ID   FEN1A_XENLA             Reviewed;         382 AA.
AC   P70040; B7ZQC8; O57351; Q08AW7;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1997, sequence version 1.
DT   09-APR-2025, entry version 111.
DE   RecName: Full=Flap endonuclease 1-A {ECO:0000255|HAMAP-Rule:MF_03140};
DE            Short=FEN-1-A {ECO:0000255|HAMAP-Rule:MF_03140};
DE            EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_03140};
DE   AltName: Full=Flap structure-specific endonuclease 1-A {ECO:0000255|HAMAP-Rule:MF_03140};
DE            Short=xFEN-1a;
GN   Name=fen1-a;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:AAB88707.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, IDENTIFICATION IN A COMPLEX WITH
RP   PCNA, AND VARIANT ILE-33.
RC   TISSUE=Oocyte {ECO:0000269|PubMed:9535864};
RX   PubMed=9535864; DOI=10.1074/jbc.273.15.8842;
RA   Kim K., Biade S., Matsumoto Y.;
RT   "Involvement of flap endonuclease 1 in base excision DNA repair.";
RL   J. Biol. Chem. 273:8842-8848(1998).
RN   [2] {ECO:0000305, ECO:0000312|EMBL:AAB06176.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, COFACTOR, IDENTIFICATION IN A COMPLEX
RP   WITH PCNA, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND VARIANT ILE-33.
RC   TISSUE=Tadpole head {ECO:0000269|PubMed:9852084};
RX   PubMed=9852084; DOI=10.1074/jbc.273.51.34222;
RA   Bibikova M., Wu B., Chi E., Kim K.-H., Trautman J.K., Carroll D.;
RT   "Characterization of FEN-1 from Xenopus laevis. cDNA cloning and role in
RT   DNA metabolism.";
RL   J. Biol. Chem. 273:34222-34229(1998).
RN   [3] {ECO:0000312|EMBL:AAD02814.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Li J.-L., Cox L.S.;
RT   "Cloning and investigation of Xenopus Fen1: developmental expression and
RT   function in DNA replication.";
RL   Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN   [4] {ECO:0000312|EMBL:AAD02814.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ILE-33.
RC   TISSUE=Oocyte, and Ovary;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (OCT-2006) 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       ECO:0000269|PubMed:9535864, ECO:0000269|PubMed:9852084}.
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000255|HAMAP-
CC         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: Interacts with PCNA. Three molecules of fen1 bind to one PCNA
CC       trimer with each molecule binding to one PCNA monomer. PCNA stimulates
CC       the nuclease activity without altering cleavage specificity.
CC       {ECO:0000255|HAMAP-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   -!- DEVELOPMENTAL STAGE: First expressed at a low level in stage II
CC       oocytes. Expression increases dramatically from oocyte stages III to V
CC       (at protein level). Also expressed in embryos.
CC       {ECO:0000269|PubMed:9852084}.
CC   -!- PTM: Phosphorylated. Phosphorylation upon DNA damage induces
CC       relocalization to the nuclear plasma. {ECO:0000255|HAMAP-
CC       Rule:MF_03140}.
CC   -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. FEN1
CC       subfamily. {ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
CC       Rule:MF_03140}.
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DR   EMBL; AF036327; AAB88707.1; -; mRNA.
DR   EMBL; U64563; AAB06176.1; -; mRNA.
DR   EMBL; AF065397; AAD02814.1; -; mRNA.
DR   EMBL; BC169761; AAI69761.1; -; mRNA.
DR   EMBL; BC169765; AAI69765.1; -; mRNA.
DR   EMBL; BC124977; AAI24978.1; -; mRNA.
DR   RefSeq; NP_001080960.1; NM_001087491.1.
DR   AlphaFoldDB; P70040; -.
DR   SMR; P70040; -.
DR   BioGRID; 98905; 1.
DR   IntAct; P70040; 2.
DR   DNASU; 394303; -.
DR   GeneID; 394303; -.
DR   KEGG; xla:394303; -.
DR   AGR; Xenbase:XB-GENE-955523; -.
DR   CTD; 394303; -.
DR   Xenbase; XB-GENE-955523; fen1.L.
DR   OMA; IQEVHID; -.
DR   OrthoDB; 1937206at2759; -.
DR   Proteomes; UP000186698; Chromosome 4L.
DR   Bgee; 394303; Expressed in testis and 19 other cell types or tissues.
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; IDA:UniProtKB.
DR   GO; GO:0008409; F:5'-3' exonuclease activity; IBA:GO_Central.
DR   GO; GO:0017108; F:5'-flap endonuclease activity; IDA:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0000287; F:magnesium ion binding; IBA:GO_Central.
DR   GO; GO:0030145; F:manganese ion binding; IBA:GO_Central.
DR   GO; GO:0004523; F:RNA-DNA hybrid ribonuclease activity; IBA:GO_Central.
DR   GO; GO:0006284; P:base-excision repair; IDA:UniProtKB.
DR   GO; GO:0006260; P:DNA replication; IPI:UniProtKB.
DR   GO; GO:0043137; P:DNA replication, removal of RNA primer; IEA:UniProtKB-UniRule.
DR   CDD; cd09907; H3TH_FEN1-Euk; 1.
DR   CDD; cd09867; PIN_FEN1; 1.
DR   FunFam; 1.10.150.20:FF:000009; Flap endonuclease 1; 1.
DR   FunFam; 3.40.50.1010:FF:000003; Flap endonuclease 1; 1.
DR   Gene3D; 1.10.150.20; 5' to 3' exonuclease, C-terminal subdomain; 1.
DR   Gene3D; 3.40.50.1010; 5'-nuclease; 1.
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:SF73; FLAP ENDONUCLEASE 1; 1.
DR   PANTHER; PTHR11081; FLAP ENDONUCLEASE FAMILY MEMBER; 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; 5' to 3' exonuclease, C-terminal subdomain; 1.
DR   SUPFAM; SSF88723; PIN domain-like; 1.
DR   PROSITE; PS00841; XPG_1; 1.
PE   1: Evidence at protein level;
KW   DNA damage; DNA repair; DNA replication; Endonuclease; Exonuclease;
KW   Hydrolase; Magnesium; Metal-binding; Mitochondrion; Nuclease; Nucleus;
KW   Phosphoprotein; Reference proteome.
FT   CHAIN           1..382
FT                   /note="Flap endonuclease 1-A"
FT                   /id="PRO_0000244491"
FT   REGION          1..104
FT                   /note="N-domain"
FT                   /evidence="ECO:0000255"
FT   REGION          122..253
FT                   /note="I-domain"
FT                   /evidence="ECO:0000255"
FT   REGION          336..344
FT                   /note="Interaction with PCNA"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT   REGION          350..382
FT                   /note="Disordered"
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:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT                   Rule:MF_03140"
FT   BINDING         70
FT                   /ligand="DNA"
FT                   /ligand_id="ChEBI:CHEBI:16991"
FT                   /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT                   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:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT                   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:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT                   Rule:MF_03140"
FT   BINDING         233
FT                   /ligand="DNA"
FT                   /ligand_id="ChEBI:CHEBI:16991"
FT                   /evidence="ECO:0000250|UniProtKB:P39748, ECO:0000255|HAMAP-
FT                   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   VARIANT         33
FT                   /note="V -> I (in allele fen-1a')"
FT                   /evidence="ECO:0000269|PubMed:9535864,
FT                   ECO:0000269|PubMed:9852084, ECO:0000269|Ref.4"
SQ   SEQUENCE   382 AA;  42668 MW;  9B1DB0EDAD158D57 CRC64;
     MGIHGLAKLI ADVAPAAIKE HDIKSYFGRK VAVDASMCIY QFLIAVRQDG NTLQNEEGET
     TSHLMGMFYR TIRMVEHGIK PVYVFDGKPP QMKSGELAKR SERRAEAEKL LEAAEEAGEV
     ENIEKFTKRL VKVTKQHNEE CKKLLTLMGI PYVDAPCEAE ATCAALVKAG KVYAAATEDM
     DALTFGTPVL LRHLTASEAK KLPIQEFHLN RVIQDIGITH EQFVDLCILL GSDYCETIRG
     IGPKRAIDLI RQHKTIDEII DNIDLKKYPV PENWLHKEAK HLFLEPEVVD TDITELKWIE
     PDEEGLVAFM CGEKQFSEDR IRNGAKKLAK NRQGSTQGRL DDFFKVTGSV SSTKRKEAES
     KGSAKKKAKT GGTPAGKFKR GK
//