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P01555 (CHTA_VIBCH) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cholera enterotoxin subunit A
Alternative name(s):
Cholera enterotoxin, A chain

Cleaved into the following 2 chains:

  1. Cholera enterotoxin subunit A1
    EC=2.4.2.-
    Alternative name(s):
    Cholera enterotoxin A1 chain
    Cholera enterotoxin alpha chain
    NAD(+)--diphthamide ADP-ribosyltransferase
  2. Cholera enterotoxin subunit A2
    Alternative name(s):
    Cholera enterotoxin A2 chain
    Cholera enterotoxin gamma chain
Gene names
Name:ctxA
Synonyms:toxA
Ordered Locus Names:VC_1457
OrganismVibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961) [Reference proteome] [HAMAP]
Taxonomic identifier243277 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaVibrionalesVibrionaceaeVibrio

Protein attributes

Sequence length258 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 structure

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. Ref.14 Ref.17

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.

Sequence similarities

Belongs to the enterotoxin A family.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ctxBP015565EBI-1038392,EBI-1038383

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Ref.9 Ref.10
Chain19 – 212194Cholera enterotoxin subunit A1
PRO_0000019342
Chain213 – 25846Cholera enterotoxin subunit A2
PRO_0000019343

Regions

Nucleotide binding25 – 284NAD
Nucleotide binding41 – 433NAD

Sites

Active site1301 By similarity

Amino acid modifications

Disulfide bond205 ↔ 217Interchain (between A1 and A2 chains)

Experimental info

Sequence conflict201D → N AA sequence Ref.9
Sequence conflict371S → R AA sequence Ref.10
Sequence conflict391G → L AA sequence Ref.11
Sequence conflict45 – 462QS → SE AA sequence Ref.11
Sequence conflict1111N → L AA sequence Ref.11
Sequence conflict1321S → A AA sequence Ref.11
Sequence conflict2131M → I in CAA24995. Ref.1
Sequence conflict247 – 2482DI → ID AA sequence Ref.12
Sequence conflict2561D → N AA sequence Ref.12

Secondary structure

................................................... 258
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01555 [UniParc].

Last modified October 23, 1986. Version 1.
Checksum: 0F7EBAE62069A5D0

FASTA25829,336
        10         20         30         40         50         60 
MVKIIFVFFI FLSSFSYAND DKLYRADSRP PDEIKQSGGL MPRGQSEYFD RGTQMNINLY 

        70         80         90        100        110        120 
DHARGTQTGF VRHDDGYVST SISLRSAHLV GQTILSGHST YYIYVIATAP NMFNVNDVLG 

       130        140        150        160        170        180 
AYSPHPDEQE VSALGGIPYS QIYGWYRVHF GVLDEQLHRN RGYRDRYYSN LDIAPAADGY 

       190        200        210        220        230        240 
GLAGFPPEHR AWREEPWIHH APPGCGNAPR SSMSNTCDEK TQSLGVKFLD EYQSKVKRQI 

       250 
FSGYQSDIDT HNRIKDEL 

« Hide

References

« Hide 'large scale' references
[1]"Cholera toxin genes: nucleotide sequence, deletion analysis and vaccine development."
Mekalanos J.J., Swartz D.J., Pearson G.D.N., Harford N., Groyne F., de Wilde M.
Nature 306:551-557(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: ATCC 39050 / El Tor Inaba 2125 / Serotype O1.
[2]"Nucleotide sequence analysis of the CT operon of the Vibrio cholerae classical strain 569B."
Dams E., de Wolf M., Dierick W.
Biochim. Biophys. Acta 1090:139-141(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: ATCC 25870 / Classical Inaba 569B / Serotype O1.
[3]Yamamoto K., Do V.G.R.F., Xu M., Iida T., Miwatani T., Albert M.J., Honda T.
Submitted (MAY-1994) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 1854 / O139-Bengal.
[4]Dams E., de Wolf M., Dierick W.
Submitted (MAY-1991) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: ATCC 39050 / El Tor Inaba 2125 / Serotype O1.
[5]"Cloning and nucleotide sequence analysis of the virulence gene cassette from Vibrio cholerae KNIH002 isolated in Korea."
Shin H.J., Park Y.C., Kim Y.C.
Misainmurhag Hoiji 35:205-210(1999)
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: KNIH002.
[6]"DNA sequence of both chromosomes of the cholera pathogen Vibrio cholerae."
Heidelberg J.F., Eisen J.A., Nelson W.C., Clayton R.A., Gwinn M.L., Dodson R.J., Haft D.H., Hickey E.K., Peterson J.D., Umayam L.A., Gill S.R., Nelson K.E., Read T.D., Tettelin H., Richardson D.L., Ermolaeva M.D., Vamathevan J.J., Bass S. expand/collapse author list , Qin H., Dragoi I., Sellers P., McDonald L.A., Utterback T.R., Fleischmann R.D., Nierman W.C., White O., Salzberg S.L., Smith H.O., Colwell R.R., Mekalanos J.J., Venter J.C., Fraser C.M.
Nature 406:477-483(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: ATCC 39315 / El Tor Inaba N16961.
[7]"Vibrio cholerae enterotoxin genes: nucleotide sequence analysis of DNA encoding ADP-ribosyltransferase."
Lockman H.A., Galen J.E., Kaper J.B.
J. Bacteriol. 159:1086-1089(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-212.
Strain: ATCC 25870 / Classical Inaba 569B / Serotype O1.
[8]"Nucleotide sequence analysis of the A2 and B subunits of Vibrio cholerae enterotoxin."
Lockman H., Kaper J.B.
J. Biol. Chem. 258:13722-13726(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 213-258.
[9]"Isolation and characterization of a precursor form of the 'A' subunit of cholera toxin."
Duffy L.K., Peterson J.W., Kurosky A.
FEBS Lett. 126:187-190(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 19-27.
[10]"Subunit structure and N-terminal amino acid sequence of the three chains of cholera enterotoxin."
Klapper D.G., Finkelstein R.A., Capra J.D.
Immunochemistry 13:605-611(1976) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 19-38 AND 213-232.
[11]"Primary structure of cholera toxin subunit A1: isolation, partial sequences and alignment of the BrCN fragments."
Lai C.-Y., Cancedda F., Chang D.
FEBS Lett. 100:85-89(1979) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 27-72 AND 111-139.
[12]"Covalent structure of the gamma chain of the A subunit of cholera toxin."
Duffy L.K., Peterson J.W., Kurosky A.
J. Biol. Chem. 256:12252-12256(1981) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 213-258.
[13]"Stimulation of intestinal adenyl cyclase by cholera toxin."
Sharp G.W., Hynie S.
Nature 229:266-269(1971) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION BETWEEN CHOLERA TOXIN AND ADENYLATE CYCLASE.
[14]"The arrangement of subunits in cholera toxin."
Gill D.M.
Biochemistry 15:1242-1248(1976) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[15]"Gangliosides that associate with lipid rafts mediate transport of cholera and related toxins from the plasma membrane to endoplasmic reticulm."
Fujinaga Y., Wolf A.A., Rodighiero C., Wheeler H., Tsai B., Allen L., Jobling M.G., Rapoport T., Holmes R.K., Lencer W.I.
Mol. Biol. Cell 14:4783-4793(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TRANSPORT OF CHOLERA TOXIN WITHIN THE INTESTINAL CELL.
[16]"The three-dimensional crystal structure of cholera toxin."
Zhang R.-G., Scott D.L., Westbrook M.L., Nance S., Spangler B.D., Shipley G.G., Westbrook E.M.
J. Mol. Biol. 251:563-573(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[17]"Structural basis for the activation of cholera toxin by human ARF6-GTP."
O'Neal C.J., Jobling M.G., Holmes R.K., Hol W.G.
Science 309:1093-1096(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 19-210 IN COMPLEX WITH NAD AND HUMAN ARF6, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X00171 Genomic DNA. Translation: CAA24995.1.
X58785 Genomic DNA. Translation: CAA41590.1.
D30053 Genomic DNA. Translation: BAA06290.1.
X58786 Genomic DNA. Translation: CAA41592.1.
K02679 Genomic DNA. Translation: AAA27514.1.
AF175708 Genomic DNA. Translation: AAD51359.1.
AE003852 Genomic DNA. Translation: AAF94614.1.
K01170 Genomic DNA. Translation: AAA27572.1.
D30052 Genomic DNA. Translation: BAA06288.1.
PIRXVVCA. A05129.
RefSeqNP_231100.1. NC_002505.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1S5BX-ray2.13A19-258[»]
1S5CX-ray2.50A19-258[»]
1S5DX-ray1.75A19-258[»]
1S5EX-ray1.90A/B19-258[»]
1S5FX-ray2.60A19-258[»]
1XTCX-ray2.40A19-212[»]
C213-258[»]
2A5DX-ray1.80B19-210[»]
2A5FX-ray2.02B19-210[»]
2A5GX-ray2.66B19-210[»]
DisProtDP00250.
ProteinModelPortalP01555.
SMRP01555. Positions 19-258.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-6255N.
IntActP01555. 2 interactions.
STRING243277.VC1457.

Protocols and materials databases

DNASU2613963.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAF94614; AAF94614; VC_1457.
GeneID2613963.
KEGGvch:VC1457.
PATRIC20081976. VBIVibCho83274_1387.

Phylogenomic databases

eggNOGNOG262323.
KOK10928.
OMANITFIFF.
OrthoDBEOG6GXTN0.

Enzyme and pathway databases

BioCycVCHO:VC1457-MONOMER.

Family and domain databases

InterProIPR001144. Enterotoxin_A.
[Graphical view]
PfamPF01375. Enterotoxin_a. 1 hit.
[Graphical view]
PRINTSPR00771. ENTEROTOXINA.
ProtoNetSearch...

Other

EvolutionaryTraceP01555.
PROP01555.

Entry information

Entry nameCHTA_VIBCH
AccessionPrimary (citable) accession number: P01555
Secondary accession number(s): Q56634, Q9JPV1
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: October 23, 1986
Last modified: June 11, 2014
This is version 121 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references