Search Results
Overview
| Uniprot ID | Q13426 |
|---|---|
| Protein Name | DNA repair protein XRCC4 |
| Gene Name | XRCC4 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 187 | FILVLNEKKTKIRSL |
| 188 | ILVLNEKKTKIRSLH |
| 197 | KIRSLHNKLLNAAQE |
| 285 | RNLGTEPKMAPQENQ |
Function
DNA non-homologous end joining (NHEJ) core factor, required for double-strand break repair and V(D)J recombination (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:16412978, PubMed:17124166, PubMed:17290226, PubMed:22228831, PubMed:25597996, PubMed:25742519, PubMed:25934149, PubMed:26100018, PubMed:26774286, PubMed:8548796). Acts as a scaffold protein that regulates recruitment of other proteins to DNA double-strand breaks (DSBs) (PubMed:15385968, PubMed:20852255, PubMed:26774286, PubMed:27437582). Associates with NHEJ1/XLF to form alternating helical filaments that bridge DNA and act like a bandage, holding together the broken DNA until it is repaired (PubMed:21768349, PubMed:21775435, PubMed:22287571, PubMed:26100018, PubMed:27437582, PubMed:28500754). The XRCC4-NHEJ1/XLF subcomplex binds to the DNA fragments of a DSB in a highly diffusive manner and robustly bridges two independent DNA molecules, holding the broken DNA fragments in close proximity to one other (PubMed:27437582). The mobility of the bridges ensures that the ends remain accessible for further processing by other repair factors (PubMed:27437582). Plays a key role in the NHEJ ligation step of the broken DNA during DSB repair via direct interaction with DNA ligase IV (LIG4): the LIG4-XRCC4 subcomplex reseals the DNA breaks after the gap filling is completed (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:19837014, PubMed:9242410). XRCC4 stabilizes LIG4, regulates its subcellular localization and enhances LIG4's joining activity (PubMed:10757784, PubMed:10854421, PubMed:12517771, PubMed:17290226, PubMed:21982441, PubMed:22228831, PubMed:9242410). Binding of the LIG4-XRCC4 subcomplex to DNA ends is dependent on the assembly of the DNA-dependent protein kinase complex DNA-PK to these DNA ends (PubMed:10757784, PubMed:10854421). Promotes displacement of PNKP from processed strand break termini (PubMed:20852255, PubMed:28453785)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0032807 | DNA ligase IV complex |
| Cellular Component | GO:0005958 | DNA-dependent protein kinase-DNA ligase 4 complex |
| Cellular Component | GO:0070419 | nonhomologous end joining complex |
| Cellular Component | GO:0005654 | nucleoplasm |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0035861 | site of double-strand break |
| Molecular Function | GO:0003677 | DNA binding |
| Molecular Function | GO:0019899 | enzyme binding |
| Molecular Function | GO:0070975 | FHA domain binding |
| Molecular Function | GO:0042802 | identical protein binding |
| Molecular Function | GO:0030674 | protein-macromolecule adaptor activity |
| Biological Process | GO:0006284 | base-excision repair |
| Biological Process | GO:1990683 | DNA double-strand break attachment to nuclear envelope |
| Biological Process | GO:0006302 | double-strand break repair |
| Biological Process | GO:0006303 | double-strand break repair via nonhomologous end joining |
| Biological Process | GO:0033152 | immunoglobulin V(D)J recombination |
| Biological Process | GO:0051351 | positive regulation of ligase activity |
| Biological Process | GO:1990166 | protein localization to site of double-strand break |
| Biological Process | GO:0010165 | response to X-ray |
Reference
[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[2] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.
[3] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.
[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.
[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.