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Q5EK40 (CHXA_VIBCL) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 43. 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

Names and origin

Protein namesRecommended name:
Cholix toxin

EC=2.4.2.36
Alternative name(s):
Exotoxin A
NAD(+)--diphthamide ADP-ribosyltransferase
Gene names
Name:chxA
Synonyms:toxA
OrganismVibrio cholerae
Taxonomic identifier666 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaVibrionalesVibrionaceaeVibrio

Protein attributes

Sequence length666 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

An NAD-dependent ADP-ribosyltransferase (ADPRT), it catalyzes the transfer of the ADP-ribosyl moiety of oxidized NAD onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. It probably uses the eukaryotic prolow-density lipoprotein receptor-related protein 1 (LRP1) to enter mouse cells, although there seems to be at least one other receptor as well. Is active against mouse fibroblasts, Chinese hamster ovary eEF-2, brine shrimp (Artemia spp. nauplii) and upon expression in S.cerevisiae. Ref.2 Ref.3

Catalytic activity

NAD+ + diphthamide-[translation elongation factor 2] = nicotinamide + N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2].

Enzyme regulation

Partially inhibited by 1,8-naphthalimide (NAP). Ref.3

Post-translational modification

Probably requires further proteolytic processing to generate a fragment with toxic activity.

Miscellaneous

Exotoxins are often highly strain specific; not encoded in strain ATCC 39315 / El Tor Inabe N16961.

Biophysicochemical properties

Kinetic parameters:

For ADP-ribosyltransferase activity of a catalytic fragment of residues 459-666.

KM=45 µM for NAD Ref.2

Ontologies

Keywords
   DomainSignal
   LigandNAD
   Molecular functionGlycosyltransferase
Toxin
Transferase
   PTMDisulfide bond
   Technical term3D-structure
Gene Ontology (GO)
   Molecular_functionNAD+-diphthamide ADP-ribosyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232 Potential
Chain33 – 666634Cholix toxin
PRO_0000409819

Sites

Active site6131 Probable

Amino acid modifications

Disulfide bond43 ↔ 47
Disulfide bond240 ↔ 257
Disulfide bond310 ↔ 332
Disulfide bond426 ↔ 433

Experimental info

Mutagenesis6061E → A: Loss of ADPRT activity, loss of toxicity against yeast. Ref.3
Mutagenesis6131E → A: Loss of ADPRT activity, loss of toxicity against mouse cells, brine shrimp and yeast. Ref.2

Secondary structure

........................................................................................................... 666
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q5EK40 [UniParc].

Last modified March 15, 2005. Version 1.
Checksum: 3A76A86E0BC7FDD7

FASTA66674,293
        10         20         30         40         50         60 
MYLTFYLEKV MKKMLLIAGA TVISSMAHPT FAVEDELNIF DECRSPCSLT PEPGKPIQSK 

        70         80         90        100        110        120 
LSIPSDVVLD EGVLYYSMTI NDEQNDIKDE DKGESIITIG EFATVRATRH YVNQDAPFGV 

       130        140        150        160        170        180 
IHLDITTENG TKTYSYNRKE GEFAINWLVP IGEDSPASIK ISVDELDQQR NIIEVPKLYS 

       190        200        210        220        230        240 
IDLDNQTLEQ WKTQGNVSFS VTRPEHNIAI SWPSVSYKAA QKEGSRHKRW AHWHTGLALC 

       250        260        270        280        290        300 
WLVPMDAIYN YITQQNCTLG DNWFGGSYET VAGTPKVITV KQGIEQKPVE QRIHFSKGNA 

       310        320        330        340        350        360 
MSALAAHRVC GVPLETLARS RKPRDLTDDL SCAYQAQNIV SLFVATRILF SHLDSVFTLN 

       370        380        390        400        410        420 
LDEQEPEVAE RLSDLRRINE NNPGMVTQVL TVARQIYNDY VTHHPGLTPE QTSAGAQAAD 

       430        440        450        460        470        480 
ILSLFCPDAD KSCVASNNDQ ANINIESRSG RSYLPENRAV ITPQGVTNWT YQELEATHQA 

       490        500        510        520        530        540 
LTREGYVFVG YHGTNHVAAQ TIVNRIAPVP RGNNTENEEK WGGLYVATHA EVAHGYARIK 

       550        560        570        580        590        600 
EGTGEYGLPT RAERDARGVM LRVYIPRASL ERFYRTNTPL ENAEEHITQV IGHSLPLRNE 

       610        620        630        640        650        660 
AFTGPESAGG EDETVIGWDM AIHAVAIPST IPGNAYEELA IDEEAVAKEQ SISTKPPYKE 


RKDELK 

« Hide

References

[1]"A glimpse into the expanded genome content of Vibrio cholerae through identification of genes present in environmental strains."
Purdy A., Rohwer F., Edwards R., Azam F., Bartlett D.H.
J. Bacteriol. 187:2992-3001(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: TP.
[2]"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: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 459-666 IN COMPLEX WITH INHIBITOR AND (2.1 ANGSTROMS) OF 33-666, FUNCTION AS A TOXIN, FUNCTION AS A GLYCOHYDROLASE, FUNCTION AS AN ADP-RIBOSYLTRANSFERASE, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF GLU-613.
Strain: TP.
[3]"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: X-RAY CRYSTALLOGRAPHY (1.19 ANGSTROMS) OF 459-665 IN COMPLEX WITH INHIBITOR, FUNCTION AS A TOXIN, ENZYME REGULATION, MUTAGENESIS OF GLU-606.
Strain: TP.
[4]"Newly discovered and characterized antivirulence compounds inhibit bacterial mono-ADP-ribosyltransferase toxins."
Turgeon Z., Jorgensen R., Visschedyk D., Edwards P.R., Legree S., McGregor C., Fieldhouse R.J., Mangroo D., Schapira M., Merrill A.R.
Antimicrob. Agents Chemother. 55:983-991(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.27 ANGSTROMS) OF 459-665 IN COMPLEX WITH INHIBITORS.
Strain: TP.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY876053 Genomic DNA. Translation: AAW80252.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2Q5TX-ray2.10A33-666[»]
2Q6MX-ray1.25A459-666[»]
3ESSX-ray1.19A459-665[»]
3KI0X-ray1.29A459-665[»]
3KI1X-ray1.43A459-665[»]
3KI2X-ray1.28A459-665[»]
3KI3X-ray1.27A459-665[»]
3KI4X-ray1.65A459-665[»]
3KI5X-ray1.55A459-665[»]
3KI6X-ray1.54A459-665[»]
3KI7X-ray1.32A459-665[»]
3NY6X-ray1.68A459-665[»]
3Q9OX-ray1.79A33-666[»]
ProteinModelPortalQ5EK40.
SMRQ5EK40. Positions 37-662.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D2.60.120.200. 1 hit.
3.90.1350.10. 1 hit.
InterProIPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR015185. Exotox-A_bind.
IPR015099. Exotox-A_cataly_dom.
IPR015186. Exotox-A_middle_dom.
[Graphical view]
PfamPF09101. Exotox-A_bind. 1 hit.
PF09009. Exotox-A_cataly. 1 hit.
PF09102. Exotox-A_target. 1 hit.
[Graphical view]
SUPFAMSSF49899. SSF49899. 1 hit.
SSF56864. SSF56864. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ5EK40.

Entry information

Entry nameCHXA_VIBCL
AccessionPrimary (citable) accession number: Q5EK40
Entry history
Integrated into UniProtKB/Swiss-Prot: June 28, 2011
Last sequence update: March 15, 2005
Last modified: April 16, 2014
This is version 43 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references