FEN1_THEAN
ID FEN1_THEAN Reviewed; 506 AA.
AC Q4UFP0;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 87.
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=TA15785;
OS Theileria annulata.
OC Eukaryota; Sar; Alveolata; Apicomplexa; Aconoidasida; Piroplasmida;
OC Theileriidae; Theileria.
OX NCBI_TaxID=5874;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Ankara;
RX PubMed=15994557; DOI=10.1126/science.1110418;
RA Pain A., Renauld H., Berriman M., Murphy L., Yeats C.A., Weir W.,
RA Kerhornou A., Aslett M., Bishop R., Bouchier C., Cochet M., Coulson R.M.R.,
RA Cronin A., de Villiers E.P., Fraser A., Fosker N., Gardner M., Goble A.,
RA Griffiths-Jones S., Harris D.E., Katzer F., Larke N., Lord A., Maser P.,
RA McKellar S., Mooney P., Morton F., Nene V., O'Neil S., Price C.,
RA Quail M.A., Rabbinowitsch E., Rawlings N.D., Rutter S., Saunders D.,
RA Seeger K., Shah T., Squares R., Squares S., Tivey A., Walker A.R.,
RA Woodward J., Dobbelaere D.A.E., Langsley G., Rajandream M.A., McKeever D.,
RA Shiels B., Tait A., Barrell B.G., Hall N.;
RT "Genome of the host-cell transforming parasite Theileria annulata compared
RT with T. parva.";
RL Science 309:131-133(2005).
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; CR940348; CAI74076.1; -; Genomic_DNA.
DR RefSeq; XP_951808.1; XM_946715.1.
DR AlphaFoldDB; Q4UFP0; -.
DR SMR; Q4UFP0; -.
DR STRING; 5874.XP_951808.1; -.
DR PRIDE; Q4UFP0; -.
DR GeneID; 3861997; -.
DR KEGG; tan:TA15785; -.
DR VEuPathDB; PiroplasmaDB:TA15785; -.
DR eggNOG; KOG2519; Eukaryota.
DR InParanoid; Q4UFP0; -.
DR OMA; GSQDYDS; -.
DR OrthoDB; 1094524at2759; -.
DR Proteomes; UP000001950; Chromosome 2.
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; 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; Reference proteome.
FT CHAIN 1..506
FT /note="Flap endonuclease 1"
FT /id="PRO_0000403544"
FT REGION 1..106
FT /note="N-domain"
FT REGION 124..253
FT /note="I-domain"
FT REGION 330..338
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT REGION 338..388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 338..352
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..388
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 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"
SQ SEQUENCE 506 AA; 57281 MW; 994DBD606E44699D CRC64;
MGIKGLIPFL SEKVPSSISE LSLECLSGES LAIDASAALY QFTIAIRDSS YFSSLVNSKG
ESTSHIYGLM NRCSKLLEYG IKPVFVFDSK PPELKSKTLD KRRQKREEAK TDFKKAISEG
DKESAKKLVG RTVKVTKDMN DSAKKLLRLM GIPVIEALEE AEAQCAYLVT KNLCHFVASE
DTDTLVFGGW FLLRNVTSSA NKKIVKVDLQ KVLDGLEFNF DQFVDFCILC GCDYCDTLEG
VGPKTAYSLV KKYQSLEEIV RFKGGDYDEF KEAKDYFLSP KVNEYDENSV KMGTIDPEGL
TEFLVQENNF SKERVEKFIE KLLKFKTKKI QTSLLSFLTN PQPTNKSKSL DEGPKQSSTE
DYKVNTNPST KGSNVYTTDT NSTKDTKGIE CTATTTNNNL ENKVKIENEE NDTGRRDSID
DLFKEFEDET NLFEQDEFEP KSKEYNLEKQ HELELNVHNR NVILIDDDDD EVLTTANSEK
MNCEIGKVKE EPNKKGKFSL ISIYIF
