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Protein

Pertussis toxin subunit 1

Gene

ptxA

Organism
Bordetella pertussis (strain Tohama I / ATCC BAA-589 / NCTC 13251)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

S1 is an NAD-dependent ADP-ribosyltransferase, which plays a crucial role in the pathogenesis of B.pertussis causing disruption of normal host cellular regulation. It catalyzes the ADP-ribosylation of a cysteine in the alpha subunit of host heterotrimeric G proteins. In the absence of G proteins it also catalyzes the cleavage of NAD+ into ADP-ribose and nicotinamide. It irreversibly uncouples the G-alpha GTP-binding proteins from their membrane receptors.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei60 – 601NAD
Active sitei69 – 691
Active sitei163 – 1631

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Glycosyltransferase, Toxin, Transferase

Keywords - Biological processi

Virulence

Keywords - Ligandi

NAD

Enzyme and pathway databases

BioCyciBPER257313:BP3783-MONOMER.

Protein family/group databases

TCDBi1.C.72.1.1. the pertussis toxin (ptx) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Pertussis toxin subunit 1
Short name:
PTX S1
Alternative name(s):
Islet-activating protein S1
Short name:
IAP S1
NAD-dependent ADP-ribosyltransferase (EC:2.4.2.-)
Gene namesi
Name:ptxA
Ordered Locus Names:BP3783
OrganismiBordetella pertussis (strain Tohama I / ATCC BAA-589 / NCTC 13251)
Taxonomic identifieri257313 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaBetaproteobacteriaBurkholderialesAlcaligenaceaeBordetella
Proteomesi
  • UP000002676 Componenti: Chromosome

Subcellular locationi

  • Secreted 1 Publication

  • Note: The individual chains are secreted by a sec-dependent mechanism into the periplasm. Then, S1 associates with the outer membrane before it joins with the B subunit to form the secretion-competent holotoxin. The type IV secretion system ptl mediates secretion of assembled toxin through the outer membrane.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

Currently used in vaccines available under the names Daptacel (Sanofi Pasteur), Infanrix (GlaxoSmithKline), Pediarix (GlaxoSmithKline), TriHIBit (Sanofi Pasteur) and Tripedia (Sanofi Pasteur).

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi75 – 751C → G: 38% of wild-type NAD-glycohydrolase activity. 1 Publication
Mutagenesisi75 – 751C → S: 33% of wild-type NAD-glycohydrolase activity. 1 Publication
Mutagenesisi75 – 751Missing : More than 100-fold reduction of NAD-glycohydrolase activity. 1 Publication
Mutagenesisi88 – 881S → G: No functional toxin produced although some mature size S1 protein accumulates in the periplasm. 1 Publication
Mutagenesisi89 – 891S → G: Very low amount of final toxin secreted; approximately 50% of wild-type toxin level accumulate in the periplasm despite near wild-type levels of mature size S1 in the periplasm. 1 Publication
Mutagenesisi90 – 901S → G: Very low amount of final toxin secreted; approximately 50% of wild-type toxin level accumulate in the periplasm despite near wild-type levels of mature size S1 in the periplasm. 1 Publication
Mutagenesisi91 – 911R → K: Very low amounts of final toxin secreted; about 60% of wild-type toxin levels accumulate in the periplasm. Near wild-type levels of mature size S1 in the periplasm. 1 Publication
Mutagenesisi163 – 1631E → D: Reduction of several orders of magnitude of enzymatic activity. 1 Publication
Mutagenesisi163 – 1631Missing : Dramatic decrease in enzymatic activity. 1 Publication
Mutagenesisi269 – 2691Missing : Affects both protein stability and outer membrane targeting. 1 Publication

Keywords - Diseasei

Whooping cough

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3434Add
BLAST
Chaini35 – 269235Pertussis toxin subunit 1PRO_0000019359Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi75 ↔ 235

Keywords - PTMi

Disulfide bond

Expressioni

Inductioni

Activated by the two-component regulatory system BvgS/BvgA.

Interactioni

Subunit structurei

Pertussis toxin contains five different chains, S1-S5. They are organized into 2 functional subunits: A, composed of S1 (which is toxic) and B, containing S2, S3, S5, and two copies of S4 (B binds to the membrane receptors). Dimers of S2-S4 and S3-S4 are held together by S5.1 Publication

Protein-protein interaction databases

STRINGi257313.BP3783.

Structurei

Secondary structure

1
269
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi39 – 479Combined sources
Helixi49 – 557Combined sources
Helixi66 – 705Combined sources
Helixi73 – 753Combined sources
Turni77 – 793Combined sources
Beta strandi82 – 898Combined sources
Helixi91 – 10919Combined sources
Turni110 – 1123Combined sources
Beta strandi116 – 12611Combined sources
Beta strandi131 – 1333Combined sources
Helixi134 – 14512Combined sources
Helixi147 – 1493Combined sources
Helixi152 – 16110Combined sources
Beta strandi163 – 1708Combined sources
Helixi172 – 1743Combined sources
Beta strandi175 – 18410Combined sources
Turni185 – 1884Combined sources
Beta strandi189 – 1946Combined sources
Beta strandi208 – 2103Combined sources
Beta strandi225 – 2273Combined sources
Turni228 – 2314Combined sources
Helixi234 – 2407Combined sources
Beta strandi259 – 2613Combined sources
Helixi262 – 2654Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BCPX-ray2.70A/G35-269[»]
1PRTX-ray2.90A/G36-269[»]
1PTOX-ray3.50A/G26-269[»]
ProteinModelPortaliP04977.
SMRiP04977. Positions 36-269.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04977.

Family & Domainsi

Domaini

The region which spans amino acids 42-49 is required for enzymatic activity and contributes to the formation of a potentially important antigenic determinant.1 Publication

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG4106DF6. Bacteria.
ENOG410XY7Z. LUCA.
HOGENOMiHOG000154667.
KOiK11023.
OMAiPPDIVWR.
OrthoDBiEOG6NKQZB.

Family and domain databases

InterProiIPR003898. Borpert_toxA.
[Graphical view]
PfamiPF02917. Pertussis_S1. 1 hit.
[Graphical view]
PRINTSiPR01395. BORPETOXINA.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P04977-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRCTRAIRQT ARTGWLTWLA ILAVTAPVTS PAWADDPPAT VYRYDSRPPE
60 70 80 90 100
DVFQNGFTAW GNNDNVLDHL TGRSCQVGSS NSAFVSTSSS RRYTEVYLEH
110 120 130 140 150
RMQEAVEAER AGRGTGHFIG YIYEVRADNN FYGAASSYFE YVDTYGDNAG
160 170 180 190 200
RILAGALATY QSEYLAHRRI PPENIRRVTR VYHNGITGET TTTEYSNARY
210 220 230 240 250
VSQQTRANPN PYTSRRSVAS IVGTLVRMAP VIGACMARQA ESSEAMAAWS
260
ERAGEAMVLV YYESIAYSF
Length:269
Mass (Da):29,974
Last modified:August 13, 1987 - v1
Checksum:iF6C88C16DA6B08AB
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti68 – 681D → E in strain: 10536, CZ, 18323 and B6.
Natural varianti129 – 1291N → S in strain: CS.
Natural varianti196 – 1961S → P in strain: CZ and 18323.
Natural varianti228 – 2281M → I in strain: 287, Al1561, B572, CHANG and HAV.
Natural varianti232 – 2321I → M in strain: CZ and 18323.
Natural varianti232 – 2321I → V in strain: 10536 and B6.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14378 Genomic DNA. Translation: AAA83980.1.
M13223 Genomic DNA. Translation: AAA22981.1.
X16347 Genomic DNA. Translation: CAA34397.1.
AJ245366 Genomic DNA. Translation: CAB51472.1.
AJ245367 Genomic DNA. Translation: CAB51542.1.
AJ245368 Genomic DNA. Translation: CAB51543.1.
AJ506996 Genomic DNA. Translation: CAD44970.1.
AJ006151 Genomic DNA. Translation: CAA06893.1.
AJ006153 Genomic DNA. Translation: CAA06895.1.
AJ006155 Genomic DNA. Translation: CAA06897.1.
AJ006157 Genomic DNA. Translation: CAA06899.1.
AJ006159 Genomic DNA. Translation: CAA06901.1.
AJ007363 Genomic DNA. Translation: CAA07478.1.
AJ007364 Genomic DNA. Translation: CAA07479.1.
AJ506994 Genomic DNA. Translation: CAD44968.1.
AJ506995 Genomic DNA. Translation: CAD44969.1.
AY879289 Genomic DNA. Translation: AAW72734.1.
AJ920066 Genomic DNA. Translation: CAI72620.1.
BX640422 Genomic DNA. Translation: CAE44038.1.
PIRiA24144. WEBR1P.
A24394. WEBR11.
RefSeqiNP_882282.1. NC_002929.2.
WP_010931648.1. NC_002929.2.

Genome annotation databases

EnsemblBacteriaiCAE44038; CAE44038; BP3783.
GeneIDi2665068.
KEGGibpe:BP3783.
PATRICi21161246. VBIBorPer7866_4087.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14378 Genomic DNA. Translation: AAA83980.1.
M13223 Genomic DNA. Translation: AAA22981.1.
X16347 Genomic DNA. Translation: CAA34397.1.
AJ245366 Genomic DNA. Translation: CAB51472.1.
AJ245367 Genomic DNA. Translation: CAB51542.1.
AJ245368 Genomic DNA. Translation: CAB51543.1.
AJ506996 Genomic DNA. Translation: CAD44970.1.
AJ006151 Genomic DNA. Translation: CAA06893.1.
AJ006153 Genomic DNA. Translation: CAA06895.1.
AJ006155 Genomic DNA. Translation: CAA06897.1.
AJ006157 Genomic DNA. Translation: CAA06899.1.
AJ006159 Genomic DNA. Translation: CAA06901.1.
AJ007363 Genomic DNA. Translation: CAA07478.1.
AJ007364 Genomic DNA. Translation: CAA07479.1.
AJ506994 Genomic DNA. Translation: CAD44968.1.
AJ506995 Genomic DNA. Translation: CAD44969.1.
AY879289 Genomic DNA. Translation: AAW72734.1.
AJ920066 Genomic DNA. Translation: CAI72620.1.
BX640422 Genomic DNA. Translation: CAE44038.1.
PIRiA24144. WEBR1P.
A24394. WEBR11.
RefSeqiNP_882282.1. NC_002929.2.
WP_010931648.1. NC_002929.2.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1BCPX-ray2.70A/G35-269[»]
1PRTX-ray2.90A/G36-269[»]
1PTOX-ray3.50A/G26-269[»]
ProteinModelPortaliP04977.
SMRiP04977. Positions 36-269.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi257313.BP3783.

Protein family/group databases

TCDBi1.C.72.1.1. the pertussis toxin (ptx) family.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiCAE44038; CAE44038; BP3783.
GeneIDi2665068.
KEGGibpe:BP3783.
PATRICi21161246. VBIBorPer7866_4087.

Phylogenomic databases

eggNOGiENOG4106DF6. Bacteria.
ENOG410XY7Z. LUCA.
HOGENOMiHOG000154667.
KOiK11023.
OMAiPPDIVWR.
OrthoDBiEOG6NKQZB.

Enzyme and pathway databases

BioCyciBPER257313:BP3783-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP04977.

Family and domain databases

InterProiIPR003898. Borpert_toxA.
[Graphical view]
PfamiPF02917. Pertussis_S1. 1 hit.
[Graphical view]
PRINTSiPR01395. BORPETOXINA.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and sequencing of the pertussis toxin genes: operon structure and gene duplication."
    Nicosia A., Perugini M., Franzini C., Casagli M.C., Borri M.G., Antoni G., Almoni M., Neri P., Ratti G., Rappuoli R.
    Proc. Natl. Acad. Sci. U.S.A. 83:4631-4635(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: BP165.
  2. "Pertussis toxin gene: nucleotide sequence and genetic organization."
    Locht C., Keith J.M.
    Science 232:1258-1264(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 3779.
  3. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 10536.
  4. "Polymorphism in the Bordetella pertussis virulence factors P.69/pertactin and pertussis toxin in The Netherlands: temporal trends and evidence for vaccine-driven evolution."
    Mooi F.R., van Oirschot H., Heuvelman K., van der Heide H.G., Gaastra W., Willems R.J.
    Infect. Immun. 66:670-675(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: B572, B592 and B6.
  5. "Intranasal murine model of Bordetella pertussis infection: II. Sequence variation and protection induced by a tricomponent acellular vaccine."
    Boursaux-Eude C., Thiberge S., Carletti G., Guiso N.
    Vaccine 17:2651-2660(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 18323, 287, Al1561, CZ, HAV, Tohama I / ATCC BAA-589 / NCTC 13251 and Wellcome 28.
  6. "Temporal trends in circulating Bordetella pertussis strains in Australia."
    Poynten M., McIntyre P.B., Mooi F.R., Heuvelman G.L., Gilbert G.L.
    Epidemiol. Infect. 132:185-193(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: CHANG.
  7. Wang Y., Zhang S., Lei D.
    Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: CS.
  8. "Bordetella pertussis toxin gene encoding subunit S1."
    Mallya A.D., Kumar M., Reddy M.N., Seshubabu B., Deobagkar D.D., Kapre S.V.
    Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 134.
  9. "Comparative analysis of the genome sequences of Bordetella pertussis, Bordetella parapertussis and Bordetella bronchiseptica."
    Parkhill J., Sebaihia M., Preston A., Murphy L.D., Thomson N.R., Harris D.E., Holden M.T.G., Churcher C.M., Bentley S.D., Mungall K.L., Cerdeno-Tarraga A.-M., Temple L., James K.D., Harris B., Quail M.A., Achtman M., Atkin R., Baker S.
    , Basham D., Bason N., Cherevach I., Chillingworth T., Collins M., Cronin A., Davis P., Doggett J., Feltwell T., Goble A., Hamlin N., Hauser H., Holroyd S., Jagels K., Leather S., Moule S., Norberczak H., O'Neil S., Ormond D., Price C., Rabbinowitsch E., Rutter S., Sanders M., Saunders D., Seeger K., Sharp S., Simmonds M., Skelton J., Squares R., Squares S., Stevens K., Unwin L., Whitehead S., Barrell B.G., Maskell D.J.
    Nat. Genet. 35:32-40(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Tohama I / ATCC BAA-589 / NCTC 13251.
  10. "Identification of a region in the S1 subunit of pertussis toxin that is required for enzymatic activity and that contributes to the formation of a neutralizing antigenic determinant."
    Cieplak W., Burnette W.N., Mar V.L., Kaljot K.T., Morris C.F., Chen K.K., Sato H., Keith J.M.
    Proc. Natl. Acad. Sci. U.S.A. 85:4667-4671(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 35-64, DOMAIN.
  11. "Identification of an active-site residue in subunit S1 of pertussis toxin by photocrosslinking to NAD."
    Cockle S.A.
    FEBS Lett. 249:329-332(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 153-169, ACTIVE SITE.
    Strain: 10536.
  12. "Role of tryptophan 26 in the NAD glycohydrolase reaction of the S-1 subunit of pertussis toxin."
    Cortina G., Barbieri J.T.
    J. Biol. Chem. 264:17322-17328(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: ROLE OF TRP-60.
  13. "Further analysis of the sequence of the S1 subunit of pertussis toxin."
    Pizza M., Bugnoli M., Puccini P., Siciliano R., Marino G., Rappuoli R.
    Infect. Immun. 59:1177-1179(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
  14. "A proposed mechanism of ADP-ribosylation catalyzed by the pertussis toxin S1 subunit."
    Locht C., Antoine R.
    Biochimie 77:333-340(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACTIVE SITE, CATALYTIC MECHANISM, MUTAGENESIS OF CYS-75 AND GLU-163.
  15. "Synergistic binding of RNA polymerase and BvgA phosphate to the pertussis toxin promoter of Bordetella pertussis."
    Boucher P.E., Stibitz S.
    J. Bacteriol. 177:6486-6491(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: REGULATION BY BVGA.
    Strain: Tohama I / ATCC BAA-589 / NCTC 13251.
  16. "Mutations in the S1 subunit of pertussis toxin that affect secretion."
    Craig-Mylius K.A., Stenson T.H., Weiss A.A.
    Infect. Immun. 68:1276-1281(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF SER-88; SER-89; SER-90 AND ARG-91.
    Strain: Tohama I / BP338.
  17. "Membrane localization of the S1 subunit of pertussis toxin in Bordetella pertussis and implications for pertussis toxin secretion."
    Farizo K.M., Fiddner S., Cheung A.M., Burns D.L.
    Infect. Immun. 70:1193-1201(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TOXIN ASSEMBLY AND SECRETION, MUTAGENESIS OF PHE-269.
    Strain: Tohama I / ATCC BAA-589 / NCTC 13251.
  18. "DsbA and DsbC are required for secretion of pertussis toxin by Bordetella pertussis."
    Stenson T.H., Weiss A.A.
    Infect. Immun. 70:2297-2303(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PERIPLASMIC TOXIN ASSEMBLY.
    Strain: Tohama I / BP338.
  19. "Temporal expression of pertussis toxin and Ptl secretion proteins by Bordetella pertussis."
    Rambow-Larsen A.A., Weiss A.A.
    J. Bacteriol. 186:43-50(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: TOXIN ASSEMBLY AND SECRETION.
    Strain: Tohama I / BP338.
  20. Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
    Strain: 10536.
  21. "Crystal structure of the pertussis toxin-ATP complex: a molecular sensor."
    Hazes B., Boodhoo A., Cockle S.A., Read R.J.
    J. Mol. Biol. 258:661-671(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH ATP.

Entry informationi

Entry nameiTOX1_BORPE
AccessioniPrimary (citable) accession number: P04977
Secondary accession number(s): O69258
, O70057, Q599G4, Q5EIB9, Q93V22
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: August 13, 1987
Last modified: May 11, 2016
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Thiol:disulfide oxidoreductases DsbA and DsbB are required for periplasmic toxin assembly, whereas DbsC is important for extracellular toxin secretion.
Experiments with temporal expression of PTX indicate that holotoxin secretion is at a rate of 3 molecules/min/cell. Also, more of toxin chains S1, S2 and S3 are produced than secreted; one half of each chain is incorporated into holotoxin.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Pharmaceutical, 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.