Rubratoxin B
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Basic Info
| Common Name | Rubratoxin B(F04977) |
| 2D Structure | |
| Description | Rubratoxin B is a mycotoxin produced by fungi such as Penicillum rubrum and Penicillum purpurogenum, which are common soil fungi that sometimes contaminate animal feeds. Rubratoxin B has been shown to be hepatotoxic, nephrotoxic, and splenotoxic. (A2985) |
| FRCD ID | F04977 |
| CAS Number | 21794-01-4 |
| PubChem CID | 11969548 |
| Formula | C26H30O11 |
| IUPAC Name | None |
| InChI Key | ZJTBTDVZNGBSNG-RETZLTROSA-N |
| InChI | InChI=1S/C26H30O11/c1-2-3-4-5-7-15(27)20-18-13(23(31)36-25(18)33)10-12(21(29)16-8-6-9-17(28)35-16)11-14-19(22(20)30)26(34)37-24(14)32/h6,9,12,15-16,20-22,27,29-30H,2-5,7-8,10-11H2,1H3/t12-,15+,16-,20+,21-,22-/m0/s1 |
| Canonical SMILES | CCCCCCC(C1C(C2=C(CC(CC3=C1C(=O)OC3=O)C(C4CC=CC(=O)O4)O)C(=O)OC2=O)O)O |
| Isomeric SMILES | CCCCCC[C@H]([C@H]1[C@H](C2=C(C[C@H](CC3=C1C(=O)OC3=O)[C@@H]([C@@H]4CC=CC(=O)O4)O)C(=O)OC2=O)O)O |
| Synonyms |
UNII-J38U4758MY
EINECS 244-582-6
RUBRATOXIN B
J38U4758MY
21794-01-4
CCRIS 4939
HSDB 3533
NSC126729
NSC 126729
BRN 1633114
|
| 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 | Pentacarboxylic acids and derivatives |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Pentacarboxylic acids and derivatives |
| Alternative Parents | |
| Molecular Framework | Aliphatic heteropolycyclic compounds |
| Substituents | Pentacarboxylic acid or derivatives - Fatty alcohol - Dihydropyranone - 2-furanone - Fatty acyl - Pyran - Carboxylic acid anhydride - Dihydrofuran - Alpha,beta-unsaturated carboxylic ester - Enoate ester - Carboxylic acid ester - Lactone - Secondary alcohol - Organoheterocyclic compound - Oxacycle - Hydrocarbon derivative - Alcohol - Organic oxide - Carbonyl group - Organooxygen compound - Organic oxygen compound - Aliphatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as pentacarboxylic acids and derivatives. These are carboxylic acids containing exactly five carboxyl groups. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 518.515 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 11 |
| Rotatable Bond Count | 8 |
| Complexity | 1100 |
| Monoisotopic Mass | 518.179 |
| Exact Mass | 518.179 |
| XLogP | 2 |
| Formal Charge | 0 |
| Heavy Atom Count | 37 |
| Defined Atom Stereocenter Count | 6 |
| 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+ | 0.7141 |
| Human Intestinal Absorption | HIA+ | 0.9569 |
| Caco-2 Permeability | Caco2- | 0.7037 |
| P-glycoprotein Substrate | Substrate | 0.7623 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.8445 |
| Non-inhibitor | 0.8900 | |
| Renal Organic Cation Transporter | Non-inhibitor | 0.8680 |
| Distribution | ||
| Subcellular localization | Mitochondria | 0.8173 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8706 |
| CYP450 2D6 Substrate | Non-substrate | 0.8782 |
| CYP450 3A4 Substrate | Substrate | 0.5722 |
| CYP450 1A2 Inhibitor | Non-inhibitor | 0.8122 |
| CYP450 2C9 Inhibitor | Non-inhibitor | 0.8976 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.9095 |
| CYP450 2C19 Inhibitor | Non-inhibitor | 0.8369 |
| CYP450 3A4 Inhibitor | Non-inhibitor | 0.5415 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.9099 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.8489 |
| Non-inhibitor | 0.8155 | |
| AMES Toxicity | Non AMES toxic | 0.6981 |
| Carcinogens | Non-carcinogens | 0.9773 |
| Fish Toxicity | High FHMT | 0.9792 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.9955 |
| Honey Bee Toxicity | High HBT | 0.7698 |
| Biodegradation | Not ready biodegradable | 0.7342 |
| Acute Oral Toxicity | II | 0.7169 |
| Carcinogenicity (Three-class) | Non-required | 0.5227 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.6116 | LogS |
| Caco-2 Permeability | 0.1838 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 3.0818 | LD50, mol/kg |
| Fish Toxicity | 1.0767 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.6734 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Rubratoxin-B-induced secretion of chemokine ligands of cysteine-cysteine motif chemokine receptor 5 (CCR5) and its dependence on heat shock protein 90 in HL60 cells. | Environ Toxicol Pharmacol | 2015 Nov | 26595743 |
| Rubratoxin B induces signs of fatty acid oxidation disorders (FAODs) in mice. | Toxicol Lett | 2011 Oct 10 | 21835235 |
| Rubratoxin B induces interleukin-6 secretion in mouse white adipose tissues and 3T3-L1 adipocytes. | Toxicol Lett | 2008 Nov 10 | 18804154 |
| Induced secretion of insulin-like growth factor binding protein-1 (IGFBP-1) in human hepatoma cell HepG2 by rubratoxin B. | Arch Toxicol | 2007 May | 17109117 |
| Induced secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) in vivo and in vitro by hepatotoxin rubratoxin B. | Food Chem Toxicol | 2006 Jul | 16530906 |
| Stress-activated MAP kinases regulate rubratoxin B-caused cytotoxicity and cytokine secretion in hepatocyte-derived HepG2 cells. | Toxicol Lett | 2005 Feb 15 | 15603921 |
| Penicillium expansum: consistent production of patulin, chaetoglobosins, and other secondary metabolites in culture and their natural occurrence in fruit products. | J Agric Food Chem | 2004 Apr 21 | 15080656 |
| Rubratoxin B induced the secretion of hepatic injury-related colony stimulating factors in human hepatoma cells. | Toxicol Lett | 2003 Nov 30 | 14581167 |
| Hepatotoxin rubratoxin B induced the secretion of TNF-alpha, IL-8, and MCP-1 in HL60 cells. | Biochem Biophys Res Commun | 2001 Oct 5 | 11573937 |
| Calcium channel blockers verapamil and diltiazem impaired rubratoxin B-caused toxicity in HL60 cells. | Toxicol Lett | 2000 Dec 20 | 11137308 |
| Physionutritional effects of rubratoxin-B on rabbits. | Arch Tierernahr | 1988 Sep | 3214267 |
| Rubratoxin B mycotoxicosis in the Swiss ICR mouse. | Food Chem Toxicol | 1988 May | 3391470 |
| Rubratoxin B mycotoxicosis in the Syrian hamster. | Food Chem Toxicol | 1987 Sep | 3653822 |
| Rubratoxin B mycotoxicosis in the Mongolian gerbil. | Food Chem Toxicol | 1987 Nov | 2961671 |
| Mycotoxins in cereal grain. Part XI. Simple multidetection procedure for determination of 11 mycotoxins in cereals. | Nahrung | 1985 | 3158819 |
| Growth of larvae of Tenebrio molitor L. fed diets containing penicillic acid, aflatoxin B1, ochratoxin A, or rubratoxin B at three dietary protein levels (1). | Arch Int Physiol Biochim | 1982 Nov | 6188434 |
| Procedure for minimizing losses in sample processing and assay of rubratoxin B from mixed feed. | J Agric Food Chem | 1981 Nov-Dec | 6895639 |
| Effects of mycotoxins on mixed-function oxidase and adenosine triphosphatase systems in neonatal rats. I. aflatoxin B1/rubratoxin B. | Food Cosmet Toxicol | 1980 Jun | 6448193 |
| Detection of rubratoxin B and seven other mycotoxins in corn. | J Agric Food Chem | 1980 Jul-Aug | 6893994 |
| In vitro metabolism of [14C]rubratoxin B by rat hepatic subcellular fractions. | Food Cosmet Toxicol | 1979 Apr | 39021 |
Targets
- 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:
- Rubratoxin A is a potent inhibitor of protein phosphatase 2A, exerting antitumor and antimetastatic effects. Inhibition may cause the phosphorylation of CREB and subsequent activation of natural killer cells via the stimulation of interleukin-2 release from T cells, contributing to antimetastatic effects. Focal adhesion kinase phosphorylation and paxillin phosphorylation that interfere with cell adhesion could be another antimetastatic effect.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- 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
- Mechanism of Action:
- Rubratoxin B inhibits the activity of matrix metalloproteinase-2 and -9.
References
- Wang T, Zhang Y, Wang Y, Pei YH: Anti-tumor effects of Rubratoxin B on cell toxicity, inhibition of cell proliferation, cytotoxic activity and matrix metalloproteinase-2,9. Toxicol In Vitro. 2007 Jun;21(4):646-50. Epub 2007 Jan 11. [17306501 ]
- 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:
- Rubratoxin A is a potent inhibitor of protein phosphatase 2A, exerting antitumor and antimetastatic effects. Inhibition may cause the phosphorylation of CREB and subsequent activation of natural killer cells via the stimulation of interleukin-2 release from T cells, contributing to antimetastatic effects. Focal adhesion kinase phosphorylation and paxillin phosphorylation that interfere with cell adhesion could be another antimetastatic effect.
References
- Wada S, Usami I, Umezawa Y, Inoue H, Ohba S, Someno T, Kawada M, Ikeda D: Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis. Cancer Sci. 2010 Mar;101(3):743-50. doi: 10.1111/j.1349-7006.2009.01438.x. Epub 2009 Nov 14. [20028386 ]
- General Function:
- Steroid hormone binding
- Specific Function:
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
- Gene Name:
- ATP1A1
- Uniprot ID:
- P05023
- Molecular Weight:
- 112895.01 Da
- Mechanism of Action:
- Rubratoxin B inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Steroid hormone binding
- Specific Function:
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients.
- Gene Name:
- ATP1A2
- Uniprot ID:
- P50993
- Molecular Weight:
- 112264.385 Da
- Mechanism of Action:
- Rubratoxin B inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Steroid hormone binding
- Specific Function:
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients.
- Gene Name:
- ATP1A3
- Uniprot ID:
- P13637
- Molecular Weight:
- 111747.51 Da
- Mechanism of Action:
- Rubratoxin B inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Sodium:potassium-exchanging atpase activity
- Specific Function:
- This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. Plays a role in sperm motility.
- Gene Name:
- ATP1A4
- Uniprot ID:
- Q13733
- Molecular Weight:
- 114165.44 Da
- Mechanism of Action:
- Rubratoxin B inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Sodium:potassium-exchanging atpase activity
- Specific Function:
- This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane.Involved in cell adhesion and establishing epithelial cell polarity.
- Gene Name:
- ATP1B1
- Uniprot ID:
- P05026
- Molecular Weight:
- 35061.07 Da
- Mechanism of Action:
- Rubratoxin B inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Sodium:potassium-exchanging atpase activity
- Specific Function:
- This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-2 subunit is not known.Mediates cell adhesion of neurons and astrocytes, and promotes neurite outgrowth.
- Gene Name:
- ATP1B2
- Uniprot ID:
- P14415
- Molecular Weight:
- 33366.925 Da
- Mechanism of Action:
- Rubratoxin B inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Sodium:potassium-exchanging atpase activity
- Specific Function:
- This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-3 subunit is not known.
- Gene Name:
- ATP1B3
- Uniprot ID:
- P54709
- Molecular Weight:
- 31512.34 Da
- Mechanism of Action:
- Rubratoxin B inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- General Function:
- Transporter activity
- Specific Function:
- May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.
- Gene Name:
- FXYD2
- Uniprot ID:
- P54710
- Molecular Weight:
- 7283.265 Da
- Mechanism of Action:
- Rubratoxin B inhibits Na+/K+-transporting ATPases in the brain.
References
- Phillips TD, Hayes AW: Structural modification of polyfunctional rubratoxin B: effects on mammalian adenosine triphosphatase. J Environ Pathol Toxicol. 1979 Jan-Feb;2(3):853-60. [217944 ]
- 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:
- 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:
- 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:
- Protein serine/threonine phosphatase activity
- Specific Function:
- The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Required for proper chromosome segregation and for centromeric localization of SGOL1 in mitosis.
- Gene Name:
- PPP2R1A
- Uniprot ID:
- P30153
- Molecular Weight:
- 65307.81 Da
- Mechanism of Action:
- Rubratoxin A is a potent inhibitor of protein phosphatase 2A, exerting antitumor and antimetastatic effects. Inhibition may cause the phosphorylation of CREB and subsequent activation of natural killer cells via the stimulation of interleukin-2 release from T cells, contributing to antimetastatic effects. Focal adhesion kinase phosphorylation and paxillin phosphorylation that interfere with cell adhesion could be another antimetastatic effect.
References
- Wada S, Usami I, Umezawa Y, Inoue H, Ohba S, Someno T, Kawada M, Ikeda D: Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis. Cancer Sci. 2010 Mar;101(3):743-50. doi: 10.1111/j.1349-7006.2009.01438.x. Epub 2009 Nov 14. [20028386 ]
- General Function:
- Zinc ion binding
- Specific Function:
- Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.
- Gene Name:
- MMP2
- Uniprot ID:
- P08253
- Molecular Weight:
- 73881.695 Da
- Mechanism of Action:
- Rubratoxin B inhibits the activity of matrix metalloproteinase-2 and -9.
References
- Wang T, Zhang Y, Wang Y, Pei YH: Anti-tumor effects of Rubratoxin B on cell toxicity, inhibition of cell proliferation, cytotoxic activity and matrix metalloproteinase-2,9. Toxicol In Vitro. 2007 Jun;21(4):646-50. Epub 2007 Jan 11. [17306501 ]
- General Function:
- Protein phosphatase type 2a regulator activity
- Specific Function:
- The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit.
- Gene Name:
- PPP2R1B
- Uniprot ID:
- P30154
- Molecular Weight:
- 66212.77 Da
- Mechanism of Action:
- Rubratoxin A is a potent inhibitor of protein phosphatase 2A, exerting antitumor and antimetastatic effects. Inhibition may cause the phosphorylation of CREB and subsequent activation of natural killer cells via the stimulation of interleukin-2 release from T cells, contributing to antimetastatic effects. Focal adhesion kinase phosphorylation and paxillin phosphorylation that interfere with cell adhesion could be another antimetastatic effect.
References
- Wada S, Usami I, Umezawa Y, Inoue H, Ohba S, Someno T, Kawada M, Ikeda D: Rubratoxin A specifically and potently inhibits protein phosphatase 2A and suppresses cancer metastasis. Cancer Sci. 2010 Mar;101(3):743-50. doi: 10.1111/j.1349-7006.2009.01438.x. Epub 2009 Nov 14. [20028386 ]
- 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:
- 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:
- 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 ]