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Database: UniProt/SWISS-PROT
Entry: LIGD_MYCTU
LinkDB: LIGD_MYCTU
Original site: LIGD_MYCTU 
ID   LIGD_MYCTU              Reviewed;         759 AA.
AC   P9WNV3; L0T5C5; O05865; P71571;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   26-FEB-2020, entry version 44.
DE   RecName: Full=Multifunctional non-homologous end joining DNA repair protein LigD;
DE            Short=NHEJ DNA repair protein D;
DE   AltName: Full=Mt-Lig;
DE   AltName: Full=NHEJ DNA polymerase;
DE   Includes:
DE     RecName: Full=DNA repair polymerase;
DE              Short=Pol;
DE     AltName: Full=Polymerase/primase;
DE   Includes:
DE     RecName: Full=3'-phosphoesterase;
DE              Short=3'-ribonuclease/3'-phosphatase;
DE              Short=PE;
DE   Includes:
DE     RecName: Full=DNA ligase;
DE              Short=Lig;
DE              EC=6.5.1.1 {ECO:0000269|PubMed:12215643, ECO:0000269|PubMed:16023671, ECO:0000269|PubMed:16476729};
DE     AltName: Full=Polydeoxyribonucleotide synthase [ATP];
GN   Name=ligD; OrderedLocusNames=Rv0938; ORFNames=MTCY08D9.01c, MTCY10D7.36c;
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 [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   [2]
RP   FUNCTION AS A LIGASE, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION
RP   WITH MKU, SUBUNIT, DNA-BINDING, ACTIVE SITE, AND MUTAGENESIS OF LYS-481.
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=12215643; DOI=10.1126/science.1074584;
RA   Weller G.R., Kysela B., Roy R., Tonkin L.M., Scanlan E., Della M.,
RA   Devine S.K., Day J.P., Wilkinson A., d'Adda di Fagagna F., Devine K.M.,
RA   Bowater R.P., Jeggo P.A., Jackson S.P., Doherty A.J.;
RT   "Identification of a DNA nonhomologous end-joining complex in bacteria.";
RL   Science 297:1686-1689(2002).
RN   [3]
RP   FUNCTION, COFACTOR, SUBUNIT, DOMAIN, AND DISRUPTION PHENOTYPE.
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=14985346; DOI=10.1074/jbc.m401841200;
RA   Gong C., Martins A., Bongiorno P., Glickman M., Shuman S.;
RT   "Biochemical and genetic analysis of the four DNA ligases of
RT   mycobacteria.";
RL   J. Biol. Chem. 279:20594-20606(2004).
RN   [4]
RP   FUNCTION IN DNA REPAIR, COFACTOR, SUBUNIT, AND MUTAGENESIS OF
RP   137-ASP--ASP-139 AND HIS-373.
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=15499016; DOI=10.1126/science.1099824;
RA   Della M., Palmbos P.L., Tseng H.M., Tonkin L.M., Daley J.M., Topper L.M.,
RA   Pitcher R.S., Tomkinson A.E., Wilson T.E., Doherty A.J.;
RT   "Mycobacterial Ku and ligase proteins constitute a two-component NHEJ
RT   repair machine.";
RL   Science 306:683-685(2004).
RN   [5]
RP   FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH MKU,
RP   SUBUNIT, COFACTOR, DOMAIN, DNA-BINDING, AND MUTAGENESIS OF 137-ASP--ASP-139
RP   AND LYS-481.
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=16023671; DOI=10.1016/j.jmb.2005.06.038;
RA   Pitcher R.S., Tonkin L.M., Green A.J., Doherty A.J.;
RT   "Domain structure of a NHEJ DNA repair ligase from Mycobacterium
RT   tuberculosis.";
RL   J. Mol. Biol. 351:531-544(2005).
RN   [6]
RP   FUNCTION, INTERACTION WITH KU, AND DOMAIN.
RX   PubMed=15778718; DOI=10.1038/nsmb915;
RA   Gong C., Bongiorno P., Martins A., Stephanou N.C., Zhu H., Shuman S.,
RA   Glickman M.S.;
RT   "Mechanism of nonhomologous end-joining in mycobacteria: a low-fidelity
RT   repair system driven by Ku, ligase D and ligase C.";
RL   Nat. Struct. Mol. Biol. 12:304-312(2005).
RN   [7]
RP   FUNCTION, AND PROBABLE INTERACTION WITH VIRAL KU.
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=16949369; DOI=10.1016/j.molcel.2006.07.009;
RA   Pitcher R.S., Tonkin L.M., Daley J.M., Palmbos P.L., Green A.J.,
RA   Velting T.L., Brzostek A., Korycka-Machala M., Cresawn S., Dziadek J.,
RA   Hatfull G.F., Wilson T.E., Doherty A.J.;
RT   "Mycobacteriophage exploit NHEJ to facilitate genome circularization.";
RL   Mol. Cell 23:743-748(2006).
RN   [8]
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   [9]
RP   INTERACTION WITH SIR2, AND SUBUNIT.
RX   PubMed=21637345; DOI=10.1371/journal.pone.0020045;
RA   Li Z., Wen J., Lin Y., Wang S., Xue P., Zhang Z., Zhou Y., Wang X., Sui L.,
RA   Bi L.J., Zhang X.E.;
RT   "A Sir2-like protein participates in mycobacterial NHEJ.";
RL   PLoS ONE 6:E20045-E20045(2011).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 452-759 IN COMPLEX WITH DIVALENT
RP   CATION, CATALYTIC ACTIVITY FOR LIGASE, ACTIVE SITE, AND MUTAGENESIS OF
RP   LYS-481; ASP-483; GLU-530; GLU-613; LYS-635 AND LYS-637.
RC   STRAIN=ATCC 25618 / H37Rv;
RX   PubMed=16476729; DOI=10.1074/jbc.m513550200;
RA   Akey D., Martins A., Aniukwu J., Glickman M.S., Shuman S., Berger J.M.;
RT   "Crystal structure and nonhomologous end-joining function of the ligase
RT   component of Mycobacterium DNA ligase D.";
RL   J. Biol. Chem. 281:13412-13423(2006).
RN   [11]
RP   X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 1-300 OF APOENZYME AND IN COMPLEX
RP   WITH MANGANESE AND SUBSTRATE, FUNCTION, COFACTOR, AND DNA-BINDING.
RX   PubMed=17174332; DOI=10.1016/j.jmb.2006.10.046;
RA   Pitcher R.S., Brissett N.C., Picher A.J., Andrade P., Juarez R.,
RA   Thompson D., Fox G.C., Blanco L., Doherty A.J.;
RT   "Structure and function of a mycobacterial NHEJ DNA repair polymerase.";
RL   J. Mol. Biol. 366:391-405(2007).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-300 IN COMPLEX WITH DNA,
RP   FUNCTION, SUBUNIT, DOMAIN, DNA-BINDING, AND MUTAGENESIS OF LYS-16 AND
RP   83-HIS--SER-85.
RX   PubMed=17947582; DOI=10.1126/science.1145112;
RA   Brissett N.C., Pitcher R.S., Juarez R., Picher A.J., Green A.J.,
RA   Dafforn T.R., Fox G.C., Blanco L., Doherty A.J.;
RT   "Structure of a NHEJ polymerase-mediated DNA synaptic complex.";
RL   Science 318:456-459(2007).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 1-300 IN PRETERNARY COMPLEX WITH
RP   DNA, SUBSTRATE AND MANGANESE, COFACTOR, DNA-BINDING, AND MUTAGENESIS OF
RP   ARG-220.
RX   PubMed=21255731; DOI=10.1016/j.molcel.2010.12.026;
RA   Brissett N.C., Martin M.J., Pitcher R.S., Bianchi J., Juarez R.,
RA   Green A.J., Fox G.C., Blanco L., Doherty A.J.;
RT   "Structure of a preternary complex involving a prokaryotic NHEJ DNA
RT   polymerase.";
RL   Mol. Cell 41:221-231(2011).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-300 IN COMPLEX WITH DNA,
RP   REACTION MECHANISM, DNA-BINDING, AND MUTAGENESIS OF ARG-53; PHE-63; PHE-64;
RP   83-HIS--SER-85; LYS-217; GLN-230 AND LYS-235.
RX   PubMed=24239356; DOI=10.1016/j.celrep.2013.10.016;
RA   Brissett N.C., Martin M.J., Bartlett E.J., Bianchi J., Blanco L.,
RA   Doherty A.J.;
RT   "Molecular basis for DNA double-strand break annealing and primer extension
RT   by an NHEJ DNA polymerase.";
RL   Cell Rep. 5:1108-1120(2013).
CC   -!- FUNCTION: With Ku forms a non-homologous end joining (NHEJ) repair
CC       enzyme which repairs DNA double-strand breaks (DSB) with reduced
CC       fidelity. Recognizes, processes and reseals DSBs, including repairs on
CC       incompatible DSB which require 3'-resection, gap filling and ligation.
CC       Anneals the 3' overhanging strands from opposing breaks to form a
CC       gapped intermediate, which then can be extended in trans by using the
CC       termini as primers for extension of the annealed break. Binds to the
CC       recessed 5'-phosphate moiety of the downstream DNA strand forming a
CC       stable synaptic complex even when the 3'-protruding ends of the
CC       template DNA strands are not complementary. Has numerous activites; gap
CC       filling copies the template strand, and prefers a 5'-phosphate in the
CC       gap and rNTPS (PubMed:17174332, PubMed:17947582), DNA-directed DNA or
CC       RNA polymerase on 5'-overhangs, terminal transferase (extending ssDNA
CC       or blunt dsDNA in a non-templated fashion, preferentially with rNTPs),
CC       DNA-dependent RNA primase (synthesizes short RNAs on unprimed closed
CC       ssDNA) and 3'- to 5'-exonuclease on ssDNA (PubMed:15499016). Isolated
CC       Pol domain (and presumably the holoenzyme) is able to form complexes
CC       between 2 noncompatible protruding 3'-ends DNA ends via microhomologous
CC       DNA strands, in a end-bridging function to which it adds a templated
CC       nucleotide (PubMed:17947582). Minimal primer length is 2 nucleotides
CC       (PubMed:21255731). {ECO:0000269|PubMed:15499016,
CC       ECO:0000269|PubMed:17174332, ECO:0000269|PubMed:17947582,
CC       ECO:0000269|PubMed:21255731}.
CC   -!- FUNCTION: The preference of the polymerase domain for rNTPs over dNTPs
CC       may be advantageous in dormant cells, where the dNTP pool is limiting.
CC   -!- FUNCTION: In conjunction with endogenous or Mycobacterium phage Omega
CC       Ku (AC Q853W0) can reconstitute NHEJ in Saccharomyces cerevisiae.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + (deoxyribonucleotide)(n)-3'-hydroxyl + 5'-phospho-
CC         (deoxyribonucleotide)(m) = (deoxyribonucleotide)(n+m) + AMP +
CC         diphosphate.; EC=6.5.1.1; Evidence={ECO:0000269|PubMed:12215643,
CC         ECO:0000269|PubMed:16023671, ECO:0000269|PubMed:16476729};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000305|PubMed:14985346, ECO:0000305|PubMed:15499016,
CC         ECO:0000305|PubMed:16023671, ECO:0000305|PubMed:17174332,
CC         ECO:0000305|PubMed:21255731};
CC       Note=Binds 4 Mn(2+); 2 Mn(2+) for polymerase/primase activity, 1 each
CC       for 3-phosphoesterase and ligase. {ECO:0000305|PubMed:14985346,
CC       ECO:0000305|PubMed:15499016, ECO:0000305|PubMed:16023671,
CC       ECO:0000305|PubMed:17174332, ECO:0000305|PubMed:21255731};
CC   -!- ACTIVITY REGULATION: The polymerase, exonuclease and ligase activities
CC       are stimulated by Ku. Polymerase activity is inhibited by EDTA.
CC       {ECO:0000269|PubMed:12215643, ECO:0000269|PubMed:16023671}.
CC   -!- SUBUNIT: Monomer. Component of the NHEJ repair enzyme with mKu.
CC       Interacts with Ku in the absence of DSB via the Pol domain. In
CC       structures of the Pol domain with template DNA 2 Pol domains are bound
CC       to microhomologous DNA complexes to form an end-bridging complex.
CC       Probably interacts with Mycobacterium phage Omega and Corndog Ku
CC       homologs (AC Q853W0, AC Q856K7). Interacts with Sir2; may form a
CC       trimeric complex with LigD during NHEJ. {ECO:0000269|PubMed:12215643,
CC       ECO:0000269|PubMed:14985346, ECO:0000269|PubMed:15499016,
CC       ECO:0000269|PubMed:15778718, ECO:0000269|PubMed:16023671,
CC       ECO:0000269|PubMed:16476729, ECO:0000269|PubMed:17174332,
CC       ECO:0000269|PubMed:17947582, ECO:0000269|PubMed:21637345,
CC       ECO:0000269|PubMed:24239356}.
CC   -!- DOMAIN: The N-terminal Mn(2+)-dependent polymerase/primase domain (Pol)
CC       functions as an independent domain, binds DNA, is sufficient for DNA-
CC       directed and non-DNA-directed DNA synthesis (PubMed:15778718) and
CC       interacts with Ku (PubMed:16023671). {ECO:0000269|PubMed:15778718,
CC       ECO:0000269|PubMed:16023671}.
CC   -!- DOMAIN: The central 3'-phosphoesterase domain (PE) has exonuclease
CC       activity probably constituted of 3'-ribonuclease and 3'-phosphatase
CC       activity (PubMed:15499016). It does not function as an independent
CC       domain (PubMed:16023671). {ECO:0000269|PubMed:15499016,
CC       ECO:0000269|PubMed:16023671}.
CC   -!- DOMAIN: The C-terminal ligase domain (Lig) binds dsDNA and functions as
CC       an independent domain (PubMed:14985346, PubMed:16023671).
CC       {ECO:0000269|PubMed:14985346, ECO:0000269|PubMed:16023671}.
CC   -!- DISRUPTION PHENOTYPE: Not essential for growth, 80% reduction in NHEJ
CC       (in strain Erdman). {ECO:0000269|PubMed:14985346}.
CC   -!- MISCELLANEOUS: LigD has variable architecture; domain order can be
CC       permutated, domains can be independently encoded, while some bacteria
CC       lack the 3'-phosphoesterase domain entirely.
CC   -!- MISCELLANEOUS: It is not clear whether there is a 5- to 3'-exonuclease
CC       activity associated with the enzyme.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the LigD polymerase
CC       family. {ECO:0000305}.
CC   -!- SIMILARITY: In the central section; belongs to the LigD 3'-
CC       phosphoesterase family. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the ATP-dependent DNA
CC       ligase family. {ECO:0000305}.
DR   EMBL; AL123456; CCP43686.1; -; Genomic_DNA.
DR   PIR; B70585; B70585.
DR   RefSeq; NP_215453.1; NC_000962.3.
DR   RefSeq; WP_003911307.1; NZ_NVQJ01000001.1.
DR   PDB; 1VS0; X-ray; 2.40 A; A/B=452-759.
DR   PDB; 2IRU; X-ray; 1.65 A; A/B=1-300.
DR   PDB; 2IRX; X-ray; 1.80 A; A=1-300.
DR   PDB; 2IRY; X-ray; 1.78 A; A/B=1-300.
DR   PDB; 2R9L; X-ray; 2.40 A; A/B=1-300.
DR   PDB; 3PKY; X-ray; 3.10 A; A/B=1-300.
DR   PDB; 4MKY; X-ray; 2.40 A; A/B/C/D=1-300.
DR   PDBsum; 1VS0; -.
DR   PDBsum; 2IRU; -.
DR   PDBsum; 2IRX; -.
DR   PDBsum; 2IRY; -.
DR   PDBsum; 2R9L; -.
DR   PDBsum; 3PKY; -.
DR   PDBsum; 4MKY; -.
DR   SMR; P9WNV3; -.
DR   STRING; 83332.Rv0938; -.
DR   PaxDb; P9WNV3; -.
DR   EnsemblBacteria; CCP43686; CCP43686; Rv0938.
DR   GeneID; 885561; -.
DR   KEGG; mtu:Rv0938; -.
DR   KEGG; mtv:RVBD_0938; -.
DR   TubercuList; Rv0938; -.
DR   eggNOG; ENOG4105DQE; Bacteria.
DR   eggNOG; COG1793; LUCA.
DR   eggNOG; COG3285; LUCA.
DR   KO; K01971; -.
DR   OMA; AAPRTWD; -.
DR   PhylomeDB; P9WNV3; -.
DR   BioCyc; MTBH37RV:G185E-5093-MONOMER; -.
DR   Proteomes; UP000001584; Chromosome.
DR   GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR   GO; GO:0005524; F:ATP binding; IDA:MTBBASE.
DR   GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR   GO; GO:0003910; F:DNA ligase (ATP) activity; IDA:UniProtKB.
DR   GO; GO:0003909; F:DNA ligase activity; IDA:UniProtKB.
DR   GO; GO:0003896; F:DNA primase activity; IDA:MTBBASE.
DR   GO; GO:0003899; F:DNA-directed 5'-3' RNA polymerase activity; IDA:MTBBASE.
DR   GO; GO:0003887; F:DNA-directed DNA polymerase activity; IDA:MTBBASE.
DR   GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR   GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IDA:UniProtKB.
DR   GO; GO:0000166; F:nucleotide binding; IDA:UniProtKB.
DR   GO; GO:0004652; F:polynucleotide adenylyltransferase activity; IDA:MTBBASE.
DR   GO; GO:0032553; F:ribonucleotide binding; IDA:UniProtKB.
DR   GO; GO:0008310; F:single-stranded DNA 3'-5' exodeoxyribonuclease activity; IDA:MTBBASE.
DR   GO; GO:0006266; P:DNA ligation; IDA:UniProtKB.
DR   GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR   GO; GO:0006269; P:DNA replication, synthesis of RNA primer; IDA:MTBBASE.
DR   GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB.
DR   GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IDA:UniProtKB.
DR   GO; GO:0016032; P:viral process; IEA:UniProtKB-KW.
DR   CDD; cd04863; MtLigD_Pol_like; 1.
DR   InterPro; IPR012309; DNA_ligase_ATP-dep_C.
DR   InterPro; IPR012310; DNA_ligase_ATP-dep_cent.
DR   InterPro; IPR014146; LigD_ligase_dom.
DR   InterPro; IPR014144; LigD_PE_domain.
DR   InterPro; IPR014145; LigD_pol_dom.
DR   InterPro; IPR033649; MtLigD_Pol-like.
DR   InterPro; IPR012340; NA-bd_OB-fold.
DR   Pfam; PF04679; DNA_ligase_A_C; 1.
DR   Pfam; PF01068; DNA_ligase_A_M; 1.
DR   Pfam; PF13298; LigD_N; 1.
DR   SUPFAM; SSF50249; SSF50249; 1.
DR   TIGRFAMs; TIGR02777; LigD_PE_dom; 1.
DR   TIGRFAMs; TIGR02778; ligD_pol; 1.
DR   TIGRFAMs; TIGR02779; NHEJ_ligase_lig; 1.
DR   PROSITE; PS50160; DNA_LIGASE_A3; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; DNA damage; DNA recombination; DNA repair;
KW   DNA-binding; DNA-directed DNA polymerase; Exonuclease;
KW   Host-virus interaction; Hydrolase; Ligase; Manganese; Metal-binding;
KW   Multifunctional enzyme; Nuclease; Nucleotide-binding;
KW   Nucleotidyltransferase; Reference proteome; Transferase.
FT   CHAIN           1..759
FT                   /note="Multifunctional non-homologous end joining DNA
FT                   repair protein LigD"
FT                   /id="PRO_0000059627"
FT   DNA_BIND        13..16
FT                   /note="Interaction with target DNA"
FT   DNA_BIND        26
FT                   /note="Interaction with target DNA"
FT   DNA_BIND        53..55
FT                   /note="Interaction with target DNA"
FT   DNA_BIND        63..67
FT                   /note="Interaction with target DNA"
FT   DNA_BIND        71
FT                   /note="Interaction with target DNA"
FT   DNA_BIND        83..88
FT                   /note="Interaction with target DNA"
FT   DNA_BIND        104
FT                   /note="Interaction with target DNA"
FT   NP_BIND         137..139
FT                   /note="Substrate; for polymerase activity"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   DNA_BIND        137
FT                   /note="Interaction with target DNA"
FT   NP_BIND         172..178
FT                   /note="Substrate; for polymerase activity"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   DNA_BIND        215..220
FT                   /note="Interaction with target DNA"
FT   DNA_BIND        227..235
FT                   /note="Interaction with target DNA"
FT   REGION          1..411
FT                   /note="Not required for ligase activity"
FT   REGION          9..261
FT                   /note="DNA repair polymerase domain (Pol); interacts with
FT                   Ku"
FT   REGION          297..446
FT                   /note="3-phosphoesterase domain (PE)"
FT   REGION          460..757
FT                   /note="Ligase domain (Lig)"
FT   ACT_SITE        481
FT                   /note="N6-AMP-lysine intermediate; for ligase activity"
FT                   /evidence="ECO:0000269|PubMed:12215643,
FT                   ECO:0000269|PubMed:16476729"
FT   METAL           137
FT                   /note="Manganese 1"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   METAL           137
FT                   /note="Manganese 2"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   METAL           139
FT                   /note="Manganese 1"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   METAL           139
FT                   /note="Manganese 2"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   METAL           227
FT                   /note="Manganese 2"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   METAL           331
FT                   /note="Manganese 3; via pros nitrogen; catalytic; for 3'-
FT                   phosphoesterase activity"
FT                   /evidence="ECO:0000250"
FT   METAL           337
FT                   /note="Manganese 3; via tele nitrogen; catalytic; for 3'-
FT                   phosphoesterase activity"
FT                   /evidence="ECO:0000250"
FT   METAL           339
FT                   /note="Manganese 3; catalytic; for 3'-phosphoesterase
FT                   activity"
FT                   /evidence="ECO:0000250"
FT   METAL           483
FT                   /note="Manganese 4"
FT                   /evidence="ECO:0000305|PubMed:17174332"
FT   METAL           613
FT                   /note="Manganese 4"
FT                   /evidence="ECO:0000305|PubMed:17174332"
FT   BINDING         52
FT                   /note="Substrate; for polymerase activity"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   BINDING         111
FT                   /note="Substrate; for polymerase activity"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   BINDING         230
FT                   /note="Substrate; for polymerase activity"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   BINDING         236
FT                   /note="Substrate; for polymerase activity"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   BINDING         244
FT                   /note="Substrate; for polymerase activity"
FT                   /evidence="ECO:0000269|PubMed:17174332"
FT   SITE            373
FT                   /note="Transition state stabilizer; for 3'-phosphoesterase
FT                   activity"
FT                   /evidence="ECO:0000250"
FT   MUTAGEN         16
FT                   /note="K->A: Loss of DNA-binding, no polymerase activity,
FT                   no effect of gap-filling (in Pol domain)."
FT                   /evidence="ECO:0000269|PubMed:17947582"
FT   MUTAGEN         53
FT                   /note="R->A: On substrate with 5'-phosphate, 1 base pair
FT                   (bp) complementarity and 1 nucleotide (nt) gap, greatly
FT                   reduced DNA-binding and gap-filling. Barely detectable
FT                   activity on substrate with high complementarity and 3'-
FT                   overhang (in Pol domain)."
FT                   /evidence="ECO:0000269|PubMed:24239356"
FT   MUTAGEN         63
FT                   /note="F->A: On substrate with 5'-phosphate, 1 bp
FT                   complementarity and 1 nt gap, greatly reduced DNA-binding
FT                   and gap-filling. No activity on substrate with high
FT                   complementarity and 3'-overhang (in Pol domain)."
FT                   /evidence="ECO:0000269|PubMed:24239356"
FT   MUTAGEN         64
FT                   /note="F->A: On substrate with 5'-phosphate, 1 bp
FT                   complementarity and 1 nt gap, greatly reduced DNA-binding
FT                   and gap-filling. Barely detectable activity on substrate
FT                   with high complementarity and 3'-overhang (in Pol domain)."
FT                   /evidence="ECO:0000269|PubMed:24239356"
FT   MUTAGEN         83..85
FT                   /note="HRS->AAA: Binds DNA, no formation of DNA end-
FT                   bridging complex, no polymerase activity. Significantly
FT                   decreased ability to fill in 2 nt gaps (in Pol domain)."
FT                   /evidence="ECO:0000269|PubMed:17947582,
FT                   ECO:0000269|PubMed:24239356"
FT   MUTAGEN         137..139
FT                   /note="DLD->ALA: Loss of polymerase activities, no DNA
FT                   repair (in Pol domain)."
FT                   /evidence="ECO:0000269|PubMed:15499016,
FT                   ECO:0000269|PubMed:16023671"
FT   MUTAGEN         217
FT                   /note="K->A: Better than wild-type DNA-binding and filling
FT                   on single nt gaps, impaired gap filling on more complicated
FT                   templates (in Pol domain)."
FT                   /evidence="ECO:0000269|PubMed:24239356"
FT   MUTAGEN         220
FT                   /note="R->A: Binds DNA, no gap-filling (in Pol domain)."
FT                   /evidence="ECO:0000269|PubMed:21255731"
FT   MUTAGEN         230
FT                   /note="Q->A: Wild-type filling on single nt gaps, impaired
FT                   gap filling on more complicated templates (in Pol domain)."
FT                   /evidence="ECO:0000269|PubMed:24239356"
FT   MUTAGEN         235
FT                   /note="K->A: Wild-type filling on single nt gaps, impaired
FT                   gap filling on more complicated templates (in Pol domain)."
FT                   /evidence="ECO:0000269|PubMed:24239356"
FT   MUTAGEN         373
FT                   /note="H->A: Loss of exonuclease, no DNA repair."
FT                   /evidence="ECO:0000269|PubMed:15499016"
FT   MUTAGEN         481
FT                   /note="K->A: Loss of adenyltransferase activity, no N6-AMP-
FT                   lysine formation and loss of ligase activity. No effect on
FT                   phosphodiester bond formation on pre-adenylated nicked DNA,
FT                   or on DNA polymerase."
FT                   /evidence="ECO:0000269|PubMed:12215643,
FT                   ECO:0000269|PubMed:16023671, ECO:0000269|PubMed:16476729"
FT   MUTAGEN         483
FT                   /note="D->A: No ligase of singly nicked dsDNA activity, no
FT                   N6-AMP-lysine intermediate formed, decreased phosphodiester
FT                   bond formation on pre-adenylated nicked DNA, no effect on
FT                   DNA polymerase."
FT                   /evidence="ECO:0000269|PubMed:16476729"
FT   MUTAGEN         530
FT                   /note="E->A: No ligase of singly nicked dsDNA activity, no
FT                   N6-AMP-lysine intermediate formed, no phosphodiester bond
FT                   formation on pre-adenylated nicked DNA, no effect on DNA
FT                   polymerase."
FT                   /evidence="ECO:0000269|PubMed:16476729"
FT   MUTAGEN         613
FT                   /note="E->A: No ligase of singly nicked dsDNA activity, no
FT                   N6-AMP-lysine intermediate formed, decreased phosphodiester
FT                   bond formation on pre-adenylated nicked DNA, no effect on
FT                   DNA polymerase."
FT                   /evidence="ECO:0000269|PubMed:16476729"
FT   MUTAGEN         635
FT                   /note="K->A: 20% ligase activity for singly nicked dsDNA,
FT                   normal N6-AMP-lysine intermediate formed, no effect on
FT                   phosphodiester bond formation, no effect on DNA
FT                   polymerase."
FT                   /evidence="ECO:0000269|PubMed:16476729"
FT   MUTAGEN         637
FT                   /note="K->A: No ligase of singly nicked dsDNA activity, 25%
FT                   N6-AMP-lysine intermediate formed, decreased phosphodiester
FT                   bond formation, no effect on DNA polymerase."
FT                   /evidence="ECO:0000269|PubMed:16476729"
FT   STRAND          17..19
FT                   /evidence="ECO:0000244|PDB:4MKY"
FT   TURN            20..22
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   HELIX           26..44
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          50..53
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          63..65
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          76..81
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          88..92
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   HELIX           96..104
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          109..112
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          114..119
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   TURN            121..123
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          126..140
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   HELIX           146..161
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   TURN            162..164
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          168..171
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          173..175
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          177..187
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   HELIX           189..206
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   TURN            208..210
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          211..214
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   HELIX           217..219
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   TURN            220..222
FT                   /evidence="ECO:0000244|PDB:4MKY"
FT   STRAND          223..227
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   HELIX           229..231
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   STRAND          246..248
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   HELIX           257..260
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   HELIX           270..280
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   TURN            283..287
FT                   /evidence="ECO:0000244|PDB:2IRU"
FT   HELIX           455..457
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          462..465
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   TURN            473..475
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          476..481
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          484..492
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          495..500
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   HELIX           507..509
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   HELIX           511..513
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   HELIX           514..519
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   TURN            520..522
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          524..532
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   HELIX           542..546
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          555..564
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   HELIX           574..587
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   HELIX           600..609
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          614..619
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          629..650
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          662..669
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          672..679
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   HELIX           685..695
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   HELIX           696..698
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          704..707
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   HELIX           711..714
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          717..720
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          725..731
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   STRAND          743..747
FT                   /evidence="ECO:0000244|PDB:1VS0"
FT   HELIX           753..755
FT                   /evidence="ECO:0000244|PDB:1VS0"
SQ   SEQUENCE   759 AA;  83572 MW;  81BD49222EE09E36 CRC64;
     MGSASEQRVT LTNADKVLYP ATGTTKSDIF DYYAGVAEVM LGHIAGRPAT RKRWPNGVDQ
     PAFFEKQLAL SAPPWLSRAT VAHRSGTTTY PIIDSATGLA WIAQQAALEV HVPQWRFVAE
     PGSGELNPGP ATRLVFDLDP GEGVMMAQLA EVARAVRDLL ADIGLVTFPV TSGSKGLHLY
     TPLDEPVSSR GATVLAKRVA QRLEQAMPAL VTSTMTKSLR AGKVFVDWSQ NSGSKTTIAP
     YSLRGRTHPT VAAPRTWAEL DDPALRQLSY DEVLTRIARD GDLLERLDAD APVADRLTRY
     RRMRDASKTP EPIPTAKPVT GDGNTFVIQE HHARRPHYDF RLECDGVLVS WAVPKNLPDN
     TSVNHLAIHT EDHPLEYATF EGAIPSGEYG AGKVIIWDSG TYDTEKFHDD PHTGEVIVNL
     HGGRISGRYA LIRTNGDRWL AHRLKNQKDQ KVFEFDNLAP MLATHGTVAG LKASQWAFEG
     KWDGYRLLVE ADHGAVRLRS RSGRDVTAEY PQLRALAEDL ADHHVVLDGE AVVLDSSGVP
     SFSQMQNRGR DTRVEFWAFD LLYLDGRALL GTRYQDRRKL LETLANATSL TVPELLPGDG
     AQAFACSRKH GWEGVIAKRR DSRYQPGRRC ASWVKDKHWN TQEVVIGGWR AGEGGRSSGV
     GSLLMGIPGP GGLQFAGRVG TGLSERELAN LKEMLAPLHT DESPFDVPLP ARDAKGITYV
     KPALVAEVRY SEWTPEGRLR QSSWRGLRPD KKPSEVVRE
//
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