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Annotation rule MF_03140 |
General rule information
[?]
Accession |
MF_03140 |
Dates |
18-NOV-2010 (Created) 19-NOV-2022 (Last updated, Version 12) |
case <OC:Eukaryota>
end case
Propagated annotation
[?]
Identifier, protein and gene names
[?]
Protein name |
RecName:
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Full=Flap endonuclease 1;
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Short=FEN-1;
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EC 3.1.-.-;
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AltName:
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Full=Flap structure-specific endonuclease 1;
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case <OC:Saccharomyces> or <OC:Candida>
else case <OC:Schizosaccharomyces>
else case <OC:Caenorhabditis>
else case <OC:Dictyostelia>
else case <OC:Arthropoda>
else
end case
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. |
case <FTTag:acet>
end case
case <FTTag:meth>
end case
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.
From: FEN1_HUMAN (P39748) |
Key
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From
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To
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Description
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Tag
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Condition
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FTGroup
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REGION
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1
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104
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N-domain
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|
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|
|
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REGION
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122
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253
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|
I-domain
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|
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REGION (Optional)
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336
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344
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Interaction with PCNA
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x-Q-x(2)-[ILM]-x(2)-F-[FYLI]
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BINDING
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34
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34
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/ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="1
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|
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D
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BINDING
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86
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86
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/ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="1
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|
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D
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BINDING
|
|
158
|
|
158
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/ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="1
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|
|
|
E
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BINDING
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160
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160
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/ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="1
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|
|
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E
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BINDING
|
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179
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179
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/ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="2
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|
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D
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BINDING
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181
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181
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/ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="2
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|
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D
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BINDING
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233
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|
233
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/ligand="Mg(2+)" /ligand_id="ChEBI:CHEBI:18420" /ligand_label="2
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|
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D
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BINDING
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47
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47
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/ligand="DNA" /ligand_id="ChEBI:CHEBI:16991
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R
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BINDING
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70
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70
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/ligand="DNA" /ligand_id="ChEBI:CHEBI:16991
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R
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BINDING
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158
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158
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/ligand="DNA" /ligand_id="ChEBI:CHEBI:16991
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E
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BINDING
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231
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231
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/ligand="DNA" /ligand_id="ChEBI:CHEBI:16991
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G
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BINDING
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233
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233
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/ligand="DNA" /ligand_id="ChEBI:CHEBI:16991
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D
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case <OC:Mammalia>
MOD_RES
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19
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19
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Symmetric dimethylarginine; by PRMT5
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meth
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R
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MOD_RES
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100
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100
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Symmetric dimethylarginine; by PRMT5
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meth
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R
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MOD_RES
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104
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104
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Symmetric dimethylarginine; by PRMT5
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meth
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R
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MOD_RES
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192
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192
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Symmetric dimethylarginine; by PRMT5
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meth192
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R
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MOD_RES
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187
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187
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Phosphoserine; by CDK2
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phospho187
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S
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MOD_RES
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354
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354
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N6-acetyllysine
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acet
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K
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MOD_RES
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375
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375
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N6-acetyllysine
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acet
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K
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MOD_RES
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377
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377
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N6-acetyllysine
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acet
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K
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MOD_RES
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380
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380
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N6-acetyllysine
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acet
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K
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end case
Additional information
[?]
Size range |
345-672 amino acids |
Related rules |
None |
Fusion |
None |