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Details on Person UniProt:P49917 LIG4

Class:IdReferenceGeneProduct:53792
_chainChangeLogchain:1-911 added on Fri February 6 2015
_displayNameUniProt:P49917 LIG4
_timestamp2025-02-21 19:58:20
chainchain:1-911
checksum2122813E1EFA63B9
commentFUNCTION DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination (PubMed:12517771, PubMed:17290226, PubMed:23523427, PubMed:29980672, PubMed:33586762, PubMed:8798671, PubMed:9242410, PubMed:9809069). Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction (PubMed:12517771, PubMed:17290226, PubMed:9242410, PubMed:9809069). LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps (PubMed:17290226). Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4 (PubMed:9242410, PubMed:9809069). 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 (PubMed:10854421). LIG4 regulates nuclear localization of XRCC4 (PubMed:24984242).CATALYTIC ACTIVITY ATP + (deoxyribonucleotide)n-3'-hydroxyl + 5'-phospho-(deoxyribonucleotide)m = (deoxyribonucleotide)n+m + AMP + diphosphate.COFACTOR Can also use manganese, calcium, nickel and cobalt ions in the ligation reaction.SUBUNIT Interacts with XRCC4; the LIG4-XRCC4 subcomplex has a 1:2 stoichiometry and XRCC4 is required for LIG4 stability (PubMed:10854421, PubMed:11702069, PubMed:12517771, PubMed:17290226, PubMed:19332554, PubMed:19837014, PubMed:21982441, PubMed:22658747, PubMed:24984242, PubMed:25934149, PubMed:9259561, PubMed:9809069, PubMed:17567543). Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (PubMed:12547193, PubMed:22658747, PubMed:25670504, PubMed:33854234, PubMed:34352203, PubMed:17567543). Additional component of the NHEJ complex includes PAXX (PubMed:25574025, PubMed:25941166). Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (PubMed:33854234). Interacts with DCLRE1C; the interaction is direct (PubMed:23219551, PubMed:23523427). Interacts with APLF (PubMed:17396150).INTERACTION Testis, thymus, prostate and heart.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the ATP-dependent DNA ligase family.SEQUENCE CAUTION LIG4 mutation dbONLINE INFORMATION DNA ligase entry
descriptionrecommendedName: fullName evidence="41"DNA ligase 4 ecNumber evidence="4 22 29 37"6.5.1.1 alternativeName: fullName evidence="40"DNA ligase IV alternativeName: Polydeoxyribonucleotide synthase [ATP] 4
geneNameLIG4
identifierP49917
isSequenceChangedFALSE
keyword3D-structure
ATP-binding
Cell cycle
Cell division
Direct protein sequencing
Disease variant
DNA damage
DNA recombination
DNA repair
Ligase
Magnesium
Metal-binding
Nucleotide-binding
Nucleus
Proteomics identification
Reference proteome
Repeat
SCID
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9862192] Weiser, Joel, 2024-02-26
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
nameLIG4
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8994181] ENSEMBL:ENSG00000174405 LIG4 [Homo sapiens]
secondaryIdentifierDNLI4_HUMAN
Q8IY66
Q8TEU5
sequenceLength911
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:53791] LIG4 [nucleoplasm] [Homo sapiens]
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