FEN1_HUMAN
ID FEN1_HUMAN Reviewed; 380 AA.
AC P39748;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 212.
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=DNase IV;
DE AltName: Full=Flap structure-specific endonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03140};
DE AltName: Full=Maturation factor 1;
DE Short=MF1;
DE Short=hFEN-1;
GN Name=FEN1 {ECO:0000255|HAMAP-Rule:MF_03140}; Synonyms=RAD2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8007985; DOI=10.1128/mcb.14.7.4878-4888.1994;
RA Murray J.M., Tavassoli M., Al-Harithy R., Sheldrick K.S., Lehmann A.R.,
RA Carr A.M., Watts F.Z.;
RT "Structural and functional conservation of the human homolog of the
RT Schizosaccharomyces pombe rad2 gene, which is required for chromosome
RT segregation and recovery from DNA damage.";
RL Mol. Cell. Biol. 14:4878-4888(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Leukemic T-cell;
RX PubMed=7774922; DOI=10.1016/0888-7543(95)80129-a;
RA Hiraoka L.R., Harrington J.J., Gerhard D.S., Lieber M.R., Hsieh C.-L.;
RT "Sequence of human FEN-1, a structure-specific endonuclease, and
RT chromosomal localization of the gene (FEN1) in mouse and human.";
RL Genomics 25:220-225(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=7961795; DOI=10.1016/s0021-9258(19)61935-6;
RA Robins P., Pappin D.J.C., Wood R.D., Lindahl T.;
RT "Structural and functional homology between mammalian DNase IV and the 5'-
RT nuclease domain of Escherichia coli DNA polymerase I.";
RL J. Biol. Chem. 269:28535-28538(1994).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE-BINDING SITES, AND MUTAGENESIS OF
RP ASP-34; ASP-86; ARG-103; GLU-158; ASP-179; ASP-181; GLY-231 AND ASP-233.
RX PubMed=8621570; DOI=10.1074/jbc.271.16.9173;
RA Shen B., Nolan J.P., Sklar L.A., Park M.S.;
RT "Essential amino acids for substrate binding and catalysis of human flap
RT endonuclease 1.";
RL J. Biol. Chem. 271:9173-9176(1996).
RN [8]
RP INTERACTION WITH PCNA.
RX PubMed=9305916; DOI=10.1074/jbc.272.39.24522;
RA Gary R., Ludwig D.L., Cornelius H.L., MacInnes M.A., Park M.S.;
RT "The DNA repair endonuclease XPG binds to proliferating cell nuclear
RT antigen (PCNA) and shares sequence elements with the PCNA-binding regions
RT of FEN-1 and cyclin-dependent kinase inhibitor p21.";
RL J. Biol. Chem. 272:24522-24529(1997).
RN [9]
RP FUNCTION.
RX PubMed=10744741; DOI=10.1074/jbc.275.14.10498;
RA Tom S., Henricksen L.A., Bambara R.A.;
RT "Mechanism whereby proliferating cell nuclear antigen stimulates flap
RT endonuclease 1.";
RL J. Biol. Chem. 275:10498-10505(2000).
RN [10]
RP INTERACTION WITH PCNA AND P300, AND ACETYLATION AT LYS-354; LYS-375;
RP LYS-377 AND LYS-380.
RX PubMed=11430825; DOI=10.1016/s1097-2765(01)00272-6;
RA Hasan S., Stucki M., Hassa P.O., Imhof R., Gehrig P., Hunziker P.,
RA Hubscher U., Hottiger M.O.;
RT "Regulation of human flap endonuclease-1 activity by acetylation through
RT the transcriptional coactivator p300.";
RL Mol. Cell 7:1221-1231(2001).
RN [11]
RP FUNCTION, SUBSTRATE-BINDING SITES ARG-47 AND ARG-70, AND MUTAGENESIS OF
RP ARG-29; ARG-47; ARG-70; ARG-73 AND LYS-80.
RX PubMed=11986308; DOI=10.1074/jbc.m111941200;
RA Qiu J., Bimston D.N., Partikian A., Shen B.;
RT "Arginine residues 47 and 70 of human flap endonuclease-1 are involved in
RT DNA substrate interactions and cleavage site determination.";
RL J. Biol. Chem. 277:24659-24666(2002).
RN [12]
RP INTERACTION WITH DDX11.
RX PubMed=18499658; DOI=10.1074/jbc.m802696200;
RA Farina A., Shin J.H., Kim D.H., Bermudez V.P., Kelman Z., Seo Y.S.,
RA Hurwitz J.;
RT "Studies with the human cohesin establishment factor, ChlR1. Association of
RT ChlR1 with Ctf18-RFC and Fen1.";
RL J. Biol. Chem. 283:20925-20936(2008).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF
RP SER-187.
RX PubMed=18443037; DOI=10.1128/mcb.00200-08;
RA Guo Z., Qian L., Liu R., Dai H., Zhou M., Zheng L., Shen B.;
RT "Nucleolar localization and dynamic roles of flap endonuclease 1 in
RT ribosomal DNA replication and damage repair.";
RL Mol. Cell. Biol. 28:4310-4319(2008).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-80 AND LYS-375, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [15]
RP FUNCTION, MUTAGENESIS OF ARG-192, METHYLATION AT ARG-19; ARG-100; ARG-104
RP AND ARG-192, AND PHOSPHORYLATION AT SER-187.
RX PubMed=20729856; DOI=10.1038/nchembio.422;
RA Guo Z., Zheng L., Xu H., Dai H., Zhou M., Pascua M.R., Chen Q.M., Shen B.;
RT "Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA
RT binding.";
RL Nat. Chem. Biol. 6:766-773(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197 AND THR-364, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-255; SER-293; SER-335 AND
RP THR-336, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP ALTERNATIVE INITIATION (ISOFORM FENMIT), AND SUBCELLULAR LOCATION (ISOFORM
RP FENMIT).
RX PubMed=23675412; DOI=10.1371/journal.pone.0062340;
RA Kazak L., Reyes A., He J., Wood S.R., Brea-Calvo G., Holen T.T., Holt I.J.;
RT "A cryptic targeting signal creates a mitochondrial FEN1 isoform with
RT tailed R-loop binding properties.";
RL PLoS ONE 8:E62340-E62340(2013).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP FUNCTION, AND INTERACTION WITH WDR4.
RX PubMed=26751069; DOI=10.1371/journal.pbio.1002349;
RA Cheng I.C., Chen B.C., Shuai H.H., Chien F.C., Chen P., Hsieh T.S.;
RT "Wuho is a new member in maintaining genome stability through its
RT interaction with flap endonuclease 1.";
RL PLoS Biol. 14:E1002349-E1002349(2016).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) OF 331-350.
RX PubMed=15576034; DOI=10.1016/j.str.2004.09.018;
RA Bruning J.B., Shamoo Y.;
RT "Structural and thermodynamic analysis of human PCNA with peptides derived
RT from DNA polymerase-delta p66 subunit and flap endonuclease-1.";
RL Structure 12:2209-2219(2004).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 2-380 IN COMPLEX WITH PCNA AND
RP MAGNESIUM IONS.
RX PubMed=15616578; DOI=10.1038/sj.emboj.7600519;
RA Sakurai S., Kitano K., Yamaguchi H., Hamada K., Okada K., Fukuda K.,
RA Uchida M., Ohtsuka E., Morioka H., Hakoshima T.;
RT "Structural basis for recruitment of human flap endonuclease 1 to PCNA.";
RL EMBO J. 24:683-693(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 ECO:0000269|PubMed:10744741, ECO:0000269|PubMed:11986308,
CC ECO:0000269|PubMed:18443037, ECO:0000269|PubMed:20729856,
CC ECO:0000269|PubMed:26751069, ECO:0000269|PubMed:7961795,
CC ECO:0000269|PubMed:8621570}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
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.;
CC -!- SUBUNIT: Three molecules of FEN1 bind to one PCNA trimer with each
CC molecule binding to one PCNA monomer (PubMed:15616578). PCNA stimulates
CC the nuclease activity without altering cleavage specificity
CC (PubMed:15616578). The C-terminal domain binds EP300; can bind
CC simultaneously to both PCNA and EP300 (PubMed:11430825). Interacts with
CC PCNA; can bind simultaneously to both PCNA and EP300 (PubMed:9305916,
CC PubMed:11430825). Interacts with DDX11; this interaction is direct and
CC increases flap endonuclease activity of FEN1 (PubMed:18499658).
CC Interacts with WDR4; regulating its endonuclease activity
CC (PubMed:26751069). {ECO:0000255|HAMAP-Rule:MF_03140,
CC ECO:0000269|PubMed:11430825, ECO:0000269|PubMed:15616578,
CC ECO:0000269|PubMed:18499658, ECO:0000269|PubMed:26751069,
CC ECO:0000269|PubMed:9305916}.
CC -!- INTERACTION:
CC P39748; P54132: BLM; NbExp=4; IntAct=EBI-707816, EBI-621372;
CC P39748; Q96NY9: MUS81; NbExp=5; IntAct=EBI-707816, EBI-2370806;
CC P39748; P12004: PCNA; NbExp=19; IntAct=EBI-707816, EBI-358311;
CC P39748; P57081: WDR4; NbExp=8; IntAct=EBI-707816, EBI-750427;
CC P39748; Q14191: WRN; NbExp=9; IntAct=EBI-707816, EBI-368417;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleolus. Nucleus,
CC nucleoplasm. Note=Resides mostly in the nucleoli and relocalizes to the
CC nucleoplasm upon DNA damage.
CC -!- SUBCELLULAR LOCATION: [Isoform FENMIT]: Mitochondrion
CC {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:23675412}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1;
CC IsoId=P39748-1; Sequence=Displayed;
CC Name=FENMIT;
CC IsoId=P39748-2; Sequence=VSP_047520;
CC -!- PTM: Acetylated by EP300. Acetylation inhibits both endonuclease and
CC exonuclease activity. Acetylation also reduces DNA-binding activity but
CC does not affect interaction with PCNA or EP300. {ECO:0000255|HAMAP-
CC Rule:MF_03140, ECO:0000269|PubMed:11430825}.
CC -!- PTM: Phosphorylation upon DNA damage induces relocalization to the
CC nuclear plasma. Phosphorylation at Ser-187 by CDK2 occurs during late
CC S-phase and results in dissociation from PCNA. {ECO:0000255|HAMAP-
CC Rule:MF_03140, ECO:0000269|PubMed:20729856}.
CC -!- PTM: Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation
CC and increases interaction with PCNA. {ECO:0000255|HAMAP-Rule:MF_03140,
CC ECO:0000269|PubMed:20729856}.
CC -!- MISCELLANEOUS: [Isoform FENMIT]: No nuclease activity. Binds
CC preferentially to RNA flap structures and R-loops. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. FEN1
CC subfamily. {ECO:0000255|HAMAP-Rule:MF_03140}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/fen1/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/FEN1ID40543ch11q12.html";
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DR EMBL; X76771; CAA54166.1; -; mRNA.
DR EMBL; L37374; AAA91331.1; -; mRNA.
DR EMBL; AF523117; AAM74238.1; -; Genomic_DNA.
DR EMBL; AC004770; AAC23394.1; -; Genomic_DNA.
DR EMBL; BC000323; AAH00323.1; -; mRNA.
DR CCDS; CCDS8010.1; -. [P39748-1]
DR PIR; A56531; A56531.
DR RefSeq; NP_004102.1; NM_004111.5. [P39748-1]
DR PDB; 1U7B; X-ray; 1.88 A; B=331-350.
DR PDB; 1UL1; X-ray; 2.90 A; X/Y/Z=2-380.
DR PDB; 3Q8K; X-ray; 2.20 A; A=2-336.
DR PDB; 3Q8L; X-ray; 2.32 A; A=2-336.
DR PDB; 3Q8M; X-ray; 2.60 A; A/B=2-336.
DR PDB; 3UVU; X-ray; 2.38 A; B=352-370.
DR PDB; 5E0V; X-ray; 2.07 A; C/D=335-350.
DR PDB; 5FV7; X-ray; 2.84 A; A/B=1-336.
DR PDB; 5K97; X-ray; 2.10 A; A=2-336.
DR PDB; 5KSE; X-ray; 2.10 A; A=2-336.
DR PDB; 5UM9; X-ray; 2.81 A; A=2-336.
DR PDB; 5ZOD; X-ray; 1.90 A; A=1-333.
DR PDB; 5ZOE; X-ray; 1.95 A; A=1-333.
DR PDB; 5ZOF; X-ray; 2.25 A; A=1-333.
DR PDB; 5ZOG; X-ray; 2.30 A; A=1-333.
DR PDB; 6TNZ; EM; 4.05 A; H=1-380.
DR PDBsum; 1U7B; -.
DR PDBsum; 1UL1; -.
DR PDBsum; 3Q8K; -.
DR PDBsum; 3Q8L; -.
DR PDBsum; 3Q8M; -.
DR PDBsum; 3UVU; -.
DR PDBsum; 5E0V; -.
DR PDBsum; 5FV7; -.
DR PDBsum; 5K97; -.
DR PDBsum; 5KSE; -.
DR PDBsum; 5UM9; -.
DR PDBsum; 5ZOD; -.
DR PDBsum; 5ZOE; -.
DR PDBsum; 5ZOF; -.
DR PDBsum; 5ZOG; -.
DR PDBsum; 6TNZ; -.
DR AlphaFoldDB; P39748; -.
DR SMR; P39748; -.
DR BioGRID; 108528; 138.
DR CORUM; P39748; -.
DR DIP; DIP-24216N; -.
DR ELM; P39748; -.
DR IntAct; P39748; 51.
DR MINT; P39748; -.
DR STRING; 9606.ENSP00000305480; -.
DR BindingDB; P39748; -.
DR ChEMBL; CHEMBL5027; -.
DR DrugBank; DB14490; Ferrous ascorbate.
DR DrugBank; DB14491; Ferrous fumarate.
DR DrugBank; DB14488; Ferrous gluconate.
DR DrugBank; DB14501; Ferrous glycine sulfate.
DR DrugBank; DB14489; Ferrous succinate.
DR DrugBank; DB01592; Iron.
DR GlyGen; P39748; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P39748; -.
DR MetOSite; P39748; -.
DR PhosphoSitePlus; P39748; -.
DR SwissPalm; P39748; -.
DR BioMuta; FEN1; -.
DR DMDM; 729475; -.
DR CPTAC; CPTAC-1409; -.
DR CPTAC; CPTAC-1410; -.
DR CPTAC; CPTAC-1411; -.
DR CPTAC; CPTAC-3230; -.
DR CPTAC; CPTAC-700; -.
DR EPD; P39748; -.
DR jPOST; P39748; -.
DR MassIVE; P39748; -.
DR MaxQB; P39748; -.
DR PaxDb; P39748; -.
DR PeptideAtlas; P39748; -.
DR PRIDE; P39748; -.
DR ProteomicsDB; 55319; -. [P39748-1]
DR TopDownProteomics; P39748-1; -. [P39748-1]
DR ABCD; P39748; 1 sequenced antibody.
DR Antibodypedia; 1878; 596 antibodies from 40 providers.
DR CPTC; P39748; 1 antibody.
DR DNASU; 2237; -.
DR Ensembl; ENST00000305885.3; ENSP00000305480.2; ENSG00000168496.4. [P39748-1]
DR GeneID; 2237; -.
DR KEGG; hsa:2237; -.
DR MANE-Select; ENST00000305885.3; ENSP00000305480.2; NM_004111.6; NP_004102.1.
DR CTD; 2237; -.
DR DisGeNET; 2237; -.
DR GeneCards; FEN1; -.
DR HGNC; HGNC:3650; FEN1.
DR HPA; ENSG00000168496; Tissue enhanced (lymphoid).
DR MIM; 600393; gene.
DR neXtProt; NX_P39748; -.
DR OpenTargets; ENSG00000168496; -.
DR PharmGKB; PA28090; -.
DR VEuPathDB; HostDB:ENSG00000168496; -.
DR eggNOG; KOG2519; Eukaryota.
DR GeneTree; ENSGT00940000155807; -.
DR HOGENOM; CLU_032444_2_0_1; -.
DR InParanoid; P39748; -.
DR OMA; GSQDYDS; -.
DR PhylomeDB; P39748; -.
DR TreeFam; TF105701; -.
DR BRENDA; 3.1.99.B1; 2681.
DR PathwayCommons; P39748; -.
DR Reactome; R-HSA-110362; POLB-Dependent Long Patch Base Excision Repair.
DR Reactome; R-HSA-162594; Early Phase of HIV Life Cycle.
DR Reactome; R-HSA-174437; Removal of the Flap Intermediate from the C-strand.
DR Reactome; R-HSA-5651801; PCNA-Dependent Long Patch Base Excision Repair.
DR Reactome; R-HSA-5685939; HDR through MMEJ (alt-NHEJ).
DR Reactome; R-HSA-69166; Removal of the Flap Intermediate.
DR SignaLink; P39748; -.
DR SIGNOR; P39748; -.
DR BioGRID-ORCS; 2237; 517 hits in 1085 CRISPR screens.
DR ChiTaRS; FEN1; human.
DR EvolutionaryTrace; P39748; -.
DR GeneWiki; Flap_structure-specific_endonuclease_1; -.
DR GenomeRNAi; 2237; -.
DR Pharos; P39748; Tchem.
DR PRO; PR:P39748; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P39748; protein.
DR Bgee; ENSG00000168496; Expressed in endometrium epithelium and 191 other tissues.
DR ExpressionAtlas; P39748; baseline and differential.
DR Genevisible; P39748; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; HDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0008409; F:5'-3' exonuclease activity; IDA:UniProtKB.
DR GO; GO:0017108; F:5'-flap endonuclease activity; IDA:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; TAS:ProtInc.
DR GO; GO:0003677; F:DNA binding; IMP:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; TAS:ProtInc.
DR GO; GO:0008309; F:double-stranded DNA exodeoxyribonuclease activity; TAS:ProtInc.
DR GO; GO:0004519; F:endonuclease activity; TAS:ProtInc.
DR GO; GO:0004527; F:exonuclease activity; TAS:ProtInc.
DR GO; GO:0048256; F:flap endonuclease activity; IDA:UniProtKB.
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; IDA:UniProtKB.
DR GO; GO:0006287; P:base-excision repair, gap-filling; TAS:Reactome.
DR GO; GO:0006281; P:DNA repair; TAS:ProtInc.
DR GO; GO:0006260; P:DNA replication; TAS:ProtInc.
DR GO; GO:0043137; P:DNA replication, removal of RNA primer; IDA:UniProtKB.
DR GO; GO:0006302; P:double-strand break repair; TAS:ProtInc.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; TAS:Reactome.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IDA:UniProtKB.
DR GO; GO:0045876; P:positive regulation of sister chromatid cohesion; IMP:UniProtKB.
DR GO; GO:0032201; P:telomere maintenance via semi-conservative replication; TAS:Reactome.
DR GO; GO:0009650; P:UV protection; TAS:ProtInc.
DR DisProt; DP01974; -.
DR HAMAP; MF_00614; Fen; 1.
DR IDEAL; IID00044; -.
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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative initiation;
KW Direct protein sequencing; DNA damage; DNA repair; DNA replication;
KW Endonuclease; Exonuclease; Hydrolase; Magnesium; Metal-binding;
KW Methylation; Mitochondrion; Nuclease; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..380
FT /note="Flap endonuclease 1"
FT /id="PRO_0000154069"
FT REGION 1..104
FT /note="N-domain"
FT REGION 122..253
FT /note="I-domain"
FT REGION 327..380
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 336..344
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000269|PubMed:9305916"
FT COMPBIAS 328..342
FT /note="Polar residues"
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:0000269|PubMed:15616578,
FT ECO:0007744|PDB:1UL1"
FT BINDING 47
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT BINDING 70
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT BINDING 86
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15616578,
FT ECO:0007744|PDB:1UL1, ECO:0007744|PDB:5FV7"
FT BINDING 158
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT BINDING 158
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15616578,
FT ECO:0007744|PDB:1UL1, ECO:0007744|PDB:5FV7"
FT BINDING 160
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15616578,
FT ECO:0007744|PDB:1UL1, ECO:0007744|PDB:5FV7,
FT ECO:0007744|PDB:5ZOD"
FT BINDING 179
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:5FV7, ECO:0007744|PDB:5ZOD"
FT BINDING 181
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:15616578,
FT ECO:0007744|PDB:1UL1, ECO:0007744|PDB:5FV7,
FT ECO:0007744|PDB:5ZOD"
FT BINDING 231
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT BINDING 233
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT BINDING 233
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:5ZOD"
FT MOD_RES 19
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140,
FT ECO:0000269|PubMed:20729856"
FT MOD_RES 80
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 100
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140,
FT ECO:0000269|PubMed:20729856"
FT MOD_RES 104
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140,
FT ECO:0000269|PubMed:20729856"
FT MOD_RES 187
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140,
FT ECO:0000269|PubMed:20729856"
FT MOD_RES 192
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140,
FT ECO:0000269|PubMed:20729856"
FT MOD_RES 197
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 293
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 335
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 336
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 354
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140,
FT ECO:0000269|PubMed:11430825"
FT MOD_RES 364
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 375
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140,
FT ECO:0000269|PubMed:11430825, ECO:0007744|PubMed:19608861"
FT MOD_RES 377
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140,
FT ECO:0000269|PubMed:11430825"
FT MOD_RES 380
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03140,
FT ECO:0000269|PubMed:11430825"
FT VAR_SEQ 1..64
FT /note="Missing (in isoform FENMIT)"
FT /evidence="ECO:0000305"
FT /id="VSP_047520"
FT MUTAGEN 29
FT /note="R->A: No significant effect on exonuclease activity
FT or flap endonuclease activity."
FT /evidence="ECO:0000269|PubMed:11986308"
FT MUTAGEN 34
FT /note="D->A: Loss of flap endonuclease activity but
FT substrate binding activity is retained."
FT /evidence="ECO:0000269|PubMed:8621570"
FT MUTAGEN 47
FT /note="R->A: Significantly reduced exonuclease activity and
FT reduced substrate binding. The positions of the cleavage
FT sites are also shifted."
FT /evidence="ECO:0000269|PubMed:11986308"
FT MUTAGEN 70
FT /note="R->A: Loss of exonuclease activity and reduced
FT endonuclease activity. Reduced substrate binding."
FT /evidence="ECO:0000269|PubMed:11986308"
FT MUTAGEN 73
FT /note="R->A: No significant effect on exonuclease activity
FT or flap endonuclease activity."
FT /evidence="ECO:0000269|PubMed:11986308"
FT MUTAGEN 80
FT /note="K->A: No significant effect on exonuclease activity
FT or flap endonuclease activity."
FT /evidence="ECO:0000269|PubMed:11986308"
FT MUTAGEN 86
FT /note="D->A: Loss of flap endonuclease activity but
FT substrate binding activity is retained."
FT /evidence="ECO:0000269|PubMed:8621570"
FT MUTAGEN 103
FT /note="R->A: No effect on flap endonuclease activity or
FT substrate binding."
FT /evidence="ECO:0000269|PubMed:8621570"
FT MUTAGEN 158
FT /note="E->A: Loss of flap endonuclease activity and
FT substrate binding."
FT /evidence="ECO:0000269|PubMed:8621570"
FT MUTAGEN 179
FT /note="D->A: No effect on flap endonuclease activity or
FT substrate binding."
FT /evidence="ECO:0000269|PubMed:8621570"
FT MUTAGEN 181
FT /note="D->A: Loss of flap endonuclease activity but
FT substrate binding activity is retained."
FT /evidence="ECO:0000269|PubMed:8621570"
FT MUTAGEN 187
FT /note="S->A: Fails to translocate from nucleoli to the
FT nuclear plasma."
FT /evidence="ECO:0000269|PubMed:18443037"
FT MUTAGEN 187
FT /note="S->D: Diminishes nucleolar localization."
FT /evidence="ECO:0000269|PubMed:18443037"
FT MUTAGEN 192
FT /note="R->K: Impairs ability to localize to sites of DNA
FT replication or repair."
FT /evidence="ECO:0000269|PubMed:20729856"
FT MUTAGEN 231
FT /note="G->A: Loss of flap endonuclease activity and
FT substrate binding."
FT /evidence="ECO:0000269|PubMed:8621570"
FT MUTAGEN 233
FT /note="D->A: Loss of flap endonuclease activity and
FT substrate binding."
FT /evidence="ECO:0000269|PubMed:8621570"
FT HELIX 6..13
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 15..17
FT /evidence="ECO:0007829|PDB:5ZOD"
FT STRAND 18..21
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 23..26
FT /evidence="ECO:0007829|PDB:5ZOD"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:5ZOD"
FT TURN 35..37
FT /evidence="ECO:0007829|PDB:5ZOD"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:5ZOE"
FT HELIX 64..76
FT /evidence="ECO:0007829|PDB:5ZOD"
FT STRAND 80..85
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:5K97"
FT HELIX 94..116
FT /evidence="ECO:0007829|PDB:5K97"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:5K97"
FT HELIX 123..129
FT /evidence="ECO:0007829|PDB:5K97"
FT HELIX 139..148
FT /evidence="ECO:0007829|PDB:5ZOD"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 159..168
FT /evidence="ECO:0007829|PDB:5ZOD"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 181..184
FT /evidence="ECO:0007829|PDB:5ZOD"
FT STRAND 188..193
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 198..200
FT /evidence="ECO:0007829|PDB:5ZOD"
FT STRAND 204..208
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 209..216
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 220..230
FT /evidence="ECO:0007829|PDB:5ZOD"
FT STRAND 232..235
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 243..253
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 256..262
FT /evidence="ECO:0007829|PDB:5ZOD"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 276..284
FT /evidence="ECO:0007829|PDB:5ZOD"
FT TURN 291..293
FT /evidence="ECO:0007829|PDB:5ZOE"
FT HELIX 303..311
FT /evidence="ECO:0007829|PDB:5ZOD"
FT TURN 312..314
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 318..330
FT /evidence="ECO:0007829|PDB:5ZOD"
FT HELIX 340..342
FT /evidence="ECO:0007829|PDB:1U7B"
FT STRAND 344..351
FT /evidence="ECO:0007829|PDB:1UL1"
SQ SEQUENCE 380 AA; 42593 MW; 5154F2F6E57592C5 CRC64;
MGIQGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG DVLQNEEGET
TSHLMGMFYR TIRMMENGIK PVYVFDGKPP QLKSGELAKR SERRAEAEKQ LQQAQAAGAE
QEVEKFTKRL VKVTKQHNDE CKHLLSLMGI PYLDAPSEAE ASCAALVKAG KVYAAATEDM
DCLTFGSPVL MRHLTASEAK KLPIQEFHLS RILQELGLNQ EQFVDLCILL GSDYCESIRG
IGPKRAVDLI QKHKSIEEIV RRLDPNKYPV PENWLHKEAH QLFLEPEVLD PESVELKWSE
PNEEELIKFM CGEKQFSEER IRSGVKRLSK SRQGSTQGRL DDFFKVTGSL SSAKRKEPEP
KGSTKKKAKT GAAGKFKRGK
