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Overview

Uniprot ID	Q6NS38
Protein Name	DNA oxidative demethylase ALKBH2
Gene Name	ALKBH2
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
261	RKILLTKK*******
7	*MDRFLVKGAQGGLL

Function

Dioxygenase that repairs alkylated nucleic acid bases by direct reversal oxidative dealkylation. Can process both double-stranded (ds) and single-stranded (ss) DNA substrates, with a strong preference for dsDNA (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:20714506, PubMed:23972994, PubMed:25797601). Uses molecular oxygen, 2-oxoglutarate and iron as cofactors to oxidize the alkyl groups that are subsequently released as aldehydes, regenerating the undamaged bases. Probes the base pair stability, locates a weakened base pair and flips the damaged base to accommodate the lesion in its active site for efficient catalysis (PubMed:18432238, PubMed:22659876). Repairs monoalkylated bases, specifically N1-methyladenine and N3-methylcytosine, as well as higher order alkyl adducts such as bases modified with exocyclic bridged adducts known as etheno adducts including 1,N6-ethenoadenine, 3,N4-ethenocytosine and 1,N2-ethenoguanine (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:20714506, PubMed:23972994, PubMed:25797601, PubMed:26408825). Acts as a gatekeeper of genomic integrity under alkylation stress. Efficiently repairs alkylated lesions in ribosomal DNA (rDNA). These lesions can cause ss- and dsDNA strand breaks that severely impair rDNA transcription (PubMed:23972994). In a response mechanism to DNA damage, associates with PCNA at replication forks to repair alkylated adducts prior to replication (PubMed:19736315, PubMed:26408825)

Protein Sequence

10 MDRFLVKGAQ 20 GGLLRKQEEQ 30 EPTGEEPAVL 40 GGDKESTRKR 50 PRREAPGNGG 60 HSAGPSWRHI 70 RAEGLDCSYT 80 VLFGKAEADE 90 IFQELEKEVE 100 YFTGALARVQ 110 VFGKWHSVPR 120 KQATYGDAGL 130 TYTFSGLTLS 140 PKPWIPVLER 150 IRDHVSGVTG 160 QTFNFVLINR 170 YKDGCDHIGE 180 HRDDERELAP 190 GSPIASVSFG 200 ACRDFVFRHK 210 DSRGKSPSRR 220 VAVVRLPLAH 230 GSLLMMNHPT 240 NTHWYHSLPV 250 RKKVLAPRVN 260 LTFRKILLTK K

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005730	nucleolus
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Molecular Function	GO:0035516	broad specificity oxidative DNA demethylase activity
Molecular Function	GO:0051747	cytosine C-5 DNA demethylase activity
Molecular Function	GO:0008198	ferrous iron binding
Molecular Function	GO:0000182	rDNA binding
Biological Process	GO:0006307	DNA alkylation repair

Reference

[1] 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.

[2] 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.

[3] 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.