Cholera enterotoxin subunit A precursor - Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)

Contribute

Send feedback

Read comments (?) or add your own

P01555 (CHTA_VIBCH) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 113. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

text xml rdf/xml gff fasta

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Cholera enterotoxin subunit A

Alternative name(s):
Cholera enterotoxin, A chain

Cleaved into the following 2 chains:

Cholera enterotoxin subunit A1
EC=2.4.2.36
Alternative name(s):
Cholera enterotoxin A1 chain
Cholera enterotoxin alpha chain
NAD(+)--diphthamide ADP-ribosyltransferase
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

Organism

Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961) [Reference proteome] [HAMAP]

Taxonomic identifier

243277 [NCBI]

Taxonomic lineage

Bacteria › Proteobacteria › Gammaproteobacteria › Vibrionales › Vibrionaceae › Vibrio ›

Protein attributes

Sequence length	258 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Catalytic activity	NAD⁺ + peptide diphthamide = nicotinamide + peptide N-(ADP-D-ribosyl)diphthamide.
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. Ref.14
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.

Ontologies

Keywords
Domain	Signal
Ligand	NAD
Molecular function	Enterotoxin Glycosyltransferase Toxin Transferase
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	killing of cells of other organism Inferred from mutant phenotype Ref.1. Source: TIGR pathogenesis Inferred from mutant phenotype Ref.1. Source: TIGR protein ADP-ribosylation Inferred from mutant phenotype Ref.1. Source: TIGR
Cellular_component	extracellular region Inferred from electronic annotation. Source: InterPro
Molecular_function	NAD+ ADP-ribosyltransferase activity Inferred from mutant phenotype Ref.1. Source: TIGR NAD+-diphthamide ADP-ribosyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ctxB	P01556	5	EBI-1038392,EBI-1038383

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

Ref.9 Ref.10

Chain

19 – 212

194

Cholera enterotoxin subunit A1

PRO_0000019342

Chain

213 – 258

Cholera enterotoxin subunit A2

PRO_0000019343

Sites

Active site

130

By similarity

Binding site

NAD By similarity

Binding site

NAD By similarity

Amino acid modifications

Disulfide bond

205 ↔ 217

Interchain (between A1 and A2 chains)

Experimental info

Sequence conflict

D → N AA sequence Ref.9

Sequence conflict

S → R AA sequence Ref.10

Sequence conflict

G → L AA sequence Ref.11

Sequence conflict

45 – 46

QS → SE AA sequence Ref.11

Sequence conflict

111

N → L AA sequence Ref.11

Sequence conflict

132

S → A AA sequence Ref.11

Sequence conflict

213

M → I in CAA24995. Ref.1

Sequence conflict

247 – 248

DI → ID AA sequence Ref.12

Sequence conflict

256

D → N AA sequence Ref.12

Secondary structure

258

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P01555 [UniParc].

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

FASTA

258

29,336

        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' referencesShow '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. 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).
+	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.

PIR

XVVCA. A05129.

RefSeq

NP_231100.1. NC_002505.1.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

DisProt

DP00250.

ProteinModelPortal

P01555.

SMR

P01555. Positions 19-258.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-6255N.

IntAct

P01555. 2 interactions.

STRING

243277.VC1457.

Protocols and materials databases

DNASU

2613963.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAF94614; AAF94614; VC_1457.

GeneID

2613963.

KEGG

vch:VC1457.

PATRIC

20081976. VBIVibCho83274_1387.

Phylogenomic databases

eggNOG

NOG262323.

K10928.

OMA

NITFIFF.

ProtClustDB

CLSK874386.

Family and domain databases

InterPro

IPR001144. Enterotoxin_A.
[Graphical view]

Pfam

PF01375. Enterotoxin_a. 1 hit.
[Graphical view]

PRINTS

PR00771. ENTEROTOXINA.

ProtoNet

Search...

Other

EvolutionaryTrace

P01555.

Entry information

Entry name

CHTA_VIBCH

Accession

Primary (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:	May 1, 2013
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Cleaved into the following 2 chains:

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Genome annotation databases

Phylogenomic databases

Family and domain databases

Other

Entry information

Relevant documents