Affinage

NEIL2

Endonuclease 8-like 2 · UniProt Q969S2

Length
332 aa
Mass
36.8 kDa
Annotated
2026-06-10
55 papers in source corpus 23 papers cited in narrative 23 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NEIL2 is a bifunctional DNA glycosylase/AP lyase of the Fpg/Nei family that initiates base excision repair (BER) of oxidized base lesions, with a distinctive preference for excising damage from DNA bubble and single-stranded substrates rather than duplex DNA, implicating it in repair coupled to transcription and replication (PMID:14522990, PMID:16793361). Its substrate range spans oxidized cytosines, hydantoin lesions (Gh/Ia and Sp), 5-hydroxyuracil, formamidopyrimidines, and abasic sites, with biochemical and structural analysis revealing a strong bias toward its lyase activity at abasic sites (PMID:15533836, PMID:37971311). Catalysis and DNA binding depend on a structural C-terminal CHCC zinc finger, and crystallographic and solution studies show NEIL2 is conformationally dynamic, shifting from an 'open' unliganded state to a 'closed' state that positions the enzyme on DNA (PMID:15339932, PMID:32846144, PMID:37971311). NEIL2 organizes an APE1-independent repair complex: after strand cleavage it requires polynucleotide kinase (PNK) to process the 3'-phosphate, and its N-terminal segment mediates stable interactions with Pol beta, Lig IIIalpha, and XRCC1 to complete repair (PMID:16982218). This complex is stimulated by YB-1, which translocates to the nucleus and activates NEIL2 under oxidative stress, and by Cockayne syndrome B protein (CSB), which links NEIL2 to transcription-coupled repair (PMID:17686777, PMID:24406253). Consistent with a transcription-associated role, NEIL2 co-occupies transcribed genes with RNA polymerase II, CSB, and TFIIH, and Neil2-null mice accumulate oxidative damage preferentially in transcribed sequences and show telomere loss and genomic instability (PMID:26245904). NEIL2 also localizes to mitochondria, associating with mitochondrial genes and Pol gamma to protect the mitochondrial genome, loss of which triggers TP53-dependent apoptosis during neural crest development (PMID:22130663, PMID:31566562). Activity is tuned by post-translational modification, including inactivating p300-mediated acetylation of Lys49 and PKC-mediated phosphorylation that suppresses repair (PMID:15175427, PMID:36829914). Beyond repair, NEIL2 exerts non-canonical functions: it directly binds the Rel homology region of RelA (p65) to block NF-κB promoter binding and suppress proinflammatory gene expression, and it binds the SARS-CoV-2 5'-UTR to block viral protein synthesis (PMID:33932404, PMID:38071370).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2003 High

    Established that NEIL2 has a substrate preference distinct from other oxidized-base glycosylases, defining its niche in repair of non-duplex DNA structures arising during transcription and replication.

    Evidence In vitro glycosylase and affinity assays comparing bubble, single-stranded, and duplex substrates

    PMID:14522990

    Open questions at the time
    • Did not establish which cellular processes generate the bubble substrates NEIL2 acts on
    • In vivo relevance of the bubble preference not yet demonstrated
  2. 2004 High

    Identified acetylation by p300 at Lys49 as a reversible switch that inactivates NEIL2, providing a mechanism for regulating repair activity in vivo.

    Evidence Co-IP, in vitro p300 acetylation, site-directed mutagenesis with activity readout

    PMID:15175427

    Open questions at the time
    • Deacetylase counteracting p300 not identified in this study
    • Physiological stimuli controlling Lys49 acetylation not defined
  3. 2004 High

    Defined the C-terminal CHCC zinc finger as essential for DNA binding, structural integrity, and catalysis, explaining the structural basis of NEIL2 activity.

    Evidence Zinc quantification, mutagenesis, CD spectroscopy, molecular modeling, activity assays

    PMID:15339932

    Open questions at the time
    • High-resolution structure of the zinc finger not yet available at this stage
    • How the zinc finger contributes to bubble-substrate recognition unresolved
  4. 2006 High

    Showed NEIL2 nucleates an APE1-independent BER pathway requiring PNK for 3'-end processing and assembling Pol beta, Lig IIIalpha, and XRCC1 via its N-terminus, distinguishing its repair route from NEIL1.

    Evidence Reconstituted repair of 5-OHU, reciprocal Co-IP from human cells, domain mapping

    PMID:16982218

    Open questions at the time
    • Stoichiometry and assembly order of the complex not defined
    • Whether the complex is preformed or damage-induced not resolved
  5. 2007 High

    Identified YB-1 as a stress-responsive activator that translocates to the nucleus and stimulates NEIL2-initiated repair, linking oxidative stress signaling to NEIL2 function.

    Evidence MS of NEIL2 immunocomplex, Co-IP, in vitro stimulation, siRNA knockdown, fractionation under UVA

    PMID:17686777

    Open questions at the time
    • Mechanism by which YB-1 stimulates excision not defined
    • Signaling pathway driving YB-1 nuclear translocation not mapped
  6. 2011 High

    Demonstrated NEIL2 localizes to mitochondria and maintains the mitochondrial genome, extending its protective role beyond the nucleus.

    Evidence Mitochondrial fractionation, confocal co-localization, ChIP, PLA, siRNA with mtDNA damage readout

    PMID:22130663

    Open questions at the time
    • Mitochondrial import mechanism not defined
    • Mitochondrial BER partners of NEIL2 not fully enumerated
  7. 2012 High

    Linked NEIL2 loss to elevated spontaneous mutation and showed the R257L variant impairs repair by weakening interaction with Pol beta, connecting protein-protein contacts to genome stability.

    Evidence siRNA depletion with HPRT mutation assay, reconstituted BER, variant biochemistry

    PMID:22497777

    Open questions at the time
    • Frequency and clinical significance of R257L in populations not addressed
    • Structural basis of reduced Pol beta affinity not determined
  8. 2014 High

    Established CSB as a DNA-independent NEIL2 partner that stimulates its glycosylase activity and links NEIL2 to transcription-coupled repair.

    Evidence Reciprocal Co-IP, in vitro stimulation, immunofluorescence under stress and transcription stalling, knockdown

    PMID:24406253

    Open questions at the time
    • Mechanism of CSB-mediated stimulation not defined
    • Cytoplasmic co-localization significance unclear
  9. 2015 High

    Demonstrated in vivo that NEIL2 associates with the transcription machinery (RNA Pol II, CSB, TFIIH) and preferentially repairs transcribed genes, with loss causing telomere instability.

    Evidence Neil2-null mice, tissue Co-IP and ChIP, LA-QPCR for transcribed-region damage, telomere FISH

    PMID:26245904

    Open questions at the time
    • How NEIL2 is recruited specifically to active genes not resolved
    • Mechanism connecting NEIL2 loss to telomere attrition not defined
  10. 2019 High

    Showed NEIL-dependent mitochondrial genome protection is required for cranial neural crest development via prevention of TP53-driven apoptosis, independent of epigenetic demethylation.

    Evidence Xenopus and mouse ESC knockdown/KO, Tdg epistasis, TP53 inhibitor rescue, mtDNA damage assays

    PMID:31566562

    Open questions at the time
    • Relative contributions of NEIL1 vs NEIL2 not fully separated
    • Whether the requirement is mitochondrial-genome-specific in all lineages unclear
  11. 2020 High

    Provided the first mammalian NEIL2 crystal structure, revealing an unusual open conformation and conformational dynamics predicted to close on substrate.

    Evidence X-ray crystallography and SAXS, biochemical characterization of cancer variants

    PMID:32846144

    Open questions at the time
    • Liganded conformation not yet captured at this stage
    • Functional consequence of dynamics not directly tested
  12. 2021 High

    Defined a non-canonical anti-inflammatory function: NEIL2 directly binds the RelA Rel homology region to block NF-κB promoter binding and suppress proinflammatory genes.

    Evidence Co-IP, ChIP, EMSA, Neil2-null mice, intrapulmonary recombinant NEIL2 rescue

    PMID:33932404

    Open questions at the time
    • Whether this function requires catalytic activity not resolved
    • Structural detail of the NEIL2-RelA interface not determined
  13. 2021 Medium

    Characterized NEIL2 as intrinsically flexible with a disordered N-terminal insert, supporting its capacity for protein-protein interactions and non-canonical substrate engagement.

    Evidence HDX-MS, homology modeling, MD simulations

    PMID:34757057

    Open questions at the time
    • No functional validation of the structural dynamics
    • Single lab, computational support only
  14. 2021 Medium

    Positioned NEIL2 as a backup glycosylase for OGG1, with prolonged NEIL2 retention at damage when OGG1 is absent or inhibited.

    Evidence Live-cell recruitment imaging, chromatin fractionation, siRNA, OGG1 inhibition, 8-oxoG immunofluorescence

    PMID:33925271

    Open questions at the time
    • Single lab with limited mechanistic depth
    • Quantitative division of labor between OGG1 and NEIL2 not defined
  15. 2022 Medium

    Showed the zinc-finger beta-turn variant P304T markedly reduces NEIL2 catalytic efficiency and DNA affinity, linking specific residues to functional integrity.

    Evidence Steady-state kinetics and DNA binding of recombinant variants

    PMID:35216329

    Open questions at the time
    • Single in vitro study without cellular validation
    • Disease association of P304T not established
  16. 2023 High

    Captured the liganded NEIL2 structure, revealing a large interdomain shift on DNA binding and confirming a strong preference for lyase activity at abasic sites.

    Evidence X-ray crystallography of abasic-analog DNA complex at 2.08 Å, comparison with apo structure, biochemical assays

    PMID:37971311

    Open questions at the time
    • Structure with a bona fide oxidized-base substrate not solved
    • How the open→closed transition is triggered in bubble DNA unresolved
  17. 2023 Medium

    Identified PKC and CDK5 phosphorylation as modulators of NEIL2, with PKC reducing repair activity and stress-induced dephosphorylation restoring function.

    Evidence In vitro kinase assays, in-cell phosphorylation in SH-SY5Y, activity assays, oxidative stress monitoring

    PMID:36829914

    Open questions at the time
    • Phosphorylation sites not mapped
    • Phosphatase responsible for stress-induced dephosphorylation not identified
  18. 2023 Medium

    Revealed an antiviral role: NEIL2 binds the SARS-CoV-2 5'-UTR to block viral protein synthesis and reduce viral yield and inflammation.

    Evidence RNA binding assay, recombinant NEIL2 delivery, viral replication and proinflammatory gene readouts

    PMID:38071370

    Open questions at the time
    • Structural basis and sequence specificity of RNA binding not defined
    • Whether this reflects a general RNA-binding capacity unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How NEIL2's repair, transcription-coupling, anti-inflammatory, and antiviral functions are coordinated and selectively engaged in vivo remains unresolved.
  • No unified model integrating catalytic and non-canonical functions
  • Recruitment mechanism to active genes and to RelA/RNA targets not mechanistically connected
  • No human disease causation established despite multiple characterized variants

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140097 catalytic activity, acting on DNA 5 GO:0003677 DNA binding 3 GO:0016829 lyase activity 2 GO:0003723 RNA binding 1 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 2 GO:0005739 mitochondrion 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-73894 DNA Repair 5 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-168256 Immune System 2
Partners
EP300ERCC6LIG3PNKPPOLBRELAXRCC1YBX1
Complex memberships
NEIL2-PNK-Pol beta-Lig IIIalpha-XRCC1 BER complex

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 NEIL2 has a unique preference for excising oxidized base lesions from DNA bubble structures (single-stranded/bubble DNA), in contrast to NTH1 and OGG1 which are only active with duplex DNA. NEIL2 shows higher affinity for bubble structures of both damaged and undamaged DNA relative to duplex, suggesting preferential involvement in repair during transcription and/or replication. In vitro DNA glycosylase assays with bubble, single-stranded, and duplex DNA substrates containing oxidized bases; affinity binding studies The Journal of biological chemistry High 14522990
2004 The transcriptional coactivator p300 stably interacts with and acetylates NEIL2. Lys49 and Lys153 are the major acetylation sites. Acetylation of Lys49 (conserved among Nei orthologs), or its mutation to Arg, inactivates both base excision and AP lyase activities of NEIL2; acetylation of Lys153 has no effect. Reversible acetylation of Lys49 thus regulates NEIL2 repair activity in vivo. Co-immunoprecipitation, in vitro acetylation assay with p300, site-directed mutagenesis, in vivo and in vitro activity assays Nucleic acids research High 15175427
2004 NEIL2 contains a zinc finger motif with a CHCC (Cys-X2-His-X16-Cys-X2-Cys) motif near its C-terminus. Individual mutations of Cys-291, His-295, Cys-315, and Cys-318 inactivate the enzyme by abolishing DNA binding. H295A and C318S mutants lack bound zinc and show significant secondary structure changes. Arg-310, in the zinc-binding pocket, is critical for activity. The zinc finger motif is essential for NEIL2 structural integrity and enzyme activity. ICP mass spectrometry (zinc quantification), site-directed mutagenesis, CD spectra analysis, molecular modeling, in vitro activity assays The Journal of biological chemistry High 15339932
2005 NEIL1 and NEIL2 recognize and cleave DNA containing guanidinohydantoin (Gh)/iminoallantoin (Ia) and spiroiminodihydantoin (Sp) lesions (further oxidation products of 8-oxoguanine) via beta- and delta-elimination mechanism. NEIL2 shows little cleavage activity against Sp in duplex DNA but binds and recognizes it (shown by DNA trapping studies). Both enzymes excise Gh/Ia opposite all four natural bases in double-stranded DNA. In vitro DNA glycosylase cleavage assays with defined damaged substrates (single-stranded and duplex DNA), DNA trapping studies DNA repair High 15533836
2006 NEIL2-initiated repair of 5-hydroxyuracil (5-OHU) requires polynucleotide kinase (PNK) rather than APE1 to remove the 3'-phosphate terminus generated after strand cleavage. NEIL2 stably interacts with BER proteins DNA polymerase beta (Pol beta), DNA ligase IIIalpha (Lig IIIalpha), and XRCC1 (but not APE1). The essential N-terminal segment of NEIL2 mediates these interactions (unlike NEIL1 which uses its C-terminal region). A complex containing NEIL2, PNK, Pol beta, Lig IIIalpha, and XRCC1 can be isolated from human cells and is competent for repair of 5-OHU in plasmid DNA. In vitro repair assay with 5-OHU substrate, co-immunoprecipitation from human cells, domain mapping of protein-protein interactions, reconstituted repair assay in plasmid DNA DNA repair High 16982218
2007 Y box-binding protein (YB-1) is a stably interacting partner of NEIL2 (identified by mass spectrometry of NEIL2 immunocomplex). YB-1 stimulates NEIL2 base excision activity ~7-fold. YB-1 also interacts with DNA ligase IIIalpha and DNA polymerase beta, forming a large multiprotein complex. YB-1 normally cytoplasmic translocates to the nucleus during UVA-induced oxidative stress, concomitantly increasing its association with and activation of NEIL2. NEIL2-initiated base excision activity is significantly reduced in YB-1-depleted cells. Mass spectrometry of NEIL2 immunocomplex, co-immunoprecipitation, in vitro stimulation assay, YB-1 siRNA knockdown, nuclear/cytoplasmic fractionation, UVA treatment The Journal of biological chemistry High 17686777
2006 Recombinant NEIL2 purified from E. coli has biochemically characterized DNA glycosylase/AP lyase activity with unique preference for bubble or single-stranded DNA substrates over duplex DNA, unlike NTH1 and OGG1. NEIL2 and NEIL1 are distinct mammalian orthologs of E. coli Nei and Fpg in reaction mechanism. Purification of recombinant protein from E. coli, in vitro DNA glycosylase assays with bubble, single-stranded, and duplex DNA substrates Methods in enzymology High 16793361
2005 Murine NEIL2 (mNEIL2) associates with microtubules in situ and in vitro. Purified recombinant mNEIL2 co-precipitates with microtubules and associates with the microtubule network during interphase and with the spindle assembly at mitosis, as shown by in situ localization, microtubule co-precipitation, and site-directed photochemical experiments. In situ localization with fluorochrome-conjugated recombinant protein, microtubule co-precipitation, site-directed photochemical crosslinking DNA repair Medium 15725623
2010 Pyridoxal-5'-phosphate (PLP) inhibits NEIL2 specifically among six bifunctional DNA repair glycosylases tested. Inhibition is through Schiff base formation between PLP and Lys50 of NEIL2, abolishing DNA binding. The beta2/beta3 loop where Lys50 is located is important for DNA binding and likely lies next to a phosphate-binding site. Enzyme inhibition assay, LC/nanoESI-MS/MS identification of modified residue, DNA binding assay Biochemical and biophysical research communications Medium 20175991
2011 NEIL2 is present in purified human mitochondrial extracts and co-localizes with the mitochondrion-specific protein MT-CO2 by confocal microscopy. ChIP analysis shows NEIL2 associates with mitochondrial genes MT-CO2 and MT-CO3, and with mitochondrial DNA polymerase gamma. Individual depletion of NEIL2 in HEK293 cells causes increased levels of oxidized bases in the mitochondrial genome, demonstrating NEIL2's role in mitochondrial genome maintenance. Mitochondrial extract purification, confocal microscopy, chromatin immunoprecipitation, proximity ligation assay, NEIL2 siRNA knockdown with mt-DNA damage quantification The Journal of biological chemistry High 22130663
2012 Depletion of NEIL2 causes a 6-7-fold increase in spontaneous mutation frequency in the HPRT gene. The NEIL2 variant R257L has modestly decreased DNA glycosylase activity, but shows ~5-fold decreased repair in reconstituted BER assays due to lower affinity for Pol beta and other repair proteins. Cells expressing R257L show increased endogenous DNA damage relative to WT. siRNA depletion with HPRT mutation assay, reconstituted BER assay, biochemical characterization of variant proteins, protein-protein interaction assays DNA repair High 22497777
2014 Cockayne Syndrome B (CSB) protein physically interacts with NEIL2 independently of DNA. CSB stimulates NEIL2 glycosylase activity on 5-hydroxyuracil lesion in a DNA bubble substrate and also stimulates a novel NEIL2 activity toward 4,6-diamino-5-formamidopyrimidine (FapyA). Immunofluorescence shows increased cytoplasmic co-localization of CSB and NEIL2 after oxidative stress. Stalling transcription with alpha-amanitin increases CSB-NEIL2 co-localization. CSB knockdown reduces NEIL2-dependent incision activity in whole cell extracts. Co-immunoprecipitation with recombinant proteins and cell extracts (DNA-independent), in vitro stimulation assay, immunofluorescence, transcription stalling with alpha-amanitin, siRNA knockdown with activity readout Mechanisms of ageing and development High 24406253
2015 Neil2-null mice accumulate oxidized DNA bases preferentially in transcriptionally active (transcribed) genomic sequences. In vivo immunopulldown from mouse tissue shows NEIL2 associates with RNA polymerase II, Cockayne syndrome group B protein (CSB), and TFIIH. ChIP from mouse tissue demonstrates co-occupancy of NEIL2 and RNA Pol II exclusively on transcribed genes. Neil2-null mouse embryonic fibroblasts show increased telomere loss and genomic instability. Neil2-null mice are more responsive to inflammatory agents, producing higher levels of inflammatory genes. Neil2-null mouse generation, co-immunoprecipitation from mouse tissue, ChIP from mouse tissue, LA-QPCR for oxidative DNA damage in transcribed regions, telomere FISH The Journal of biological chemistry High 26245904
2019 Depletion of NEIL1 and NEIL2 in Xenopus embryos and differentiating mouse ESCs causes a defect in cranial neural crest cell (cNCC) development via oxidative stress-induced TP53-dependent DNA damage response. Neil-deficiency causes oxidative damage specifically to mitochondrial DNA, triggering TP53-mediated intrinsic apoptosis. Epistasis with Tdg-deficient mESCs shows the cNCC defect is NOT due to impaired epigenetic DNA demethylation. Xenopus embryo knockdown, mouse ESC differentiation with NEIL KO, epistasis experiments with Tdg KO, TP53 inhibitor rescue, mitochondrial DNA damage assays eLife High 31566562
2020 Crystal structure of mammalian NEIL2 (opossum Monodelphis domestica) reveals an unusual 'open' conformation not seen in NEIL1 or NEIL3. Combined crystallographic and solution-scattering (SAXS) studies show NEIL2 is conformationally dynamic, predicted to adopt a 'closed' conformation upon substrate binding. Three cancer variants (S140N, G230W, G303R) were biochemically characterized. X-ray crystallography (crystal structure), small-angle X-ray scattering (SAXS), biochemical characterization of cancer variants Structure High 32846144
2021 NEIL2 has a non-canonical function as a direct suppressor of NF-κB signaling. NEIL2 directly interacts with the Rel homology region of RelA (p65), blocking NF-κB binding to target gene promoters and repressing proinflammatory gene expression (Cxcl1, Cxcl2, Cxcl10, Il6, Tnfa). Neil2-null mice show significantly higher expression of proinflammatory genes. Intrapulmonary delivery of purified recombinant NEIL2 decreases NF-κB-DNA binding and reduces proinflammatory gene expression and neutrophil recruitment. Co-immunoprecipitation, ChIP, electrophoretic mobility shift assay (EMSA), Neil2-null mouse model, intrapulmonary administration of recombinant NEIL2 protein The Journal of biological chemistry High 33932404
2021 NEIL2 conformation in solution is predominantly 'open'; its large N-terminal insert (absent from other DNA glycosylases) is unstructured in solution. HDX-MS combined with homology modeling and MD simulations shows NEIL2 is a conformationally flexible protein, consistent with its role in repair of non-canonical DNA structures and protein-protein interactions. Hydrogen/deuterium exchange mass spectrometry (HDX-MS), homology modeling, molecular dynamics simulations Journal of molecular biology Medium 34757057
2021 In cells depleted of OGG1 or treated with OGG1 inhibitor TH5487, NEIL2 accumulation at DNA damage sites is prolonged and NEIL2 retention at damaged chromatin is increased. NEIL2-depleted cells oxidatively stressed with OGG1 also inhibited show excessive genomic 8-oxoG accumulation, indicating NEIL2 serves as a backup BER enzyme for OGG1. Live cell imaging of NEIL2 recruitment kinetics, chromatin fractionation, siRNA depletion, pharmacological OGG1 inhibition, immunofluorescence for 8-oxoG International journal of molecular sciences Medium 33925271
2022 NEIL2 polymorphic variant P304T (Pro304 in the beta-turn of the zinc finger motif) has ~5-fold reduced catalytic efficiency (kcat/KM) compared to wild-type, lower DNA affinity, and reduced proficiency in removing damaged bases from single-stranded and bubble-containing DNA. R103W variant is much less affected. Biochemical characterization of recombinant variant proteins, steady-state kinetics, DNA binding assays International journal of molecular sciences Medium 35216329
2023 NEIL2 directly binds to the 5'-UTR of SARS-CoV-2 genomic RNA and blocks viral protein synthesis. Delivery of recombinant NEIL2 into ACE2-expressing cells decreases expression of proinflammatory genes, viral E-gene expression, and lowers yield of viral progeny. RNA binding assay (NEIL2 binding to 5'-UTR of viral RNA), recombinant NEIL2 delivery into cells, measurement of viral replication and proinflammatory gene expression Nature communications Medium 38071370
2023 Crystal structure of mammalian NEIL2 in complex with an abasic site analog-containing DNA duplex at 2.08 Å reveals a large interdomain conformational shift upon DNA binding compared to the unliganded structure, with local changes in C-terminal zinc finger and N-terminal void-filling loop required to position the enzyme on DNA. Biochemical analysis shows NEIL2 has a significant preference for its lyase activity, particularly relevant for abasic sites. Detailed substrate range characterization confirms preference for oxidized cytosine products and abasic sites. X-ray crystallography (liganded structure at 2.08 Å), comparison with unliganded structure, biochemical assays with array of oxidized base lesions Nucleic acids research High 37971311
2023 NEIL2 is phosphorylated by CDK5 and PKC in vitro and in SH-SY5Y neuroblastoma cells. Phosphorylation by PKC causes a substantial reduction in NEIL2 repair activity. CDK5 phosphorylation does not directly alter enzymatic activity. NEIL2 undergoes rapid dephosphorylation in response to oxidative stress in SH-SY5Y cells, indicating phosphorylation is an important modulator of NEIL2 function during oxidative stress. In vitro kinase assays with CDK5 and PKC, in vivo phosphorylation in SH-SY5Y cells, DNA repair activity assay after phosphorylation, oxidative stress treatment with phosphorylation status monitoring Antioxidants Medium 36829914
2019 Sirt3 deacetylates NEIL2 (along with NEIL1, OGG1, MUTYH, APE1, and LIG3) in colorectal cancer cells, modulating mitochondrial BER activity; NEIL2 is identified as a substrate for Sirt3-mediated deacetylation. Deacetylation assay with Sirt3 and NEIL2 as substrate Polski przeglad chirurgiczny Low 32312920

Source papers

Stage 0 corpus · 55 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes & development 3093 9887101
2006 Keap1 recruits Neh2 through binding to ETGE and DLG motifs: characterization of the two-site molecular recognition model. Molecular and cellular biology 628 16581765
2005 Modifying specific cysteines of the electrophile-sensing human Keap1 protein is insufficient to disrupt binding to the Nrf2 domain Neh2. Proceedings of the National Academy of Sciences of the United States of America 406 16006525
2004 Redox-regulated turnover of Nrf2 is determined by at least two separate protein domains, the redox-sensitive Neh2 degron and the redox-insensitive Neh6 degron. The Journal of biological chemistry 336 15143058
2003 Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2. The Journal of biological chemistry 294 14522990
2005 Recognition of the oxidized lesions spiroiminodihydantoin and guanidinohydantoin in DNA by the mammalian base excision repair glycosylases NEIL1 and NEIL2. DNA repair 141 15533836
2006 NEIL2-initiated, APE-independent repair of oxidized bases in DNA: Evidence for a repair complex in human cells. DNA repair 118 16982218
2007 Stimulation of NEIL2-mediated oxidized base excision repair via YB-1 interaction during oxidative stress. The Journal of biological chemistry 111 17686777
2015 Neil2-null Mice Accumulate Oxidized DNA Bases in the Transcriptionally Active Sequences of the Genome and Are Susceptible to Innate Inflammation. The Journal of biological chemistry 87 26245904
2011 Development of Neh2-luciferase reporter and its application for high throughput screening and real-time monitoring of Nrf2 activators. Chemistry & biology 83 21700211
2004 Acetylation of the human DNA glycosylase NEIL2 and inhibition of its activity. Nucleic acids research 78 15175427
2011 Role of human DNA glycosylase Nei-like 2 (NEIL2) and single strand break repair protein polynucleotide kinase 3'-phosphatase in maintenance of mitochondrial genome. The Journal of biological chemistry 76 22130663
2006 Evaluation of NTHL1, NEIL1, NEIL2, MPG, TDG, UNG and SMUG1 genes in familial colorectal cancer predisposition. BMC cancer 68 17029639
2020 Helicobacter pylori infection downregulates the DNA glycosylase NEIL2, resulting in increased genome damage and inflammation in gastric epithelial cells. The Journal of biological chemistry 57 32518160
2020 The DNA Glycosylase NEIL2 Suppresses Fusobacterium-Infection-Induced Inflammation and DNA Damage in Colonic Epithelial Cells. Cells 53 32872214
2016 Abnormal Expressions of DNA Glycosylase Genes NEIL1, NEIL2, and NEIL3 Are Associated with Somatic Mutation Loads in Human Cancer. Oxidative medicine and cellular longevity 46 27042257
2012 Increased risk of lung cancer associated with a functionally impaired polymorphic variant of the human DNA glycosylase NEIL2. DNA repair 44 22497777
2016 PEG-functionalized zinc oxide nanoparticles induce apoptosis in breast cancer cells through reactive oxygen species-dependent impairment of DNA damage repair enzyme NEIL2. Free radical biology & medicine 42 27940348
2014 Cockayne Syndrome group B protein stimulates NEIL2 DNA glycosylase activity. Mechanisms of ageing and development 37 24406253
2006 Purification and characterization of NEIL1 and NEIL2, members of a distinct family of mammalian DNA glycosylases for repair of oxidized bases. Methods in enzymology 37 16793361
2015 Genetic Variation of BCL2 (rs2279115), NEIL2 (rs804270), LTA (rs909253), PSCA (rs2294008) and PLCE1 (rs3765524, rs10509670) Genes and Their Correlation to Gastric Cancer Risk Based on Universal Tagged Arrays and Fe3O4 Magnetic Nanoparticles. Journal of biomedical nanotechnology 36 26554163
2014 NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells. PloS one 35 24595271
2004 Identification of a zinc finger domain in the human NEIL2 (Nei-like-2) protein. The Journal of biological chemistry 35 15339932
2019 NEIL1 and NEIL2 DNA glycosylases protect neural crest development against mitochondrial oxidative stress. eLife 32 31566562
2008 Functional variants of the NEIL1 and NEIL2 genes and risk and progression of squamous cell carcinoma of the oral cavity and oropharynx. Clinical cancer research : an official journal of the American Association for Cancer Research 31 18594018
2021 NEIL1 and NEIL2 Are Recruited as Potential Backup for OGG1 upon OGG1 Depletion or Inhibition by TH5487. International journal of molecular sciences 22 33925271
2021 Intrapulmonary administration of purified NEIL2 abrogates NF-κB-mediated inflammation. The Journal of biological chemistry 21 33932404
2020 Unique Structural Features of Mammalian NEIL2 DNA Glycosylase Prime Its Activity for Diverse DNA Substrates and Environments. Structure (London, England : 1993) 20 32846144
2015 Polymorphisms in NEIL-2, APE-1, CYP2E1 and MDM2 Genes are Independent Predictors of Gastric Cancer Risk in a Northern Jiangsu Population (China). Journal of nanoscience and nanotechnology 20 26373042
2013 Structural investigation of a viral ortholog of human NEIL2/3 DNA glycosylases. DNA repair 18 24120312
2019 Sirt3 regulates the level of mitochondrial DNA repair activity through deacetylation of NEIL1, NEIL2, OGG1, MUTYH, APE1 and LIG3 in colorectal cancer. Polski przeglad chirurgiczny 17 32312920
2019 A variant in a microRNA binding site in NEIL2 3'UTR confers susceptibility to age-related cataracts. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 31253066
2017 Genetic variation in the NEIL2 DNA glycosylase gene is associated with oxidative DNA damage in BRCA2 mutation carriers. Oncotarget 15 29383107
2009 Regulatory regions responsive to oxidative stress in the promoter of the human DNA glycosylase gene NEIL2. Mutagenesis 15 19945985
2021 NEIL1 and NEIL2 DNA glycosylases modulate anxiety and learning in a cooperative manner in mice. Communications biology 13 34857879
2005 The murine DNA glycosylase NEIL2 (mNEIL2) and human DNA polymerase beta bind microtubules in situ and in vitro. DNA repair 13 15725623
2021 DNA glycosylase NEIL2 functions in multiple cellular processes. Progress in biophysics and molecular biology 12 33753087
2022 A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase. International journal of molecular sciences 11 35216329
2021 Dynamics and Conformational Changes in Human NEIL2 DNA Glycosylase Analyzed by Hydrogen/Deuterium Exchange Mass Spectrometry. Journal of molecular biology 11 34757057
2010 Inactivation of NEIL2 DNA glycosylase by pyridoxal phosphate reveals a loop important for substrate binding. Biochemical and biophysical research communications 10 20175991
2023 The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection. Nature communications 9 38071370
2010 Induction of NEIL1 and NEIL2 DNA glycosylases in aniline-induced splenic toxicity. Toxicology and applied pharmacology 9 21145906
2021 Genetic variations in 3'UTRs of SMUG1 and NEIL2 genes modulate breast cancer risk, survival and therapy response. Mutagenesis 8 34097065
2023 Functional roles and cancer variants of the bifunctional glycosylase NEIL2. Environmental and molecular mutagenesis 7 37310399
2020 Cervical carcinoma risk associate with genetic polymorphisms of NEIL2 gene in Chinese population and its significance as predictive biomarker. Scientific reports 7 32198476
2023 Phosphorylation of the Human DNA Glycosylase NEIL2 Is Affected by Oxidative Stress and Modulates Its Activity. Antioxidants (Basel, Switzerland) 5 36829914
2020 DNA glycosylase Neil2 contributes to genomic responses in the spleen during clinical prion disease. Free radical biology & medicine 5 32259578
2021 Breaking the Rules: Protein Sculpting in NEIL2 Regulation. Structure (London, England : 1993) 4 33417890
2022 The DNA glycosylase NEIL2 plays a vital role in combating SARS-CoV-2 infection. Research square 3 35665009
2023 Structural and biochemical insights into NEIL2's preference for abasic sites. Nucleic acids research 2 37971311
2022 Establishment of Neh2-Cre:tdTomato reporter mouse for monitoring the exposure history to electrophilic stress. Free radical biology & medicine 2 36368569
2020 Salinomycin enhances radiotherapy sensitivity and reduces expressions of BIRC5 and NEIL2 in nasopharyngeal carcinoma. European review for medical and pharmacological sciences 2 32572938
2021 Dataset for dynamics and conformational changes in human NEIL2 protein analyzed by integrative structural biology approach. Data in brief 1 35005149
2025 Low levels of DNA repair enzyme NEIL2 May exacerbate inflammation and genomic damage in subjects with stable COPD and during severe exacerbations. Respiratory research 0 40296120
2024 Suppression of the DNA repair enzyme NEIL2 promotes persistent inflammation and genomic damage in subjects with stable COPD and during severe exacerbations. Research square 0 39281860

Missed literature

Know a paper Affinage missed for NEIL2? Flag it for the maintainers and the community.

No submissions yet.