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    NEIL2 nei like DNA glycosylase 2 [ Homo sapiens (human) ]

    Gene ID: 252969, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NEIL2provided by HGNC
    Official Full Name
    nei like DNA glycosylase 2provided by HGNC
    Primary source
    HGNC:HGNC:18956
    See related
    Ensembl:ENSG00000154328 MIM:608933; AllianceGenome:HGNC:18956
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    NEH2; NEI2
    Summary
    This gene encodes a member of the Fpg/Nei family of DNA glycosylases. These glycosylases initiate the first step in base excision repair by cleaving oxidatively damaged bases and introducing a DNA strand break via their abasic site lyase activity. This enzyme is primarily associated with DNA repair during transcription and acts prefentially on cytosine-derived lesions, particularly 5-hydroxyuracil and 5-hydroxycytosine. It contains an N-terminal catalytic domain, a hinge region, and a C-terminal DNA-binding domain with helix-two-turn-helix and zinc finger motifs. This enzyme interacts with the X-ray cross complementing factor 1 scaffold protein as part of a multi-protein DNA repair complex. A pseudogene of this gene has been identified. [provided by RefSeq, Mar 2017]
    Expression
    Ubiquitous expression in testis (RPKM 14.3), brain (RPKM 9.4) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NEIL2 in Genome Data Viewer
    Location:
    8p23.1
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (11769710..11787345)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (7952965..7970597, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (11627219..11644854)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene GATA binding protein 4 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:11566565-11567490 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:11567491-11568414 Neighboring gene small nucleolar RNA, H/ACA box 99 Neighboring gene HNF4 motif-containing MPRA enhancer 121 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:11584607-11585590 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:11593264-11593764 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27031 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:11594517-11595018 Neighboring gene VISTA enhancer hs2205 Neighboring gene VISTA enhancer hs508 Neighboring gene long intergenic non-protein coding RNA 2905 Neighboring gene uncharacterized LOC124901888 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:11627369-11627869 Neighboring gene uncharacterized LOC105379243 Neighboring gene Sharpr-MPRA regulatory region 11637 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:11657524-11658167 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:11658297-11659039 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:11659040-11659781 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27032 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18940 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18941 Neighboring gene SUB1 pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27033 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18942 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18943 Neighboring gene farnesyl-diphosphate farnesyltransferase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27034 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27035

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection. Tapryal N, et al. Nat Commun, 2023 Dec 9. PMID 38071370, Free PMC Article
    2. New paradigms in the repair of oxidative damage in human genome: mechanisms ensuring repair of mutagenic base lesions during replication and involvement of accessory proteins. Dutta A, et al. Cell Mol Life Sci, 2015 May. PMID 25575562, Free PMC Article
    3. NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells. Sarker AH, et al. PLoS One, 2014. PMID 24595271, Free PMC Article
    4. DNA glycosylases search for and remove oxidized DNA bases. Wallace SS. Environ Mol Mutagen, 2013 Dec. PMID 24123395, Free PMC Article
    5. Increased risk of lung cancer associated with a functionally impaired polymorphic variant of the human DNA glycosylase NEIL2. Dey S, et al. DNA Repair (Amst), 2012 Jun 1. PMID 22497777, Free PMC Article

    See all (69) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Functional roles and cancer variants of the bifunctional glycosylase NEIL2.
      Title: Functional roles and cancer variants of the bifunctional glycosylase NEIL2.
    2. Structural and biochemical insights into NEIL2's preference for abasic sites.
      Title: Structural and biochemical insights into NEIL2's preference for abasic sites.
    3. The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection.
      Title: The DNA glycosylase NEIL2 is protective during SARS-CoV-2 infection.
    4. A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase.
      Title: A Low-Activity Polymorphic Variant of Human NEIL2 DNA Glycosylase.
    5. Mendelian Randomization Analysis Identified Potential Genes Pleiotropically Associated with Polycystic Ovary Syndrome.
      Title: Mendelian Randomization Analysis Identified Potential Genes Pleiotropically Associated with Polycystic Ovary Syndrome.
    6. Dynamics and Conformational Changes in Human NEIL2 DNA Glycosylase Analyzed by Hydrogen/Deuterium Exchange Mass Spectrometry.
      Title: Dynamics and Conformational Changes in Human NEIL2 DNA Glycosylase Analyzed by Hydrogen/Deuterium Exchange Mass Spectrometry.
    7. Genetic variations in 3'UTRs of SMUG1 and NEIL2 genes modulate breast cancer risk, survival and therapy response.
      Title: Genetic variations in 3'UTRs of SMUG1 and NEIL2 genes modulate breast cancer risk, survival and therapy response.
    8. Unique Structural Features of Mammalian NEIL2 DNA Glycosylase Prime Its Activity for Diverse DNA Substrates and Environments.
      Title: Unique Structural Features of Mammalian NEIL2 DNA Glycosylase Prime Its Activity for Diverse DNA Substrates and Environments.
    9. NEIL1 and NEIL2 Are Recruited as Potential Backup for OGG1 upon OGG1 Depletion or Inhibition by TH5487.
      Title: NEIL1 and NEIL2 Are Recruited as Potential Backup for OGG1 upon OGG1 Depletion or Inhibition by TH5487.
    10. Helicobacter pylori infection downregulates the DNA glycosylase NEIL2, resulting in increased genome damage and inflammation in gastric epithelial cells.
      Title: Helicobacter pylori infection downregulates the DNA glycosylase NEIL2, resulting in increased genome damage and inflammation in gastric epithelial cells.
    Submit: New GeneRIF Correction See all GeneRIFs (41)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    EBI GWAS Catalog

    Description
    A genome-wide association study of behavioral disinhibition.
    EBI GWAS Catalog
    Duffy-null-associated low neutrophil counts influence HIV-1 susceptibility in high-risk South African black women.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • MGC2832, MGC4505, FLJ31644

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables DNA N-glycosylase activity TAS
    Traceable Author Statement
    more info
    		  
    enables class I DNA-(apurinic or apyrimidinic site) endonuclease activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables damaged DNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables microtubule binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in depyrimidination TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
    		  
    located_in mitotic spindle IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    endonuclease 8-like 2
    Names
    DNA glycosylase/AP lyase Neil2
    DNA-(apurinic or apyrimidinic site) lyase Neil2
    nei endonuclease VIII-like 2
    nei homolog 2
    nei-like protein 2
    NP_001129218.1
    NP_001129219.1
    NP_001129220.1
    NP_001336368.1
    NP_001336369.1
    NP_001336370.1
    NP_001336371.1
    NP_659480.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_053043.1 RefSeqGene

      Range
      5048..22683
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001135746.3 → NP_001129218.1  endonuclease 8-like 2 isoform a

      See identical proteins and their annotated locations for NP_001129218.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 8 encode the same isoform (a).
      Source sequence(s)
      AB079070, AC069185, AK056206, DA207321, DB452586
      Consensus CDS
      CCDS5984.1
      UniProtKB/Swiss-Prot
      B4DFR7, Q7Z3Q7, Q8N842, Q8NG52, Q969S2
      Related
      ENSP00000394023.2, ENST00000436750.7
      Conserved Domains (2) summary
      cd08968
      Location:1 → 185
      MeNeil2_N; N-terminal domain of metazoan Nei-like glycosylase 2 (NEIL2)
      cl26942
      Location:155 → 320
      H2TH; Formamidopyrimidine-DNA glycosylase H2TH domain

    2. NM_001135747.3 → NP_001129219.1  endonuclease 8-like 2 isoform b

      See identical proteins and their annotated locations for NP_001129219.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks an alternate exon in the 5' coding region, and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (b) has a shorter N-terminus compared to isoform a. Variants 3 and 5-7 encode the same isoform (b).
      Source sequence(s)
      AB079070, AC069185, AK097389
      Consensus CDS
      CCDS47803.1
      UniProtKB/Swiss-Prot
      Q969S2
      Related
      ENSP00000384070.3, ENST00000403422.7
      Conserved Domains (2) summary
      cl03119
      Location:62 → 124
      FpgNei_N; N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII) base-excision repair DNA glycosylases
      cl26942
      Location:94 → 259
      H2TH; Formamidopyrimidine-DNA glycosylase H2TH domain

    3. NM_001135748.3 → NP_001129220.1  endonuclease 8-like 2 isoform c

      See identical proteins and their annotated locations for NP_001129220.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in the 5' UTR and lacks an alternate exon compared to variant 1. The encoded isoform (c) has the same N- and C-termini but is shorter compared to isoform a.
      Source sequence(s)
      AB079070, AC069185, AK294224
      Consensus CDS
      CCDS47802.1
      UniProtKB/Swiss-Prot
      Q969S2
      Related
      ENSP00000435657.1, ENST00000528323.5
      Conserved Domains (2) summary
      pfam06831
      Location:104 → 150
      H2TH; Formamidopyrimidine-DNA glycosylase H2TH domain
      cl03119
      Location:1 → 69
      FpgNei_N; N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII) base-excision repair DNA glycosylases

    4. NM_001349439.2 → NP_001336368.1  endonuclease 8-like 2 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) differs in the 5' UTR and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (b) has a shorter N-terminus compared to isoform a. Variants 3 and 5-7 encode the same isoform (b).
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS47803.1
      Conserved Domains (2) summary
      cl03119
      Location:62 → 124
      FpgNei_N; N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII) base-excision repair DNA glycosylases
      cl26942
      Location:94 → 259
      H2TH; Formamidopyrimidine-DNA glycosylase H2TH domain

    5. NM_001349440.2 → NP_001336369.1  endonuclease 8-like 2 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (6) differs in the 5' UTR and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (b) has a shorter N-terminus compared to isoform a. Variants 3 and 5-7 encode the same isoform (b).
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS47803.1
      Conserved Domains (2) summary
      cl03119
      Location:62 → 124
      FpgNei_N; N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII) base-excision repair DNA glycosylases
      cl26942
      Location:94 → 259
      H2TH; Formamidopyrimidine-DNA glycosylase H2TH domain

    6. NM_001349441.2 → NP_001336370.1  endonuclease 8-like 2 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (7) lacks an alternate exon in the 5' UTR and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (b) has a shorter N-terminus compared to isoform a. Variants 3 and 5-7 encode the same isoform (b).
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS47803.1
      Conserved Domains (2) summary
      cl03119
      Location:62 → 124
      FpgNei_N; N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII) base-excision repair DNA glycosylases
      cl26942
      Location:94 → 259
      H2TH; Formamidopyrimidine-DNA glycosylase H2TH domain

    7. NM_001349442.2 → NP_001336371.1  endonuclease 8-like 2 isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (8) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 8 encode the same isoform (a).
      Source sequence(s)
      AC069185
      Consensus CDS
      CCDS5984.1
      UniProtKB/Swiss-Prot
      B4DFR7, Q7Z3Q7, Q8N842, Q8NG52, Q969S2
      Related
      ENSP00000397538.2, ENST00000455213.6
      Conserved Domains (2) summary
      cd08968
      Location:1 → 185
      MeNeil2_N; N-terminal domain of metazoan Nei-like glycosylase 2 (NEIL2)
      cl26942
      Location:155 → 320
      H2TH; Formamidopyrimidine-DNA glycosylase H2TH domain

    8. NM_145043.4 → NP_659480.1  endonuclease 8-like 2 isoform a

      See identical proteins and their annotated locations for NP_659480.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Variants 1, 2, and 8 encode the same isoform (a).
      Source sequence(s)
      AB079070, AC069185, AK056206, DA205315, DB452586
      Consensus CDS
      CCDS5984.1
      UniProtKB/Swiss-Prot
      B4DFR7, Q7Z3Q7, Q8N842, Q8NG52, Q969S2
      Related
      ENSP00000284503.6, ENST00000284503.7
      Conserved Domains (2) summary
      cd08968
      Location:1 → 185
      MeNeil2_N; N-terminal domain of metazoan Nei-like glycosylase 2 (NEIL2)
      cl26942
      Location:155 → 320
      H2TH; Formamidopyrimidine-DNA glycosylase H2TH domain

    RNA

    1. NR_146180.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (9) uses two alternate splice sites compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC069185

    2. NR_146181.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (10) uses an alternate 5' and 3' exon structure, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC069185

    3. NR_146182.2 RNA Sequence

      Status: REVIEWED

      Description
      Transcript Variant: This variant (11) uses an alternate splice site and lacks an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AC069185, DA037395

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      11769710..11787345
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_018654717.1 Reference GRCh38.p14 PATCHES

      Range
      1560751..1578390 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      7952965..7970597 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q969S2.3 GenPept UniProtKB/Swiss-Prot:Q969S2

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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