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FLASH GENE
Symbol NEIL1 contributors: mct/npt/pgu - updated : 18-12-2014
HGNC name nei endonuclease VIII-like 1 (E. coli)
HGNC id 18448
Location 15q24.2      Physical location : 75.639.330 - 75.647.586
Synonym name
  • endonuclease VIII
  • DNA-(apurinic or apyrimidinic site) lyase Neil1
  • Nei-like 1
  • Synonym symbol(s) NEI1, FLJ22402, FPG1, NEH1
    EC.number 4.2.99.18, 3.2.2.-
    DNA
    TYPE functioning gene
    STRUCTURE 8.26 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 1907 - 390 - 2008 18662981
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   moderately
    Endocrinepancreas   moderately
    Lymphoid/Immunelymph node   highly
     thymus   highly
     tonsils   highly
    Nervousbrain    
    Reproductivemale systemmale genital tract   
     male systemprostate   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N terminal active site (residues Pro2Glu3)
  • three DNA-contracting twins (beta3-beta4, beta5-beta6, beta8-beta9)
  • nuclear localization signal (NLS)
  • a domain located in a region near the C terminus, dispensable for base excision activity, but implicated in interaction with PCNA , the common interaction domain (CID), with a critical role of in the coordination of overall repair
  • secondary structure
  • helix
  • hairpin helix (H2TH) motif
  • HOMOLOGY
    interspecies ortholog to murine Neil
    homolog to E.coli endonuclease VIII
    Homologene
    FAMILY
  • DNA glycosylases family
  • FPG family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    intracellular,nucleus,chromatin/chromosome
    text
  • centrosomal localization and also associated with mitotic condensed chromosomes
  • colocalize in the nucleus with FEN1
  • presence of NEIL1, NEIL2 and PNKP in mitochondria
  • basic FUNCTION
  • involved in DNA repair by glycosylase activity and AP lyase activity
  • initiating base excision repair of ring-fragmented purines and some saturated pyrimidines
  • playing a role in repair of oxidative damage in mt DNA
  • playing a role in the prevention of the diseases associated with obesity, hypertension, dyslipidemia, and fatty liver disease
  • specific for repair of oxidatively damaged bases in the genome via the base excision repair pathway
  • major DNA glycosylase that processes 5-hydroxyuracil in the proximity of a DNA single-strand break
  • initiates base excision repair (BER) of a number of oxidized purines and pyrimidines in cellular DNA
  • able to excise base lesions from single-stranded DNA regions suggesting their preferential involvement in repair during replication and/or transcription
  • having a function in preferential repair of oxidized bases in DNA prior to replication
  • can efficiently remove 8-oxo-7,8 dihydroadenine (8-oxoAde) from 8-oxoAde:cyt pairs, causing an abortive initiation of repair in DNA
  • DNA glycosylase that is involved in the first step of base excision repair (BER) of oxidatively induced DNA damage
  • involved in nucleotide excision repair (NER)in addition to its function as a DNA glycosylase in base excision repair
  • plays a key role in the initiation of base excision repair of oxidized base lesions by catalyzing the cleavage of the N-glycosidic linkage to the 2prime-deoxyribose
  • glycosylase playing central roles in facilitating repair and initiating different repair pathways dependent on the context and type of lesion encountered
  • the two forms of the NEIL1 protein (edited and unedited) have distinct enzymatic properties with changes observed for both glycosylase activity and lesion specificity
  • initiates prereplicative repair by acting as a "cowcatcher" and preventing nascent chain growth
  • NEIL1-mediated prereplicative repair of oxidized bases in the replicating strand, with NEIL2 providing a backup function
  • role for NEIl3 and NEIL1 is to repair DNA base damages in telomeres and NEIL3 and NEIL1 may function in quadruplex-mediated cellular events, such as gene regulation via removal of damaged bases from quadruplex DNA
  • unique among the oxidatively damaged base repair-initiating DNA glycosylases in the human genome due to its S phase-specific activation and ability to excise substrate base lesions from single-stranded DNA
  • CELLULAR PROCESS nucleotide, repair, base excision repair
    nucleotide, repair, nucleotide excision repair
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism carbohydrate
    signaling
    a component
    INTERACTION
    DNA binding to thymin glycol
    RNA
    small molecule
    protein
  • interacting with ERCC6 (plays a role in repair of formamidopyrimidines, possibly by interacting with and stimulating NEIL1, and accumulation of such modifications may have a causal role in the pathogenesis of CS
  • interacting with WRN, a member of the RecQ family of DNA helicases (associates with NEIL1 in the early damage-sensing step of base excision repair, stimulating NEIL1 in excision of oxidative lesions from bubble DNA substrates)
  • interacts with flap endonuclease 1 (FEN1), an essential component of the DNA replication (Hegde 2008)
  • stably interacts with proliferating cell nuclear antigen (PCNA), the sliding clamp for DNA replication (PCNA stimulates NEIL1 activity in excising the oxidized base 5-hydroxyuracil from single-stranded DNA sequences including fork structures)
  • PARP1 binds to the C-terminal-100 amino acids of NEIL1 and NEIL1 binds to the BRCT domain of PARP1 (NEIL1 stimulates the poly(ADP-ribosyl)ation activity of PARP1)
  • 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
    activated by stimulated in excision of oxidative lesions from bubble DNA substrates, by WRN
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    mice lacking NEIL1 have a complex severe phenotype resembling the metabolic syndrome in humans