General Information of Drug Therapeutic Target (DTT) (ID: TTCB9KW)

DTT Name X-ray repair cross-complementing 5 (Ku80)
Synonyms
X-ray repair cross-complementing protein 5; X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining); Thyroid-lupus autoantigen; TLAA; Nuclear factor IV; Lupus Ku autoantigen protein p86; Ku86; G22P2; DNA repair protein XRCC5; CTCBF; CTC85; CTC box-binding factor 85 kDa subunit; ATP-dependent DNA helicase II 80 kDa subunit; ATP-dependent DNA helicase 2 subunit 2; 86 kDa subunit of Ku antigen
Gene Name XRCC5
DTT Type
Literature-reported target
[1]
BioChemical Class
Acid anhydride hydrolase
UniProt ID
XRCC5_HUMAN
TTD ID
T53562
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 3.6.4.-
Sequence
MVRSGNKAAVVLCMDVGFTMSNSIPGIESPFEQAKKVITMFVQRQVFAENKDEIALVLFG
TDGTDNPLSGGDQYQNITVHRHLMLPDFDLLEDIESKIQPGSQQADFLDALIVSMDVIQH
ETIGKKFEKRHIEIFTDLSSRFSKSQLDIIIHSLKKCDISLQFFLPFSLGKEDGSGDRGD
GPFRLGGHGPSFPLKGITEQQKEGLEIVKMVMISLEGEDGLDEIYSFSESLRKLCVFKKI
ERHSIHWPCRLTIGSNLSIRIAAYKSILQERVKKTWTVVDAKTLKKEDIQKETVYCLNDD
DETEVLKEDIIQGFRYGSDIVPFSKVDEEQMKYKSEGKCFSVLGFCKSSQVQRRFFMGNQ
VLKVFAARDDEAAAVALSSLIHALDDLDMVAIVRYAYDKRANPQVGVAFPHIKHNYECLV
YVQLPFMEDLRQYMFSSLKNSKKYAPTEAQLNAVDALIDSMSLAKKDEKTDTLEDLFPTT
KIPNPRFQRLFQCLLHRALHPREPLPPIQQHIWNMLNPPAEVTTKSQIPLSKIKTLFPLI
EAKKKDQVTAQEIFQDNHEDGPTAKKLKTEQGGAHFSVSSLAEGSVTSVGSVNPAENFRV
LVKQKKASFEEASNQLINHIEQFLDTNETPYFMKSIDCIRAFREEAIKFSEEQRFNNFLK
ALQEKVEIKQLNHFWEIVVQDGITLITKEEASGSSVTAEEAKKFLAPKDKPSGDTAAVFE
EGGDVDDLLDMI
Function
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. Binding to DNA may be mediated by XRCC6. Involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination. The XRCC5/6 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 XRCC5/6 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. In association with NAA15, the XRCC5/6 dimer binds to the osteocalcin promoter and activates osteocalcin expression. The XRCC5/6 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 XRCC5/6 dimer together with APEX1 acts as a negative regulator of transcription. 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. Single-stranded DNA-dependent ATP-dependent helicase.
KEGG Pathway
Non-homologous end-joining (hsa03450 )
Reactome Pathway
Cytosolic sensors of pathogen-associated DNA (R-HSA-1834949 )
IRF3-mediated induction of type I IFN (R-HSA-3270619 )
Nonhomologous End-Joining (NHEJ) (R-HSA-5693571 )
Neutrophil degranulation (R-HSA-6798695 )
2-LTR circle formation (R-HSA-164843 )

References

1 XRCC5 cooperates with p300 to promote cyclooxygenase-2 expression and tumor growth in colon cancers. PLoS One. 2017 Oct 19;12(10):e0186900.