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

Eukaryota

Templates

P39748 (FEN1_HUMAN); P26793 (FEN1_YEAST); P39749 (FEN1_MOUSE): [Recover all]

case <OC:Eukaryota>

Triggered by

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

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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