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P39749

- FEN1_MOUSE

UniProt

P39749 - FEN1_MOUSE

Protein

Flap endonuclease 1

Gene

Fen1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 107 (01 Oct 2014)
      Sequence version 1 (01 Feb 1995)
      Previous versions | rss
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    Functioni

    Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structurs that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.UniRule annotation

    Cofactori

    Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding.UniRule annotation

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi34 – 341Magnesium 1UniRule annotation
    Binding sitei47 – 471DNA substrateUniRule annotation
    Binding sitei69 – 691DNA substrateUniRule annotation
    Metal bindingi84 – 841Magnesium 1UniRule annotation
    Metal bindingi156 – 1561Magnesium 1UniRule annotation
    Binding sitei156 – 1561DNA substrateUniRule annotation
    Metal bindingi158 – 1581Magnesium 1UniRule annotation
    Metal bindingi177 – 1771Magnesium 2UniRule annotation
    Metal bindingi179 – 1791Magnesium 2UniRule annotation
    Binding sitei229 – 2291DNA substrateUniRule annotation
    Metal bindingi231 – 2311Magnesium 2UniRule annotation
    Binding sitei231 – 2311DNA substrateUniRule annotation

    GO - Molecular functioni

    1. 5'-3' exonuclease activity Source: UniProtKB-HAMAP
    2. 5'-flap endonuclease activity Source: UniProtKB-HAMAP
    3. DNA binding Source: MGI
    4. exonuclease activity Source: MGI
    5. flap endonuclease activity Source: MGI
    6. magnesium ion binding Source: MGI
    7. manganese ion binding Source: MGI

    GO - Biological processi

    1. base-excision repair Source: UniProtKB-HAMAP
    2. DNA catabolic process, endonucleolytic Source: GOC
    3. DNA repair Source: MGI
    4. DNA replication Source: MGI
    5. DNA replication, removal of RNA primer Source: UniProtKB-HAMAP
    6. nucleic acid phosphodiester bond hydrolysis Source: GOC

    Keywords - Molecular functioni

    Endonuclease, Exonuclease, Hydrolase, Nuclease

    Keywords - Biological processi

    DNA damage, DNA repair, DNA replication

    Keywords - Ligandi

    Magnesium, Metal-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Flap endonuclease 1UniRule annotation (EC:3.1.-.-UniRule annotation)
    Short name:
    FEN-1UniRule annotation
    Alternative name(s):
    Flap structure-specific endonuclease 1UniRule annotation
    Gene namesi
    Name:Fen1UniRule annotation
    Synonyms:Fen-1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Unplaced

    Organism-specific databases

    MGIiMGI:102779. Fen1.

    Subcellular locationi

    Nucleusnucleolus UniRule annotation. Nucleusnucleoplasm UniRule annotation. Mitochondrion
    Note: Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.UniRule annotation

    GO - Cellular componenti

    1. mitochondrion Source: UniProtKB-SubCell
    2. nucleolus Source: UniProtKB-SubCell
    3. nucleoplasm Source: UniProtKB-SubCell
    4. nucleus Source: MGI

    Keywords - Cellular componenti

    Mitochondrion, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 378378Flap endonuclease 1PRO_0000154070Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei19 – 191Symmetric dimethylarginine; by PRMT5UniRule annotation
    Modified residuei78 – 781N6-acetyllysineUniRule annotation
    Modified residuei98 – 981Symmetric dimethylarginine; by PRMT5UniRule annotation
    Modified residuei102 – 1021Symmetric dimethylarginine; by PRMT5UniRule annotation
    Modified residuei185 – 1851Phosphoserine; by CDK2UniRule annotation
    Modified residuei190 – 1901Symmetric dimethylarginine; by PRMT5UniRule annotation
    Modified residuei195 – 1951PhosphoserineBy similarity
    Modified residuei352 – 3521N6-acetyllysineUniRule annotation
    Modified residuei373 – 3731N6-acetyllysine1 PublicationUniRule annotation
    Modified residuei378 – 3781N6-acetyllysineUniRule annotation

    Post-translational modificationi

    Acetylated by EP300. Acetylation inhibits both endonuclease and exonuclease activity. Acetylation also reduces DNA-binding activity but does not affect interaction with PCNA or EP300.UniRule annotation
    Phosphorylation upon DNA damage induces relocalization to the nuclear plasma. Phosphorylation at Ser-185 by CDK2 occurs during late S-phase and results in dissociation from PCNA.UniRule annotation
    Methylation at Arg-190 by PRMT5 impedes Ser-185 phosphorylation and increases interaction with PCNA.UniRule annotation

    Keywords - PTMi

    Acetylation, Methylation, Phosphoprotein

    Proteomic databases

    MaxQBiP39749.
    PaxDbiP39749.
    PRIDEiP39749.

    Expressioni

    Gene expression databases

    CleanExiMM_FEN1.
    GenevestigatoriP39749.

    Interactioni

    Subunit structurei

    Interacts with PCNA. Three molecules of Fen1 bind to one PCNA trimer with each molecule binding to one PCNA monomer. PCNA stimulates the nuclease activity without altering cleavage specificity. The C-terminal domain binds EP300. Can bind simultaneously to both PCNA and EP300. Interacts with DDX11.UniRule annotation

    Structurei

    3D structure databases

    ProteinModelPortaliP39749.
    SMRiP39749. Positions 2-334.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 102102N-domainAdd
    BLAST
    Regioni120 – 251132I-domainAdd
    BLAST
    Regioni334 – 3429Interaction with PCNAUniRule annotation

    Sequence similaritiesi

    Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.UniRule annotation

    Phylogenomic databases

    eggNOGiCOG0258.
    HOVERGENiHBG000844.
    InParanoidiP39749.

    Family and domain databases

    Gene3Di3.40.50.1010. 1 hit.
    HAMAPiMF_00614. Fen.
    InterProiIPR020045. 5-3_exonuclease_C.
    IPR023426. Flap_endonuc.
    IPR008918. HhH2.
    IPR029060. PIN_domain-like.
    IPR006086. XPG-I_dom.
    IPR019974. XPG_CS.
    IPR006085. XPG_DNA_repair_N.
    [Graphical view]
    PfamiPF00867. XPG_I. 1 hit.
    PF00752. XPG_N. 1 hit.
    [Graphical view]
    SMARTiSM00279. HhH2. 1 hit.
    SM00484. XPGI. 1 hit.
    SM00485. XPGN. 1 hit.
    [Graphical view]
    SUPFAMiSSF47807. SSF47807. 1 hit.
    SSF88723. SSF88723. 1 hit.
    PROSITEiPS00841. XPG_1. 1 hit.
    PS00842. XPG_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P39749-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGIHGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG    50
    DVLQNEEGET TSLMGMFYRT IRMENGIKPV YVFDGKPPQL KSGELAKRSE 100
    RRAEAEKQLQ QAQEAGMEEE VEKFTKRLVK VTKQHNDECK HLLSLMGIPY 150
    LDAPSEAEAS CAALAKAGKV YAAATEDMDC LTFGSPVLMR HLTASEAKKL 200
    PIQEFHLSRV LQELGLNQEQ FVDLCILLGS DYCESIRGIG AKRAVDLIQK 250
    HKSIEEIVRR LDPSKYPVPE NWLHKEAQQL FLEPEVVDPE SVELKWSEPN 300
    EEELVKFMCG EKQFSEERIR SGVKRLSKSR QGSTQGRLDD FFKVTGSLSS 350
    AKRKEPEPKG PAKKKAKTGG AGKFRRGK 378
    Length:378
    Mass (Da):42,315
    Last modified:February 1, 1995 - v1
    Checksum:i827946BD8BDCEF39
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L26320 mRNA. Translation: AAC37664.1.
    PIRiA53730.
    UniGeneiMm.2952.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L26320 mRNA. Translation: AAC37664.1 .
    PIRi A53730.
    UniGenei Mm.2952.

    3D structure databases

    ProteinModelPortali P39749.
    SMRi P39749. Positions 2-334.
    ModBasei Search...
    MobiDBi Search...

    Proteomic databases

    MaxQBi P39749.
    PaxDbi P39749.
    PRIDEi P39749.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Organism-specific databases

    MGIi MGI:102779. Fen1.

    Phylogenomic databases

    eggNOGi COG0258.
    HOVERGENi HBG000844.
    InParanoidi P39749.

    Miscellaneous databases

    ChiTaRSi FEN1. mouse.
    PROi P39749.
    SOURCEi Search...

    Gene expression databases

    CleanExi MM_FEN1.
    Genevestigatori P39749.

    Family and domain databases

    Gene3Di 3.40.50.1010. 1 hit.
    HAMAPi MF_00614. Fen.
    InterProi IPR020045. 5-3_exonuclease_C.
    IPR023426. Flap_endonuc.
    IPR008918. HhH2.
    IPR029060. PIN_domain-like.
    IPR006086. XPG-I_dom.
    IPR019974. XPG_CS.
    IPR006085. XPG_DNA_repair_N.
    [Graphical view ]
    Pfami PF00867. XPG_I. 1 hit.
    PF00752. XPG_N. 1 hit.
    [Graphical view ]
    SMARTi SM00279. HhH2. 1 hit.
    SM00484. XPGI. 1 hit.
    SM00485. XPGN. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47807. SSF47807. 1 hit.
    SSF88723. SSF88723. 1 hit.
    PROSITEi PS00841. XPG_1. 1 hit.
    PS00842. XPG_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Functional domains within FEN-1 and RAD2 define a family of structure-specific endonucleases: implications for nucleotide excision repair."
      Harrington J.J., Lieber M.R.
      Genes Dev. 8:1344-1355(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 260-275 AND 331-352, FUNCTION.
      Strain: BALB/c.
    2. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
      Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
      Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-373, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic fibroblast.

    Entry informationi

    Entry nameiFEN1_MOUSE
    AccessioniPrimary (citable) accession number: P39749
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: February 1, 1995
    Last modified: October 1, 2014
    This is version 107 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3