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MGP001058

UniProt Annotations

Entry Information
Gene Nameflap structure-specific endonuclease 1
Protein EntryFEN1_HUMAN
UniProt IDP39748
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative initiation; Named isoforms=2; Name=1; IsoId=P39748-1; Sequence=Displayed; Name=FENMIT; IsoId=P39748-2; Sequence=VSP_047520; Note=No nuclease activity. Binds preferentially to RNA flap structures and R-loops.;
CofactorName=Mg(2+); Xref=ChEBI:CHEBI:18420; Note=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.;
FunctionStructure-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. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:10744741, ECO:0000269|PubMed:11986308, ECO:0000269|PubMed:18443037, ECO:0000269|PubMed:20729856, ECO:0000269|PubMed:7961795, ECO:0000269|PubMed:8621570}.
InteractionP54132:BLM; NbExp=4; IntAct=EBI-707816, EBI-621372; Q96NY9:MUS81; NbExp=5; IntAct=EBI-707816, EBI-2370806; P12004:PCNA; NbExp=4; IntAct=EBI-707816, EBI-358311; Q14191:WRN; NbExp=9; IntAct=EBI-707816, EBI-368417;
PtmAcetylated by EP300. Acetylation inhibits both endonuclease and exonuclease activity. Acetylation also reduces DNA-binding activity but does not affect interaction with PCNA or EP300. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:11430825, ECO:0000269|PubMed:19608861}.
PtmMethylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:20729856}.
PtmPhosphorylation 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. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:20729856}.
SimilarityBelongs to the XPG/RAD2 endonuclease family. FEN1 subfamily. {ECO:0000255|HAMAP-Rule:MF_03140}.
Subcellular LocationIsoform 1: Nucleus, nucleolus. Nucleus, nucleoplasm. Note=Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.
Subcellular LocationIsoform FENMIT: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:23675412}.
SubunitInteracts 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. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:11430825, ECO:0000269|PubMed:15616578, ECO:0000269|PubMed:18499658, ECO:0000269|PubMed:9305916}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/FEN1ID40543ch11q12.html";
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/fen1/";
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