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P39749

- FEN1_MOUSE

UniProt

P39749 - FEN1_MOUSE

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Protein

Flap endonuclease 1

Gene

Fen1

Organism
Mus musculus (Mouse)
Status
Reviewed - 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 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 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
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
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-HAMAP
  2. nucleus Source: MGI
Complete GO annotation...

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

        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 .
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 109 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