MIG_METTF
ID MIG_METTF Reviewed; 221 AA.
AC P29588;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=Thymine/uracil-DNA glycosylase {ECO:0000305};
DE EC=3.2.2.- {ECO:0000269|PubMed:11788726, ECO:0000269|PubMed:8895589};
DE EC=3.2.2.29 {ECO:0000269|PubMed:11788726, ECO:0000269|PubMed:8895589};
DE AltName: Full=DNA mismatch glycosylase {ECO:0000303|PubMed:8895589};
DE Short=MIG {ECO:0000303|PubMed:11786018};
DE AltName: Full=G/T mismatches repair enzyme {ECO:0000305};
DE AltName: Full=Type II nicking enzyme V.MthTI {ECO:0000303|PubMed:12654995};
DE Short=V.MthTI {ECO:0000303|PubMed:12654995};
GN Name=mig {ECO:0000303|PubMed:8895589};
OS Methanothermobacter thermautotrophicus (Methanobacterium thermoformicicum).
OG Plasmid pFV1.
OC Archaea; Euryarchaeota; Methanomada group; Methanobacteria;
OC Methanobacteriales; Methanobacteriaceae; Methanothermobacter.
OX NCBI_TaxID=145262;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=DSM 3848 / THF;
RX PubMed=1336177; DOI=10.1093/nar/20.24.6501;
RA Noelling J., van Eeden F.J.M., Eggen R.I.L., de Vos W.M.;
RT "Modular organization of related Archaeal plasmids encoding different
RT restriction-modification systems in Methanobacterium thermoformicicum.";
RL Nucleic Acids Res. 20:6501-6507(1992).
RN [2]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=DSM 3848 / THF;
RX PubMed=8895589; DOI=10.1002/j.1460-2075.1996.tb00929.x;
RA Horst J.P., Fritz H.J.;
RT "Counteracting the mutagenic effect of hydrolytic deamination of DNA 5-
RT methylcytosine residues at high temperature: DNA mismatch N-glycosylase
RT Mig.Mth of the thermophilic archaeon Methanobacterium thermoautotrophicum
RT THF.";
RL EMBO J. 15:5459-5469(1996).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ALA-50 AND LEU-187.
RX PubMed=11788726; DOI=10.1093/nar/30.2.614;
RA Fondufe-Mittendorf Y.N., Haerer C., Kramer W., Fritz H.J.;
RT "Two amino acid replacements change the substrate preference of DNA
RT mismatch glycosylase Mig.MthI from T/G to A/G.";
RL Nucleic Acids Res. 30:614-621(2002).
RN [4]
RP NOMENCLATURE.
RX PubMed=12654995; DOI=10.1093/nar/gkg274;
RA Roberts R.J., Belfort M., Bestor T., Bhagwat A.S., Bickle T.A.,
RA Bitinaite J., Blumenthal R.M., Degtyarev S.K., Dryden D.T., Dybvig K.,
RA Firman K., Gromova E.S., Gumport R.I., Halford S.E., Hattman S.,
RA Heitman J., Hornby D.P., Janulaitis A., Jeltsch A., Josephsen J., Kiss A.,
RA Klaenhammer T.R., Kobayashi I., Kong H., Krueger D.H., Lacks S.,
RA Marinus M.G., Miyahara M., Morgan R.D., Murray N.E., Nagaraja V.,
RA Piekarowicz A., Pingoud A., Raleigh E., Rao D.N., Reich N., Repin V.E.,
RA Selker E.U., Shaw P.C., Stein D.C., Stoddard B.L., Szybalski W.,
RA Trautner T.A., Van Etten J.L., Vitor J.M., Wilson G.G., Xu S.Y.;
RT "A nomenclature for restriction enzymes, DNA methyltransferases, homing
RT endonucleases and their genes.";
RL Nucleic Acids Res. 31:1805-1812(2003).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS), AND MUTAGENESIS OF GLU-42; ARG-47;
RP TYR-126; ASP-144 AND ASN-146.
RX PubMed=11786018; DOI=10.1006/jmbi.2001.5264;
RA Mol C.D., Arvai A.S., Begley T.J., Cunningham R.P., Tainer J.A.;
RT "Structure and activity of a thermostable thymine-DNA glycosylase: evidence
RT for base twisting to remove mismatched normal DNA bases.";
RL J. Mol. Biol. 315:373-384(2002).
CC -!- FUNCTION: DNA glycosylase that excises thymine from T/G mismatches and
CC uracil from U/G mismatches (PubMed:8895589, PubMed:11788726). Acts as a
CC repair enzyme able to counteract the mutagenic effect of spontaneous
CC hydrolytic deamination of DNA 5-methylcytosine (5-meC) residues that
CC leads to the formation of T/G mismatches (PubMed:8895589). May also
CC repair U/G mismatches arising from hydrolytic deamination of DNA
CC cytosine residues (PubMed:8895589). G/G, A/G, T/C and U/C are minor
CC substrates (PubMed:8895589, PubMed:11788726).
CC {ECO:0000269|PubMed:11788726, ECO:0000269|PubMed:8895589}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes mismatched double-stranded DNA and polynucleotides,
CC releasing free thymine.; EC=3.2.2.29;
CC Evidence={ECO:0000269|PubMed:11788726, ECO:0000269|PubMed:8895589};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:P83847};
CC Note=Binds 1 [4Fe-4S] cluster. The cluster has a structural role.
CC {ECO:0000250|UniProtKB:P83847};
CC -!- SIMILARITY: Belongs to the Nth/MutY family. {ECO:0000305}.
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DR EMBL; X68366; CAA48433.1; -; Genomic_DNA.
DR PIR; S30312; S30312.
DR RefSeq; NP_039762.1; NC_001336.1.
DR RefSeq; WP_010889848.1; NC_001336.1.
DR PDB; 1KEA; X-ray; 2.00 A; A=1-221.
DR PDBsum; 1KEA; -.
DR AlphaFoldDB; P29588; -.
DR SMR; P29588; -.
DR REBASE; 6523; V.MthTI.
DR EvolutionaryTrace; P29588; -.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0016798; F:hydrolase activity, acting on glycosyl bonds; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006284; P:base-excision repair; IEA:InterPro.
DR CDD; cd00056; ENDO3c; 1.
DR Gene3D; 1.10.1670.10; -; 1.
DR InterPro; IPR011257; DNA_glycosylase.
DR InterPro; IPR004036; Endonuclease-III-like_CS2.
DR InterPro; IPR003651; Endonuclease3_FeS-loop_motif.
DR InterPro; IPR004035; Endouclease-III_FeS-bd_BS.
DR InterPro; IPR003265; HhH-GPD_domain.
DR InterPro; IPR023170; HhH_base_excis_C.
DR InterPro; IPR044298; MIG/MutY.
DR PANTHER; PTHR42944; PTHR42944; 1.
DR Pfam; PF00730; HhH-GPD; 1.
DR SMART; SM00478; ENDO3c; 1.
DR SMART; SM00525; FES; 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 3D-structure; 4Fe-4S; DNA damage; DNA repair; Glycosidase; Hydrolase; Iron;
KW Iron-sulfur; Metal-binding; Plasmid.
FT CHAIN 1..221
FT /note="Thymine/uracil-DNA glycosylase"
FT /id="PRO_0000102237"
FT DOMAIN 105..133
FT /note="HhH"
FT BINDING 197
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P83847"
FT BINDING 204
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P83847"
FT BINDING 207
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P83847"
FT BINDING 213
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P83847"
FT MUTAGEN 42
FT /note="E->D: 5-fold lower activity."
FT /evidence="ECO:0000269|PubMed:11786018"
FT MUTAGEN 42
FT /note="E->S: 25-fold lower activity."
FT /evidence="ECO:0000269|PubMed:11786018"
FT MUTAGEN 47
FT /note="R->A: 15-fold lower activity."
FT /evidence="ECO:0000269|PubMed:11786018"
FT MUTAGEN 50
FT /note="A->V: Affects T/G versus U/G selectivity. Changes
FT substrate discrimination between T/G and A/G by a factor of
FT 117 in favor of the latter; when associated with Q-187."
FT /evidence="ECO:0000269|PubMed:11788726"
FT MUTAGEN 126
FT /note="Y->F: 60-fold lower activity."
FT /evidence="ECO:0000269|PubMed:11786018"
FT MUTAGEN 126
FT /note="Y->K: No activity."
FT /evidence="ECO:0000269|PubMed:11786018"
FT MUTAGEN 126
FT /note="Y->S: Almost no activity."
FT /evidence="ECO:0000269|PubMed:11786018"
FT MUTAGEN 144
FT /note="D->A: 15-fold lower activity."
FT /evidence="ECO:0000269|PubMed:11786018"
FT MUTAGEN 144
FT /note="D->N: No activity."
FT /evidence="ECO:0000269|PubMed:11786018"
FT MUTAGEN 146
FT /note="N->E,H: Almost no activity."
FT /evidence="ECO:0000269|PubMed:11786018"
FT MUTAGEN 187
FT /note="L->Q: Accelerates the A/G reaction and decreases
FT activity on T/G and U/G. Changes substrate discrimination
FT between T/G and A/G by a factor of 117 in favor of the
FT latter; when associated with V-50."
FT /evidence="ECO:0000269|PubMed:11788726"
FT HELIX 5..22
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 28..31
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 35..44
FT /evidence="ECO:0007829|PDB:1KEA"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 50..63
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 67..72
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 75..81
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 88..106
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 114..118
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 125..134
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 145..155
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 157..159
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 167..176
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 182..195
FT /evidence="ECO:0007829|PDB:1KEA"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:1KEA"
FT TURN 208..212
FT /evidence="ECO:0007829|PDB:1KEA"
FT HELIX 214..217
FT /evidence="ECO:0007829|PDB:1KEA"
SQ SEQUENCE 221 AA; 25401 MW; D085FCEE1DDC4B62 CRC64;
MDDATNKKRK VFVSTILTFW NTDRRDFPWR HTRDPYVILI TEILLRRTTA GHVKKIYDKF
FVKYKCFEDI LKTPKSEIAK DIKEIGLSNQ RAEQLKELAR VVINDYGGRV PRNRKAILDL
PGVGKYTCAA VMCLAFGKKA AMVDANFVRV INRYFGGSYE NLNYNHKALW ELAETLVPGG
KCRDFNLGLM DFSAIICAPR KPKCEKCGMS KLCSYYEKCS T
