UDGA_ARCFU
ID UDGA_ARCFU Reviewed; 199 AA.
AC O28007;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Type-4 uracil-DNA glycosylase {ECO:0000305};
DE EC=3.2.2.27 {ECO:0000269|PubMed:10777501, ECO:0000269|PubMed:20453094};
DE AltName: Full=AFUDG {ECO:0000303|PubMed:10777501};
GN Name=afung {ECO:0000303|PubMed:10777501};
GN OrderedLocusNames=AF_2277 {ECO:0000312|EMBL:AAB88977.1};
OS Archaeoglobus fulgidus (strain ATCC 49558 / DSM 4304 / JCM 9628 / NBRC
OS 100126 / VC-16).
OC Archaea; Euryarchaeota; Archaeoglobi; Archaeoglobales; Archaeoglobaceae;
OC Archaeoglobus.
OX NCBI_TaxID=224325;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 49558 / DSM 4304 / JCM 9628 / NBRC 100126 / VC-16;
RX PubMed=9389475; DOI=10.1038/37052;
RA Klenk H.-P., Clayton R.A., Tomb J.-F., White O., Nelson K.E., Ketchum K.A.,
RA Dodson R.J., Gwinn M.L., Hickey E.K., Peterson J.D., Richardson D.L.,
RA Kerlavage A.R., Graham D.E., Kyrpides N.C., Fleischmann R.D.,
RA Quackenbush J., Lee N.H., Sutton G.G., Gill S.R., Kirkness E.F.,
RA Dougherty B.A., McKenney K., Adams M.D., Loftus B.J., Peterson S.N.,
RA Reich C.I., McNeil L.K., Badger J.H., Glodek A., Zhou L., Overbeek R.,
RA Gocayne J.D., Weidman J.F., McDonald L.A., Utterback T.R., Cotton M.D.,
RA Spriggs T., Artiach P., Kaine B.P., Sykes S.M., Sadow P.W., D'Andrea K.P.,
RA Bowman C., Fujii C., Garland S.A., Mason T.M., Olsen G.J., Fraser C.M.,
RA Smith H.O., Woese C.R., Venter J.C.;
RT "The complete genome sequence of the hyperthermophilic, sulphate-reducing
RT archaeon Archaeoglobus fulgidus.";
RL Nature 390:364-370(1997).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=10777501; DOI=10.1074/jbc.m001995200;
RA Sandigursky M., Franklin W.A.;
RT "Uracil-DNA glycosylase in the extreme thermophile Archaeoglobus
RT fulgidus.";
RL J. Biol. Chem. 275:19146-19149(2000).
RN [3]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 49558 / DSM 4304 / JCM 9628 / NBRC 100126 / VC-16;
RX PubMed=20453094; DOI=10.1128/jb.00135-10;
RA Knaevelsrud I., Moen M.N., Groesvik K., Haugland G.T., Birkeland N.K.,
RA Klungland A., Leiros I., Bjelland S.;
RT "The hyperthermophilic euryarchaeon Archaeoglobus fulgidus repairs uracil
RT by single-nucleotide replacement.";
RL J. Bacteriol. 192:5755-5766(2010).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND MUTAGENESIS OF CYS-85; ARG-86;
RP ARG-91; LYS-100 AND CYS-101.
RX PubMed=22646210; DOI=10.1021/bi3000462;
RA Engstrom L.M., Partington O.A., David S.S.;
RT "An iron-sulfur cluster loop motif in the Archaeoglobus fulgidus uracil-DNA
RT glycosylase mediates efficient uracil recognition and removal.";
RL Biochemistry 51:5187-5197(2012).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=ATCC 49558 / DSM 4304 / JCM 9628 / NBRC 100126 / VC-16;
RX PubMed=24936520;
RA Knaevelsrud I., Kazazic S., Birkeland N.K., Bjelland S.;
RT "The pH optimum of native uracil-DNA glycosylase of Archaeoglobus fulgidus
RT compared to recombinant enzyme indicates adaption to cytosolic pH.";
RL Acta Biochim. Pol. 61:393-395(2014).
CC -!- FUNCTION: Removes uracil bases that are present in DNA as a result of
CC either deamination of cytosine or misincorporation of dUMP instead of
CC dTMP. Can remove uracil from double-stranded DNA containing either a
CC U/G or U/A base pair as well as from single-stranded DNA.
CC {ECO:0000269|PubMed:10777501, ECO:0000269|PubMed:20453094,
CC ECO:0000269|PubMed:22646210}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolyzes single-stranded DNA or mismatched double-stranded
CC DNA and polynucleotides, releasing free uracil.; EC=3.2.2.27;
CC Evidence={ECO:0000269|PubMed:10777501, ECO:0000269|PubMed:20453094,
CC ECO:0000269|PubMed:22646210};
CC -!- ACTIVITY REGULATION: Product-inhibited by both uracil and
CC apurinic/apyrimidinic sites. {ECO:0000269|PubMed:10777501}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is around 6.2. {ECO:0000269|PubMed:24936520};
CC Temperature dependence:
CC Extremely thermostable, maintaining full activity after heating for
CC 1.5 hour at 95 degrees Celsius (PubMed:10777501). Exhibits a broad
CC temperature optimum for activity around 80 degrees Celsius
CC (PubMed:24936520). {ECO:0000269|PubMed:10777501,
CC ECO:0000269|PubMed:24936520};
CC -!- DOMAIN: Contains a pseudo-FCL region, a large solvent-exposed peptide
CC region containing an alpha helix and loop anchored on each end via
CC ligation of two cysteine thiolates to a [4Fe-4S](2+) cluster. This
CC region is involved in DNA binding and catalysis, particularly in duplex
CC DNA contexts. {ECO:0000269|PubMed:22646210}.
CC -!- SIMILARITY: Belongs to the uracil-DNA glycosylase (UDG) superfamily.
CC Type 4 (UDGa) family. {ECO:0000305}.
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DR EMBL; AE000782; AAB88977.1; -; Genomic_DNA.
DR PIR; E69534; E69534.
DR RefSeq; WP_010879766.1; NC_000917.1.
DR AlphaFoldDB; O28007; -.
DR SMR; O28007; -.
DR STRING; 224325.AF_2277; -.
DR EnsemblBacteria; AAB88977; AAB88977; AF_2277.
DR GeneID; 1485509; -.
DR KEGG; afu:AF_2277; -.
DR eggNOG; arCOG00905; Archaea.
DR HOGENOM; CLU_044815_1_3_2; -.
DR OMA; RPWLIAE; -.
DR OrthoDB; 90493at2157; -.
DR PhylomeDB; O28007; -.
DR BRENDA; 3.2.2.27; 414.
DR Proteomes; UP000002199; Chromosome.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004844; F:uracil DNA N-glycosylase activity; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IDA:UniProtKB.
DR Gene3D; 3.40.470.10; -; 1.
DR InterPro; IPR005273; Ura-DNA_glyco_family4.
DR InterPro; IPR005122; Uracil-DNA_glycosylase-like.
DR InterPro; IPR036895; Uracil-DNA_glycosylase-like_sf.
DR Pfam; PF03167; UDG; 1.
DR SMART; SM00986; UDG; 1.
DR SUPFAM; SSF52141; SSF52141; 1.
DR TIGRFAMs; TIGR00758; UDG_fam4; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; DNA damage; DNA repair; Hydrolase; Iron; Iron-sulfur;
KW Metal-binding; Reference proteome.
FT CHAIN 1..199
FT /note="Type-4 uracil-DNA glycosylase"
FT /id="PRO_0000439183"
FT REGION 77..114
FT /note="Pseudo-FCL"
FT /evidence="ECO:0000305|PubMed:22646210"
FT BINDING 14
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:Q5SKC5"
FT BINDING 17
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:Q5SKC5"
FT BINDING 41..43
FT /ligand="uracil"
FT /ligand_id="ChEBI:CHEBI:17568"
FT /evidence="ECO:0000250|UniProtKB:Q5SKC5"
FT BINDING 55
FT /ligand="uracil"
FT /ligand_id="ChEBI:CHEBI:17568"
FT /evidence="ECO:0000250|UniProtKB:Q5SKC5"
FT BINDING 81
FT /ligand="uracil"
FT /ligand_id="ChEBI:CHEBI:17568"
FT /evidence="ECO:0000250|UniProtKB:Q5SKC5"
FT BINDING 85
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:Q5SKC5"
FT BINDING 101
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:Q5SKC5"
FT BINDING 163
FT /ligand="uracil"
FT /ligand_id="ChEBI:CHEBI:17568"
FT /evidence="ECO:0000250|UniProtKB:Q5SKC5"
FT MUTAGEN 85
FT /note="C->A: Shows reduced uracil excision efficiency."
FT /evidence="ECO:0000269|PubMed:22646210"
FT MUTAGEN 86
FT /note="R->A: Shows reduced activity for uracil removal only
FT within double-stranded DNA."
FT /evidence="ECO:0000269|PubMed:22646210"
FT MUTAGEN 91
FT /note="R->A: Loss of the iron-sulfur cluster."
FT /evidence="ECO:0000269|PubMed:22646210"
FT MUTAGEN 100
FT /note="K->A: Shows increased uracil excision efficiency."
FT /evidence="ECO:0000269|PubMed:22646210"
FT MUTAGEN 101
FT /note="C->A: Shows reduced uracil excision efficiency."
FT /evidence="ECO:0000269|PubMed:22646210"
SQ SEQUENCE 199 AA; 22718 MW; BD0AA9C80750BA47 CRC64;
MESLDDIVRE IMSCRKCDLH KTKTNYVPGV GNEKAEIVFV GEAPGRDEDL KGEPFVGAAG
KLLTEMLASI GLRREDVYIT NVLKCRPPNN RDPTPEEVEK CGDYLVRQLE AIRPNVIVCL
GRFAAQFIFN LFDLEFTTIS RVKGKVYEVE RWGKKVKVIA IYHPAAVLYR PQLREEYESD
FKKIGELCGK KQPTLFDYL
