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

Gene ID: 2237, updated on 12-Aug-2018

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; Vega:OTTHUMG00000168162
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 current GRCh38.p12 (GCF_000001405.38) 11 NC_000011.10 (61792637..61797244)
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 uncharacterized LOC26070 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

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 Jun 15 11:32:44 2016

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 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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 5'-3' exodeoxyribonuclease activity IBA
Inferred from Biological aspect of Ancestor
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 
magnesium ion binding IEA
Inferred from Electronic Annotation
more info
 
manganese ion binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
single-stranded DNA 5'-3' exodeoxyribonuclease activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
DNA repair IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA repair TAS
Traceable Author Statement
more info
PubMed 
DNA replication TAS
Traceable Author Statement
more info
PubMed 
DNA replication, removal of RNA primer IBA
Inferred from Biological aspect of Ancestor
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 
apoptotic DNA fragmentation IBA
Inferred from Biological aspect of Ancestor
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
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 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_004111.5NP_004102.1  flap endonuclease 1

    See identical proteins and their annotated locations for NP_004102.1

    Status: REVIEWED

    Source sequence(s)
    BC000323, BM450370, BP244711, CN290841
    Consensus CDS
    CCDS8010.1
    UniProtKB/Swiss-Prot
    P39748
    UniProtKB/TrEMBL
    Q6FHX6
    Related
    ENSP00000305480.2, OTTHUMP00000238148, ENST00000305885.2, OTTHUMT00000398526
    Conserved Domains (1) summary
    PTZ00217
    Location:1373
    PTZ00217; flap endonuclease-1; Provisional

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p12 Primary Assembly

    Range
    61792637..61797244
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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