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Overview

Uniprot ID	P49916
Protein Name	DNA ligase 3
Gene Name	LIG3
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
114	KCKEKIVKGVCRIGK
195	AAGTPKKKAVVQAKL
201	KKAVVQAKLTTTGQV
225	VTSTNPRKFSGFSAK
253	KRSLSSSKCDPRHKD
911	VGEKLATKSSPVKVG
922	VKVGEKRKAADETLC

Function

Isoform 3 functions as a heterodimer with DNA-repair protein XRCC1 in the nucleus and can correct defective DNA strand-break repair and sister chromatid exchange following treatment with ionizing radiation and alkylating agents. Isoform 1 is targeted to mitochondria, where it functions as a DNA ligase in mitochondrial base-excision DNA repair (PubMed:10207110, PubMed:24674627)

Protein Sequence

10 MSLAFKIFFP 20 QTLRALSRKE 30 LCLFRKHHWR 40 DVRQFSQWSE 50 TDLLHGHPLF 60 LRRKPVLSFQ 70 GSHLRSRATY 80 LVFLPGLHVG 90 LCSGPCEMAE 100 QRFCVDYAKR 110 GTAGCKKCKE 120 KIVKGVCRIG 130 KVVPNPFSES 140 GGDMKEWYHI 150 KCMFEKLERA 160 RATTKKIEDL 170 TELEGWEELE 180 DNEKEQITQH 190 IADLSSKAAG 200 TPKKKAVVQA 210 KLTTTGQVTS 220 PVKGASFVTS 230 TNPRKFSGFS 240 AKPNNSGEAP 250 SSPTPKRSLS 260 SSKCDPRHKD 270 CLLREFRKLC 280 AMVADNPSYN 290 TKTQIIQDFL 300 RKGSAGDGFH 310 GDVYLTVKLL 320 LPGVIKTVYN 330 LNDKQIVKLF 340 SRIFNCNPDD 350 MARDLEQGDV 360 SETIRVFFEQ 370 SKSFPPAAKS 380 LLTIQEVDEF 390 LLRLSKLTKE 400 DEQQQALQDI 410 ASRCTANDLK 420 CIIRLIKHDL 430 KMNSGAKHVL 440 DALDPNAYEA 450 FKASRNLQDV 460 VERVLHNAQE 470 VEKEPGQRRA 480 LSVQASLMTP 490 VQPMLAEACK 500 SVEYAMKKCP 510 NGMFSEIKYD 520 GERVQVHKNG 530 DHFSYFSRSL 540 KPVLPHKVAH 550 FKDYIPQAFP 560 GGHSMILDSE 570 VLLIDNKTGK 580 PLPFGTLGVH 590 KKAAFQDANV 600 CLFVFDCIYF 610 NDVSLMDRPL 620 CERRKFLHDN 630 MVEIPNRIMF 640 SEMKRVTKAL 650 DLADMITRVI 660 QEGLEGLVLK 670 DVKGTYEPGK 680 RHWLKVKKDY 690 LNEGAMADTA 700 DLVVLGAFYG 710 QGSKGGMMSI 720 FLMGCYDPGS 730 QKWCTVTKCA 740 GGHDDATLAR 750 LQNELDMVKI 760 SKDPSKIPSW 770 LKVNKIYYPD 780 FIVPDPKKAA 790 VWEITGAEFS 800 KSEAHTADGI 810 SIRFPRCTRI 820 RDDKDWKSAT 830 NLPQLKELYQ 840 LSKEKADFTV 850 VAGDEGSSTT 860 GGSSEENKGP 870 SGSAVSRKAP 880 SKPSASTKKA 890 EGKLSNSNSK 900 DGNMQTAKPS 910 AMKVGEKLAT 920 KSSPVKVGEK 930 RKAADETLCQ 940 TKVLLDIFTG 950 VRLYLPPSTP 960 DFSRLRRYFV 970 AFDGDLVQEF 980 DMTSATHVLG 990 SRDKNPAAQQ 1000 VSPEWIWACI RKRRLVAPC

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0070421	DNA ligase III-XRCC1 complex
Cellular Component	GO:0005759	mitochondrial matrix
Cellular Component	GO:0005739	mitochondrion
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0090734	site of DNA damage
Molecular Function	GO:0005524	ATP binding
Molecular Function	GO:0003677	DNA binding
Molecular Function	GO:0003910	DNA ligase (ATP) activity
Molecular Function	GO:0003909	DNA ligase activity
Molecular Function	GO:0008270	zinc ion binding
Biological Process	GO:0006284	base-excision repair
Biological Process	GO:0006287	base-excision repair, gap-filling
Biological Process	GO:0051301	cell division
Biological Process	GO:0071897	DNA biosynthetic process
Biological Process	GO:0006302	double-strand break repair
Biological Process	GO:0097681	double-strand break repair via alternative nonhomologous end joining
Biological Process	GO:0000724	double-strand break repair via homologous recombination
Biological Process	GO:0006273	lagging strand elongation
Biological Process	GO:0043504	mitochondrial DNA repair
Biological Process	GO:0007005	mitochondrion organization
Biological Process	GO:0090298	negative regulation of mitochondrial DNA replication
Biological Process	GO:0006282	regulation of DNA repair

Reference

[1] 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.

[2] 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.

[3] 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.

[4] 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.

[5] Chao L, Xu Y, Yang Y, Ao X, Liang J. Identification of lactylation-related biomarkers for diagnosis, prognosis, and treatment responsiveness in triple-negative breast cancer.. World J Surg Oncol 24(1):77. 2026 Jan 22. PMID: 41566505.

[6] 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.