FEN1_MOUSE
ID FEN1_MOUSE Reviewed; 378 AA.
AC P39749;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=Flap endonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03140};
DE Short=FEN-1 {ECO:0000255|HAMAP-Rule:MF_03140};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_03140};
DE AltName: Full=Flap structure-specific endonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03140};
GN Name=Fen1 {ECO:0000255|HAMAP-Rule:MF_03140}; Synonyms=Fen-1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 260-275 AND 331-352, AND
RP FUNCTION.
RC STRAIN=BALB/cJ;
RX PubMed=7926735; DOI=10.1101/gad.8.11.1344;
RA Harrington J.J., Lieber M.R.;
RT "Functional domains within FEN-1 and RAD2 define a family of structure-
RT specific endonucleases: implications for nucleotide excision repair.";
RL Genes Dev. 8:1344-1355(1994).
RN [2]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [3]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-373, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Structure-specific nuclease with 5'-flap endonuclease and 5'-
CC 3' exonuclease activities involved in DNA replication and repair.
CC During DNA replication, cleaves the 5'-overhanging flap structure that
CC is generated by displacement synthesis when DNA polymerase encounters
CC the 5'-end of a downstream Okazaki fragment. It enters the flap from
CC the 5'-end and then tracks to cleave the flap base, leaving a nick for
CC ligation. Also involved in the long patch base excision repair (LP-BER)
CC pathway, by cleaving within the apurinic/apyrimidinic (AP) site-
CC terminated flap. Acts as a genome stabilization factor that prevents
CC flaps from equilibrating into structures that lead to duplications and
CC deletions. Also possesses 5'-3' exonuclease activity on nicked or
CC gapped double-stranded DNA, and exhibits RNase H activity. Also
CC involved in replication and repair of rDNA and in repairing
CC mitochondrial DNA. {ECO:0000255|HAMAP-Rule:MF_03140,
CC ECO:0000269|PubMed:7926735}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03140};
CC Note=Binds 2 magnesium ions per subunit. They probably participate in
CC the reaction catalyzed by the enzyme. May bind an additional third
CC magnesium ion after substrate binding. {ECO:0000255|HAMAP-
CC Rule:MF_03140};
CC -!- SUBUNIT: Three molecules of FEN1 bind to one PCNA trimer with each
CC molecule binding to one PCNA monomer. PCNA stimulates the nuclease
CC activity without altering cleavage specificity. The C-terminal domain
CC binds EP300; can bind simultaneously to both PCNA and EP300. Interacts
CC with PCNA; can bind simultaneously to both PCNA and EP300. Interacts
CC with DDX11; this interaction is direct and increases flap endonuclease
CC activity of FEN1. Interacts with WDR4; regulating its endonuclease
CC activity. {ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
CC Rule:MF_03140}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000255|HAMAP-
CC Rule:MF_03140}. Nucleus, nucleoplasm {ECO:0000255|HAMAP-Rule:MF_03140}.
CC Mitochondrion. Note=Resides mostly in the nucleoli and relocalizes to
CC the nucleoplasm upon DNA damage. {ECO:0000255|HAMAP-Rule:MF_03140}.
CC -!- PTM: Acetylated by EP300. Acetylation inhibits both endonuclease and
CC exonuclease activity. Acetylation also reduces DNA-binding activity but
CC does not affect interaction with PCNA or EP300. {ECO:0000255|HAMAP-
CC Rule:MF_03140}.
CC -!- PTM: Phosphorylation upon DNA damage induces relocalization to the
CC nuclear plasma. Phosphorylation at Ser-185 by CDK2 occurs during late
CC S-phase and results in dissociation from PCNA. {ECO:0000255|HAMAP-
CC Rule:MF_03140}.
CC -!- PTM: Methylation at Arg-190 by PRMT5 impedes Ser-185 phosphorylation
CC and increases interaction with PCNA. {ECO:0000255|HAMAP-Rule:MF_03140}.
CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. FEN1
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_03140}.
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DR EMBL; L26320; AAC37664.1; -; mRNA.
DR PIR; A53730; A53730.
DR AlphaFoldDB; P39749; -.
DR SMR; P39749; -.
DR IntAct; P39749; 2.
DR STRING; 10090.ENSMUSP00000025651; -.
DR iPTMnet; P39749; -.
DR PhosphoSitePlus; P39749; -.
DR EPD; P39749; -.
DR jPOST; P39749; -.
DR MaxQB; P39749; -.
DR PaxDb; P39749; -.
DR PeptideAtlas; P39749; -.
DR PRIDE; P39749; -.
DR ProteomicsDB; 270981; -.
DR MGI; MGI:102779; Fen1.
DR eggNOG; KOG2519; Eukaryota.
DR InParanoid; P39749; -.
DR Reactome; R-MMU-110362; POLB-Dependent Long Patch Base Excision Repair.
DR Reactome; R-MMU-174437; Removal of the Flap Intermediate from the C-strand.
DR Reactome; R-MMU-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR Reactome; R-MMU-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-MMU-69166; Removal of the Flap Intermediate.
DR ChiTaRS; Fen1; mouse.
DR PRO; PR:P39749; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P39749; protein.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0008409; F:5'-3' exonuclease activity; ISO:MGI.
DR GO; GO:0017108; F:5'-flap endonuclease activity; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0004527; F:exonuclease activity; IDA:MGI.
DR GO; GO:0048256; F:flap endonuclease activity; IDA:MGI.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MGI.
DR GO; GO:0030145; F:manganese ion binding; IDA:MGI.
DR GO; GO:0004523; F:RNA-DNA hybrid ribonuclease activity; ISO:MGI.
DR GO; GO:0006284; P:base-excision repair; IEA:UniProtKB-UniRule.
DR GO; GO:0006281; P:DNA repair; IMP:MGI.
DR GO; GO:0006260; P:DNA replication; IMP:MGI.
DR GO; GO:0043137; P:DNA replication, removal of RNA primer; ISO:MGI.
DR GO; GO:0007613; P:memory; ISO:MGI.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; ISO:MGI.
DR GO; GO:0045876; P:positive regulation of sister chromatid cohesion; ISO:MGI.
DR HAMAP; MF_00614; Fen; 1.
DR InterPro; IPR036279; 5-3_exonuclease_C_sf.
DR InterPro; IPR023426; Flap_endonuc.
DR InterPro; IPR008918; HhH2.
DR InterPro; IPR029060; PIN-like_dom_sf.
DR InterPro; IPR006086; XPG-I_dom.
DR InterPro; IPR006084; XPG/Rad2.
DR InterPro; IPR019974; XPG_CS.
DR InterPro; IPR006085; XPG_DNA_repair_N.
DR PANTHER; PTHR11081; PTHR11081; 1.
DR Pfam; PF00867; XPG_I; 1.
DR Pfam; PF00752; XPG_N; 1.
DR PRINTS; PR00853; XPGRADSUPER.
DR SMART; SM00279; HhH2; 1.
DR SMART; SM00484; XPGI; 1.
DR SMART; SM00485; XPGN; 1.
DR SUPFAM; SSF47807; SSF47807; 1.
DR SUPFAM; SSF88723; SSF88723; 1.
DR PROSITE; PS00841; XPG_1; 1.
DR PROSITE; PS00842; XPG_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; DNA damage; DNA repair;
KW DNA replication; Endonuclease; Exonuclease; Hydrolase; Magnesium;
KW Metal-binding; Methylation; Mitochondrion; Nuclease; Nucleus;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..378
FT /note="Flap endonuclease 1"
FT /id="PRO_0000154070"
FT REGION 1..102
FT /note="N-domain"
FT REGION 120..251
FT /note="I-domain"
FT REGION 325..378
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 334..342
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT COMPBIAS 326..340
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 350..364
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 34
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 47
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 69
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 84
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 156
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 156
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 158
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 177
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 179
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 229
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 231
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 231
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT MOD_RES 19
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 78
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 98
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 102
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 185
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 190
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT MOD_RES 291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT MOD_RES 334
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT MOD_RES 352
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 373
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 378
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
SQ SEQUENCE 378 AA; 42315 MW; 827946BD8BDCEF39 CRC64;
MGIHGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG DVLQNEEGET
TSLMGMFYRT IRMENGIKPV YVFDGKPPQL KSGELAKRSE RRAEAEKQLQ QAQEAGMEEE
VEKFTKRLVK VTKQHNDECK HLLSLMGIPY LDAPSEAEAS CAALAKAGKV YAAATEDMDC
LTFGSPVLMR HLTASEAKKL PIQEFHLSRV LQELGLNQEQ FVDLCILLGS DYCESIRGIG
AKRAVDLIQK HKSIEEIVRR LDPSKYPVPE NWLHKEAQQL FLEPEVVDPE SVELKWSEPN
EEELVKFMCG EKQFSEERIR SGVKRLSKSR QGSTQGRLDD FFKVTGSLSS AKRKEPEPKG
PAKKKAKTGG AGKFRRGK
