Details for: NEIL2

Gene ID: 252969

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: NEIL2

Ensembl ID: ENSG00000154328

Description: nei like DNA glycosylase 2

Cell Significance Landscape

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • ON-bipolar cell CL0000749
    CSI 4.05
    rCSI 6.02%
    PRS 97.75
  • retinal cone cell CL0000573
    CSI 3.61
    rCSI 5.82%
    PRS 95.77
  • rod bipolar cell CL0000751
    CSI 3.39
    rCSI 6.09%
    PRS 96.82
  • epithelial cell CL0000066
    CSI 3.37
    rCSI 5.18%
    PRS 93.73
  • OFF-bipolar cell CL0000750
    CSI 3.13
    rCSI 4.29%
    PRS 97.61
  • megakaryocyte-erythroid progenitor cell CL0000050
    CSI 3.12
    rCSI 2.82%
    PRS 98.57
  • ciliated epithelial cell CL0000067
    CSI 2.89
    rCSI 2.54%
    PRS 95.66
  • mature B cell CL0000785
    CSI 2.83
    rCSI 2.46%
    PRS 99.57
  • progenitor cell CL0011026
    CSI 2.42
    rCSI 5.15%
    PRS 96.33
  • retina horizontal cell CL0000745
    CSI 2.37
    rCSI 3.61%
    PRS 97.42
  • club cell CL0000158
    CSI 2.27
    rCSI 3.33%
    PRS 98.16

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [NEIL2](/details-gene/252969) (Nei Like DNA Glycosylase 2) is a protein-coding gene located on chromosome 8p23.1. It encodes a DNA glycosylase that plays a critical role in the base excision repair (BER) pathway, a primary cellular defense mechanism against DNA damage. The [NEIL2](/details-gene/252969) protein specifically recognizes and excises oxidized pyrimidine bases from the DNA backbone, thereby initiating the repair process to maintain genomic integrity ([Link](https://doi.org/10.1074/jbc.c200355200)). **Overall**, expression data indicates that [NEIL2](/details-gene/252969) is particularly significant in specialized, high-metabolism neuronal cells of the retina, such as [ON-bipolar cell](/details-cell/CL0000749) and [retinal cone cell](/details-cell/CL0000573), as well as in various [epithelial cell](/details-cell/CL0000066) types and progenitor cells. This expression pattern suggests a key role in protecting terminally differentiated and rapidly dividing cells from the consequences of oxidative DNA damage. ## Cellular Roles and Expression Landscape The expression profile of [NEIL2](/details-gene/252969) highlights its importance in tissues with high metabolic activity, high cell turnover, or direct exposure to environmental mutagens. In the **Overall** context, the gene shows its highest significance in the retina. It is a top marker for several classes of retinal neurons, including [ON-bipolar cell](/details-cell/CL0000749) (CSI: 4.05), [retinal cone cell](/details-cell/CL0000573) (CSI: 3.61), [rod bipolar cell](/details-cell/CL0000751) (CSI: 3.39), and [OFF-bipolar cell](/details-cell/CL0000750) (CSI: 3.13). The retina is a site of intense oxidative stress due to high oxygen consumption and constant light exposure, and the prominent expression of a DNA repair enzyme like [NEIL2](/details-gene/252969) is consistent with a crucial role in safeguarding these non-replicating neurons from accumulating DNA damage. Beyond the retina, [NEIL2](/details-gene/252969) is also highly significant in various epithelial tissues, as shown by its high CSI in [epithelial cell](/details-cell/CL0000066) (CSI: 3.37) and [ciliated epithelial cell](/details-cell/CL0000067) (CSI: 2.89). This suggests a protective function in barrier tissues that are frequently exposed to external insults. Furthermore, its notable significance in progenitor populations, such as [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050) (CSI: 3.12) and generic [progenitor cell](/details-cell/CL0011026) (CSI: 2.42), points to a role in maintaining genomic stability during rapid cell proliferation and differentiation. Its expression is also notable in [mature B cell](/details-cell/CL0000785) (CSI: 2.83), a cell type involved in somatic hypermutation, where precise DNA repair is critical. ## Pathways and Molecular Function Functional annotation data firmly places [NEIL2](/details-gene/252969) within the core machinery of [DNA repair](/details-gene/R-HSA-73894). Its primary function is categorized within the [Base excision repair (BER)](/details-gene/R-HSA-73884) pathway, a multi-step process that handles small, non-helix-distorting base lesions. **Molecular Function:** [NEIL2](/details-gene/252969) acts as a [DNA N-glycosylase](/details-gene/GO:0019104), an enzyme that initiates BER by recognizing and cleaving the N-glycosidic bond between a damaged base and the sugar-phosphate backbone. It exhibits specificity for oxidized pyrimidines and is involved in processes like [depyrimidination](/details-gene/GO:0045008) ([Link](https://reactome.org/content/detail/R-HSA-73928)). This initial step creates an apurinic/apyrimidinic (AP) site, which is further processed by other enzymes. [NEIL2](/details-gene/252969) also possesses an associated AP lyase activity, allowing it to cleave the DNA strand at the AP site. This is reflected in its annotation for [Class i dna-(apurinic or apyrimidinic site) endonuclease activity](/details-gene/GO:0140078). Its function is dependent on its ability for [damaged dna binding](/details-gene/GO:0003684) and requires [zinc ion binding](/details-gene/GO:0008270) for structural stability and catalytic activity ([Link](https://doi.org/10.1074/jbc.m406224200)). **Cellular Component:** Consistent with its role in DNA maintenance, [NEIL2](/details-gene/252969) is localized to the [nucleus](/details-gene/GO:0005634) and specifically the [nucleoplasm](/details-gene/GO:0005654). Interestingly, it is also annotated to the [mitotic spindle](/details-gene/GO:0072686), which may suggest a secondary role in safeguarding chromosome integrity during cell division. ## Research Directions The robust and specific expression of [NEIL2](/details-gene/252969) in retinal neurons, coupled with its known function in repairing oxidative DNA damage, provides a strong basis for further investigation into its role in retinal health and disease. **Proposed Hypotheses:** 1. The high constitutive expression of [NEIL2](/details-gene/252969) in retinal cells, particularly photoreceptors like [retinal cone cell](/details-cell/CL0000573), serves as a critical defense mechanism against photo-oxidative stress. A decline in [NEIL2](/details-gene/252969) function or expression with age could be a contributing factor to the pathogenesis of age-related macular degeneration (AMD) or other retinopathies characterized by oxidative damage. 2. The reported association of [NEIL2](/details-gene/252969) with the [mitotic spindle](/details-gene/GO:0072686) suggests a function beyond interphase BER. It may be recruited to chromosomes during mitosis in progenitor cells, such as [megakaryocyte-erythroid progenitor cell](/details-cell/CL0000050), to resolve DNA lesions that could otherwise lead to segregation errors or genomic instability in daughter cells. **Key Experimental Approach:** To test the first hypothesis regarding the protective role of [NEIL2](/details-gene/252969) in the retina, a powerful approach would involve using a mouse model. A conditional knockout of *Neil2* specifically in retinal cells could be generated. These mice, along with wild-type controls, would be subjected to chronic, low-level light-induced oxidative stress. The impact could be assessed by quantifying levels of oxidative DNA lesions (e.g., 8-oxoguanine) in retinal tissue, measuring photoreceptor apoptosis via TUNEL staining, and evaluating retinal function over time using electroretinography (ERG). A significant increase in DNA damage and accelerated functional decline in the knockout mice would strongly support the hypothesis. **Therapeutic Potential:** As a guardian of the genome, [NEIL2](/details-gene/252969) is a potential target for therapeutic enhancement rather than inhibition. In degenerative diseases linked to oxidative stress, such as AMD or certain neurodegenerative disorders, strategies aimed at upregulating [NEIL2](/details-gene/252969) expression or enhancing its enzymatic activity could be beneficial. This might be achieved through small-molecule activators or gene therapy approaches designed to boost the cell's endogenous DNA repair capacity. However, direct enzymatic activation is challenging, and a more feasible initial step may be to evaluate [NEIL2](/details-gene/252969) as a biomarker for cellular stress and DNA repair capacity in patient populations.

Genular Protein ID: 118585772

Symbol: NEIL2_HUMAN

Name: Endonuclease 8-like 2

UniProtKB Accession Codes:

Q969S2 B4DFR7 Q7Z3Q7 Q8N842 Q8NG52

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 3 CDD 1 CORUM 1 CTD 1 ChEBI 5 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 7 EC 3 EMBL 9 Ensembl 10 ExpressionAtlas 1 GO 13 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 4 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 4 Pumba 1 RNAct 1 Reactome 3 RefSeq 7 Rhea 4 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12200441

Title: A back-up glycosylase in Nth1 knock-out mice is a functional Nei (endonuclease VIII) homologue.

PubMed ID: 12200441

DOI: 10.1074/jbc.m206884200

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 16421571

Title: DNA sequence and analysis of human chromosome 8.

PubMed ID: 16421571

DOI: 10.1038/nature04406

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 12097317

Title: Identification and characterization of a novel human DNA glycosylase for repair of cytosine-derived lesions.

PubMed ID: 12097317

DOI: 10.1074/jbc.c200355200

PubMed ID: 14522990

Title: Repair of oxidized bases in DNA bubble structures by human DNA glycosylases NEIL1 and NEIL2.

PubMed ID: 14522990

DOI: 10.1074/jbc.m308658200

PubMed ID: 15175427

Title: Acetylation of the human DNA glycosylase NEIL2 and inhibition of its activity.

PubMed ID: 15175427

DOI: 10.1093/nar/gkh632

PubMed ID: 15339932

Title: Identification of a zinc finger domain in the human NEIL2 (Nei-like-2) protein.

PubMed ID: 15339932

DOI: 10.1074/jbc.m406224200

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

Sequence Information:

  • Length: 332
  • Mass: 36826
  • Checksum: 8A8E76B75ABADE6D
  • Sequence:
    • MPEGPLVRKF HHLVSPFVGQ QVVKTGGSSK KLQPASLQSL WLQDTQVHGK KLFLRFDLDE 
EMGPPGSSPT PEPPQKEVQK EGAADPKQVG EPSGQKTLDG SSRSAELVPQ GEDDSEYLER 
DAPAGDAGRW LRVSFGLFGS VWVNDFSRAK KANKRGDWRD PSPRLVLHFG GGGFLAFYNC 
QLSWSSSPVV TPTCDILSEK FHRGQALEAL GQAQPVCYTL LDQRYFSGLG NIIKNEALYR 
AGIHPLSLGS VLSASRREVL VDHVVEFSTA WLQGKFQGRP QHTQVYQKEQ CPAGHQVMKE 
AFGPEDGLQR LTWWCPQCQP QLSEEPEQCQ FS