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HAMAP 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(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 [?]

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 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>
SUBUNITInteracts 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
SUBUNITInteracts 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 LOCATIONNucleus, nucleolus. Nucleus, nucleoplasm. Mitochondrion. Note=Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.
case <OC:Mammalia>
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.
end case
case <OC:Mammalia> and <FTTag:phospho187> and <FTTag:meth192>
PTMMethylation at #{Arg-192} by PRMT5 impedes #{Ser-187} phosphorylation and increases interaction with PCNA.
end case
case <OC:Mammalia> and <FTTag:phospho187>
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.
else
PTMPhosphorylated. Phosphorylation upon DNA damage induces relocalization to the nuclear plasma.
end case
SIMILARITYBelongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.

Keywords [?]


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 To Description Tag Condition FTGroup
REGION 1 104 /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 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 /note="Symmetric dimethylarginine; by PRMT5" meth R
MOD_RES 100 100 /note="Symmetric dimethylarginine; by PRMT5" meth R
MOD_RES 104 104 /note="Symmetric dimethylarginine; by PRMT5" meth R
MOD_RES 192 192 /note="Symmetric dimethylarginine; by PRMT5" meth192 R
MOD_RES 187 187 /note="Phosphoserine; by CDK2" phospho187 S
MOD_RES 354 354 /note="N6-acetyllysine" acet K
MOD_RES 375 375 /note="N6-acetyllysine" acet K
MOD_RES 377 377 /note="N6-acetyllysine" acet K
MOD_RES 380 380 /note="N6-acetyllysine" acet K
end case

Additional information [?]

Size range 345-672 amino acids
Related rules None
Fusion Nter: None Cter: None



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