Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

FEN1 (P39748) - Overview - Molecular Target Synopsis


FEN1, Flap endonuclease 1
Enzyme Classification 3.1.-.-
UniProt P39748

Also Known as FEN1_HUMAN, FEN1, RAD2

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. Three molecules of FEN1 bind to one PCNA trimer with each molecule binding to one PCNA monomer (PubMed:15616578). PCNA stimulates the nuclease activity without altering cleavage specificity (PubMed:15616578). The C-terminal domain binds EP300; can bind simultaneously to both PCNA and EP300 (PubMed:11430825). Interacts with PCNA; can bind simultaneously to both PCNA and EP300 (PubMed:9305916, PubMed:11430825). Interacts with DDX11; this interaction is direct and increases flap endonuclease activity of FEN1 (PubMed:18499658). Interacts with WDR4; regulating its endonuclease activity (PubMed:26751069).

Inspect Structure
See all 3D Structures for FEN1

Isoforms / Transcripts (Protein Coding)

Sub-cellular localization

UniProt: FEN1 is active in the following subcellular-locations: mitochondrion, nucleolus, nucleoplasm, nucleus.
GO terms: FEN1 is active in the following subcellular-locations: membrane, mitochondrion, nuclear chromosome, nucleolus, nucleoplasm, nucleus, protein-containing complex.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project FEN1 has gain in 0 cell-lines, loss in 0 cell-lines and no signal in 1005 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: RPMI_8226, OVCAR_5, MDA_MB_435

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: LN-18, LN-229, COV318

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HeLa-S3, A549, HMEC

(see details)

3D Structures

For FEN1 there are:
15 structures (20 chains) solved
1 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

FEN1 has been screened with 138 compounds (143 bioactivities), 35 compounds have bioactivities that show binding affinity of <= 500nM (39 bioactivities). (see details)