhanced Raman Spectroscopy. | Molecules | 2018 Aug 5 | 30081585 |
| Rapid Determination of Thiabendazole Pesticides in Rape by Surface Enhanced RamanSpectroscopy. | Sensors (Basel) | 2018 Apr 4 | 29617288 |
| Organic Solvent as Internal Standards for Quantitative and High-Throughput LiquidInterfacial SERS Analysis in Complex Media. | Anal Chem | 2018 Apr 17 | 29584402 |
| Terminalia catappa: Chemical composition, in vitro and in vivo effects onHaemonchus contortus. | Vet Parasitol | 2017 Nov 15 | 28969774 |
| Investigation of Pesticide Penetration and Persistence on Harvested and LiveBasil Leaves Using Surface-Enhanced Raman Scattering Mapping. | J Agric Food Chem | 2017 May 3 | 28393527 |
| Characterization of Postharvest Fungicide-Resistant Botrytis cinerea IsolatesFrom Commercially Stored Apple Fruit. | Phytopathology | 2017 Mar | 27841961 |
| Edible coating composed of chitosan and Salvia fruticosa Mill. extract for thecontrol of grey mould of table grapes. | J Sci Food Agric | 2017 Jan | 27059447 |
| Chemometric-assisted QuEChERS extraction method for post-harvest pesticidedetermination in fruits and vegetables. | Sci Rep | 2017 Feb 22 | 28225030 |
| Distribution of Animal Drugs among Curd, Whey, and Milk Protein Fractions inSpiked Skim Milk and Whey. | J Agric Food Chem | 2017 Feb 1 | 28052193 |
| Evaluation of the Penetration of Multiple Classes of Pesticides in Fresh Produce Using Surface-Enhanced Raman Scattering Mapping. | J Food Sci | 2016 Oct 6 | 27711977 |
| Simultaneous determination of plant growth regulator and pesticides in beansprouts by liquid chromatography-tandem mass spectrometry. | Food Chem | 2016 Oct 1 | 27132845 |
| Residual Behaviors of Six Pesticides in Shiitake from Cultivation to Postharvest Drying Process and Risk Assessment. | J Agric Food Chem | 2016 Nov 30 | 27933868 |
| Molecular characterization, fitness and mycotoxin production of Fusarium graminearum laboratory strains resistant to benzimidazoles. | Pestic Biochem Physiol | 2016 Mar | 26969433 |
| Chronic dietary exposure to pesticide residues and associated risk in the French ELFE cohort of pregnant women. | Environ Int | 2016 Jul-Aug | 27187793 |
| Land Spreading of Wastewaters from the Fruit-Packaging Industry and Potential Effects on Soil Microbes: Effects of the Antioxidant Ethoxyquin and Its Metabolites on Ammonia Oxidizers. | Appl Environ Microbiol | 2016 Jan 15 | 26590271 |
| Distribution of Animal Drugs between Skim Milk and Milk Fat Fractions in SpikedWhole Milk: Understanding the Potential Impact on Commercial Milk Products. | J Agric Food Chem | 2016 Jan 13 | 26652058 |
| Detection of Aryl Hydrocarbon Receptor Activation by Some Chemicals in Food Usinga Reporter Gene Assay. | Foods | 2016 Feb 25 | 28231110 |
Targets
- General Function:
- Steroid 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. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
- Gene Name:
- CYP2C9
- Uniprot ID:
- P11712
- Molecular Weight:
- 55627.365 Da
References
- Afzelius L, Zamora I, Masimirembwa CM, Karlen A, Andersson TB, Mecucci S, Baroni M, Cruciani G: Conformer- and alignment-independent model for predicting structurally diverse competitive CYP2C9 inhibitors. J Med Chem. 2004 Feb 12;47(4):907-14. [14761192 ]
- General Function:
- Metalloexopeptidase activity
- Specific Function:
- Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). Required for normal progression through the cell cycle.
- Gene Name:
- METAP1
- Uniprot ID:
- P53582
- Molecular Weight:
- 43214.885 Da
References
- Altmeyer MA, Marschner A, Schiffmann R, Klein CD: Subtype-selectivity of metal-dependent methionine aminopeptidase inhibitors. Bioorg Med Chem Lett. 2010 Jul 15;20(14):4038-44. doi: 10.1016/j.bmcl.2010.05.093. Epub 2010 May 27. [20621724 ]
- General Function:
- Poly(a) rna binding
- Specific Function:
- Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val). The catalytic activity of human METAP2 toward Met-Val peptides is consistently two orders of magnitude higher than that of METAP1, suggesting that it is responsible for processing proteins containing N-terminal Met-Val and Met-Thr sequences in vivo.Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.
- Gene Name:
- METAP2
- Uniprot ID:
- P50579
- Molecular Weight:
- 52891.145 Da
References
- Altmeyer MA, Marschner A, Schiffmann R, Klein CD: Subtype-selectivity of metal-dependent methionine aminopeptidase inhibitors. Bioorg Med Chem Lett. 2010 Jul 15;20(14):4038-44. doi: 10.1016/j.bmcl.2010.05.093. Epub 2010 May 27. [20621724 ]
- General Function:
- Monovalent cation:proton antiporter activity
- Specific Function:
- Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfate, acyclovir, ganciclovir and also the zwitterionic cephalosporin, cephalexin and cephradin. Seems to also play a role in the uptake of oxaliplatin (a new platinum anticancer agent). Able to transport paraquat (PQ or N,N-dimethyl-4-4'-bipiridinium); a widely used herbicid. Responsible for the secretion of cationic drugs across the brush border membranes.
- Gene Name:
- SLC47A1
- Uniprot ID:
- Q96FL8
- Molecular Weight:
- 61921.585 Da
References
- Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM: Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J Med Chem. 2013 Feb 14;56(3):781-95. doi: 10.1021/jm301302s. Epub 2013 Jan 22. [23241029 ]
- General Function:
- Type i transforming growth factor beta receptor binding
- Specific Function:
- Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruites SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
- Gene Name:
- FKBP1A
- Uniprot ID:
- P62942
- Molecular Weight:
- 11950.665 Da
References
- Stebbins JL, Zhang Z, Chen J, Wu B, Emdadi A, Williams ME, Cashman J, Pellecchia M: Nuclear magnetic resonance fragment-based identification of novel FKBP12 inhibitors. J Med Chem. 2007 Dec 27;50(26):6607-17. Epub 2007 Nov 27. [18038971 ]
- General Function:
- Receptor binding
- Specific Function:
- Chemotactic for monocytes and T-lymphocytes. Binds to CXCR3.
- Gene Name:
- CXCL10
- Uniprot ID:
- P02778
- Molecular Weight:
- 10880.915 Da
References
- 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:
- May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
- Gene Name:
- MMP9
- Uniprot ID:
- P14780
- Molecular Weight:
- 78457.51 Da
References
- 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:
- Urokinase plasminogen activator receptor activity
- Specific Function:
- Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form.
- Gene Name:
- PLAUR
- Uniprot ID:
- Q03405
- Molecular Weight:
- 36977.62 Da
References
- 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:
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- 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. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen. Participates in the bioactivation of carcinogenic aromatic and heterocyclic amines. Catalizes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin.
- Gene Name:
- CYP1A2
- Uniprot ID:
- P05177
- Molecular Weight:
- 58293.76 Da
References
- 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:
- 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
- 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:
- Steroid 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. Acts as a 1,4-cineole 2-exo-monooxygenase.
- Gene Name:
- CYP2B6
- Uniprot ID:
- P20813
- Molecular Weight:
- 56277.81 Da
References
- 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:
- Transcription regulatory region dna binding
- Specific Function:
- Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
- Gene Name:
- AHR
- Uniprot ID:
- P35869
- Molecular Weight:
- 96146.705 Da
References
- 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
References
- 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:
- Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity.
- Gene Name:
- MMP1
- Uniprot ID:
- P03956
- Molecular Weight:
- 54006.61 Da
References
- 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:
- Sh2 domain binding
- Specific Function:
- Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. Mediates essential signaling events in both innate and adaptive immunity. In the cytoplasm, plays a pivotal role in signal transduction via its association with type I receptors such as growth hormone (GHR), prolactin (PRLR), leptin (LEPR), erythropoietin (EPOR), thrombopoietin (THPO); or type II receptors including IFN-alpha, IFN-beta, IFN-gamma and multiple interleukins. Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. Subsequently, phosphorylates the STATs proteins once they are recruited to the receptor. Phosphorylated STATs then form homodimer or heterodimers and translocate to the nucleus to activate gene transcription. For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. Then, STAT5 (STAT5A or STAT5B) is recruited, phosphorylated and activated by JAK2. Once activated, dimerized STAT5 translocates into the nucleus and promotes the transcription of several essential genes involved in the modulation of erythropoiesis. In addition, JAK2 mediates angiotensin-2-induced ARHGEF1 phosphorylation. Plays a role in cell cycle by phosphorylating CDKN1B. Cooperates with TEC through reciprocal phosphorylation to mediate cytokine-driven activation of FOS transcription. In the nucleus, plays a key role in chromatin by specifically mediating phosphorylation of 'Tyr-41' of histone H3 (H3Y41ph), a specific tag that promotes exclusion of CBX5 (HP1 alpha) from chromatin.
- Gene Name:
- JAK2
- Uniprot ID:
- O60674
- Molecular Weight:
- 130672.475 Da
References
- 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:
- 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, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression.
- Gene Name:
- CYP1B1
- Uniprot ID:
- Q16678
- Molecular Weight:
- 60845.33 Da
References
- 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:
- Protein serine/threonine/tyrosine kinase activity
- Specific Function:
- Mitotic serine/threonine kinases that contributes to the regulation of cell cycle progression. Associates with the centrosome and the spindle microtubules during mitosis and plays a critical role in various mitotic events including the establishment of mitotic spindle, centrosome duplication, centrosome separation as well as maturation, chromosomal alignment, spindle assembly checkpoint, and cytokinesis. Required for initial activation of CDK1 at centrosomes. Phosphorylates numerous target proteins, including ARHGEF2, BORA, BRCA1, CDC25B, DLGP5, HDAC6, KIF2A, LATS2, NDEL1, PARD3, PPP1R2, PLK1, RASSF1, TACC3, p53/TP53 and TPX2. Regulates KIF2A tubulin depolymerase activity. Required for normal axon formation. Plays a role in microtubule remodeling during neurite extension. Important for microtubule formation and/or stabilization. Also acts as a key regulatory component of the p53/TP53 pathway, and particularly the checkpoint-response pathways critical for oncogenic transformation of cells, by phosphorylating and stabilizing p53/TP53. Phosphorylates its own inhibitors, the protein phosphatase type 1 (PP1) isoforms, to inhibit their activity. Necessary for proper cilia disassembly prior to mitosis.
- Gene Name:
- AURKA
- Uniprot ID:
- O14965
- Molecular Weight:
- 45809.03 Da
References
- 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 ]