FEN1_SHEEP
ID FEN1_SHEEP Reviewed; 380 AA.
AC C8BKD0;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 13-OCT-2009, sequence version 1.
DT 03-AUG-2022, entry version 56.
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};
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Liu G.Y.;
RL Submitted (MAY-2009) to the EMBL/GenBank/DDBJ databases.
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 -!- 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 {ECO:0000255|HAMAP-Rule:MF_03140}. Note=Resides mostly in
CC the nucleoli and relocalizes to the nucleoplasm upon DNA damage.
CC {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-187 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-192 by PRMT5 impedes Ser-187 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; GQ221048; ACV04829.1; -; mRNA.
DR RefSeq; NP_001159668.1; NM_001166196.1.
DR AlphaFoldDB; C8BKD0; -.
DR SMR; C8BKD0; -.
DR STRING; 9940.ENSOARP00000016769; -.
DR PRIDE; C8BKD0; -.
DR GeneID; 100307042; -.
DR KEGG; oas:100307042; -.
DR CTD; 2237; -.
DR eggNOG; KOG2519; Eukaryota.
DR OrthoDB; 1094524at2759; -.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0008409; F:5'-3' exonuclease activity; IEA:UniProtKB-UniRule.
DR GO; GO:0017108; F:5'-flap endonuclease activity; IEA:UniProtKB-UniRule.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0006284; P:base-excision repair; IEA:UniProtKB-UniRule.
DR GO; GO:0043137; P:DNA replication, removal of RNA primer; IEA:UniProtKB-UniRule.
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 2: Evidence at transcript level;
KW Acetylation; DNA damage; DNA repair; DNA replication; Endonuclease;
KW Exonuclease; Hydrolase; Magnesium; Metal-binding; Methylation;
KW Mitochondrion; Nuclease; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..380
FT /note="Flap endonuclease 1"
FT /id="PRO_0000403484"
FT REGION 1..104
FT /note="N-domain"
FT REGION 122..253
FT /note="I-domain"
FT REGION 336..344
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT REGION 349..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..366
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 70
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 86
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="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
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 160
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
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 181
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
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 233
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 233
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 80
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 100
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 104
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 187
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 192
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT MOD_RES 336
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT MOD_RES 354
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 375
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 377
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
FT MOD_RES 380
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT Rule:MF_03140"
SQ SEQUENCE 380 AA; 42676 MW; DB3E132126470419 CRC64;
MGIQGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG DVLQNEEGET
TSHLMGMFYR TIRMMENGIK PVYVFDGKPP QLKSGELAKR SERRAEAEKQ LQQAQAAGAE
TEVEKFTKRL VKVTKQHNDE CKHLLSLMGI PYLDAPSEAE ASCAALVKAG KVYAAATEDM
DCLTFGSPVL MRHLTASEAK KLPIQEFHLS RILQELGLNQ EQFVDLCILL GSDYCESIRG
IGPKRAVDLI QKHKSIEEIV RRLDPNKYPV PENWLHKEAQ QLFLEPEVLD PESVELKWSE
PNEEELVRFM CGEKQFSEER IRSGVRRLSK SRQGSTQGRL DDFFKVTGSL SSAKRKEPEP
KGAAKKKQRL GPAGKFKRGK
