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Annotation rule MF_03140
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General rule information [?]

Accession MF_03140
Dates 18-NOV-2010 (Created)
19-NOV-2022 (Last updated, Version 12)
Name Fen_euk
Scope
Eukaryota
Templates P39748 (FEN1_HUMAN); P26793 (FEN1_YEAST); P39749 (FEN1_MOUSE): [Recover all]
case <OC:Eukaryota>
Triggered by
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
RAD27, FEN1
else case <OC:Schizosaccharomyces>
Gene name
rad2, fen1
else case <OC:Caenorhabditis>
Gene name
crn-1
else case <OC:Dictyostelia>
Gene name
repG
else case <OC:Arthropoda>
Gene name
Fen1
else
Gene 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 Mg(2+)
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;
PF00752; XPG_N; 1;
PRINTS PR00853; XPGRADSUPER; 1;
PROSITE PS00841; XPG_1; 1;
PS00842; XPG_2; 1;

Features [?]

From: FEN1_HUMAN (P39748)
Key     From     To       Description   Tag   Condition   FTGroup
REGION     1     104       N-domain        
REGION     122     253       I-domain        
REGION (Optional)     336     344       Interaction with PCNA     x-Q-x(2)-[ILM]-x(2)-F-[FYLI]  
BINDING     34     34       /ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="1     D  
BINDING     86     86       /ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="1     D  
BINDING     158     158       /ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="1     E  
BINDING     160     160       /ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="1     E  
BINDING     179     179       /ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="2     D  
BINDING     181     181       /ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="2     D  
BINDING     233     233       /ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="2     D  
BINDING     47     47       /ligand="DNA" /ligand_id="ChEBI:CHEBI:16991     R  
BINDING     70     70       /ligand="DNA" /ligand_id="ChEBI:CHEBI:16991     R  
BINDING     158     158       /ligand="DNA" /ligand_id="ChEBI:CHEBI:16991     E  
BINDING     231     231       /ligand="DNA" /ligand_id="ChEBI:CHEBI:16991     G  
BINDING     233     233       /ligand="DNA" /ligand_id="ChEBI:CHEBI:16991     D  
case <OC:Mammalia>
MOD_RES     19     19       Symmetric dimethylarginine; by PRMT5   meth   R  
MOD_RES     100     100       Symmetric dimethylarginine; by PRMT5   meth   R  
MOD_RES     104     104       Symmetric dimethylarginine; by PRMT5   meth   R  
MOD_RES     192     192       Symmetric dimethylarginine; by PRMT5   meth192   R  
MOD_RES     187     187       Phosphoserine; by CDK2   phospho187   S  
MOD_RES     354     354       N6-acetyllysine   acet   K  
MOD_RES     375     375       N6-acetyllysine   acet   K  
MOD_RES     377     377       N6-acetyllysine   acet   K  
MOD_RES     380     380       N6-acetyllysine   acet   K  
end case

Additional information [?]

Size range 345-672 amino acids
Related rules None
Fusion None


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