Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0009285
UniProt IDQ05513
Primary gene name(s)PRKCZ
Synonym gene name(s)PKC2
Protein nameProtein kinase C zeta type
Protein functionCalcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase, PI3K pathway and mitogen-activated protein, MAP kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation, LTP. Upon lipopolysaccharide, LPS treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2, Th2 differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation, asthma, a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis. Phosphorylates VAMP2 in vitro, PubMed:17313651. {ECO:0000269|PubMed:11035106, ECO:0000269|PubMed:12162751, ECO:0000269|PubMed:15084291, ECO:0000269|PubMed:15324659, ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:18321849, ECO:0000269|PubMed:9447975}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:17313651, ECO:0000269|PubMed:9566925}. Endosome {ECO:0000269|PubMed:9566925}. Cell junction {ECO:0000269|PubMed:7597083}. Note=In the retina, localizes in the terminals of the rod bipolar cells. Associates with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction. Colocalizes with VAMP2 and WDFY2 in intracellular vesicles. {ECO:0000269|PubMed:17313651}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q05513
Gene Ontology
(Biological Process)
Complete annatation
actin cytoskeleton reorganization [GO:0031532];
activation of phospholipase D activity [GO:0031584];
activation of protein kinase B activity [GO:0032148];
cell migration [GO:0016477];
establishment of cell polarity [GO:0030010];
inflammatory response [GO:0006954];
insulin receptor signaling pathway [GO:0008286];
long-term memory [GO:0007616];
long-term synaptic potentiation [GO:0060291];
membrane depolarization [GO:0051899];
membrane hyperpolarization [GO:0060081];
microtubule cytoskeleton organization [GO:0000226];
negative regulation of apoptotic process [GO:0043066];
negative regulation of hydrolase activity [GO:0051346];
negative regulation of insulin receptor signaling pathway [GO:0046627];
negative regulation of peptidyl-tyrosine phosphorylation [GO:0050732];
negative regulation of protein complex assembly [GO:0031333];
neuron projection extension [GO:1990138];
peptidyl-serine phosphorylation [GO:0018105];
positive regulation of cell-matrix adhesion [GO:0001954];
positive regulation of cell proliferation [GO:0008284];
positive regulation of ERK1 and ERK2 cascade [GO:0070374];
positive regulation of excitatory postsynaptic potential [GO:2000463];
positive regulation of glucose import [GO:0046326];
positive regulation of insulin receptor signaling pathway [GO:0046628];
positive regulation of interleukin-10 secretion [GO:2001181];
positive regulation of interleukin-13 secretion [GO:2000667];
positive regulation of interleukin-4 production [GO:0032753];
positive regulation of interleukin-5 secretion [GO:2000664];
positive regulation of NF-kappaB transcription factor activity [GO:0051092];
positive regulation of T-helper 2 cell cytokine production [GO:2000553];
positive regulation of T-helper 2 cell differentiation [GO:0045630];
protein heterooligomerization [GO:0051291];
protein kinase C signaling [GO:0070528];
protein localization to plasma membrane [GO:0072659];
protein phosphorylation [GO:0006468];
signal transduction [GO:0007165];
transforming growth factor beta receptor signaling pathway [GO:0007179];
vesicle transport along microtubule [GO:0047496]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
insulin receptor substrate binding [GO:0043560];
metal ion binding [GO:0046872];
potassium channel regulator activity [GO:0015459];
protein kinase activity [GO:0004672];
protein kinase C activity [GO:0004697];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
apical cortex [GO:0045179];
apical plasma membrane [GO:0016324];
axon hillock [GO:0043203];
bicellular tight junction [GO:0005923];
cell-cell junction [GO:0005911];
cell junction [GO:0030054];
cell leading edge [GO:0031252];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endosome [GO:0005768];
extracellular exosome [GO:0070062];
filamentous actin [GO:0031941];
membrane [GO:0016020];
membrane raft [GO:0045121];
microtubule organizing center [GO:0005815];
myelin sheath abaxonal region [GO:0035748];
nuclear envelope [GO:0005635];
nuclear matrix [GO:0016363];
perinuclear region of cytoplasm [GO:0048471];
plasma membrane [GO:0005886];
vesicle [GO:0031982]
Protein-protein interaction111576
Phylogenetic treeQ05513
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
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. CD3-0.2118505573819610.5270667442639920.641727923866781
AZA vs. DISU-0.07770721365506520.7671445798491330.976021571236163
AZA vs. IL7-0.01225201934805420.9524086219105020.999311006273513
AZA vs. SAHA0.3274508856304130.1976363907557320.565352164897242
DISU vs. CD30.1217615147635650.740941253813940.818970735960072
DISU vs. IL70.05530256781075240.8319822548718390.964820397354322
DISU vs. SAHA0.4073882912860090.1731262543079880.536716541988804
DMSO vs. AZA0.1164630147770740.5228193367066261
DMSO vs. CD30.3177916931437060.330332830783350.444247821438241
DMSO vs. DISU0.1923516659283590.4463514142770220.887026602921028
DMSO vs. IL7-0.121272649652140.5273824884472260.894429468001295
DMSO vs. SAHA0.2057473705847480.4000210561742150.743093471909478
HIV vs. Mock in Activation0.3667998923031550.5644395294894770.999983755607037
HIV vs. Mock in Latency0.01710889028128260.9592629665368030.999834320637052
IL7 vs. CD30.2043907360867090.5334391283997680.659167730969806
SAHA vs. CD30.5155300216301040.1522067242482370.243627757240673
SAHA vs. IL70.3374394661619370.1815870729870640.410116365728503
(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) unknown
(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 -0.305701 0.60251
(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

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB00675 Tamoxifen approved unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

not found

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 interacts with 11141237
115049231970444
22114277
3259291
8599832
Vpr regulated by 24447338
Tat activates 8627654
9446795
9671211
10843712
11044099
11154208
11833470
11919157
12482669
Envelope transmembrane glycoprotein gp41 inhibits 1832084
21396767850771
Tat phosphorylated by 8914829
21651489
Pr55(Gag) interacts with 24447338
Pr55(Gag) binds 24447338
Pr55(Gag) phosphorylated by 24447338
matrix phosphorylated by 7876252
8473314
9151826
21651489
Envelope surface glycoprotein gp160; precursor interacts with 7642615
retropepsin inhibited by 10491200
reverse transcriptase phosphorylated by 10641798
Tat cooperates with 20336759
Tat regulated by 18760839
2182321
18577246
Envelope surface glycoprotein gp120 upregulates 8206685
Envelope surface glycoprotein gp120 activates 19363595
Envelope surface glycoprotein gp120 regulated by 15689238

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa04015 Rap1 signaling pathway - Homo sapiens (human)
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04144 Endocytosis - Homo sapiens (human)
hsa04360 Axon guidance - Homo sapiens (human)
hsa04390 Hippo signaling pathway - Homo sapiens (human)
hsa04530 Tight junction - Homo sapiens (human)
hsa04611 Platelet activation - Homo sapiens (human)
hsa04910 Insulin signaling pathway - Homo sapiens (human)
hsa04930 Type II diabetes mellitus - Homo sapiens (human)
hsa04931 Insulin resistance - Homo sapiens (human)
hsa04933 AGE-RAGE signaling pathway in diabetic complications - Homo sapiens (human)
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