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Protein

Flap endonuclease 1

Gene

Fen1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 annotation

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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi34 – 341Magnesium 1UniRule annotation
Binding sitei47 – 471DNA substrateUniRule annotation
Binding sitei70 – 701DNA substrateUniRule annotation
Metal bindingi86 – 861Magnesium 1UniRule annotation
Metal bindingi158 – 1581Magnesium 1UniRule annotation
Binding sitei158 – 1581DNA substrateUniRule annotation
Metal bindingi160 – 1601Magnesium 1UniRule annotation
Metal bindingi179 – 1791Magnesium 2UniRule annotation
Metal bindingi181 – 1811Magnesium 2UniRule annotation
Binding sitei231 – 2311DNA substrateUniRule annotation
Metal bindingi233 – 2331Magnesium 2UniRule annotation
Binding sitei233 – 2331DNA substrateUniRule annotation

GO - Molecular functioni

GO - Biological processi

  • DNA repair Source: UniProtKB-KW
  • DNA replication, removal of RNA primer Source: Ensembl
  • memory Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Exonuclease, Hydrolase, Nuclease

Keywords - Biological processi

DNA damage, DNA repair, DNA replication

Keywords - Ligandi

Magnesium, Metal-binding

Enzyme and pathway databases

ReactomeiR-RNO-110362. POLB-Dependent Long Patch Base Excision Repair.
R-RNO-174437. Removal of the Flap Intermediate from the C-strand.
R-RNO-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-RNO-5685939. HDR through MMEJ (alt-NHEJ).
R-RNO-69166. Removal of the Flap Intermediate.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi621821. Fen1.

Subcellular locationi

  • Nucleusnucleolus UniRule annotation
  • Nucleusnucleoplasm UniRule annotation
  • Mitochondrion UniRule annotation

  • 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)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 380380Flap endonuclease 1PRO_0000403485Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei19 – 191Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity
Modified residuei80 – 801N6-acetyllysineUniRule annotationBy similarity
Modified residuei100 – 1001Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity
Modified residuei104 – 1041Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity
Modified residuei187 – 1871Phosphoserine; by CDK2UniRule annotationBy similarity
Modified residuei192 – 1921Symmetric dimethylarginine; by PRMT5UniRule annotationBy similarity
Modified residuei197 – 1971PhosphoserineBy similarity
Modified residuei354 – 3541N6-acetyllysineUniRule annotationBy similarity
Modified residuei375 – 3751N6-acetyllysineUniRule annotationBy similarity
Modified residuei380 – 3801N6-acetyllysineUniRule annotationBy similarity

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-187 by CDK2 occurs during late S-phase and results in dissociation from PCNA.UniRule annotation
Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA.UniRule annotation

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

PaxDbiQ5XIP6.
PRIDEiQ5XIP6.

PTM databases

iPTMnetiQ5XIP6.

Expressioni

Gene expression databases

GenevisibleiQ5XIP6. RN.

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

Protein-protein interaction databases

IntActiQ5XIP6. 1 interaction.
STRINGi10116.ENSRNOP00000027842.

Structurei

3D structure databases

ProteinModelPortaliQ5XIP6.
SMRiQ5XIP6. Positions 2-356.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 104104N-domainAdd
BLAST
Regioni122 – 253132I-domainAdd
BLAST
Regioni336 – 3449Interaction with PCNAUniRule annotation

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00640000091478.
HOGENOMiHOG000193853.
HOVERGENiHBG000844.
InParanoidiQ5XIP6.
KOiK04799.
OMAiGSQDYDS.
OrthoDBiEOG72JWHG.
PhylomeDBiQ5XIP6.
TreeFamiTF105701.

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.
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.

Q5XIP6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGIQGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG
60 70 80 90 100
DVLQNEEGET TSHLMGMFYR TIRMMENGIK PVYIFDGKPP QLKSGELAKR
110 120 130 140 150
SERRAEAEKQ LQQAQEAGAE EEVEKFTKRL VKVTKQHNDE CKHLLSLMGI
160 170 180 190 200
PYLDAPSEAE ASCAALAKAG KVYAAATEDM DCLTFGSPVL MRHLTASEAK
210 220 230 240 250
KLPIQEFHLS RVLQELGLNQ EQFVDLCILL GSDYCESVRG IGPKRAVDLI
260 270 280 290 300
QKHKSIEEIV RRLDPSKYPV PENWLHKEAR QLFLEPEVLD PESVELKWSE
310 320 330 340 350
PNEEELVKFM CGEKQFSEER IRSGVKRLNK SRQGSTQGRL DDFFKVTGSL
360 370 380
SSAKRKEPEP KGPAKKKAKT GGAGKFRRGK
Length:380
Mass (Da):42,609
Last modified:November 23, 2004 - v1
Checksum:i3732F5FF0E121670
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti95 – 962GE → AQ in AAF81265 (Ref. 1) Curated
Sequence conflicti289 – 2891L → V in AAF81265 (Ref. 1) Curated
Sequence conflicti372 – 3721G → A in AAF81265 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281018 mRNA. Translation: AAF81265.1.
CH473953 Genomic DNA. Translation: EDM12793.1.
BC083630 mRNA. Translation: AAH83630.1.
RefSeqiNP_445882.1. NM_053430.1.
XP_006231135.1. XM_006231073.2.
XP_006231136.1. XM_006231074.2.
XP_008758467.1. XM_008760245.1.
XP_008758468.1. XM_008760246.1.
UniGeneiRn.16664.

Genome annotation databases

EnsembliENSRNOT00000027842; ENSRNOP00000027842; ENSRNOG00000020531.
GeneIDi84490.
KEGGirno:84490.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF281018 mRNA. Translation: AAF81265.1.
CH473953 Genomic DNA. Translation: EDM12793.1.
BC083630 mRNA. Translation: AAH83630.1.
RefSeqiNP_445882.1. NM_053430.1.
XP_006231135.1. XM_006231073.2.
XP_006231136.1. XM_006231074.2.
XP_008758467.1. XM_008760245.1.
XP_008758468.1. XM_008760246.1.
UniGeneiRn.16664.

3D structure databases

ProteinModelPortaliQ5XIP6.
SMRiQ5XIP6. Positions 2-356.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ5XIP6. 1 interaction.
STRINGi10116.ENSRNOP00000027842.

PTM databases

iPTMnetiQ5XIP6.

Proteomic databases

PaxDbiQ5XIP6.
PRIDEiQ5XIP6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000027842; ENSRNOP00000027842; ENSRNOG00000020531.
GeneIDi84490.
KEGGirno:84490.

Organism-specific databases

CTDi2237.
RGDi621821. Fen1.

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00640000091478.
HOGENOMiHOG000193853.
HOVERGENiHBG000844.
InParanoidiQ5XIP6.
KOiK04799.
OMAiGSQDYDS.
OrthoDBiEOG72JWHG.
PhylomeDBiQ5XIP6.
TreeFamiTF105701.

Enzyme and pathway databases

ReactomeiR-RNO-110362. POLB-Dependent Long Patch Base Excision Repair.
R-RNO-174437. Removal of the Flap Intermediate from the C-strand.
R-RNO-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-RNO-5685939. HDR through MMEJ (alt-NHEJ).
R-RNO-69166. Removal of the Flap Intermediate.

Miscellaneous databases

NextBioi617038.
PROiQ5XIP6.

Gene expression databases

GenevisibleiQ5XIP6. RN.

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.
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...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of a rat DNA structure-specific endonuclease (Fen-1)."
    Chen D., Cao G., Yang S., Li M., Chen J.
    Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Brown Norway.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.

Entry informationi

Entry nameiFEN1_RAT
AccessioniPrimary (citable) accession number: Q5XIP6
Secondary accession number(s): Q9JHW7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2011
Last sequence update: November 23, 2004
Last modified: May 11, 2016
This is version 87 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, Reference proteome

Documents

  1. 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.