Format

Send to:

Choose Destination

LIG4 DNA ligase 4 [ Homo sapiens (human) ]

Gene ID: 3981, updated on 10-Oct-2019

Summary

Official Symbol
LIG4provided by HGNC
Official Full Name
DNA ligase 4provided by HGNC
Primary source
HGNC:HGNC:6601
See related
Ensembl:ENSG00000174405 MIM:601837
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
LIG4S
Summary
The protein encoded by this gene is a DNA ligase that joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. This protein is essential for V(D)J recombination and DNA double-strand break (DSB) repair through nonhomologous end joining (NHEJ). This protein forms a complex with the X-ray repair cross complementing protein 4 (XRCC4), and further interacts with the DNA-dependent protein kinase (DNA-PK). Both XRCC4 and DNA-PK are known to be required for NHEJ. The crystal structure of the complex formed by this protein and XRCC4 has been resolved. Defects in this gene are the cause of LIG4 syndrome. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in brain (RPKM 5.8), testis (RPKM 4.8) and 25 other tissues See more
Orthologs

Genomic context

See LIG4 in Genome Data Viewer
Location:
13q33.3
Exon count:
6
Annotation release Status Assembly Chr Location
109.20190905 current GRCh38.p13 (GCF_000001405.39) 13 NC_000013.11 (108207442..108218349, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (108859790..108870716, complement)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene family with sequence similarity 155 member A Neighboring gene uncharacterized LOC107984581 Neighboring gene FAM155A intronic transcript 1 Neighboring gene uncharacterized LOC112268111 Neighboring gene Sharpr-MPRA regulatory region 13792 Neighboring gene abhydrolase domain containing 13 Neighboring gene TNF superfamily member 13b Neighboring gene RNA, 5S ribosomal pseudogene 39

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Lig4 syndrome
MedGen: C1847827 OMIM: 606593 GeneReviews: Not available
Compare labs
Multiple myeloma
MedGen: C0026764 OMIM: 254500 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Conduct disorder and ADHD: evaluation of conduct problems as a categorical and quantitative trait in the international multicentre ADHD genetics study.
NHGRI GWA Catalog

Pathways from BioSystems

  • 2-LTR circle formation, organism-specific biosystem (from REACTOME)
    2-LTR circle formation, organism-specific biosystemThe formation of 2-LTR circles requires the action of the cellular non-homologous DNA end-joining pathway. Specifically the cellular Ku, XRCC4 and ligase IV proteins are needed. Evidence for this i...
  • DNA Double-Strand Break Repair, organism-specific biosystem (from REACTOME)
    DNA Double-Strand Break Repair, organism-specific biosystemNumerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-s...
  • DNA Repair, organism-specific biosystem (from REACTOME)
    DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • Early Phase of HIV Life Cycle, organism-specific biosystem (from REACTOME)
    Early Phase of HIV Life Cycle, organism-specific biosystemIn the early phase of HIV lifecycle, an active virion binds and enters a target cell mainly by specific interactions of the viral envelope proteins with host cell surface receptors. The virion core...
  • HIV Infection, organism-specific biosystem (from REACTOME)
    HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
  • HIV Life Cycle, organism-specific biosystem (from REACTOME)
    HIV Life Cycle, organism-specific biosystemThe life cycle of HIV-1 is divided into early and late phases, shown schematically in the figure. In the early phase, an HIV-1 virion binds to receptors and co-receptors on the human host cell surfac...
  • Infectious disease, organism-specific biosystem (from REACTOME)
    Infectious disease, organism-specific biosystem
    Infectious disease
  • Integration of provirus, organism-specific biosystem (from REACTOME)
    Integration of provirus, organism-specific biosystemFor retroviral DNA to direct production of progeny virions it must become covalently integrated into the host cell chromosome (reviewed in Coffin et al. 1997; Hansen et al. 1998). Analyses of mutants...
  • Non-homologous end-joining, organism-specific biosystem (from KEGG)
    Non-homologous end-joining, organism-specific biosystemNonhomologous end joining (NHEJ) eliminates DNA double-strand breaks (DSBs) by direct ligation. NHEJ involves binding of the KU heterodimer to double-stranded DNA ends, recruitment of DNA-PKcs (MRX c...
  • Non-homologous end-joining, conserved biosystem (from KEGG)
    Non-homologous end-joining, conserved biosystemNonhomologous end joining (NHEJ) eliminates DNA double-strand breaks (DSBs) by direct ligation. NHEJ involves binding of the KU heterodimer to double-stranded DNA ends, recruitment of DNA-PKcs (MRX c...
  • Nonhomologous End-Joining (NHEJ), organism-specific biosystem (from REACTOME)
    Nonhomologous End-Joining (NHEJ), organism-specific biosystemThe nonhomologous end joining (NHEJ) pathway is initiated in response to the formation of DNA double-strand breaks (DSBs) induced by DNA-damaging agents, such as ionizing radiation. DNA DSBs are reco...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
DNA ligase (ATP) activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA ligase (ATP) activity IDA
Inferred from Direct Assay
more info
PubMed 
DNA ligase activity IDA
Inferred from Direct Assay
more info
PubMed 
DNA ligase activity TAS
Traceable Author Statement
more info
 
ligase activity IDA
Inferred from Direct Assay
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein C-terminus binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
DNA biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
DNA ligation IDA
Inferred from Direct Assay
more info
PubMed 
DNA ligation involved in DNA recombination ISS
Inferred from Sequence or Structural Similarity
more info
 
DNA ligation involved in DNA repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA ligation involved in DNA repair IDA
Inferred from Direct Assay
more info
PubMed 
DNA ligation involved in DNA repair ISS
Inferred from Sequence or Structural Similarity
more info
 
DNA replication IEA
Inferred from Electronic Annotation
more info
 
T cell differentiation in thymus ISS
Inferred from Sequence or Structural Similarity
more info
 
T cell receptor V(D)J recombination ISS
Inferred from Sequence or Structural Similarity
more info
 
V(D)J recombination IDA
Inferred from Direct Assay
more info
PubMed 
cell cycle IEA
Inferred from Electronic Annotation
more info
 
cell division IEA
Inferred from Electronic Annotation
more info
 
cell proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
cellular response to ionizing radiation IGI
Inferred from Genetic Interaction
more info
PubMed 
cellular response to lithium ion IEA
Inferred from Electronic Annotation
more info
 
central nervous system development ISS
Inferred from Sequence or Structural Similarity
more info
 
chromosome organization ISS
Inferred from Sequence or Structural Similarity
more info
 
double-strand break repair IDA
Inferred from Direct Assay
more info
PubMed 
double-strand break repair ISS
Inferred from Sequence or Structural Similarity
more info
 
double-strand break repair via classical nonhomologous end joining IMP
Inferred from Mutant Phenotype
more info
PubMed 
double-strand break repair via nonhomologous end joining IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
double-strand break repair via nonhomologous end joining IDA
Inferred from Direct Assay
more info
PubMed 
double-strand break repair via nonhomologous end joining IGI
Inferred from Genetic Interaction
more info
PubMed 
double-strand break repair via nonhomologous end joining IMP
Inferred from Mutant Phenotype
more info
PubMed 
double-strand break repair via nonhomologous end joining ISS
Inferred from Sequence or Structural Similarity
more info
 
double-strand break repair via nonhomologous end joining TAS
Traceable Author Statement
more info
 
establishment of integrated proviral latency TAS
Traceable Author Statement
more info
 
immunoglobulin V(D)J recombination IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
in utero embryonic development ISS
Inferred from Sequence or Structural Similarity
more info
 
isotype switching ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of neuron apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
 
neuron apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
 
nucleotide-excision repair, DNA gap filling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleotide-excision repair, DNA gap filling IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of chromosome organization IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of fibroblast proliferation ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of neurogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
pro-B cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
 
response to X-ray IMP
Inferred from Mutant Phenotype
more info
PubMed 
response to gamma radiation ISS
Inferred from Sequence or Structural Similarity
more info
 
single strand break repair IDA
Inferred from Direct Assay
more info
PubMed 
somatic stem cell population maintenance ISS
Inferred from Sequence or Structural Similarity
more info
 
Component Evidence Code Pubs
DNA ligase IV complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA ligase IV complex IMP
Inferred from Mutant Phenotype
more info
PubMed 
DNA-dependent protein kinase-DNA ligase 4 complex IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA-dependent protein kinase-DNA ligase 4 complex IDA
Inferred from Direct Assay
more info
PubMed 
DNA-dependent protein kinase-DNA ligase 4 complex ISS
Inferred from Sequence or Structural Similarity
more info
 
condensed chromosome IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasmic ribonucleoprotein granule IDA
Inferred from Direct Assay
more info
 
nonhomologous end joining complex IDA
Inferred from Direct Assay
more info
PubMed 
nuclear chromosome, telomeric region IC
Inferred by Curator
more info
PubMed 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
DNA ligase 4
Names
DNA joinase
DNA ligase IV
DNA repair enzyme
ligase IV, DNA, ATP-dependent
polydeoxyribonucleotide synthase [ATP] 4
polynucleotide ligase
sealase
NP_001091738.1
NP_001317524.1
NP_001339527.1
NP_001339528.1
NP_001339529.1
NP_001339530.1
NP_001339531.1
NP_001339532.1
NP_001339533.1
NP_002303.2
NP_996820.1

NCBI Reference Sequences (RefSeq)

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.

Genomic

  1. NG_007396.1 RefSeqGene

    Range
    2167..13093
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_79

mRNA and Protein(s)

  1. NM_001098268.2NP_001091738.1  DNA ligase 4 isoform 1

    See identical proteins and their annotated locations for NP_001091738.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1-3 and 5-10 all encode the same isoform (1).
    Source sequence(s)
    BC037491, BX648833
    Consensus CDS
    CCDS9508.1
    UniProtKB/Swiss-Prot
    P49917
    UniProtKB/TrEMBL
    A0A024RE06
    Related
    ENSP00000385955.1, ENST00000405925.2
    Conserved Domains (3) summary
    TIGR00574
    Location:81602
    dnl1; DNA ligase I, ATP-dependent (dnl1)
    pfam00533
    Location:656730
    BRCT; BRCA1 C Terminus (BRCT) domain
    pfam11411
    Location:750783
    DNA_ligase_IV; DNA ligase IV
  2. NM_001330595.1NP_001317524.1  DNA ligase 4 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a dowstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1.
    Source sequence(s)
    AK292419, BC037491, BX648833, DC372305
    Consensus CDS
    CCDS81779.1
    UniProtKB/Swiss-Prot
    P49917
    UniProtKB/TrEMBL
    A0A0C4DGV9, A8K8Q4
    Related
    ENSP00000480814.1, ENST00000614526.1
  3. NM_001352598.2NP_001339527.1  DNA ligase 4 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5), as well as variants 1-3 and 6-10, encodes isoform 1.
    Source sequence(s)
    AL157762
    Consensus CDS
    CCDS9508.1
    Conserved Domains (3) summary
    TIGR00574
    Location:81602
    dnl1; DNA ligase I, ATP-dependent (dnl1)
    pfam00533
    Location:656730
    BRCT; BRCA1 C Terminus (BRCT) domain
    pfam11411
    Location:750783
    DNA_ligase_IV; DNA ligase IV
  4. NM_001352599.2NP_001339528.1  DNA ligase 4 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6), as well as variants 1-3, 5, and 7-10, encodes isoform 1.
    Source sequence(s)
    AL157762
    Consensus CDS
    CCDS9508.1
    Conserved Domains (3) summary
    TIGR00574
    Location:81602
    dnl1; DNA ligase I, ATP-dependent (dnl1)
    pfam00533
    Location:656730
    BRCT; BRCA1 C Terminus (BRCT) domain
    pfam11411
    Location:750783
    DNA_ligase_IV; DNA ligase IV
  5. NM_001352600.2NP_001339529.1  DNA ligase 4 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7), as well as variants 1-3, 5, 6, and 8-10, encodes isoform 1.
    Source sequence(s)
    AL157762
    Consensus CDS
    CCDS9508.1
    Conserved Domains (3) summary
    TIGR00574
    Location:81602
    dnl1; DNA ligase I, ATP-dependent (dnl1)
    pfam00533
    Location:656730
    BRCT; BRCA1 C Terminus (BRCT) domain
    pfam11411
    Location:750783
    DNA_ligase_IV; DNA ligase IV
  6. NM_001352601.2NP_001339530.1  DNA ligase 4 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8), as well as variants 1-3, 5-7, 9, and 10, encodes isoform 1.
    Source sequence(s)
    AL157762
    Consensus CDS
    CCDS9508.1
    Conserved Domains (3) summary
    TIGR00574
    Location:81602
    dnl1; DNA ligase I, ATP-dependent (dnl1)
    pfam00533
    Location:656730
    BRCT; BRCA1 C Terminus (BRCT) domain
    pfam11411
    Location:750783
    DNA_ligase_IV; DNA ligase IV
  7. NM_001352602.2NP_001339531.1  DNA ligase 4 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9), as well as variants 1-3, 5-8, and 10, encodes isoform 1.
    Source sequence(s)
    AL157762
    Consensus CDS
    CCDS9508.1
    Conserved Domains (3) summary
    TIGR00574
    Location:81602
    dnl1; DNA ligase I, ATP-dependent (dnl1)
    pfam00533
    Location:656730
    BRCT; BRCA1 C Terminus (BRCT) domain
    pfam11411
    Location:750783
    DNA_ligase_IV; DNA ligase IV
  8. NM_001352603.1NP_001339532.1  DNA ligase 4 isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (10), as well as variants 1-3 and 5-9, encodes isoform 1.
    Source sequence(s)
    AL157762
    Consensus CDS
    CCDS9508.1
    Conserved Domains (3) summary
    TIGR00574
    Location:81602
    dnl1; DNA ligase I, ATP-dependent (dnl1)
    pfam00533
    Location:656730
    BRCT; BRCA1 C Terminus (BRCT) domain
    pfam11411
    Location:750783
    DNA_ligase_IV; DNA ligase IV
  9. NM_001352604.1NP_001339533.1  DNA ligase 4 isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (11) encodes the longest isoform (3).
    Source sequence(s)
    AL157762
    Conserved Domains (3) summary
    TIGR00574
    Location:93614
    dnl1; DNA ligase I, ATP-dependent (dnl1)
    pfam00533
    Location:668742
    BRCT; BRCA1 C Terminus (BRCT) domain
    pfam11411
    Location:762795
    DNA_ligase_IV; DNA ligase IV
  10. NM_002312.3NP_002303.2  DNA ligase 4 isoform 1

    See identical proteins and their annotated locations for NP_002303.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1), as well as variants 2, 3, and 5-10, encodes isoform 1.
    Source sequence(s)
    AI809944, BC037491, CD102896, X83441
    Consensus CDS
    CCDS9508.1
    UniProtKB/Swiss-Prot
    P49917
    UniProtKB/TrEMBL
    A0A024RE06
    Related
    ENSP00000349393.3, ENST00000356922.5
    Conserved Domains (3) summary
    TIGR00574
    Location:81602
    dnl1; DNA ligase I, ATP-dependent (dnl1)
    pfam00533
    Location:656730
    BRCT; BRCA1 C Terminus (BRCT) domain
    pfam11411
    Location:750783
    DNA_ligase_IV; DNA ligase IV
  11. NM_206937.2NP_996820.1  DNA ligase 4 isoform 1

    See identical proteins and their annotated locations for NP_996820.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1-3 and 5-10 all encode the same isoform (1).
    Source sequence(s)
    AL157762, BC037491, BX648833
    Consensus CDS
    CCDS9508.1
    UniProtKB/Swiss-Prot
    P49917
    UniProtKB/TrEMBL
    A0A024RE06
    Related
    ENSP00000402030.1, ENST00000442234.5
    Conserved Domains (3) summary
    TIGR00574
    Location:81602
    dnl1; DNA ligase I, ATP-dependent (dnl1)
    pfam00533
    Location:656730
    BRCT; BRCA1 C Terminus (BRCT) domain
    pfam11411
    Location:750783
    DNA_ligase_IV; DNA ligase IV

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20190905

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000013.11 Reference GRCh38.p13 Primary Assembly

    Range
    108207442..108218349 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Support Center