NTH2_YEAST
ID NTH2_YEAST Reviewed; 380 AA.
AC Q08214; D6W223;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Endonuclease III homolog 2 {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, ECO:0000269|PubMed:14500818};
DE AltName: Full=Bifunctional DNA N-glycosylase/DNA-(apurinic or apyrimidinic site) lyase 2 {ECO:0000255|HAMAP-Rule:MF_03183};
DE Short=DNA glycosylase/AP lyase 2 {ECO:0000255|HAMAP-Rule:MF_03183};
DE AltName: Full=Endonuclease III-like glycosylase 2;
DE AltName: Full=Redoxyendonuclease 2;
GN Name=NTG2; Synonyms=SCR2; OrderedLocusNames=YOL043C;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169874;
RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J.,
RA Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A.,
RA Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B.,
RA Dang V.-D., de Haan M., Delius H., Durand P., Fairhead C., Feldmann H.,
RA Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E.,
RA Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U.,
RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B.,
RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A.,
RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C.,
RA Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G.,
RA Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B.,
RA Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F.,
RA Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E.,
RA Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I.,
RA Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H.,
RA Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV.";
RL Nature 387:98-102(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP FUNCTION.
RX PubMed=9020769; DOI=10.1021/bi9625511;
RA Augeri L., Lee Y.M., Barton A.B., Doetsch P.W.;
RT "Purification, characterization, gene cloning, and expression of
RT Saccharomyces cerevisiae redoxyendonuclease, a homolog of Escherichia coli
RT endonuclease III.";
RL Biochemistry 36:721-729(1997).
RN [4]
RP FUNCTION, SUBSTRATES, INDUCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9558341; DOI=10.1021/bi973042h;
RA You H.J., Swanson R.L., Doetsch P.W.;
RT "Saccharomyces cerevisiae possesses two functional homologues of
RT Escherichia coli endonuclease III.";
RL Biochemistry 37:6033-6040(1998).
RN [5]
RP FUNCTION, SUBSTRATES, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9826748; DOI=10.1093/nar/26.23.5270;
RA Senturker S., Auffret van der Kemp P., You H.J., Doetsch P.W.,
RA Dizdaroglu M., Boiteux S.;
RT "Substrate specificities of the ntg1 and ntg2 proteins of Saccharomyces
RT cerevisiae for oxidized DNA bases are not identical.";
RL Nucleic Acids Res. 26:5270-5276(1998).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10471279; DOI=10.1021/bi991121i;
RA You H.J., Swanson R.L., Harrington C., Corbett A.H., Jinks-Robertson S.,
RA Sentuerker S., Wallace S.S., Boiteux S., Dizdaroglu M., Doetsch P.W.;
RT "Saccharomyces cerevisiae Ntg1p and Ntg2p: broad specificity N-glycosylases
RT for the repair of oxidative DNA damage in the nucleus and mitochondria.";
RL Biochemistry 38:11298-11306(1999).
RN [7]
RP FUNCTION IN OXIDATIVE DNA DAMAGE REPAIR, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, AND INDUCTION.
RX PubMed=10207101; DOI=10.1128/mcb.19.5.3779;
RA Alseth I., Eide L., Pirovano M., Rognes T., Seeberg E., Bjoras M.;
RT "The Saccharomyces cerevisiae homologues of endonuclease III from
RT Escherichia coli, Ntg1 and Ntg2, are both required for efficient repair of
RT spontaneous and induced oxidative DNA damage in yeast.";
RL Mol. Cell. Biol. 19:3779-3787(1999).
RN [8]
RP FUNCTION.
RX PubMed=11478780; DOI=10.1006/bbrc.2001.5305;
RA Kim J.E., You H.J., Choi J.Y., Doetsch P.W., Kim J.S., Chung M.H.;
RT "Ntg2 of Saccharomyces cerevisiae repairs the oxidation products of 8-
RT hydroxyguanine.";
RL Biochem. Biophys. Res. Commun. 285:1186-1191(2001).
RN [9]
RP INTERACTION WITH MLH1, AND MUTAGENESIS OF SER-24; TYR-26 AND PHE-27.
RX PubMed=12042306; DOI=10.1074/jbc.m202963200;
RA Gellon L., Werner M., Boiteux S.;
RT "Ntg2p, a Saccharomyces cerevisiae DNA N-glycosylase/apurinic or
RT apyrimidinic lyase involved in base excision repair of oxidative DNA
RT damage, interacts with the DNA mismatch repair protein Mlh1p.
RT Identification of a Mlh1p binding motif.";
RL J. Biol. Chem. 277:29963-29972(2002).
RN [10]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=14500818; DOI=10.1093/nar/gkg749;
RA Meadows K.L., Song B., Doetsch P.W.;
RT "Characterization of AP lyase activities of Saccharomyces cerevisiae Ntg1p
RT and Ntg2p: implications for biological function.";
RL Nucleic Acids Res. 31:5560-5567(2003).
RN [12]
RP FUNCTION IN DNA ALKYLATION DAMAGE REPAIR.
RX PubMed=14697759; DOI=10.1016/j.dnarep.2003.09.005;
RA Hanna M., Chow B.L., Morey N.J., Jinks-Robertson S., Doetsch P.W., Xiao W.;
RT "Involvement of two endonuclease III homologs in the base excision repair
RT pathway for the processing of DNA alkylation damage in Saccharomyces
RT cerevisiae.";
RL DNA Repair 3:51-59(2004).
RN [13]
RP FUNCTION.
RX PubMed=15449310; DOI=10.1002/yea.1144;
RA Melo R.G., Leitao A.C., Padula M.;
RT "Role of OGG1 and NTG2 in the repair of oxidative DNA damage and
RT mutagenesis induced by hydrogen peroxide in Saccharomyces cerevisiae:
RT relationships with transition metals iron and copper.";
RL Yeast 21:991-1003(2004).
RN [14]
RP FUNCTION, AND SUBSTRATES.
RX PubMed=18983898; DOI=10.1016/j.bbagen.2008.10.001;
RA Gasparutto D., Muller E., Boiteux S., Cadet J.;
RT "Excision of the oxidatively formed 5-hydroxyhydantoin and 5-hydroxy-5-
RT methylhydantoin pyrimidine lesions by Escherichia coli and Saccharomyces
RT cerevisiae DNA N-glycosylases.";
RL Biochim. Biophys. Acta 1790:16-24(2009).
RN [15]
RP SUBCELLULAR LOCATION, AND SUMOYLATION.
RX PubMed=19029246; DOI=10.1128/mcb.01357-08;
RA Griffiths L.M., Swartzlander D., Meadows K.L., Wilkinson K.D.,
RA Corbett A.H., Doetsch P.W.;
RT "Dynamic compartmentalization of base excision repair proteins in response
RT to nuclear and mitochondrial oxidative stress.";
RL Mol. Cell. Biol. 29:794-807(2009).
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, but also purine-derived
CC lesions, alkylation damage as well as abasic sites. Can also repair the
CC oxidation products of 8-oxoguanine. {ECO:0000255|HAMAP-Rule:MF_03183,
CC ECO:0000269|PubMed:10207101, ECO:0000269|PubMed:10471279,
CC ECO:0000269|PubMed:11478780, ECO:0000269|PubMed:14500818,
CC ECO:0000269|PubMed:14697759, ECO:0000269|PubMed:15449310,
CC ECO:0000269|PubMed:18983898, ECO:0000269|PubMed:9020769,
CC ECO:0000269|PubMed:9558341, ECO:0000269|PubMed:9826748}.
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, ECO:0000269|PubMed:14500818};
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=160 nM for dihydrouracil containing duplex oligonucleotides (N-
CC glycosylase activity) {ECO:0000269|PubMed:14500818,
CC ECO:0000269|PubMed:9558341, ECO:0000269|PubMed:9826748};
CC KM=178 nM for 5-hydroxy-6-hydrothymine containing duplex
CC oligonucleotides (N-glycosylase activity)
CC {ECO:0000269|PubMed:14500818, ECO:0000269|PubMed:9558341,
CC ECO:0000269|PubMed:9826748};
CC KM=557 nM for 5-hydroxy-6-hydrouracil containing duplex
CC oligonucleotides (N-glycosylase activity)
CC {ECO:0000269|PubMed:14500818, ECO:0000269|PubMed:9558341,
CC ECO:0000269|PubMed:9826748};
CC KM=431 nM for 5-hydroxyuracil containing duplex oligonucleotides (N-
CC glycosylase activity) {ECO:0000269|PubMed:14500818,
CC ECO:0000269|PubMed:9558341, ECO:0000269|PubMed:9826748};
CC KM=419 nM for 5-hydroxycytosine containing duplex oligonucleotides
CC (N-glycosylase activity) {ECO:0000269|PubMed:14500818,
CC ECO:0000269|PubMed:9558341, ECO:0000269|PubMed:9826748};
CC KM=1000 nM for thymine glycol containing duplex oligonucleotides (N-
CC glycosylase activity) {ECO:0000269|PubMed:14500818,
CC ECO:0000269|PubMed:9558341, ECO:0000269|PubMed:9826748};
CC KM=824 nM for 2,6-diamino-4-hydroxy-5-formamidopyrimidine FapyAde)
CC containing duplex oligonucleotides (N-glycosylase activity)
CC {ECO:0000269|PubMed:14500818, ECO:0000269|PubMed:9558341,
CC ECO:0000269|PubMed:9826748};
CC KM=2529 nM for 4,6-diamino-5-formamidopyrimidine (FapyGua) containing
CC duplex oligonucleotides (N-glycosylase activity)
CC {ECO:0000269|PubMed:14500818, ECO:0000269|PubMed:9558341,
CC ECO:0000269|PubMed:9826748};
CC Vmax=0.2 nmol/min/ng enzyme for dihydrouracil containing duplex
CC oligonucleotides (N-glycosylase activity)
CC {ECO:0000269|PubMed:14500818, ECO:0000269|PubMed:9558341,
CC ECO:0000269|PubMed:9826748};
CC -!- SUBUNIT: Interacts with MLH1. {ECO:0000269|PubMed:12042306}.
CC -!- INTERACTION:
CC Q08214; P38920: MLH1; NbExp=3; IntAct=EBI-12303, EBI-11003;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03183,
CC ECO:0000269|PubMed:10207101, ECO:0000269|PubMed:10471279,
CC ECO:0000269|PubMed:19029246}. Note=Exclusively nuclear and not
CC responsive to changes in either nuclear or mitochondrial oxidative
CC stress.
CC -!- INDUCTION: Constitutively expressed. {ECO:0000269|PubMed:10207101,
CC ECO:0000269|PubMed:9558341}.
CC -!- PTM: Monosumoylated.
CC -!- DISRUPTION PHENOTYPE: Greatly increases spontaneous and hydrogen
CC peroxide-induced mutation frequency. {ECO:0000269|PubMed:10207101}.
CC -!- MISCELLANEOUS: Present with 125 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the Nth/MutY family. {ECO:0000255|HAMAP-
CC Rule:MF_03183}.
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DR EMBL; Z74785; CAA99045.1; -; Genomic_DNA.
DR EMBL; BK006948; DAA10739.1; -; Genomic_DNA.
DR PIR; S66728; S66728.
DR RefSeq; NP_014599.1; NM_001183297.1.
DR PDB; 4FMN; X-ray; 2.69 A; C=22-29.
DR PDBsum; 4FMN; -.
DR AlphaFoldDB; Q08214; -.
DR SMR; Q08214; -.
DR BioGRID; 34359; 159.
DR DIP; DIP-2956N; -.
DR IntAct; Q08214; 2.
DR MINT; Q08214; -.
DR STRING; 4932.YOL043C; -.
DR MaxQB; Q08214; -.
DR PaxDb; Q08214; -.
DR PRIDE; Q08214; -.
DR TopDownProteomics; Q08214; -.
DR EnsemblFungi; YOL043C_mRNA; YOL043C; YOL043C.
DR GeneID; 854114; -.
DR KEGG; sce:YOL043C; -.
DR SGD; S000005403; NTG2.
DR VEuPathDB; FungiDB:YOL043C; -.
DR eggNOG; KOG1921; Eukaryota.
DR GeneTree; ENSGT00510000047513; -.
DR HOGENOM; CLU_012862_4_3_1; -.
DR InParanoid; Q08214; -.
DR OMA; RGKRCDL; -.
DR BioCyc; YEAST:G3O-33457-MON; -.
DR Reactome; R-SCE-110329; Cleavage of the damaged pyrimidine.
DR PRO; PR:Q08214; -.
DR Proteomes; UP000002311; Chromosome XV.
DR RNAct; Q08214; protein.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-UniRule.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
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:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000703; F:oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity; IDA:SGD.
DR GO; GO:0006284; P:base-excision repair; IDA:SGD.
DR GO; GO:0006285; P:base-excision repair, AP site formation; IDA:SGD.
DR GO; GO:0006296; P:nucleotide-excision repair, DNA incision, 5'-to lesion; IBA:GO_Central.
DR CDD; cd00056; ENDO3c; 1.
DR Gene3D; 1.10.1670.10; -; 1.
DR HAMAP; MF_03183; Endonuclease_III_Nth; 1.
DR InterPro; IPR011257; DNA_glycosylase.
DR InterPro; IPR004036; Endonuclease-III-like_CS2.
DR InterPro; IPR003651; Endonuclease3_FeS-loop_motif.
DR InterPro; IPR003265; HhH-GPD_domain.
DR InterPro; IPR023170; HhH_base_excis_C.
DR InterPro; IPR030841; NTH1.
DR Pfam; PF00730; HhH-GPD; 1.
DR SMART; SM00478; ENDO3c; 1.
DR SMART; SM00525; FES; 1.
DR SUPFAM; SSF48150; SSF48150; 1.
DR PROSITE; PS01155; ENDONUCLEASE_III_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; DNA damage; DNA repair; Glycosidase; Hydrolase; Iron;
KW Iron-sulfur; Isopeptide bond; Lyase; Metal-binding; Nucleus;
KW Reference proteome; Ubl conjugation.
FT CHAIN 1..380
FT /note="Endonuclease III homolog 2"
FT /id="PRO_0000102238"
FT DOMAIN 228..252
FT /note="HhH"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT REGION 15..40
FT /note="Interaction with MLH1"
FT /evidence="ECO:0000269|PubMed:12042306"
FT MOTIF 8..12
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 376..380
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT ACT_SITE 248
FT /note="Nucleophile; for N-glycosylase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT BINDING 319
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT BINDING 326
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT BINDING 329
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT BINDING 335
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT SITE 267
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT CROSSLNK 194
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000255"
FT MUTAGEN 24
FT /note="S->A: Abolishes interaction with MLH1."
FT /evidence="ECO:0000269|PubMed:12042306"
FT MUTAGEN 26
FT /note="Y->A: Abolishes interaction with MLH1."
FT /evidence="ECO:0000269|PubMed:12042306"
FT MUTAGEN 27
FT /note="F->A: Abolishes interaction with MLH1."
FT /evidence="ECO:0000269|PubMed:12042306"
SQ SEQUENCE 380 AA; 43844 MW; 517F81C3BA3DDCF7 CRC64;
MREESRSRKR KHIPVDIEEV EVRSKYFKKN ERTVELVKEN KINKDLQNYG GVNIDWIKAL
KPIEYFEWIE SRTCDDPRTW GRPITKEEMI NDSGAKVPES FLPIYNRVRL MRSKVKTPVD
AMGCSMIPVL VSNKCGIPSE KVDPKNFRLQ FLIGTMLSAQ TRDERMAQAA LNITEYCLNT
LKIAEGITLD GLLKIDEPVL ANLIRCVSFY TRKANFIKRT AQLLVDNFDS DIPYDIEGIL
SLPGVGPKMG YLTLQKGWGL IAGICVDVHV HRLCKMWNWV DPIKCKTAEH TRKELQVWLP
HSLWYEINTV LVGFGQLICM ARGKRCDLCL ANDVCNARNE KLIESSKFHQ LEDKEDIEKV
YSHWLDTVTN GITTERHKKK
