Protein: X-ray repair cross-complementing protein 5 (EC 3.6.4.-) (86 kDa subunit of Ku antigen) (ATP-dependent DNA helicase 2 subunit 2) (ATP-dependent DNA helicase II 80 kDa subunit) (CTC box-binding factor 85 kDa subunit) (CTC85) (CTCBF) (DNA repair protein XRCC5) (Ku80) (Ku86) (Lupus Ku autoantigen protein p86) (Nuclear factor IV) (Thyroid-lupus autoantigen) (TLAA) (X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining)) (P13010)
Organism: Homo sapiens (Human)
Function: Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA. Required for double-strand break repair and V(D)J recombination. Also has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection. Binding to DNA may be mediated by XRCC6. The XRCC5-XRRC6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. The XRCC5-XRRC6 dimer probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. XRCC5 probably acts as the catalytic subunit of 5'-dRP activity, and allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription. In association with NAA15, the XRCC5-XRRC6 dimer binds to the osteocalcin promoter and activates osteocalcin expression. As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome. Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome. Plays a role in the regulation of DNA virus-mediated innate immune response by assembling into the HDP-RNP complex, a complex that serves as a platform for IRF3 phosphorylation and subsequent innate immune response activation through the cGAS-STING pathway.
Subcellular location: Nucleus {ECO:0000269|PubMed:15023334, ECO:0000269|PubMed:22442688, ECO:0000269|PubMed:32103174}. Nucleus, nucleolus {ECO:0000269|PubMed:22002106, ECO:0000269|PubMed:32103174}. Chromosome {ECO:0000269|PubMed:22442688}.
InterPro domains:
- IPR002035: von Willebrand factor, type A (domain) [7-249]
- IPR016194: SPOC-like, C-terminal domain superfamily (homologous_superfamily) [243-545]
- IPR006164: Ku70/Ku80, DNA-binding domain (domain) [253-453]
- IPR036494: Ku, C-terminal domain superfamily (homologous_superfamily) [559-710]
- IPR005161: Ku70/Ku80, N-terminal alpha/beta (domain) [9-243]
- IPR024193: Ku80 (family) [1-708]
- IPR005160: Ku70/Ku80 C-terminal arm (domain) [477-568]
- IPR036465: von Willebrand factor A-like domain superfamily (homologous_superfamily) [1-242]
- IPR014893: Ku, C-terminal (domain) [593-705]
Sequence:
MVRSGNKAAVVLCMDVGFTMSNSIPGIESPFEQAKKVITMFVQRQVFAENKDEIALVLFGTDGTDNPLSGGDQYQNITVHRHLMLPDFDLLEDIESKIQPGSQQADFLDALIVSMDVIQHETIGKKFEKRHIEIFTDLSSRFSKSQLDIIIHSLKKCDISLQFFLPFSLGKEDGSGDRGDGPFRLGGHGPSFPLKGITEQQKEGLEIVKMVMISLEGEDGLDEIYSFSESLRKLCVFKKIERHSIHWPCRLTIGSNLSIRIAAYKSILQERVKKTWTVVDAKTLKKEDIQKETVYCLNDDDETEVLKEDIIQGFRYGSDIVPFSKVDEEQMKYKSEGKCFSVLGFCKSSQVQRRFFMGNQVLKVFAARDDEAAAVALSSLIHALDDLDMVAIVRYAYDKRANPQVGVAFPHIKHNYECLVYVQLPFMEDLRQYMFSSLKNSKKYAPTEAQLNAVDALIDSMSLAKKDEKTDTLEDLFPTTKIPNPRFQRLFQCLLHRALHPREPLPPIQQHIWNMLNPPAEVTTKSQIPLSKIKTLFPLIEAKKKDQVTAQEIFQDNHEDGPTAKKLKTEQGGAHFSVSSLAEGSVTSVGSVNPAENFRVLVKQKKASFEEASNQLINHIEQFLDTNETPYFMKSIDCIRAFREEAIKFSEEQRFNNFLKALQEKVEIKQLNHFWEIVVQDGITLITKEEASGSSVTAEEAKKFLAPKDKPSGDTAAVFEEGGDVDDLLDMI
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:1901363 (heterocyclic compound binding), GO:0016787 (hydrolase activity), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0016788 (hydrolase activity, acting on ester bonds), GO:0003677 (DNA binding), GO:0003723 (RNA binding), GO:0003690 (double-stranded DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0003697 (single-stranded DNA binding), GO:1990837 (sequence-specific double-stranded DNA binding), GO:0098847 (sequence-specific single stranded DNA binding), GO:0042162 (telomeric DNA binding), GO:0043047 (single-stranded telomeric DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0051179 (localization), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0051641 (cellular localization), GO:0044237 (cellular metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0051716 (cellular response to stimulus), GO:0071840 (cellular component organization or biogenesis), GO:0006950 (response to stress), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0033036 (macromolecule localization), GO:1901360 (organic cyclic compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0033554 (cellular response to stress), GO:0070727 (cellular macromolecule localization), GO:0016043 (cellular component organization), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0090304 (nucleic acid metabolic process), GO:0006974 (cellular response to DNA damage stimulus), GO:0006259 (DNA metabolic process), GO:0008104 (protein localization), GO:0006996 (organelle organization), GO:0000723 (telomere maintenance), GO:0006281 (DNA repair), GO:0051276 (chromosome organization), GO:0032200 (telomere organization), GO:0006302 (double-strand break repair), GO:0006303 (double-strand break repair via nonhomologous end joining)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0000785 (chromatin), GO:0005829 (cytosol), GO:0140513 (nuclear protein-containing complex), GO:0005737 (cytoplasm), GO:0005667 (transcription regulator complex), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0090575 (RNA polymerase II transcription regulator complex), GO:0043228 (non-membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0031981 (nuclear lumen), GO:0005694 (chromosome), GO:0005634 (nucleus)