Rubratoxin A (T3D3731)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (12)XML
Targets (12)
Record Information
Version2.0
Creation Date2010-05-05 14:57:46 UTC
Update Date2014-12-24 20:26:27 UTC
Accession NumberT3D3731
Identification
Common NameRubratoxin A
ClassSmall Molecule
DescriptionRubratoxin A is a mycotoxin produced by fungi such as Penicillum rubrum and Penicillum purpurogenum, which are common soil fungi that sometimes contaminate animal feeds. Rubratoxins have been shown to be hepatotoxic, nephrotoxic, and splenotoxic. Studies on Rubratoxin A however have also indicated it may also have valuable antitumor and antimetastatic effects. (1, 4)
Compound Type
  • Ester
  • Fungal Toxin
  • Mycotoxin
  • Natural Compound
  • Organic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
10-((3,6-Dihydro-6-oxo-2H-pyran-2-yl)hydroxymethyl)-4,5,8,9,10,11-hexahydro-4,8-dihydroxy-5-(1-hydroxyheptyl)-1H-cyclonona(1,2-c:5,6-c')difuran-1,3,6-trione
5-19-08-00329 (Beilstein Handbook Reference)
Rubratoxin
Rubratoxin a
Chemical FormulaC26H32O11
Average Molecular Mass520.526 g/mol
Monoisotopic Mass520.194 g/mol
CAS Registry Number22467-31-8
IUPAC Name3,13-dihydroxy-10-[hydroxy(6-oxo-3,6-dihydro-2H-pyran-2-yl)methyl]-2-(1-hydroxyheptyl)-6,14-dioxatricyclo[10.3.0.0⁴,⁸]pentadeca-1(12),4(8)-diene-5,7,15-trione
Traditional Namerubratoxin A
SMILESCCCCCCC(O)C1C(O)C2=C(CC(CC3=C1C(=O)OC3O)C(O)C1CC=CC(=O)O1)C(=O)OC2=O
InChI IdentifierInChI=1S/C26H32O11/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/h6,9,12,15-16,20-23,27,29-31H,2-5,7-8,10-11H2,1H3
InChI KeyInChIKey=XOEFANNJIKAWGX-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as tetracarboxylic acids and derivatives. These are carboxylic acids containing exactly four carboxyl groups.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassCarboxylic acids and derivatives
Sub ClassTetracarboxylic acids and derivatives
Direct ParentTetracarboxylic acids and derivatives
Alternative Parents
Substituents
  • Tetracarboxylic 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
  • Hemiacetal
  • Lactone
  • Secondary alcohol
  • Organoheterocyclic compound
  • Oxacycle
  • Hydrocarbon derivative
  • Alcohol
  • Organic oxide
  • Organic oxygen compound
  • Organooxygen compound
  • Carbonyl group
  • Aliphatic heteropolycyclic compound
Molecular FrameworkAliphatic heteropolycyclic compounds
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.51 g/LALOGPS
logP1.03ALOGPS
logP1.84ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)5.82ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area176.89 ŲChemAxon
Rotatable Bond Count8ChemAxon
Refractivity126.97 m³·mol⁻¹ChemAxon
Polarizability52.8 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0uki-0000950000-7dab2fb6e40a70c46ab92016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fbi-2002920000-eb130d29e6a6b2f8c4bc2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00or-8009700000-6d3e8e7485ab269744dd2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00or-0000950000-15f346a9acb50bd3c1562016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-1104920000-2776f3274c8bf8769f482016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-06rf-9007700000-03fc72dc99c97d1eba362016-08-03View Spectrum
Toxicity Profile
Route of ExposureOral, dermal, inhalation, and parenteral (contaminated drugs). (5)
Mechanism of ToxicityRubratoxin 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. Rubratoxin A has also been shown to inhibit Na+/K+-transporting ATPases. (3, 4)
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesRubratoxin A is a mycotoxin produced by fungi such as Penicillum rubrum and Penicillum purpurogenum, which are common soil fungi that sometimes contaminate animal feeds. (1, 4)
Minimum Risk LevelNot Available
Health EffectsRubratoxins are hepatotoxic, nephrotoxic, and splenotoxic, causing congestive, hemorrhagic and degenerative lesions. (1, 2)
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID31181
ChEMBL IDNot Available
ChemSpider ID28923
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. 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 ]
  2. Watson SA, Hayes AW: Binding of rubratoxin B to mouse hepatic microsomes and in vitro effects of the mycotoxin on polysome binding to microsomal membranes as measured by the activity of an enzyme catalyzing disulphide interchange. Toxicon. 1981;19(4):509-16. [6895804 ]
  3. 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 ]
  4. 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 ]
  5. Peraica M, Domijan AM: Contamination of food with mycotoxins and human health. Arh Hig Rada Toksikol. 2001 Mar;52(1):23-35. [11370295 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform
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
References
  1. 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 ]
Target Details
2. Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform
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
References
  1. 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 ]
Target Details
3. Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform
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
References
  1. 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 ]
Target Details
4. Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform
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
References
  1. 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 ]
Target Details
5. Sodium/potassium-transporting ATPase subunit alpha-1
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
References
  1. 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 ]
Target Details
6. Sodium/potassium-transporting ATPase subunit alpha-2
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
References
  1. 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 ]
Target Details
7. Sodium/potassium-transporting ATPase subunit alpha-3
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
References
  1. 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 ]
Target Details
8. Sodium/potassium-transporting ATPase subunit alpha-4
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
References
  1. 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 ]
Target Details
9. Sodium/potassium-transporting ATPase subunit beta-1
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
References
  1. 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 ]
Target Details
10. Sodium/potassium-transporting ATPase subunit beta-2
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
References
  1. 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 ]
Target Details
11. Sodium/potassium-transporting ATPase subunit beta-3
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
References
  1. 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 ]
Target Details
12. Sodium/potassium-transporting ATPase subunit gamma
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
References
  1. 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 ]