FEN1A_DANRE
ID FEN1A_DANRE Reviewed; 380 AA.
AC Q6TNU4; Q6DRB5; Q7ZWH1;
DT 11-JAN-2011, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 117.
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;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney marrow;
RX PubMed=15520368; DOI=10.1073/pnas.0407241101;
RA Song H.-D., Sun X.-J., Deng M., Zhang G.-W., Zhou Y., Wu X.-Y., Sheng Y.,
RA Chen Y., Ruan Z., Jiang C.-L., Fan H.-Y., Zon L.I., Kanki J.P., Liu T.X.,
RA Look A.T., Chen Z.;
RT "Hematopoietic gene expression profile in zebrafish kidney marrow.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:16240-16245(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15256591; DOI=10.1073/pnas.0403929101;
RA Amsterdam A., Nissen R.M., Sun Z., Swindell E.C., Farrington S.,
RA Hopkins N.;
RT "Identification of 315 genes essential for early zebrafish development.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12792-12797(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Embryo;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (JUN-2004) 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 -!- 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6TNU4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6TNU4-2; Sequence=VSP_040394;
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; AY391423; AAQ91235.1; -; mRNA.
DR EMBL; AY648844; AAT68162.1; -; mRNA.
DR EMBL; BC049413; AAH49413.1; -; mRNA.
DR EMBL; BC071488; AAH71488.1; -; mRNA.
DR RefSeq; NP_001315436.1; NM_001328507.1. [Q6TNU4-1]
DR RefSeq; XP_017209293.1; XM_017353804.1. [Q6TNU4-1]
DR AlphaFoldDB; Q6TNU4; -.
DR SMR; Q6TNU4; -.
DR STRING; 7955.ENSDARP00000004016; -.
DR PaxDb; Q6TNU4; -.
DR PRIDE; Q6TNU4; -.
DR Ensembl; ENSDART00000024224; ENSDARP00000004016; ENSDARG00000011404. [Q6TNU4-1]
DR Ensembl; ENSDART00000178622; ENSDARP00000144222; ENSDARG00000011404. [Q6TNU4-1]
DR GeneID; 386707; -.
DR KEGG; dre:386707; -.
DR CTD; 2237; -.
DR ZFIN; ZDB-GENE-031112-11; fen1.
DR eggNOG; KOG2519; Eukaryota.
DR GeneTree; ENSGT00940000155807; -.
DR HOGENOM; CLU_032444_2_0_1; -.
DR InParanoid; Q6TNU4; -.
DR OMA; GSQDYDS; -.
DR OrthoDB; 1094524at2759; -.
DR PhylomeDB; Q6TNU4; -.
DR TreeFam; TF105701; -.
DR Reactome; R-DRE-110362; POLB-Dependent Long Patch Base Excision Repair.
DR Reactome; R-DRE-174437; Removal of the Flap Intermediate from the C-strand.
DR Reactome; R-DRE-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR Reactome; R-DRE-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-DRE-69166; Removal of the Flap Intermediate.
DR PRO; PR:Q6TNU4; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 24.
DR Bgee; ENSDARG00000011404; Expressed in somite and 39 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; IBA:GO_Central.
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; 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; IEA:UniProtKB-UniRule.
DR GO; GO:0043137; P:DNA replication, removal of RNA primer; IEA:UniProtKB-UniRule.
DR GO; GO:0060041; P:retina development in camera-type eye; IMP:ZFIN.
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.
DR PROSITE; PS00842; XPG_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; DNA damage; DNA repair; DNA replication;
KW Endonuclease; Exonuclease; Hydrolase; Magnesium; Metal-binding;
KW Mitochondrion; Nuclease; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..380
FT /note="Flap endonuclease 1"
FT /id="PRO_0000403488"
FT REGION 1..104
FT /note="N-domain"
FT REGION 122..253
FT /note="I-domain"
FT REGION 336..344
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140"
FT REGION 346..380
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:0000255|HAMAP-Rule:MF_03140"
FT BINDING 70
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000255|HAMAP-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:0000255|HAMAP-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: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"
FT VAR_SEQ 223..380
FT /note="FIDLCILLGCDYCGTIKGIGPKRAIDLIKQHGSIEEILENIDPNKHPAPEDW
FT LYKEARGLFLEPEVVDGTSVDLKWNEPDEDGLIQFMCAEKQFSEDRIRNGCKKITKSRQ
FT GSTQGRLDTFFTVTGSISSKRKEPETKGSAKKKQKTSATPGKFKKGK -> AVDTSVGQ
FT ASSQQLVLTSQSISQSNNQQPVHGSSVFTAKPSGLTPLKPHKGRHQLGFMLPSSTSTLH
FT TPSSSFVVQTPSQIPVQDSYISGVQSASQKSGQTSYLSVAL (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_040394"
FT CONFLICT 181
FT /note="D -> A (in Ref. 2; AAT68162)"
FT /evidence="ECO:0000305"
FT CONFLICT 269
FT /note="P -> R (in Ref. 2; AAT68162)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 380 AA; 42536 MW; 6A8962C32067CBD2 CRC64;
MGIHGLAKLI ADHAPSAIKE HEIKSYFGRK IAIDASMCIY QFLIAVRQDG NVLQNEDGET
TSHLMGMFYR TIRMLESGIK PVYVFDGKPP QLKSGELEKR VERRAEAEKL LAQAQEAGEQ
ENIDKFSKRL VKVTKQHNEE CKKLLSLMGV PYIEAPCEAE ASCAALVKAG KVYATATEDM
DGLTFGTTVL LRHLTASEAK KLPIQEFHFS RILQDMELTH QQFIDLCILL GCDYCGTIKG
IGPKRAIDLI KQHGSIEEIL ENIDPNKHPA PEDWLYKEAR GLFLEPEVVD GTSVDLKWNE
PDEDGLIQFM CAEKQFSEDR IRNGCKKITK SRQGSTQGRL DTFFTVTGSI SSKRKEPETK
GSAKKKQKTS ATPGKFKKGK
