Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002377
UniProt IDQ9Y2R2
Primary gene name(s)PTPN22
Synonym gene name(s)PTPN8
Protein nameTyrosine-protein phosphatase non-receptor type 22
Protein functionActs as negative regulator of T-cell receptor, TCR signaling by direct dephosphorylation of the Src family kinases LCK and FYN, ITAMs of the TCRz/CD3 complex, as well as ZAP70, VAV, VCP and other key signaling molecules, PubMed:16461343, PubMed:18056643. Associates with and probably dephosphorylates CBL. Dephosphorylates LCK at its activating 'Tyr-394' residue, PubMed:21719704. Dephosphorylates ZAP70 at its activating 'Tyr-493' residue, PubMed:16461343. Dephosphorylates the immune system activator SKAP2, PubMed:21719704. Positively regulates toll-like receptor, TLR-induced type 1 interferon production, PubMed:23871208. Promotes host antiviral responses mediated by type 1 interferon, By similarity. Regulates NOD2-induced pro-inflammatory cytokine secretion and autophagy, PubMed:23991106. {ECO:0000250|UniProtKB:P29352, ECO:0000269|PubMed:16461343, ECO:0000269|PubMed:18056643, ECO:0000269|PubMed:19167335, ECO:0000269|PubMed:21719704, ECO:0000269|PubMed:23871208, ECO:0000269|PubMed:23991106}.
Subcellular locationCytoplasm {ECO:0000250}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9Y2R2
Gene Ontology
(Biological Process)
Complete annatation
autophagy [GO:0006914];
cellular response to muramyl dipeptide [GO:0071225];
lipopolysaccharide-mediated signaling pathway [GO:0031663];
negative regulation of autophagy [GO:0010507];
negative regulation of gene expression [GO:0010629];
negative regulation of interleukin-6 secretion [GO:1900165];
negative regulation of interleukin-8 secretion [GO:2000483];
negative regulation of JUN kinase activity [GO:0043508];
negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway [GO:0070433];
negative regulation of p38MAPK cascade [GO:1903753];
negative regulation of T cell activation [GO:0050868];
negative regulation of T cell receptor signaling pathway [GO:0050860];
negative regulation of tumor necrosis factor production [GO:0032720];
phosphoanandamide dephosphorylation [GO:0035644];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of gene expression [GO:0010628];
positive regulation of interferon-gamma secretion [GO:1902715];
positive regulation of protein K63-linked ubiquitination [GO:1902523];
positive regulation of toll-like receptor 3 signaling pathway [GO:0034141];
positive regulation of toll-like receptor 4 signaling pathway [GO:0034145];
positive regulation of type I interferon production [GO:0032481];
protein dephosphorylation [GO:0006470];
regulation of B cell receptor signaling pathway [GO:0050855];
regulation of innate immune response [GO:0045088];
regulation of natural killer cell proliferation [GO:0032817];
regulation of NIK/NF-kappaB signaling [GO:1901222];
response to lipopolysaccharide [GO:0032496];
T cell differentiation [GO:0030217]
Gene Ontology
(Molecular Function)
Complete annatation
kinase binding [GO:0019900];
phosphatase activity [GO:0016791];
protein tyrosine phosphatase activity [GO:0004725];
SH3 domain binding [GO:0017124];
ubiquitin protein ligase binding [GO:0031625]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
cytoplasmic side of plasma membrane [GO:0009898];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471]
Protein-protein interaction117604
Phylogenetic treeQ9Y2R2
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. CD3-0.3211133758844940.3269587255175950.447053579269101
AZA vs. DISU0.08301652230897180.7425562713506390.976008954784031
AZA vs. IL70.009236759461557810.9616213321310430.999311006273513
AZA vs. SAHA-0.3095877856183720.2041393718023240.572035079910209
DISU vs. CD30.3917266392476380.2816524283250670.411323559740527
DISU vs. IL7-0.08334854141936270.74031722340360.936419844268076
DISU vs. SAHA-0.390895060476470.1803012632543390.546133519985236
DMSO vs. AZA-0.09829342485167150.5565411122321081
DMSO vs. CD30.2153044088505220.500459527872950.608705214549168
DMSO vs. DISU-0.1820621501107060.4556748921954290.890202310783654
DMSO vs. IL70.1141564186029860.525201510358370.893007878750195
DMSO vs. SAHA-0.2183774869414660.3537622065618110.70328813860816
HIV vs. Mock in Activation-0.1604747898943280.7964125878079210.999983755607037
HIV vs. Mock in Latency0.2824246379730110.08774233747281620.999834320637052
IL7 vs. CD30.337217572373070.2952664612567590.433059391896773
SAHA vs. CD3-0.01218334156840880.972462610781130.981252865381428
SAHA vs. IL7-0.3212780552182120.187276673193550.41741957292911
(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 0.0795875 0.739865
(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
unknown unknown unknown unknown unknown
(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
2P6X X-ray 1.9Å A/B=1-302.
2QCJ X-ray 3.0Å A/B=1-294.
2QCT X-ray 2.8Å A/B=1-294.
3BRH X-ray 2.2Å A/B=1-310.
3H2X X-ray 2.2Å A=1-302.
3OLR X-ray 2.5Å A/B/C/D=1-294.
3OMH X-ray 2.9Å A/B/C/D=1-294.
4J51 X-ray 2.3Å A/B=1-303.

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
not found