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Showing Protein DNA ligase 4 (HMDBP00588)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 4 metabolites
Identification
HMDB Protein ID HMDBP00588
Secondary Accession Numbers
  • 5860
Name DNA ligase 4
Synonyms
  1. DNA ligase IV
  2. Polydeoxyribonucleotide synthase [ATP] 4
Gene Name LIG4
Protein Type Enzyme
Biological Properties
General Function Involved in DNA ligase (ATP) activity
Specific Function Efficiently joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The LIG4-XRCC4 complex is responsible for the NHEJ ligation step, and XRCC4 enhances the joining activity of LIG4. Binding of the LIG4-XRCC4 complex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends.
Pathways
  • Non-homologous end-joining
Reactions
Adenosine triphosphate + (deoxyribonucleotide)(n) + (deoxyribonucleotide)(m) → Adenosine monophosphate + Pyrophosphate + (deoxyribonucleotide)(n+m) details
GO Classification
Biological Process
cell cycle
cell division
DNA ligation involved in DNA repair
lagging strand elongation
nucleotide-excision repair, DNA gap filling
cellular response to lithium ion
chromosome organization
DNA ligation involved in DNA recombination
double-strand break repair via nonhomologous end joining
immunoglobulin V(D)J recombination
negative regulation of neuron apoptotic process
neuron apoptotic process
positive regulation of fibroblast proliferation
positive regulation of neurogenesis
pro-B cell differentiation
single strand break repair
somatic stem cell maintenance
T cell differentiation in thymus
T cell receptor V(D)J recombination
response to gamma radiation
cell proliferation
in utero embryonic development
isotype switching
response to X-ray
viral reproduction
central nervous system development
Cellular Component
condensed chromosome
DNA ligase IV complex
DNA-dependent protein kinase-DNA ligase 4 complex
focal adhesion
cytoplasm
plasma membrane
nucleoplasm
Component
cell part
intracellular
Function
binding
catalytic activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
ligase activity
dna ligase (atp) activity
ligase activity, forming phosphoric ester bonds
dna ligase activity
nucleic acid binding
dna binding
Molecular Function
DNA ligase (ATP) activity
metal ion binding
ATP binding
DNA binding
Process
metabolic process
macromolecule metabolic process
cellular macromolecule metabolic process
dna metabolic process
dna replication
dna ligation
dna ligation involved in dna repair
dna recombination
dna repair
Cellular Location
  1. Nucleus
Gene Properties
Chromosome Location 13
Locus 13q33-q34
SNPs LIG4
Gene Sequence 
>2736 bp
ATGGCTGCCTCACAAACTTCACAAACTGTTGCATCTCACGTTCCTTTTGCAGATTTGTGT
TCAACTTTAGAACGAATACAGAAAAGTAAAGGACGTGCAGAAAAAATCAGACACTTCAGG
GAATTTTTAGATTCTTGGAGAAAATTTCATGATGCTCTTCATAAGAACCACAAAGATGTC
ACAGACTCTTTTTATCCAGCAATGAGACTAATTCTTCCTCAGCTAGAAAGAGAGAGAATG
GCCTATGGAATTAAAGAAACTATGCTTGCTAAGCTTTATATTGAGTTGCTTAATTTACCT
AGAGATGGAAAAGATGCCCTCAAACTTTTAAACTACAGAACACCCACTGGAACTCATGGA
GATGCTGGAGACTTTGCAATGATTGCATATTTTGTGTTGAAGCCAAGATGTTTACAGAAA
GGAAGTTTAACCATACAGCAAGTAAACGACCTTTTAGACTCAATTGCCAGCAATAATTCT
GCTAAAAGAAAAGACCTAATAAAAAAGAGCCTTCTTCAACTTATAACTCAGAGTTCAGCA
CTTGAGCAAAAGTGGCTTATACGGATGATCATAAAGGATTTAAAGCTTGGTGTTAGTCAG
CAAACTATCTTTTCTGTTTTTCATAATGATGCTGCTGAGTTGCATAATGTCACTACAGAT
CTGGAAAAAGTCTGTAGGCAACTGCATGATCCTTCTGTAGGACTCAGTGATATTTCTATC
ACTTTATTTTCTGCATTTAAACCAATGCTAGCTGCTATTGCAGATATTGAGCACATTGAG
AAGGATATGAAACATCAGAGTTTCTACATAGAAACCAAGCTAGATGGTGAACGTATGCAA
ATGCACAAAGATGGAGATGTATATAAATACTTCTCTCGAAATGGATATAACTACACTGAT
CAGTTTGGTGCTTCTCCTACTGAAGGTTCTCTTACCCCATTCATTCATAATGCATTCAAA
GCAGATATACAAATCTGTATTCTTGATGGTGAGATGATGGCCTATAATCCTAATACACAA
ACTTTCATGCAAAAGGGAACTAAGTTTGATATTAAAAGAATGGTAGAGGATTCTGATCTG
CAAACTTGTTATTGTGTTTTTGATGTATTGATGGTTAATAATAAAAAGCTAGGGCATGAG
ACTCTGAGAAAGAGGTATGAGATTCTTAGTAGTATTTTTACACCAATTCCAGGTAGAATA
GAAATAGTGCAGAAAACACAAGCTCATACTAAGAATGAAGTAATTGATGCATTGAATGAA
GCAATAGATAAAAGAGAAGAGGGAATTATGGTAAAACAACCTCTATCCATCTACAAGCCA
GACAAAAGAGGTGAAGGGTGGTTAAAAATTAAACCAGAGTATGTCAGTGGACTAATGGAT
GAATTGGACATTTTAATTGTTGGAGGATATTGGGGTAAAGGATCACGGGGTGGAATGATG
TCTCATTTTCTGTGTGCAGTAGCAGAGAAGCCCCCTCCTGGTGAGAAGCCATCTGTGTTT
CATACTCTCTCTCGTGTTGGGTCTGGCTGCACCATGAAAGAACTGTATGATCTGGGTTTG
AAATTGGCCAAGTATTGGAAGCCTTTTCATAGAAAAGCTCCACCAAGCAGCATTTTATGT
GGAACAGAGAAGCCAGAAGTATACATTGAACCTTGTAATTCTGTCATTGTTCAGATTAAA
GCAGCAGAGATCGTACCCAGTGATATGTATAAAACTGGCTGCACCTTGCGTTTTCCACGA
ATTGAAAAGATAAGAGATGACAAGGAGTGGCATGAGTGCATGACCCTGGACGACCTAGAA
CAACTTAGGGGGAAGGCATCTGGTAAGCTCGCATCTAAACACCTTTATATAGGTGGTGAT
GATGAACCACAAGAAAAAAAGCGGAAAGCTGCCCCAAAGATGAAGAAAGTTATTGGAATT
ATTGAGCACTTAAAAGCACCTAACCTTACTAACGTTAACAAAATTTCTAATATATTTGAA
GATGTAGAGTTTTGTGTTATGAGTGGAACAGATAGCCAGCCAAAGCCTGACCTGGAGAAC
AGAATTGCAGAATTTGGTGGTTATATAGTACAAAATCCAGGCCCAGACACGTACTGTGTA
ATTGCAGGGTCTGAGAACATCAGAGTGAAAAACATAATTTTGTCAAATAAACATGATGTT
GTCAAGCCTGCATGGCTTTTAGAATGTTTTAAGACCAAAAGCTTTGTACCATGGCAGCCT
CGCTTTATGATTCATATGTGCCCATCAACCAAAGAACATTTTGCCCGTGAATATGATTGC
TATGGTGATAGTTATTTCATTGATACAGACTTGAACCAACTGAAGGAAGTATTCTCAGGA
ATTAAAAATTCTAACGAGCAGACTCCTGAAGAAATGGCTTCTCTGATTGCTGATTTAGAA
TATCGGTATTCCTGGGATTGCTCTCCTCTCAGTATGTTTCGACGCCACACCGTTTATTTG
GACTCGTATGCTGTTATTAATGACCTGAGTACCAAAAATGAGGGGACAAGGTTAGCTATT
AAAGCCTTGGAGCTTCGGTTTCATGGAGCAAAAGTAGTTTCTTGTTTAGCTGAGGGAGTG
TCTCATGTAATAATTGGGGAAGATCATAGTCGTGTTGCAGATTTTAAAGCTTTTAGAAGA
ACTTTTAAGAGAAAGTTTAAAATCCTAAAAGAAAGTTGGGTAACTGATTCAATAGACAAG
TGTGAATTACAAGAAGAAAACCAGTATTTGATTTAA
Protein Properties
Number of Residues 911
Molecular Weight 103969.85
Theoretical pI 7.959
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence 
>DNA ligase 4
MAASQTSQTVASHVPFADLCSTLERIQKSKGRAEKIRHFREFLDSWRKFHDALHKNHKDV
TDSFYPAMRLILPQLERERMAYGIKETMLAKLYIELLNLPRDGKDALKLLNYRTPTGTHG
DAGDFAMIAYFVLKPRCLQKGSLTIQQVNDLLDSIASNNSAKRKDLIKKSLLQLITQSSA
LEQKWLIRMIIKDLKLGVSQQTIFSVFHNDAAELHNVTTDLEKVCRQLHDPSVGLSDISI
TLFSAFKPMLAAIADIEHIEKDMKHQSFYIETKLDGERMQMHKDGDVYKYFSRNGYNYTD
QFGASPTEGSLTPFIHNAFKADIQICILDGEMMAYNPNTQTFMQKGTKFDIKRMVEDSDL
QTCYCVFDVLMVNNKKLGHETLRKRYEILSSIFTPIPGRIEIVQKTQAHTKNEVIDALNE
AIDKREEGIMVKQPLSIYKPDKRGEGWLKIKPEYVSGLMDELDILIVGGYWGKGSRGGMM
SHFLCAVAEKPPPGEKPSVFHTLSRVGSGCTMKELYDLGLKLAKYWKPFHRKAPPSSILC
GTEKPEVYIEPCNSVIVQIKAAEIVPSDMYKTGCTLRFPRIEKIRDDKEWHECMTLDDLE
QLRGKASGKLASKHLYIGGDDEPQEKKRKAAPKMKKVIGIIEHLKAPNLTNVNKISNIFE
DVEFCVMSGTDSQPKPDLENRIAEFGGYIVQNPGPDTYCVIAGSENIRVKNIILSNKHDV
VKPAWLLECFKTKSFVPWQPRFMIHMCPSTKEHFAREYDCYGDSYFIDTDLNQLKEVFSG
IKNSNEQTPEEMASLIADLEYRYSWDCSPLSMFRRHTVYLDSYAVINDLSTKNEGTRLAI
KALELRFHGAKVVSCLAEGVSHVIIGEDHSRVADFKAFRRTFKRKFKILKESWVTDSIDK
CELQEENQYLI
GenBank ID Protein 148539894
UniProtKB/Swiss-Prot ID P49917
UniProtKB/Swiss-Prot Entry Name DNLI4_HUMAN
PDB IDs
GenBank Gene ID NM_001098268.1
GeneCard ID LIG4
GenAtlas ID LIG4
HGNC ID HGNC:6601
References
General References
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  4. 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. [PubMed:7760816 ]
  5. Robins P, Lindahl T: DNA ligase IV from HeLa cell nuclei. J Biol Chem. 1996 Sep 27;271(39):24257-61. [PubMed:8798671 ]
  6. Grawunder U, Zimmer D, Fugmann S, Schwarz K, Lieber MR: DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes. Mol Cell. 1998 Oct;2(4):477-84. [PubMed:9809069 ]
  7. Critchlow SE, Bowater RP, Jackson SP: Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV. Curr Biol. 1997 Aug 1;7(8):588-98. [PubMed:9259561 ]
  8. Chen L, Trujillo K, Sung P, Tomkinson AE: Interactions of the DNA ligase IV-XRCC4 complex with DNA ends and the DNA-dependent protein kinase. J Biol Chem. 2000 Aug 25;275(34):26196-205. [PubMed:10854421 ]
  9. Calsou P, Delteil C, Frit P, Drouet J, Salles B: Coordinated assembly of Ku and p460 subunits of the DNA-dependent protein kinase on DNA ends is necessary for XRCC4-ligase IV recruitment. J Mol Biol. 2003 Feb 7;326(1):93-103. [PubMed:12547193 ]
  10. Kanno S, Kuzuoka H, Sasao S, Hong Z, Lan L, Nakajima S, Yasui A: A novel human AP endonuclease with conserved zinc-finger-like motifs involved in DNA strand break responses. EMBO J. 2007 Apr 18;26(8):2094-103. Epub 2007 Mar 29. [PubMed:17396150 ]
  11. Sibanda BL, Critchlow SE, Begun J, Pei XY, Jackson SP, Blundell TL, Pellegrini L: Crystal structure of an Xrcc4-DNA ligase IV complex. Nat Struct Biol. 2001 Dec;8(12):1015-9. [PubMed:11702069 ]
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  13. Riballo E, Doherty AJ, Dai Y, Stiff T, Oettinger MA, Jeggo PA, Kysela B: Cellular and biochemical impact of a mutation in DNA ligase IV conferring clinical radiosensitivity. J Biol Chem. 2001 Aug 17;276(33):31124-32. Epub 2001 May 10. [PubMed:11349135 ]
  14. O'Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B, Hirsch B, Gennery A, Palmer SE, Seidel J, Gatti RA, Varon R, Oettinger MA, Neitzel H, Jeggo PA, Concannon P: DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol Cell. 2001 Dec;8(6):1175-85. [PubMed:11779494 ]
  15. Roddam PL, Rollinson S, O'Driscoll M, Jeggo PA, Jack A, Morgan GJ: Genetic variants of NHEJ DNA ligase IV can affect the risk of developing multiple myeloma, a tumour characterised by aberrant class switch recombination. J Med Genet. 2002 Dec;39(12):900-5. [PubMed:12471202 ]
  16. van der Burg M, van Veelen LR, Verkaik NS, Wiegant WW, Hartwig NG, Barendregt BH, Brugmans L, Raams A, Jaspers NG, Zdzienicka MZ, van Dongen JJ, van Gent DC: A new type of radiosensitive T-B-NK+ severe combined immunodeficiency caused by a LIG4 mutation. J Clin Invest. 2006 Jan;116(1):137-45. Epub 2005 Dec 15. [PubMed:16357942 ]