END8A_MYCTU
ID END8A_MYCTU Reviewed; 268 AA.
AC P9WNB9; L0TCL5; O53191; P64158;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 43.
DE RecName: Full=Endonuclease 8 1;
DE AltName: Full=DNA glycosylase/AP lyase Nei 1;
DE EC=3.2.2.-;
DE AltName: Full=DNA-(apurinic or apyrimidinic site) lyase Nei 1;
DE EC=4.2.99.18;
DE AltName: Full=Endonuclease VIII 1;
GN Name=nei1; Synonyms=nei2; OrderedLocusNames=Rv2464c; ORFNames=MTV008.20c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION, AND DNA-BINDING.
RC STRAIN=36KAZ;
RX PubMed=18457574; DOI=10.1134/s0006297908040093;
RA Sidorenko V.S., Rot M.A., Filipenko M.L., Nevinsky G.A., Zharkov D.O.;
RT "Novel DNA glycosylases from Mycobacterium tuberculosis.";
RL Biochemistry (Mosc.) 73:442-450(2008).
RN [3]
RP INDUCTION.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=19496823; DOI=10.1111/j.1574-695x.2009.00562.x;
RA Olsen I., Balasingham S.V., Davidsen T., Debebe E., Rodland E.A.,
RA van Soolingen D., Kremer K., Alseth I., Tonjum T.;
RT "Characterization of the major formamidopyrimidine-DNA glycosylase homolog
RT in Mycobacterium tuberculosis and its linkage to variable tandem repeats.";
RL FEMS Immunol. Med. Microbiol. 56:151-161(2009).
RN [4]
RP FUNCTION, AND SUBSTRATES.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=20031487; DOI=10.1016/j.dnarep.2009.11.008;
RA Guo Y., Bandaru V., Jaruga P., Zhao X., Burrows C.J., Iwai S.,
RA Dizdaroglu M., Bond J.P., Wallace S.S.;
RT "The oxidative DNA glycosylases of Mycobacterium tuberculosis exhibit
RT different substrate preferences from their Escherichia coli counterparts.";
RL DNA Repair 9:177-190(2010).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [6]
RP REVIEW.
RX PubMed=21764637; DOI=10.1016/j.tube.2011.06.005;
RA Kurthkoti K., Varshney U.;
RT "Base excision and nucleotide excision repair pathways in mycobacteria.";
RL Tuberculosis 91:533-543(2011).
CC -!- FUNCTION: Involved in base excision repair of DNA damaged by oxidation
CC or by mutagenic agents. DNA glycosylase that recognizes and removes
CC damaged pyrimidines. Excises Tg:A (thymine glycol, prefers 5R isomers),
CC Tg:G, 5,6-dihydrouracil:G base pairs and urea:A, also excises oxidized
CC purine derivatives guanidinohydantoin:C and spiroiminodihydantoin:C.
CC Poorly cleaves dsDNA with uracil substitutions, thus also acting as a
CC weak uracil-DNA glycosylase. Acts on DNA bubble and 3'-fork structures,
CC suggesting a role in replication-associated DNA repair. Activity on
CC 7,8-dihydro-8-oxoguanine (8-oxoG) is debated; a report shows weak
CC activity (PubMed:18457574), whereas another shows none
CC (PubMed:20031487). Has AP (apurinic/apyrimidinic) activity and
CC introduces nicks in dsDNA strand, inefficiently cleaves ssDNA with AP
CC sites and uracil. Probably cleaves the DNA backbone by beta-delta
CC elimination to generate a single-strand break at the site of the
CC removed base with both 3'- and 5'-phosphates. Cleaves ssDNA containing
CC an AP site. Complements an E.coli fpg mutY but not nei nth double
CC mutant (PubMed:18457574). {ECO:0000269|PubMed:18457574,
CC ECO:0000269|PubMed:20031487}.
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 -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00391};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00391};
CC -!- INDUCTION: Expressed in mid-log phase. {ECO:0000269|PubMed:19496823}.
CC -!- SIMILARITY: Belongs to the FPG family. {ECO:0000305}.
CC -!- CAUTION: There are 2 paralogs in M.tuberculosis, in some references
CC this gene is called nei2 (PubMed:18457574 and PubMed:19496823).
CC {ECO:0000305}.
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DR EMBL; AL123456; CCP45257.1; -; Genomic_DNA.
DR PIR; G70865; G70865.
DR RefSeq; NP_216980.1; NC_000962.3.
DR RefSeq; WP_003412657.1; NZ_NVQJ01000024.1.
DR AlphaFoldDB; P9WNB9; -.
DR SMR; P9WNB9; -.
DR STRING; 83332.Rv2464c; -.
DR PaxDb; P9WNB9; -.
DR DNASU; 888500; -.
DR GeneID; 888500; -.
DR KEGG; mtu:Rv2464c; -.
DR TubercuList; Rv2464c; -.
DR eggNOG; COG0266; Bacteria.
DR OMA; ARNLFWC; -.
DR PhylomeDB; P9WNB9; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0140078; F:class I DNA-(apurinic or apyrimidinic site) endonuclease activity; IEA:UniProtKB-EC.
DR GO; GO:0003684; F:damaged DNA binding; IEA:InterPro.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IDA:MTBBASE.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:MTBBASE.
DR GO; GO:0008534; F:oxidized purine nucleobase lesion DNA N-glycosylase activity; IDA:MTBBASE.
DR GO; GO:0000703; F:oxidized pyrimidine nucleobase lesion DNA N-glycosylase activity; IDA:MTBBASE.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:MTBBASE.
DR GO; GO:0004844; F:uracil DNA N-glycosylase activity; IDA:MTBBASE.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006284; P:base-excision repair; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:MTBBASE.
DR GO; GO:0006281; P:DNA repair; IDA:MTBBASE.
DR GO; GO:0006289; P:nucleotide-excision repair; IMP:MTBBASE.
DR GO; GO:0006979; P:response to oxidative stress; IDA:MTBBASE.
DR Gene3D; 3.20.190.10; -; 1.
DR InterPro; IPR015886; DNA_glyclase/AP_lyase_DNA-bd.
DR InterPro; IPR015887; DNA_glyclase_Znf_dom_DNA_BS.
DR InterPro; IPR012319; FPG_cat.
DR InterPro; IPR035937; MutM-like_N-ter.
DR InterPro; IPR010979; Ribosomal_S13-like_H2TH.
DR InterPro; IPR000214; Znf_DNA_glyclase/AP_lyase.
DR InterPro; IPR010663; Znf_FPG/IleRS.
DR Pfam; PF01149; Fapy_DNA_glyco; 1.
DR Pfam; PF06831; H2TH; 1.
DR Pfam; PF06827; zf-FPG_IleRS; 1.
DR SMART; SM00898; Fapy_DNA_glyco; 1.
DR SMART; SM01232; H2TH; 1.
DR SUPFAM; SSF46946; SSF46946; 1.
DR SUPFAM; SSF81624; SSF81624; 1.
DR PROSITE; PS01242; ZF_FPG_1; 1.
DR PROSITE; PS51066; ZF_FPG_2; 1.
PE 1: Evidence at protein level;
KW DNA damage; DNA repair; DNA-binding; Glycosidase; Hydrolase; Lyase;
KW Metal-binding; Multifunctional enzyme; Reference proteome; Zinc;
KW Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250"
FT CHAIN 2..268
FT /note="Endonuclease 8 1"
FT /id="PRO_0000170903"
FT ZN_FING 234..268
FT /note="FPG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00391"
FT ACT_SITE 2
FT /note="Schiff-base intermediate with DNA"
FT /evidence="ECO:0000250"
FT ACT_SITE 3
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT ACT_SITE 52
FT /note="Proton donor; for beta-elimination activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 258
FT /note="Proton donor; for delta-elimination activity"
FT /evidence="ECO:0000250"
FT BINDING 125
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 166
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
SQ SEQUENCE 268 AA; 29714 MW; 1142DE185BD14F24 CRC64;
MPEGHTLHRL ARLHQRRFAG APVSVSSPQG RFADSASALN GRVLRRASAW GKHLFHHYVG
GPVVHVHLGL YGTFTEWARP TDGWLPEPAG QVRMRMVGAE FGTDLRGPTV CESIDDGEVA
DVVARLGPDP LRSDANPSSA WSRITKSRRP IGALLMDQTV IAGVGNVYRN ELLFRHRIDP
QRPGRGIGEP EFDAAWNDLV SLMKVGLRRG KIIVVRPEHD HGLPSYLPDR PRTYVYRRAG
EPCRVCGGVI RTALLEGRNV FWCPVCQT
