Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000958
UniProt IDQ9Y6X5
Primary gene name(s)ENPP4
Synonym gene name(s)KIAA0879, NPP4
Protein nameBis(5'-adenosyl-triphosphatase ENPP4
Protein functionHydrolyzes extracellular Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Ap3A and Ap4A are diadenosine polyphosphates thought to induce proliferation of vascular smooth muscle cells. Acts as a procoagulant, mediating platelet aggregation at the site of nascent thrombus via release of ADP from Ap3A and activation of ADP receptors. {ECO:0000269|PubMed:22995898, ECO:0000269|PubMed:24338010}.
Subcellular locationCell membrane {ECO:0000269|PubMed:22995898};
Single-pass type I membrane protein {ECO:0000269|PubMed:22995898}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9Y6X5
Gene Ontology
(Biological Process)
Complete annatation
blood coagulation [GO:0007596];
positive regulation of blood coagulation [GO:0030194];
purine ribonucleoside catabolic process [GO:0046130]
Gene Ontology
(Molecular Function)
Complete annatation
bis(5'-adenosyl-triphosphatase activity [GO:0047710];
metal ion binding [GO:0046872]
Gene Ontology
(Cellular Component)
Complete annatation
extracellular exosome [GO:0070062];
integral component of membrane [GO:0016021];
membrane [GO:0016020];
plasma membrane [GO:0005886]
Protein-protein interaction116542
Phylogenetic treeQ9Y6X5
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. CD31.061044599951880.001778811767415230.00599379632427507
AZA vs. DISU0.1985273984454230.4473829545188620.918669250520452
AZA vs. IL70.2885592600438080.1565530176196850.922406965798721
AZA vs. SAHA0.2036855128388590.4269839721559750.778704815490668
DISU vs. CD3-0.8738447264373290.01821233117546330.0475381264309842
DISU vs. IL70.08213715223368030.7506800313881510.939908760230596
DISU vs. SAHA0.004305230214096740.9885209343155250.999274089415579
DMSO vs. AZA0.06654550426374120.7135692561925821
DMSO vs. CD3-1.004321062338360.002358055609346540.00718911217704454
DMSO vs. DISU-0.1331711927961310.5964932239778490.937098979571498
DMSO vs. IL70.22868507475720.2297589000583940.737798490610338
DMSO vs. SAHA0.1288967284883180.6013906154331580.86514324352221
HIV vs. Mock in Activation-0.2425305454291210.6998368417665690.999983755607037
HIV vs. Mock in Latency0.1713802054200440.3259832149643870.999834320637052
IL7 vs. CD3-0.7618207555840220.02006667359866070.0524748388536801
SAHA vs. CD3-0.8842421452219320.01381644870839350.0336915666724094
SAHA vs. IL7-0.09103785433886760.7178528314160470.870275032183115
(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
unknown unknown unknown unknown unknown unknown
(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) TRUE
(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 0.277175 0.0514143
(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
unknown unknown

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
0.998 1.155 1.306 1.448 1.225
(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
unknown unknown unknown unknown

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
4LQY X-ray 1.5Å A=16-407.
4LR2 X-ray 1.5Å A=16-407.

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

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00230 Purine metabolism - Homo sapiens (human)