LIGD_MYCS2
ID LIGD_MYCS2 Reviewed; 762 AA.
AC A0R3R7; I7FKR9;
DT 19-MAR-2014, integrated into UniProtKB/Swiss-Prot.
DT 19-MAR-2014, sequence version 2.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Multifunctional non-homologous end joining protein LigD;
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;
DE AltName: Full=Polydeoxyribonucleotide synthase [ATP];
GN Name=ligD; OrderedLocusNames=MSMEG_5570, MSMEI_5419;
OS Mycolicibacterium smegmatis (strain ATCC 700084 / mc(2)155) (Mycobacterium
OS smegmatis).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycolicibacterium.
OX NCBI_TaxID=246196;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RA Fleischmann R.D., Dodson R.J., Haft D.H., Merkel J.S., Nelson W.C.,
RA Fraser C.M.;
RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17295914; DOI=10.1186/gb-2007-8-2-r20;
RA Deshayes C., Perrodou E., Gallien S., Euphrasie D., Schaeffer C.,
RA Van-Dorsselaer A., Poch O., Lecompte O., Reyrat J.-M.;
RT "Interrupted coding sequences in Mycobacterium smegmatis: authentic
RT mutations or sequencing errors?";
RL Genome Biol. 8:R20.1-R20.9(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18955433; DOI=10.1101/gr.081901.108;
RA Gallien S., Perrodou E., Carapito C., Deshayes C., Reyrat J.-M.,
RA Van Dorsselaer A., Poch O., Schaeffer C., Lecompte O.;
RT "Ortho-proteogenomics: multiple proteomes investigation through orthology
RT and a new MS-based protocol.";
RL Genome Res. 19:128-135(2009).
RN [4]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASP-136 AND ASP-138.
RC STRAIN=ATCC 700084 / mc(2)155;
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 [5]
RP FUNCTION, PROBABLE ACTIVE SITE, AND MUTAGENESIS OF LYS-484.
RC STRAIN=ATCC 700084 / mc(2)155;
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 [6]
RP FUNCTION IN VIRAL REPLICATION, INTERACTION WITH VIRAL KU HOMOLOGS,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF 136-ASP--ASP-138 AND LYS-484.
RC STRAIN=ATCC 700084 / mc(2)155;
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 [7]
RP FUNCTION, AND MUTAGENESIS OF 136-ASP--ASP-138.
RX PubMed=16446439; DOI=10.1073/pnas.0509083103;
RA Zhu H., Nandakumar J., Aniukwu J., Wang L.K., Glickman M.S., Lima C.D.,
RA Shuman S.;
RT "Atomic structure and nonhomologous end-joining function of the polymerase
RT component of bacterial DNA ligase D.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:1711-1716(2006).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17360246; DOI=10.1016/j.dnarep.2007.02.009;
RA Pitcher R.S., Green A.J., Brzostek A., Korycka-Machala M., Dziadek J.,
RA Doherty A.J.;
RT "NHEJ protects mycobacteria in stationary phase against the harmful effects
RT of desiccation.";
RL DNA Repair 6:1271-1276(2007).
RN [9]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=17496093; DOI=10.1128/jb.00332-07;
RA Stephanou N.C., Gao F., Bongiorno P., Ehrt S., Schnappinger D., Shuman S.,
RA Glickman M.S.;
RT "Mycobacterial nonhomologous end joining mediates mutagenic repair of
RT chromosomal double-strand DNA breaks.";
RL J. Bacteriol. 189:5237-5246(2007).
RN [10]
RP FUNCTION IN GAP FILLING, COFACTOR, DOMAIN, 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 [11]
RP FUNCTION, DOMAIN, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP 136-ASP--ASP-138; GLU-310; HIS-336; LYS-484 AND GLU-533.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=18281464; DOI=10.1101/gad.1631908;
RA Aniukwu J., Glickman M.S., Shuman S.;
RT "The pathways and outcomes of mycobacterial NHEJ depend on the structure of
RT the broken DNA ends.";
RL Genes Dev. 22:512-527(2008).
RN [12]
RP DISRUPTION PHENOTYPE.
RC STRAIN=ATCC 700084 / mc(2)155;
RX PubMed=21219454; DOI=10.1111/j.1365-2958.2010.07463.x;
RA Gupta R., Barkan D., Redelman-Sidi G., Shuman S., Glickman M.S.;
RT "Mycobacteria exploit three genetically distinct DNA double-strand break
RT repair pathways.";
RL Mol. Microbiol. 79:316-330(2011).
RN [13]
RP INTERACTION WITH SIR2, AND SUBUNIT.
RC STRAIN=ATCC 700084 / mc(2)155;
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).
CC -!- FUNCTION: With Ku forms a non-homologous end joining (NHEJ) repair
CC enzyme which repairs blunt-end and 5'-overhang DNA double strand breaks
CC (DSB) with about 50% fidelity, and DSB with non-complementary 3' ends.
CC Plays a partial role in NHEJ during 3'-overhang repair. NHEJ repairs
CC DSB with blunt ends and 5' overhangs with a high level of nucleotide
CC insertion/deletion, without a need for microhomology. Acts as a DNA
CC ligase on singly nicked dsDNA, as a DNA-directed DNA polymerase on 5'
CC overhangs, and adds non-templated nucleotides to 3' overhangs (terminal
CC transferase). Fills in gaps in dsDNA, prefers a 5'-phosphate in the
CC gap. Site-directed mutations leading to ligase loss alter the bias from
CC insertion to deletion mutations, and indicate another ligase (LigC1
CC and/or LigC2) can compensate.
CC -!- FUNCTION: The preference of the polymerase domain for rNTPs over dNTPs
CC may be advantageous in dormant cells, where the dNTP pool may be
CC limiting. {ECO:0000250, ECO:0000269|PubMed:15778718,
CC ECO:0000269|PubMed:16446439, ECO:0000269|PubMed:16476729,
CC ECO:0000269|PubMed:16949369, ECO:0000269|PubMed:17174332,
CC ECO:0000269|PubMed:17360246, ECO:0000269|PubMed:18281464}.
CC -!- FUNCTION: The ligase activity is required for replication of viruses
CC with short cos ends (4 bases) such as Mycobacterium phage Omega and
CC Corndog, but not D29 which has a 9 base cos end. Stimulates dsDNA end
CC joining by LigD; when expressed with endogenous or Mycobacterium phage
CC Omega Ku, can reconstitute NHEJ in S.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;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 4 Mn(2+); 2 Mn(2+) for polymerase/primase activity, 1 each
CC for 3-phosphoesterase and ligase. {ECO:0000250};
CC -!- SUBUNIT: Interacts with Sir2 and probably also with Ku; may form a
CC trimeric complex during NHEJ. Interacts with Mycobacterium phage Omega
CC and Corndog Ku homologs (AC Q853W0, AC Q856K7).
CC {ECO:0000269|PubMed:16949369, ECO:0000269|PubMed:21637345}.
CC -!- DOMAIN: The N-terminal divalent cation-dependent polymerase/primase
CC domain (Pol) functions as an independent domain (PubMed:17174332).
CC Deletion of the Pol domain (residues 1-288) yields a protein severely
CC impaired in NHEJ on blunt or 5'-overhangs (PubMed:18281464).
CC {ECO:0000269|PubMed:17174332, ECO:0000269|PubMed:18281464}.
CC -!- DOMAIN: The central 3'-phosphoesterase domain (PE) (PubMed:17174332).
CC Mutations in the PE domain argue against this domain being involved in
CC residue deletion during NHEJ (PubMed:18281464).
CC {ECO:0000269|PubMed:17174332, ECO:0000269|PubMed:18281464}.
CC -!- DOMAIN: The C-terminal ATP-dependent ligase domain (Lig) functions as
CC an independent domain (PubMed:17174332). Loss of the Lig domain
CC (residues 449 to 762) forces NHEJ to rely on another ligase, which
CC decreases fidelity for blunt and 5'-overhang DSB (PubMed:18281464).
CC {ECO:0000269|PubMed:17174332, ECO:0000269|PubMed:18281464}.
CC -!- DISRUPTION PHENOTYPE: Not essential for growth in the absence of DNA
CC damage. 320-fold reduction in NHEJ on blunt-ended DSB, with a loss of
CC nucleotide insertions. 100-fold less efficient repair of 5'-overhang
CC DSBs with little nucleotide insertion. Upon deletion, the fidelity of
CC DNA repair depends on the form of the DSB; for blunt-ends fidelity is
CC very low, for 5'-overhangs remains 50% faithful, for 3'-overhangs
CC repair is fully faithful. NHEJ on blunt-ended plasmid is 24-fold
CC further decreased in a triple ligC1-ligC2-ligD deletion. In quadruple
CC ligB-ligC1-ligC2-ligD deletions NHEJ on blunt and 5'-overhangs is 0.22
CC and 0.12% of wild-type respectively; only 4-fold decrease in 3'-
CC overhang NHEJ. 100-fold decrease in viability when exposed to ionizing
CC radiation in late and stationary phase; 1000-fold decrease in a double
CC ligD-ku deletion. Decreased resistance to desiccation-induced DSBs.
CC Mycobacterium phage Omega and Corndog are unable to infect a deletion
CC strain. Loss of NHEJ on incompatible 3'-chromosomal overhangs, partial
CC reduction in single-strand annealing DSB repair.
CC {ECO:0000269|PubMed:15778718, ECO:0000269|PubMed:16949369,
CC ECO:0000269|PubMed:17360246, ECO:0000269|PubMed:17496093,
CC ECO:0000269|PubMed:18281464, ECO:0000269|PubMed:21219454}.
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 -!- 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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABK75957.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; CP000480; ABK75957.1; ALT_INIT; Genomic_DNA.
DR EMBL; CP001663; AFP41860.1; -; Genomic_DNA.
DR RefSeq; YP_889805.1; NC_008596.1.
DR AlphaFoldDB; A0R3R7; -.
DR SMR; A0R3R7; -.
DR STRING; 246196.MSMEI_5419; -.
DR EnsemblBacteria; ABK75957; ABK75957; MSMEG_5570.
DR EnsemblBacteria; AFP41860; AFP41860; MSMEI_5419.
DR KEGG; msg:MSMEI_5419; -.
DR KEGG; msm:MSMEG_5570; -.
DR PATRIC; fig|246196.19.peg.5431; -.
DR eggNOG; COG1793; Bacteria.
DR eggNOG; COG3285; Bacteria.
DR Proteomes; UP000000757; Chromosome.
DR Proteomes; UP000006158; Chromosome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003910; F:DNA ligase (ATP) activity; IEA:UniProtKB-EC.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0004527; F:exonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006310; P:DNA recombination; IEA:UniProtKB-KW.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR CDD; cd04863; MtLigD_Pol_like; 1.
DR Gene3D; 2.40.50.140; -; 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 ATP-binding; DNA damage; 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; Reference proteome;
KW Transferase.
FT CHAIN 1..762
FT /note="Multifunctional non-homologous end joining protein
FT LigD"
FT /id="PRO_0000425949"
FT DNA_BIND 18..21
FT /evidence="ECO:0000250"
FT DNA_BIND 31
FT /evidence="ECO:0000250"
FT DNA_BIND 58..60
FT /evidence="ECO:0000250"
FT DNA_BIND 68..72
FT /evidence="ECO:0000250"
FT DNA_BIND 76
FT /evidence="ECO:0000250"
FT DNA_BIND 88..93
FT /evidence="ECO:0000250"
FT DNA_BIND 109
FT /evidence="ECO:0000250"
FT DNA_BIND 233..234
FT /evidence="ECO:0000250"
FT REGION 14..260
FT /note="DNA repair polymerase domain (Pol)"
FT REGION 296..453
FT /note="3'-phosphoesterase domain (PE)"
FT REGION 463..760
FT /note="Ligase domain (Lig)"
FT REGION 735..762
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 484
FT /note="N6-AMP-lysine intermediate"
FT /evidence="ECO:0000305"
FT BINDING 57
FT /ligand="substrate"
FT /ligand_note="for polymerase activity"
FT /evidence="ECO:0000250"
FT BINDING 116
FT /ligand="substrate"
FT /ligand_note="for polymerase activity"
FT /evidence="ECO:0000250"
FT BINDING 136..138
FT /ligand="substrate"
FT /ligand_note="for polymerase activity"
FT /evidence="ECO:0000250"
FT BINDING 136
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 136
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 138
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 138
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 171..177
FT /ligand="substrate"
FT /ligand_note="for polymerase activity"
FT /evidence="ECO:0000250"
FT BINDING 226
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 229
FT /ligand="substrate"
FT /ligand_note="for polymerase activity"
FT /evidence="ECO:0000250"
FT BINDING 235
FT /ligand="substrate"
FT /ligand_note="for polymerase activity"
FT /evidence="ECO:0000250"
FT BINDING 243
FT /ligand="substrate"
FT /ligand_note="for polymerase activity"
FT /evidence="ECO:0000250"
FT BINDING 330
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="3"
FT /ligand_note="catalytic; for 3'-phosphoesterase activity"
FT /evidence="ECO:0000250"
FT BINDING 336
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="3"
FT /ligand_note="catalytic; for 3'-phosphoesterase activity"
FT /evidence="ECO:0000250"
FT BINDING 338
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="3"
FT /ligand_note="catalytic; for 3'-phosphoesterase activity"
FT /evidence="ECO:0000250"
FT BINDING 486
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 616
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT SITE 372
FT /note="Transition state stabilizer; for 3'-phosphoesterase
FT activity"
FT /evidence="ECO:0000250"
FT MUTAGEN 136..138
FT /note="DLD->ALA: In vivo 30% reduction in NHEJ on blunt-end
FT DSB, fidelity doubles, loss of non-templated nucleotide
FT insertion during NHEJ. No effect on efficiency of DSB on
FT 5'- or 3'-overhangs, increased fidelity on 5'-overhangs. No
FT effect on viral infection."
FT /evidence="ECO:0000269|PubMed:16446439,
FT ECO:0000269|PubMed:16949369, ECO:0000269|PubMed:18281464"
FT MUTAGEN 136
FT /note="D->A: Loss of templated and non-templated DNA
FT synthesis, but not ligase activity."
FT /evidence="ECO:0000269|PubMed:15778718"
FT MUTAGEN 138
FT /note="D->A: Loss of templated and non-templated DNA
FT synthesis, but not ligase activity."
FT /evidence="ECO:0000269|PubMed:15778718"
FT MUTAGEN 310
FT /note="E->A: No effect on efficiency or fidelity on NHEJ of
FT blunt, 5'-overhangs or 3'-overhangs."
FT /evidence="ECO:0000269|PubMed:18281464"
FT MUTAGEN 336
FT /note="H->A: No effect on efficiency or fidelity on NHEJ of
FT blunt, 5'-overhangs or 3'-overhangs."
FT /evidence="ECO:0000269|PubMed:18281464"
FT MUTAGEN 484
FT /note="K->A: 2.7 and 3.7-fold decrease in efficiency of
FT NHEJ on blunt and 5'-overhangs respectively. Considerably
FT decreases NHEJ fidelity on both DSBs. No viral infection."
FT /evidence="ECO:0000269|PubMed:16476729,
FT ECO:0000269|PubMed:16949369, ECO:0000269|PubMed:18281464"
FT MUTAGEN 533
FT /note="E->A: 3-fold and 9-fold decrease in efficiency of
FT NHEJ on blunt and 5'-overhangs respectively, with very
FT decreased fidelity on both DSBs. No viral infection."
FT /evidence="ECO:0000269|PubMed:18281464"
SQ SEQUENCE 762 AA; 85516 MW; ED1853A73A3E552E CRC64;
MARHPWGMER YERVRLTNPD KVLYPATGTT KAEVFDYYLS IAQVMVPHIA GRPVTRKRWP
NGVAEEAFFE KQLASSAPSW LERGSITHKS GTTTYPIINT REGLAWVAQQ ASLEVHVPQW
RFEDGDQGPA TRIVFDLDPG EGVTMTQLCE IAHEVRALMT DLDLETYPLT SGSKGLHLYV
PLAEPISSRG ASVLARRVAQ QLEQAMPKLV TATMTKSLRA GKVFLDWSQN NAAKTTIAPY
SLRGRDHPTV AAPRTWDEIA DPELRHLRFD EVLDRLDEYG DLLAPLDADA PIADKLTTYR
SMRDASKTPE PVPKEIPKTG NNDKFVIQEH HARRLHYDLR LERDGVLVSF AVPKNLPETT
AENRLAVHTE DHPIEYLAFH GSIPKGEYGA GDMVIWDSGS YETEKFRVPE ELDNPDDSHG
EIIVTLHGEK VDGRYALIQT KGKNWLAHRM KDQKNARPED FAPMLATEGS VAKYKAKQWA
FEGKWDGYRV IIDADHGQLQ IRSRTGREVT GEYPQFKALA ADLAEHHVVL DGEAVALDES
GVPSFGQMQN RARSTRVEFW AFDILWLDGR SLLRAKYSDR RKILEALADG GGLIVPDQLP
GDGPEAMEHV RKKRFEGVVA KKWDSTYQPG RRSSSWIKDK IWNTQEVVIG GWRQGEGGRS
SGIGALVLGI PGPEGLQFVG RVGTGFTEKE LSKLKDMLKP LHTDESPFNA PLPKVDARGV
TFVRPELVGE VRYSERTSDG RLRQPSWRGL RPDKTPDEVV WE
