NTH_CAEEL
ID NTH_CAEEL Reviewed; 298 AA.
AC P54137; C7G4V3; D5MCR0; D5MCR1; D5MCR2;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Endonuclease III homolog {ECO:0000255|HAMAP-Rule:MF_03183};
DE Short=CeNTH;
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=nth-1 {ECO:0000255|HAMAP-Rule:MF_03183}; ORFNames=R10E4.5;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D), FUNCTION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND DISRUPTION PHENOTYPE.
RX PubMed=19481506; DOI=10.1016/j.dnarep.2009.04.020;
RA Morinaga H., Yonekura S., Nakamura N., Sugiyama H., Yonei S.,
RA Zhang-Akiyama Q.M.;
RT "Purification and characterization of Caenorhabditis elegans NTH, a homolog
RT of human endonuclease III: essential role of N-terminal region.";
RL DNA Repair 8:844-851(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], ALTERNATIVE INITIATION, AND
RP ALTERNATIVE SPLICING.
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP DISRUPTION PHENOTYPE.
RX PubMed=16783005; DOI=10.1534/genetics.106.059840;
RA Denver D.R., Feinberg S., Steding C., Durbin M., Lynch M.;
RT "The relative roles of three DNA repair pathways in preventing
RT Caenorhabditis elegans mutation accumulation.";
RL Genetics 174:57-65(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, ECO:0000269|PubMed:19481506}.
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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Temperature dependence:
CC Optimum temperature is 26 degrees Celsius.
CC {ECO:0000269|PubMed:19481506};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|HAMAP-Rule:MF_03183}.
CC Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03183}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=4;
CC Name=d;
CC IsoId=P54137-1; Sequence=Displayed;
CC Name=a;
CC IsoId=P54137-2; Sequence=VSP_041641;
CC Name=b;
CC IsoId=P54137-3; Sequence=VSP_041642;
CC Name=c;
CC IsoId=P54137-4; Sequence=VSP_041643;
CC -!- DISRUPTION PHENOTYPE: Increases the total average mutation rate 17-
CC fold. No significant abnormality in lifespan or sensitivity to
CC oxidizing agents such as hydrogen peroxide and methyl viologen (MV);
CC due to the redundancy with other DNA glycosylases.
CC {ECO:0000269|PubMed:16783005, ECO:0000269|PubMed:19481506}.
CC -!- MISCELLANEOUS: [Isoform a]: Produced by alternative initiation.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform b]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform c]: Produced by alternative splicing.
CC {ECO:0000305}.
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; AB518695; BAI22676.1; -; mRNA.
DR EMBL; Z50874; CAA90766.2; -; Genomic_DNA.
DR EMBL; Z50874; CBK55598.1; -; Genomic_DNA.
DR EMBL; Z50874; CBK55599.1; -; Genomic_DNA.
DR EMBL; Z50874; CBK55600.1; -; Genomic_DNA.
DR PIR; T24131; T24131.
DR RefSeq; NP_001254906.1; NM_001267977.1.
DR RefSeq; NP_001254907.1; NM_001267978.1. [P54137-2]
DR RefSeq; NP_001254908.1; NM_001267979.1. [P54137-3]
DR RefSeq; NP_001254909.1; NM_001267980.1. [P54137-4]
DR AlphaFoldDB; P54137; -.
DR SMR; P54137; -.
DR BioGRID; 52453; 4.
DR STRING; 6239.R10E4.5d; -.
DR EPD; P54137; -.
DR PaxDb; P54137; -.
DR PeptideAtlas; P54137; -.
DR EnsemblMetazoa; R10E4.5a.1; R10E4.5a.1; WBGene00011201. [P54137-2]
DR EnsemblMetazoa; R10E4.5b.1; R10E4.5b.1; WBGene00011201. [P54137-3]
DR EnsemblMetazoa; R10E4.5c.1; R10E4.5c.1; WBGene00011201. [P54137-4]
DR EnsemblMetazoa; R10E4.5d.1; R10E4.5d.1; WBGene00011201. [P54137-1]
DR GeneID; 187770; -.
DR CTD; 187770; -.
DR WormBase; R10E4.5a; CE44645; WBGene00011201; nth-1. [P54137-2]
DR WormBase; R10E4.5b; CE44659; WBGene00011201; nth-1. [P54137-3]
DR WormBase; R10E4.5c; CE44689; WBGene00011201; nth-1. [P54137-4]
DR WormBase; R10E4.5d; CE44095; WBGene00011201; nth-1. [P54137-1]
DR eggNOG; KOG1921; Eukaryota.
DR GeneTree; ENSGT00510000047513; -.
DR InParanoid; P54137; -.
DR OMA; KRERWEP; -.
DR OrthoDB; 1322642at2759; -.
DR PhylomeDB; P54137; -.
DR Reactome; R-CEL-110329; Cleavage of the damaged pyrimidine.
DR Reactome; R-CEL-110357; Displacement of DNA glycosylase by APEX1.
DR PRO; PR:P54137; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00011201; Expressed in germ line (C elegans) and 4 other tissues.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:WormBase.
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:WormBase.
DR GO; GO:0034043; F:5-hydroxymethyluracil DNA N-glycosylase activity; IDA:WormBase.
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; IBA:GO_Central.
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:WormBase.
DR GO; GO:0006285; P:base-excision repair, AP site formation; IBA:GO_Central.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IGI:WormBase.
DR GO; GO:0045008; P:depyrimidination; IDA:WormBase.
DR GO; GO:0006281; P:DNA repair; IMP:WormBase.
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; IPR004035; Endouclease-III_FeS-bd_BS.
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; PS00764; ENDONUCLEASE_III_1; 1.
DR PROSITE; PS01155; ENDONUCLEASE_III_2; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Alternative initiation; Alternative splicing; DNA damage;
KW DNA repair; Glycosidase; Hydrolase; Iron; Iron-sulfur; Lyase;
KW Metal-binding; Mitochondrion; Nucleus; Reference proteome.
FT CHAIN 1..298
FT /note="Endonuclease III homolog"
FT /id="PRO_0000102229"
FT DOMAIN 138..165
FT /note="HhH"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT REGION 249..298
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..279
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 158
FT /note="Nucleophile; for N-glycosylase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT BINDING 226
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 BINDING 236
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT BINDING 242
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT SITE 177
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03183"
FT VAR_SEQ 1..158
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_041643"
FT VAR_SEQ 1..74
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_041642"
FT VAR_SEQ 1..5
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_041641"
SQ SEQUENCE 298 AA; 33117 MW; ACD504175243F42A CRC64;
MHSFSMKRVV ASSSVAAVAT CDVEGTVVAW RRDVELIRKM RKDMIAPVDT MGCHKLADPL
AAPPVHRFQV LVALMLSSQT RDEVNAAAMK RLKDHGLSIG KILEFKVPDL ETILCPVGFY
KRKAVYLQKT AKILKDDFSG DIPDSLDGLC ALPGVGPKMA NLVMQIAWGE CVGIAVDTHV
HRISNRLGWI KTSTPEKTQK ALEILLPKSE WQPINHLLVG FGQMQCQPVR PKCGTCLCRF
TCPSSTAKNV KSETEETSTS IEVKQEVEDE FEDEKPAKKI KKTRKTRTKI EVKTESET
