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Protein FULL name: flap structure-specific endonuclease 1 [Homo sapiens].
FEN1 (Homo sapiens) is product of expression of
FEN1
gene.
FEN1 is involved in:
BER in Homo sapiens
Keywords:
FUNCTION: Endonuclease that cleaves the 5'-overhanging flap
structure that is generated by displacement synthesis when DNA
polymerase encounters the 5'-end of a downstream Okazaki fragment.
Also possesses 5' to 3' exonuclease activity on niked or gapped
double-stranded DNA, and exhibits RNase H activity.
COFACTOR: Binds 2 magnesium ions per subunit. They probably
participate in the reaction catalyzed by the enzyme. May bind an
additional third magnesium ion after substrate binding.
SUBUNIT: Interacts with PCNA. The C-terminal domain binds EP300.
Can bind simultaneously to both PCNA and EP300.
INTERACTION:
P54132:BLM; NbExp=3; IntAct=EBI-707816, EBI-621372;
P12004:PCNA; NbExp=2; IntAct=EBI-707816, EBI-358311;
Q14191:WRN; NbExp=7; IntAct=EBI-707816, EBI-368417;
SUBCELLULAR LOCATION: Nucleus.
PTM: Acetylated by EP300. Acetylation inhibits both endonuclease
and exonuclease activity. Acetylation also reduces DNA-binding
activity but does not affect interaction with PCNA or EP300.
SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. FEN1
subfamily.
WEB RESOURCE: Name=NIEHS-SNPs;
[LINK]
Links to other databases:
Protein sequence:
MGIQGLAKLIADVAPSAIRENDIKSYFGRKVAIDASMSIYQFLIAVRQGG
DVLQNEEGETTSHLMGMFYRTIRMMENGIKPVYVFDGKPPQLKSGELAKR
SERRAEAEKQLQQAQAAGAEQEVEKFTKRLVKVTKQHNDECKHLLSLMGI
PYLDAPSEAEASCAALVKAGKVYAAATEDMDCLTFGSPVLMRHLTASEAK
KLPIQEFHLSRILQELGLNQEQFVDLCILLGSDYCESIRGIGPKRAVDLI
QKHKSIEEIVRRLDPNKYPVPENWLHKEAHQLFLEPEVLDPESVELKWSE
PNEEELIKFMCGEKQFSEERIRSGVKRLSKSRQGSTQGRLDDFFKVTGSL
SSAKRKEPEPKGSTKKKAKTGAAGKFKRGK
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FEN1 (Homo sapiens) is able to recognize following damages:
References:
Title
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Authors
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Journal
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Structural and functional conservation of the human homolog of the Schizosaccharomyces pombe rad2 gene, which is required for chromosome segregation and recovery from DNA damage.
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Murray JM, Tavassoli M, al-Harithy R, Sheldrick KS, Lehmann AR, Carr AM, Watts FZ
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Mol Cell Biol
July 1, 1994
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Structural and functional homology between mammalian DNase IV and the 5'-nuclease domain of Escherichia coli DNA polymerase I.
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Robins P, Pappin DJ, Wood RD, Lindahl T
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J Biol Chem
Nov. 18, 1994
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Sequence of human FEN-1, a structure-specific endonuclease, and chromosomal localization of the gene (FEN1) in mouse and human.
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Hiraoka LR, Harrington JJ, Gerhard DS, Lieber MR, Hsieh CL
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Genomics
Feb. 1, 1995
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Essential amino acids for substrate binding and catalysis of human flap endonuclease 1.
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Shen B, Nolan JP, Sklar LA, Park MS
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J Biol Chem
April 19, 1996
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The DNA repair endonuclease XPG binds to proliferating cell nuclear antigen (PCNA) and shares sequence elements with the PCNA-binding regions of FEN-1 and cyclin-dependent kinase inhibitor p21.
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Gary R, Ludwig DL, Cornelius HL, MacInnes MA, Park MS
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J Biol Chem
Sept. 26, 1997
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Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300.
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Hasan S, Stucki M, Hassa PO, Imhof R, Gehrig P, Hunziker P, Hubscher U, Hottiger MO
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Mol Cell
June 1, 2001
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Arginine residues 47 and 70 of human flap endonuclease-1 are involved in DNA substrate interactions and cleavage site determination.
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Qiu J, Bimston DN, Partikian A, Shen B
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J Biol Chem
July 5, 2002
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The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
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Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J
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Genome Res
Oct. 1, 2004
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Structural and thermodynamic analysis of human PCNA with peptides derived from DNA polymerase-delta p66 subunit and flap endonuclease-1.
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Bruning JB, Shamoo Y
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Structure
Dec. 1, 2004
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Structural basis for recruitment of human flap endonuclease 1 to PCNA.
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Sakurai S, Kitano K, Yamaguchi H, Hamada K, Okada K, Fukuda K, Uchida M, Ohtsuka E, Morioka H, Hakoshima T
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EMBO J
Jan. 23, 2005
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Human chromosome 11 DNA sequence and analysis including novel gene identification.
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Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, FitzGerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y
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Nature
March 23, 2006
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Lysine acetylation targets protein complexes and co-regulates major cellular functions.
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Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M
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Science
Aug. 14, 2009
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Last modification of this entry: Oct. 12, 2010.
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