ID NTH_ENCCU Reviewed; 238 AA. AC Q8SRB8; DT 01-SEP-2009, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2002, sequence version 1. DT 03-MAY-2023, entry version 107. DE RecName: Full=Endonuclease III homolog {ECO:0000255|HAMAP-Rule:MF_03183}; DE EC=3.2.2.- {ECO:0000255|HAMAP-Rule:MF_03183}; DE EC=4.2.99.18 {ECO:0000255|HAMAP-Rule:MF_03183}; DE AltName: Full=Bifunctional DNA N-glycosylase/DNA-(apurinic or apyrimidinic site) lyase {ECO:0000255|HAMAP-Rule:MF_03183}; DE Short=DNA glycosylase/AP lyase {ECO:0000255|HAMAP-Rule:MF_03183}; GN Name=NTH1 {ECO:0000255|HAMAP-Rule:MF_03183}; GN OrderedLocusNames=ECU08_0880; OS Encephalitozoon cuniculi (strain GB-M1) (Microsporidian parasite). OC Eukaryota; Fungi; Fungi incertae sedis; Microsporidia; Unikaryonidae; OC Encephalitozoon. OX NCBI_TaxID=284813; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=GB-M1; RX PubMed=11719806; DOI=10.1038/35106579; RA Katinka M.D., Duprat S., Cornillot E., Metenier G., Thomarat F., RA Prensier G., Barbe V., Peyretaillade E., Brottier P., Wincker P., RA Delbac F., El Alaoui H., Peyret P., Saurin W., Gouy M., Weissenbach J., RA Vivares C.P.; RT "Genome sequence and gene compaction of the eukaryote parasite RT Encephalitozoon cuniculi."; RL Nature 414:450-453(2001). RN [2] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], DEVELOPMENTAL RP STAGE, AND SUBCELLULAR LOCATION. RX PubMed=16691553; DOI=10.1002/pmic.200500796; RA Brosson D., Kuhn L., Delbac F., Garin J., Vivares C.P., Texier C.; RT "Proteomic analysis of the eukaryotic parasite Encephalitozoon cuniculi RT (microsporidia): a reference map for proteins expressed in late sporogonial RT stages."; RL Proteomics 6:3625-3635(2006). CC -!- FUNCTION: Bifunctional DNA N-glycosylase with associated CC apurinic/apyrimidinic (AP) lyase function that catalyzes the first step CC in base excision repair (BER), the primary repair pathway for the CC repair of oxidative DNA damage. The DNA N-glycosylase activity releases CC the damaged DNA base from DNA by cleaving the N-glycosidic bond, CC leaving an AP site. The AP lyase activity cleaves the phosphodiester CC bond 3' to the AP site by a beta-elimination. Primarily recognizes and CC repairs oxidative base damage of pyrimidines. {ECO:0000255|HAMAP- CC Rule:MF_03183}. CC -!- CATALYTIC ACTIVITY: CC Reaction=2'-deoxyribonucleotide-(2'-deoxyribose 5'-phosphate)-2'- CC deoxyribonucleotide-DNA = a 3'-end 2'-deoxyribonucleotide-(2,3- CC dehydro-2,3-deoxyribose 5'-phosphate)-DNA + a 5'-end 5'-monophospho- CC 2'-deoxyribonucleoside-DNA + H(+); Xref=Rhea:RHEA:66592, Rhea:RHEA- CC COMP:13180, Rhea:RHEA-COMP:16897, Rhea:RHEA-COMP:17067, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:136412, ChEBI:CHEBI:157695, CC ChEBI:CHEBI:167181; EC=4.2.99.18; Evidence={ECO:0000255|HAMAP- CC Rule:MF_03183}; CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03183}; CC Note=Binds 1 [4Fe-4S] cluster. The cluster does not appear to play a CC role in catalysis, but is probably involved in the proper positioning CC of the enzyme along the DNA strand. {ECO:0000255|HAMAP-Rule:MF_03183}; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03183}. CC Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03183}. CC -!- DEVELOPMENTAL STAGE: Expressed in late sporogonial stages. CC {ECO:0000269|PubMed:16691553}. CC -!- SIMILARITY: Belongs to the Nth/MutY family. {ECO:0000255|HAMAP- CC Rule:MF_03183}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL590448; CAD26394.1; -; Genomic_DNA. DR RefSeq; NP_597218.1; NM_001041827.1. DR AlphaFoldDB; Q8SRB8; -. DR SMR; Q8SRB8; -. DR STRING; 284813.Q8SRB8; -. DR GeneID; 859640; -. DR KEGG; ecu:ECU08_0880; -. DR VEuPathDB; MicrosporidiaDB:ECU08_0880; -. DR HOGENOM; CLU_012862_3_4_1; -. DR InParanoid; Q8SRB8; -. DR OMA; QIIWYGR; -. DR OrthoDB; 3377194at2759; -. DR Proteomes; UP000000819; Chromosome VIII. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-UniRule. DR GO; GO:0140078; F:class I DNA-(apurinic or apyrimidinic site) endonuclease activity; IEA:UniProtKB-EC. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000703; F:oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity; IEA:UniProtKB-UniRule. DR GO; GO:0006285; P:base-excision repair, AP site formation; IEA:UniProtKB-UniRule. DR CDD; cd00056; ENDO3c; 1. DR Gene3D; 1.10.1670.10; Helix-hairpin-Helix base-excision DNA repair enzymes (C-terminal); 1. DR HAMAP; MF_03183; Endonuclease_III_Nth; 1. DR InterPro; IPR011257; DNA_glycosylase. DR InterPro; IPR003651; Endonuclease3_FeS-loop_motif. DR InterPro; IPR004035; Endouclease-III_FeS-bd_BS. DR InterPro; IPR003265; HhH-GPD_domain. DR InterPro; IPR023170; HhH_base_excis_C. DR InterPro; IPR030841; NTH1. DR PANTHER; PTHR43286; ENDONUCLEASE III-LIKE PROTEIN 1; 1. DR PANTHER; PTHR43286:SF1; ENDONUCLEASE III-LIKE PROTEIN 1; 1. DR Pfam; PF00730; HhH-GPD; 1. DR PIRSF; PIRSF001435; Nth; 1. DR SMART; SM00478; ENDO3c; 1. DR SMART; SM00525; FES; 1. DR SUPFAM; SSF48150; DNA-glycosylase; 1. DR PROSITE; PS00764; ENDONUCLEASE_III_1; 1. PE 1: Evidence at protein level; KW 4Fe-4S; DNA damage; DNA repair; Glycosidase; Hydrolase; Iron; Iron-sulfur; KW Lyase; Metal-binding; Mitochondrion; Nucleus; Reference proteome; KW Transit peptide. FT CHAIN 1..238 FT /note="Endonuclease III homolog" FT /id="PRO_0000382919" FT DOMAIN 129..155 FT /note="HhH" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183" FT ACT_SITE 149 FT /note="Nucleophile; for N-glycosylase activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183" FT BINDING 217 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183" FT BINDING 224 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183" FT BINDING 227 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183" FT BINDING 233 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183" FT SITE 168 FT /note="Important for catalytic activity" FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183" SQ SEQUENCE 238 AA; 26755 MW; 3D9D7B774187F35B CRC64; MGSASGEERE GPLGLYLEIK MQRKDIVSPV DTMGCSITPS CRTEEERRFH ILVSLLLSSQ TKDEVTYEAM ARLRKLLPES AATDGEARGG LTIERVANSD VKHINECIKK VGFHNRKAAN LKKIAEILRE KGLPREMKDL ISLPGIGNKM ALLYMSHACN RTVGISVDTH VHRISNRIGL VRTRDVESTR RELERVVPRK EWKTINNILV GFGQTICVAK RPRCEECCIR GRCPSSLF //