NTH_SCHPO
ID NTH_SCHPO Reviewed; 355 AA.
AC Q09907; Q588X4;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 149.
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, ECO:0000269|PubMed:9425081};
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; ORFNames=SPAC30D11.07;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16076563; DOI=10.1016/j.dnarep.2005.06.009;
RA Sugimoto T., Igawa E., Tanihigashi H., Matsubara M., Ide H., Ikeda S.;
RT "Roles of base excision repair enzymes Nth1p and Apn2p from
RT Schizosaccharomyces pombe in processing alkylation and oxidative DNA
RT damage.";
RL DNA Repair 4:1270-1280(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP FUNCTION, AND SUBSTRATES.
RX PubMed=8811082; DOI=10.1093/nar/24.17.3307;
RA Roldan-Arjona T., Anselmino C., Lindahl T.;
RT "Molecular cloning and functional analysis of a Schizosaccharomyces pombe
RT homologue of Escherichia coli endonuclease III.";
RL Nucleic Acids Res. 24:3307-3312(1996).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9425081; DOI=10.1021/bi971660s;
RA Karahalil B., Roldan-Arjona T., Dizdaroglu M.;
RT "Substrate specificity of Schizosaccharomyces pombe Nth protein for
RT products of oxidative DNA damage.";
RL Biochemistry 37:590-595(1998).
RN [5]
RP FUNCTION IN MMS-DAMAGE REPAIR.
RX PubMed=12675805; DOI=10.1046/j.1365-2958.2003.03440.x;
RA Osman F., Bjoras M., Alseth I., Morland I., McCready S., Seeberg E.,
RA Tsaneva I.;
RT "A new Schizosaccharomyces pombe base excision repair mutant, nth1, reveals
RT overlapping pathways for repair of DNA base damage.";
RL Mol. Microbiol. 48:465-480(2003).
RN [6]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [7]
RP FUNCTION, AND SUBSTRATES.
RX PubMed=17641464; DOI=10.1269/jrr.07042;
RA Yonekura S., Nakamura N., Doi T., Sugiyama H., Yamamoto K., Yonei S.,
RA Zhang Q.M.;
RT "Recombinant Schizosaccharomyces pombe Nth1 protein exhibits DNA
RT glycosylase activities for 8-oxo-7,8-dihydroguanine and thymine residues
RT oxidized in the methyl group.";
RL J. Radiat. Res. 48:417-424(2007).
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. Has also 8-oxo-7,8-
CC dihydroguanine (8-oxoG) DNA glycosylase activity. Also involved in the
CC repair of 7-methylguanine lesions, although it cannot directly repair
CC alkylated DNA bases. Probably does so via excision of
CC methylformamidopyrimidine (mFapy) lesions, a spontaneous processing
CC product of 7-methylguanine. {ECO:0000255|HAMAP-Rule:MF_03183,
CC ECO:0000269|PubMed:12675805, ECO:0000269|PubMed:16076563,
CC ECO:0000269|PubMed:17641464, ECO:0000269|PubMed:8811082,
CC ECO:0000269|PubMed:9425081}.
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:9425081};
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=963 nM for 5-hydroxy-6-hydrothymine containing duplex
CC oligonucleotides (N-glycosylase activity)
CC {ECO:0000269|PubMed:9425081};
CC KM=173 nM for 5-hydroxyuracil containing duplex oligonucleotides (N-
CC glycosylase activity) {ECO:0000269|PubMed:9425081};
CC KM=360 nM for 5-hydroxycytosine containing duplex oligonucleotides
CC (N-glycosylase activity) {ECO:0000269|PubMed:9425081};
CC KM=1741 nM for thymine glycol containing duplex oligonucleotides (N-
CC glycosylase activity) {ECO:0000269|PubMed:9425081};
CC KM=111 nM for 5,6-dihydroxycytosine containing duplex
CC oligonucleotides (N-glycosylase activity)
CC {ECO:0000269|PubMed:9425081};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03183,
CC ECO:0000269|PubMed:16076563, ECO:0000269|PubMed:16823372}.
CC Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03183}.
CC -!- SIMILARITY: Belongs to the Nth/MutY family. {ECO:0000255|HAMAP-
CC Rule:MF_03183}.
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DR EMBL; AB191154; BAD93307.1; -; mRNA.
DR EMBL; CU329670; CAA91893.1; -; Genomic_DNA.
DR PIR; JC6066; S62565.
DR RefSeq; NP_593210.1; NM_001018606.2.
DR AlphaFoldDB; Q09907; -.
DR SMR; Q09907; -.
DR BioGRID; 279928; 51.
DR STRING; 4896.SPAC30D11.07.1; -.
DR iPTMnet; Q09907; -.
DR MaxQB; Q09907; -.
DR PaxDb; Q09907; -.
DR PRIDE; Q09907; -.
DR EnsemblFungi; SPAC30D11.07.1; SPAC30D11.07.1:pep; SPAC30D11.07.
DR GeneID; 2543510; -.
DR KEGG; spo:SPAC30D11.07; -.
DR PomBase; SPAC30D11.07; nth1.
DR VEuPathDB; FungiDB:SPAC30D11.07; -.
DR eggNOG; KOG1921; Eukaryota.
DR HOGENOM; CLU_012862_4_2_1; -.
DR InParanoid; Q09907; -.
DR OMA; HREINHM; -.
DR PhylomeDB; Q09907; -.
DR Reactome; R-SPO-110329; Cleavage of the damaged pyrimidine.
DR PRO; PR:Q09907; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:PomBase.
DR GO; GO:0005634; C:nucleus; IDA:PomBase.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-UniRule.
DR GO; GO:0034042; F:5-formyluracil DNA N-glycosylase activity; IDA:PomBase.
DR GO; GO:0034043; F:5-hydroxymethyluracil DNA N-glycosylase activity; IDA:PomBase.
DR GO; GO:0034039; F:8-oxo-7,8-dihydroguanine DNA N-glycosylase activity; IDA:PomBase.
DR GO; GO:0140078; F:class I DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA:PomBase.
DR GO; GO:0003677; F:DNA binding; ISM:PomBase.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008534; F:oxidized purine nucleobase lesion DNA N-glycosylase activity; IMP:PomBase.
DR GO; GO:0000703; F:oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity; IDA:PomBase.
DR GO; GO:0006284; P:base-excision repair; IDA:PomBase.
DR GO; GO:0006285; P:base-excision repair, AP site formation; IDA:PomBase.
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; IPR003265; HhH-GPD_domain.
DR InterPro; IPR023170; HhH_base_excis_C.
DR InterPro; IPR000445; HhH_motif.
DR InterPro; IPR030841; NTH1.
DR Pfam; PF00633; HHH; 1.
DR Pfam; PF00730; HhH-GPD; 1.
DR SMART; SM00478; ENDO3c; 1.
DR SUPFAM; SSF48150; SSF48150; 1.
DR PROSITE; PS01155; ENDONUCLEASE_III_2; 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.
FT CHAIN 1..355
FT /note="Endonuclease III homolog"
FT /id="PRO_0000102226"
FT DOMAIN 122..149
FT /note="HhH"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT REGION 303..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 44..50
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOTIF 252..255
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 338..355
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 142
FT /note="Nucleophile; for N-glycosylase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT BINDING 210
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
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 220
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT BINDING 228
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT SITE 161
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
SQ SEQUENCE 355 AA; 40227 MW; D2E8C93A0DFA60EB CRC64;
MSKDYGTPPE NWREVYDEIC KMKAKVVAPV DVQGCHTLGE RNDPKKFRFQ TLVALMLSSQ
TKDIVLGPTM RNLKEKLAGG LCLEDIQNID EVSLNKLIEK VGFHNRKTIY LKQMARILSE
KFQGDIPDTV EDLMTLPGVG PKMGYLCMSI AWNKTVGIGV DVHVHRICNL LHWCNTKTEE
QTRAALQSWL PKELWFELNH TLVGFGQTIC LPRGRRCDMC TLSSKGLCPS AFKEKSGITI
TKRKVKTIKR VKKRPASESP PLSPLSLPTD DLYYQSIEDK SLIKLEDLDP VDSISHMNEP
LKKEPAADID VDQKPPVAFH STTKETRSLR RSKRVAKKSS QYFSQQSLQD IEDLV
