NTH_MOUSE
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 03-AUG-2022, entry version 161.
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 -!- 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};
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; 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; O35980; -.
DR PRIDE; O35980; -.
DR ProteomicsDB; 295540; -.
DR Antibodypedia; 23443; 256 antibodies from 28 providers.
DR DNASU; 18207; -.
DR Ensembl; ENSMUST00000047611; ENSMUSP00000047413; ENSMUSG00000041429.
DR GeneID; 18207; -.
DR KEGG; mmu:18207; -.
DR UCSC; uc008axi.2; mouse.
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; 1322642at2759; -.
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 109 CRISPR screens.
DR ChiTaRS; Nthl1; mouse.
DR PRO; PR:O35980; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; O35980; protein.
DR Bgee; ENSMUSG00000041429; Expressed in animal zygote and 126 other tissues.
DR Genevisible; O35980; MM.
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 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; IPR000445; HhH_motif.
DR InterPro; IPR030841; NTH1.
DR Pfam; PF00633; HHH; 1.
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 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.
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
