PROSITE documentation PDOC00615
Endonuclease III signatures


Escherichia coli endonuclease III (EC (gene nth) [1] is a DNA repair enzyme that acts both as a DNA N-glycosylase, removing oxidized pyrimidines from DNA, and as an apurinic/apyrimidinic (AP) endonuclease, introducing a single-strand nick at the site from which the damaged base was removed. Endonuclease III is an iron-sulfur protein that binds a single 4Fe-4S cluster. The 4Fe-4S cluster does not seem to be important for catalytic activity, but is probably involved in the proper positioning of the enzyme along the DNA strand [2].

Endonuclease III is evolutionary related to the following proteins:

  • Fission yeast endonuclease III homolog (gene nth1) [3].
  • Escherichia coli and related protein DNA repair protein mutY, which is an adenine glycosylase. MutY is a larger protein (350 amino acids) than endonuclease III (211 amino acids).
  • Micrococcus luteus ultraviolet N-glycosylase/AP lyase which initiates repair at cis-syn pyrimidine dimers.
  • ORF10 in plasmid pFV1 of the thermophilic archaebacteria Methanobacterium thermoformicicum [4]. Restriction methylase m.MthTI, which is encoded by this plasmid, generates 5-methylcytosine which is subject to deamination resulting in G-T mismatches. This protein could correct these mismatches.
  • Yeast hypothetical protein YAL015c.
  • Fission yeast hypothetical protein SpAC26A3.02.
  • Caenorhabditis elegans hypothetical protein R10E4.5.
  • Methanococcus jannaschii hypothetical protein MJ0613.

The 4Fe-4S cluster is bound by four cysteines which are all located in a 17 amino acid region at the C-terminal end of endonuclease III. A similar region is also present in the central section of mutY and in the C-terminus of ORF10 and of the Micrococcus UV endonuclease. The 4Fe-4S cluster region does not exist in YAL015c.

We developed two signature patterns for these proteins: the first corresponds to the core of the iron-sulfur binding domain, the second corresponds to the best conserved region in the catalytic core of these enzymes.

Last update:

December 2004 / Pattern and text revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

ENDONUCLEASE_III_1, PS00764; Endonuclease III iron-sulfur binding region signature  (PATTERN)

ENDONUCLEASE_III_2, PS01155; Endonuclease III family signature  (PATTERN)


1AuthorsKuo C.-F. McRee D.E. Fisher C.L. O'Handley S.F. Cunningham R.P. Tainer J.A.
TitleAtomic structure of the DNA repair [4Fe-4S] enzyme endonuclease III.
SourceScience 258:434-440(1992).
PubMed ID1411536

2AuthorsThomson A.J.
TitleCrosslinked by a cluster.
SourceCurr. Biol. 3:173-174(1993).
PubMed ID15335790

3AuthorsRoldan-Arjona T. Anselmino C. Lindahl T.
SourceNucleic Acids Res. 24:3307-3312(1996).

4AuthorsNoelling J. van Eeden F.J.M. Eggen R.I.L. de Vos W.M.
SourceNucleic Acids Res. 20:6501-6507(1992).

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