ID   DPO1_MYCTU              Reviewed;         904 AA.
AC   P9WNU5; L0TA70; P0A550; Q07700;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   03-AUG-2022, entry version 44.
DE   RecName: Full=DNA polymerase I;
DE            Short=POL I;
DE            EC=2.7.7.7;
GN   Name=polA; OrderedLocusNames=Rv1629; ORFNames=MTCY01B2.21;
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 [GENOMIC DNA].
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=8294019; DOI=10.1016/0378-1119(93)90481-h;
RA   Mizrahi V., Huberts P., Dawes S.S., Dudding L.R.;
RT   "A PCR method for the sequence analysis of the gyrA, polA and rnhA gene
RT   segments from mycobacteria.";
RL   Gene 136:287-290(1993).
RN   [2]
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   [3]
RP   IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX   PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA   Raman K., Yeturu K., Chandra N.;
RT   "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT   through an interactome, reactome and genome-scale structural analysis.";
RL   BMC Syst. Biol. 2:109-109(2008).
RN   [4]
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   [5]
RP   SUBUNIT.
RC   STRAIN=H37Rv;
RX   PubMed=32634279; DOI=10.1111/mmi.14571;
RA   Zaveri A., Wang R., Botella L., Sharma R., Zhu L., Wallach J.B., Song N.,
RA   Jansen R.S., Rhee K.Y., Ehrt S., Schnappinger D.;
RT   "Depletion of the DarG antitoxin in Mycobacterium tuberculosis triggers the
RT   DNA-damage response and leads to cell death.";
RL   Mol. Microbiol. 114:641-652(2020).
CC   -!- FUNCTION: In addition to polymerase activity, this DNA polymerase
CC       exhibits 3'-5' and 5'-3' exonuclease activity.
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: Single-chain monomer with multiple functions. Co-
CC       immunoprecipitates with DarG in the presence and absence of darT
CC       (PubMed:32634279). {ECO:0000269|PubMed:32634279}.
CC   -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC       {ECO:0000269|PubMed:9634230}.
CC   -!- SIMILARITY: Belongs to the DNA polymerase type-A family. {ECO:0000305}.
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DR   EMBL; L11920; AAB46393.1; -; Genomic_DNA.
DR   EMBL; AL123456; CCP44393.1; -; Genomic_DNA.
DR   PIR; C70559; C70559.
DR   RefSeq; NP_216145.1; NC_000962.3.
DR   RefSeq; WP_003408063.1; NZ_NVQJ01000016.1.
DR   AlphaFoldDB; P9WNU5; -.
DR   SMR; P9WNU5; -.
DR   STRING; 83332.Rv1629; -.
DR   PaxDb; P9WNU5; -.
DR   GeneID; 885074; -.
DR   KEGG; mtu:Rv1629; -.
DR   TubercuList; Rv1629; -.
DR   eggNOG; COG0258; Bacteria.
DR   eggNOG; COG0749; Bacteria.
DR   OMA; NRPPMPD; -.
DR   PhylomeDB; P9WNU5; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR   GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR   GO; GO:0008408; F:3'-5' exonuclease activity; IEA:InterPro.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003887; F:DNA-directed DNA polymerase activity; IBA:GO_Central.
DR   GO; GO:0006261; P:DNA-templated DNA replication; IEA:InterPro.
DR   GO; GO:0006302; P:double-strand break repair; IBA:GO_Central.
DR   CDD; cd09898; H3TH_53EXO; 1.
DR   Gene3D; 3.30.420.10; -; 1.
DR   InterPro; IPR002562; 3'-5'_exonuclease_dom.
DR   InterPro; IPR020046; 5-3_exonucl_a-hlix_arch_N.
DR   InterPro; IPR002421; 5-3_exonuclease.
DR   InterPro; IPR036279; 5-3_exonuclease_C_sf.
DR   InterPro; IPR019760; DNA-dir_DNA_pol_A_CS.
DR   InterPro; IPR001098; DNA-dir_DNA_pol_A_palm_dom.
DR   InterPro; IPR043502; DNA/RNA_pol_sf.
DR   InterPro; IPR020045; DNA_polI_H3TH.
DR   InterPro; IPR018320; DNA_polymerase_1.
DR   InterPro; IPR002298; DNA_polymerase_A.
DR   InterPro; IPR008918; HhH2.
DR   InterPro; IPR029060; PIN-like_dom_sf.
DR   InterPro; IPR012337; RNaseH-like_sf.
DR   InterPro; IPR036397; RNaseH_sf.
DR   PANTHER; PTHR10133; PTHR10133; 2.
DR   Pfam; PF01367; 5_3_exonuc; 1.
DR   Pfam; PF02739; 5_3_exonuc_N; 1.
DR   Pfam; PF00476; DNA_pol_A; 1.
DR   PRINTS; PR00868; DNAPOLI.
DR   SMART; SM00474; 35EXOc; 1.
DR   SMART; SM00475; 53EXOc; 1.
DR   SMART; SM00279; HhH2; 1.
DR   SMART; SM00482; POLAc; 1.
DR   SUPFAM; SSF47807; SSF47807; 1.
DR   SUPFAM; SSF53098; SSF53098; 1.
DR   SUPFAM; SSF56672; SSF56672; 1.
DR   SUPFAM; SSF88723; SSF88723; 1.
DR   TIGRFAMs; TIGR00593; pola; 1.
DR   PROSITE; PS00447; DNA_POLYMERASE_A; 1.
PE   1: Evidence at protein level;
KW   DNA damage; DNA repair; DNA replication; DNA-binding;
KW   DNA-directed DNA polymerase; Exonuclease; Hydrolase; Nuclease;
KW   Nucleotidyltransferase; Reference proteome; Transferase.
FT   CHAIN           1..904
FT                   /note="DNA polymerase I"
FT                   /id="PRO_0000101247"
FT   DOMAIN          186..279
FT                   /note="5'-3' exonuclease"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          317..493
FT                   /note="3'-5' exonuclease"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   904 AA;  98472 MW;  1C8E560FE5F74323 CRC64;
     MVTTASAPSE DRAKPTLMLL DGNSLAFRAF YALPAENFKT RGGLTTNAVY GFTAMLINLL
     RDEAPTHIAA AFDVSRQTFR LQRYPEYKAN RSSTPDEFAG QIDITKEVLG ALGITVLSEP
     GFEADDLIAT LATQAENEGY RVLVVTGDRD ALQLVSDDVT VLYPRKGVSE LTRFTPEAVV
     EKYGLTPRQY PDFAALRGDP SDNLPGIPGV GEKTAAKWIA EYGSLRSLVD NVDAVRGKVG
     DALRANLASV VRNRELTDLV RDVPLAQTPD TLRLQPWDRD HIHRLFDDLE FRVLRDRLFD
     TLAAAGGPEV DEGFDVRGGA LAPGTVRQWL AEHAGDGRRA GLTVVGTHLP HGGDATAMAV
     AAADGEGAYL DTATLTPDDD AALAAWLADP AKPKALHEAK AAVHDLAGRG WTLEGVTSDT
     ALAAYLVRPG QRSFTLDDLS LRYLRRELRA ETPQQQQLSL LDDDDTDAET IQTTILRARA
     VIDLADALDA ELARIDSTAL LGEMELPVQR VLAKMESAGI AVDLPMLTEL QSQFGDQIRD
     AAEAAYGVIG KQINLGSPKQ LQVVLFDELG MPKTKRTKTG YTTDADALQS LFDKTGHPFL
     QHLLAHRDVT RLKVTVDGLL QAVAADGRIH TTFNQTIAAT GRLSSTEPNL QNIPIRTDAG
     RRIRDAFVVG DGYAELMTAD YSQIEMRIMA HLSGDEGLIE AFNTGEDLHS FVASRAFGVP
     IDEVTGELRR RVKAMSYGLA YGLSAYGLSQ QLKISTEEAN EQMDAYFARF GGVRDYLRAV
     VERARKDGYT STVLGRRRYL PELDSSNRQV REAAERAALN APIQGSAADI IKVAMIQVDK
     ALNEAQLASR MLLQVHDELL FEIAPGERER VEALVRDKMG GAYPLDVPLE VSVGYGRSWD
     AAAH