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    FEN1 flap structure-specific endonuclease 1 [ Homo sapiens (human) ]

    Gene ID: 2237, updated on 7-Jul-2019

    Summary

    Official Symbol
    FEN1provided by HGNC
    Official Full Name
    flap structure-specific endonuclease 1provided by HGNC
    Primary source
    HGNC:HGNC:3650
    See related
    Ensembl:ENSG00000168496 MIM:600393
    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
    MF1; RAD2; FEN-1
    Summary
    The protein encoded by this gene removes 5' overhanging flaps in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. Direct physical interaction between this protein and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, thus passing the substrate from one enzyme to another. The protein is a member of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free DNA replication. DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by the protein encoded by this gene. Therefore, secondary structure can deter the protective function of this protein, leading to site-specific trinucleotide expansions. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in lymph node (RPKM 16.0), bone marrow (RPKM 13.0) and 24 other tissues See more
    Orthologs

    Genomic context

    See FEN1 in Genome Data Viewer
    Location:
    11q12.2
    Exon count:
    2
    Annotation release Status Assembly Chr Location
    109.20190607 current GRCh38.p13 (GCF_000001405.39) 11 NC_000011.10 (61792911..61797238)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (61560109..61564716)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene MYRF antisense RNA 1 Neighboring gene myelin regulatory factor Neighboring gene transmembrane protein 258 Neighboring gene microRNA 611 Neighboring gene fatty acid desaturase 1 Neighboring gene microRNA 1908 Neighboring gene fatty acid desaturase 2 Neighboring gene Sharpr-MPRA regulatory region 6587

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Phenotypes

    NHGRI GWAS Catalog

    Description
    An atlas of genetic influences on human blood metabolites.
    NHGRI GWA Catalog
    Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.
    NHGRI GWA Catalog
    Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes.
    NHGRI GWA Catalog
    Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortiu
    NHGRI GWA Catalog
    Genome-wide association study identifies three susceptibility loci for laryngeal squamous cell carcinoma in the Chinese population.
    NHGRI GWA Catalog
    Genome-wide association study of plasma N6 polyunsaturated fatty acids within the cohorts for heart and aging research in genomic epidemiology consortium.
    NHGRI GWA Catalog
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    NHGRI GWA Catalog
    Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk.
    NHGRI GWA Catalog
    New gene functions in megakaryopoiesis and platelet formation.
    NHGRI GWA Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    integrase gag-pol FEN-1 is stimulated by HIV-1 Integrase and is hypothesized to play a role in the processing of HIV-1 integration intermediates PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from BioSystems

    • Base Excision Repair, organism-specific biosystem (from REACTOME)
      Base Excision Repair, organism-specific biosystemOf the three major pathways involved in the repair of nucleotide damage in DNA, base excision repair (BER) involves the greatest number of individual enzymatic activities. This is the consequence of ...
    • Base excision repair, organism-specific biosystem (from KEGG)
      Base excision repair, organism-specific biosystemBase excision repair (BER) is the predominant DNA damage repair pathway for the processing of small base lesions, derived from oxidation and alkylation damages. BER is normally defined as DNA repair ...
    • Base excision repair, conserved biosystem (from KEGG)
      Base excision repair, conserved biosystemBase excision repair (BER) is the predominant DNA damage repair pathway for the processing of small base lesions, derived from oxidation and alkylation damages. BER is normally defined as DNA repair ...
    • Cell Cycle, organism-specific biosystem (from REACTOME)
      Cell Cycle, organism-specific biosystem
      Cell Cycle
    • Cell Cycle, Mitotic, organism-specific biosystem (from REACTOME)
      Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
    • Chromosome Maintenance, organism-specific biosystem (from REACTOME)
      Chromosome Maintenance, organism-specific biosystemChromosome maintenance is critical for stable chromosome function in mammalian and other eukaryotic cells. Aspects of telomere maintenance and nucleosome assembly are covered here.
    • DNA Double-Strand Break Repair, organism-specific biosystem (from REACTOME)
      DNA Double-Strand Break Repair, organism-specific biosystemNumerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-s...
    • DNA Repair, organism-specific biosystem (from REACTOME)
      DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
    • DNA Replication, organism-specific biosystem (from REACTOME)
      DNA Replication, organism-specific biosystemStudies in the past decade have suggested that the basic mechanism of DNA replication initiation is conserved in all kingdoms of life. Initiation in unicellular eukaryotes, in particular Saccharomyce...
    • DNA replication, organism-specific biosystem (from KEGG)
      DNA replication, organism-specific biosystemA complex network of interacting proteins and enzymes is required for DNA replication. Generally, DNA replication follows a multistep enzymatic pathway. At the DNA replication fork, a DNA helicase (D...
    • DNA replication, conserved biosystem (from KEGG)
      DNA replication, conserved biosystemA complex network of interacting proteins and enzymes is required for DNA replication. Generally, DNA replication follows a multistep enzymatic pathway. At the DNA replication fork, a DNA helicase (D...
    • DNA strand elongation, organism-specific biosystem (from REACTOME)
      DNA strand elongation, organism-specific biosystemAccurate and efficient genome duplication requires coordinated processes to replicate two template strands at eucaryotic replication forks. Knowledge of the fundamental reactions involved in replicat...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Early Phase of HIV Life Cycle, organism-specific biosystem (from REACTOME)
      Early Phase of HIV Life Cycle, organism-specific biosystemIn the early phase of HIV lifecycle, an active virion binds and enters a target cell mainly by specific interactions of the viral envelope proteins with host cell surface receptors. The virion core...
    • Extension of Telomeres, organism-specific biosystem (from REACTOME)
      Extension of Telomeres, organism-specific biosystemTelomerase acts as reverse transcriptase in the elongation of telomeres (Smogorzewska and de Lange 2004).
    • HDR through MMEJ (alt-NHEJ), organism-specific biosystem (from REACTOME)
      HDR through MMEJ (alt-NHEJ), organism-specific biosystemHomology directed repair (HDR) through microhomology-mediated end joining (MMEJ) is an error prone process also known as alternative nonhomologous end joining (alt-NHEJ), although it does not involve...
    • HIV Infection, organism-specific biosystem (from REACTOME)
      HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
    • HIV Life Cycle, organism-specific biosystem (from REACTOME)
      HIV Life Cycle, organism-specific biosystemThe life cycle of HIV-1 is divided into early and late phases, shown schematically in the figure. In the early phase, an HIV-1 virion binds to receptors and co-receptors on the human host cell surfac...
    • Homology Directed Repair, organism-specific biosystem (from REACTOME)
      Homology Directed Repair, organism-specific biosystemHomology directed repair (HDR) of DNA double strand breaks (DSBs) requires resection of DNA DSB ends. Resection creates 3'-ssDNA overhangs which then anneal with a homologous DNA sequence. This homol...
    • Infectious disease, organism-specific biosystem (from REACTOME)
      Infectious disease, organism-specific biosystem
      Infectious disease
    • Lagging Strand Synthesis, organism-specific biosystem (from REACTOME)
      Lagging Strand Synthesis, organism-specific biosystemDue to the antiparallel nature of DNA, DNA polymerization is unidirectional, and one strand is synthesized discontinuously. This strand is called the lagging strand. Although the polymerase switching...
    • Non-homologous end-joining, organism-specific biosystem (from KEGG)
      Non-homologous end-joining, organism-specific biosystemNonhomologous end joining (NHEJ) eliminates DNA double-strand breaks (DSBs) by direct ligation. NHEJ involves binding of the KU heterodimer to double-stranded DNA ends, recruitment of DNA-PKcs (MRX c...
    • Non-homologous end-joining, conserved biosystem (from KEGG)
      Non-homologous end-joining, conserved biosystemNonhomologous end joining (NHEJ) eliminates DNA double-strand breaks (DSBs) by direct ligation. NHEJ involves binding of the KU heterodimer to double-stranded DNA ends, recruitment of DNA-PKcs (MRX c...
    • PCNA-Dependent Long Patch Base Excision Repair, organism-specific biosystem (from REACTOME)
      PCNA-Dependent Long Patch Base Excision Repair, organism-specific biosystemLong-patch base excision repair (BER) can proceed through PCNA-dependent DNA strand displacement synthesis by replicative DNA polymerases - DNA polymerase delta complex (POLD) or DNA polymerase epsil...
    • POLB-Dependent Long Patch Base Excision Repair, organism-specific biosystem (from REACTOME)
      POLB-Dependent Long Patch Base Excision Repair, organism-specific biosystemDuring POLB-dependent long patch base excision repair (BER), PARP1 and/or PARP2 is recruited to the BER site along with flap endonuclease FEN1. PARP1 and/or PARP2 and FEN1 facilitate POLB-mediated st...
    • Processive synthesis on the C-strand of the telomere, organism-specific biosystem (from REACTOME)
      Processive synthesis on the C-strand of the telomere, organism-specific biosystemOnce polymerase switching from pol alpha to pol delta is complete the processive synthesis of a short run of DNA called an Okazaki fragment begins. DNA synthesis is discontinuous and as the extending...
    • Processive synthesis on the lagging strand, organism-specific biosystem (from REACTOME)
      Processive synthesis on the lagging strand, organism-specific biosystemThe key event that allows the processive synthesis on the lagging strand, is polymerase switching from pol alpha to pol delta, as on the leading strand. However, the processive synthesis on the laggi...
    • Removal of the Flap Intermediate, organism-specific biosystem (from REACTOME)
      Removal of the Flap Intermediate, organism-specific biosystemTwo endonucleases, Dna2 and flap endonuclease 1 (FEN-1), are responsible for resolving the nascent flap structure (Tsurimoto and Stillman 1991). The Dna2 endonuclease/helicase in yeast is a monomer o...
    • Removal of the Flap Intermediate from the C-strand, organism-specific biosystem (from REACTOME)
      Removal of the Flap Intermediate from the C-strand, organism-specific biosystemTwo endonucleases, Dna2 and flap endonuclease 1 (FEN-1), are responsible for resolving the nascent flap structure (Tsurimoto and Stillman 1991). The Dna2 endonuclease/helicase in yeast is a monomer o...
    • Resolution of AP sites via the multiple-nucleotide patch replacement pathway, organism-specific biosystem (from REACTOME)
      Resolution of AP sites via the multiple-nucleotide patch replacement pathway, organism-specific biosystemWhile the single nucleotide replacement pathway appears to facilitate the repair of most damaged bases, an alternative BER pathway is evoked when the structure of the 5'-terminal sugar phosphate is s...
    • Resolution of Abasic Sites (AP sites), organism-specific biosystem (from REACTOME)
      Resolution of Abasic Sites (AP sites), organism-specific biosystemResolution of AP sites can occur through the single nucleotide replacement pathway or through the multiple nucleotide patch replacement pathway, also known as the long-patch base excision repair (BER...
    • S Phase, organism-specific biosystem (from REACTOME)
      S Phase, organism-specific biosystemDNA synthesis occurs in the S phase, or the synthesis phase, of the cell cycle. The cell duplicates its hereditary material, and two copies of the chromosome are formed. As DNA replication continues,...
    • Synthesis of DNA, organism-specific biosystem (from REACTOME)
      Synthesis of DNA, organism-specific biosystemThe actual synthesis of DNA occurs in the S phase of the cell cycle. This includes the initiation of DNA replication, when the first nucleotide of the new strand is laid down during the synthesis of ...
    • Telomere C-strand (Lagging Strand) Synthesis, organism-specific biosystem (from REACTOME)
      Telomere C-strand (Lagging Strand) Synthesis, organism-specific biosystemDue to the antiparallel nature of DNA, DNA polymerization is unidirectional, and one strand is synthesized discontinuously. This strand is called the lagging strand. Although the polymerase switching...
    • Telomere Maintenance, organism-specific biosystem (from REACTOME)
      Telomere Maintenance, organism-specific biosystemTelomeres are protein-DNA complexes at the ends of linear chromosomes that are important for genome stability. Telomeric DNA in humans, as in many eukaryotic organisms, consists of tandem repeats (B...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    5'-3' exonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    5'-3' exonuclease activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    5'-flap endonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    5'-flap endonuclease activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    5'-flap endonuclease activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    5'-flap endonuclease activity TAS
    Traceable Author Statement
    more info
     
    DNA binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    RNA-DNA hybrid ribonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    RNA-DNA hybrid ribonuclease activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    damaged DNA binding TAS
    Traceable Author Statement
    more info
    PubMed 
    double-stranded DNA binding TAS
    Traceable Author Statement
    more info
    PubMed 
    double-stranded DNA exodeoxyribonuclease activity TAS
    Traceable Author Statement
    more info
    PubMed 
    endonuclease activity TAS
    Traceable Author Statement
    more info
    PubMed 
    exonuclease activity TAS
    Traceable Author Statement
    more info
    PubMed 
    flap endonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    flap endonuclease activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    magnesium ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    manganese ion binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    DNA repair TAS
    Traceable Author Statement
    more info
    PubMed 
    DNA replication TAS
    Traceable Author Statement
    more info
    PubMed 
    DNA replication, removal of RNA primer IDA
    Inferred from Direct Assay
    more info
    PubMed 
    RNA phosphodiester bond hydrolysis, endonucleolytic IEA
    Inferred from Electronic Annotation
    more info
     
    UV protection TAS
    Traceable Author Statement
    more info
    PubMed 
    base-excision repair IEA
    Inferred from Electronic Annotation
    more info
     
    double-strand break repair TAS
    Traceable Author Statement
    more info
    PubMed 
    double-strand break repair via homologous recombination TAS
    Traceable Author Statement
    more info
     
    memory IEA
    Inferred from Electronic Annotation
    more info
     
    nucleic acid phosphodiester bond hydrolysis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of sister chromatid cohesion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    telomere maintenance via semi-conservative replication TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    membrane HDA PubMed 
    mitochondrion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nuclear chromosome, telomeric region HDA PubMed 
    colocalizes_with nuclear chromosome, telomeric region IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleolus IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein-containing complex IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    flap endonuclease 1
    Names
    DNase IV
    maturation factor-1
    NP_004102.1

    NCBI Reference Sequences (RefSeq)

    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_004111.6NP_004102.1  flap endonuclease 1

      See identical proteins and their annotated locations for NP_004102.1

      Status: REVIEWED

      Source sequence(s)
      BC000323, BP244711
      Consensus CDS
      CCDS8010.1
      UniProtKB/Swiss-Prot
      P39748
      UniProtKB/TrEMBL
      Q6FHX6
      Related
      ENSP00000305480.2, ENST00000305885.3
      Conserved Domains (1) summary
      PTZ00217
      Location:1373
      PTZ00217; flap endonuclease-1; Provisional

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000011.10 Reference GRCh38.p13 Primary Assembly

      Range
      61792911..61797238
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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