DNA ligase 3

NameDNA ligase 3
Synonyms
  • 6.5.1.1
  • DNA ligase III
  • Polydeoxyribonucleotide synthase [ATP] 3
Gene NameLIG3
OrganismHuman
Amino acid sequence
>lcl|BSEQ0036963|DNA ligase 3
MSLAFKIFFPQTLRALSRKELCLFRKHHWRDVRQFSQWSETDLLHGHPLFLRRKPVLSFQ
GSHLRSRATYLVFLPGLHVGLCSGPCEMAEQRFCVDYAKRGTAGCKKCKEKIVKGVCRIG
KVVPNPFSESGGDMKEWYHIKCMFEKLERARATTKKIEDLTELEGWEELEDNEKEQITQH
IADLSSKAAGTPKKKAVVQAKLTTTGQVTSPVKGASFVTSTNPRKFSGFSAKPNNSGEAP
SSPTPKRSLSSSKCDPRHKDCLLREFRKLCAMVADNPSYNTKTQIIQDFLRKGSAGDGFH
GDVYLTVKLLLPGVIKTVYNLNDKQIVKLFSRIFNCNPDDMARDLEQGDVSETIRVFFEQ
SKSFPPAAKSLLTIQEVDEFLLRLSKLTKEDEQQQALQDIASRCTANDLKCIIRLIKHDL
KMNSGAKHVLDALDPNAYEAFKASRNLQDVVERVLHNAQEVEKEPGQRRALSVQASLMTP
VQPMLAEACKSVEYAMKKCPNGMFSEIKYDGERVQVHKNGDHFSYFSRSLKPVLPHKVAH
FKDYIPQAFPGGHSMILDSEVLLIDNKTGKPLPFGTLGVHKKAAFQDANVCLFVFDCIYF
NDVSLMDRPLCERRKFLHDNMVEIPNRIMFSEMKRVTKALDLADMITRVIQEGLEGLVLK
DVKGTYEPGKRHWLKVKKDYLNEGAMADTADLVVLGAFYGQGSKGGMMSIFLMGCYDPGS
QKWCTVTKCAGGHDDATLARLQNELDMVKISKDPSKIPSWLKVNKIYYPDFIVPDPKKAA
VWEITGAEFSKSEAHTADGISIRFPRCTRIRDDKDWKSATNLPQLKELYQLSKEKADFTV
VAGDEGSSTTGGSSEENKGPSGSAVSRKAPSKPSASTKKAEGKLSNSNSKDGNMQTAKPS
AMKVGEKLATKSSPVKVGEKRKAADETLCQTKVLLDIFTGVRLYLPPSTPDFSRLRRYFV
AFDGDLVQEFDMTSATHVLGSRDKNPAAQQVSPEWIWACIRKRRLVAPC
Number of residues1009
Molecular Weight112905.96
Theoretical pI9.17
GO Classification
Functions
  • zinc ion binding
  • ATP binding
  • DNA binding
  • DNA ligase (ATP) activity
  • DNA ligase activity
Processes
  • double-strand break repair via homologous recombination
  • base-excision repair, DNA ligation
  • DNA biosynthetic process
  • DNA ligation
  • DNA replication
  • double-strand break repair via alternative nonhomologous end joining
  • DNA repair
  • double-strand break repair via nonhomologous end joining
  • global genome nucleotide-excision repair
  • mitochondrial DNA repair
  • cell division
  • mitochondrion organization
  • negative regulation of DNA recombination
  • cell cycle
  • negative regulation of mitochondrial DNA replication
  • nucleotide-excision repair
  • nucleotide-excision repair, DNA gap filling
  • base-excision repair
  • transcription-coupled nucleotide-excision repair
  • double-strand break repair
Components
  • DNA ligase III-XRCC1 complex
  • mitochondrion
  • synaptonemal complex
  • nucleus
  • nucleoplasm
General FunctionZinc ion binding
Specific FunctionIsoform 3 functions as heterodimer with DNA-repair protein XRCC1 in the nucleus and can correct defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents. Isoform 1 is targeted to mitochondria, where it functions as DNA ligase in mitochondrial base-excision DNA repair (PubMed:10207110, PubMed:24674627).
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID860963
UniProtKB IDP49916
UniProtKB Entry NameDNLI3_HUMAN
Cellular LocationMitochondrion
Gene sequence
>lcl|BSEQ0009981|DNA ligase 3 (LIG3)
ATGTCTTTGGCTTTCAAGATCTTCTTTCCACAAACCCTCCGTGCACTCAGCCGAAAAGAA
CTGTGCCTATTCCGAAAACATCACTGGCGTGATGTAAGACAATTCAGCCAGTGGTCAGAA
ACAGATCTGCTTCATGGACATCCCCTCTTCCTGAGAAGAAAGCCTGTTCTATCATTCCAG
GGAAGCCATCTAAGATCACGTGCCACCTACCTTGTTTTCTTGCCAGGGTTGCATGTGGGA
CTCTGCAGTGGCCCCTGTGAGATGGCTGAGCAACGGTTCTGTGTGGACTATGCCAAGCGT
GGCACAGCTGGCTGCAAAAAATGCAAGGAAAAGATTGTGAAGGGCGTATGCCGAATTGGC
AAAGTGGTGCCCAATCCCTTCTCAGAGTCTGGGGGTGATATGAAAGAGTGGTACCACATT
AAATGCATGTTTGAGAAACTAGAGCGGGCCCGGGCCACCACAAAAAAAATCGAGGACCTC
ACAGAGCTGGAAGGCTGGGAAGAGCTGGAAGATAATGAGAAGGAACAGATAACCCAGCAC
ATTGCAGATCTGTCTTCTAAGGCAGCAGGTACACCAAAGAAGAAAGCTGTTGTCCAGGCT
AAGTTGACAACCACTGGCCAGGTGACTTCTCCAGTGAAAGGCGCCTCATTTGTCACCAGT
ACCAATCCCCGGAAATTTTCTGGCTTTTCAGCCAAGCCCAACAACTCTGGGGAAGCCCCC
TCGAGCCCCACCCCTAAGAGAAGTCTGTCTTCAAGCAAATGTGACCCCAGGCATAAGGAC
TGTCTGCTACGGGAGTTTCGAAAGTTATGCGCCATGGTGGCCGATAATCCTAGCTACAAC
ACGAAGACCCAGATCATCCAGGACTTCCTTCGGAAAGGCTCAGCAGGAGATGGTTTCCAC
GGTGATGTGTACCTAACAGTGAAGCTGCTGCTGCCAGGAGTCATTAAGACTGTTTACAAC
TTGAACGATAAGCAGATTGTGAAGCTTTTCAGTCGCATTTTTAACTGCAACCCAGATGAT
ATGGCACGGGACCTAGAGCAGGGTGACGTGTCAGAGACAATCAGAGTCTTCTTTGAGCAG
AGCAAGTCTTTCCCCCCAGCTGCCAAGAGCCTCCTTACCATCCAGGAAGTGGATGAGTTC
CTTCTGCGGCTGTCCAAGCTCACCAAGGAGGATGAGCAGCAACAGGCCCTACAGGACATT
GCCTCCAGGTGTACAGCCAATGACCTTAAATGCATCATCAGGTTGATCAAACATGATCTG
AAGATGAACTCAGGTGCAAAACATGTGTTAGACGCCCTTGACCCCAATGCCTATGAAGCC
TTCAAAGCCTCGCGCAACCTGCAGGATGTGGTGGAGCGGGTCCTTCACAACGCGCAGGAG
GTGGAGAAGGAGCCGGGCCAGAGACGAGCTCTGAGCGTCCAGGCCTCGCTGATGACACCT
GTGCAGCCCATGTTGGCGGAGGCCTGCAAGTCCGTTGAGTATGCAATGAAGAAATGTCCC
AATGGCATGTTCTCTGAGATCAAGTACGATGGAGAGCGAGTCCAGGTGCATAAGAATGGA
GACCACTTCAGCTACTTCAGCCGCAGTCTCAAGCCCGTCCTTCCTCACAAGGTGGCCCAC
TTTAAGGACTACATTCCCCAGGCTTTTCCTGGGGGCCACAGCATGATCTTGGATTCTGAA
GTGCTTCTGATTGACAACAAGACAGGCAAACCACTGCCCTTTGGGACTCTGGGAGTACAC
AAGAAAGCAGCCTTCCAGGATGCTAATGTCTGCCTGTTTGTTTTTGATTGTATCTACTTT
AATGATGTCAGCTTGATGGACAGACCTCTGTGTGAGCGGCGGAAGTTTCTTCATGACAAC
ATGGTTGAAATTCCAAACCGGATCATGTTCTCAGAAATGAAGCGAGTCACAAAAGCTTTG
GACTTGGCTGACATGATAACCCGGGTGATCCAGGAGGGATTGGAGGGGCTGGTGCTGAAG
GATGTGAAGGGTACATATGAGCCTGGGAAGCGGCACTGGCTGAAAGTGAAGAAAGACTAT
TTGAACGAGGGGGCCATGGCCGACACAGCTGACCTGGTGGTCCTTGGAGCCTTCTATGGG
CAAGGGAGCAAAGGCGGCATGATGTCAATCTTCCTCATGGGCTGCTACGACCCTGGCAGC
CAGAAGTGGTGCACAGTCACCAAGTGTGCAGGAGGCCATGATGATGCCACGCTTGCCCGC
CTGCAGAATGAACTAGACATGGTGAAGATCAGCAAGGACCCCAGCAAAATACCCAGCTGG
TTGAAGGTCAACAAGATCTACTATCCTGACTTCATCGTCCCAGACCCAAAGAAAGCTGCC
GTGTGGGAGATCACAGGGGCTGAATTCTCCAAATCGGAGGCTCATACAGCTGACGGGATC
TCCATCCGATTCCCTCGCTGCACCCGAATCCGAGATGATAAGGACTGGAAATCTGCCACT
AACCTTCCCCAACTCAAGGAACTGTACCAGTTGTCCAAGGAGAAGGCAGACTTCACTGTA
GTGGCTGGAGATGAGGGGAGCTCCACTACAGGGGGTAGCAGTGAAGAGAATAAGGGTCCC
TCAGGGTCTGCTGTGTCCCGCAAGGCCCCCAGCAAGCCCTCAGCCAGTACCAAGAAAGCA
GAAGGGAAGCTGAGTAACTCCAACAGCAAAGATGGCAACATGCAGACTGCAAAGCCTTCC
GCTATGAAGGTGGGGGAGAAGCTGGCCACAAAGTCTTCTCCAGTGAAAGTAGGGGAGAAG
CGGAAAGCTGCTGATGAGACGCTGTGCCAAACAAAGAGGCGGCCAGCCAGTGAGCAGAGA
GGAAGAACTGTGCCAGCAGGCAGGAGATAG
GenBank Gene IDX84740
GeneCard IDNot Available
GenAtlas IDLIG3
HGNC IDHGNC:6600
Chromosome Location17
Locus17q11.2-q12
References
  1. Wei YF, Robins P, Carter K, Caldecott K, Pappin DJ, Yu GL, Wang RP, Shell BK, Nash RA, Schar P, et al.: Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination. Mol Cell Biol. 1995 Jun;15(6):3206-16. 7760816
  2. Chen J, Tomkinson AE, Ramos W, Mackey ZB, Danehower S, Walter CA, Schultz RA, Besterman JM, Husain I: Mammalian DNA ligase III: molecular cloning, chromosomal localization, and expression in spermatocytes undergoing meiotic recombination. Mol Cell Biol. 1995 Oct;15(10):5412-22. 7565692
  3. Wang W, Shen P, Thiyagarajan S, Lin S, Palm C, Horvath R, Klopstock T, Cutler D, Pique L, Schrijver I, Davis RW, Mindrinos M, Speed TP, Scharfe C: Identification of rare DNA variants in mitochondrial disorders with improved array-based sequencing. Nucleic Acids Res. 2011 Jan;39(1):44-58. doi: 10.1093/nar/gkq750. Epub 2010 Sep 15. 20843780
  4. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. 16625196
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  6. Lakshmipathy U, Campbell C: The human DNA ligase III gene encodes nuclear and mitochondrial proteins. Mol Cell Biol. 1999 May;19(5):3869-76. 10207110
  7. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. 17081983
  8. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. 16964243
  9. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. 18669648
  10. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. 19413330
  11. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. 19690332
  12. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. 20068231
  13. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. 21269460
  14. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. 21406692
  15. Akbari M, Keijzers G, Maynard S, Scheibye-Knudsen M, Desler C, Hickson ID, Bohr VA: Overexpression of DNA ligase III in mitochondria protects cells against oxidative stress and improves mitochondrial DNA base excision repair. DNA Repair (Amst). 2014 Apr;16:44-53. doi: 10.1016/j.dnarep.2014.01.015. Epub 2014 Feb 27. 24674627
  16. Thornton KH, Krishnan VV, West MG, Popham J, Ramirez M, Thelen MP, Cosman M: Expression, purification, and biophysical characterization of the BRCT domain of human DNA ligase IIIalpha. Protein Expr Purif. 2001 Apr;21(3):401-11. 11281714
  17. Kulczyk AW, Yang JC, Neuhaus D: Solution structure and DNA binding of the zinc-finger domain from DNA ligase IIIalpha. J Mol Biol. 2004 Aug 13;341(3):723-38. 15288782
  18. Cotner-Gohara E, Kim IK, Hammel M, Tainer JA, Tomkinson AE, Ellenberger T: Human DNA ligase III recognizes DNA ends by dynamic switching between two DNA-bound states. Biochemistry. 2010 Jul 27;49(29):6165-76. doi: 10.1021/bi100503w. 20518483
  19. Cuneo MJ, Gabel SA, Krahn JM, Ricker MA, London RE: The structural basis for partitioning of the XRCC1/DNA ligase III-alpha BRCT-mediated dimer complexes. Nucleic Acids Res. 2011 Sep 1;39(17):7816-27. doi: 10.1093/nar/gkr419. Epub 2011 Jun 7. 21652643
  20. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. 16959974