Flap endonuclease 1

Details

Name
Flap endonuclease 1
Synonyms
  • 3.1.-.-
  • DNase IV
  • FEN-1
  • Flap structure-specific endonuclease 1
  • hFEN-1
  • Maturation factor 1
  • MF1
  • RAD2
Gene Name
FEN1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0049739|Flap endonuclease 1
MGIQGLAKLIADVAPSAIRENDIKSYFGRKVAIDASMSIYQFLIAVRQGGDVLQNEEGET
TSHLMGMFYRTIRMMENGIKPVYVFDGKPPQLKSGELAKRSERRAEAEKQLQQAQAAGAE
QEVEKFTKRLVKVTKQHNDECKHLLSLMGIPYLDAPSEAEASCAALVKAGKVYAAATEDM
DCLTFGSPVLMRHLTASEAKKLPIQEFHLSRILQELGLNQEQFVDLCILLGSDYCESIRG
IGPKRAVDLIQKHKSIEEIVRRLDPNKYPVPENWLHKEAHQLFLEPEVLDPESVELKWSE
PNEEELIKFMCGEKQFSEERIRSGVKRLSKSRQGSTQGRLDDFFKVTGSLSSAKRKEPEP
KGSTKKKAKTGAAGKFKRGK
Number of residues
380
Molecular Weight
42592.635
Theoretical pI
Not Available
GO Classification
Functions
5'-3' exonuclease activity / 5'-flap endonuclease activity / damaged DNA binding / DNA binding / double-stranded DNA binding / double-stranded DNA exodeoxyribonuclease activity / endonuclease activity / exonuclease activity / flap endonuclease activity / metal ion binding / RNA-DNA hybrid ribonuclease activity
Processes
DNA repair / DNA replication / DNA replication, removal of RNA primer / double-strand break repair / double-strand break repair via homologous recombination / memory / nucleic acid phosphodiester bond hydrolysis / positive regulation of sister chromatid cohesion / telomere maintenance via recombination / UV protection
Components
membrane / mitochondrion / nuclear chromosome, telomeric region / nucleolus / nucleoplasm / nucleus / protein complex
General Function
Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structurs that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.
Specific Function
5'-3' exonuclease activity
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0049740|Flap endonuclease 1 (FEN1)
ATGGGAATTCAAGGCCTGGCCAAACTAATTGCTGATGTGGCCCCCAGTGCCATCCGGGAG
AATGACATCAAGAGCTACTTTGGCCGTAAGGTGGCCATTGATGCCTCTATGAGCATTTAT
CAGTTCCTGATTGCTGTTCGCCAGGGTGGGGATGTGCTGCAGAATGAGGAGGGTGAGACC
ACCAGCCACCTGATGGGCATGTTCTACCGCACCATTCGCATGATGGAGAACGGCATCAAG
CCCGTGTATGTCTTTGATGGCAAGCCGCCACAGCTCAAGTCAGGCGAGCTGGCCAAACGC
AGTGAGCGGCGGGCTGAGGCAGAGAAGCAGCTGCAGCAGGCTCAGGCTGCTGGGGCCGAG
CAGGAGGTGGAAAAATTCACTAAGCGGCTGGTGAAGGTCACTAAGCAGCACAATGATGAG
TGCAAACATCTGCTGAGCCTCATGGGCATCCCTTATCTTGATGCACCCAGTGAGGCAGAG
GCCAGCTGTGCTGCCCTGGTGAAGGCTGGCAAAGTCTATGCTGCGGCTACCGAGGACATG
GACTGCCTCACCTTCGGCAGCCCTGTGCTAATGCGACACCTGACTGCCAGTGAAGCCAAA
AAGCTGCCAATCCAGGAATTCCACCTGAGCCGGATTCTGCAGGAGCTGGGCCTGAACCAG
GAACAGTTTGTGGATCTGTGCATCCTGCTAGGCAGTGACTACTGTGAGAGTATCCGGGGT
ATTGGGCCCAAGCGGGCTGTGGACCTCATCCAGAAGCACAAGAGCATCGAGGAGATCGTG
CGGCGACTTGACCCCAACAAGTACCCTGTGCCAGAAAATTGGCTCCACAAGGAGGCTCAC
CAGCTCTTCTTGGAACCTGAGGTGCTGGACCCAGAGTCTGTGGAGCTGAAGTGGAGCGAG
CCAAATGAAGAAGAGCTGATCAAGTTCATGTGTGGTGAAAAGCAGTTCTCTGAGGAGCGA
ATCCGCAGTGGGGTCAAGAGGCTGAGTAAGAGCCGCCAAGGCAGCACCCAGGGCCGCCTG
GATGATTTCTTCAAGGTGACCGGCTCACTCTCTTCAGCTAAGCGCAAGGAGCCAGAACCC
AAGGGATCCACTAAGAAGAAGGCAAAGACTGGGGCAGCAGGGAAGTTTAAAAGGGGAAAA
TAA
Chromosome Location
11
Locus
11q12.2
External Identifiers
ResourceLink
UniProtKB IDP39748
UniProtKB Entry NameFEN1_HUMAN
HGNC IDHGNC:3650
General References
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  2. Hiraoka LR, Harrington JJ, Gerhard DS, Lieber MR, Hsieh CL: Sequence of human FEN-1, a structure-specific endonuclease, and chromosomal localization of the gene (FEN1) in mouse and human. Genomics. 1995 Jan 1;25(1):220-5. [Article]
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  5. Robins P, Pappin DJ, Wood RD, Lindahl T: Structural and functional homology between mammalian DNase IV and the 5'-nuclease domain of Escherichia coli DNA polymerase I. J Biol Chem. 1994 Nov 18;269(46):28535-8. [Article]
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  7. Gary R, Ludwig DL, Cornelius HL, MacInnes MA, Park MS: 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. J Biol Chem. 1997 Sep 26;272(39):24522-9. [Article]
  8. Tom S, Henricksen LA, Bambara RA: Mechanism whereby proliferating cell nuclear antigen stimulates flap endonuclease 1. J Biol Chem. 2000 Apr 7;275(14):10498-505. [Article]
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  10. Qiu J, Bimston DN, Partikian A, Shen B: Arginine residues 47 and 70 of human flap endonuclease-1 are involved in DNA substrate interactions and cleavage site determination. J Biol Chem. 2002 Jul 5;277(27):24659-66. Epub 2002 May 1. [Article]
  11. Farina A, Shin JH, Kim DH, Bermudez VP, Kelman Z, Seo YS, Hurwitz J: Studies with the human cohesin establishment factor, ChlR1. Association of ChlR1 with Ctf18-RFC and Fen1. J Biol Chem. 2008 Jul 25;283(30):20925-36. doi: 10.1074/jbc.M802696200. Epub 2008 May 21. [Article]
  12. Guo Z, Qian L, Liu R, Dai H, Zhou M, Zheng L, Shen B: Nucleolar localization and dynamic roles of flap endonuclease 1 in ribosomal DNA replication and damage repair. Mol Cell Biol. 2008 Jul;28(13):4310-9. doi: 10.1128/MCB.00200-08. Epub 2008 Apr 28. [Article]
  13. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  14. Guo Z, Zheng L, Xu H, Dai H, Zhou M, Pascua MR, Chen QM, Shen B: Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding. Nat Chem Biol. 2010 Oct;6(10):766-73. doi: 10.1038/nchembio.422. Epub 2010 Aug 22. [Article]
  15. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
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  17. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
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  19. Kazak L, Reyes A, He J, Wood SR, Brea-Calvo G, Holen TT, Holt IJ: A cryptic targeting signal creates a mitochondrial FEN1 isoform with tailed R-Loop binding properties. PLoS One. 2013 May 13;8(5):e62340. doi: 10.1371/journal.pone.0062340. Print 2013. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01592IronapprovedunknownDetails
DB14488Ferrous gluconateapprovedunknownDetails
DB14489Ferrous succinateapprovedunknownDetails
DB14490Ferrous ascorbateapprovedunknownDetails
DB14491Ferrous fumarateapprovedunknownDetails
DB14501Ferrous glycine sulfateapprovedunknownDetails