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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: 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)DescriptionActionsGraphical viewLength
Active sitei130By similarity1

Regions

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

GO - Molecular functioni

  • NAD+ ADP-ribosyltransferase activity Source: TIGR

GO - Biological processi

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

Keywords - Molecular functioni

Enterotoxin, Glycosyltransferase, Toxin, Transferase

Keywords - Ligandi

NAD

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

Complete GO annotation...

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.
IntActiP01555. 2 interactors.
STRINGi243277.VC1457.

Structurei

Secondary structure

1258
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi22 – 29Combined sources8
Helixi31 – 37Combined sources7
Helixi43 – 45Combined sources3
Beta strandi51 – 53Combined sources3
Helixi59 – 64Combined sources6
Beta strandi70 – 72Combined sources3
Beta strandi77 – 83Combined sources7
Helixi84 – 94Combined sources11
Turni95 – 97Combined sources3
Beta strandi99 – 107Combined sources9
Beta strandi112 – 114Combined sources3
Helixi115 – 119Combined sources5
Helixi120 – 122Combined sources3
Helixi126 – 128Combined sources3
Beta strandi131 – 134Combined sources4
Helixi139 – 141Combined sources3
Beta strandi142 – 149Combined sources8
Beta strandi152 – 154Combined sources3
Beta strandi156 – 159Combined sources4
Helixi165 – 169Combined sources5
Helixi176 – 178Combined sources3
Helixi180 – 182Combined sources3
Helixi190 – 193Combined sources4
Helixi197 – 200Combined sources4
Helixi217 – 244Combined sources28
Turni245 – 247Combined sources3
Turni250 – 252Combined sources3
Helixi254 – 257Combined sources4

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...

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.
OMAiNITFIFF.

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

        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.
PATRICi20081976. VBIVibCho83274_1387.

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.
IntActiP01555. 2 interactors.
STRINGi243277.VC1457.

Protocols and materials databases

DNASUi2613963.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Phylogenomic databases

eggNOGiENOG4107927. Bacteria.
ENOG410Y5VZ. LUCA.
KOiK10928.
OMAiNITFIFF.

Enzyme and pathway databases

BioCyciMetaCyc:VC1457-MONOMER.
VCHO:VC1457-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP01555.
PROiP01555.

Family and domain databases

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

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: November 2, 2016
This is version 135 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.