Details of Host Protein

KEGG: hsa03030 Pathway Download ×

KEGG: hsa03410 Pathway Download ×

KEGG: hsa03450 Pathway Download ×

Host Protein General Information (ID: PT0448)
Protein Name	Flap endonuclease 1 (FEN1)	Gene Name	FEN1
Host Species	Homo sapiens	Uniprot Entry Name	FEN1_HUMAN
Protein Families	XPG/RAD2 endonuclease family
EC Number	3.1.-.-
Subcellular Location	Nucleus; nucleolus
External Link
	NCBI Gene ID	2237
	Uniprot ID	P39748
	Ensembl ID	ENSG00000168496
	HGNC ID	HGNC:3650
Function in Host	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 thatis generated by displacement synthesis when DNA polymerase encountersthe 5'-end of a downstream Okazaki fragment. It enters the flap fromthe 5'-end and then tracks to cleave the flap base, leaving a nick forligation. 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 preventsflaps from equilibrating into structures that lead to duplications anddeletions. Also possesses 5'-3' exonuclease activity on nicked orgapped double-stranded DNA, and exhibits RNase H activity. Alsoinvolved in replication and repair of rDNA and in repairingmitochondrial DNA. [1-7] Click to Show/Hide
Related KEGG Pathway
	DNA replication	hsa03030		Pathway Map
	Base excision repair	hsa03410		Pathway Map
	Non-homologous end-joining	hsa03450		Pathway Map
3D Structure	PDB ID: 1U7B FASTA Download 2D PNG Download PDB File Download

Function of This Protein During Virus Infection
Virus Name	SARS-COV-2	Protein Function	Anti-viral	[8]
Infected Tissue	Lung	Infection Time	7-9 Days
Infected Cell	Calu-3 Cells (Human epithelial cell line)	Cellosaurus ID	CVCL_0609
Method Description	To detect the role of host protein FEN1 in viral infection, FEN1 protein knockout Calu-3 Cells were infected with SARS-COV-2 for 7 - 9 Days , and the effects on infection was detected through CRISPR-based genome-wide gene-knockout screen.
Results	It is reported that knockout of FEN1 increases SARS-CoV-2 RNA levels compared with control group.

Full List of Virus RNA Interacting with This Protien
*RNA Region: Not Specified Virus Region (hCoV-19/USA/WA1/2020 )*
RNA Region Details	RNA Info Click to show the detail information of this RNA binding region	[9]
Strains Name	hCoV-19/USA/WA1/2020
Strains Family	Alpha (B.1.1.7)
RNA Binding Region	Not Specified Virus Region
Virus Name	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Infection Cells	Huh7.5 cells (Hepatocyte derived cellular carcinoma cell) (CVCL_7927 )
Cell Originated Tissue	Liver
Infection Time	48 h
Interaction Score	FDR ≤ 0.05
Method Description	comprehensive identification of RNA-binding proteins by massspectrometry (ChIRP-MS)

Differential Gene Expression During SARS-COV-2 Infection

GEO Accession: GSE152641

Sample Type: Blood

Samples Details: Healthy Control: 24; COVID-19: 62

Platform: GPL24676 Illumina NovaSeq 6000

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GEO Accession: GSE162835

Sample Type: Nasopharyngeal Swabs

Samples Details: COVID-19 (Mild Symptoms): 37; COVID-19 (Moderate Symptoms): 10; COVID-19 (Severe Symptoms): 3

Platform: GPL24676 Illumina NovaSeq 6000

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GEO Accession: GSE175779

Sample Type: Human Bronchial Epithelial Cells

Samples Details: Healthy Control: 4 (0, 24, 48, 72 and 96 h); COVID-19: 4 (24, 48, 72 and 96 h)

Platform: GPL18573 Illumina NextSeq 500

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Protein Sequence Information
MGIQGLAKLIADVAPSAIRENDIKSYFGRKVAIDASMSIYQFLIAVRQGGDVLQNEEGETTSHLMGMFYRTIRMMENGIKPVYVFDGKPPQLKSGELAKRSERRAEAEKQLQQAQAAGAEQEVEKFTKRLVKVTKQHNDECKHLLSLMGIPYLDAPSEAEASCAALVKAGKVYAAATEDMDCLTFGSPVLMRHLTASEAKKLPIQEFHLSRILQELGLNQEQFVDLCILLGSDYCESIRGIGPKRAVDLIQKHKSIEEIVRRLDPNKYPVPENWLHKEAHQLFLEPEVLDPESVELKWSEPNEEELIKFMCGEKQFSEERIRSGVKRLSKSRQGSTQGRLDDFFKVTGSLSSAKRKEPEPKGSTKKKAKTGAAGKFKRGK Click to Show/Hide

References
1	Wuho Is a New Member in Maintaining Genome Stability through its Interaction with Flap Endonuclease 1. PLoS Biol. 2016 Jan 11;14(1):e1002349.
2	Methylation of FEN1 suppresses nearby phosphorylation and facilitates PCNA binding. Nat Chem Biol. 2010 Oct;6(10):766-73.
3	Nucleolar localization and dynamic roles of flap endonuclease 1 in ribosomal DNA replication and damage repair. Mol Cell Biol. 2008 Jul;28(13):4310-9.
4	Arginine residues 47 and 70 of human flap endonuclease-1 are involved in DNA substrate interactions and cleavage site determination. J Biol Chem. 2002 Jul 5;277(27):24659-66.
5	Mechanism whereby proliferating cell nuclear antigen stimulates flap endonuclease 1. J Biol Chem. 2000 Apr 7;275(14):10498-505.
6	Essential amino acids for substrate binding and catalysis of human flap endonuclease 1. J Biol Chem. 1996 Apr 19;271(16):9173-6.
7	Structural and functional homology between mammalian DNase IV and the 5 -nuclease domain of Escherichia coli DNA polymerase I. J Biol Chem. 1994 Nov 18;269(46):28535-8.
8	Genome-wide CRISPR screens identify GATA6 as a proviral host factor for SARS-CoV-2 via modulation of ACE2. Nat Commun. 2022 Apr 25;13(1):2237.
9	Discovery and functional interrogation of SARS-CoV-2 RNA-host protein interactions. Cell. 2021 Apr 29;184(9):2394-2411.e16.