FEN1
entrez
2237
canonical
uniprot
P39748
canonical
ensembl
ENSG00000168496
resolver
ensp
ENSP00000305480
resolver
genesymbol
FEN1
resolver
genesymbol_syn
RAD2
resolver
hgnc
HGNC:3650
resolver
uniprot
Q6FHX6
resolver
uniprot_entry
FEN1_HUMAN
resolver
uniprot_entry
Q6FHX6_HUMAN
resolver
amino_acid_sequence
MGIQGLAKLIADVAPSAIRENDIKSYFGRKVAIDASMSIYQFLIAVRQGGDVLQNEEGETTSHLMGMFYRTIRMMENGIKPVYVFDGKPPQLKSGELAKRSERRAEAEKQLQQAQAAGAEQEVEKFTKRLVKVTKQHNDECKHLLSLMGIPYLDAPSEAEASCAALVKAGKVYAAATEDMDCLTFGSPVLMRHLTASEAKKLPIQEFHLSRILQELGLNQEQFVDLCILLGSDYCESIRGIGPKRAVDLIQKHKSIEEIVRRLDPNKYPVPENWLHKEAHQLFLEPEVLDPESVELKWSEPNEEELIKFMCGEKQFSEERIRSGVKRLSKSRQGSTQGRLDDFFKVTGSLSSAKRKEPEPKGSTKKKAKTGAAGKFKRGK
uniprot
proteins
ec_number
3.1.-.-
uniprot
proteins
function
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 structures 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. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:10744741, ECO:0000269|PubMed:11986308, ECO:0000269|PubMed:18443037, ECO:0000269|PubMed:20729856, ECO:0000269|PubMed:26751069, ECO:0000269|PubMed:7961795, ECO:0000269|PubMed:8621570}.
uniprot
proteins
mass_dalton
42593
uniprot
proteins
mutagenesis
MUTAGEN 29; /note="R->A: No significant effect on exonuclease activity or flap endonuclease activity."; /evidence="ECO:0000269|PubMed:11986308"; MUTAGEN 34; /note="D->A: Loss of flap endonuclease activity but substrate binding activity is retained."; /evidence="ECO:0000269|PubMed:8621570"; MUTAGEN 47; /note="R->A: Significantly reduced exonuclease activity and reduced substrate binding. The positions of the cleavage sites are also shifted."; /evidence="ECO:0000269|PubMed:11986308"; MUTAGEN 70; /note="R->A: Loss of exonuclease activity and reduced endonuclease activity. Reduced substrate binding."; /evidence="ECO:0000269|PubMed:11986308"; MUTAGEN 73; /note="R->A: No significant effect on exonuclease activity or flap endonuclease activity."; /evidence="ECO:0000269|PubMed:11986308"; MUTAGEN 80; /note="K->A: No significant effect on exonuclease activity or flap endonuclease activity."; /evidence="ECO:0000269|PubMed:11986308"; MUTAGEN 86; /note="D->A: Loss of flap endonuclease activity but substrate binding activity is retained."; /evidence="ECO:0000269|PubMed:8621570"; MUTAGEN 103; /note="R->A: No effect on flap endonuclease activity or substrate binding."; /evidence="ECO:0000269|PubMed:8621570"; MUTAGEN 158; /note="E->A: Loss of flap endonuclease activity and substrate binding."; /evidence="ECO:0000269|PubMed:8621570"; MUTAGEN 179; /note="D->A: No effect on flap endonuclease activity or substrate binding."; /evidence="ECO:0000269|PubMed:8621570"; MUTAGEN 181; /note="D->A: Loss of flap endonuclease activity but substrate binding activity is retained."; /evidence="ECO:0000269|PubMed:8621570"; MUTAGEN 187; /note="S->A: Fails to translocate from nucleoli to the nuclear plasma."; /evidence="ECO:0000269|PubMed:18443037"; MUTAGEN 187; /note="S->D: Diminishes nucleolar localization."; /evidence="ECO:0000269|PubMed:18443037"; MUTAGEN 192; /note="R->K: Impairs ability to localize to sites of DNA replication or repair."; /evidence="ECO:0000269|PubMed:20729856"; MUTAGEN 231; /note="G->A: Loss of flap endonuclease activity and substrate binding."; /evidence="ECO:0000269|PubMed:8621570"; MUTAGEN 233; /note="D->A: Loss of flap endonuclease activity and substrate binding."; /evidence="ECO:0000269|PubMed:8621570
uniprot
proteins
post_translational_modification
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. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:11430825}.; PTM: Phosphorylation upon DNA damage induces relocalization to the nuclear plasma. Phosphorylation at Ser-187 by CDK2 occurs during late S-phase and results in dissociation from PCNA. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:20729856}.; PTM: Methylation at Arg-192 by PRMT5 impedes Ser-187 phosphorylation and increases interaction with PCNA. {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:20729856}.
uniprot
proteins
protein_family
FEN1 subfamily
uniprot
proteins
protein_family
XPG/RAD2 endonuclease family
uniprot
proteins
pubmed
10744741
uniprot
proteins
pubmed
11430825
uniprot
proteins
pubmed
11986308
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15576034
uniprot
proteins
pubmed
15616578
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
18443037
uniprot
proteins
pubmed
18499658
uniprot
proteins
pubmed
19336415
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20729856
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23675412
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26751069
uniprot
proteins
pubmed
26760506
uniprot
proteins
pubmed
7774922
uniprot
proteins
pubmed
7961795
uniprot
proteins
pubmed
8007985
uniprot
proteins
pubmed
8621570
uniprot
proteins
pubmed
9305916
uniprot
proteins
sequence_length
380
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Isoform 1]: Nucleus, nucleolus. Nucleus, nucleoplasm. Note=Resides mostly in the nucleoli and relocalizes to the nucleoplasm upon DNA damage.; SUBCELLULAR LOCATION: [Isoform FENMIT]: Mitochondrion {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:23675412}.
uniprot
proteins