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Bujnicki Lab Homepage

FEN1

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]


NCBI GenPept GI number(s): 119594378
4758356
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot P39748 P39748
PFAM: - P39748 (Link - using uniprot id)
InterPro: - P39748 (Link - using uniprot id)
CATH: - -
SCOP: - -
PDB: - -


Protein sequence:
MGIQGLAKLIADVAPSAIRENDIKSYFGRKVAIDASMSIYQFLIAVRQGG
DVLQNEEGETTSHLMGMFYRTIRMMENGIKPVYVFDGKPPQLKSGELAKR
SERRAEAEKQLQQAQAAGAEQEVEKFTKRLVKVTKQHNDECKHLLSLMGI
PYLDAPSEAEASCAALVKAGKVYAAATEDMDCLTFGSPVLMRHLTASEAK
KLPIQEFHLSRILQELGLNQEQFVDLCILLGSDYCESIRGIGPKRAVDLI
QKHKSIEEIVRRLDPNKYPVPENWLHKEAHQLFLEPEVLDPESVELKWSE
PNEEELIKFMCGEKQFSEERIRSGVKRLSKSRQGSTQGRLDDFFKVTGSL
SSAKRKEPEPKGSTKKKAKTGAAGKFKRGK

FEN1 (Homo sapiens) is able to recognize following damages:
References:

Title Authors Journal
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. Murray JM, Tavassoli M, al-Harithy R, Sheldrick KS, Lehmann AR, Carr AM, Watts FZ Mol Cell Biol July 1, 1994
Structural and functional homology between mammalian DNase IV and the 5'-nuclease domain of Escherichia coli DNA polymerase I. Robins P, Pappin DJ, Wood RD, Lindahl T J Biol Chem Nov. 18, 1994
Sequence of human FEN-1, a structure-specific endonuclease, and chromosomal localization of the gene (FEN1) in mouse and human. Hiraoka LR, Harrington JJ, Gerhard DS, Lieber MR, Hsieh CL Genomics Feb. 1, 1995
Essential amino acids for substrate binding and catalysis of human flap endonuclease 1. Shen B, Nolan JP, Sklar LA, Park MS J Biol Chem April 19, 1996
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. Gary R, Ludwig DL, Cornelius HL, MacInnes MA, Park MS J Biol Chem Sept. 26, 1997
Regulation of human flap endonuclease-1 activity by acetylation through the transcriptional coactivator p300. Hasan S, Stucki M, Hassa PO, Imhof R, Gehrig P, Hunziker P, Hubscher U, Hottiger MO Mol Cell June 1, 2001
Arginine residues 47 and 70 of human flap endonuclease-1 are involved in DNA substrate interactions and cleavage site determination. Qiu J, Bimston DN, Partikian A, Shen B J Biol Chem July 5, 2002
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). 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 Genome Res Oct. 1, 2004
Structural and thermodynamic analysis of human PCNA with peptides derived from DNA polymerase-delta p66 subunit and flap endonuclease-1. Bruning JB, Shamoo Y Structure Dec. 1, 2004
Structural basis for recruitment of human flap endonuclease 1 to PCNA. Sakurai S, Kitano K, Yamaguchi H, Hamada K, Okada K, Fukuda K, Uchida M, Ohtsuka E, Morioka H, Hakoshima T EMBO J Jan. 23, 2005
Human chromosome 11 DNA sequence and analysis including novel gene identification. 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 Nature March 23, 2006
Lysine acetylation targets protein complexes and co-regulates major cellular functions. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M Science Aug. 14, 2009


Last modification of this entry: Oct. 12, 2010.

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