Lig4 ligase IV, DNA, ATP-dependent [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Lig4provided by MGI
Official Full Name: ligase IV, DNA, ATP-dependentprovided by MGI
Primary source: MGI:MGI:1335098
See related: Ensembl:ENSMUSG00000049717 AllianceGenome:MGI:1335098
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: tiny; 5830471N16Rik
Summary: Enables ATP binding activity and DNA ligase (ATP) activity. Involved in double-strand break repair via nonhomologous end joining. Acts upstream of or within several processes, including DNA metabolic process; hemopoiesis; and nervous system development. Part of DNA-dependent protein kinase-DNA ligase 4 complex. Is expressed in metanephros. Used to study DNA ligase IV deficiency. Human ortholog(s) of this gene implicated in several diseases, including DNA ligase IV deficiency; colorectal cancer; high grade glioma; multiple myeloma; and prostate cancer. Orthologous to human LIG4 (DNA ligase 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Ubiquitous expression in thymus adult (RPKM 7.2), testis adult (RPKM 3.8) and 28 other tissues See more
Orthologs: human all
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Genomic context

Location:: 8 A1.1; 8 4.52 cM

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	8	NC_000074.7 (10020020..10027680, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	8	NC_000074.6 (9970020..9977680, complement)

Chromosome 8 - NC_000074.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Deficiency of ligase IV leads to reduced NHEJ, accumulation of DNA damage, and can sensitize cells to cancer therapeutics.
Title: Deficiency of ligase IV leads to reduced NHEJ, accumulation of DNA damage, and can sensitize cells to cancer therapeutics.
Hypomorphic Lig4 mutation Promotes nonprogressive microcephaly.
Title: Spatiotemporal Gradient of Cortical Neuron Death Contributes to Microcephaly in Knock-In Mouse Model of Ligase 4 Syndrome.
The data firmly demonstrate Lig4(R278H) activity renders nonhomologous end-joining (NHEJ) DNA repair to be more error-prone, and predict increased error-prone NHEJ and A-EJ suppression as the cause of defective B lymphopoiesis in Lig4 patients.
Title: The DNA Ligase IV Syndrome R278H Mutation Impairs B Lymphopoiesis via Error-Prone Nonhomologous End-Joining.
To promote homology-directed r at the expense of nonhomologous end joining , we targeted DNA ligase IV, a key enzyme in the NHEJ pathway, using the inhibitor Scr7. This approach should be applicable to other customizable endonucleases
Title: Increasing the efficiency of precise genome editing with CRISPR-Cas9 by inhibition of nonhomologous end joining.
Lig4 and XRCC1 double-deficient cells switch as efficiently as Lig4-deficient cells, clearly indicating that XRCC1 is dispensable for A-EJ in CH12F3 cells during class switch recombination
Title: X-ray repair cross-complementing protein 1 (XRCC1) deficiency enhances class switch recombination and is permissive for alternative end joining.
These studies provide insight into the interplay between DNA damage responses in the developing brain and the DNA ligase IV plat the role in repairing endogenously arising DNA double-strand breaks.
Title: Requirement for DNA ligase IV during embryonic neuronal development.
Lig4-deficient B cells have reduced, but still substantial, immunoglobulins class switch recombination
Title: Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4.
Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome.
Title: Homozygous DNA ligase IV R278H mutation in mice leads to leaky SCID and represents a model for human LIG4 syndrome.
the Lig4Y288C mutation leads to multiple defects in lymphocyte development and function, including impaired V(D)J recombination, peripheral lymphocyte survival and proliferation, and B cell class switch recombination
Title: Impaired lymphocyte development and antibody class switching and increased malignancy in a murine model of DNA ligase IV syndrome.
particular features of the c-Myc locus select it as a preferential translocation/amplification target, compared to the endogenous N-myc locus, in Lig4/p53-deficient pro-B cell lymphomas
Title: Chromosomal location targets different MYC family gene members for oncogenic translocations.

Submit: New GeneRIF Correction See all GeneRIFs (16)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (3)
Endonuclease-mediated (1)
Targeted (6) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Lig4 (e-PCR), detects polymorphism
- UniSTS:496714

Lig4 (e-PCR), detects polymorphism
- UniSTS:507028

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IBA Inferred from Biological aspect of Ancestor more info
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables ATP binding	ISO Inferred from Sequence Orthology more info
enables DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables DNA binding	ISO Inferred from Sequence Orthology more info
enables DNA ligase (ATP) activity	IBA Inferred from Biological aspect of Ancestor more info
enables DNA ligase (ATP) activity	IDA Inferred from Direct Assay more info	PubMed
enables DNA ligase (ATP) activity	ISO Inferred from Sequence Orthology more info
enables DNA ligase activity	ISO Inferred from Sequence Orthology more info
enables ligase activity	ISO Inferred from Sequence Orthology more info
enables magnesium ion binding	ISO Inferred from Sequence Orthology more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within DN2 thymocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA biosynthetic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within DNA damage response	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within DNA ligation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within DNA ligation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA ligation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within DNA ligation involved in DNA recombination	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within DNA ligation involved in DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in DNA ligation involved in DNA repair	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within DNA recombination	IEA Inferred from Electronic Annotation more info
involved_in DNA recombination	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within T cell receptor V(D)J recombination	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within V(D)J recombination	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within V(D)J recombination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in V(D)J recombination	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within cell cycle	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cell division	IEA Inferred from Electronic Annotation more info
involved_in cellular response to ionizing radiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within central nervous system development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within central nervous system development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within chromosome organization	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within double-strand break repair	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within double-strand break repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair	ISO Inferred from Sequence Orthology more info
involved_in double-strand break repair via classical nonhomologous end joining	ISO Inferred from Sequence Orthology more info
involved_in double-strand break repair via nonhomologous end joining	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within double-strand break repair via nonhomologous end joining	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair via nonhomologous end joining	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in double-strand break repair via nonhomologous end joining	ISO Inferred from Sequence Orthology more info
acts_upstream_of fibroblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within fibroblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in immunoglobulin V(D)J recombination	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within immunoglobulin V(D)J recombination	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within in utero embryonic development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within isotype switching	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of neuron apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within negative regulation of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of neurogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of neuron apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within neuron apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nucleotide-excision repair, DNA gap filling	IBA Inferred from Biological aspect of Ancestor more info
involved_in nucleotide-excision repair, DNA gap filling	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of chromosome organization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of fibroblast proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of neurogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within pro-B cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to X-ray	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within response to gamma radiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within response to ionizing radiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in single strand break repair	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within somatic stem cell population maintenance	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within stem cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of DNA ligase IV complex	IBA Inferred from Biological aspect of Ancestor more info
part_of DNA ligase IV complex	ISO Inferred from Sequence Orthology more info
part_of DNA-dependent protein kinase-DNA ligase 4 complex	IBA Inferred from Biological aspect of Ancestor more info
part_of DNA-dependent protein kinase-DNA ligase 4 complex	IDA Inferred from Direct Assay more info	PubMed
part_of DNA-dependent protein kinase-DNA ligase 4 complex	ISO Inferred from Sequence Orthology more info
located_in condensed chromosome	ISO Inferred from Sequence Orthology more info
located_in intracellular membrane-bounded organelle	ISO Inferred from Sequence Orthology more info
part_of nonhomologous end joining complex	ISO Inferred from Sequence Orthology more info
located_in nucleoplasm	ISO Inferred from Sequence Orthology more info
is_active_in nucleus	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: DNA ligase 4

Names: DNA ligase IV; polydeoxyribonucleotide synthase [ATP] 4

NP_001363971.1

EC 6.5.1.1

NP_795927.2

EC 6.5.1.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001377042.1 → NP_001363971.1 DNA ligase 4

Status: VALIDATED

Source sequence(s)

AC138397, AK030029

UniProtKB/Swiss-Prot

G3UWC4, Q3UG76, Q8BTF7

UniProtKB/TrEMBL

Q8BTF5

Related

ENSMUSP00000130807.2, ENSMUST00000170033.2

Conserved Domains (4) summary

TIGR00574
Location:81 → 602

dnl1; DNA ligase I, ATP-dependent (dnl1)

cd17717
Location:813 → 900

BRCT_DNA_ligase_IV_rpt2; second BRCT domain of DNA ligase 4 (LIG4) and similar proteins

cd17722
Location:658 → 745

BRCT_DNA_ligase_IV_rpt1; first BRCT domain of DNA ligase 4 (LIG4) and similar proteins

pfam11411
Location:750 → 782

DNA_ligase_IV; DNA ligase IV
NM_176953.4 → NP_795927.2 DNA ligase 4

See identical proteins and their annotated locations for NP_795927.2

Status: VALIDATED

Source sequence(s)

AC138397, AK030966, CJ088420

Consensus CDS

CCDS22092.1

UniProtKB/Swiss-Prot

G3UWC4, Q3UG76, Q8BTF7

UniProtKB/TrEMBL

Q8BTF5

Related

ENSMUSP00000093130.5, ENSMUST00000095476.6

Conserved Domains (4) summary

TIGR00574
Location:81 → 602

dnl1; DNA ligase I, ATP-dependent (dnl1)

cd17717
Location:813 → 900

BRCT_DNA_ligase_IV_rpt2; second BRCT domain of DNA ligase 4 (LIG4) and similar proteins

cd17722
Location:658 → 745

BRCT_DNA_ligase_IV_rpt1; first BRCT domain of DNA ligase 4 (LIG4) and similar proteins

pfam11411
Location:750 → 782

DNA_ligase_IV; DNA ligase IV