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XRCC4

The protein encoded by this gene functions together with DNA ligase IV and the DNA-dependent protein kinase in the repair of DNA double-strand breaks. This protein plays a role in both non-homologous end joining and the completion of V(D)J recombination. Mutations in this gene can cause short stature, microcephaly, and endocrine dysfunction (SSMED). Alternate transcript variants such as NM_022406 are unlikely to be expressed in some individuals due to a polymorphism (rs1805377) in the last splice acceptor site.
Protein class

Cancer-related genes, Disease related genes, Human disease related genes

Predicted location

Intracellular

Single cell type specificity

Cell type enhanced (Oligodendrocytes, Pancreatic endocrine cells)

Immune cell specificity

Low immune cell specificity

Cell line specificity

Cell line enhanced (RH-30)

Interaction

[DNA repair protein XRCC4]: Homodimer and homotetramer in solution (PubMed:25574025, PubMed:25670504, PubMed:25941166, PubMed:31548606, PubMed:11080143). Interacts with NHEJ1/XLF; the interaction is direct and is mediated via a head-to-head interaction between N-terminal head regions (PubMed:16439205, PubMed:18158905, PubMed:20558749, PubMed:22228831, PubMed:26100018, PubMed:27437582, PubMed:21936820, PubMed:21775435, PubMed:22287571, PubMed:21768349). Interacts with LIG4; the LIG4-XRCC4 subcomplex has a 1:2 stoichiometry and XRCC4 is required for LIG4 stability (PubMed:9259561, PubMed:12517771, PubMed:17290226, PubMed:21982441, PubMed:24984242, PubMed:25934149, PubMed:11702069, PubMed:19332554, PubMed:9242410). Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (PubMed:10757784, PubMed:10854421, PubMed:17124166, PubMed:12547193, PubMed:26774286, PubMed:33854234). Additional component of the NHEJ complex includes PAXX (PubMed:16439205). Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (PubMed:33854234). Interacts with PRKDC; the interaction is direct (PubMed:12509254). Interacts with XRCC6/Ku70; the interaction is direct (PubMed:17124166). Interacts with APTX and APLF (PubMed:15380105, PubMed:17396150, PubMed:17353262, PubMed:18077224). Forms a heterotetramer with IFFO1; the interaction involves LIG4-free XRCC4 and leads to the relocalization of IFFO1 to the sites of DNA damage (PubMed:31548606). Interacts with PNKP; mainly interacts with PNKP when phosphorylated at Thr-233, but is also able to interact at much lower level with PNKP when not unphosphorylated (PubMed:15385968, PubMed:20852255, PubMed:28453785). Interacts with POLL (DNA polymerase lambda) (PubMed:30250067). [Protein XRCC4, C-terminus]: Interacts with XKR4; interacts with the processed form of XKR4, which is cleaved by caspase.

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