Fumonisin B1
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Basic Info
| Common Name | Fumonisin B1(F04877) |
| 2D Structure | |
| Description | Fumonisin B1 is from Fusarium moniliforme Fumonisin B1 is an inhibitor of ceramide synthase. Fumonisin B1 belongs to the family of Monoterpenes. These are compounds contaning a chain of two isoprene units. |
| FRCD ID | F04877 |
| CAS Number | 116355-83-0 |
| PubChem CID | 3431 |
| Formula | C34H59NO15 |
| IUPAC Name | 2-[2-[19-amino-6-(3,4-dicarboxybutanoyloxy)-11,16,18-trihydroxy-5,9-dimethylicosan-7-yl]oxy-2-oxoethyl]butanedioic acid |
| InChI Key | UVBUBMSSQKOIBE-UHFFFAOYSA-N |
| InChI | InChI=1S/C34H59NO15/c1-5-6-9-20(3)32(50-31(44)17-23(34(47)48)15-29(41)42)27(49-30(43)16-22(33(45)46)14-28(39)40)13-19(2)12-24(36)10-7-8-11-25(37)18-26(38)21(4)35/h19-27,32,36-38H,5-18,35H2,1-4H3,(H,39,40)(H,41,42)(H,45,46)(H,47,48) |
| Canonical SMILES | CCCCC(C)C(C(CC(C)CC(CCCCC(CC(C(C)N)O)O)O)OC(=O)CC(CC(=O)O)C(=O)O)OC(=O)CC(CC(=O)O)C(=O)O |
| Isomeric SMILES | CCCCC(C)C(C(CC(C)CC(CCCCC(CC(C(C)N)O)O)O)OC(=O)CC(CC(=O)O)C(=O)O)OC(=O)CC(CC(=O)O)C(=O)O |
| Wikipedia | Fumonisin B1 |
| Synonyms |
fumonisin b1
Macrofusin
Macrofusine
Fumonisin B1, Fusarium moniliforme
NSC629151
116355-83-0
FB1
Fungal metabolite from Fusarium monliforme
AC1L1FX5
AC1Q5V8H
|
| Classifies |
Fungal Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Organic acids and derivatives |
| Class | Carboxylic acids and derivatives |
| Subclass | Fumonisins |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Fumonisins |
| Alternative Parents | |
| Molecular Framework | Aliphatic acyclic compounds |
| Substituents | Fumonisin-skeleton - Fumonisin skeleton - Hexacarboxylic acid or derivatives - Fatty acid ester - Fatty acyl - 1,2-aminoalcohol - Amino acid or derivatives - Carboxylic acid ester - Secondary alcohol - Amino acid - Polyol - Carboxylic acid - Organooxygen compound - Organonitrogen compound - Primary aliphatic amine - Organopnictogen compound - Organic oxygen compound - Organic nitrogen compound - Carbonyl group - Primary amine - Amine - Organic oxide - Alcohol - Hydrocarbon derivative - Aliphatic acyclic compound |
| Description | This compound belongs to the class of organic compounds known as fumonisins. These are diesters of propane-1,2,3-tricarboxylic acid (TCA) and similar long-chain aminopolyol backbones (for FB1: 2S-amino-12S,16R-dimethyl-3S,5R,10R,14S,15R-pentahydroxyeicosane). Structurally, fumonisins resemble the sphingoid bases sphinganine (SA) and sphingosine (SO) to which TCA groups have been added at the C-14 and C-15 positions. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 721.838 |
| Hydrogen Bond Donor Count | 8 |
| Hydrogen Bond Acceptor Count | 16 |
| Rotatable Bond Count | 31 |
| Complexity | 1070 |
| Monoisotopic Mass | 721.388 |
| Exact Mass | 721.388 |
| XLogP | -0.5 |
| Formal Charge | 0 |
| Heavy Atom Count | 50 |
| Defined Atom Stereocenter Count | 0 |
| Undefined Atom Stereocenter Count | 10 |
| 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+ | 0.5619 |
| Human Intestinal Absorption | HIA+ | 0.5634 |
| Caco-2 Permeability | Caco2- | 0.7199 |
| P-glycoprotein Substrate | Substrate | 0.5704 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8210 |
| Inhibitor | 0.5955 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.9648 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.5542 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8843 |
| CYP450 2D6 Substrate | Non-substrate | 0.8295 |
| CYP450 3A4 Substrate | Non-substrate | 0.6124 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.5945 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8342 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.8325 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.7989 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.6368 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9392 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9872 |
| Non-inhibitor | 0.8509 | |
| AMES Toxicity | Non AMES toxic | 0.9132 |
| Carcinogens | Non-carcinogens | 0.8856 |
| Fish Toxicity | High FHMT | 0.8887 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9969 |
| Honey Bee Toxicity | Low HBT | 0.5187 |
| Biodegradation | Not ready biodegradable | 0.5092 |
| Acute Oral Toxicity | III | 0.6849 |
| Carcinogenicity (Three-class) | Non-required | 0.6442 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -2.1266 | LogS |
| Caco-2 Permeability | -0.4619 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.1733 | LD50, mol/kg |
| Fish Toxicity | 1.8001 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.5213 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Contaminants in Grain-A Major Risk for Whole Grain Safety? | Nutrients | 2018 Sep 2 | 30200531 |
| Fumonisin B<sub>1</sub> exposure increases Hsp70 expression in the lung and kidney of rats without inducing significant oxidative stress. | Acta Vet Hung | 2018 Sep | 30264617 |
| Fumonisins and their analogues in contaminated corn and its processed foods - a review. | Food Addit Contam Part A Chem Anal Control Expo Risk Assess | 2018 Oct 12 | 30028638 |
| Encapsulation of cinnamon essential oil in whey protein enhances the protective effect against single or combined sub-chronic toxicity of fumonisin B<sub>1</sub> and/or aflatoxin B<sub>1</sub> in rats. | Environ Sci Pollut Res Int | 2018 Oct | 30112645 |
| Assessing the combined toxicity of the natural toxins, aflatoxin B<sub>1</sub>, fumonisin B<sub>1</sub> and microcystin-LR by high content analysis. | Food Chem Toxicol | 2018 Nov | 30253246 |
| Toxicological effects of fumonisin B<sub>1</sub> in combination with other Fusarium toxins. | Food Chem Toxicol | 2018 Nov | 30248478 |
| Stability of fumonisin B<sub>1</sub>, deoxynivalenol, zearalenone, and T-2 toxin during processing of traditional Nigerian beer and spices. | Mycotoxin Res | 2018 Nov | 29725912 |
| Evaluation of gaseous allyl isothiocyanate against the growth of mycotoxigenic fungi and mycotoxin production in corn stored for 6 months. | J Sci Food Agric | 2018 Nov | 29652439 |
| Mycotoxins in commercial dry pet food in China. | Food Addit Contam Part B Surveill | 2018 May 10 | 29747556 |
| Optimized QuEChERS Method Combined with UHPLC-MS/MS for the Simultaneous Determination of 15 Mycotoxins in Liquorice. | J AOAC Int | 2018 May 1 | 29073944 |
| Modulation of key lipid raft constituents in primary rat hepatocytes by fumonisin B<sub>1</sub> - Implications for cancer promotion in the liver. | Food Chem Toxicol | 2018 May | 29510220 |
| Effects of T-2 and Fumonisin B1 combined treatment on in vitro mouse embryo development and blastocyst quality. | Toxicol Ind Health | 2018 May | 29591888 |
| Three kinds of lateral flow immunochromatographic assays based on the use ofnanoparticle labels for fluorometric determination of zearalenone. | Mikrochim Acta | 2018 Mar 24 | 29594745 |
| Effects of fumonisin B1 and mycotoxin binders on growth performance, tibia characteristics, gut physiology, and stress indicators in broiler chickens raised in different stocking densities. | Poult Sci | 2018 Mar 1 | 29272444 |
| Multimycotoxin and fungal analysis of maize grains from south and southwestern Ethiopia. | Food Addit Contam Part B Surveill | 2018 Mar | 29258380 |
| Production of fumonisins by endophytic strains of Tolypocladium cylindrosporumand its relation to fungal virus infection. | Mycotoxin Res | 2018 Mar | 29143925 |
| Fumonisin-Exposure Impairs Age-Related Ecological Succession of Bacterial Speciesin Weaned Pig Gut Microbiota. | Toxins (Basel) | 2018 Jun 5 | 29874877 |
| Determination of mycotoxins by HPLC, LC-ESI-MS/MS, and MALDI-TOF MS in Fusariumspecies-infected sugarcane. | Microb Pathog | 2018 Jun 30 | 29964151 |
| <i>Fusarium</i> Molds and Mycotoxins: Potential Species-Specific Effects. | Toxins (Basel) | 2018 Jun 15 | 29914090 |
| Effects of fusariotoxin co-exposure on THP-1 human immune cells. | Cell Biol Toxicol | 2018 Jun | 28822000 |
Targets
- General Function:
- Signal transducer activity
- Specific Function:
- Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling. Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB.
- Gene Name:
- PPM1A
- Uniprot ID:
- P35813
- Molecular Weight:
- 42447.455 Da
- Mechanism of Action:
- Fumonisin B1's carcinogenicity is thought to be caused by its inhibition of protein serine/threonine phosphatases.
References
- Fukuda H, Shima H, Vesonder RF, Tokuda H, Nishino H, Katoh S, Tamura S, Sugimura T, Nagao M: Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin. Biochem Biophys Res Commun. 1996 Mar 7;220(1):160-5. [8602837 ]
- 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
- Mechanism of Action:
- Fumonisin B1's carcinogenicity is thought to be caused by its inhibition of protein serine/threonine phosphatases.
References
- Fukuda H, Shima H, Vesonder RF, Tokuda H, Nishino H, Katoh S, Tamura S, Sugimura T, Nagao M: Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin. Biochem Biophys Res Commun. 1996 Mar 7;220(1):160-5. [8602837 ]
- General Function:
- Protein serine/threonine phosphatase activity
- Specific Function:
- Calcium-dependent, calmodulin-stimulated protein phosphatase. Many of the substrates contain a PxIxIT motif. This subunit may have a role in the calmodulin activation of calcineurin. Dephosphorylates DNM1L, HSPB1 and SSH1.
- Gene Name:
- PPP3CA
- Uniprot ID:
- Q08209
- Molecular Weight:
- 58687.27 Da
- Mechanism of Action:
- Fumonisin B1's carcinogenicity is thought to be caused by its inhibition of protein serine/threonine phosphatases.
References
- Fukuda H, Shima H, Vesonder RF, Tokuda H, Nishino H, Katoh S, Tamura S, Sugimura T, Nagao M: Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin. Biochem Biophys Res Commun. 1996 Mar 7;220(1):160-5. [8602837 ]
- General Function:
- Protein serine/threonine phosphatase activity
- Specific Function:
- Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin.
- Gene Name:
- PPP3CB
- Uniprot ID:
- P16298
- Molecular Weight:
- 59023.735 Da
- Mechanism of Action:
- Fumonisin B1's carcinogenicity is thought to be caused by its inhibition of protein serine/threonine phosphatases.
References
- Fukuda H, Shima H, Vesonder RF, Tokuda H, Nishino H, Katoh S, Tamura S, Sugimura T, Nagao M: Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin. Biochem Biophys Res Commun. 1996 Mar 7;220(1):160-5. [8602837 ]
- General Function:
- Phosphoprotein phosphatase activity
- Specific Function:
- Calcium-dependent, calmodulin-stimulated protein phosphatase. This subunit may have a role in the calmodulin activation of calcineurin.
- Gene Name:
- PPP3CC
- Uniprot ID:
- P48454
- Molecular Weight:
- 58128.865 Da
- Mechanism of Action:
- Fumonisin B1's carcinogenicity is thought to be caused by its inhibition of protein serine/threonine phosphatases.
References
- Fukuda H, Shima H, Vesonder RF, Tokuda H, Nishino H, Katoh S, Tamura S, Sugimura T, Nagao M: Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin. Biochem Biophys Res Commun. 1996 Mar 7;220(1):160-5. [8602837 ]
- General Function:
- Protein serine/threonine phosphatase activity
- Specific Function:
- Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Dephosphorylates RPS6KB1. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).
- Gene Name:
- PPP1CC
- Uniprot ID:
- P36873
- Molecular Weight:
- 36983.4 Da
- Mechanism of Action:
- Fumonisin B1's carcinogenicity is thought to be caused by its inhibition of protein serine/threonine phosphatases.
References
- Fukuda H, Shima H, Vesonder RF, Tokuda H, Nishino H, Katoh S, Tamura S, Sugimura T, Nagao M: Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin. Biochem Biophys Res Commun. 1996 Mar 7;220(1):160-5. [8602837 ]
- General Function:
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function:
- Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
- Gene Name:
- SLC22A11
- Uniprot ID:
- Q9NSA0
- Molecular Weight:
- 59970.945 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
- General Function:
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function:
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-independent uptake of p-aminohippurate (PAH), ochratoxin (OTA), acyclovir (ACV), 3'-azido-3-'deoxythymidine (AZT), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), hippurate (HA), indoleacetate (IA), indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF), cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl) guanine (PMEG), 9-(2-phosphonylmethoxyethyl) diaminopurine (PMEDAP) and edaravone sulfate. PAH uptake is inhibited by p-chloromercuribenzenesulphonate (PCMBS), diethyl pyrocarbonate (DEPC), sulindac, diclofenac, carprofen, glutarate and okadaic acid (By similarity). PAH uptake is inhibited by benzothiazolylcysteine (BTC), S-chlorotrifluoroethylcysteine (CTFC), cysteine S-conjugates S-dichlorovinylcysteine (DCVC), furosemide, steviol, phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, benzylpenicillin, furosemide, indomethacin, bumetamide, losartan, probenecid, phenol red, urate, and alpha-ketoglutarate.
- Gene Name:
- SLC22A6
- Uniprot ID:
- Q4U2R8
- Molecular Weight:
- 61815.78 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
- General Function:
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function:
- Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulfate, allopurinol, 5-fluorouracil, paclitaxel, L-ascorbic acid, salicylate, ethotrexate, and alpha-ketoglutarate.
- Gene Name:
- SLC22A7
- Uniprot ID:
- Q9Y694
- Molecular Weight:
- 60025.025 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
- General Function:
- Toxic substance binding
- Specific Function:
- Is indirectly involved in the control of blood pressure.
- Gene Name:
- ASS1
- Uniprot ID:
- P00966
- Molecular Weight:
- 46530.055 Da
- Mechanism of Action:
- Fumonisin B1 inhibits the enzyme argininosuccinate synthase.
References
- Jenkins GR, Tolleson WH, Newkirk DK, Roberts DW, Rowland KL, Saheki T, Kobayashi K, Howard PC, Melchior WB Jr: Identification of fumonisin B1 as an inhibitor of argininosuccinate synthetase using fumonisin affinity chromatography and in vitro kinetic studies. J Biochem Mol Toxicol. 2000;14(6):320-8. [11083085 ]
- General Function:
- Ceramide glucosyltransferase activity
- Specific Function:
- Catalyzes the first glycosylation step in glycosphingolipid biosynthesis, the transfer of glucose to ceramide. May also serve as a "flippase".
- Gene Name:
- UGCG
- Uniprot ID:
- Q16739
- Molecular Weight:
- 44853.255 Da
- Mechanism of Action:
- Fumonisins are similar in structure to the long-chain base backbones of sphingolipids, allowing it to inhibit of the biosynthesis of sphingosine and more complex sphingolipids by inhibiting the enzyme ceramide synthase. This causes the accumulation of sphinganine, sphingosine, and possibly also sphingosine 1-phosphate in cells and tissues, leading to apoptosis.
References
- Stockmann-Juvala H, Savolainen K: A review of the toxic effects and mechanisms of action of fumonisin B1. Hum Exp Toxicol. 2008 Nov;27(11):799-809. doi: 10.1177/0960327108099525. [19244287 ]
- 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
- Mechanism of Action:
- Fumonisin B1's carcinogenicity is thought to be caused by its inhibition of protein serine/threonine phosphatases.
References
- Fukuda H, Shima H, Vesonder RF, Tokuda H, Nishino H, Katoh S, Tamura S, Sugimura T, Nagao M: Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin. Biochem Biophys Res Commun. 1996 Mar 7;220(1):160-5. [8602837 ]
- General Function:
- Signal transducer activity
- Specific Function:
- Serine/threonine-protein phosphatase that dephosphorylates a myriad of proteins involved in different signaling pathways including the kinases CSNK1E, ASK1/MAP3K5, PRKDC and RAF1, the nuclear receptors NR3C1, PPARG, ESR1 and ESR2, SMAD proteins and TAU/MAPT. Implicated in wide ranging cellular processes, including apoptosis, differentiation, DNA damage response, cell survival, regulation of ion channels or circadian rhythms, in response to steroid and thyroid hormones, calcium, fatty acids, TGF-beta as well as oxidative and genotoxic stresses. Participates in the control of DNA damage response mechanisms such as checkpoint activation and DNA damage repair through, for instance, the regulation ATM/ATR-signaling and dephosphorylation of PRKDC and TP53BP1. Inhibits ASK1/MAP3K5-mediated apoptosis induced by oxidative stress. Plays a positive role in adipogenesis, mainly through the dephosphorylation and activation of PPARG transactivation function. Also dephosphorylates and inhibits the anti-adipogenic effect of NR3C1. Regulates the circadian rhythms, through the dephosphorylation and activation of CSNK1E. May modulate TGF-beta signaling pathway by the regulation of SMAD3 phosphorylation and protein expression levels. Dephosphorylates and may play a role in the regulation of TAU/MAPT. Through their dephosphorylation, may play a role in the regulation of ions channels such as KCNH2.
- Gene Name:
- PPP5C
- Uniprot ID:
- P53041
- Molecular Weight:
- 56878.22 Da
- Mechanism of Action:
- Fumonisin B1's carcinogenicity is thought to be caused by its inhibition of protein serine/threonine phosphatases.
References
- Fukuda H, Shima H, Vesonder RF, Tokuda H, Nishino H, Katoh S, Tamura S, Sugimura T, Nagao M: Inhibition of protein serine/threonine phosphatases by fumonisin B1, a mycotoxin. Biochem Biophys Res Commun. 1996 Mar 7;220(1):160-5. [8602837 ]
- General Function:
- Secondary active organic cation transmembrane transporter activity
- Specific Function:
- Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
- Gene Name:
- SLC22A1
- Uniprot ID:
- O15245
- Molecular Weight:
- 61153.345 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
- General Function:
- Quaternary ammonium group transmembrane transporter activity
- Specific Function:
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creatinine, amantadine, memantine, acriflavine, 4-[4-(dimethylamino)-styryl]-N-methylpyridinium ASP, amiloride, metformin, N-1-methylnicotinamide (NMN), tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, cisplatin and oxaliplatin. Cisplatin may develop a nephrotoxic action. Transport of creatinine is inhibited by fluoroquinolones such as DX-619 and LVFX. This transporter is a major determinant of the anticancer activity of oxaliplatin and may contribute to antitumor specificity.
- Gene Name:
- SLC22A2
- Uniprot ID:
- O15244
- Molecular Weight:
- 62579.99 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]
- General Function:
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function:
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
- Gene Name:
- SLC22A8
- Uniprot ID:
- Q8TCC7
- Molecular Weight:
- 59855.585 Da
- Mechanism of Action:
- Mycotoxins are often able to enter the liver and kidney by human organic anion transporters (hOATs) and human organic cation transporters (hOCTs). They can also inhibit uptake of anions and cations by these transporters, interefering with the secretion of endogenous metabolites, drugs, and xenobiotics including themselves. This results in increased cellular accumulation of toxic compounds causing nephro- and hepatotoxicity.
References
- Tachampa K, Takeda M, Khamdang S, Noshiro-Kofuji R, Tsuda M, Jariyawat S, Fukutomi T, Sophasan S, Anzai N, Endou H: Interactions of organic anion transporters and organic cation transporters with mycotoxins. J Pharmacol Sci. 2008 Mar;106(3):435-43. Epub 2008 Mar 5. [18319568 ]