Details of Host Protein

KEGG: hsa01100 Pathway Download ×

KEGG: hsa00230 Pathway Download ×

Host Protein General Information (ID: PT0226)
Protein Name	Bis(5'-adenosyl)-triphosphatase ENPP4 (E-NPP 4)	Gene Name	ENPP4
Host Species	Homo sapiens	Uniprot Entry Name	ENPP4_HUMAN
Protein Families	Nucleotide pyrophosphatase/phosphodiesterase family
EC Number	3.6.1.29
Subcellular Location	Plasma membrane
External Link
	NCBI Gene ID	22875
	Uniprot ID	Q9Y6X5
	Ensembl ID	ENSG00000001561
	HGNC ID	HGNC:3359
Function in Host	Hydrolyzes extracellular Ap3A into AMP and ADP, and Ap4A intoAMP and ATP. Ap3A and Ap4A are diadenosine polyphosphates thought toinduce proliferation of vascular smooth muscle cells. Acts as aprocoagulant, mediating platelet aggregation at the site of nascentthrombus via release of ADP from Ap3A and activation of ADP receptors. [1-2] Click to Show/Hide
Related KEGG Pathway
	Metabolic pathways	hsa01100		Pathway Map
	Purine metabolism	hsa00230		Pathway Map
3D Structure	PDB ID: 4LQY FASTA Download 2D PNG Download PDB File Download

Function of This Protein During Virus Infection
Virus Name	SARS-COV-2	Protein Function	Pro-viral	[3]
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 ENPP4 in viral infection, ENPP4 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 ENPP4 leads to the decreased SARS-CoV-2 RNA levels compared with control group.

Full List of Virus RNA Interacting with This Protien
*RNA Region: 3'-UTR (hCoV-19/Wuhan-Hu-1/2019 )*
RNA Region Details	RNA Info Click to show the detail information of this RNA binding region	[4]
Strains Name	hCoV-19/Wuhan-Hu-1/2019
Strains Family	Beta (B.1.351)
RNA Binding Region	3'-UTR
Virus Name	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Infection Cells	HEK293 Cells (Human embryonic kidney cell) (CVCL_0045 )
Cell Originated Tissue	Liver
Infection Time	48 h
Interaction Score	Prot score = 18
Method Description	RNA-protein interaction detection (RaPID) assay; liquid chromatography with tandem mass spectrometry (LC-MS/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
MKLLVILLFSGLITGFRSDSSSSLPPKLLLVSFDGFRADYLKNYEFPHLQNFIKEGVLVEHVKNVFITKTFPNHYSIVTGLYEESHGIVANSMYDAVTKKHFSDSNDKDPFWWNEAVPIWVTNQLQENRSSAAAMWPGTDVPIHDTISSYFMNYNSSVSFEERLNNITMWLNNSNPPVTFATLYWEEPDASGHKYGPEDKENMSRVLKKIDDLIGDLVQRLKMLGLWENLNVIITSDHGMTQCSQDRLINLDSCIDHSYYTLIDLSPVAAILPKINRTEVYNKLKNCSPHMNVYLKEDIPNRFYYQHNDRIQPIILVADEGWTIVLNESSQKLGDHGYDNSLPSMHPFLAAHGPAFHKGYKHSTINIVDIYPMMCHILGLKPHPNNGTFGHTKCLLVDQWCINLPEAIAIVIGSLLVLTMLTCLIIIMQNRLSVPRPFSRLQLQEDDDDPLIG Click to Show/Hide

References
1	Molecular basis of purinergic signal metabolism by ectonucleotide pyrophosphatase/phosphodiesterases 4 and 1 and implications in stroke. J Biol Chem. 2014 Feb 7;289(6):3294-306.
2	NPP4 is a procoagulant enzyme on the surface of vascular endothelium. Blood. 2012 Nov 22;120(22):4432-40.
3	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.
4	RNA-Protein Interaction Analysis of SARS-CoV-2 5 and 3 Untranslated Regions Reveals a Role of Lysosome-Associated Membrane Protein-2a during Viral Infection. mSystems. 2021 Aug 31;6(4):e0064321.