Search Results

Overview

Uniprot ID	P12956
Protein Name	DNA repair protein Ku70
Gene Name	XRCC6
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
114	ELDNPGAKRILELDQ
123	ILELDQFKGQQGQKR
287	ALKPPPIKLYRETNE
297	RETNEPVKTKTRTFN
317	LLLPSDTKRSQIYGS
357	FKPLVLLKKHHYLRP
445	PFADDKRKMPFTEKI
451	RKMPFTEKIMATPEQ
461	ATPEQVGKMKAIVEK
463	PEQVGKMKAIVEKLR
468	KMKAIVEKLRFTYRS
516	PKVEAMNKRLGSLVD
539	PDYNPEGKVTKRKHD
544	EGKVTKRKHDNEGSG
553	DNEGSGSKRPKVEYS
556	GSGSKRPKVEYSEEE
570	ELKTHISKGTLGKFT
591	ACRAYGLKSGLKKQE
596	GLKSGLKKQELLEAL

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 XRCC5 (Ku80), 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:20493174, PubMed:33854234, PubMed:34352203, PubMed:9742108). 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). Additionally, it negatively regulates apoptosis by interacting with BAX, sequestering it from the mitochondria, and may possess deubiquitination activity targeting BAX (PubMed:15023334, PubMed:18362350, PubMed:35545041)

Protein Sequence

10 MSGWESYYKT 20 EGDEEAEEEQ 30 EENLEASGDY 40 KYSGRDSLIF 50 LVDASKAMFE 60 SQSEDELTPF 70 DMSIQCIQSV 80 YISKIISSDR 90 DLLAVVFYGT 100 EKDKNSVNFK 110 NIYVLQELDN 120 PGAKRILELD 130 QFKGQQGQKR 140 FQDMMGHGSD 150 YSLSEVLWVC 160 ANLFSDVQFK 170 MSHKRIMLFT 180 NEDNPHGNDS 190 AKASRARTKA 200 GDLRDTGIFL 210 DLMHLKKPGG 220 FDISLFYRDI 230 ISIAEDEDLR 240 VHFEESSKLE 250 DLLRKVRAKE 260 TRKRALSRLK 270 LKLNKDIVIS 280 VGIYNLVQKA 290 LKPPPIKLYR 300 ETNEPVKTKT 310 RTFNTSTGGL 320 LLPSDTKRSQ 330 IYGSRQIILE 340 KEETEELKRF 350 DDPGLMLMGF 360 KPLVLLKKHH 370 YLRPSLFVYP 380 EESLVIGSST 390 LFSALLIKCL 400 EKEVAALCRY 410 TPRRNIPPYF 420 VALVPQEEEL 430 DDQKIQVTPP 440 GFQLVFLPFA 450 DDKRKMPFTE 460 KIMATPEQVG 470 KMKAIVEKLR 480 FTYRSDSFEN 490 PVLQQHFRNL 500 EALALDLMEP 510 EQAVDLTLPK 520 VEAMNKRLGS 530 LVDEFKELVY 540 PPDYNPEGKV 550 TKRKHDNEGS 560 GSKRPKVEYS 570 EEELKTHISK 580 GTLGKFTVPM 590 LKEACRAYGL 600 KSGLKKQELL EALTKHFQD

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0000781	chromosome, telomeric region
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:0030332	cyclin binding
Molecular Function	GO:0003684	damaged DNA binding
Molecular Function	GO:0003677	DNA binding
Molecular Function	GO:0003678	DNA helicase activity
Molecular Function	GO:0044877	protein-containing complex binding
Molecular Function	GO:0003723	RNA binding
Molecular Function	GO:0097110	scaffold protein binding
Molecular Function	GO:0042162	telomeric DNA binding
Molecular Function	GO:0000976	transcription cis-regulatory region binding
Biological Process	GO:0002218	activation of innate immune response
Biological Process	GO:0071475	cellular hyperosmotic salinity response
Biological Process	GO:0071480	cellular response to gamma radiation
Biological Process	GO:0071481	cellular response to X-ray
Biological Process	GO:0006351	DNA-templated transcription
Biological Process	GO:0097680	double-strand break repair via classical nonhomologous end joining
Biological Process	GO:0006303	double-strand break repair via nonhomologous end joining
Biological Process	GO:0045087	innate immune response
Biological Process	GO:0045892	negative regulation of DNA-templated transcription
Biological Process	GO:0045893	positive regulation of DNA-templated transcription
Biological Process	GO:0045621	positive regulation of lymphocyte differentiation
Biological Process	GO:0045944	positive regulation of transcription by RNA polymerase II
Biological Process	GO:0000725	recombinational repair
Biological Process	GO:0048660	regulation of smooth muscle cell proliferation
Biological Process	GO:0000723	telomere maintenance
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:1904813	ficolin-1-rich granule lumen
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:0034774	secretory granule lumen
Cellular Component	GO:0005667	transcription regulator complex
Molecular Function	GO:0043138	3'-5' DNA helicase activity
Molecular Function	GO:0051575	5'-deoxyribose-5-phosphate lyase activity
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0016887	ATP hydrolysis activity

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] 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.

[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[4] 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.

[5] 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.

[6] 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.

[7] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.

[8] 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.

[9] 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.

[10] 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.

[11] 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.