CHTA_VIBCH
ID CHTA_VIBCH Reviewed; 258 AA.
AC P01555; Q56634; Q9JPV1;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-1986, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Cholera enterotoxin subunit A;
DE AltName: Full=Cholera enterotoxin, A chain;
DE Contains:
DE RecName: Full=Cholera enterotoxin subunit A1;
DE EC=2.4.2.-;
DE AltName: Full=Cholera enterotoxin A1 chain;
DE AltName: Full=Cholera enterotoxin alpha chain;
DE AltName: Full=NAD(+)--diphthamide ADP-ribosyltransferase;
DE Contains:
DE RecName: Full=Cholera enterotoxin subunit A2;
DE AltName: Full=Cholera enterotoxin A2 chain;
DE AltName: Full=Cholera enterotoxin gamma chain;
DE Flags: Precursor;
GN Name=ctxA; Synonyms=toxA; OrderedLocusNames=VC_1457;
OS Vibrio cholerae serotype O1 (strain ATCC 39315 / El Tor Inaba N16961).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Vibrionales; Vibrionaceae;
OC Vibrio.
OX NCBI_TaxID=243277;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 39050 / El Tor Inaba 2125 / Serotype O1;
RX PubMed=6646234; DOI=10.1038/306551a0;
RA Mekalanos J.J., Swartz D.J., Pearson G.D.N., Harford N., Groyne F.,
RA de Wilde M.;
RT "Cholera toxin genes: nucleotide sequence, deletion analysis and vaccine
RT development.";
RL Nature 306:551-557(1983).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 25870 / Classical Inaba 569B / Serotype O1;
RX PubMed=1883840; DOI=10.1016/0167-4781(91)90050-v;
RA Dams E., de Wolf M., Dierick W.;
RT "Nucleotide sequence analysis of the CT operon of the Vibrio cholerae
RT classical strain 569B.";
RL Biochim. Biophys. Acta 1090:139-141(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=1854 / O139-Bengal;
RA Yamamoto K., Do V.G.R.F., Xu M., Iida T., Miwatani T., Albert M.J.,
RA Honda T.;
RL Submitted (MAY-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 39050 / El Tor Inaba 2125 / Serotype O1;
RA Dams E., de Wolf M., Dierick W.;
RL Submitted (MAY-1991) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=KNIH002;
RA Shin H.J., Park Y.C., Kim Y.C.;
RT "Cloning and nucleotide sequence analysis of the virulence gene cassette
RT from Vibrio cholerae KNIH002 isolated in Korea.";
RL Misainmurhag Hoiji 35:205-210(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 39315 / El Tor Inaba N16961;
RX PubMed=10952301; DOI=10.1038/35020000;
RA Heidelberg J.F., Eisen J.A., Nelson W.C., Clayton R.A., Gwinn M.L.,
RA Dodson R.J., Haft D.H., Hickey E.K., Peterson J.D., Umayam L.A., Gill S.R.,
RA Nelson K.E., Read T.D., Tettelin H., Richardson D.L., Ermolaeva M.D.,
RA Vamathevan J.J., Bass S., Qin H., Dragoi I., Sellers P., McDonald L.A.,
RA Utterback T.R., Fleischmann R.D., Nierman W.C., White O., Salzberg S.L.,
RA Smith H.O., Colwell R.R., Mekalanos J.J., Venter J.C., Fraser C.M.;
RT "DNA sequence of both chromosomes of the cholera pathogen Vibrio
RT cholerae.";
RL Nature 406:477-483(2000).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-212.
RC STRAIN=ATCC 25870 / Classical Inaba 569B / Serotype O1;
RX PubMed=6090390; DOI=10.1128/jb.159.3.1086-1089.1984;
RA Lockman H.A., Galen J.E., Kaper J.B.;
RT "Vibrio cholerae enterotoxin genes: nucleotide sequence analysis of DNA
RT encoding ADP-ribosyltransferase.";
RL J. Bacteriol. 159:1086-1089(1984).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 213-258.
RX PubMed=6315707; DOI=10.1016/s0021-9258(17)43977-9;
RA Lockman H., Kaper J.B.;
RT "Nucleotide sequence analysis of the A2 and B subunits of Vibrio cholerae
RT enterotoxin.";
RL J. Biol. Chem. 258:13722-13726(1983).
RN [9]
RP PROTEIN SEQUENCE OF 19-27.
RX PubMed=7238869; DOI=10.1016/0014-5793(81)80238-4;
RA Duffy L.K., Peterson J.W., Kurosky A.;
RT "Isolation and characterization of a precursor form of the 'A' subunit of
RT cholera toxin.";
RL FEBS Lett. 126:187-190(1981).
RN [10]
RP PROTEIN SEQUENCE OF 19-38 AND 213-232.
RX PubMed=955672; DOI=10.1016/0019-2791(76)90173-7;
RA Klapper D.G., Finkelstein R.A., Capra J.D.;
RT "Subunit structure and N-terminal amino acid sequence of the three chains
RT of cholera enterotoxin.";
RL Immunochemistry 13:605-611(1976).
RN [11]
RP PROTEIN SEQUENCE OF 27-72 AND 111-139.
RX PubMed=437113; DOI=10.1016/0014-5793(79)81136-9;
RA Lai C.-Y., Cancedda F., Chang D.;
RT "Primary structure of cholera toxin subunit A1: isolation, partial
RT sequences and alignment of the BrCN fragments.";
RL FEBS Lett. 100:85-89(1979).
RN [12]
RP PROTEIN SEQUENCE OF 213-258.
RX PubMed=7028752; DOI=10.1016/s0021-9258(18)43262-0;
RA Duffy L.K., Peterson J.W., Kurosky A.;
RT "Covalent structure of the gamma chain of the A subunit of cholera toxin.";
RL J. Biol. Chem. 256:12252-12256(1981).
RN [13]
RP INTERACTION BETWEEN CHOLERA TOXIN AND ADENYLATE CYCLASE.
RX PubMed=4323551; DOI=10.1038/229266a0;
RA Sharp G.W., Hynie S.;
RT "Stimulation of intestinal adenyl cyclase by cholera toxin.";
RL Nature 229:266-269(1971).
RN [14]
RP SUBUNIT.
RX PubMed=3214; DOI=10.1021/bi00651a011;
RA Gill D.M.;
RT "The arrangement of subunits in cholera toxin.";
RL Biochemistry 15:1242-1248(1976).
RN [15]
RP TRANSPORT OF CHOLERA TOXIN WITHIN THE INTESTINAL CELL.
RX PubMed=13679513; DOI=10.1091/mbc.e03-06-0354;
RA Fujinaga Y., Wolf A.A., Rodighiero C., Wheeler H., Tsai B., Allen L.,
RA Jobling M.G., Rapoport T., Holmes R.K., Lencer W.I.;
RT "Gangliosides that associate with lipid rafts mediate transport of cholera
RT and related toxins from the plasma membrane to endoplasmic reticulum.";
RL Mol. Biol. Cell 14:4783-4793(2003).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=7658473; DOI=10.1006/jmbi.1995.0456;
RA Zhang R.-G., Scott D.L., Westbrook M.L., Nance S., Spangler B.D.,
RA Shipley G.G., Westbrook E.M.;
RT "The three-dimensional crystal structure of cholera toxin.";
RL J. Mol. Biol. 251:563-573(1995).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 19-210 IN COMPLEX WITH NAD AND
RP HUMAN ARF6, AND SUBUNIT.
RX PubMed=16099990; DOI=10.1126/science.1113398;
RA O'Neal C.J., Jobling M.G., Holmes R.K., Hol W.G.;
RT "Structural basis for the activation of cholera toxin by human ARF6-GTP.";
RL Science 309:1093-1096(2005).
CC -!- FUNCTION: The A1 chain catalyzes the ADP-ribosylation of Gs alpha, a
CC GTP-binding regulatory protein, to activate the adenylate cyclase. This
CC leads to an overproduction of cAMP and eventually to a hypersecretion
CC of chloride and bicarbonate followed by water, resulting in the
CC characteristic cholera stool. The A2 chain tethers A1 to the pentameric
CC ring.
CC -!- SUBUNIT: The holotoxin (choleragen) consists of a pentameric ring of B
CC subunits whose central pore is occupied by the A subunit. The A subunit
CC contains two chains, A1 and A2, linked by a disulfide bridge.
CC Interaction with the host protein ARF6 causes a conformation change so
CC that the enterotoxin subunit A1 can bind NAD and catalyze the ADP-
CC ribosylation of the host Gs alpha. {ECO:0000269|PubMed:16099990,
CC ECO:0000269|PubMed:3214}.
CC -!- INTERACTION:
CC P01555; P01556: ctxB; NbExp=5; IntAct=EBI-1038392, EBI-1038383;
CC -!- DOMAIN: The four C-terminal residues of the A2 chain occupy the central
CC pore of the holotoxin. Deletion of these residues weakens the
CC interaction between the A subunit and the B pentamer without impairing
CC the pentamer formation.
CC -!- MISCELLANEOUS: After binding to gangliosides GM1 in lipid rafts,
CC through the subunit B pentamer, the holotoxin and the gangliosides are
CC internalized. The holotoxin remains bound to GM1 until arrival in the
CC ER. The A subunit has previously been cleaved in the intestinal lumen
CC but the A1 and A2 chains have remained associated. In the ER, the A
CC subunit disulfide bridge is reduced, the A1 chain is unfolded by the
CC PDI and disassembled from the rest of the toxin. Then, the membrane-
CC associated ER oxidase ERO1 oxidizes PDI, which releases the unfolded A1
CC chain. The next step is the retrotranslocation of A1 into the cytosol.
CC This might be mediated by the protein-conducting pore SEC61. Upon
CC arrival in the cytosol, A1 refolds and avoids proteasome degradation.
CC In one way or another, A1 finally reaches its target and induces
CC toxicity.
CC -!- SIMILARITY: Belongs to the enterotoxin A family. {ECO:0000305}.
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DR EMBL; X00171; CAA24995.1; -; Genomic_DNA.
DR EMBL; X58785; CAA41590.1; -; Genomic_DNA.
DR EMBL; D30053; BAA06290.1; -; Genomic_DNA.
DR EMBL; X58786; CAA41592.1; -; Genomic_DNA.
DR EMBL; K02679; AAA27514.1; -; Genomic_DNA.
DR EMBL; AF175708; AAD51359.1; -; Genomic_DNA.
DR EMBL; AE003852; AAF94614.1; -; Genomic_DNA.
DR EMBL; K01170; AAA27572.1; -; Genomic_DNA.
DR EMBL; D30052; BAA06288.1; -; Genomic_DNA.
DR PIR; A05129; XVVCA.
DR RefSeq; NP_231100.1; NC_002505.1.
DR RefSeq; WP_001881225.1; NZ_LT906614.1.
DR PDB; 1S5B; X-ray; 2.13 A; A=19-258.
DR PDB; 1S5C; X-ray; 2.50 A; A=19-258.
DR PDB; 1S5D; X-ray; 1.75 A; A=19-258.
DR PDB; 1S5E; X-ray; 1.90 A; A/B=19-258.
DR PDB; 1S5F; X-ray; 2.60 A; A=19-258.
DR PDB; 1XTC; X-ray; 2.40 A; A=19-212, C=213-258.
DR PDB; 2A5D; X-ray; 1.80 A; B=19-210.
DR PDB; 2A5F; X-ray; 2.02 A; B=19-210.
DR PDB; 2A5G; X-ray; 2.66 A; B=19-210.
DR PDBsum; 1S5B; -.
DR PDBsum; 1S5C; -.
DR PDBsum; 1S5D; -.
DR PDBsum; 1S5E; -.
DR PDBsum; 1S5F; -.
DR PDBsum; 1XTC; -.
DR PDBsum; 2A5D; -.
DR PDBsum; 2A5F; -.
DR PDBsum; 2A5G; -.
DR AlphaFoldDB; P01555; -.
DR BMRB; P01555; -.
DR SMR; P01555; -.
DR DIP; DIP-6255N; -.
DR ELM; P01555; -.
DR IntAct; P01555; 2.
DR STRING; 243277.VC_1457; -.
DR DNASU; 2613963; -.
DR EnsemblBacteria; AAF94614; AAF94614; VC_1457.
DR GeneID; 57740120; -.
DR KEGG; vch:VC_1457; -.
DR PATRIC; fig|243277.26.peg.1387; -.
DR eggNOG; ENOG5033C2P; Bacteria.
DR HOGENOM; CLU_091751_0_0_6; -.
DR OMA; PRGHNEY; -.
DR BioCyc; MetaCyc:VC1457-MON; -.
DR BioCyc; VCHO:VC1457-MON; -.
DR EvolutionaryTrace; P01555; -.
DR PHI-base; PHI:698; -.
DR PRO; PR:P01555; -.
DR Proteomes; UP000000584; Chromosome 1.
DR GO; GO:1902494; C:catalytic complex; IMP:CAFA.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0042597; C:periplasmic space; IMP:CAFA.
DR GO; GO:0005534; F:galactose binding; IMP:CAFA.
DR GO; GO:0016757; F:glycosyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; IDA:CACAO.
DR DisProt; DP00250; -.
DR InterPro; IPR001144; Enterotoxin_A.
DR Pfam; PF01375; Enterotoxin_a; 1.
DR PRINTS; PR00771; ENTEROTOXINA.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond; Enterotoxin;
KW Glycosyltransferase; NAD; Nucleotidyltransferase; Reference proteome;
KW Signal; Toxin; Transferase; Virulence.
FT SIGNAL 1..18
FT /evidence="ECO:0000269|PubMed:7238869,
FT ECO:0000269|PubMed:955672"
FT CHAIN 19..212
FT /note="Cholera enterotoxin subunit A1"
FT /id="PRO_0000019342"
FT CHAIN 213..258
FT /note="Cholera enterotoxin subunit A2"
FT /id="PRO_0000019343"
FT ACT_SITE 130
FT /evidence="ECO:0000250"
FT BINDING 25..28
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16099990"
FT BINDING 41..43
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:16099990"
FT DISULFID 205..217
FT /note="Interchain (between A1 and A2 chains)"
FT CONFLICT 20
FT /note="D -> N (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 37
FT /note="S -> R (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 39
FT /note="G -> L (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 45..46
FT /note="QS -> SE (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="N -> L (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 132
FT /note="S -> A (in Ref. 11; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 213
FT /note="M -> I (in Ref. 1; CAA24995)"
FT /evidence="ECO:0000305"
FT CONFLICT 247..248
FT /note="DI -> ID (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="D -> N (in Ref. 12; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 22..29
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 31..37
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:1S5D"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:1XTC"
FT HELIX 59..64
FT /evidence="ECO:0007829|PDB:1S5D"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:1S5D"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 84..94
FT /evidence="ECO:0007829|PDB:1S5D"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:2A5D"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:1S5D"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 115..119
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 126..128
FT /evidence="ECO:0007829|PDB:1S5D"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 139..141
FT /evidence="ECO:0007829|PDB:1S5D"
FT STRAND 142..149
FT /evidence="ECO:0007829|PDB:1S5D"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:1S5B"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:1S5B"
FT HELIX 165..169
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 190..193
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 197..200
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 217..244
FT /evidence="ECO:0007829|PDB:1S5D"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:1S5D"
FT TURN 250..252
FT /evidence="ECO:0007829|PDB:1S5D"
FT HELIX 254..257
FT /evidence="ECO:0007829|PDB:1XTC"
SQ SEQUENCE 258 AA; 29336 MW; 0F7EBAE62069A5D0 CRC64;
MVKIIFVFFI FLSSFSYAND DKLYRADSRP PDEIKQSGGL MPRGQSEYFD RGTQMNINLY
DHARGTQTGF VRHDDGYVST SISLRSAHLV GQTILSGHST YYIYVIATAP NMFNVNDVLG
AYSPHPDEQE VSALGGIPYS QIYGWYRVHF GVLDEQLHRN RGYRDRYYSN LDIAPAADGY
GLAGFPPEHR AWREEPWIHH APPGCGNAPR SSMSNTCDEK TQSLGVKFLD EYQSKVKRQI
FSGYQSDIDT HNRIKDEL
