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Protein

Flap endonuclease 1

Gene

Fen1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 annotation1 Publication

Cofactori

Mg2+UniRule annotationNote: 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)DescriptionActionsGraphical viewLength
Metal bindingi34Magnesium 1UniRule annotation1
Binding sitei47DNA substrateUniRule annotation1
Binding sitei69DNA substrateUniRule annotation1
Metal bindingi84Magnesium 1UniRule annotation1
Metal bindingi156Magnesium 1UniRule annotation1
Binding sitei156DNA substrateUniRule annotation1
Metal bindingi158Magnesium 1UniRule annotation1
Metal bindingi177Magnesium 2UniRule annotation1
Metal bindingi179Magnesium 2UniRule annotation1
Binding sitei229DNA substrateUniRule annotation1
Metal bindingi231Magnesium 2UniRule annotation1
Binding sitei231DNA substrateUniRule annotation1

GO - Molecular functioni

  • 5'-3' exonuclease activity Source: MGI
  • 5'-flap endonuclease activity Source: MGI
  • DNA binding Source: MGI
  • exonuclease activity Source: MGI
  • flap endonuclease activity Source: MGI
  • magnesium ion binding Source: MGI
  • manganese ion binding Source: MGI
  • RNA-DNA hybrid ribonuclease activity Source: MGI

GO - Biological processi

  • base-excision repair Source: UniProtKB-HAMAP
  • DNA repair Source: MGI
  • DNA replication Source: MGI
  • DNA replication, removal of RNA primer Source: MGI
  • nucleic acid phosphodiester bond hydrolysis Source: MGI
  • positive regulation of sister chromatid cohesion Source: MGI
Complete GO annotation...

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
Proteomesi
  • UP000000589 Componenti: 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

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001540701 – 378Flap endonuclease 1Add BLAST378

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei19Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity1
Modified residuei78N6-acetyllysineUniRule annotationBy similarity1
Modified residuei98Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity1
Modified residuei102Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity1
Modified residuei185Phosphoserine; by CDK2UniRule annotationBy similarity1
Modified residuei190Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity1
Modified residuei195PhosphoserineBy similarity1
Modified residuei253PhosphoserineBy similarity1
Modified residuei291PhosphoserineBy similarity1
Modified residuei333PhosphoserineBy similarity1
Modified residuei334PhosphothreonineBy similarity1
Modified residuei352N6-acetyllysineUniRule annotationBy similarity1
Modified residuei373N6-acetyllysineCombined sources1
Modified residuei378N6-acetyllysineUniRule annotationBy similarity1

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

EPDiP39749.
MaxQBiP39749.
PaxDbiP39749.
PeptideAtlasiP39749.
PRIDEiP39749.

PTM databases

iPTMnetiP39749.
PhosphoSitePlusiP39749.

Expressioni

Gene expression databases

CleanExiMM_FEN1.

Interactioni

Subunit structurei

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 PCNA; can bind simultaneously to both PCNA and EP300. Interacts with DDX11; this interaction is direct and increases flap endonuclease activity of FEN1.UniRule annotationBy similarity

Protein-protein interaction databases

IntActiP39749. 2 interactors.
STRINGi10090.ENSMUSP00000025651.

Structurei

3D structure databases

ProteinModelPortaliP39749.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 102N-domainAdd BLAST102
Regioni120 – 251I-domainAdd BLAST132
Regioni334 – 342Interaction with PCNAUniRule annotation9

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
HOVERGENiHBG000844.
InParanoidiP39749.

Family and domain databases

CDDicd09867. PIN_FEN1. 1 hit.
Gene3Di3.40.50.1010. 1 hit.
HAMAPiMF_00614. Fen. 1 hit.
InterProiIPR020045. 5-3_exonuclease_C.
IPR023426. Flap_endonuc.
IPR008918. HhH2.
IPR029060. PIN_domain-like.
IPR006086. XPG-I_dom.
IPR006084. XPG/Rad2.
IPR019974. XPG_CS.
IPR006085. XPG_DNA_repair_N.
[Graphical view]
PANTHERiPTHR11081. PTHR11081. 1 hit.
PfamiPF00867. XPG_I. 1 hit.
PF00752. XPG_N. 1 hit.
[Graphical view]
PRINTSiPR00853. XPGRADSUPER.
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

        10         20         30         40         50
MGIHGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG
60 70 80 90 100
DVLQNEEGET TSLMGMFYRT IRMENGIKPV YVFDGKPPQL KSGELAKRSE
110 120 130 140 150
RRAEAEKQLQ QAQEAGMEEE VEKFTKRLVK VTKQHNDECK HLLSLMGIPY
160 170 180 190 200
LDAPSEAEAS CAALAKAGKV YAAATEDMDC LTFGSPVLMR HLTASEAKKL
210 220 230 240 250
PIQEFHLSRV LQELGLNQEQ FVDLCILLGS DYCESIRGIG AKRAVDLIQK
260 270 280 290 300
HKSIEEIVRR LDPSKYPVPE NWLHKEAQQL FLEPEVVDPE SVELKWSEPN
310 320 330 340 350
EEELVKFMCG EKQFSEERIR SGVKRLSKSR QGSTQGRLDD FFKVTGSLSS
360 370
AKRKEPEPKG PAKKKAKTGG AGKFRRGK
Length:378
Mass (Da):42,315
Last modified:February 1, 1995 - v1
Checksum:i827946BD8BDCEF39
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L26320 mRNA. Translation: AAC37664.1.
PIRiA53730.
UniGeneiMm.2952.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L26320 mRNA. Translation: AAC37664.1.
PIRiA53730.
UniGeneiMm.2952.

3D structure databases

ProteinModelPortaliP39749.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP39749. 2 interactors.
STRINGi10090.ENSMUSP00000025651.

PTM databases

iPTMnetiP39749.
PhosphoSitePlusiP39749.

Proteomic databases

EPDiP39749.
MaxQBiP39749.
PaxDbiP39749.
PeptideAtlasiP39749.
PRIDEiP39749.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:102779. Fen1.

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
HOVERGENiHBG000844.
InParanoidiP39749.

Miscellaneous databases

ChiTaRSiFen1. mouse.
PROiP39749.
SOURCEiSearch...

Gene expression databases

CleanExiMM_FEN1.

Family and domain databases

CDDicd09867. PIN_FEN1. 1 hit.
Gene3Di3.40.50.1010. 1 hit.
HAMAPiMF_00614. Fen. 1 hit.
InterProiIPR020045. 5-3_exonuclease_C.
IPR023426. Flap_endonuc.
IPR008918. HhH2.
IPR029060. PIN_domain-like.
IPR006086. XPG-I_dom.
IPR006084. XPG/Rad2.
IPR019974. XPG_CS.
IPR006085. XPG_DNA_repair_N.
[Graphical view]
PANTHERiPTHR11081. PTHR11081. 1 hit.
PfamiPF00867. XPG_I. 1 hit.
PF00752. XPG_N. 1 hit.
[Graphical view]
PRINTSiPR00853. XPGRADSUPER.
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]
ProtoNetiSearch...

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: November 30, 2016
This is version 128 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.