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P39749 (FEN1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Flap endonuclease 1

Short name=FEN-1
EC=3.1.-.-
Alternative name(s):
Flap structure-specific endonuclease 1
Gene names
Name:Fen1
Synonyms:Fen-1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length378 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. Ref.1

Cofactor

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 By similarity.

Subunit structure

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 By similarity.

Subcellular location

Nucleusnucleolus By similarity. Nucleusnucleoplasm By similarity. Mitochondrion. Note: Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage By similarity. HAMAP-Rule MF_03140

Post-translational modification

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 By similarity. HAMAP-Rule MF_03140

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 By similarity. HAMAP-Rule MF_03140

Methylation at Arg-190 by PRMT5 impedes Ser-185 phosphorylation and increases interaction with PCNA By similarity. HAMAP-Rule MF_03140

Sequence similarities

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 378378Flap endonuclease 1 HAMAP-Rule MF_03140
PRO_0000154070

Regions

Region1 – 102102N-domain HAMAP-Rule MF_03140
Region120 – 251132I-domain HAMAP-Rule MF_03140
Region334 – 3429Interaction with PCNA By similarity

Sites

Metal binding341Magnesium 1 By similarity
Metal binding841Magnesium 1 By similarity
Metal binding1561Magnesium 1 By similarity
Metal binding1581Magnesium 1 By similarity
Metal binding1771Magnesium 2 By similarity
Metal binding1791Magnesium 2 By similarity
Metal binding2311Magnesium 2 By similarity
Binding site471DNA substrate By similarity
Binding site691DNA substrate By similarity
Binding site1561DNA substrate By similarity
Binding site2291DNA substrate By similarity
Binding site2311DNA substrate By similarity

Amino acid modifications

Modified residue191Symmetric dimethylarginine; by PRMT5 By similarity
Modified residue781N6-acetyllysine By similarity
Modified residue981Symmetric dimethylarginine; by PRMT5 By similarity
Modified residue1021Symmetric dimethylarginine; by PRMT5 By similarity
Modified residue1851Phosphoserine; by CDK2 By similarity
Modified residue1901Symmetric dimethylarginine; by PRMT5 By similarity
Modified residue1951Phosphoserine By similarity
Modified residue3521N6-acetyllysine By similarity
Modified residue3731N6-acetyllysine
Modified residue3781N6-acetyllysine By similarity

Sequences

Sequence LengthMass (Da)Tools
P39749 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: 827946BD8BDCEF39

FASTA37842,315
        10         20         30         40         50         60 
MGIHGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG DVLQNEEGET 

        70         80         90        100        110        120 
TSLMGMFYRT IRMENGIKPV YVFDGKPPQL KSGELAKRSE RRAEAEKQLQ QAQEAGMEEE 

       130        140        150        160        170        180 
VEKFTKRLVK VTKQHNDECK HLLSLMGIPY LDAPSEAEAS CAALAKAGKV YAAATEDMDC 

       190        200        210        220        230        240 
LTFGSPVLMR HLTASEAKKL PIQEFHLSRV LQELGLNQEQ FVDLCILLGS DYCESIRGIG 

       250        260        270        280        290        300 
AKRAVDLIQK HKSIEEIVRR LDPSKYPVPE NWLHKEAQQL FLEPEVVDPE SVELKWSEPN 

       310        320        330        340        350        360 
EEELVKFMCG EKQFSEERIR SGVKRLSKSR QGSTQGRLDD FFKVTGSLSS AKRKEPEPKG 

       370 
PAKKKAKTGG AGKFRRGK 

« Hide

References

« Hide 'large scale' references
[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L26320 mRNA. Translation: AAC37664.1.
PIRA53730.
UniGeneMm.2952.

3D structure databases

ProteinModelPortalP39749.
SMRP39749. Positions 2-334.
ModBaseSearch...
MobiDBSearch...

Proteomic databases

PaxDbP39749.
PRIDEP39749.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:102779. Fen1.

Phylogenomic databases

eggNOGCOG0258.
HOVERGENHBG000844.
InParanoidP39749.

Gene expression databases

CleanExMM_FEN1.
GenevestigatorP39749.

Family and domain databases

HAMAPMF_00614. Fen.
InterProIPR020045. 5-3_exonuclease_C.
IPR023426. Flap_endonuc.
IPR008918. HhH2.
IPR006086. XPG-I_dom.
IPR006084. XPG/Rad2.
IPR019974. XPG_CS.
IPR006085. XPG_DNA_repair_N.
[Graphical view]
PANTHERPTHR11081. PTHR11081. 1 hit.
PfamPF00867. XPG_I. 1 hit.
PF00752. XPG_N. 1 hit.
[Graphical view]
PRINTSPR00853. XPGRADSUPER.
SMARTSM00279. HhH2. 1 hit.
SM00484. XPGI. 1 hit.
SM00485. XPGN. 1 hit.
[Graphical view]
SUPFAMSSF47807. SSF47807. 1 hit.
PROSITEPS00841. XPG_1. 1 hit.
PS00842. XPG_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFEN1. mouse.
PROP39749.
SOURCESearch...

Entry information

Entry nameFEN1_MOUSE
AccessionPrimary (citable) accession number: P39749
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: March 19, 2014
This is version 102 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot