HAMAP rule MF_03140

General rule information [?]

Accession	MF_03140
Dates	18-NOV-2010 (Created) 19-NOV-2022 (Last updated, Version 12)
Name	Fen_euk
Scope(s)	Eukaryota
Template(s)	P39748 (FEN1_HUMAN); P26793 (FEN1_YEAST); P39749 (FEN1_MOUSE); [ Recover all ]
Triggered by	case c? <OC:Eukaryota> HAMAP; MF_00614 (Get profile general information and statistics) end case

Propagated annotation [?]

Identifier, protein and gene names [?]

Identifier	FEN1
Protein name	RecName: Full=Flap endonuclease 1; Short=FEN-1; EC=3.1.-.-; AltName: Full=Flap structure-specific endonuclease 1;
case <OC:Saccharomyces> or <OC:Candida>
Gene name	Name=RAD27; Synonyms=FEN1;
else case <OC:Schizosaccharomyces>
Gene name	Name=rad2; Synonyms=fen1;
else case <OC:Caenorhabditis>
Gene name	Name=crn-1;
else case <OC:Dictyostelia>
Gene name	Name=repG;
else case <OC:Arthropoda>
Gene name	Name=Fen1;
else
Gene name	Name=FEN1;
end case

Comments [?]

FUNCTION	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 structures 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.
COFACTOR	Name=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.;
case <OC:Mammalia>
SUBUNIT	Interacts with PCNA. Three molecules of 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.
else
SUBUNIT	Interacts with PCNA. Three molecules of bind to one PCNA trimer with each molecule binding to one PCNA monomer. PCNA stimulates the nuclease activity without altering cleavage specificity.
end case
SUBCELLULAR LOCATION	Nucleus, nucleolus. Nucleus, nucleoplasm. Mitochondrion. Note=Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.
case <OC:Mammalia>
PTM	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.
end case
case <OC:Mammalia> and <FTTag:phospho187> and <FTTag:meth192>
PTM	Methylation at #{Arg-192} by PRMT5 impedes #{Ser-187} phosphorylation and increases interaction with PCNA.
end case
case <OC:Mammalia> and <FTTag:phospho187>
PTM	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.
else
PTM	Phosphorylated. Phosphorylation upon DNA damage induces relocalization to the nuclear plasma.
end case
SIMILARITY	Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.

Keywords [?]

case <FTTag:acet>
Acetylation
end case
case <FTTag:meth>
Methylation
end case
Endonuclease
Exonuclease
DNA damage
DNA repair
DNA replication
Hydrolase
Magnesium
Metal-binding
Mitochondrion
Nuclease
Nucleus
Phosphoprotein

Gene Ontology [?]

GO:0005634; Cellular component:nucleus

GO:0005739; Cellular component:mitochondrion

GO:0003677; Molecular function:DNA binding

GO:0008409; Molecular function:5'-3' exonuclease activity

GO:0017108; Molecular function:5'-flap endonuclease activity

GO:0000287; Molecular function:magnesium ion binding

GO:0006284; Biological process:base-excision repair

GO:0043137; Biological process:DNA replication, removal of RNA primer

Cross-references [?]

Pfam	PF00867; XPG_I; 1;
Pfam	PF00752; XPG_N; 1;
PRINTS	PR00853; XPGRADSUPER; 1;
PROSITE	PS00841; XPG_1; 1;
PROSITE	PS00842; XPG_2; 1;

Features [?]

From: FEN1_HUMAN (P39748)

Key

From

Description

Tag

Condition

FTGroup

REGION

104

/note="N-domain"

REGION

122

253

/note="I-domain"

REGION

336

344

/note="Interaction with PCNA"

x-Q-x(2)-[ILM]-x(2)-F-[FYLI]

BINDING

/ligand="Mg(2+)"
/ligand_id="ChEBI:CHEBI:18420"
/ligand_label="1"

BINDING

/ligand="Mg(2+)"
/ligand_id="ChEBI:CHEBI:18420"
/ligand_label="1"

BINDING

158

/ligand="Mg(2+)"
/ligand_id="ChEBI:CHEBI:18420"
/ligand_label="1"

BINDING

160

/ligand="Mg(2+)"
/ligand_id="ChEBI:CHEBI:18420"
/ligand_label="1"

BINDING

179

/ligand="Mg(2+)"
/ligand_id="ChEBI:CHEBI:18420"
/ligand_label="2"

BINDING

181

/ligand="Mg(2+)"
/ligand_id="ChEBI:CHEBI:18420"
/ligand_label="2"

BINDING

233

/ligand="Mg(2+)"
/ligand_id="ChEBI:CHEBI:18420"
/ligand_label="2"

BINDING