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    Fen1 flap structure specific endonuclease 1 [ Mus musculus (house mouse) ]

    Gene ID: 14156, updated on 21-Apr-2024

    Summary

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    Official Symbol
    Fen1provided by MGI
    Official Full Name
    flap structure specific endonuclease 1provided by MGI
    Primary source
    MGI:MGI:102779
    See related
    Ensembl:ENSMUSG00000024742 AllianceGenome:MGI:102779
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Mus musculus
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
    Also known as
    FEN-1
    Summary
    Enables DNA binding activity; metal ion binding activity; and nuclease activity. Acts upstream of or within DNA repair and DNA replication. Predicted to be located in mitochondrion; nucleolus; and nucleoplasm. Predicted to be part of protein-containing complex. Predicted to be active in nucleus. Predicted to colocalize with chromosome, telomeric region. Is expressed in several structures, including brain; genitourinary system; liver; lung; and spleen. Orthologous to human FEN1 (flap structure-specific endonuclease 1). [provided by Alliance of Genome Resources, Apr 2022]
    Expression
    Broad expression in liver E14 (RPKM 32.5), liver E14.5 (RPKM 31.6) and 24 other tissues See more
    Orthologs
    human all
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    Genomic context

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    Location:
    19 A; 19 6.54 cM
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    RS_2024_02 current GRCm39 (GCF_000001635.27) 19 NC_000085.7 (10176496..10181757, complement)
    108.20200622 previous assembly GRCm38.p6 (GCF_000001635.26) 19 NC_000085.6 (10199132..10204393, complement)

    Chromosome 19 - NC_000085.7Genomic Context describing neighboring genes Neighboring gene vesicle-associated membrane protein 3 pseudogene Neighboring gene fatty acid desaturase 1 Neighboring gene microRNA 6993 Neighboring gene STARR-positive B cell enhancer ABC_E11020 Neighboring gene transmembrane protein 258 Neighboring gene myelin regulatory factor Neighboring gene diacylglycerol lipase, alpha Neighboring gene STARR-seq mESC enhancer starr_45549 Neighboring gene predicted gene, 30042

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Mouse ENCODE transcriptome data
    • Description: RNA profiling data sets generated by the Mouse ENCODE project.
    • BioProject: PRJNA66167
    • Publication: PMID 25409824
    • Analysis date: n/a

    Bibliography

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    Related articles in PubMed

    1. Flap Endonuclease 1 Mutations A159V and E160D Cause Genomic Instability by Slowing Reaction on Double-Flap Substrates. Algasaier SI, et al. Biochemistry, 2018 Dec 18. PMID 30472848
    2. Triptolide inhibits Wnt signaling in NSCLC through upregulation of multiple Wnt inhibitory factors via epigenetic modifications to Histone H3. Nardi I, et al. Int J Cancer, 2018 Nov 15. PMID 30006924, Free PMC Article
    3. Triptolide-Assisted Phosphorylation of p53 Suppresses Inflammation-Induced NF-κB Survival Pathways in Cancer Cells. Zheng L, et al. Mol Cell Biol, 2017 Aug 1. PMID 28533220, Free PMC Article
    4. Interacting partners of FEN1 and its role in the development of anticancer therapeutics. Kathera C, et al. Oncotarget, 2017 Apr 18. PMID 28187440, Free PMC Article
    5. Okazaki fragment maturation involves α-segment error editing by the mammalian FEN1/MutSα functional complex. Liu S, et al. EMBO J, 2015 Jul 2. PMID 25921062, Free PMC Article

    See all (61) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Kinetic measurements showed that the active site mutants A159V and E160D reduce the rates of hydrolysis under multiple- and single-turnover conditions on all substrates. Consistent with their dominant negative effects in heterozygotes, neither mutation affects the adoption of the substrate duplex arms in the bent conformation on the enzyme surface, although decreases in substrate binding affinity are observed.
      Title: Flap Endonuclease 1 Mutations A159V and E160D Cause Genomic Instability by Slowing Reaction on Double-Flap Substrates.
    2. These results reveal an important role of FEN1 phosphorylation to counteract oxygen-induced stress in the heart during the fetal-to-neonatal transition.
      Title: Role of FEN1 S187 phosphorylation in counteracting oxygen-induced stress and regulating postnatal heart development.
    3. WDR4 regulates FEN1's potential DNA cleavage threat near the site of replication.
      Title: Wuho Is a New Member in Maintaining Genome Stability through its Interaction with Flap Endonuclease 1.
    4. The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers.
      Title: The FEN1 E359K germline mutation disrupts the FEN1-WRN interaction and FEN1 GEN activity, causing aneuploidy-associated cancers.
    5. PARP1 is required for FEN1 recruitment to DNA repair intermediates in base excision repair.
      Title: Kinetics of endogenous mouse FEN1 in base excision repair.
    6. FFAA Fen1 mutation causes defective Pcna -coordinated Okazaki fragment maturation.
      Title: Fen1 mutations that specifically disrupt its interaction with PCNA cause aneuploidy-associated cancer.
    7. A point mutation in the base excision repair gene flap endonuclease 1 causes a functional deficiency in repairing base damage, such that individuals carrying the mutation or similar mutations are predisposed to chemical-induced cancer development.
      Title: Chemical-induced cancer incidence and underlying mechanisms in Fen1 mutant mice.
    8. The stoichiometry of base excision repair enzymes is one critical factor underlying the tissue selectivity of somatic CAG expansion.
      Title: Stoichiometry of base excision repair proteins correlates with increased somatic CAG instability in striatum over cerebellum in Huntington's disease transgenic mice.
    9. FEN1 localization within the mitochondrial compartment of mouse brain tissue
      Title: Evidence for a role of FEN1 in maintaining mitochondrial DNA integrity.
    10. Loss of Fen1 is associated with early-onset lymphoma and extensive embryonic apoptosis
      Title: Early-onset lymphoma and extensive embryonic apoptosis in two domain-specific Fen1 mice mutants.
    Submit: New GeneRIF Correction See all GeneRIFs (17)

    Variation

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    Alleles

    Alleles of this type are documented at Mouse Genome Informatics  (MGI)
    • Targeted (9)  1 citation
    • Endonuclease-mediated (4) 

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by MGI

    Function Evidence Code Pubs
    enables 5'-3' exonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 5'-3' exonuclease activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables 5'-flap endonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 5'-flap endonuclease activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables DNA binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables DNA binding ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables RNA-DNA hybrid ribonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables RNA-DNA hybrid ribonuclease activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables catalytic activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables endonuclease activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables exonuclease activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables flap endonuclease activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables flap endonuclease activity ISO
    Inferred from Sequence Orthology
    more info
    		  
    enables hydrolase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables hydrolase activity, acting on ester bonds IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables magnesium ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables manganese ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables manganese ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables nuclease activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    acts_upstream_of_or_within DNA damage response IEA
    Inferred from Electronic Annotation
    more info
    		  
    acts_upstream_of_or_within DNA repair IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within DNA replication IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in DNA replication, removal of RNA primer ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in memory ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in nucleic acid metabolic process ISO
    Inferred from Sequence Orthology
    more info
    		  
    involved_in positive regulation of sister chromatid cohesion ISO
    Inferred from Sequence Orthology
    more info
    		  
    Component Evidence Code Pubs
    colocalizes_with chromosome, telomeric region ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in mitochondrion ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in nucleolus ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in nucleoplasm ISO
    Inferred from Sequence Orthology
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus ISO
    Inferred from Sequence Orthology
    more info
    		  
    located_in nucleus TAS
    Traceable Author Statement
    more info
    		 PubMed 
    part_of protein-containing complex ISO
    Inferred from Sequence Orthology
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    flap endonuclease 1
    NP_001258543.1
    NP_001258544.1
    NP_001397211.1
    NP_032025.2
    XP_006526726.1

    NCBI Reference Sequences (RefSeq)

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    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.

    mRNA and Protein(s)

    1. NM_001271614.2 → NP_001258543.1  flap endonuclease 1

      See identical proteins and their annotated locations for NP_001258543.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AC132148
      Consensus CDS
      CCDS29573.1
      UniProtKB/TrEMBL
      Q3TGH6, Q8C952, Q8R069, Q91Z50
      Related
      ENSMUSP00000119221.2, ENSMUST00000142241.2
      Conserved Domains (1) summary
      PTZ00217
      Location:1 → 359
      PTZ00217; flap endonuclease-1; Provisional

    2. NM_001271615.3 → NP_001258544.1  flap endonuclease 1

      See identical proteins and their annotated locations for NP_001258544.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AC132148
      Consensus CDS
      CCDS29573.1
      UniProtKB/TrEMBL
      Q3TGH6, Q8C952, Q8R069, Q91Z50
      Conserved Domains (1) summary
      PTZ00217
      Location:1 → 359
      PTZ00217; flap endonuclease-1; Provisional

    3. NM_001410282.1 → NP_001397211.1  flap endonuclease 1

      Status: VALIDATED

      Source sequence(s)
      AC132148
      UniProtKB/TrEMBL
      Q91Z50
      Related
      ENSMUSP00000025651.5, ENSMUST00000025651.6

    4. NM_007999.6 → NP_032025.2  flap endonuclease 1

      See identical proteins and their annotated locations for NP_032025.2

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the longest transcript. Variants 1, 2 and 3 encode the same protein.
      Source sequence(s)
      AC132148
      Consensus CDS
      CCDS29573.1
      UniProtKB/TrEMBL
      Q3TGH6, Q8C952, Q8R069, Q91Z50
      Related
      ENSMUSP00000117246.2, ENSMUST00000156291.2
      Conserved Domains (1) summary
      PTZ00217
      Location:1 → 359
      PTZ00217; flap endonuclease-1; Provisional

    RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

    Reference GRCm39 C57BL/6J

    Genomic

    1. NC_000085.7 Reference GRCm39 C57BL/6J

      Range
      10176496..10181757 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006526663.4 → XP_006526726.1  flap endonuclease 1 isoform X1

      See identical proteins and their annotated locations for XP_006526726.1

      UniProtKB/TrEMBL
      Q3TGH6, Q8C952, Q8R069, Q91Z50
      Conserved Domains (1) summary
      PTZ00217
      Location:1 → 359
      PTZ00217; flap endonuclease-1; Provisional
    Nucleotide Protein Strain
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P39749.1 GenPept UniProtKB/Swiss-Prot:P39749

    Gene LinkOut

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

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