AC MF_03140; DC Protein; auto c? TR HAMAP; MF_00614; -; 1; level=0 XX Names: Fen_euk XX ID FEN1 DE RecName: Full=Flap endonuclease 1; DE Short=FEN-1; DE EC=3.1.-.-; DE AltName: Full=Flap structure-specific endonuclease 1; case or GN Name=RAD27; Synonyms=FEN1; else case GN Name=rad2; Synonyms=fen1; else case GN Name=crn-1; else case GN Name=repG; else case GN Name=Fen1; else GN Name=FEN1; end case XX CC -!- FUNCTION: Structure-specific nuclease with 5'-flap endonuclease and 5'- CC 3' exonuclease activities involved in DNA replication and repair. CC During DNA replication, cleaves the 5'-overhanging flap structure that CC is generated by displacement synthesis when DNA polymerase encounters CC the 5'-end of a downstream Okazaki fragment. It enters the flap from CC the 5'-end and then tracks to cleave the flap base, leaving a nick for CC ligation. Also involved in the long patch base excision repair (LP-BER) CC pathway, by cleaving within the apurinic/apyrimidinic (AP) site- CC terminated flap. Acts as a genome stabilization factor that prevents CC flaps from equilibrating into structures that lead to duplications and CC deletions. Also possesses 5'-3' exonuclease activity on nicked or CC gapped double-stranded DNA, and exhibits RNase H activity. Also CC involved in replication and repair of rDNA and in repairing CC mitochondrial DNA. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Note=Binds 2 magnesium ions per subunit. They probably participate in CC the reaction catalyzed by the enzyme. May bind an additional third CC magnesium ion after substrate binding.; case CC -!- SUBUNIT: Interacts with PCNA. Three molecules of bind to CC one PCNA trimer with each molecule binding to one PCNA monomer. PCNA CC stimulates the nuclease activity without altering cleavage specificity. CC The C-terminal domain binds EP300. Can bind simultaneously to both PCNA CC and EP300. Interacts with DDX11. else CC -!- SUBUNIT: Interacts with PCNA. Three molecules of bind to CC one PCNA trimer with each molecule binding to one PCNA monomer. PCNA CC stimulates the nuclease activity without altering cleavage specificity. end case CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus. Nucleus, nucleoplasm. CC Mitochondrion. Note=Resides mostly in the nucleoli and relocalizes to CC the nucleoplasm upon DNA damage. case CC -!- PTM: Acetylated by EP300. Acetylation inhibits both endonuclease and CC exonuclease activity. Acetylation also reduces DNA-binding activity but CC does not affect interaction with PCNA or EP300. end case case and and CC -!- PTM: Methylation at #{Arg-192} by PRMT5 impedes #{Ser-187} CC phosphorylation and increases interaction with PCNA. end case case and CC -!- PTM: Phosphorylation upon DNA damage induces relocalization to the CC nuclear plasma. Phosphorylation at #{Ser-187} by CDK2 occurs during CC late S-phase and results in dissociation from PCNA. else CC -!- PTM: Phosphorylated. Phosphorylation upon DNA damage induces CC relocalization to the nuclear plasma. end case CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. FEN1 CC subfamily. XX DR Pfam; PF00867; XPG_I; 1; trigger=no DR Pfam; PF00752; XPG_N; 1; trigger=no DR PRINTS; PR00853; XPGRADSUPER; 1; trigger=no DR PROSITE; PS00841; XPG_1; 1; trigger=no DR PROSITE; PS00842; XPG_2; 1; trigger=no XX case KW Acetylation end case case KW Methylation end case KW Endonuclease KW Exonuclease KW DNA damage KW DNA repair KW DNA replication KW Hydrolase KW Magnesium KW Metal-binding KW Mitochondrion KW Nuclease KW Nucleus KW Phosphoprotein XX GO GO:0005634; C:nucleus GO GO:0005739; C:mitochondrion GO GO:0003677; F:DNA binding GO GO:0008409; F:5'-3' exonuclease activity GO GO:0017108; F:5'-flap endonuclease activity GO GO:0000287; F:magnesium ion binding GO GO:0006284; P:base-excision repair GO GO:0043137; P:DNA replication, removal of RNA primer XX FT From: FEN1_HUMAN (P39748) FT REGION 1..104 FT /note="N-domain" FT REGION 122..253 FT /note="I-domain" FT REGION 336..344 FT /note="Interaction with PCNA" FT Optional; Condition: x-Q-x(2)-[ILM]-x(2)-F-[FYLI] FT BINDING 34 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT Condition: D FT BINDING 86 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT Condition: D FT BINDING 158 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT Condition: E FT BINDING 160 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="1" FT Condition: E FT BINDING 179 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT Condition: D FT BINDING 181 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT Condition: D FT BINDING 233 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /ligand_label="2" FT Condition: D FT BINDING 47 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT Condition: R FT BINDING 70 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT Condition: R FT BINDING 158 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT Condition: E FT BINDING 231 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT Condition: G FT BINDING 233 FT /ligand="DNA" FT /ligand_id="ChEBI:CHEBI:16991" FT Condition: D case FT MOD_RES 19 FT /note="Symmetric dimethylarginine; by PRMT5" FT Tag: meth; Condition: R FT MOD_RES 100 FT /note="Symmetric dimethylarginine; by PRMT5" FT Tag: meth; Condition: R FT MOD_RES 104 FT /note="Symmetric dimethylarginine; by PRMT5" FT Tag: meth; Condition: R FT MOD_RES 192 FT /note="Symmetric dimethylarginine; by PRMT5" FT Tag: meth192; Condition: R FT MOD_RES 187 FT /note="Phosphoserine; by CDK2" FT Tag: phospho187; Condition: S FT MOD_RES 354 FT /note="N6-acetyllysine" FT Tag: acet; Condition: K FT MOD_RES 375 FT /note="N6-acetyllysine" FT Tag: acet; Condition: K FT MOD_RES 377 FT /note="N6-acetyllysine" FT Tag: acet; Condition: K FT MOD_RES 380 FT /note="N6-acetyllysine" FT Tag: acet; Condition: K end case XX Size: 345-672; Related: None; Template: P39748; P26793; P39749; Scope: Eukaryota Fusion: Nter: None Cter: None Duplicate: in DANRE, LACBS, ORYSI, ORYSJ, PARTE, PHYPA, SORBI, XENLA Plasmid: None Comments: None XX # Revision 1.12 2022/11/19 //