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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   05-DEC-2018, entry version 37.
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;
GN   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.,
RA   Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III,
RA   Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T.,
RA   Connor R., Davies R.M., Devlin K., Feltwell T., Gentles S., Hamlin N.,
RA   Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S.,
RA   Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A.,
RA   Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R.,
RA   Sulston J.E., Taylor K., Whitehead S., Barrell B.G.;
RT   "Deciphering the biology of Mycobacterium tuberculosis from the
RT   complete genome sequence.";
RL   Nature 393:537-544(1998).
RN   [2]
RP   FUNCTION AS A LIGASE, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP   INTERACTION WITH MKU, SUBUNIT, DNA-BINDING, ACTIVE SITE, AND
RP   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.,
RA   Devine K.M., Bowater R.P., Jeggo P.A., Jackson S.P., Doherty A.J.;
RT   "Identification of a DNA nonhomologous end-joining complex in
RT   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.,
RA   Topper L.M., 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
RP   MKU, SUBUNIT, COFACTOR, DOMAIN, DNA-BINDING, AND MUTAGENESIS OF
RP   137-ASP--ASP-139 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-
RT   fidelity 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
RT   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.,
RA   Yadav A.K., Shrivastava P., Marimuthu A., Anand S., Sundaram H.,
RA   Kingsbury R., Harsha H.C., Nair B., Prasad T.S., Chauhan D.S.,
RA   Katoch K., Katoch V.M., Kumar P., Chaerkady R., Ramachandran S.,
RA   Dash D., Pandey A.;
RT   "Proteogenomic analysis of Mycobacterium tuberculosis by high
RT   resolution 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.,
RA   Sui L., 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
RP   DIVALENT CATION, CATALYTIC ACTIVITY FOR LIGASE, ACTIVE SITE, AND
RP   MUTAGENESIS OF LYS-481; ASP-483; GLU-530; GLU-613; LYS-635 AND
RP   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.,
RA   Berger J.M.;
RT   "Crystal structure and nonhomologous end-joining function of the
RT   ligase 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
RP   COMPLEX WITH MANGANESE AND SUBSTRATE, FUNCTION, COFACTOR, AND
RP   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
RT   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
RP   WITH DNA, SUBSTRATE AND MANGANESE, COFACTOR, DNA-BINDING, AND
RP   MUTAGENESIS OF 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;
RP   PHE-64; 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
RT   extension 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
CC       repairs on incompatible DSB which require 3'-resection, gap
CC       filling and ligation. Anneals the 3' overhanging strands from
CC       opposing breaks to form a gapped intermediate, which then can be
CC       extended in trans by using the termini as primers for extension of
CC       the annealed break. Binds to the recessed 5'-phosphate moiety of
CC       the downstream DNA strand forming a stable synaptic complex even
CC       when the 3'-protruding ends of the template DNA strands are not
CC       complementary. Has numerous activites; gap filling copies the
CC       template strand, and prefers a 5'-phosphate in the gap and rNTPS
CC       (PubMed:17174332, PubMed:17947582), DNA-directed DNA or RNA
CC       polymerase on 5'-overhangs, terminal transferase (extending ssDNA
CC       or blunt dsDNA in a non-templated fashion, preferentially with
CC       rNTPs), DNA-dependent RNA primase (synthesizes short RNAs on
CC       unprimed closed ssDNA) and 3'- to 5'-exonuclease on ssDNA
CC       (PubMed:15499016). Isolated Pol domain (and presumably the
CC       holoenzyme) is able to form complexes between 2 noncompatible
CC       protruding 3'-ends DNA ends via microhomologous DNA strands, in a
CC       end-bridging function to which it adds a templated nucleotide
CC       (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
CC       dNTPs may be advantageous in dormant cells, where the dNTP pool is
CC       limiting.
CC   -!- FUNCTION: In conjunction with endogenous or Mycobacterium phage
CC       Omega Ku (AC Q853W0) can reconstitute NHEJ in Saccharomyces
CC       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,
CC         ECO:0000305|PubMed:15499016, ECO:0000305|PubMed:16023671,
CC         ECO:0000305|PubMed:17174332, ECO:0000305|PubMed:21255731};
CC       Note=Binds 4 Mn(2+); 2 Mn(2+) for polymerase/primase activity, 1
CC       each for 3-phosphoesterase and ligase.
CC       {ECO:0000305|PubMed:14985346, ECO:0000305|PubMed:15499016,
CC       ECO:0000305|PubMed:16023671, ECO:0000305|PubMed:17174332,
CC       ECO:0000305|PubMed:21255731};
CC   -!- ACTIVITY REGULATION: The polymerase, exonuclease and ligase
CC       activities are stimulated by Ku. Polymerase activity is inhibited
CC       by EDTA. {ECO:0000269|PubMed:12215643,
CC       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
CC       bound to microhomologous DNA complexes to form an end-bridging
CC       complex. Probably interacts with Mycobacterium phage Omega and
CC       Corndog Ku homologs (AC Q853W0, AC Q856K7). Interacts with Sir2;
CC       may form a trimeric complex with LigD during NHEJ.
CC       {ECO:0000269|PubMed:12215643, ECO:0000269|PubMed:14985346,
CC       ECO:0000269|PubMed:15499016, ECO:0000269|PubMed:15778718,
CC       ECO:0000269|PubMed:16023671, ECO:0000269|PubMed:16476729,
CC       ECO:0000269|PubMed:17174332, ECO:0000269|PubMed:17947582,
CC       ECO:0000269|PubMed:21637345, ECO:0000269|PubMed:24239356}.
CC   -!- DOMAIN: The N-terminal Mn(2+)-dependent polymerase/primase domain
CC       (Pol) functions as an independent domain, binds DNA, is sufficient
CC       for DNA-directed and non-DNA-directed DNA synthesis
CC       (PubMed:15778718) and interacts with Ku (PubMed:16023671).
CC       {ECO:0000269|PubMed:15778718, ECO:0000269|PubMed:16023671}.
CC   -!- DOMAIN: The central 3'-phosphoesterase domain (PE) has exonuclease
CC       activity probably constituted of 3'-ribonuclease and 3'-
CC       phosphatase activity (PubMed:15499016). It does not function as an
CC       independent domain (PubMed:16023671).
CC       {ECO:0000269|PubMed:15499016, ECO:0000269|PubMed:16023671}.
CC   -!- DOMAIN: The C-terminal ligase domain (Lig) binds dsDNA and
CC       functions as an independent domain (PubMed:14985346,
CC       PubMed:16023671). {ECO:0000269|PubMed:14985346,
CC       ECO:0000269|PubMed:16023671}.
CC   -!- DISRUPTION PHENOTYPE: Not essential for growth, 80% reduction in
CC       NHEJ (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
CC       bacteria lack the 3'-phosphoesterase domain entirely.
CC   -!- MISCELLANEOUS: It is not clear whether there is a 5- to 3'-
CC       exonuclease activity associated with the enzyme.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the LigD
CC       polymerase 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-
CC       dependent DNA 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   ProteinModelPortal; P9WNV3; -.
DR   SMR; P9WNV3; -.
DR   STRING; 83332.Rv0938; -.
DR   PaxDb; P9WNV3; -.
DR   EnsemblBacteria; CCP43686; CCP43686; Rv0938.
DR   GeneID; 885561; -.
DR   KEGG; mtu:Rv0938; -.
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   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; Complete proteome; DNA damage;
KW   DNA recombination; DNA repair; DNA-binding;
KW   DNA-directed DNA polymerase; Exonuclease; Host-virus interaction;
KW   Hydrolase; Ligase; Manganese; Metal-binding; Multifunctional enzyme;
KW   Nuclease; Nucleotide-binding; Nucleotidyltransferase;
KW   Reference proteome; Transferase.
FT   CHAIN         1    759       Multifunctional non-homologous end
FT                                joining DNA repair protein LigD.
FT                                /FTId=PRO_0000059627.
FT   DNA_BIND     13     16       Interaction with target DNA.
FT   DNA_BIND     26     26       Interaction with target DNA.
FT   DNA_BIND     53     55       Interaction with target DNA.
FT   DNA_BIND     63     67       Interaction with target DNA.
FT   DNA_BIND     71     71       Interaction with target DNA.
FT   DNA_BIND     83     88       Interaction with target DNA.
FT   DNA_BIND    104    104       Interaction with target DNA.
FT   NP_BIND     137    139       Substrate; for polymerase activity.
FT                                {ECO:0000269|PubMed:17174332}.
FT   DNA_BIND    137    137       Interaction with target DNA.
FT   NP_BIND     172    178       Substrate; for polymerase activity.
FT                                {ECO:0000269|PubMed:17174332}.
FT   DNA_BIND    215    220       Interaction with target DNA.
FT   DNA_BIND    227    235       Interaction with target DNA.
FT   REGION        1    411       Not required for ligase activity.
FT   REGION        9    261       DNA repair polymerase domain (Pol);
FT                                interacts with Ku.
FT   REGION      297    446       3-phosphoesterase domain (PE).
FT   REGION      460    757       Ligase domain (Lig).
FT   ACT_SITE    481    481       N6-AMP-lysine intermediate; for ligase
FT                                activity. {ECO:0000269|PubMed:12215643,
FT                                ECO:0000269|PubMed:16476729}.
FT   METAL       137    137       Manganese 1.
FT                                {ECO:0000269|PubMed:17174332}.
FT   METAL       137    137       Manganese 2.
FT                                {ECO:0000269|PubMed:17174332}.
FT   METAL       139    139       Manganese 1.
FT                                {ECO:0000269|PubMed:17174332}.
FT   METAL       139    139       Manganese 2.
FT                                {ECO:0000269|PubMed:17174332}.
FT   METAL       227    227       Manganese 2.
FT                                {ECO:0000269|PubMed:17174332}.
FT   METAL       331    331       Manganese 3; via pros nitrogen;
FT                                catalytic; for 3'-phosphoesterase
FT                                activity. {ECO:0000250}.
FT   METAL       337    337       Manganese 3; via tele nitrogen;
FT                                catalytic; for 3'-phosphoesterase
FT                                activity. {ECO:0000250}.
FT   METAL       339    339       Manganese 3; catalytic; for 3'-
FT                                phosphoesterase activity. {ECO:0000250}.
FT   METAL       483    483       Manganese 4.
FT                                {ECO:0000305|PubMed:17174332}.
FT   METAL       613    613       Manganese 4.
FT                                {ECO:0000305|PubMed:17174332}.
FT   BINDING      52     52       Substrate; for polymerase activity.
FT                                {ECO:0000269|PubMed:17174332}.
FT   BINDING     111    111       Substrate; for polymerase activity.
FT                                {ECO:0000269|PubMed:17174332}.
FT   BINDING     230    230       Substrate; for polymerase activity.
FT                                {ECO:0000269|PubMed:17174332}.
FT   BINDING     236    236       Substrate; for polymerase activity.
FT                                {ECO:0000269|PubMed:17174332}.
FT   BINDING     244    244       Substrate; for polymerase activity.
FT                                {ECO:0000269|PubMed:17174332}.
FT   SITE        373    373       Transition state stabilizer; for 3'-
FT                                phosphoesterase activity. {ECO:0000250}.
FT   MUTAGEN      16     16       K->A: Loss of DNA-binding, no polymerase
FT                                activity, no effect of gap-filling (in
FT                                Pol domain).
FT                                {ECO:0000269|PubMed:17947582}.
FT   MUTAGEN      53     53       R->A: On substrate with 5'-phosphate, 1
FT                                base pair (bp) complementarity and 1
FT                                nucleotide (nt) gap, greatly reduced DNA-
FT                                binding and gap-filling. Barely
FT                                detectable activity on substrate with
FT                                high complementarity and 3'-overhang (in
FT                                Pol domain).
FT                                {ECO:0000269|PubMed:24239356}.
FT   MUTAGEN      63     63       F->A: On substrate with 5'-phosphate, 1
FT                                bp complementarity and 1 nt gap, greatly
FT                                reduced DNA-binding and gap-filling. No
FT                                activity on substrate with high
FT                                complementarity and 3'-overhang (in Pol
FT                                domain). {ECO:0000269|PubMed:24239356}.
FT   MUTAGEN      64     64       F->A: On substrate with 5'-phosphate, 1
FT                                bp complementarity and 1 nt gap, greatly
FT                                reduced DNA-binding and gap-filling.
FT                                Barely detectable activity on substrate
FT                                with high complementarity and 3'-overhang
FT                                (in Pol domain).
FT                                {ECO:0000269|PubMed:24239356}.
FT   MUTAGEN      83     85       HRS->AAA: Binds DNA, no formation of DNA
FT                                end-bridging complex, no polymerase
FT                                activity. Significantly decreased ability
FT                                to fill in 2 nt gaps (in Pol domain).
FT                                {ECO:0000269|PubMed:17947582,
FT                                ECO:0000269|PubMed:24239356}.
FT   MUTAGEN     137    139       DLD->ALA: Loss of polymerase activities,
FT                                no DNA repair (in Pol domain).
FT                                {ECO:0000269|PubMed:15499016,
FT                                ECO:0000269|PubMed:16023671}.
FT   MUTAGEN     217    217       K->A: Better than wild-type DNA-binding
FT                                and filling on single nt gaps, impaired
FT                                gap filling on more complicated templates
FT                                (in Pol domain).
FT                                {ECO:0000269|PubMed:24239356}.
FT   MUTAGEN     220    220       R->A: Binds DNA, no gap-filling (in Pol
FT                                domain). {ECO:0000269|PubMed:21255731}.
FT   MUTAGEN     230    230       Q->A: Wild-type filling on single nt
FT                                gaps, impaired gap filling on more
FT                                complicated templates (in Pol domain).
FT                                {ECO:0000269|PubMed:24239356}.
FT   MUTAGEN     235    235       K->A: Wild-type filling on single nt
FT                                gaps, impaired gap filling on more
FT                                complicated templates (in Pol domain).
FT                                {ECO:0000269|PubMed:24239356}.
FT   MUTAGEN     373    373       H->A: Loss of exonuclease, no DNA repair.
FT                                {ECO:0000269|PubMed:15499016}.
FT   MUTAGEN     481    481       K->A: Loss of adenyltransferase activity,
FT                                no N6-AMP-lysine formation and loss of
FT                                ligase activity. No effect on
FT                                phosphodiester bond formation on pre-
FT                                adenylated nicked DNA, or on DNA
FT                                polymerase. {ECO:0000269|PubMed:12215643,
FT                                ECO:0000269|PubMed:16023671,
FT                                ECO:0000269|PubMed:16476729}.
FT   MUTAGEN     483    483       D->A: No ligase of singly nicked dsDNA
FT                                activity, no N6-AMP-lysine intermediate
FT                                formed, decreased phosphodiester bond
FT                                formation on pre-adenylated nicked DNA,
FT                                no effect on DNA polymerase.
FT                                {ECO:0000269|PubMed:16476729}.
FT   MUTAGEN     530    530       E->A: No ligase of singly nicked dsDNA
FT                                activity, no N6-AMP-lysine intermediate
FT                                formed, no phosphodiester bond formation
FT                                on pre-adenylated nicked DNA, no effect
FT                                on DNA polymerase.
FT                                {ECO:0000269|PubMed:16476729}.
FT   MUTAGEN     613    613       E->A: No ligase of singly nicked dsDNA
FT                                activity, no N6-AMP-lysine intermediate
FT                                formed, decreased phosphodiester bond
FT                                formation on pre-adenylated nicked DNA,
FT                                no effect on DNA polymerase.
FT                                {ECO:0000269|PubMed:16476729}.
FT   MUTAGEN     635    635       K->A: 20% ligase activity for singly
FT                                nicked dsDNA, normal N6-AMP-lysine
FT                                intermediate formed, no effect on
FT                                phosphodiester bond formation, no effect
FT                                on DNA polymerase.
FT                                {ECO:0000269|PubMed:16476729}.
FT   MUTAGEN     637    637       K->A: No ligase of singly nicked dsDNA
FT                                activity, 25% N6-AMP-lysine intermediate
FT                                formed, decreased phosphodiester bond
FT                                formation, no effect on DNA polymerase.
FT                                {ECO:0000269|PubMed:16476729}.
FT   STRAND       17     19       {ECO:0000244|PDB:4MKY}.
FT   TURN         20     22       {ECO:0000244|PDB:2IRU}.
FT   HELIX        26     44       {ECO:0000244|PDB:2IRU}.
FT   STRAND       50     53       {ECO:0000244|PDB:2IRU}.
FT   STRAND       63     65       {ECO:0000244|PDB:2IRU}.
FT   STRAND       76     81       {ECO:0000244|PDB:2IRU}.
FT   STRAND       88     92       {ECO:0000244|PDB:2IRU}.
FT   HELIX        96    104       {ECO:0000244|PDB:2IRU}.
FT   STRAND      109    112       {ECO:0000244|PDB:2IRU}.
FT   STRAND      114    119       {ECO:0000244|PDB:2IRU}.
FT   TURN        121    123       {ECO:0000244|PDB:2IRU}.
FT   STRAND      126    140       {ECO:0000244|PDB:2IRU}.
FT   HELIX       146    161       {ECO:0000244|PDB:2IRU}.
FT   TURN        162    164       {ECO:0000244|PDB:2IRU}.
FT   STRAND      168    171       {ECO:0000244|PDB:2IRU}.
FT   STRAND      173    175       {ECO:0000244|PDB:2IRU}.
FT   STRAND      177    187       {ECO:0000244|PDB:2IRU}.
FT   HELIX       189    206       {ECO:0000244|PDB:2IRU}.
FT   TURN        208    210       {ECO:0000244|PDB:2IRU}.
FT   STRAND      211    214       {ECO:0000244|PDB:2IRU}.
FT   HELIX       217    219       {ECO:0000244|PDB:2IRU}.
FT   TURN        220    222       {ECO:0000244|PDB:4MKY}.
FT   STRAND      223    227       {ECO:0000244|PDB:2IRU}.
FT   HELIX       229    231       {ECO:0000244|PDB:2IRU}.
FT   STRAND      246    248       {ECO:0000244|PDB:2IRU}.
FT   HELIX       257    260       {ECO:0000244|PDB:2IRU}.
FT   HELIX       270    280       {ECO:0000244|PDB:2IRU}.
FT   TURN        283    287       {ECO:0000244|PDB:2IRU}.
FT   HELIX       455    457       {ECO:0000244|PDB:1VS0}.
FT   STRAND      462    465       {ECO:0000244|PDB:1VS0}.
FT   TURN        473    475       {ECO:0000244|PDB:1VS0}.
FT   STRAND      476    481       {ECO:0000244|PDB:1VS0}.
FT   STRAND      484    492       {ECO:0000244|PDB:1VS0}.
FT   STRAND      495    500       {ECO:0000244|PDB:1VS0}.
FT   HELIX       507    509       {ECO:0000244|PDB:1VS0}.
FT   HELIX       511    513       {ECO:0000244|PDB:1VS0}.
FT   HELIX       514    519       {ECO:0000244|PDB:1VS0}.
FT   TURN        520    522       {ECO:0000244|PDB:1VS0}.
FT   STRAND      524    532       {ECO:0000244|PDB:1VS0}.
FT   HELIX       542    546       {ECO:0000244|PDB:1VS0}.
FT   STRAND      555    564       {ECO:0000244|PDB:1VS0}.
FT   HELIX       574    587       {ECO:0000244|PDB:1VS0}.
FT   HELIX       600    609       {ECO:0000244|PDB:1VS0}.
FT   STRAND      614    619       {ECO:0000244|PDB:1VS0}.
FT   STRAND      629    650       {ECO:0000244|PDB:1VS0}.
FT   STRAND      662    669       {ECO:0000244|PDB:1VS0}.
FT   STRAND      672    679       {ECO:0000244|PDB:1VS0}.
FT   HELIX       685    695       {ECO:0000244|PDB:1VS0}.
FT   HELIX       696    698       {ECO:0000244|PDB:1VS0}.
FT   STRAND      704    707       {ECO:0000244|PDB:1VS0}.
FT   HELIX       711    714       {ECO:0000244|PDB:1VS0}.
FT   STRAND      717    720       {ECO:0000244|PDB:1VS0}.
FT   STRAND      725    731       {ECO:0000244|PDB:1VS0}.
FT   STRAND      743    747       {ECO:0000244|PDB:1VS0}.
FT   HELIX       753    755       {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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