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P01555

- CHTA_VIBCH

UniProt

P01555 - CHTA_VIBCH

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Protein
Cholera enterotoxin subunit A
Gene
ctxA, toxA, VC_1457
Organism
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei130 – 1301 By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi25 – 284NAD
Nucleotide bindingi41 – 433NAD

GO - Molecular functioni

  1. NAD+ ADP-ribosyltransferase activity Source: TIGR
  2. protein binding Source: IntAct

GO - Biological processi

  1. killing of cells of other organism Source: TIGR
  2. pathogenesis Source: TIGR
  3. positive regulation of cAMP biosynthetic process Source: CACAO
  4. positive regulation of tyrosine phosphorylation of Stat3 protein Source: CACAO
  5. protein ADP-ribosylation Source: TIGR
Complete GO annotation...

Keywords - Molecular functioni

Enterotoxin, Glycosyltransferase, Toxin, Transferase

Keywords - Ligandi

NAD

Enzyme and pathway databases

BioCyciVCHO:VC1457-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Cholera enterotoxin subunit A
Alternative name(s):
Cholera enterotoxin, A chain
Cleaved into the following 2 chains:
Alternative name(s):
Cholera enterotoxin A1 chain
Cholera enterotoxin alpha chain
NAD(+)--diphthamide ADP-ribosyltransferase
Alternative name(s):
Cholera enterotoxin A2 chain
Cholera enterotoxin gamma chain
Gene namesi
Name:ctxA
Synonyms:toxA
Ordered Locus Names:VC_1457
OrganismiVibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Taxonomic identifieri243277 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaVibrionalesVibrionaceaeVibrio
ProteomesiUP000000584: Chromosome 1

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: InterPro
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 18182 Publications
Add
BLAST
Chaini19 – 212194Cholera enterotoxin subunit A1
PRO_0000019342Add
BLAST
Chaini213 – 25846Cholera enterotoxin subunit A2
PRO_0000019343Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi205 ↔ 217Interchain (between A1 and A2 chains)

Keywords - PTMi

Disulfide bond

Interactioni

Subunit structurei

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.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ctxBP015565EBI-1038392,EBI-1038383

Protein-protein interaction databases

DIPiDIP-6255N.
IntActiP01555. 2 interactions.
STRINGi243277.VC1457.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi22 – 298
Helixi31 – 377
Helixi43 – 453
Beta strandi51 – 533
Helixi59 – 646
Beta strandi70 – 723
Beta strandi77 – 837
Helixi84 – 9411
Turni95 – 973
Beta strandi99 – 1079
Beta strandi112 – 1143
Helixi115 – 1195
Helixi120 – 1223
Helixi126 – 1283
Beta strandi131 – 1344
Helixi139 – 1413
Beta strandi142 – 1498
Beta strandi152 – 1543
Beta strandi156 – 1594
Helixi165 – 1695
Helixi176 – 1783
Helixi180 – 1823
Helixi190 – 1934
Helixi197 – 2004
Helixi217 – 24428
Turni245 – 2473
Turni250 – 2523
Helixi254 – 2574

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
DisProtiDP00250.
ProteinModelPortaliP01555.
SMRiP01555. Positions 19-258.

Miscellaneous databases

EvolutionaryTraceiP01555.

Family & Domainsi

Domaini

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.

Sequence similaritiesi

Belongs to the enterotoxin A family.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG262323.
KOiK10928.
OMAiNITFIFF.
OrthoDBiEOG6GXTN0.

Family and domain databases

InterProiIPR001144. Enterotoxin_A.
[Graphical view]
PfamiPF01375. Enterotoxin_a. 1 hit.
[Graphical view]
PRINTSiPR00771. ENTEROTOXINA.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P01555-1 [UniParc]FASTAAdd to Basket

« Hide

MVKIIFVFFI FLSSFSYAND DKLYRADSRP PDEIKQSGGL MPRGQSEYFD    50
RGTQMNINLY DHARGTQTGF VRHDDGYVST SISLRSAHLV GQTILSGHST 100
YYIYVIATAP NMFNVNDVLG AYSPHPDEQE VSALGGIPYS QIYGWYRVHF 150
GVLDEQLHRN RGYRDRYYSN LDIAPAADGY GLAGFPPEHR AWREEPWIHH 200
APPGCGNAPR SSMSNTCDEK TQSLGVKFLD EYQSKVKRQI FSGYQSDIDT 250
HNRIKDEL 258
Length:258
Mass (Da):29,336
Last modified:October 23, 1986 - v1
Checksum:i0F7EBAE62069A5D0
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti20 – 201D → N AA sequence 1 Publication
Sequence conflicti37 – 371S → R AA sequence 1 Publication
Sequence conflicti39 – 391G → L AA sequence 1 Publication
Sequence conflicti45 – 462QS → SE AA sequence 1 Publication
Sequence conflicti111 – 1111N → L AA sequence 1 Publication
Sequence conflicti132 – 1321S → A AA sequence 1 Publication
Sequence conflicti213 – 2131M → I in CAA24995. 1 Publication
Sequence conflicti247 – 2482DI → ID AA sequence 1 Publication
Sequence conflicti256 – 2561D → N AA sequence 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
PIRiA05129. XVVCA.
RefSeqiNP_231100.1. NC_002505.1.
WP_001881225.1. NC_002505.1.

Genome annotation databases

EnsemblBacteriaiAAF94614; AAF94614; VC_1457.
GeneIDi2613963.
KEGGivch:VC1457.
PATRICi20081976. VBIVibCho83274_1387.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
PIRi A05129. XVVCA.
RefSeqi NP_231100.1. NC_002505.1.
WP_001881225.1. NC_002505.1.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1S5B X-ray 2.13 A 19-258 [» ]
1S5C X-ray 2.50 A 19-258 [» ]
1S5D X-ray 1.75 A 19-258 [» ]
1S5E X-ray 1.90 A/B 19-258 [» ]
1S5F X-ray 2.60 A 19-258 [» ]
1XTC X-ray 2.40 A 19-212 [» ]
C 213-258 [» ]
2A5D X-ray 1.80 B 19-210 [» ]
2A5F X-ray 2.02 B 19-210 [» ]
2A5G X-ray 2.66 B 19-210 [» ]
DisProti DP00250.
ProteinModelPortali P01555.
SMRi P01555. Positions 19-258.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

DIPi DIP-6255N.
IntActi P01555. 2 interactions.
STRINGi 243277.VC1457.

Protocols and materials databases

DNASUi 2613963.
Structural Biology Knowledgebase Search...

Genome annotation databases

EnsemblBacteriai AAF94614 ; AAF94614 ; VC_1457 .
GeneIDi 2613963.
KEGGi vch:VC1457.
PATRICi 20081976. VBIVibCho83274_1387.

Phylogenomic databases

eggNOGi NOG262323.
KOi K10928.
OMAi NITFIFF.
OrthoDBi EOG6GXTN0.

Enzyme and pathway databases

BioCyci VCHO:VC1457-MONOMER.

Miscellaneous databases

EvolutionaryTracei P01555.
PROi P01555.

Family and domain databases

InterProi IPR001144. Enterotoxin_A.
[Graphical view ]
Pfami PF01375. Enterotoxin_a. 1 hit.
[Graphical view ]
PRINTSi PR00771. ENTEROTOXINA.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. 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.

Entry informationi

Entry nameiCHTA_VIBCH
AccessioniPrimary (citable) accession number: P01555
Secondary accession number(s): Q56634, Q9JPV1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: October 23, 1986
Last modified: September 3, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

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.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi