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	PROSITE documentation PDOC00615

Endonuclease III signatures

Escherichia coli endonuclease III (EC 4.2.99.18) (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.

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

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

• Consensus pattern:
  C-x(3)-[KRSN]-P-[KRAGL]-C-x(2)-C-x(5)-C
  The 4 C's are 4Fe-4S ligands
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 53
  • detected by PS00764: 29 (true positives)
  • undetected by PS00764: 24 (23 false negatives and 1 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS00764:
  NONE.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00764
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS00764
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS00764
• View ligand binding statistics of PS00764
• Matching PDB structures: 1KEA 1KG2 1KG3 1KG4 ... [ALL]

ENDONUCLEASE_III_2, PS01155; Endonuclease III family signature  (PATTERN)

• Consensus pattern:
  [GSTENA]-x-[LIVMF]-P-x(5)-[LIVMW]-x(2,3)-[LI]-[PAS]-G-[IV]-[GA]-x(3)-[GAC]-x(2,3)-[LIVMA]-x(1,2)-[GSALVI]-[LIVMFYW]-[GANKD]
• Sequences in UniProtKB/Swiss-Prot known to belong to this class: 48
  • detected by PS01155: 42 (true positives)
  • undetected by PS01155: 6 (5 false negatives and 1 'partial')
• Other sequence(s) in UniProtKB/Swiss-Prot detected by PS01155:
  1 false positive.
• Retrieve an alignment of UniProtKB/Swiss-Prot true positive hits:
  Clustal format, color, condensed view  /  Clustal format, color  /  Clustal format, plain text  /  Fasta format
• Retrieve the sequence logo from the alignment
• Taxonomic distribution of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS01155
• Retrieve a list of all UniProtKB (Swiss-Prot + TrEMBL) entries matching PS01155
• Scan UniProtKB (Swiss-Prot and/or TrEMBL) entries against PS01155
• View ligand binding statistics of PS01155
• Matching PDB structures: 1KEA 1KG2 1KG3 1KG4 ... [ALL]

1	Authors	Kuo C.-F., McRee D.E., Fisher C.L., O'Handley S.F., Cunningham R.P., Tainer J.A.
	Title	Atomic structure of the DNA repair [4Fe-4S] enzyme endonuclease III.
	Source	Science 258:434-440(1992).
	PubMed ID	1411536

2	Authors	Thomson A.J.
	Title	Crosslinked by a cluster.
	Source	Curr. Biol. 3:173-174(1993).
	PubMed ID	15335790

3	Authors	Roldan-Arjona T., Anselmino C., Lindahl T.
	Source	Nucleic Acids Res. 24:3307-3312(1996).

4	Authors	Noelling J., van Eeden F.J.M., Eggen R.I.L., de Vos W.M.
	Source	Nucleic Acids Res. 20:6501-6507(1992).

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