{PDOC00615} {PS00764; ENDONUCLEASE_III_1} {PS01155; ENDONUCLEASE_III_2} {BEGIN} ******************************* * 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. -Consensus pattern: C-x(3)-[KRSN]-P-[KRAGL]-C-x(2)-C-x(5)-C [The 4 C's are 4Fe-4S ligands] -Sequences known to belong to this class detected by the pattern: ALL, except for nth1 and MJ0613. -Other sequence(s) detected in Swiss-Prot: NONE. -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 known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: December 2004 / Pattern and text revised. [ 1] Kuo C.-F., McRee D.E., Fisher C.L., O'Handley S.F., Cunningham R.P., Tainer J.A. "Atomic structure of the DNA repair [4Fe-4S] enzyme endonuclease III." Science 258:434-440(1992). PubMed=1411536 [ 2] Thomson A.J. "Crosslinked by a cluster." Curr. Biol. 3:173-174(1993). PubMed=15335790 [ 3] Roldan-Arjona T., Anselmino C., Lindahl T. Nucleic Acids Res. 24:3307-3312(1996). [ 4] Noelling J., van Eeden F.J.M., Eggen R.I.L., de Vos W.M. Nucleic Acids Res. 20:6501-6507(1992). -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}