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Protein

Flap endonuclease 1

Gene

Fen1

Organism
Mus musculus (Mouse)
Status
Unreviewed-Annotation score: Annotation score: 4 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 annotationSAAS 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

Complete GO annotation...

Keywords - Molecular functioni

EndonucleaseUniRule annotationImported, ExonucleaseUniRule annotation, Hydrolase, Nuclease

Keywords - Biological processi

DNA damage, DNA repairUniRule annotation, DNA replicationUniRule annotation

Keywords - Ligandi

MagnesiumUniRule annotation, Metal-bindingUniRule annotation

Enzyme and pathway databases

ReactomeiR-MMU-110362. POLB-Dependent Long Patch Base Excision Repair.
R-MMU-174437. Removal of the Flap Intermediate from the C-strand.
R-MMU-5651801. PCNA-Dependent Long Patch Base Excision Repair.
R-MMU-5685939. HDR through MMEJ (alt-NHEJ).
R-MMU-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 annotationImported
ORF Names:mCG_1942Imported
OrganismiMus musculus (Mouse)Imported
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:102779. Fen1.

Subcellular locationi

  • Mitochondrion SAAS annotation
  • 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

MitochondrionUniRule annotationSAAS annotation, NucleusUniRule annotationSAAS annotation

PTM / Processingi

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei19 – 191Symmetric dimethylarginine; by PRMT5UniRule annotation
Modified residuei100 – 1001Symmetric dimethylarginine; by PRMT5UniRule annotation
Modified residuei104 – 1041Symmetric dimethylarginine; by PRMT5UniRule annotation
Modified residuei187 – 1871Phosphoserine; by CDK2UniRule annotation
Modified residuei192 – 1921Symmetric dimethylarginine; by PRMT5UniRule annotation
Modified residuei354 – 3541N6-acetyllysineUniRule annotation
Modified residuei375 – 3751N6-acetyllysineUniRule annotation
Modified residuei380 – 3801N6-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
Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA.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

Keywords - PTMi

AcetylationUniRule annotation, MethylationUniRule annotation, PhosphoproteinUniRule annotation

Expressioni

Gene expression databases

BgeeiENSMUSG00000024742.

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

STRINGi10090.ENSMUSP00000025651.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1 – 107107XPGNInterPro annotationAdd
BLAST
Domaini146 – 21873XPGIInterPro annotationAdd
BLAST

Region

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

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili97 – 12428Sequence analysisAdd
BLAST

Sequence similaritiesi

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

Keywords - Domaini

Coiled coilSequence analysis

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00640000091478.
HOVERGENiHBG000844.
KOiK04799.
OMAiGSQDYDS.
OrthoDBiEOG091G0C0E.
TreeFamiTF105701.

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.

Q91Z50-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGIHGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG
60 70 80 90 100
DVLQNEEGET TSHLMGMFYR TIRMMENGIK PVYVFDGKPP QLKSGELAKR
110 120 130 140 150
SERRAEAEKQ LQQAQEAGME EEVEKFTKRL VKVTKQHNDE CKHLLSLMGI
160 170 180 190 200
PYLDAPSEAE ASCAALAKAG KVYAAATEDM DCLTFGSPVL MRHLTASEAK
210 220 230 240 250
KLPIQEFHLS RVLQELGLNQ EQFVDLCILL GSDYCESIRG IGPKRAVDLI
260 270 280 290 300
QKHKSIEEIV RRLDPSKYPV PENWLHKEAQ QLFLEPEVLD PESVELKWSE
310 320 330 340 350
PNEEELVKFM CGEKQFSEER IRSGVKRLSK SRQGSTQGRL DDFFKVTGSL
360 370 380
SSAKRKEPEP KGPAKKKAKT GGAGKFRRGK
Length:380
Mass (Da):42,623
Last modified:December 1, 2001 - v1
Checksum:i1BE903288B46520D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC132148 Genomic DNA. No translation available.
BC010203 mRNA. Translation: AAH10203.1.
AK046256 mRNA. Translation: BAC32660.1.
AK078778 mRNA. Translation: BAC37390.1.
AB191468 Genomic DNA. Translation: BAD52443.1.
AK153889 mRNA. Translation: BAE32236.1.
AK161047 mRNA. Translation: BAE36169.1.
AK166948 mRNA. Translation: BAE39135.1.
CH466534 Genomic DNA. Translation: EDL41342.1.
RefSeqiNP_001258543.1. NM_001271614.1.
NP_001258544.1. NM_001271615.1.
NP_032025.2. NM_007999.4.
XP_006526724.1. XM_006526661.2.
XP_006526725.1. XM_006526662.2.
XP_006526726.1. XM_006526663.2.
XP_006526727.1. XM_006526664.2.
UniGeneiMm.2952.

Genome annotation databases

EnsembliENSMUST00000025651; ENSMUSP00000025651; ENSMUSG00000024742.
ENSMUST00000116542; ENSMUSP00000112241; ENSMUSG00000024742.
ENSMUST00000142241; ENSMUSP00000119221; ENSMUSG00000024742.
ENSMUST00000156291; ENSMUSP00000117246; ENSMUSG00000024742.
GeneIDi14156.
KEGGimmu:14156.
UCSCiuc008gpf.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC132148 Genomic DNA. No translation available.
BC010203 mRNA. Translation: AAH10203.1.
AK046256 mRNA. Translation: BAC32660.1.
AK078778 mRNA. Translation: BAC37390.1.
AB191468 Genomic DNA. Translation: BAD52443.1.
AK153889 mRNA. Translation: BAE32236.1.
AK161047 mRNA. Translation: BAE36169.1.
AK166948 mRNA. Translation: BAE39135.1.
CH466534 Genomic DNA. Translation: EDL41342.1.
RefSeqiNP_001258543.1. NM_001271614.1.
NP_001258544.1. NM_001271615.1.
NP_032025.2. NM_007999.4.
XP_006526724.1. XM_006526661.2.
XP_006526725.1. XM_006526662.2.
XP_006526726.1. XM_006526663.2.
XP_006526727.1. XM_006526664.2.
UniGeneiMm.2952.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000025651.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025651; ENSMUSP00000025651; ENSMUSG00000024742.
ENSMUST00000116542; ENSMUSP00000112241; ENSMUSG00000024742.
ENSMUST00000142241; ENSMUSP00000119221; ENSMUSG00000024742.
ENSMUST00000156291; ENSMUSP00000117246; ENSMUSG00000024742.
GeneIDi14156.
KEGGimmu:14156.
UCSCiuc008gpf.2. mouse.

Organism-specific databases

CTDi2237.
MGIiMGI:102779. Fen1.

Phylogenomic databases

eggNOGiKOG2519. Eukaryota.
COG0258. LUCA.
GeneTreeiENSGT00640000091478.
HOVERGENiHBG000844.
KOiK04799.
OMAiGSQDYDS.
OrthoDBiEOG091G0C0E.
TreeFamiTF105701.

Enzyme and pathway databases

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

Miscellaneous databases

ChiTaRSiFen1. mouse.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024742.

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 nameiQ91Z50_MOUSE
AccessioniPrimary (citable) accession number: Q91Z50
Entry historyi
Integrated into UniProtKB/TrEMBL: December 1, 2001
Last sequence update: December 1, 2001
Last modified: September 7, 2016
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusiUnreviewed (UniProtKB/TrEMBL)

Miscellaneousi

Keywords - Technical termi

Complete proteome, Proteomics identificationCombined sources, Reference proteomeImported

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.