ID DPO3E_ECOLI Reviewed; 243 AA. AC P03007; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1988, sequence version 1. DT 04-NOV-2026, entry version 214. DE RecName: Full=DNA polymerase III subunit epsilon; DE EC=2.7.7.7; GN Name=dnaQ; Synonyms=mutD; OrderedLocusNames=b0215, JW0205; OS Escherichia coli (strain K12). OC Bacteria; Pseudomonadati; Pseudomonadota; Gammaproteobacteria; OC Enterobacterales; Enterobacteriaceae; Escherichia. OX NCBI_TaxID=83333; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3023634; DOI=10.1016/0022-2836(86)90080-x; RA Cox E.C., Horner D.L.; RT "DNA sequence and coding properties of mutD(dnaQ) a dominant Escherichia RT coli mutator gene."; RL J. Mol. Biol. 190:113-117(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6316347; DOI=10.1073/pnas.80.23.7137; RA Maki H., Horiuchi T., Sekiguchi M.; RT "Structure and expression of the dnaQ mutator and the RNase H genes of RT Escherichia coli: overlap of the promoter regions."; RL Proc. Natl. Acad. Sci. U.S.A. 80:7137-7141(1983). RN [3] RP SEQUENCE REVISION. RX PubMed=3540531; DOI=10.1007/bf02428026; RA Takano K., Nakabeppu Y., Maki H., Horiuchi T., Sekiguchi M.; RT "Structure and function of dnaQ and mutD mutators of Escherichia coli."; RL Mol. Gen. Genet. 205:9-13(1986). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RA Takemoto K., Mori H., Murayama N., Kataoka K., Yano M., Itoh T., RA Yamamoto Y., Inokuchi H., Miki T., Hatada E., Fukuda R., Ichihara S., RA Mizuno T., Makino K., Nakata A., Yura T., Sampei G., Mizobuchi K.; RT "Systematic sequencing of the Escherichia coli genome: analysis of the 4.0 RT - 6.0 min (189,987 - 281,416bp) region."; RL Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / MG1655 / ATCC 47076; RA Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M., RA Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D., RA Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.; RT "Sequence of minutes 4-25 of Escherichia coli."; RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=9278503; DOI=10.1126/science.277.5331.1453; RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., RA Shao Y.; RT "The complete genome sequence of Escherichia coli K-12."; RL Science 277:1453-1462(1997). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=16738553; DOI=10.1038/msb4100049; RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.; RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 RT and W3110."; RL Mol. Syst. Biol. 2:E1-E5(2006). RN [8] RP FUNCTION AS THE EXONUCLEASE SUBUNIT. RX PubMed=6340117; DOI=10.1073/pnas.80.8.2189; RA Echols H., Lu C., Burgers P.M.; RT "Mutator strains of Escherichia coli, mutD and dnaQ, with defective RT exonucleolytic editing by DNA polymerase III holoenzyme."; RL Proc. Natl. Acad. Sci. U.S.A. 80:2189-2192(1983). RN [9] RP REVIEW. RX PubMed=1575709; DOI=10.1002/bies.950140206; RA O'Donnell M.; RT "Accessory protein function in the DNA polymerase III holoenzyme from E. RT coli."; RL Bioessays 14:105-111(1992). RN [10] RP IDENTIFICATION BY 2D-GEL. RX PubMed=9298644; DOI=10.1002/elps.1150180805; RA VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C.; RT "Escherichia coli proteome analysis using the gene-protein database."; RL Electrophoresis 18:1243-1251(1997). RN [11] RP REPLISOME COMPLEX, AND SUBUNIT. RX PubMed=20413500; DOI=10.1126/science.1185757; RA Reyes-Lamothe R., Sherratt D.J., Leake M.C.; RT "Stoichiometry and architecture of active DNA replication machinery in RT Escherichia coli."; RL Science 328:498-501(2010). RN [12] RP REPLISOME COMPLEX, AND SUBUNIT. RX PubMed=22157955; DOI=10.1038/nsmb.2179; RA Georgescu R.E., Kurth I., O'Donnell M.E.; RT "Single-molecule studies reveal the function of a third polymerase in the RT replisome."; RL Nat. Struct. Mol. Biol. 19:113-116(2011). RN [13] RP MUTAGENESIS OF THR-15. RC STRAIN=K12 / AB1157; RX PubMed=26544712; DOI=10.1371/journal.pgen.1005651; RA Brown L.T., Sutera V.A. Jr., Zhou S., Weitzel C.S., Cheng Y., Lovett S.T.; RT "Connecting replication and repair: YoaA, a helicase-related protein, RT promotes azidothymidine tolerance through association with Chi, an RT accessory clamp loader protein."; RL PLoS Genet. 11:E1005651-E1005651(2015). RN [14] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH METAL IONS AND SUBSTRATE ANALOG. RX PubMed=11937058; DOI=10.1016/s0969-2126(02)00738-4; RA Hamdan S., Carr P.D., Brown S.E., Ollis D.L., Dixon N.E.; RT "Structural basis for proofreading during replication of the Escherichia RT coli chromosome."; RL Structure 10:535-546(2002). RN [15] {ECO:0007744|PDB:5FKU, ECO:0007744|PDB:5FKV, ECO:0007744|PDB:5FKW} RP STRUCTURE BY ELECTRON MICROSCOPY OF DNAE; DNAN; DNAQ; DNAX WITH AND WITHOUT RP DNA, SUBUNIT, AND MUTAGENESIS OF 183-THR--PHE-187. RX PubMed=26499492; DOI=10.7554/elife.11134; RA Fernandez-Leiro R., Conrad J., Scheres S.H., Lamers M.H.; RT "cryo-EM structures of the E. coli replicative DNA polymerase reveal its RT dynamic interactions with the DNA sliding clamp, exonuclease and tau."; RL Elife 4:0-0(2015). CC -!- FUNCTION: DNA polymerase III is a complex, multichain enzyme CC responsible for most of the replicative synthesis in bacteria. The CC epsilon subunit contain the editing function and is a proofreading 3'- CC 5' exonuclease (PubMed:6340117). Contacts both the beta sliding clamp CC (dnaN) and the polymerase subunit (dnaE), stabilizing their interaction CC (PubMed:26499492). {ECO:0000269|PubMed:26499492, CC ECO:0000269|PubMed:6340117}. CC -!- CATALYTIC ACTIVITY: CC Reaction=DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + CC diphosphate; Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA- CC COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112; CC EC=2.7.7.7; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Note=Binds 2 divalent metal cations. Magnesium or manganese.; CC -!- SUBUNIT: In a ternary complex this subunit contacts both the beta CC sliding clamp (dnaN) and the polymerase subunit (dnaE) CC (PubMed:26499492). The DNA polymerase III holoenzyme complex contains CC at least 10 different subunits organized into 3 functionally essential CC subassemblies: the Pol III core, the beta sliding clamp processivity CC factor and the clamp-loading complex. The Pol III core (subunits alpha, CC epsilon and theta) contains the polymerase and the 3'-5' exonuclease CC proofreading activities (PubMed:6340117). The polymerase is tethered to CC the template via the dimeric beta sliding clamp processivity factor. CC The clamp loader (also called gamma complex) assembles the beta sliding CC clamp onto the primed template and plays a central role in the CC organization and communication at the replication fork. The clamp- CC loading complex contains delta, delta', psi and chi, and 3 copies of CC either or both of two different DnaX proteins, gamma and tau. The DNA CC replisome complex has a single clamp loader (3 tau and 1 each of delta, CC delta', psi and chi subunits) which binds 3 Pol III cores (1 core on CC the leading strand and 2 on the lagging strand) each with a beta CC sliding clamp dimer. Additional proteins in the replisome are other CC copies of gamma, psi and chi, Ssb, DNA helicase and RNA primase CC (PubMed:20413500, PubMed:22157955). {ECO:0000269|PubMed:11937058, CC ECO:0000269|PubMed:20413500, ECO:0000269|PubMed:22157955, CC ECO:0000269|PubMed:26499492, ECO:0000269|PubMed:6340117}. CC -!- INTERACTION: CC P03007; P10443: dnaE; NbExp=25; IntAct=EBI-549131, EBI-549111; CC P03007; P0A988: dnaN; NbExp=6; IntAct=EBI-549131, EBI-542385; CC P03007; P06710: dnaX; NbExp=6; IntAct=EBI-549131, EBI-549140; CC P03007; P28630: holA; NbExp=3; IntAct=EBI-549131, EBI-549153; CC P03007; P0ABS8: holE; NbExp=13; IntAct=EBI-549131, EBI-549182; CC -!- SEQUENCE CAUTION: CC Sequence=AAB08637.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; 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; X04027; CAA27661.1; -; Genomic_DNA. DR EMBL; K00985; AAA24564.1; -; Genomic_DNA. DR EMBL; U70214; AAB08637.1; ALT_INIT; Genomic_DNA. DR EMBL; U00096; AAC73320.1; -; Genomic_DNA. DR EMBL; AP009048; BAA77886.1; -; Genomic_DNA. DR PIR; A64746; IQECQ. DR RefSeq; NP_414751.1; NC_000913.3. DR RefSeq; WP_001340895.1; NZ_CP009789.1. DR PDB; 1J53; X-ray; 1.80 A; A=1-186. DR PDB; 1J54; X-ray; 1.70 A; A=1-186. DR PDB; 2GUI; X-ray; 1.60 A; A=1-191. DR PDB; 2IDO; X-ray; 2.10 A; A/C=1-186. DR PDB; 2XY8; NMR; -; A=1-186. DR PDB; 4GX8; X-ray; 1.70 A; A/B/C/D=208-243. DR PDB; 4GX9; X-ray; 2.15 A; A/B/C/D=200-243. DR PDB; 5FKU; EM; 8.34 A; D=1-243. DR PDB; 5FKV; EM; 8.00 A; D=1-243. DR PDB; 5FKW; EM; 7.30 A; D=1-243. DR PDB; 5M1S; EM; 6.70 A; D=1-243. DR BMRB; P03007; -. DR SMR; P03007; -. DR BioGRID; 4262121; 77. DR BioGRID; 850796; 6. DR ComplexPortal; CPX-1925; DNA polymerase III core complex. DR DIP; DIP-9462N; -. DR IntAct; P03007; 30. DR STRING; 511145.b0215; -. DR ChEMBL; CHEMBL1075047; -. DR DrugBank; DB01643; Thymidine monophosphate. DR PaxDb; 511145-b0215; -. DR jPOST; P03007; -. DR EnsemblBacteria; AAC73320; AAC73320; b0215. DR GeneID; 946441; -. DR KEGG; ecj:JW0205; -. DR KEGG; eco:b0215; -. DR PATRIC; fig|511145.12.peg.217; -. DR EchoBASE; EB0239; -. DR eggNOG; COG0847; Bacteria. DR HOGENOM; CLU_047806_2_0_6; -. DR InParanoid; P03007; -. DR OMA; AACMEIF; -. DR OrthoDB; 9804290at2; -. DR PhylomeDB; P03007; -. DR BioCyc; EcoCyc:EG10243-MONOMER; -. DR BioCyc; MetaCyc:EG10243-MONOMER; -. DR EvolutionaryTrace; P03007; -. DR PRO; PR:P03007; -. DR CDD; cd06131; DNA_pol_III_epsilon_Ecoli_like; 1. DR FunFam; 3.30.420.10:FF:000012; DNA polymerase III subunit epsilon; 1. DR Gene3D; 3.20.20.140; Metal-dependent hydrolases; 1. DR Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 1. DR InterPro; IPR006054; DnaQ. DR InterPro; IPR006309; DnaQ_proteo. DR InterPro; IPR013520; Ribonucl_H. DR InterPro; IPR012337; RNaseH-like_sf. DR InterPro; IPR036397; RNaseH_sf. DR PANTHER; PTHR30231; DNA POLYMERASE III SUBUNIT EPSILON; 1. DR PANTHER; PTHR30231:SF41; DNA POLYMERASE III SUBUNIT EPSILON; 1. DR Pfam; PF00929; RNase_T; 1. DR SMART; SM00479; EXOIII; 1. DR SUPFAM; SSF53098; Ribonuclease H-like; 1. DR NCBIfam; NF004316; dnaQ; 1. DR NCBIfam; TIGR00573; dnaq; 1. DR NCBIfam; TIGR01406; dnaQ_proteo; 1. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0009360; C:DNA polymerase III complex; NAS:ComplexPortal. DR GO; GO:0044776; C:DNA polymerase III, core complex; IDA:EcoCyc. DR GO; GO:0030894; C:replisome; NAS:ComplexPortal. DR GO; GO:0008408; F:3'-5' exonuclease activity; IBA:GO_Central. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IEA:UniProtKB-EC. DR GO; GO:0004527; F:exonuclease activity; IDA:EcoCyc. DR GO; GO:0045004; P:DNA replication proofreading; IMP:EcoCyc. DR GO; GO:0006261; P:DNA-templated DNA replication; NAS:ComplexPortal. DR GO; GO:0006273; P:lagging strand elongation; IDA:ComplexPortal. DR GO; GO:0006272; P:leading strand elongation; IDA:ComplexPortal. DR Proteomes; UP000000625; Chromosome. DR AlphaFoldDB; P03007; -. DR EMDB; EMD-3198; -. DR EMDB; EMD-3201; -. DR EMDB; EMD-3202; -. DR EMDB; EMD-4141; -. DR FunCoup; P03007; 156. PE 1: Evidence at protein level; KW 3D-structure; DNA replication; DNA-directed DNA polymerase; Exonuclease; KW Hydrolase; Magnesium; Manganese; Metal-binding; Nuclease; KW Nucleotidyltransferase; Reference proteome; Transferase. FT CHAIN 1..243 FT /note="DNA polymerase III subunit epsilon" FT /id="PRO_0000105483" FT ACT_SITE 162 FT /note="Proton acceptor" FT BINDING 12 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="1" FT /ligand_note="catalytic" FT BINDING 12 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="2" FT /ligand_note="catalytic" FT BINDING 12 FT /ligand="substrate" FT BINDING 14 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="1" FT /ligand_note="catalytic" FT BINDING 14 FT /ligand="substrate" FT BINDING 61 FT /ligand="substrate" FT BINDING 66 FT /ligand="substrate" FT BINDING 167 FT /ligand="a divalent metal cation" FT /ligand_id="ChEBI:CHEBI:60240" FT /ligand_label="1" FT /ligand_note="catalytic" FT BINDING 167 FT /ligand="substrate" FT MUTAGEN 15 FT /note="T->I: In mutD5, reduces suppression of AZT FT sensitivity of holC or yoaA knockouts, reduces exonuclease FT activity." FT /evidence="ECO:0000269|PubMed:26544712" FT MUTAGEN 183..187 FT /note="TSMAF->LSLPL: Increases binding to beta sliding FT clamp (dnaN), increases stability of enzyme complex." FT /evidence="ECO:0000269|PubMed:26499492" FT STRAND 7..16 FT /evidence="ECO:0007829|PDB:2GUI" FT STRAND 20..23 FT /evidence="ECO:0007829|PDB:2GUI" FT TURN 24..27 FT /evidence="ECO:0007829|PDB:2GUI" FT STRAND 30..39 FT /evidence="ECO:0007829|PDB:2GUI" FT STRAND 48..51 FT /evidence="ECO:0007829|PDB:2GUI" FT HELIX 60..66 FT /evidence="ECO:0007829|PDB:2GUI" FT HELIX 70..73 FT /evidence="ECO:0007829|PDB:2GUI" FT HELIX 79..90 FT /evidence="ECO:0007829|PDB:2GUI" FT STRAND 93..97 FT /evidence="ECO:0007829|PDB:2GUI" FT HELIX 100..113 FT /evidence="ECO:0007829|PDB:2GUI" FT HELIX 121..123 FT /evidence="ECO:0007829|PDB:2GUI" FT STRAND 125..129 FT /evidence="ECO:0007829|PDB:2GUI" FT HELIX 130..137 FT /evidence="ECO:0007829|PDB:2GUI" FT HELIX 145..151 FT /evidence="ECO:0007829|PDB:2GUI" FT STRAND 156..158 FT /evidence="ECO:0007829|PDB:2XY8" FT HELIX 164..178 FT /evidence="ECO:0007829|PDB:2GUI" FT HELIX 219..236 FT /evidence="ECO:0007829|PDB:4GX8" FT HELIX 240..242 FT /evidence="ECO:0007829|PDB:4GX8" SQ SEQUENCE 243 AA; 27099 MW; 4211C9A00744964F CRC64; MSTAITRQIV LDTETTGMNQ IGAHYEGHKI IEIGAVEVVN RRLTGNNFHV YLKPDRLVDP EAFGVHGIAD EFLLDKPTFA EVADEFMDYI RGAELVIHNA AFDIGFMDYE FSLLKRDIPK TNTFCKVTDS LAVARKMFPG KRNSLDALCA RYEIDNSKRT LHGALLDAQI LAEVYLAMTG GQTSMAFAME GETQQQQGEA TIQRIVRQAS KLRVVFATDE EIAAHEARLD LVQKKGGSCL WRA //