FEN1
Flap endonuclease 1
Also known as: FEN-1, FEN1_HUMAN, MF1, RAD2
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P39748
- Gene
- FEN1
- Ensembl
- ENSG00000168496
- Chromosome
- 11
- Canonical length
- 380 aa
- Protein class
- Cancer-related genes, Plasma proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Nucleoli
OverviewNCBI Gene
The protein encoded by this gene removes 5' overhanging flaps in DNA repair and processes the 5' ends of Okazaki fragments in lagging strand DNA synthesis. Direct physical interaction between this protein and AP endonuclease 1 during long-patch base excision repair provides coordinated loading of the proteins onto the substrate, thus passing the substrate from one enzyme to another. The protein is a member of the XPG/RAD2 endonuclease family and is one of ten proteins essential for cell-free DNA replication. DNA secondary structure can inhibit flap processing at certain trinucleotide repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by the protein encoded by this gene. Therefore, secondary structure can deter the protective function of this protein, leading to site-specific trinucleotide expansions. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
380 residues, UniProt reviewed canonical sequence.
>P39748|FEN1
1 MGIQGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG DVLQNEEGET
61 TSHLMGMFYR TIRMMENGIK PVYVFDGKPP QLKSGELAKR SERRAEAEKQ LQQAQAAGAE
121 QEVEKFTKRL VKVTKQHNDE CKHLLSLMGI PYLDAPSEAE ASCAALVKAG KVYAAATEDM
181 DCLTFGSPVL MRHLTASEAK KLPIQEFHLS RILQELGLNQ EQFVDLCILL GSDYCESIRG
241 IGPKRAVDLI QKHKSIEEIV RRLDPNKYPV PENWLHKEAH QLFLEPEVLD PESVELKWSE
301 PNEEELIKFM CGEKQFSEER IRSGVKRLSK SRQGSTQGRL DDFFKVTGSL SSAKRKEPEP
361 KGSTKKKAKT GAAGKFKRGKLocalizationUniProt · AlphaFold · HPA
Whether an antibody against FEN1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.3
- Highest tissue expression
- 43 nTPM
Expression across tissuesHPA
Tissue
- thymus: 43 nTPM
- bone marrow: 37 nTPM
- tonsil: 35 nTPM
- lymph node: 32 nTPM
- appendix: 20 nTPM
- testis: 20 nTPM
Single-cell type
- oocytes: 4.6 nCPM
- early primary spermatocytes: 3.8 nCPM
- erythrocyte progenitors: 3.5 nCPM
- late primary spermatocytes: 1.8 nCPM
- megakaryocyte progenitors: 1.5 nCPM
- early spermatids: 1.3 nCPM
Immune cell
- T-reg: 25 nTPM
- basophil: 25 nTPM
- plasmacytoid DC: 25 nTPM
- NK-cell: 20 nTPM
- MAIT T-cell: 17 nTPM
- gdT-cell: 16 nTPM
Brain region
- cerebellum: 20 nTPM
- pons: 20 nTPM
- choroid plexus: 17 nTPM
- thalamus: 16 nTPM
- cerebral cortex: 15 nTPM
- midbrain: 15 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.28
- gnomAD pLI
- 0
- gnomAD missense Z
- 1.36
- DepMap mean gene effect
- -0.82
- DepMap dependency class
- common
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- base-excision repair, gap-filling
- DNA repair
- DNA replication
- DNA replication, removal of RNA primer
- double-strand break repair
- double-strand break repair via homologous recombination
- memory
- positive regulation of sister chromatid cohesion
- telomere maintenance via semi-conservative replication
- UV protection
Molecular 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
- magnesium ion binding
- manganese ion binding
- RNA-DNA hybrid ribonuclease activity
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of FEN1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads FEN1 as an antibody target. Whether an autoantibody or antibody against FEN1 could matter depends on whether native FEN1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
FEN1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label FEN1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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