UniProt functional annotation for P49917

UniProt code: P49917.

Organism: Homo sapiens (Human).
Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
 
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.
 
Catalytic activity: ATP + (deoxyribonucleotide)(n) + (deoxyribonucleotide)(m) = AMP + diphosphate + (deoxyribonucleotide)(n+m).
Cofactor: Magnesium (By similarity).
Subunit: Binds to XRCC4. The LIG4-XRCC4 complex has probably a 1:2 stoichiometry. The LIG4-XRCC4 heteromer associates in a DNA- dependent manner with the DNA-dependent protein kinase complex DNA-PK, formed by the Ku p70/p86 dimer (G22P1/G22P2) and PRKDC. Interacts with APLF.
Subcellular location: Nucleus.
Tissue specificity: Testis, thymus, prostate and heart.
Disease: 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. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease: 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.
Similarity: Belongs to the ATP-dependent DNA ligase family.
Similarity: Contains 2 BRCT domains.
Sequence caution: Sequence=AAL77435.1; Type=Erroneous initiation; Sequence=CAA58467.1; Type=Erroneous initiation;

Annotations taken from UniProtKB at the EBI.