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P00588 (DTX_CORBE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 90. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Diphtheria toxin
Short name=DT
Alternative name(s):
NAD(+)--diphthamide ADP-ribosyltransferase
EC=2.4.2.36

Cleaved into the following 2 chains:

  1. Diphtheria toxin fragment A
  2. Diphtheria toxin fragment B
OrganismCorynephage beta
Taxonomic identifier10703 [NCBI]
Taxonomic lineageViruses › dsDNA viruses, no RNA stage › Caudovirales › Siphoviridae › Lambdalikevirus › unclassified Lambda-like viruses
Virus hostCorynebacterium diphtheriae [TaxID: 1717]

Protein attributes

Sequence length567 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Diphtheria toxin, produced by a phage infecting Corynebacterium diphtheriae, is a proenzyme that, after activation, catalyzes the covalent attachment of the ADP ribose moiety of NAD to eukaryotic elongation factor 2 (eEF-2). Fragment A is the catalytic portion responsible for enzymatic ADP-ribosylation of elongation factor 2, while fragment B is responsible for binding of toxin to cell receptors and entry of fragment A. Ref.5 Ref.6

Catalytic activity

NAD+ + peptide diphthamide = nicotinamide + peptide N-(ADP-D-ribosyl)diphthamide.

Enzyme regulation

Partially inhibited by 1,8-naphthalimide (NAP). Ref.6

Subunit structure

Homodimer.

Sequence caution

The sequence AAA32182.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
   DomainSignal
   LigandNAD
   Molecular functionGlycosyltransferase
Toxin
Transferase
   PTMCleavage on pair of basic residues
Disulfide bond
   Technical term3D-structure
Direct protein sequencing
Gene Ontology (GO)
   Biological_processpathogenesis

Inferred from electronic annotation. Source: InterPro

   Cellular_componentextracellular region

Inferred from electronic annotation. Source: InterPro

   Molecular_functionNAD+-diphthamide ADP-ribosyltransferase activity

Inferred from electronic annotation. Source: EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232 Ref.2
Chain33 – 225193Diphtheria toxin fragment A
PRO_0000019345
Chain226 – 567342Diphtheria toxin fragment B
PRO_0000019346

Sites

Active site1801
Binding site531NAD
Binding site971NAD
Site1851Modification inactivates enzyme

Amino acid modifications

Disulfide bond218 ↔ 233
Disulfide bond493 ↔ 503

Experimental info

Mutagenesis1801E → A: Loss of toxicity. Ref.6
Sequence conflict178 – 1803SVE → VES AA sequence Ref.2

Secondary structure

1 ............................................................................................................. 567
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P00588 [UniParc].

Last modified May 1, 1991. Version 2.
Checksum: CAF82A75EA693FF8

FASTA56761,602
        10         20         30         40         50         60 
MLVRGYVVSR KLFASILIGA LLGIGAPPSA HAGADDVVDS SKSFVMENFS SYHGTKPGYV 

        70         80         90        100        110        120 
DSIQKGIQKP KSGTQGNYDD DWKGFYSTDN KYDAAGYSVD NENPLSGKAG GVVKVTYPGL 

       130        140        150        160        170        180 
TKVLALKVDN AETIKKELGL SLTEPLMEQV GTEEFIKRFG DGASRVVLSL PFAEGSSSVE 

       190        200        210        220        230        240 
YINNWEQAKA LSVELEINFE TRGKRGQDAM YEYMAQACAG NRVRRSVGSS LSCINLDWDV 

       250        260        270        280        290        300 
IRDKTKTKIE SLKEHGPIKN KMSESPNKTV SEEKAKQYLE EFHQTALEHP ELSELKTVTG 

       310        320        330        340        350        360 
TNPVFAGANY AAWAVNVAQV IDSETADNLE KTTAALSILP GIGSVMGIAD GAVHHNTEEI 

       370        380        390        400        410        420 
VAQSIALSSL MVAQAIPLVG ELVDIGFAAY NFVESIINLF QVVHNSYNRP AYSPGHKTQP 

       430        440        450        460        470        480 
FLHDGYAVSW NTVEDSIIRT GFQGESGHDI KITAENTPLP IAGVLLPTIP GKLDVNKSKT 

       490        500        510        520        530        540 
HISVNGRKIR MRCRAIDGDV TFCRPKSPVY VGNGVHANLH VAFHRSSSEK IHSNEISSDS 

       550        560 
IGVLGYQKTV DHTKVNSKLS LFFEIKS

« Hide

References

[1]"Nucleotide sequence of the structural gene for diphtheria toxin carried by corynebacteriophage beta."
Greenfield L., Bjorn M.J., Horn G., Fong D., Buck G.A., Collier R.J., Kaplan D.A.
Proc. Natl. Acad. Sci. U.S.A. 80:6853-6857(1983) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"The amino acid sequence of fragment A, an enzymically active fragment of diphtheria toxin. III. The chymotryptic peptides, the peptides derived by cleavage at tryptophan residues, and the complete sequence of the protein."
Delange R.J., Williams L.C., Drazin R.E., Collier R.J.
J. Biol. Chem. 254:5838-5842(1979) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 33-225.
[3]"Occurrence of tryptophan in the enzymically active site of diphtheria toxin fragment A."
Michel A., Dirkx J.
Biochim. Biophys. Acta 491:286-295(1977) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITE TRP-185.
[4]"Tyrosine 65 is photolabeled by 8-azidoadenine and 8-azidoadenosine at the NAD binding site of diphtheria toxin."
Papini E., Santucci A., Schiavo G., Domenighini M., Neri P., Rappuoli R., Montecucco C.
J. Biol. Chem. 266:2494-2498(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITE TYR-97.
[5]"Cholix toxin, a novel ADP-ribosylating factor from Vibrio cholerae."
Jorgensen R., Purdy A.E., Fieldhouse R.J., Kimber M.S., Bartlett D.H., Merrill A.R.
J. Biol. Chem. 283:10671-10678(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS AN ADP-RIBOSYLTRANSFERASE.
[6]"Yeast as a tool for characterizing mono-ADP-ribosyltransferase toxins."
Turgeon Z., White D., Jorgensen R., Visschedyk D., Fieldhouse R.J., Mangroo D., Merrill A.R.
FEMS Microbiol. Lett. 300:97-106(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A TOXIN, FUNCTION AS AN ADP-RIBOSYLTRANSFERASE, ENZYME REGULATION, EXPRESSION IN YEAST, MUTAGENESIS OF GLU-180.
[7]"The crystal structure of diphtheria toxin."
Choe S., Bennett M.J., Fujii G., Curmi P.M.G., Kantardjieff K.A., Collier R.J., Eisenberg D.
Nature 357:216-222(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[8]"Crystal structure of diphtheria toxin bound to nicotinamide adenine dinucleotide."
Bell C.E., Eisenberg D.
Biochemistry 35:1137-1149(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[9]"Crystal structure of nucleotide-free diphtheria toxin."
Bell C.E., Eisenberg D.
Biochemistry 36:481-488(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[10]"Crystal structure of the complex of diphtheria toxin with an extracellular fragment of its receptor."
Louie G.V., Yang W., Bowman M.E., Choe S.
Mol. Cell 1:67-78(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF COMPLEX WITH RECEPTOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		K01722 Genomic DNA. Translation: AAA32182.1. Different initiation.
X00703 Genomic DNA. Translation: CAA25302.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1DDTX-ray2.00A33-567[»]
1DTPX-ray2.50A33-222[»]
1F0LX-ray1.55A/B33-560[»]
1MDTX-ray2.30A/B33-567[»]
1SGKX-ray2.30A33-567[»]
1TOXX-ray2.30A/B33-567[»]
1XDTX-ray2.65T33-567[»]
4AE0X-ray2.00A33-567[»]
4AE1X-ray2.08A/B33-567[»]
ProteinModelPortalP00588.
SMRP00588. Positions 33-567.
ModBaseSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Enzyme and pathway databases

BioCycMetaCyc:MONOMER-15583.

Family and domain databases

Gene3D1.10.490.40. 1 hit.
2.60.40.700. 1 hit.
InterProIPR000512. Diphtheria_toxin.
IPR022406. Diphtheria_toxin_catalytic_dom.
IPR022404. Diphtheria_toxin_rcpt-bd_dom.
IPR022405. Diphtheria_toxin_translocation.
[Graphical view]
PfamPF02763. Diphtheria_C. 1 hit.
PF01324. Diphtheria_R. 1 hit.
PF02764. Diphtheria_T. 1 hit.
[Graphical view]
PIRSFPIRSF000490. Diphtheria_toxin. 1 hit.
PRINTSPR00769. DPTHRIATOXIN.
SUPFAMSSF49380. Diphtheria_tox. 1 hit.
SSF56845. Diphtheria_tox. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP00588.
PMAP-CutDBP00588.

Entry information

Entry nameDTX_CORBE
AccessionPrimary (citable) accession number: P00588
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: May 1, 1991
Last modified: May 1, 2013
This is version 90 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents