Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001073
UniProt IDP39748
Primary gene name(s)FEN1
Synonym gene name(s)RAD2
Protein nameFlap endonuclease 1
Protein functionStructure-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. {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:7961795, ECO:0000269|PubMed:8621570}.
Subcellular locationIsoform 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}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P39748
Gene Ontology
(Biological Process)
Complete annatation
base-excision repair [GO:0006284];
DNA repair [GO:0006281];
DNA replication [GO:0006260];
DNA replication, removal of RNA primer [GO:0043137];
double-strand break repair [GO:0006302];
double-strand break repair via homologous recombination [GO:0000724];
memory [GO:0007613];
nucleic acid phosphodiester bond hydrolysis [GO:0090305];
positive regulation of sister chromatid cohesion [GO:0045876];
telomere maintenance via recombination [GO:0000722];
UV protection [GO:0009650]
Gene Ontology
(Molecular Function)
Complete annatation
5'-3' exonuclease activity [GO:0008409];
5'-flap endonuclease activity [GO:0017108];
damaged DNA binding [GO:0003684];
DNA binding [GO:0003677];
double-stranded DNA binding [GO:0003690];
double-stranded DNA exodeoxyribonuclease activity [GO:0008309];
endonuclease activity [GO:0004519];
exonuclease activity [GO:0004527];
metal ion binding [GO:0046872];
RNA-DNA hybrid ribonuclease activity [GO:0004523]
Gene Ontology
(Cellular Component)
Complete annatation
membrane [GO:0016020];
mitochondrion [GO:0005739];
nuclear chromosome, telomeric region [GO:0000784];
nucleolus [GO:0005730];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
plasma membrane [GO:0005886];
protein complex [GO:0043234]
Protein-protein interaction108528
Phylogenetic treeP39748
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD32.48076614580886.17159350156937e-050.000314144739127503
AZA vs. DISU0.1557816738798010.5428760396138840.94388010296314
AZA vs. IL70.6942176982896380.0009815777126599420.0782821209678482
AZA vs. SAHA-0.3029677525119250.2198811778752660.588196783547784
DISU vs. CD3-2.337071878081680.0002386286295146260.0012111407277116
DISU vs. IL70.529413929267550.07219777517199510.356954404536297
DISU vs. SAHA-0.4573827088720410.1227767439248070.449882885409863
DMSO vs. AZA0.01427245095283530.9334878594583691
DMSO vs. CD3-2.47895016863546.64980827315143e-050.000313256290290889
DMSO vs. DISU-0.1436546907824530.5605008172100820.925732173460781
DMSO vs. IL70.6872927902511590.0015585639492750.0750650208796188
DMSO vs. SAHA-0.3235898284153630.1750268704729630.506100721825534
HIV vs. Mock in Activation-0.03262423585788810.9796546116528320.999983755607037
HIV vs. Mock in Latency-0.07736232681631220.6495242048215530.999834320637052
IL7 vs. CD3-1.77905527264240.004657159544435240.0157888811995664
SAHA vs. CD3-2.808223106589211.0536261662919e-056.58570979926127e-05
SAHA vs. IL7-0.9997474030138396.21938503690966e-050.0013354844735951
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
2 0.001564404 1.3 0.123099842 1.2 0.259572323
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.484064 0.000305467
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
0.067 0.006

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.03 0.982 0.946 0.888 0.96
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
204767_s_at 1.9 No upregulated in CD8+ cells
204768_s_at 1.82 No upregulated in CD8+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1U7B X-ray 1.8Å B=331-350.
1UL1 X-ray 2.9Å X/Y/Z=2-380.
3Q8K X-ray 2.2Å A=2-336.
3Q8L X-ray 2.3Å A=2-336.
3Q8M X-ray 2.6Å A/B=2-336.
3UVU X-ray 2.3Å B=352-370.
5E0V X-ray 2.0Å C/D=335-350.
5FV7 X-ray 2.8Å A/B=1-336.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
integrase stimulates 12065902

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03030 DNA replication - Homo sapiens (human)
hsa03410 Base excision repair - Homo sapiens (human)
hsa03450 Non-homologous end-joining - Homo sapiens (human)