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FLASH GENE
Symbol NEIL2 contributors: mct/npt - updated : 18-12-2014
HGNC name nei like 2 (E. coli)
HGNC id 18956
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a N-terminal Pro as the active site
  • a potential helix-2-turn-helix motif
  • zinc finger motifs, essential for its structural integrity and enzyme activity
  • Cys-X2-His-X16-Cys-X2-Cys (CHCC) motif present near the C terminus is distinct from the zinc finger motifs of NEI/Fpg
  • HOMOLOGY
    interspecies ortholog to E.coli MutM/Nei
    Homologene
    FAMILY
  • E.coli MutM/Nei family
  • DNA glycosylases family
  • FPG family
  • CATEGORY enzyme , DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus
    text
  • predominantly localized in the nucleus despite the absence of a nuclear localization signal
  • in spindle microtubules
  • presence of NEIL2 and PNKP in mitochondria
  • basic FUNCTION
  • DNA glycosylase/AP lyase activity, involved in repair of lesions in DNA generated during transcription and/or replication, mainly by removing oxidative products of cytosine
  • may have a novel regulatory role in NEIL2-mediated repair under oxidative stress (Das 2007)
  • recognizes an apurinic/apyrimidinic site exclusively
  • able to excise base lesions from single-stranded DNA regions suggesting their preferential involvement in repair during replication and/or transcription (Dou 2008)
  • excises oxidized DNA lesions from bubble or single-stranded structures, suggesting its involvement in transcription-coupled DNA repair (Kinslow 2008)
  • critical role of NEIL2 and PNKP in maintenance of the mammalian mitochondrial genome
  • oxidized base-specific DNA glycosylase, that is unique in preferentially repairing oxidative damage in transcribed genes
  • NEIL1-mediated prereplicative repair of oxidized bases in the replicating strand, with NEIL2 providing a backup function
  • biological role for ERCC6 and NEIL2 in transcription associated base excision repair
  • CELLULAR PROCESS nucleotide, repair, base excision repair
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • Y box-binding (YBX1) protein is a stably interacting partner of NEIL2 (not only interacts physically with NEIL2, but it also cooperates functionally by stimulating its base excision activity by 7-fold)(Das 2007)
  • co-association of NEIL2 and PNKP with POLG on the mitochondrial genome
  • ERCC6, and NEIL2 were found to physically interact independently of DNA
  • NEIL1 and NEIL2 DNA glycosylases coordinate abasic-site processing during TET-TDG DNA demethylation, and NEIL1 and NEIL2 cooperate with TDG during base excision
  • cell & other
    REGULATION
    inhibited by significantly inhibited by
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional   deletion    
    in congenital heart disease
    Susceptibility
  • to familial colorectal cancer
  • to lung cancer development
  • Variant & Polymorphism other
  • missense variants increasing the risk of colorectal cancer
  • decreased DNA repair capacity of the R257L variant can induce mutations that lead to lung cancer development
  • Candidate gene
  • polymorphisms of the NEIL2 gene may be markers for risk and progression of squamous cell carcinoma of the oral cavity and oropharynx, particularly in patients with oropharyngeal cancer (Zhai 2008)
  • Marker
    Therapy target
    ANIMAL & CELL MODELS