InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: LIG4

Summary

InnateDB Protein

IDBP-293708.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

LIG4

Protein Name

ligase IV, DNA, ATP-dependent

Synonyms

LIG4S;

Species

Homo sapiens

Ensembl Protein

ENSP00000385955

InnateDB Gene

IDBG-49744 (LIG4)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10854421, ECO:0000269PubMed:9809069}.

Subcellular Localization

Nucleus.

Disease Associations

LIG4 syndrome (LIG4S) [MIM:606593]: Characterized by immunodeficiency and developmental and growth delay. Patients display unusual facial features, microcephaly, growth and/or developmental delay, pancytopenia, and various skin abnormalities. {ECO:0000269PubMed:11779494}. Note=The disease is caused by mutations affecting the gene represented in this entry.Severe combined immunodeficiency autosomal recessive T- cell-negative/B-cell-negative/NK-cell-positive with sensitivity to ionizing radiation (RSSCID) [MIM:602450]: A form of severe combined immunodeficiency, a genetically and clinically heterogeneous group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. Patients present in infancy with recurrent, persistent infections by opportunistic organisms. The common characteristic of all types of SCID is absence of T- cell-mediated cellular immunity due to a defect in T-cell development. Individuals affected by RS-SCID show defects in the DNA repair machinery necessary for coding joint formation and the completion of V(D)J recombination. A subset of cells from such patients show increased radiosensitivity. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Testis, thymus, prostate and heart.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 160 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	160 [view]
Protein-Protein	160 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003909	DNA ligase activity
GO:0003910	DNA ligase (ATP) activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008022	protein C-terminus binding
GO:0016874	ligase activity
GO:0046872	metal ion binding

Biological Process

GO:0000012	single strand break repair
GO:0001701	in utero embryonic development
GO:0002328	pro-B cell differentiation
GO:0006266	DNA ligation
GO:0006273	lagging strand elongation
GO:0006281	DNA repair
GO:0006297	nucleotide-excision repair, DNA gap filling
GO:0006302	double-strand break repair
GO:0006303	double-strand break repair via nonhomologous end joining
GO:0006310	DNA recombination
GO:0007049	cell cycle
GO:0007417	central nervous system development
GO:0008283	cell proliferation
GO:0010165	response to X-ray
GO:0010332	response to gamma radiation
GO:0016032	viral process
GO:0033077	T cell differentiation in thymus
GO:0033151	V(D)J recombination
GO:0033153	T cell receptor V(D)J recombination
GO:0035019	somatic stem cell maintenance
GO:0043524	negative regulation of neuron apoptotic process
GO:0045190	isotype switching
GO:0048146	positive regulation of fibroblast proliferation
GO:0050769	positive regulation of neurogenesis
GO:0051102	DNA ligation involved in DNA recombination
GO:0051103	DNA ligation involved in DNA repair
GO:0051276	chromosome organization
GO:0051301	cell division
GO:0051402	neuron apoptotic process
GO:0071897	DNA biosynthetic process
GO:0075713	establishment of integrated proviral latency

Cellular Component

GO:0000793	condensed chromosome
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0005925	focal adhesion
GO:0005958	DNA-dependent protein kinase-DNA ligase 4 complex
GO:0032807	DNA ligase IV complex
GO:0070419	nonhomologous end joining complex

Protein Structure and Domains

PDB ID

InterPro

IPR000977 DNA ligase, ATP-dependent
IPR001357 BRCT domain
IPR012308 DNA ligase, ATP-dependent, N-terminal
IPR012309 DNA ligase, ATP-dependent, C-terminal
IPR012310 DNA ligase, ATP-dependent, central
IPR012340 Nucleic acid-binding, OB-fold
IPR021536 DNA ligase IV domain

PFAM

PF00533
PF12738
PF04675
PF04679
PF01068
PF11411

PRINTS

PIRSF

SMART

SM00292

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P49917