ID HOLA_ECOLI Reviewed; 343 AA. AC P28630; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-1992, sequence version 1. DT 24-JAN-2024, entry version 183. DE RecName: Full=DNA polymerase III subunit delta; DE EC=2.7.7.7; GN Name=holA; OrderedLocusNames=b0640, JW0635; OS Escherichia coli (strain K12). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Enterobacteriaceae; Escherichia. OX NCBI_TaxID=83333; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=K12; RX PubMed=8505303; DOI=10.1016/s0021-9258(19)50264-2; RA Dong Z., Onrust R., Skangalis M., O'Donnell M.; RT "DNA polymerase III accessory proteins. I. holA and holB encoding delta and RT delta'."; RL J. Biol. Chem. 268:11758-11765(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=1400251; DOI=10.1128/jb.174.21.7013-7025.1992; RA Carter J.R., Franden M.A., Aebersold R.H., McHenry C.S.; RT "Molecular cloning, sequencing, and overexpression of the structural gene RT encoding the delta subunit of Escherichia coli DNA polymerase III RT holoenzyme."; RL J. Bacteriol. 174:7013-7025(1992). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=8905232; DOI=10.1093/dnares/3.3.137; RA Oshima T., Aiba H., Baba T., Fujita K., Hayashi K., Honjo A., Ikemoto K., RA Inada T., Itoh T., Kajihara M., Kanai K., Kashimoto K., Kimura S., RA Kitagawa M., Makino K., Masuda S., Miki T., Mizobuchi K., Mori H., RA Motomura K., Nakamura Y., Nashimoto H., Nishio Y., Saito N., Sampei G., RA Seki Y., Tagami H., Takemoto K., Wada C., Yamamoto Y., Yano M., RA Horiuchi T.; RT "A 718-kb DNA sequence of the Escherichia coli K-12 genome corresponding to RT the 12.7-28.0 min region on the linkage map."; RL DNA Res. 3:137-155(1996). RN [4] 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 [5] 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 [6] 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 [7] RP PRELIMINARY NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49. RC STRAIN=K12; RX PubMed=3316191; DOI=10.1128/jb.169.12.5692-5699.1987; RA Takase I., Ishino F., Wachi M., Kamata H., Doi M., Asoh S., Matsuzawa H., RA Ohta T., Matsuhashi M.; RT "Genes encoding two lipoproteins in the leuS-dacA region of the Escherichia RT coli chromosome."; RL J. Bacteriol. 169:5692-5699(1987). RN [8] RP FUNCTION, AND SUBUNIT. RX PubMed=2040637; DOI=10.1016/s0021-9258(18)99166-0; RA Stukenberg P.T., Studwell-Vaughan P.S., O'Donnell M.; RT "Mechanism of the sliding beta-clamp of DNA polymerase III holoenzyme."; RL J. Biol. Chem. 266:11328-11334(1991). RN [9] RP CHARACTERIZATION. RX PubMed=8505304; DOI=10.1016/s0021-9258(19)50265-4; RA Onrust R., O'Donnell M.; RT "DNA polymerase III accessory proteins. II. Characterization of delta and RT delta'."; RL J. Biol. Chem. 268:11766-11772(1993). RN [10] 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 [11] 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 [12] RP FUNCTION, AND SUBUNIT. RX PubMed=9927437; DOI=10.1093/emboj/18.3.771; RA Turner J., Hingorani M.M., Kelman Z., O'Donnell M.; RT "The internal workings of a DNA polymerase clamp-loading machine."; RL EMBO J. 18:771-783(1999). RN [13] 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 [14] 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 [15] {ECO:0007744|PDB:1JQJ, ECO:0007744|PDB:1JQL} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH BETA SLIDING-CLAMP RP (DNAN), FUNCTION, AND DOMAIN. RX PubMed=11525728; DOI=10.1016/s0092-8674(01)00462-7; RA Jeruzalmi D., Yurieva O., Zhao Y., Young M., Stewart J., Hingorani M., RA O'Donnell M., Kuriyan J.; RT "Mechanism of processivity clamp opening by the delta subunit wrench of the RT clamp loader complex of E. coli DNA polymerase III."; RL Cell 106:417-428(2001). RN [16] {ECO:0007744|PDB:1JR3} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) IN COMPLEX WITH HOLB AND DNAX RP (ISOFORM GAMMA). RX PubMed=11525729; DOI=10.1016/s0092-8674(01)00463-9; RA Jeruzalmi D., O'Donnell M., Kuriyan J.; RT "Crystal structure of the processivity clamp loader gamma (gamma) complex RT of E. coli DNA polymerase III."; RL Cell 106:429-441(2001). CC -!- FUNCTION: Part of the beta sliding clamp loading complex, which CC hydrolyzes ATP to load the beta clamp onto primed DNA to form the DNA CC replication pre-initiation complex (PubMed:2040637). DNA polymerase III CC is a complex, multichain enzyme responsible for most of the replicative CC synthesis in bacteria. This DNA polymerase also exhibits 3'-5' CC exonuclease activity. The delta subunit is the wrench that will open CC the beta subunit dimer, which has been modeled to leave a gap large CC enough for ssDNA to pass through (PubMed:11525728). The gamma complex CC (gamma(3),delta,delta') is thought to load beta dimers onto DNA by CC binding ATP which alters the complex's conformation so it can bind beta CC sliding clamp dimers and open them at one interface. Primed DNA is CC recognized, ATP is hydrolyzed releasing the gamma complex and closing CC the beta sliding clamp ring around the primed DNA (PubMed:9927437). CC {ECO:0000269|PubMed:2040637, ECO:0000269|PubMed:9927437, CC ECO:0000305|PubMed:11525728}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = CC diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, CC Rhea:RHEA-COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, CC ChEBI:CHEBI:173112; EC=2.7.7.7; CC -!- SUBUNIT: The DNA polymerase III holoenzyme complex contains at least 10 CC 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:2040637). The polymerase is tethered to CC the template via the dimeric beta sliding clamp processivity factor. CC The clamp-loading complex (also called gamma complex) assembles the CC beta sliding clamp onto the primed template and plays a central role in CC the 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). The clamp loader hydrolyzes ATP to CC assemble the beta processivity factor onto the primed template CC (PubMed:2040637, PubMed:9927437) and plays a central role in the CC organization and communication at the replication fork; the minimal CC complex to load the beta sliding clamp on DNA is delta, delta', gamma CC (PubMed:9927437). {ECO:0000269|PubMed:11525729, CC ECO:0000269|PubMed:2040637, ECO:0000269|PubMed:20413500, CC ECO:0000269|PubMed:22157955, ECO:0000269|PubMed:9927437}. CC -!- INTERACTION: CC P28630; P10443: dnaE; NbExp=5; IntAct=EBI-549153, EBI-549111; CC P28630; P0A988: dnaN; NbExp=10; IntAct=EBI-549153, EBI-542385; CC P28630; P03007: dnaQ; NbExp=3; IntAct=EBI-549153, EBI-549131; CC P28630; P06710: dnaX; NbExp=19; IntAct=EBI-549153, EBI-549140; CC P28630; P06710-1: dnaX; NbExp=5; IntAct=EBI-549153, EBI-6464728; CC P28630; P06710-2: dnaX; NbExp=6; IntAct=EBI-549153, EBI-2604194; CC P28630; P28631: holB; NbExp=19; IntAct=EBI-549153, EBI-549161; CC P28630; P23367: mutL; NbExp=2; IntAct=EBI-549153, EBI-554913; CC P28630; P17117: nfsA; NbExp=3; IntAct=EBI-549153, EBI-1120624; CC P28630; P64526: yeeW; NbExp=2; IntAct=EBI-549153, EBI-9146863; CC -!- DOMAIN: Has three domains, each of which is closely related to a CC corresponding domain in the delta' stator, despite the 2 proteins CC having only 6-8% sequence identity. Interacts with the beta sliding CC clamp via domain 1 (residues 1-140, in particular residues 61-74), CC fitting into a cleft between domains 2 and 3 on the surface of the CC beta-clamp (PubMed:11525728). Residues 61-74 move about 45 degrees and CC 5.5 Angstroms in the beta-delta versus gamma-delta-delta' structure to CC contact respectively the beta or delta' (PubMed:11525728). CC {ECO:0000269|PubMed:11525728}. CC -!- SIMILARITY: Belongs to the DNA polymerase HolA subunit family. CC {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; L04576; AAA23675.1; -; Genomic_DNA. DR EMBL; M94267; AAB59047.1; -; Genomic_DNA. DR EMBL; U82598; AAB40841.1; -; Genomic_DNA. DR EMBL; U00096; AAC73741.1; -; Genomic_DNA. DR EMBL; AP009048; BAA35287.1; -; Genomic_DNA. DR EMBL; M18277; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR PIR; A45251; A45251. DR RefSeq; NP_415173.1; NC_000913.3. DR RefSeq; WP_000620535.1; NZ_SSZK01000037.1. DR PDB; 1JQJ; X-ray; 2.90 A; C/D=1-343. DR PDB; 1JQL; X-ray; 2.50 A; B=1-140. DR PDB; 1JR3; X-ray; 2.70 A; D=1-343. DR PDB; 1XXH; X-ray; 3.45 A; A/F=1-343. DR PDB; 1XXI; X-ray; 4.10 A; A/F=1-343. DR PDB; 3GLF; X-ray; 3.39 A; A/F=1-343. DR PDB; 3GLG; X-ray; 3.25 A; A/F=1-343. DR PDB; 3GLH; X-ray; 3.89 A; A/F/K=1-343. DR PDB; 3GLI; X-ray; 3.50 A; A/F=1-343. DR PDBsum; 1JQJ; -. DR PDBsum; 1JQL; -. DR PDBsum; 1JR3; -. DR PDBsum; 1XXH; -. DR PDBsum; 1XXI; -. DR PDBsum; 3GLF; -. DR PDBsum; 3GLG; -. DR PDBsum; 3GLH; -. DR PDBsum; 3GLI; -. DR AlphaFoldDB; P28630; -. DR SMR; P28630; -. DR BioGRID; 4259908; 201. DR BioGRID; 851889; 23. DR ComplexPortal; CPX-1926; DNA polymerase III clamp loader complex. DR DIP; DIP-9931N; -. DR IntAct; P28630; 49. DR STRING; 511145.b0640; -. DR jPOST; P28630; -. DR PaxDb; 511145-b0640; -. DR EnsemblBacteria; AAC73741; AAC73741; b0640. DR GeneID; 75204999; -. DR GeneID; 947573; -. DR KEGG; ecj:JW0635; -. DR KEGG; eco:b0640; -. DR PATRIC; fig|1411691.4.peg.1628; -. DR EchoBASE; EB1384; -. DR eggNOG; COG1466; Bacteria. DR HOGENOM; CLU_044694_0_2_6; -. DR InParanoid; P28630; -. DR OMA; SAQKTKW; -. DR OrthoDB; 9770982at2; -. DR PhylomeDB; P28630; -. DR BioCyc; EcoCyc:EG11412-MONOMER; -. DR BioCyc; MetaCyc:EG11412-MONOMER; -. DR BRENDA; 3.6.4.B8; 2026. DR EvolutionaryTrace; P28630; -. DR PRO; PR:P28630; -. DR Proteomes; UP000000318; Chromosome. DR Proteomes; UP000000625; Chromosome. DR GO; GO:0009360; C:DNA polymerase III complex; IDA:EcoCyc. DR GO; GO:0043846; C:DNA polymerase III, clamp loader complex; IPI:ComplexPortal. DR GO; GO:0030894; C:replisome; NAS:ComplexPortal. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IEA:UniProtKB-KW. DR GO; GO:0006260; P:DNA replication; NAS:ComplexPortal. DR GO; GO:0006261; P:DNA-templated DNA replication; IDA:EcoCyc. DR CDD; cd18138; HLD_clamp_pol_III_delta; 1. DR Gene3D; 1.10.8.60; -; 1. DR Gene3D; 1.20.272.10; -; 1. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR InterPro; IPR008921; DNA_pol3_clamp-load_cplx_C. DR InterPro; IPR032780; DNA_pol3_delt_C. DR InterPro; IPR010372; DNA_pol3_delta_N. DR InterPro; IPR005790; DNA_polIII_delta. DR InterPro; IPR027417; P-loop_NTPase. DR NCBIfam; TIGR01128; holA; 1. DR PANTHER; PTHR34388; DNA POLYMERASE III SUBUNIT DELTA; 1. DR PANTHER; PTHR34388:SF1; DNA POLYMERASE III SUBUNIT DELTA; 1. DR Pfam; PF14840; DNA_pol3_delt_C; 1. DR Pfam; PF06144; DNA_pol3_delta; 1. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF48019; post-AAA+ oligomerization domain-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; DNA replication; KW DNA-directed DNA polymerase; Nucleotidyltransferase; Reference proteome; KW Transferase. FT CHAIN 1..343 FT /note="DNA polymerase III subunit delta" FT /id="PRO_0000105505" FT REGION 1..140 FT /note="Domain 1" FT /evidence="ECO:0000305|PubMed:11525728" FT REGION 141..210 FT /note="Domain 2" FT /evidence="ECO:0000305|PubMed:11525728" FT REGION 211..343 FT /note="Domain 3" FT /evidence="ECO:0000305|PubMed:11525728" FT STRAND 2..4 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 6..8 FT /evidence="ECO:0007829|PDB:1JQL" FT HELIX 9..15 FT /evidence="ECO:0007829|PDB:1JQL" FT STRAND 19..26 FT /evidence="ECO:0007829|PDB:1JQL" FT HELIX 28..44 FT /evidence="ECO:0007829|PDB:1JQL" FT STRAND 49..51 FT /evidence="ECO:0007829|PDB:1JQL" FT HELIX 61..69 FT /evidence="ECO:0007829|PDB:1JQL" FT STRAND 73..76 FT /evidence="ECO:0007829|PDB:3GLG" FT STRAND 78..83 FT /evidence="ECO:0007829|PDB:1JQL" FT HELIX 93..103 FT /evidence="ECO:0007829|PDB:1JQL" FT STRAND 106..108 FT /evidence="ECO:0007829|PDB:3GLG" FT STRAND 110..113 FT /evidence="ECO:0007829|PDB:1JQL" FT HELIX 121..123 FT /evidence="ECO:0007829|PDB:1JQL" FT HELIX 125..130 FT /evidence="ECO:0007829|PDB:1JQL" FT HELIX 131..133 FT /evidence="ECO:0007829|PDB:1JQL" FT STRAND 135..138 FT /evidence="ECO:0007829|PDB:1JQL" FT TURN 144..146 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 147..156 FT /evidence="ECO:0007829|PDB:1JQJ" FT TURN 157..159 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 164..174 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 178..191 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 199..206 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 214..222 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 226..235 FT /evidence="ECO:0007829|PDB:1JQJ" FT TURN 236..240 FT /evidence="ECO:0007829|PDB:1JQJ" FT TURN 243..245 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 246..261 FT /evidence="ECO:0007829|PDB:1JQJ" FT TURN 262..266 FT /evidence="ECO:0007829|PDB:1JQJ" FT TURN 269..275 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 280..282 FT /evidence="ECO:0007829|PDB:3GLG" FT TURN 283..285 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 286..292 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 295..314 FT /evidence="ECO:0007829|PDB:1JQJ" FT HELIX 325..331 FT /evidence="ECO:0007829|PDB:1JQJ" SQ SEQUENCE 343 AA; 38704 MW; 87239A678FE16BE2 CRC64; MIRLYPEQLR AQLNEGLRAA YLLLGNDPLL LQESQDAVRQ VAAAQGFEEH HTFSIDPNTD WNAIFSLCQA MSLFASRQTL LLLLPENGPN AAINEQLLTL TGLLHDDLLL IVRGNKLSKA QENAAWFTAL ANRSVQVTCQ TPEQAQLPRW VAARAKQLNL ELDDAANQVL CYCYEGNLLA LAQALERLSL LWPDGKLTLP RVEQAVNDAA HFTPFHWVDA LLMGKSKRAL HILQQLRLEG SEPVILLRTL QRELLLLVNL KRQSAHTPLR ALFDKHRVWQ NRRGMMGEAL NRLSQTQLRQ AVQLLTRTEL TLKQDYGQSV WAELEGLSLL LCHKPLADVF IDG //