UniProt functional annotation for P01555



	UniProt functional annotation for P01555

UniProt code: P01555.

Organism: Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961).

Taxonomy: Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae; Vibrio.

Function: The A1 chain catalyzes the ADP-ribosylation of Gs alpha, a GTP-binding regulatory protein, to activate the adenylate cyclase. This leads to an overproduction of cAMP and eventually to a hypersecretion of chloride and bicarbonate followed by water, resulting in the characteristic cholera stool. The A2 chain tethers A1 to the pentameric ring.

Subunit: The holotoxin (choleragen) consists of a pentameric ring of B subunits whose central pore is occupied by the A subunit. The A subunit contains two chains, A1 and A2, linked by a disulfide bridge. Interaction with the host protein ARF6 causes a conformation change so that the enterotoxin subunit A1 can bind NAD and catalyze the ADP- ribosylation of the host Gs alpha. {ECO:0000269|PubMed:16099990, ECO:0000269|PubMed:3214}.

Domain: The four C-terminal residues of the A2 chain occupy the central pore of the holotoxin. Deletion of these residues weakens the interaction between the A subunit and the B pentamer without impairing the pentamer formation.

Miscellaneous: After binding to gangliosides GM1 in lipid rafts, through the subunit B pentamer, the holotoxin and the gangliosides are internalized. The holotoxin remains bound to GM1 until arrival in the ER. The A subunit has previously been cleaved in the intestinal lumen but the A1 and A2 chains have remained associated. In the ER, the A subunit disulfide bridge is reduced, the A1 chain is unfolded by the PDI and disassembled from the rest of the toxin. Then, the membrane- associated ER oxidase ERO1 oxidizes PDI, which releases the unfolded A1 chain. The next step is the retrotranslocation of A1 into the cytosol. This might be mediated by the protein-conducting pore SEC61. Upon arrival in the cytosol, A1 refolds and avoids proteasome degradation. In one way or another, A1 finally reaches its target and induces toxicity.

Similarity: Belongs to the enterotoxin A family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961).
Taxonomy:		Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae; Vibrio.



Function:		The A1 chain catalyzes the ADP-ribosylation of Gs alpha, a GTP-binding regulatory protein, to activate the adenylate cyclase. This leads to an overproduction of cAMP and eventually to a hypersecretion of chloride and bicarbonate followed by water, resulting in the characteristic cholera stool. The A2 chain tethers A1 to the pentameric ring.


Subunit:		The holotoxin (choleragen) consists of a pentameric ring of B subunits whose central pore is occupied by the A subunit. The A subunit contains two chains, A1 and A2, linked by a disulfide bridge. Interaction with the host protein ARF6 causes a conformation change so that the enterotoxin subunit A1 can bind NAD and catalyze the ADP- ribosylation of the host Gs alpha. {ECO:0000269\|PubMed:16099990, ECO:0000269\|PubMed:3214}.
Domain:		The four C-terminal residues of the A2 chain occupy the central pore of the holotoxin. Deletion of these residues weakens the interaction between the A subunit and the B pentamer without impairing the pentamer formation.
Miscellaneous:		After binding to gangliosides GM1 in lipid rafts, through the subunit B pentamer, the holotoxin and the gangliosides are internalized. The holotoxin remains bound to GM1 until arrival in the ER. The A subunit has previously been cleaved in the intestinal lumen but the A1 and A2 chains have remained associated. In the ER, the A subunit disulfide bridge is reduced, the A1 chain is unfolded by the PDI and disassembled from the rest of the toxin. Then, the membrane- associated ER oxidase ERO1 oxidizes PDI, which releases the unfolded A1 chain. The next step is the retrotranslocation of A1 into the cytosol. This might be mediated by the protein-conducting pore SEC61. Upon arrival in the cytosol, A1 refolds and avoids proteasome degradation. In one way or another, A1 finally reaches its target and induces toxicity.
Similarity:		Belongs to the enterotoxin A family. {ECO:0000305}.