Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002319
UniProt IDQ05655
Primary gene name(s)PRKCD
Synonym gene name(s)unknown
Protein nameProtein kinase C delta type
Protein functionCalcium-independent, phospholipid- and diacylglycerol, DAG-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein, XIAP, whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate, PMA-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1, CCND1 and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3, ERK1/2. Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine, fMLP-treated cells, is required for NCF1, p47-phox phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3, ERK1/2 signaling pathways. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin. The catalytic subunit phosphorylates 14-3-3 proteins, YWHAB, YWHAZ and YWHAH in a sphingosine-dependent fashion, By similarity. Phosphorylates ELAVL1 in response to angiotensin-2 treatment, PubMed:18285462. {ECO:0000250, ECO:0000269|PubMed:11748588, ECO:0000269|PubMed:11877440, ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:16940418, ECO:0000269|PubMed:18285462, ECO:0000269|PubMed:19587372, ECO:0000269|PubMed:19801500}.
Subcellular locationCytoplasm {ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:17603046, ECO:0000269|PubMed:18285462}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:17603046}. Nucleus {ECO:0000269|PubMed:15774464, ECO:0000269|PubMed:17603046, ECO:0000269|PubMed:18285462}. Cell membrane {ECO:0000269|PubMed:17603046};
Peripheral membrane protein {ECO:0000305|PubMed:17603046}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q05655
Gene Ontology
(Biological Process)
Complete annatation
activation of phospholipase C activity [GO:0007202];
activation of protein kinase activity [GO:0032147];
apoptotic process [GO:0006915];
B cell proliferation [GO:0042100];
cell chemotaxis [GO:0060326];
cell cycle [GO:0007049];
cellular component disassembly involved in execution phase of apoptosis [GO:0006921];
cellular response to angiotensin [GO:1904385];
cellular response to hydrogen peroxide [GO:0070301];
cellular response to hydroperoxide [GO:0071447];
cellular senescence [GO:0090398];
defense response to bacterium [GO:0042742];
Fc-gamma receptor signaling pathway involved in phagocytosis [GO:0038096];
histone phosphorylation [GO:0016572];
immunoglobulin mediated immune response [GO:0016064];
interferon-gamma-mediated signaling pathway [GO:0060333];
interleukin-10 production [GO:0032613];
interleukin-12 production [GO:0032615];
intrinsic apoptotic signaling pathway in response to oxidative stress [GO:0008631];
negative regulation of actin filament polymerization [GO:0030837];
negative regulation of filopodium assembly [GO:0051490];
negative regulation of glial cell apoptotic process [GO:0034351];
negative regulation of inflammatory response [GO:0050728];
negative regulation of insulin receptor signaling pathway [GO:0046627];
negative regulation of MAP kinase activity [GO:0043407];
negative regulation of peptidyl-tyrosine phosphorylation [GO:0050732];
negative regulation of platelet aggregation [GO:0090331];
negative regulation of protein binding [GO:0032091];
neutrophil activation [GO:0042119];
peptidyl-serine phosphorylation [GO:0018105];
peptidyl-threonine phosphorylation [GO:0018107];
platelet activation [GO:0030168];
positive regulation of apoptotic signaling pathway [GO:2001235];
positive regulation of ceramide biosynthetic process [GO:2000304];
positive regulation of endodeoxyribonuclease activity [GO:0032079];
positive regulation of glucosylceramide catabolic process [GO:2000753];
positive regulation of phospholipid scramblase activity [GO:1900163];
positive regulation of protein dephosphorylation [GO:0035307];
positive regulation of protein import into nucleus [GO:0042307];
positive regulation of response to DNA damage stimulus [GO:2001022];
positive regulation of sphingomyelin catabolic process [GO:2000755];
positive regulation of superoxide anion generation [GO:0032930];
protein phosphorylation [GO:0006468];
protein stabilization [GO:0050821];
regulation of actin cytoskeleton organization [GO:0032956];
regulation of mRNA stability [GO:0043488];
regulation of receptor activity [GO:0010469];
signal transduction [GO:0007165];
stimulatory C-type lectin receptor signaling pathway [GO:0002223];
termination of signal transduction [GO:0023021]
Gene Ontology
(Molecular Function)
Complete annatation
ATP binding [GO:0005524];
calcium-independent protein kinase C activity [GO:0004699];
enzyme activator activity [GO:0008047];
enzyme binding [GO:0019899];
insulin receptor substrate binding [GO:0043560];
kinase binding [GO:0019900];
metal ion binding [GO:0046872];
non-membrane spanning protein tyrosine kinase activity [GO:0004715];
protein kinase activity [GO:0004672];
protein kinase binding [GO:0019901];
protein kinase C activity [GO:0004697];
protein serine/threonine kinase activity [GO:0004674]
Gene Ontology
(Cellular Component)
Complete annatation
cell-cell junction [GO:0005911];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
endoplasmic reticulum [GO:0005783];
extracellular exosome [GO:0070062];
nuclear matrix [GO:0016363];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
perinuclear region of cytoplasm [GO:0048471];
plasma membrane [GO:0005886]
Protein-protein interaction111566
Phylogenetic treeQ05655
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. CD31.688482862693625.20625111910533e-074.31146246522833e-06
AZA vs. DISU0.3673463909050850.1491185055518380.726976828165722
AZA vs. IL70.05604551484949990.7735038922322390.999311006273513
AZA vs. SAHA0.03527336157173880.8859210741277730.975412626645391
DISU vs. CD3-1.33436237782560.0002970270008726410.0014617646135012
DISU vs. IL7-0.3207580324802160.2053672406164020.583303535074626
DISU vs. SAHA-0.3293090639353480.2612052443421920.638576741066377
DMSO vs. AZA0.007968591620499010.9627191802169771
DMSO vs. CD3-1.692881157730142.61864437911541e-072.09616777743749e-06
DMSO vs. DISU-0.3615076337595730.1408077187078090.633424573410949
DMSO vs. IL70.05547090140378460.7606226276930910.951841190064606
DMSO vs. SAHA0.0220625286806450.9260825219466480.982780458369212
HIV vs. Mock in Activation0.398676277801080.5220619373230930.999983755607037
HIV vs. Mock in Latency0.1210140840662240.4708067638396280.999834320637052
IL7 vs. CD3-1.626740881376548.19842823962524e-078.16782768044459e-06
SAHA vs. CD3-1.676777314377633.78990035754256e-062.66140719422956e-05
SAHA vs. IL7-0.02287189531323090.9258691510005160.972988816381886
(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 -0.348871 0.0692167
(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
0.947 1.021 1.115 1.344 1.227
(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
DB05013 Ingenol Mebutate approved unknown ligand
DB04376 13-Acetylphorbol experimental unknown unknown
DB00675 Tamoxifen approved unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
1YRK X-ray 1.7Å A=1-123.
2YUU NMR - A=149-218.

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

HIV Partner Interaction Type PubMed
Envelope surface glycoprotein gp120 interacts with 11141237
Tat activates 18092356
Envelope transmembrane glycoprotein gp41 inhibits 1832084
Tat phosphorylated by 8914829
Nef complexes with 18854243
matrix phosphorylated by 7876252
Envelope surface glycoprotein gp160; precursor interacts with 7642615
retropepsin inhibited by 10491200
reverse transcriptase phosphorylated by 10641798
Tat cooperates with 20336759
Tat regulated by 2182321
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
hsa04062 Chemokine signaling pathway - Homo sapiens (human)
hsa04270 Vascular smooth muscle contraction - Homo sapiens (human)
hsa04621 NOD-like receptor signaling pathway - Homo sapiens (human)
hsa04666 Fc gamma R-mediated phagocytosis - Homo sapiens (human)
hsa04722 Neurotrophin signaling pathway - Homo sapiens (human)
hsa04750 Inflammatory mediator regulation of TRP channels - Homo sapiens (human)
hsa04912 GnRH signaling pathway - Homo sapiens (human)
hsa04915 Estrogen 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)