FEN1_PLAFA
ID FEN1_PLAFA Reviewed; 650 AA.
AC Q9GZ01; Q6T7E7;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 93.
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 Plasmodium falciparum.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Haemosporida;
OC Plasmodiidae; Plasmodium; Plasmodium (Laverania).
OX NCBI_TaxID=5833;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=FCR-3/C5;
RA Casta L.J., Schmutte C., Taraschi T.F.;
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=HN/FCC-1;
RA Wang P., Li M., Wu X.;
RT "Cloning of FEN-1 from Plasmodium falciparum HN/FCC-1.";
RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, ENDONUCLEASE AND EXONUCLEASE ACTIVITIES, ACTIVITY REGULATION, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=17928073; DOI=10.1016/j.molbiopara.2007.08.008;
RA Casta L.J., Buguliskis J.S., Matsumoto Y., Taraschi T.F.;
RT "Expression and biochemical characterization of the Plasmodium falciparum
RT DNA repair enzyme, flap endonuclease-1 (PfFEN-1).";
RL Mol. Biochem. Parasitol. 157:1-12(2008).
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:17928073}.
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 -!- ACTIVITY REGULATION: Inhibited by monovalent metal ions.
CC {ECO:0000269|PubMed:17928073}.
CC -!- SUBUNIT: Interacts with PCNA1 and PCNA2 (By similarity). Three
CC molecules of FEN1 bind to one PCNA trimer with each molecule binding to
CC one PCNA monomer. PCNA stimulates the nuclease activity without
CC altering cleavage specificity. {ECO:0000250|UniProtKB:Q7K734,
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: Expressed in the ring, trophozoite and schizont
CC stages. {ECO:0000269|PubMed:17928073}.
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; AF278764; AAG01445.1; -; mRNA.
DR EMBL; AY429426; AAR01941.1; -; Genomic_DNA.
DR AlphaFoldDB; Q9GZ01; -.
DR SMR; Q9GZ01; -.
DR VEuPathDB; PlasmoDB:PF3D7_0408500; -.
DR VEuPathDB; PlasmoDB:Pf7G8-2_000101900; -.
DR VEuPathDB; PlasmoDB:Pf7G8_040013700; -.
DR VEuPathDB; PlasmoDB:PfCD01_040013500; -.
DR VEuPathDB; PlasmoDB:PfDd2_040013800; -.
DR VEuPathDB; PlasmoDB:PfGA01_040013400; -.
DR VEuPathDB; PlasmoDB:PfGB4_040013900; -.
DR VEuPathDB; PlasmoDB:PfGN01_040013800; -.
DR VEuPathDB; PlasmoDB:PfHB3_040012600; -.
DR VEuPathDB; PlasmoDB:PfIT_040013100; -.
DR VEuPathDB; PlasmoDB:PfKE01_040015100; -.
DR VEuPathDB; PlasmoDB:PfKH01_040013500; -.
DR VEuPathDB; PlasmoDB:PfKH02_040013300; -.
DR VEuPathDB; PlasmoDB:PfML01_040014300; -.
DR VEuPathDB; PlasmoDB:PfNF135_040014300; -.
DR VEuPathDB; PlasmoDB:PfNF166_040014900; -.
DR VEuPathDB; PlasmoDB:PfNF54_040014100; -.
DR VEuPathDB; PlasmoDB:PfSD01_070024000; -.
DR VEuPathDB; PlasmoDB:PfSN01_040013500; -.
DR VEuPathDB; PlasmoDB:PfTG01_040013800; -.
DR BRENDA; 3.1.16.1; 4889.
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; 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; 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; 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; 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.
DR PROSITE; PS00841; XPG_1; 1.
PE 2: Evidence at transcript level;
KW DNA damage; DNA repair; DNA replication; Endonuclease; Exonuclease;
KW Hydrolase; Magnesium; Metal-binding; Mitochondrion; Nuclease; Nucleus;
KW Phosphoprotein.
FT CHAIN 1..650
FT /note="Flap endonuclease 1"
FT /id="PRO_0000403538"
FT REGION 1..106
FT /note="N-domain"
FT REGION 124..266
FT /note="I-domain"
FT REGION 349..357
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT REGION 371..592
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 371..471
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 483..500
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 524..592
FT /note="Polar 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 72
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 88
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="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
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 162
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
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 183
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 244
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 246
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT BINDING 246
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT VARIANT 295
FT /note="S -> P (in strain: HN/FCC-1)"
FT VARIANT 388
FT /note="T -> P (in strain: HN/FCC-1)"
FT VARIANT 536..537
FT /note="Missing (in strain: HN/FCC-1)"
SQ SEQUENCE 650 AA; 73990 MW; 2E9464DAB7F45B1D CRC64;
MGIKGLTKFI ADAAPNAIKE IKIESLMGRI IAIDASMSLY QFIIAIRDSE QYGNLTNESG
ETTSHISGLM SRSIRLMENG LKPIYVFDGA PPELKGSELE KRGEKRQKAE ELLKKAKEEG
NLEEIKKQSG RTVRVTRKQN EEAKKLLTLM GIPIIEAPCE AESQCAFLTK YNLAHATATE
DADALVFGTK ILIRNLNANA TSNQNKNKNN SKRGYILTEI NLEQVLKGLN LTMDEFIDFC
ILCGCDYCDT IKGIGSKTAY NLIKEYNCIE KIIENIDQNK YQVPSNFRFQ EARKSFINPN
VLPKEDIKID WNEPQIEELK HFLIKDYNFN ELRVTNYINR LLKARKVTTQ RRLDNFFTAC
TKKSTKLIVE ETKKEQTLPA RKGKKRPTAG DKNKQKAVKR KIEQANANGH HKMKEENKSV
DNEKNEDGIK SVDNEKNEDG IKSVDDEKNL DDEKNLDDEK NKDDEKKSLD NFSSNLFDSD
KESESGNIIK NEKQNMDDEK INDNLPSLFG DHSRIRHTEN KDNISDINNN NNNNNNNSSS
NNNNISNNHF NSVSSNSTFN SSTKLKSEDT LKSNSPLKED SPNSYNNIKN NNHTININSQ
INNHKEPISN NNLNNINNST EIKKKNTLFL LPFCPKDVTN VKKKKYTQRC
