KEGG   PATHWAY: hsa05110Help
Entry
hsa05110                    Pathway                                
Name
Vibrio cholerae infection - Homo sapiens (human)
Description
Cholera toxin (CTX) is one of the main virulence factors of Vibrio cholerae. Once secreted, CTX B-chain (CTXB) binds to ganglioside GM1 on the surface of the host's cells. After binding takes place, the entire CTX complex is carried from plasma membrane (PM) to endoplasmic reticulum (ER). In the ER, the A-chain (CTXA) is recognized by protein disulfide isomerase (PDI), unfolded, and delivered to the membrane where the membrane-associated ER-oxidase, Ero1, oxidizes PDI to release the CTXA into the protein-conducting channel, Sec61. CTXA is then retro-translocated to the cytosol and induces water and electrolyte secretion by increasing cAMP levels via adenylate cyclase (AC) to exert toxicity.
Other than CTX, Vibrio cholerae generates several toxins that are perilous to eukaryotic cells. Zonula occludens toxin (ZOT) causes tight junction disruption through protein kinase C-dependent actin polymerization. RTX toxin (RtxA) causes actin depolymerization by covalently cross-linking actin monomers into dimers, trimers, and higher multimers. Vibrio cholerae cytolysin (VCC) is an important pore-forming toxin. The assembly of VCC anion channels in cells cause vacuolization and lysis.
Class
Human Diseases; Infectious diseases
BRITE hierarchy
Pathway map
Vibrio cholerae infection
hsa05110

All organismsOrtholog table
Module
Sec61 complex [PATH:hsa05110]
Disease
H00110  
Cholera
Organism
Homo sapiens (human) [GN:hsa]
Gene
523  
ATP6V1A; ATPase, H+ transporting, lysosomal 70kDa, V1 subunit A [KO:K02145] [EC:3.6.3.14]
525  
ATP6V1B1; ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B1 [KO:K02147] [EC:3.6.3.14]
526  
ATP6V1B2; ATPase, H+ transporting, lysosomal 56/58kDa, V1 subunit B2 [KO:K02147] [EC:3.6.3.14]
245973  
ATP6V1C2; ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C2 [KO:K02148] [EC:3.6.3.14]
528  
ATP6V1C1; ATPase, H+ transporting, lysosomal 42kDa, V1 subunit C1 [KO:K02148] [EC:3.6.3.14]
51382  
ATP6V1D; ATPase, H+ transporting, lysosomal 34kDa, V1 subunit D [KO:K02149] [EC:3.6.3.14]
90423  
ATP6V1E2; ATPase, H+ transporting, lysosomal 31kDa, V1 subunit E2 [KO:K02150] [EC:3.6.3.14]
529  
ATP6V1E1; ATPase, H+ transporting, lysosomal 31kDa, V1 subunit E1 [KO:K02150] [EC:3.6.3.14]
9296  
ATP6V1F; ATPase, H+ transporting, lysosomal 14kDa, V1 subunit F [KO:K02151] [EC:3.6.3.14]
9550  
ATP6V1G1; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G1 [KO:K02152] [EC:3.6.3.14]
127124  
ATP6V1G3; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G3 [KO:K02152] [EC:3.6.3.14]
534  
ATP6V1G2; ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2 [KO:K02152] [EC:3.6.3.14]
8992  
ATP6V0E1; ATPase, H+ transporting, lysosomal 9kDa, V0 subunit e1 [KO:K02153] [EC:3.6.3.14]
155066  
ATP6V0E2; ATPase, H+ transporting V0 subunit e2 [KO:K02153] [EC:3.6.3.14]
10312  
TCIRG1; T-cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 subunit A3 [KO:K02154] [EC:3.6.3.14]
23545  
ATP6V0A2; ATPase, H+ transporting, lysosomal V0 subunit a2 [KO:K02154] [EC:3.6.3.14]
50617  
ATP6V0A4; ATPase, H+ transporting, lysosomal V0 subunit a4 [KO:K02154] [EC:3.6.3.14]
535  
ATP6V0A1; ATPase, H+ transporting, lysosomal V0 subunit a1 [KO:K02154] [EC:3.6.3.14]
9114  
ATP6V0D1; ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d1 [KO:K02146] [EC:3.6.3.14]
245972  
ATP6V0D2; ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d2 [KO:K02146] [EC:3.6.3.14]
51606  
ATP6V1H; ATPase, H+ transporting, lysosomal 50/57kDa, V1 subunit H [KO:K02144] [EC:3.6.3.14]
537  
ATP6AP1; ATPase, H+ transporting, lysosomal accessory protein 1 [KO:K03662] [EC:3.6.3.14]
527  
ATP6V0C; ATPase, H+ transporting, lysosomal 16kDa, V0 subunit c [KO:K02155] [EC:3.6.3.14]
533  
ATP6V0B; ATPase, H+ transporting, lysosomal 21kDa, V0 subunit b [KO:K03661] [EC:3.6.3.14]
10945  
KDELR1; KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 1 [KO:K10949]
11014  
KDELR2; KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 2 [KO:K10949]
11015  
KDELR3; KDEL (Lys-Asp-Glu-Leu) endoplasmic reticulum protein retention receptor 3 [KO:K10949]
9601  
PDIA4; protein disulfide isomerase family A, member 4 [KO:K09582] [EC:5.3.4.1]
30001  
ERO1L; ERO1-like (S. cerevisiae) [KO:K10950] [EC:1.8.4.-]
29927  
SEC61A1; Sec61 alpha 1 subunit (S. cerevisiae) [KO:K10956]
55176  
SEC61A2; Sec61 alpha 2 subunit (S. cerevisiae) [KO:K10956]
10952  
SEC61B; Sec61 beta subunit [KO:K09481]
23480  
SEC61G; Sec61 gamma subunit [KO:K07342]
375  
ARF1; ADP-ribosylation factor 1 [KO:K07937]
2778  
GNAS; GNAS complex locus [KO:K04632]
109  
ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
115  
ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5566  
PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613  
PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
1080  
CFTR; cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7) [KO:K05031] [EC:3.6.3.49]
3784  
KCNQ1; potassium voltage-gated channel, KQT-like subfamily, member 1 [KO:K04926]
6558  
SLC12A2; solute carrier family 12 (sodium/potassium/chloride transporters), member 2 [KO:K10951]
60  
ACTB; actin, beta [KO:K05692]
71  
ACTG1; actin, gamma 1 [KO:K05692]
5335  
PLCG1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
5336  
PLCG2; phospholipase C, gamma 2 (phosphatidylinositol-specific) [KO:K05859] [EC:3.1.4.11]
5578  
PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
7082  
TJP1; tight junction protein 1 [KO:K05701]
9414  
TJP2; tight junction protein 2 [KO:K06098]
4583  
MUC2; mucin 2, oligomeric mucus/gel-forming [KO:K10955]
Compound
C00014  
Ammonia
C00080  
H+
C00165  
Diacylglycerol
C00238  
Potassium cation
C00575  
3',5'-Cyclic AMP
C00698  
Cl-
C01245  
D-myo-Inositol 1,4,5-trisphosphate
C01330  
Sodium cation
C04911  
D-Galactosyl-N-acetyl-D-galactosaminyl-(N-acetylneuraminyl)-D-galactosyl-D-glucosylceramide
Reference
  Authors
Trucksis M, Conn TL, Wasserman SS, Sears CL.
  Title
Vibrio cholerae ACE stimulates Ca(2+)-dependent Cl(-)/HCO(3)(-) secretion in T84 cells in vitro.
  Journal
Am J Physiol Cell Physiol 279:C567-77 (2000)
Reference
  Authors
Fullner KJ, Mekalanos JJ.
  Title
In vivo covalent cross-linking of cellular actin by the Vibrio cholerae RTX toxin.
  Journal
EMBO J 19:5315-23 (2000)
Reference
  Authors
Lencer WI.
  Title
Microbes and microbial Toxins: paradigms for microbial-mucosal toxins. V. Cholera: invasion of the intestinal epithelial barrier by a stably folded protein toxin.
  Journal
Am J Physiol Gastrointest Liver Physiol 280:G781-6 (2001)
Reference
  Authors
Moschioni M, Tombola F, de Bernard M, Coelho A, Zitzer A, Zoratti M, Montecucco C.
  Title
The Vibrio cholerae haemolysin anion channel is required for cell vacuolation and death.
  Journal
Cell Microbiol 4:397-409 (2002)
Reference
  Authors
Tsai B, Rapoport TA.
  Title
Unfolded cholera toxin is transferred to the ER membrane and released from protein disulfide isomerase upon oxidation by Ero1.
  Journal
J Cell Biol 159:207-16 (2002)
Reference
  Authors
Fujinaga Y, Wolf AA, Rodighiero C, Wheeler H, Tsai B, Allen L, Jobling MG, Rapoport T, Holmes RK, Lencer WI.
  Title
Gangliosides that associate with lipid rafts mediate transport of cholera and related toxins from the plasma membrane to endoplasmic reticulm.
  Journal
Mol Biol Cell 14:4783-93 (2003)
Reference
  Authors
Fasano A.
  Title
Toxins and the gut: role in human disease.
  Journal
Gut 50 Suppl 3:III9-14 (2002)
Reference
  Authors
Uzzau S, Fasano A.
  Title
Cross-talk between enteric pathogens and the intestine.
  Journal
Cell Microbiol 2:83-9 (2000)
Reference
  Authors
Sandkvist M.
  Title
Type II secretion and pathogenesis.
  Journal
Infect Immun 69:3523-35 (2001)
Reference
  Authors
Field M.
  Title
Intestinal ion transport and the pathophysiology of diarrhea.
  Journal
J Clin Invest 111:931-43 (2003)
Reference
  Authors
Lencer WI, Tsai B.
  Title
The intracellular voyage of cholera toxin: going retro.
  Journal
Trends Biochem Sci 28:639-45 (2003)
Reference
  Authors
De Haan L, Hirst TR.
  Title
Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (Review).
  Journal
Mol Membr Biol 21:77-92 (2004)
Reference
  Authors
Chinnapen DJ, Chinnapen H, Saslowsky D, Lencer WI.
  Title
Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER.
  Journal
FEMS Microbiol Lett 266:129-37 (2007)
Reference
  Authors
Sheahan KL, Cordero CL, Satchell KJ.
  Title
Autoprocessing of the Vibrio cholerae RTX toxin by the cysteine protease domain.
  Journal
EMBO J 26:2552-61 (2007)
Reference
  Authors
Fasano A.
  Title
Intestinal zonulin: open sesame!
  Journal
Gut 49:159-62 (2001)
KO pathway
 
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