Tchem FEN1 Flap endonuclease 1

Protein Summary

Description

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. 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]

Uniprot Accession IDs

• P39748
• FEN-1

Gene Name

• FEN1

Ensembl ID

• ENST00000305885
• ENSP00000305480
• ENSG00000168496

Symbol

• RAD2
• MF1
• RAD2
• FEN-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
interacting protein	0.99
molecular function	0.98
kinase perturbation	0.97
co-expressed gene	0.93
protein domain	0.92

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Nuclease / Exodeoxyribonuclease / Flap Endonuclease 1

Protein / Nucleic Acid Binding / Nuclease / Endodeoxyribonuclease / Flap Endonuclease 1

Protein / Nucleic Acid Binding / Dna Binding Protein / Exodeoxyribonuclease / Flap Endonuclease 1

Protein / Nucleic Acid Binding / Dna Binding Protein / Endodeoxyribonuclease / Flap Endonuclease 1

Protein / Nucleic Acid Binding / Dna Binding Protein / Damaged Dna-binding Protein / Flap Endonuclease 1

Protein / Hydrolase / Flap Endonuclease 1

DTO Classes

Protein / Enzyme / Nuclease / Exodeoxyribonuclease / Flap Endonuclease 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1247.13   (req: < 5)

Gene RIFs: 106   (req: <= 3)

Antibodies: 522   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1247.13   (req: >= 5)

Gene RIFs: 106   (req: > 3)

Antibodies: 522   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 26

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 35

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (35)

Explore Active Ligands

1 – 10 of 35

3-hydroxyquinazoline-2,4(1H,3H)-dione

FEN1Tchem Enzyme

pKi : 6.32

CHEMBL361962

FEN1Tchem Enzyme

pIC50 : 11

CHEMBL361011

FEN1Tchem Enzyme

pIC50 : 10.92

CHEMBL359533

FEN1Tchem Enzyme

pIC50 : 10.37

CHEMBL183133

FEN1Tchem Enzyme

pIC50 : 10.42

CHEMBL361350

FEN1Tchem Enzyme

pIC50 : 10.6

CHEMBL182381

FEN1Tchem Enzyme

pIC50 : 10.09

CHEMBL364591

FEN1Tchem Enzyme

pIC50 : 10.64

CHEMBL183792

FEN1Tchem Enzyme

pIC50 : 10.85

CHEMBL182687

FEN1Tchem Enzyme

pIC50 : 10.85

Protein-Protein Interactions (410)

Explore Interacting Targets

1 – 10 of 410

• See Interactions on String-DB

PCNA

Tchem

Novelty:  0.03909539

p_int:  0.999924849

p_ni:  0.000075151

Score:  0.999

Data Source:  BioPlex,Reactome,STRINGDB

SNRNP27

Tbio

Novelty:  0.0175187

p_int:  0.994826868

p_ni:  0.005173132

Score:  0.167

Data Source:  BioPlex,STRINGDB

GTF2E2

Tbio

Novelty:  0.18033153

p_int:  0.983600845

p_ni:  0.016399105

p_wrong:  5e-8

Score:  0.249

Data Source:  BioPlex,STRINGDB

FGB

Tbio

Novelty:  0.00437751

p_int:  0.963137954

p_ni:  0.036861984

p_wrong:  6.3e-8

Data Source:  BioPlex

DUSP19

Tbio

Family:  Enzyme

Novelty:  0.13289846

p_int:  0.942701965

p_ni:  0.057297789

p_wrong:  2.46e-7

Score:  0.315

Data Source:  BioPlex,STRINGDB

USP47

Tchem

Family:  Enzyme

Novelty:  0.07579226

p_int:  0.923865259

p_ni:  0.076050725

p_wrong:  0.000084016

Score:  0.203

Data Source:  BioPlex,STRINGDB

FAM24B

Tdark

Novelty:  1.04675689

p_int:  0.916054498

p_ni:  0.083945338

p_wrong:  1.64e-7

Data Source:  BioPlex

ACTL6A

Tbio

Novelty:  0.01892162

p_int:  0.910419609

p_ni:  0.08958039

p_wrong:  1e-9

Score:  0.394

Data Source:  BioPlex,STRINGDB

PTCRA

Tbio

Novelty:  0.01307489

p_int:  0.858701917

p_ni:  0.141298082

Score:  0.309

Data Source:  BioPlex,STRINGDB

LIG1

Tchem

Family:  Enzyme

Novelty:  0.00326816

Score:  0.999

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (33)

Reactome (29)

KEGG (3)

WikiPathways (1)

Base Excision Repair (R-HSA-73884)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Base Excision Repair	72 targets	R-HSA-73884
Reactome	Cell Cycle	597 targets	R-HSA-1640170
Reactome	Cell Cycle, Mitotic	495 targets	R-HSA-69278
Reactome	Chromosome Maintenance	88 targets	R-HSA-73886
Reactome	DNA Double-Strand Break Repair	146 targets	R-HSA-5693532

Name	Explore in Pharos	Explore in Source
Base Excision Repair	72 targets	R-HSA-73884
Cell Cycle	597 targets	R-HSA-1640170
Cell Cycle, Mitotic	495 targets	R-HSA-69278
Chromosome Maintenance	88 targets	R-HSA-73886
DNA Double-Strand Break Repair	146 targets	R-HSA-5693532

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (33)

Functions (14)

Components (7)

Processes (12)

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1 – 10 of 14

GO Term	Evidence	Assigned by
5'-3' exonuclease activity	Inferred from Direct Assay (IDA)	UniProtKB
5'-flap endonuclease activity	Inferred from Direct Assay (IDA)	UniProtKB
flap endonuclease activity	Inferred from Direct Assay (IDA)	UniProtKB
RNA-DNA hybrid ribonuclease activity	Inferred from Direct Assay (IDA)	UniProtKB
DNA binding	Inferred from Mutant Phenotype (IMP)	UniProtKB
double-stranded DNA 5'-3' exodeoxyribonuclease activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
magnesium ion binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
manganese ion binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
single-stranded DNA 5'-3' exodeoxyribonuclease activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
damaged DNA binding	Traceable Author Statement (TAS)	ProtInc

Disease Associations ()

No disease associations found

GWAS Traits (122)

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1 – 5 of 122

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
blood metabolite measurement	EFO_0005664	5	17	43		99.9
docosapentaenoic acid measurement	EFO_0006809	2	13	16		99.8
high density lipoprotein cholesterol measurement	EFO_0004612	15	23	40	1.9	99.8
serum metabolite measurement	EFO_0005653	7	47	292		99.8
linoleic acid measurement	EFO_0006807	2	9	10		99.7

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
blood metabolite measurement	EFO_0005664	43		99.9
docosapentaenoic acid measurement	EFO_0006809	16		99.8
high density lipoprotein cholesterol measurement	EFO_0004612	40	1.9	99.8
serum metabolite measurement	EFO_0005653	292		99.8
linoleic acid measurement	EFO_0006807	10		99.7

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UniProt Keyword Find Similar Targets

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3D-structure
Acetylation
Alternative initiation
Complete proteome
Direct protein sequencing
DNA damage
DNA repair
DNA replication
Endonuclease
Exonuclease

GWAS Trait Find Similar Targets

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adult onset asthma
albumin:globulin ratio measurement
alkaline phosphatase measurement
Alopecia
alpha-linolenic acid measurement
aortic stenosis
apolipoprotein A 1 measurement
apolipoprotein B measurement
arachidonic acid measurement
asthma

MGI Phenotype Find Similar Targets

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adipose tissue phenotype
cellular phenotype
digestive/alimentary phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
liver/biliary system phenotype

IDG Resources

No IDG generated resources found

Orthologs (15)

1 – 5 of 15

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	flap structure-specific endonuclease 1	VGNC:6752	451242
Macaque	flap structure-specific endonuclease 1		722348
Mouse	flap structure specific endonuclease 1	MGI:102779	14156
Rat	flap structure-specific endonuclease 1	RGD:621821	84490
Dog	flap structure-specific endonuclease 1	VGNC:40817	476063

Species	Name	OMA	EggNOG	Inparanoid
Chimp	flap structure-specific endonuclease 1
Macaque	flap structure-specific endonuclease 1
Mouse	flap structure specific endonuclease 1
Rat	flap structure-specific endonuclease 1
Dog	flap structure-specific endonuclease 1

Publication Statistics

PubMed Score 1247.13

PubMed score by year

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PubTator Score 389.82

PubTator score by year

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Related Publications

Text Mined References (161)

GeneRif Annotations (106)

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PMID	Year	Title