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P01555

- CHTA_VIBCH

UniProt

P01555 - CHTA_VIBCH

Protein

Cholera enterotoxin subunit A

Gene

ctxA

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
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    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 1 (23 Oct 1986)
      Previous versions | rss
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    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 – 1301By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi25 – 284NAD1 Publication
    Nucleotide bindingi41 – 433NAD1 Publication

    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

    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

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 18182 PublicationsAdd
    BLAST
    Chaini19 – 212194Cholera enterotoxin subunit A1PRO_0000019342Add
    BLAST
    Chaini213 – 25846Cholera enterotoxin subunit A2PRO_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

    1
    258
    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.
    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

    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

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti20 – 201D → N AA sequence (PubMed:7238869)Curated
    Sequence conflicti37 – 371S → R AA sequence (PubMed:955672)Curated
    Sequence conflicti39 – 391G → L AA sequence (PubMed:437113)Curated
    Sequence conflicti45 – 462QS → SE AA sequence (PubMed:437113)Curated
    Sequence conflicti111 – 1111N → L AA sequence (PubMed:437113)Curated
    Sequence conflicti132 – 1321S → A AA sequence (PubMed:437113)Curated
    Sequence conflicti213 – 2131M → I in CAA24995. (PubMed:6646234)Curated
    Sequence conflicti247 – 2482DI → ID AA sequence (PubMed:7028752)Curated
    Sequence conflicti256 – 2561D → N AA sequence (PubMed:7028752)Curated

    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

    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: October 1, 2014
    This is version 123 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