FPG1_MYCTU
ID FPG1_MYCTU Reviewed; 289 AA.
AC P9WNC3; L0TDY9; P64150; Q10959;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=Formamidopyrimidine-DNA glycosylase 1;
DE Short=Fapy-DNA glycosylase 1;
DE EC=3.2.2.23;
DE AltName: Full=DNA-(apurinic or apyrimidinic site) lyase MutM 1;
DE Short=AP lyase MutM 1;
DE EC=4.2.99.18;
GN Name=fpg1; Synonyms=mutM; OrderedLocusNames=Rv2924c; ORFNames=MTCY338.13c;
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.
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=17698424; DOI=10.1016/j.dnarep.2007.06.009;
RA Jain R., Kumar P., Varshney U.;
RT "A distinct role of formamidopyrimidine DNA glycosylase (MutM) in down-
RT regulation of accumulation of G, C mutations and protection against
RT oxidative stress in mycobacteria.";
RL DNA Repair 6:1774-1785(2007).
RN [3]
RP FUNCTION, SUBSTRATES, AND 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, SUBSTRATES, AND DNA-BINDING.
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. Acts as DNA glycosylase that recognizes and
CC removes damaged bases. Has a preference for oxidized purines, such as
CC 7,8-dihydro-8-oxoguanine (8-oxoG) when paired with C, G or T, as well
CC as methyl-faPy (formanidopyrimidine residues) in poly(dG-dC) and
CC spiroiminodihydantoin:C base pairs. Unlike its E.coli ortholog has no
CC activity on 8-oxoG:A. Has AP (apurinic/apyrimidinic) lyase activity and
CC introduces nicks in the DNA strand. Cleaves the DNA backbone by beta-
CC delta 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 the H(2)O(2) sensitivity of an M.smegmatis fpg
CC disruption mutant; upon expression in M.smegmatis excises 8-oxoG from
CC dsDNA. {ECO:0000269|PubMed:17698424, ECO:0000269|PubMed:19496823,
CC ECO:0000269|PubMed:20031487}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of DNA containing ring-opened 7-methylguanine
CC residues, releasing 2,6-diamino-4-hydroxy-5-(N-
CC methyl)formamidopyrimidine.; EC=3.2.2.23;
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; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- INDUCTION: Expressed in mid-log phase. {ECO:0000269|PubMed:19496823}.
CC -!- SIMILARITY: Belongs to the FPG family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45727.1; -; Genomic_DNA.
DR PIR; D70748; D70748.
DR RefSeq; NP_217440.1; NC_000962.3.
DR RefSeq; WP_003414814.1; NZ_NVQJ01000006.1.
DR AlphaFoldDB; P9WNC3; -.
DR SMR; P9WNC3; -.
DR STRING; 83332.Rv2924c; -.
DR PaxDb; P9WNC3; -.
DR DNASU; 887438; -.
DR GeneID; 45426912; -.
DR GeneID; 887438; -.
DR KEGG; mtu:Rv2924c; -.
DR TubercuList; Rv2924c; -.
DR eggNOG; COG0266; Bacteria.
DR OMA; GVHLRMT; -.
DR PhylomeDB; P9WNC3; -.
DR BRENDA; 3.2.2.23; 3445.
DR PHI-base; PHI:3627; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0034039; F:8-oxo-7,8-dihydroguanine DNA N-glycosylase activity; IDA:MTBBASE.
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:0019104; F:DNA N-glycosylase activity; IBA:GO_Central.
DR GO; GO:0003906; F:DNA-(apurinic or apyrimidinic site) endonuclease activity; IBA:GO_Central.
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:0008270; F:zinc ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006284; P:base-excision repair; IDA:MTBBASE.
DR GO; GO:0006281; P:DNA repair; IDA:MTBBASE.
DR GO; GO:0006979; P:response to oxidative stress; IDA:MTBBASE.
DR Gene3D; 3.20.190.10; -; 1.
DR HAMAP; MF_00103; Fapy_DNA_glycosyl; 1.
DR InterPro; IPR015886; DNA_glyclase/AP_lyase_DNA-bd.
DR InterPro; IPR015887; DNA_glyclase_Znf_dom_DNA_BS.
DR InterPro; IPR020629; Formamido-pyr_DNA_Glyclase.
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 TIGRFAMs; TIGR00577; fpg; 1.
DR PROSITE; PS51068; FPG_CAT; 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..289
FT /note="Formamidopyrimidine-DNA glycosylase 1"
FT /id="PRO_0000170840"
FT ZN_FING 251..285
FT /note="FPG-type"
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 61
FT /note="Proton donor; for beta-elimination activity"
FT /evidence="ECO:0000250"
FT ACT_SITE 275
FT /note="Proton donor; for delta-elimination activity"
FT /evidence="ECO:0000250"
FT BINDING 100
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 119
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 165
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
SQ SEQUENCE 289 AA; 31951 MW; E00B94A70DC2904E CRC64;
MPELPEVEVV RRGLQAHVTG RTITEVRVHH PRAVRRHDAG PADLTARLRG ARINGTDRRG
KYLWLTLNTA GVHRPTDTAL VVHLGMSGQM LLGAVPCAAH VRISALLDDG TVLSFADQRT
FGGWLLADLV TVDGSVVPVP VAHLARDPLD PRFDCDAVVK VLRRKHSELK RQLLDQRVVS
GIGNIYADEA LWRAKVNGAH VAATLRCRRL GAVLHAAADV MREALAKGGT SFDSLYVNVN
GESGYFERSL DAYGREGENC RRCGAVIRRE RFMNRSSFYC PRCQPRPRK
