Search Results

Overview

Uniprot IDP13010
Protein NameDNA repair protein Ku80
Gene NameXRCC5
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
155 DIIIHSLKKCDISLQ
265 SIRIAAYKSILQERV
274 ILQERVKKTWTVVDA
332 KVDEEQMKYKSEGKC
439 QYMFSSLKNSKKYAP
532 KSQIPLSKIKTLFPL
534 QIPLSKIKTLFPLIE
543 LFPLIEAKKKDQVTA
544 FPLIEAKKKDQVTAQ
545 PLIEAKKKDQVTAQE
565 HEDGPTAKKLKTEQG
566 EDGPTAKKLKTEQGG
568 GPTAKKLKTEQGGAH
648 AFREEAIKFSEEQRF
702 SVTAEEAKKFLAPKD
703 VTAEEAKKFLAPKDK

Function

DNA-binding protein critical for the DNA damage response, specifically in repairing double-strand breaks (DSBs) via the classical non-homologous end joining (NHEJ) pathway. It forms a heterodimer with XRCC6 (Ku70), creating the Ku70:Ku80 heterodimer (Ku complex), which serves as a DNA end-binding complex. It primarily binds DSBs and recruits essential repair factors, assembling the core long-range NHEJ complex to facilitate the alignment and ligation of broken DNA ends (PubMed:11493912, PubMed:33854234, PubMed:34352203). This pathway ensures the rapid repair of cytotoxic and mutagenic DSBs and contributes to the generation of diversity in T-cell receptors and antibodies through mechanisms such as V(D)J recombination (PubMed:9742108). Likely acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), catalyzing the beta-elimination of the 5'-deoxyribose-5-phosphate at abasic sites near DSBs. This activity cleans the termini of abasic sites, a common form of nucleotide damage, preparing broken ends for ligation (PubMed:20383123). It may also possess 3'-5' DNA helicase activity, although this has not been confirmed in vivo, and its physiological significance remains unclear (PubMed:7957065). Beyond DNA repair, the protein contributes to telomere maintenance (PubMed:29490055). It is also implicated in transcriptional regulation, acting as a cofactor for various transcription factors (PubMed:12145306, PubMed:8621488). It 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 (PubMed:28712728). Can also bind RNAs and recruits PRKDC to a wide range of cellular RNAs, including the U3 small nucleolar RNA, playing a role in the biogenesis of ribosomal RNAs (PubMed:32103174)

Protein Sequence

10 MVRSGNKAAV 20 VLCMDVGFTM 30 SNSIPGIESP 40 FEQAKKVITM 50 FVQRQVFAEN 60 KDEIALVLFG 70 TDGTDNPLSG 80 GDQYQNITVH 90 RHLMLPDFDL 100 LEDIESKIQP 110 GSQQADFLDA 120 LIVSMDVIQH 130 ETIGKKFEKR 140 HIEIFTDLSS 150 RFSKSQLDII 160 IHSLKKCDIS 170 LQFFLPFSLG 180 KEDGSGDRGD 190 GPFRLGGHGP 200 SFPLKGITEQ 210 QKEGLEIVKM 220 VMISLEGEDG 230 LDEIYSFSES 240 LRKLCVFKKI 250 ERHSIHWPCR 260 LTIGSNLSIR 270 IAAYKSILQE 280 RVKKTWTVVD 290 AKTLKKEDIQ 300 KETVYCLNDD 310 DETEVLKEDI 320 IQGFRYGSDI 330 VPFSKVDEEQ 340 MKYKSEGKCF 350 SVLGFCKSSQ 360 VQRRFFMGNQ 370 VLKVFAARDD 380 EAAAVALSSL 390 IHALDDLDMV 400 AIVRYAYDKR 410 ANPQVGVAFP 420 HIKHNYECLV 430 YVQLPFMEDL 440 RQYMFSSLKN 450 SKKYAPTEAQ 460 LNAVDALIDS 470 MSLAKKDEKT 480 DTLEDLFPTT 490 KIPNPRFQRL 500 FQCLLHRALH 510 PREPLPPIQQ 520 HIWNMLNPPA 530 EVTTKSQIPL 540 SKIKTLFPLI 550 EAKKKDQVTA 560 QEIFQDNHED 570 GPTAKKLKTE 580 QGGAHFSVSS 590 LAEGSVTSVG 600 SVNPAENFRV 610 LVKQKKASFE 620 EASNQLINHI 630 EQFLDTNETP 640 YFMKSIDCIR 650 AFREEAIKFS 660 EEQRFNNFLK 670 ALQEKVEIKQ 680 LNHFWEIVVQ 690 DGITLITKEE 700 ASGSSVTAEE 710 AKKFLAPKDK 720 PSGDTAAVFE 730 EGGDVDDLLD MI

Gene Ontology

Classification GO ID Description
Biological Process GO:0006303 double-strand break repair via nonhomologous end joining
Cellular Component GO:0000781 chromosome, telomeric region
Cellular Component GO:0005829 cytosol
Cellular Component GO:0005958 DNA-dependent protein kinase-DNA ligase 4 complex
Cellular Component GO:0005576 extracellular region
Cellular Component GO:0043564 Ku70:Ku80 complex
Cellular Component GO:0016020 membrane
Cellular Component GO:0070419 nonhomologous end joining complex
Cellular Component GO:0000783 nuclear telomere cap complex
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0032991 protein-containing complex
Cellular Component GO:0032993 protein-DNA complex
Cellular Component GO:1990904 ribonucleoprotein complex
Cellular Component GO:0034774 secretory granule lumen
Cellular Component GO:0090734 site of DNA damage
Cellular Component GO:0032040 small-subunit processome
Molecular Function GO:0043138 3'-5' DNA helicase activity
Molecular Function GO:0005524 ATP binding
Molecular Function GO:0016887 ATP hydrolysis activity
Molecular Function GO:0008094 ATP-dependent activity, acting on DNA
Molecular Function GO:0140078 class I DNA-(apurinic or apyrimidinic site) endonuclease activity
Molecular Function GO:0003684 damaged DNA binding
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0045027 DNA end binding
Molecular Function GO:0003678 DNA helicase activity
Molecular Function GO:0003690 double-stranded DNA binding
Molecular Function GO:0008047 enzyme activator activity
Molecular Function GO:0044877 protein-containing complex binding
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0042162 telomeric DNA binding
Molecular Function GO:0000976 transcription cis-regulatory region binding
Molecular Function GO:0034511 U3 snoRNA binding
Molecular Function GO:0031625 ubiquitin protein ligase binding
Biological Process GO:0002218 activation of innate immune response
Biological Process GO:0071480 cellular response to gamma radiation
Biological Process GO:0006974 DNA damage response
Biological Process GO:0006310 DNA recombination
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0006302 double-strand break repair
Biological Process GO:0045087 innate immune response
Biological Process GO:0045892 negative regulation of DNA-templated transcription
Biological Process GO:1904430 negative regulation of t-circle formation
Biological Process GO:0070198 protein localization to chromosome, telomeric region
Biological Process GO:0000725 recombinational repair
Biological Process GO:0048660 regulation of smooth muscle cell proliferation
Biological Process GO:0032204 regulation of telomere maintenance
Biological Process GO:0034462 small-subunit processome assembly
Biological Process GO:0000723 telomere maintenance
Biological Process GO:0007004 telomere maintenance via telomerase

Reference

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[3] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.

[4] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.

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[7] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.

[8] 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.

[9] 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.

[10] 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.