ID   FEN1_HUMAN     STANDARD;      PRT;   380 AA.
AC   P39748;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   07-MAR-2006, entry version 56.
DE   Flap endonuclease 1 (EC 3.1.-.-) (Maturation factor 1) (MF1).
GN   Name=FEN1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE.
RX   MEDLINE=94277093; PubMed=8007985;
RA   Murray J.M., Tavassoli M., Al-Harithy R., Sheldrick K.S.,
RA   Lehmann A.R., 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.
RC   TISSUE=Lymphocyte;
RX   PubMed=7774922;
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].
RA   Rieder M.J., Livingston R.J., Braun A.C., Montoya M.A., Chung M.-W.,
RA   Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D.,
RA   Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RT   "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT   of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL   Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG   Human chromosome 11 international sequencing consortium;
RL   Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
RX   MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA   Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA   Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA   Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA   Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA   Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA   Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA   Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA   Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA   Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA   Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA   Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA   Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA   Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA   Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA   Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA   Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA   Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT   "Generation and initial analysis of more than 15,000 full-length human
RT   and mouse cDNA sequences.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN   [6]
RP   PARTIAL PROTEIN SEQUENCE.
RX   MEDLINE=95050647; PubMed=7961795;
RA   Robins P., Pappin D.J., Wood R.D., Lindahl T.;
RT   "Structural and functional homology between mammalian DNase IV and the
RT   5'-nuclease domain of Escherichia coli DNA polymerase I.";
RL   J. Biol. Chem. 269:28535-28538(1994).
RN   [7]
RP   ACETYLATION.
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
RT   through the transcriptional coactivator p300.";
RL   Mol. Cell 7:1221-1231(2001).
RN   [8]
RP   INTERACTION WITH PCNA.
RX   MEDLINE=97450983; 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
RT   regions of FEN-1 and cyclin-dependent kinase inhibitor p21.";
RL   J. Biol. Chem. 272:24522-24529(1997).
CC   -!- FUNCTION: Endonuclease that cleave the 5'overhanging flap
CC       structure that is generated by displacement synthesis when DNA
CC       polymerase encounters the 5'end of a downstream Okazaki fragment.
CC       It fails to cleave other DNA structures, including 3'flaps and
CC       single stranded DNA (By similarity).
CC   -!- SUBUNIT: Interacts with PCNA.
CC   -!- INTERACTION:
CC       P54132:BLM; NbExp=3; IntAct=EBI-707816, EBI-621372;
CC       P12004:PCNA; NbExp=1; IntAct=EBI-707816, EBI-358311;
CC       Q14191:WRN; NbExp=7; IntAct=EBI-707816, EBI-368417;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- PTM: Acetylated by p300.
CC   -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. FEN1
CC       subfamily.
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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   PIR; A56531; A56531.
DR   PDB; 1UL1; X-ray; X/Y/Z=2-380.
DR   IntAct; P39748; -.
DR   Ensembl; ENSG00000168496; Homo sapiens.
DR   H-InvDB; HIX0009699; -.
DR   HGNC; HGNC:3650; FEN1.
DR   MIM; 600393; gene.
DR   Reactome; P39748; -.
DR   LinkHub; P39748; -.
DR   GO; GO:0003684; F:damaged DNA binding; TAS.
DR   GO; GO:0003690; F:double-stranded DNA binding; TAS.
DR   GO; GO:0008309; F:double-stranded DNA specific exodeoxyribonu...; TAS.
DR   GO; GO:0004519; F:endonuclease activity; TAS.
DR   GO; GO:0004527; F:exonuclease activity; TAS.
DR   GO; GO:0006260; P:DNA replication; NAS.
DR   GO; GO:0006302; P:double-strand break repair; TAS.
DR   GO; GO:0048015; P:phosphoinositide-mediated signaling; NAS.
DR   GO; GO:0009650; P:UV protection; TAS.
DR   InterPro; IPR000513; Exo_N_I.
DR   InterPro; IPR008918; HhH2.
DR   InterPro; IPR006086; XPG_I.
DR   InterPro; IPR006085; XPG_N.
DR   InterPro; IPR006084; XPGC_Rad.
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   PROSITE; PS00841; XPG_1; 1.
DR   PROSITE; PS00842; XPG_2; 1.
KW   3D-structure; Acetylation; Direct protein sequencing; Endonuclease;
KW   Hydrolase; Nuclear protein; Nuclease.
FT   CHAIN         1    380       Flap endonuclease 1.
FT                                /FTId=PRO_0000154069.
FT   REGION        1    104       N-domain.
FT   REGION      122    253       I-domain.
FT   REGION      328    355       Interaction with PCNA.
FT   TURN          4      5
FT   HELIX         6     11
FT   TURN         12     13
FT   TURN         15     16
FT   STRAND       17     17
FT   STRAND       20     21
FT   HELIX        23     26
FT   TURN         27     28
FT   STRAND       31     34
FT   HELIX        35     43
FT   STRAND       44     44
FT   HELIX        62     76
FT   TURN         77     78
FT   STRAND       81     85
FT   STRAND       88     88
FT   STRAND       91     91
FT   STRAND      136    136
FT   HELIX       138    148
FT   TURN        149    149
FT   STRAND      152    154
FT   STRAND      156    157
FT   HELIX       159    169
FT   TURN        170    170
FT   STRAND      171    176
FT   STRAND      178    178
FT   TURN        180    180
FT   HELIX       181    184
FT   TURN        185    186
FT   STRAND      188    192
FT   STRAND      194    195
FT   STRAND      204    208
FT   HELIX       209    216
FT   TURN        217    217
FT   HELIX       220    231
FT   STRAND      233    235
FT   TURN        239    240
FT   HELIX       243    252
FT   STRAND      253    255
FT   HELIX       256    260
FT   TURN        261    262
FT   TURN        266    267
FT   STRAND      268    268
FT   STRAND      272    273
FT   HELIX       276    284
FT   STRAND      285    285
FT   HELIX       291    293
FT   HELIX       303    309
FT   TURN        310    313
FT   STRAND      314    314
FT   HELIX       318    332
FT   STRAND      333    333
FT   STRAND      336    337
FT   HELIX       340    343
FT   STRAND      344    351
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
//