FEN1A_XENLA
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 03-AUG-2022, entry version 103.
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;
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: 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 CTD; 394303; -.
DR Xenbase; XB-GENE-955523; fen1.L.
DR OMA; EFMENDP; -.
DR OrthoDB; 1094524at2759; -.
DR Proteomes; UP000186698; Chromosome 4L.
DR Bgee; 394303; Expressed in testis and 19 other 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; IEA:UniProtKB-UniRule.
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; IEA:UniProtKB-UniRule.
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 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.
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 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: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
