Toxin A (Clostridium difficile) (T3D2597)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (20)XML
Targets (20)
Record Information
Version2.0
Creation Date2009-07-06 18:11:25 UTC
Update Date2014-12-24 20:25:45 UTC
Accession NumberT3D2597
Identification
Common NameToxin A (Clostridium difficile)
ClassProtein
DescriptionToxins A and B are toxins from Clostridium difficile; they are the major pathogenicity factors of the antibiotic-associated diarrhea and the pseudomembranous colitis. Toxins A and B belong to the large clostridial cytotoxins family. Toxins A and B are also classified in the A-B bacterial toxin family. They are single-chain protein toxins constituted with three domains: receptor-binding, translocation, and a catalytic domain exhibiting a glycosyltransferase activity. (2, 1)
Compound Type
  • Amide
  • Amine
  • Bacterial Toxin
  • Natural Compound
  • Organic Compound
  • Protein
Protein StructureT3d2597
Synonyms
Synonym
Actin-specific ADP-ribosyltransferase
cdtA
Clostridium difficile binary toxin A
Chemical FormulaNot Available
Average Molecular Mass308052.765 g/mol
CAS Registry NumberNot Available
SequenceNot Available
Chemical Taxonomy
DescriptionNot Available
KingdomOrganic Compounds
Super ClassOrganic Acids
ClassCarboxylic Acids and Derivatives
Sub ClassAmino Acids, Peptides, and Analogues
Direct ParentPeptides
Alternative ParentsNot Available
SubstituentsNot Available
Molecular FrameworkNot Available
External DescriptorsNot Available
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular LocationsNot Available
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateLiquid
AppearanceClear solution.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility>10 mg/mL
LogPNot Available
Predicted PropertiesNot Available
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Toxicity Profile
Route of ExposureIngestion (5) ; inhalation (5) ; dermal (5)
Mechanism of ToxicityRho GTPases are activated by glucosylation (for example RhoA at Thr37). The toxins catalyze the transfer of a glucosyl moiety from UDP-glucose to the Rho GTPases. The covalent attachment of the glucose moiety to a conserved threonine within the effector region of the GTPases renders the Rho-GTPases functionally inactive. As a consequence, the actin cytoskeleton is disaggregated and this is accompanied by cell rounding and formation of an arborized morphology. (2, 1)
MetabolismFree toxin may be removed by opsonization via the reticuloendothelial system (primarily the liver and kidneys) or it may be degraded through cellular internalization via the lysosomes. Lysosomes are membrane-enclosed organelles that contain an array of digestive enzymes, including several proteases.
Toxicity ValuesLD50: 500 ng/kg (Intraperitoneal, Mouse) (3)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesToxins A and B are toxins from Clostridium difficile; they are the major pathogenicity factors of the antibiotic-associated diarrhea and the pseudomembranous colitis. (2, 1)
Minimum Risk LevelNot Available
Health EffectsToxins A is an enterotoxin from Clostridium difficile and causes antibiotic-associated diarrhea and pseudomembranous colitis. (2, 1, 4)
SymptomsSymptoms of Clostridium difficile infection include bloating, constipation, and diarrhea with abdominal pain, which may become severe. Latent symptoms often mimic some flu-like symptoms. (4)
TreatmentThe antibiotics metronidazole and vancomycin have been shown to be effective against Clostridium difficile. (4)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound IDNot Available
ChEMBL IDNot Available
ChemSpider IDNot Available
KEGG IDNot Available
UniProt IDP16154
OMIM ID
ChEBI IDNot Available
BioCyc IDNot Available
CTD IDNot Available
Stitch IDToxin A
PDB ID2F6E
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Gill DM: Bacterial toxins: a table of lethal amounts. Microbiol Rev. 1982 Mar;46(1):86-94. [6806598 ]
  4. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
  5. Wikipedia. Bacterial toxin. Last Updated 27 February 2009. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Cell division control protein 42 homolog
General Function:
Ubiquitin protein ligase activity
Specific Function:
Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Mediates CDC42-dependent cell migration.
Gene Name:
CDC42
Uniprot ID:
P60953
Molecular Weight:
21258.42 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
2. Cytochrome b-245 heavy chain
General Function:
Voltage-gated ion channel activity
Specific Function:
Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. It is the terminal component of a respiratory chain that transfers single electrons from cytoplasmic NADPH across the plasma membrane to molecular oxygen on the exterior. Also functions as a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes. It participates in the regulation of cellular pH and is blocked by zinc.
Gene Name:
CYBB
Uniprot ID:
P04839
Molecular Weight:
65335.415 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
3. Ras-related C3 botulinum toxin substrate 1
General Function:
Thioesterase binding
Specific Function:
Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion. In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. Required for atypical chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3.Isoform B has an accelerated GEF-independent GDP/GTP exchange and an impaired GTP hydrolysis, which is restored partially by GTPase-activating proteins. It is able to bind to the GTPase-binding domain of PAK but not full-length PAK in a GTP-dependent manner, suggesting that the insertion does not completely abolish effector interaction.
Gene Name:
RAC1
Uniprot ID:
P63000
Molecular Weight:
21449.895 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
4. Ras-related C3 botulinum toxin substrate 3
General Function:
Gtpase activity
Specific Function:
Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as cell spreading and the formation of actin-based protusions including lamellipodia and membrane ruffles. Promotes cell adhesion and spreading on fibrinogen in a CIB1 and alpha-IIb/beta3 integrin-mediated manner.
Gene Name:
RAC3
Uniprot ID:
P60763
Molecular Weight:
21378.655 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
5. Rho-related BTB domain-containing protein 1
General Function:
Gtp binding
Specific Function:
Not Available
Gene Name:
RHOBTB1
Uniprot ID:
O94844
Molecular Weight:
79416.465 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
6. Rho-related BTB domain-containing protein 2
General Function:
Gtp binding
Specific Function:
Not Available
Gene Name:
RHOBTB2
Uniprot ID:
Q9BYZ6
Molecular Weight:
82625.62 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
7. Rho-related GTP-binding protein Rho6
General Function:
Receptor binding
Specific Function:
Lacks intrinsic GTPase activity. Has a low affinity for GDP, and constitutively binds GTP. Controls rearrangements of the actin cytoskeleton. Induces the Rac-dependent neuritic process formation in part by disruption of the cortical actin filaments. Causes the formation of many neuritic processes from the cell body with disruption of the cortical actin filaments.
Gene Name:
RND1
Uniprot ID:
Q92730
Molecular Weight:
26055.825 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
8. Rho-related GTP-binding protein RhoB
General Function:
Gtpase activity
Specific Function:
Mediates apoptosis in neoplastically transformed cells after DNA damage. Not essential for development but affects cell adhesion and growth factor signaling in transformed cells. Plays a negative role in tumorigenesis as deletion causes tumor formation. Involved in intracellular protein trafficking of a number of proteins. Targets PKN1 to endosomes and is involved in trafficking of the EGF receptor from late endosomes to lysosomes. Also required for stability and nuclear trafficking of AKT1/AKT which promotes endothelial cell survival during vascular development. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Required for genotoxic stress-induced cell death in breast cancer cells.
Gene Name:
RHOB
Uniprot ID:
P62745
Molecular Weight:
22123.185 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
9. Rho-related GTP-binding protein RhoC
General Function:
Signal transducer activity
Specific Function:
Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Regulates apical junction formation in bronchial epithelial cells.
Gene Name:
RHOC
Uniprot ID:
P08134
Molecular Weight:
22006.16 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
10. Rho-related GTP-binding protein RhoD
General Function:
Gtpase activity
Specific Function:
Involved in endosome dynamics. May coordinate membrane transport with the function of the cytoskeleton. Involved in the internalization and trafficking of activated tyrosine kinase receptors such as PDGFRB. Participates in the reorganization of actin cytoskeleton; the function seems to involve WHAMM and includes regulation of filopodia formation and actin filament bundling. Can modulate the effect of DAPK3 in reorganization of actin cytoskeleton and focal adhesion dissolution.
Gene Name:
RHOD
Uniprot ID:
O00212
Molecular Weight:
23412.695 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
11. Rho-related GTP-binding protein RhoE
General Function:
Gtpase activity
Specific Function:
Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins.
Gene Name:
RND3
Uniprot ID:
P61587
Molecular Weight:
27367.995 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
12. Rho-related GTP-binding protein RhoF
General Function:
Gtpase activity
Specific Function:
Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. Causes the formation of thin, actin-rich surface projections called filopodia. Functions cooperatively with CDC42 and Rac to generate additional structures, increasing the diversity of actin-based morphology.
Gene Name:
RHOF
Uniprot ID:
Q9HBH0
Molecular Weight:
23625.22 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
13. Rho-related GTP-binding protein RhoG
General Function:
Gtpase activity
Specific Function:
Required for the formation of membrane ruffles during macropinocytosis. Plays a role in cell migration and is required for the formation of cup-like structures during trans-endothelial migration of leukocytes. In case of Salmonella enterica infection, activated by SopB and ARHGEF26/SGEF, which induces cytoskeleton rearrangements and promotes bacterial entry.
Gene Name:
RHOG
Uniprot ID:
P84095
Molecular Weight:
21308.34 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
14. Rho-related GTP-binding protein RhoH
General Function:
Rho gtpase binding
Specific Function:
Negative regulator of hematopoietic progenitor cell proliferation, survival and migration. Critical regulator of thymocyte development and T-cell antigen receptor (TCR) signaling by mediating recruitment and activation of ZAP70. Required for phosphorylation of CD3Z, membrane translocation of ZAP70 and subsequent activation of the ZAP70-mediated pathways. Essential for efficient beta-selection and positive selection by promoting the ZAP70-dependent phosphorylation of the LAT signalosome during pre-TCR and TCR signaling. Crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Plays critical roles in mast cell function by facilitating phosphorylation of SYK in Fc epsilon RI-mediated signal transduction. Essential for the phosphorylation of LAT, LCP2, PLCG1 and PLCG2 and for Ca(2+) mobilization in mast cells (By similarity). Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins. Inhibits the activation of NF-kappa-B by TNF and IKKB and the activation of CRK/p38 by TNF. Inhibits activities of RAC1, RHOA and CDC42. Negatively regulates leukotriene production in neutrophils.
Gene Name:
RHOH
Uniprot ID:
Q15669
Molecular Weight:
21330.35 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
15. Rho-related GTP-binding protein RhoJ
General Function:
Gtpase activity
Specific Function:
GTP-binding protein with GTPase activity. Elicits the formation of F-actin-rich structures in fibroblasts and is involved in the regulation of cell morphology (By similarity).
Gene Name:
RHOJ
Uniprot ID:
Q9H4E5
Molecular Weight:
23820.345 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
16. Rho-related GTP-binding protein RhoN
General Function:
Gtpase activity
Specific Function:
May be specifically involved in neuronal and hepatic functions. Is a C3 toxin-insensitive member of the Rho subfamily (By similarity).
Gene Name:
RND2
Uniprot ID:
P52198
Molecular Weight:
25368.54 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
17. Rho-related GTP-binding protein RhoQ
General Function:
Profilin binding
Specific Function:
Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. May play a role in CFTR trafficking to the plasma membrane. Causes the formation of thin, actin-rich surface projections called filopodia.
Gene Name:
RHOQ
Uniprot ID:
P17081
Molecular Weight:
22659.26 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
18. Rho-related GTP-binding protein RhoU
General Function:
Metal ion binding
Specific Function:
Acts upstream of PAK1 to regulate the actin cytoskeleton, adhesion turnover and increase cell migration. Stimulates quiescent cells to reenter the cell cycle. Has no detectable GTPase activity but its high intrinsic guanine nucleotide exchange activity suggests it is constitutively GTP-bound. Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape.
Gene Name:
RHOU
Uniprot ID:
Q7L0Q8
Molecular Weight:
28218.035 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
19. Rho-related GTP-binding protein RhoV
General Function:
Metal ion binding
Specific Function:
Plays a role in the control of the actin cytoskeleton via activation of the JNK pathway.
Gene Name:
RHOV
Uniprot ID:
Q96L33
Molecular Weight:
26216.915 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]
Target Details
20. Transforming protein RhoA
General Function:
Myosin binding
Specific Function:
Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. Stimulates PKN2 kinase activity. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization. Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Involved in a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Plays an essential role in cleavage furrow formation. Required for the apical junction formation of keratinocyte cell-cell adhesion. May be an activator of PLCE1. Activated by ARHGEF2, which promotes the exchange of GDP for GTP. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity. In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (By similarity). Regulates KCNA2 potassium channel activity by reducing its location at the cell surface in response to CHRM1 activation; promotes KCNA2 endocytosis (PubMed:9635436, PubMed:19403695).(Microbial infection) Serves as a target for the yopT cysteine peptidase from Yersinia pestis, vector of the plague, and Yersinia pseudotuberculosis, which causes gastrointestinal disorders.
Gene Name:
RHOA
Uniprot ID:
P61586
Molecular Weight:
21767.94 Da
References
  1. Aktories K, Barbieri JT: Bacterial cytotoxins: targeting eukaryotic switches. Nat Rev Microbiol. 2005 May;3(5):397-410. [15821726 ]
  2. Just I, Gerhard R: Large clostridial cytotoxins. Rev Physiol Biochem Pharmacol. 2004;152:23-47. Epub 2004 Sep 21. [15449191 ]
  3. Wikipedia. Clostridium difficile. Last Updated 7 August 2009. [Link]