FEN1_GIAIC
ID FEN1_GIAIC Reviewed; 361 AA.
AC A8B672;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 1.
DT 03-AUG-2022, entry version 75.
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}; ORFNames=GL50803_16953;
OS Giardia intestinalis (strain ATCC 50803 / WB clone C6) (Giardia lamblia).
OC Eukaryota; Metamonada; Diplomonadida; Hexamitidae; Giardiinae; Giardia.
OX NCBI_TaxID=184922;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 50803 / WB clone C6;
RX PubMed=17901334; DOI=10.1126/science.1143837;
RA Morrison H.G., McArthur A.G., Gillin F.D., Aley S.B., Adam R.D.,
RA Olsen G.J., Best A.A., Cande W.Z., Chen F., Cipriano M.J., Davids B.J.,
RA Dawson S.C., Elmendorf H.G., Hehl A.B., Holder M.E., Huse S.M., Kim U.U.,
RA Lasek-Nesselquist E., Manning G., Nigam A., Nixon J.E.J., Palm D.,
RA Passamaneck N.E., Prabhu A., Reich C.I., Reiner D.S., Samuelson J.,
RA Svard S.G., Sogin M.L.;
RT "Genomic minimalism in the early diverging intestinal parasite Giardia
RT lamblia.";
RL Science 317:1921-1926(2007).
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: 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 -!- 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:0000255|HAMAP-Rule:MF_03140}.
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DR EMBL; AACB02000003; EDO81725.1; -; Genomic_DNA.
DR RefSeq; XP_001709399.1; XM_001709347.1.
DR AlphaFoldDB; A8B672; -.
DR SMR; A8B672; -.
DR STRING; 5741.EDO81725; -.
DR EnsemblProtists; EDO81725; EDO81725; GL50803_16953.
DR GeneID; 5702322; -.
DR KEGG; gla:GL50803_0016953; -.
DR VEuPathDB; GiardiaDB:GL50803_16953; -.
DR HOGENOM; CLU_032444_2_0_1; -.
DR InParanoid; A8B672; -.
DR OMA; GSQDYDS; -.
DR OrthoDB; 1094524at2759; -.
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:0008409; F:5'-3' exonuclease activity; IBA:GO_Central.
DR GO; GO:0017108; F:5'-flap endonuclease activity; IBA:GO_Central.
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; IPR002421; 5-3_exonuclease.
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; 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; SM00475; 53EXOc; 1.
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.
PE 3: Inferred from homology;
KW DNA damage; DNA repair; DNA replication; Endonuclease; Exonuclease;
KW Hydrolase; Magnesium; Metal-binding; Mitochondrion; Nuclease; Nucleus;
KW Phosphoprotein.
FT CHAIN 1..361
FT /note="Flap endonuclease 1"
FT /id="PRO_0000403611"
FT REGION 1..105
FT /note="N-domain"
FT REGION 123..252
FT /note="I-domain"
FT REGION 337..345
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT REGION 341..361
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 87
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 159
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 159
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 161
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 180
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 182
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 230
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 232
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 232
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
SQ SEQUENCE 361 AA; 40030 MW; C02F072DE48D005A CRC64;
MGIRGLAKLI EEVAPAAVSK RLIQHYCNKV IAIDASVMLY QFITTITSGD GTALANSSGE
VTSHLVGLLA KVIRLAEAGI KPIFVFDGKP PEDKQGELEK RRQAREAAEL EQQKAEEEGN
LERAKQLSRR TVKVTQQHCK QAERLLDTLG IPYVVAAGEA EAQCVAMAKE RVCEGVASSD
LDVLAFGSPC LIRNLAQGGD REIVEINLNT VLKELGFSYD EFLDLCILCG CDYANSLEGI
GPKTAYKLIV KHRSIEEVLA ADQGKLAEKA LNWPYVRARE LFKNPAVIDP KEIKKTLKWK
PVNRGEAMQF LVEEMEFDRE TTEKKLDKLV AARKKPKQCT IDSFFSPRSS NPEVTKTKVK
Q
