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Protein

Cholera enterotoxin subunit A

Gene

ctxA

Organism
Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961)
Status
Reviewed-Annotation score: -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.

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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei130By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi25 – 28NAD1 Publication4
Nucleotide bindingi41 – 43NAD1 Publication3

GO - Molecular functioni

  • galactose binding Source: CAFA
  • NAD+ ADP-ribosyltransferase activity Source: TIGR
  • toxin activity Source: UniProtKB-KW

GO - Biological processi

Keywordsi

Molecular functionEnterotoxin, Glycosyltransferase, Toxin, Transferase
LigandNAD

Enzyme and pathway databases

BioCyciMetaCyc:VC1457-MONOMER
VCHO: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
Proteomesi
  • UP000000584 Componenti: Chromosome 1

Subcellular locationi

GO - Cellular componenti

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 182 PublicationsAdd BLAST18
ChainiPRO_000001934219 – 212Cholera enterotoxin subunit A1Add BLAST194
ChainiPRO_0000019343213 – 258Cholera enterotoxin subunit A2Add BLAST46

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
ELMiP01555
IntActiP01555, 2 interactors
STRINGi243277.VC1457

Structurei

Secondary structure

1258
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

DisProtiDP00250
ProteinModelPortaliP01555
SMRiP01555
ModBaseiSearch...
MobiDBiSearch...

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.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG4107927 Bacteria
ENOG410Y5VZ LUCA
KOiK10928
OMAiPRGHNEY

Family and domain databases

InterProiView protein in InterPro
IPR001144 Enterotoxin_A
PfamiView protein in Pfam
PF01375 Enterotoxin_a, 1 hit
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
        10         20         30         40         50
MVKIIFVFFI FLSSFSYAND DKLYRADSRP PDEIKQSGGL MPRGQSEYFD
60 70 80 90 100
RGTQMNINLY DHARGTQTGF VRHDDGYVST SISLRSAHLV GQTILSGHST
110 120 130 140 150
YYIYVIATAP NMFNVNDVLG AYSPHPDEQE VSALGGIPYS QIYGWYRVHF
160 170 180 190 200
GVLDEQLHRN RGYRDRYYSN LDIAPAADGY GLAGFPPEHR AWREEPWIHH
210 220 230 240 250
APPGCGNAPR SSMSNTCDEK TQSLGVKFLD EYQSKVKRQI FSGYQSDIDT

HNRIKDEL
Length:258
Mass (Da):29,336
Last modified:October 23, 1986 - v1
Checksum:i0F7EBAE62069A5D0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti20D → N AA sequence (PubMed:7238869).Curated1
Sequence conflicti37S → R AA sequence (PubMed:955672).Curated1
Sequence conflicti39G → L AA sequence (PubMed:437113).Curated1
Sequence conflicti45 – 46QS → SE AA sequence (PubMed:437113).Curated2
Sequence conflicti111N → L AA sequence (PubMed:437113).Curated1
Sequence conflicti132S → A AA sequence (PubMed:437113).Curated1
Sequence conflicti213M → I in CAA24995 (PubMed:6646234).Curated1
Sequence conflicti247 – 248DI → ID AA sequence (PubMed:7028752).Curated2
Sequence conflicti256D → N AA sequence (PubMed:7028752).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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
PATRICifig|243277.26.peg.1387

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-6255N
ELMiP01555
IntActiP01555, 2 interactors
STRINGi243277.VC1457

Protocols and materials databases

DNASUi2613963
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAF94614; AAF94614; VC_1457
GeneIDi2613963
KEGGivch:VC1457
PATRICifig|243277.26.peg.1387

Phylogenomic databases

eggNOGiENOG4107927 Bacteria
ENOG410Y5VZ LUCA
KOiK10928
OMAiPRGHNEY

Enzyme and pathway databases

BioCyciMetaCyc:VC1457-MONOMER
VCHO:VC1457-MONOMER

Miscellaneous databases

EvolutionaryTraceiP01555
PROiPR:P01555

Family and domain databases

InterProiView protein in InterPro
IPR001144 Enterotoxin_A
PfamiView protein in Pfam
PF01375 Enterotoxin_a, 1 hit
PRINTSiPR00771 ENTEROTOXINA
ProtoNetiSearch...

Entry informationi

Entry nameiCHTA_VIBCH
AccessioniPrimary (citable) accession number: P01555
Secondary accession number(s): Q56634, Q9JPV1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: October 23, 1986
Last modified: July 18, 2018
This is version 140 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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