ID   NTH_MOUSE               Reviewed;         300 AA.
AC   O35980; E9QMW1;
DT   28-FEB-2003, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 2.
DT   27-MAR-2024, entry version 170.
DE   RecName: Full=Endonuclease III-like protein 1 {ECO:0000255|HAMAP-Rule:MF_03183};
DE            EC=3.2.2.- {ECO:0000255|HAMAP-Rule:MF_03183};
DE            EC=4.2.99.18 {ECO:0000250|UniProtKB:P20625, 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};
DE   Flags: Precursor;
GN   Name=Nthl1; Synonyms=Nth1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1] {ECO:0000305}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC   STRAIN=BALB/cJ; TISSUE=Leukocyte, and T-cell;
RX   PubMed=9743625; DOI=10.1006/jmbi.1998.2042;
RA   Sarker A.H., Ikeda S., Nakano H., Terato H., Ide H., Imai K., Akiyama K.,
RA   Tsutsui K., Bo Z., Kubo K., Yamamoto K., Yasui A., Yoshida M.C., Seki S.;
RT   "Cloning and characterization of a mouse homologue (mNthl1) of Escherichia
RT   coli endonuclease III.";
RL   J. Mol. Biol. 282:761-774(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC   TISSUE=Embryonic stem cell, and Lung;
RA   Luna L., Bjoras M., Rognes T., Hoff E., Seeberg E.;
RT   "Complete genomic DNA sequence of the Mus musculus endonuclease III
RT   homologue 1 gene (NTH1).";
RL   Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Cecum;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [5] {ECO:0000305}
RP   SUBCELLULAR LOCATION.
RX   PubMed=12531031; DOI=10.1016/s1568-7864(02)00145-3;
RA   Ikeda S., Kohmoto T., Tabata R., Seki Y.;
RT   "Differential intracellular localization of the human and mouse
RT   endonuclease III homologs and analysis of the sorting signals.";
RL   DNA Repair 1:847-854(2002).
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, ECO:0000269|PubMed:9743625}.
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;
CC         Evidence={ECO:0000250|UniProtKB:P20625, 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   -!- SUBUNIT: Interacts with YBX1 (By similarity). Interacts with ERCC5/XPG;
CC       the interaction stimulates NTHL1 activity and NTHL1 binding to its DNA
CC       substrate (By similarity). {ECO:0000250|UniProtKB:P78549,
CC       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       ECO:0000269|PubMed:12531031}.
CC   -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9743625}.
CC   -!- PTM: Ubiquitinated by TRIM26; leading to proteasomal degradation.
CC       {ECO:0000250|UniProtKB:P78549}.
CC   -!- SIMILARITY: Belongs to the Nth/MutY family. {ECO:0000255|HAMAP-
CC       Rule:MF_03183}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AK033701; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; AB006812; BAA22080.1; -; mRNA.
DR   EMBL; AB009371; BAA28846.1; -; Genomic_DNA.
DR   EMBL; AJ001617; CAB65239.1; -; Genomic_DNA.
DR   EMBL; Y09688; CAA70866.1; -; mRNA.
DR   EMBL; AK033701; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AC132367; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS28487.1; -.
DR   RefSeq; NP_032769.2; NM_008743.2.
DR   AlphaFoldDB; O35980; -.
DR   SMR; O35980; -.
DR   STRING; 10090.ENSMUSP00000047413; -.
DR   iPTMnet; O35980; -.
DR   PhosphoSitePlus; O35980; -.
DR   MaxQB; O35980; -.
DR   PaxDb; 10090-ENSMUSP00000047413; -.
DR   ProteomicsDB; 295540; -.
DR   Antibodypedia; 23443; 296 antibodies from 28 providers.
DR   DNASU; 18207; -.
DR   Ensembl; ENSMUST00000047611.4; ENSMUSP00000047413.3; ENSMUSG00000041429.4.
DR   GeneID; 18207; -.
DR   KEGG; mmu:18207; -.
DR   UCSC; uc008axi.2; mouse.
DR   AGR; MGI:1313275; -.
DR   CTD; 4913; -.
DR   MGI; MGI:1313275; Nthl1.
DR   VEuPathDB; HostDB:ENSMUSG00000041429; -.
DR   eggNOG; KOG1921; Eukaryota.
DR   GeneTree; ENSGT00510000047513; -.
DR   HOGENOM; CLU_012862_4_2_1; -.
DR   InParanoid; O35980; -.
DR   OMA; WQQFTHL; -.
DR   OrthoDB; 3377194at2759; -.
DR   PhylomeDB; O35980; -.
DR   TreeFam; TF314967; -.
DR   BRENDA; 4.2.99.18; 3474.
DR   Reactome; R-MMU-110329; Cleavage of the damaged pyrimidine.
DR   Reactome; R-MMU-110357; Displacement of DNA glycosylase by APEX1.
DR   BioGRID-ORCS; 18207; 4 hits in 114 CRISPR screens.
DR   ChiTaRS; Nthl1; mouse.
DR   PRO; PR:O35980; -.
DR   Proteomes; UP000000589; Chromosome 17.
DR   RNAct; O35980; Protein.
DR   Bgee; ENSMUSG00000041429; Expressed in embryonic cell in blastocyst and 128 other cell types or tissues.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
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; ISO:MGI.
DR   GO; GO:0003684; F:damaged DNA binding; ISO:MGI.
DR   GO; GO:0019104; F:DNA N-glycosylase activity; IDA:UniProtKB.
DR   GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA:UniProtKB.
DR   GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0000703; F:oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity; IBA:GO_Central.
DR   GO; GO:0006285; P:base-excision repair, AP site formation; ISO:MGI.
DR   GO; GO:0006281; P:DNA repair; TAS:MGI.
DR   GO; GO:0006289; P:nucleotide-excision repair; IDA:UniProtKB.
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; 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; IPR000445; HhH_motif.
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; PF00633; HHH; 1.
DR   Pfam; PF00730; HhH-GPD; 1.
DR   SMART; SM00478; ENDO3c; 1.
DR   SMART; SM00525; FES; 1.
DR   SUPFAM; SSF48150; DNA-glycosylase; 1.
DR   PROSITE; PS01155; ENDONUCLEASE_III_2; 1.
DR   Genevisible; O35980; MM.
PE   2: Evidence at transcript level;
KW   4Fe-4S; DNA damage; DNA repair; Glycosidase; Hydrolase; Iron; Iron-sulfur;
KW   Lyase; Metal-binding; Mitochondrion; Nucleus; Reference proteome;
KW   Transit peptide; Ubl conjugation.
FT   TRANSIT         1..19
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT   CHAIN           20..300
FT                   /note="Endonuclease III-like protein 1"
FT                   /id="PRO_0000102228"
FT   DOMAIN          187..211
FT                   /note="HhH"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT   REGION          1..53
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1..16
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        17..39
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        208
FT                   /note="Nucleophile; for N-glycosylase activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT   BINDING         278
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT   BINDING         285
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT   BINDING         288
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT   BINDING         294
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT   SITE            227
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
SQ   SEQUENCE   300 AA;  33637 MW;  09CAA1FD066F18EB CRC64;
     MNSGVRMVTR SRSRATRIAS EGCREELAPR EAAAEGRKSH RPVRHPRRTQ KTHVAYEAAN
     GEEGEDAEPL KVPVWEPQNW QQQLANIRIM RSKKDAPVDQ LGAEHCYDAS ASPKVRRYQV
     LLSLMLSSQT KDQVTAGAMQ RLRARGLTVE SILQTDDDTL GRLIYPVGFW RNKVKYIKQT
     TAILQQRYEG DIPASVAELV ALPGVGPKMA HLAMAVAWGT ISGIAVDTHV HRIANRLRWT
     KKMTKTPEET RKNLEEWLPR VLWSEVNGLL VGFGQQICLP VHPRCQACLN KALCPAAQDL
//