Browse PRKCQ

Summary
SymbolPRKCQ
Nameprotein kinase C, theta
Aliases PRKCT; nPKC-theta; Protein kinase C theta type
Chromosomal Location10p15
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Cytoplasm. Cell membrane; Peripheral membrane protein. Note=In resting T-cells, mostly localized in cytoplasm. In response to TCR stimulation, associates with lipid rafts and then localizes in the immunological synapse.
Domain PF00130 Phorbol esters/diacylglycerol binding domain (C1 domain)
PF00069 Protein kinase domain
PF00433 Protein kinase C terminal domain
Function

Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1.

> Gene Ontology
 
Biological Process GO:0000723 telomere maintenance
GO:0001558 regulation of cell growth
GO:0001819 positive regulation of cytokine production
GO:0002250 adaptive immune response
GO:0002429 immune response-activating cell surface receptor signaling pathway
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002694 regulation of leukocyte activation
GO:0002696 positive regulation of leukocyte activation
GO:0002757 immune response-activating signal transduction
GO:0002764 immune response-regulating signaling pathway
GO:0002768 immune response-regulating cell surface receptor signaling pathway
GO:0002819 regulation of adaptive immune response
GO:0002821 positive regulation of adaptive immune response
GO:0002822 regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002824 positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0006278 RNA-dependent DNA biosynthetic process
GO:0006509 membrane protein ectodomain proteolysis
GO:0006921 cellular component disassembly involved in execution phase of apoptosis
GO:0007004 telomere maintenance via telomerase
GO:0007159 leukocyte cell-cell adhesion
GO:0007409 axonogenesis
GO:0007411 axon guidance
GO:0007596 blood coagulation
GO:0007599 hemostasis
GO:0008286 insulin receptor signaling pathway
GO:0010543 regulation of platelet activation
GO:0010833 telomere maintenance via telomere lengthening
GO:0016049 cell growth
GO:0016233 telomere capping
GO:0018105 peptidyl-serine phosphorylation
GO:0018209 peptidyl-serine modification
GO:0022407 regulation of cell-cell adhesion
GO:0022409 positive regulation of cell-cell adhesion
GO:0030168 platelet activation
GO:0030193 regulation of blood coagulation
GO:0032200 telomere organization
GO:0032204 regulation of telomere maintenance
GO:0032206 positive regulation of telomere maintenance
GO:0032210 regulation of telomere maintenance via telomerase
GO:0032212 positive regulation of telomere maintenance via telomerase
GO:0032620 interleukin-17 production
GO:0032623 interleukin-2 production
GO:0032633 interleukin-4 production
GO:0032660 regulation of interleukin-17 production
GO:0032663 regulation of interleukin-2 production
GO:0032673 regulation of interleukin-4 production
GO:0032740 positive regulation of interleukin-17 production
GO:0032743 positive regulation of interleukin-2 production
GO:0032753 positive regulation of interleukin-4 production
GO:0032844 regulation of homeostatic process
GO:0032846 positive regulation of homeostatic process
GO:0032868 response to insulin
GO:0032869 cellular response to insulin stimulus
GO:0032943 mononuclear cell proliferation
GO:0032944 regulation of mononuclear cell proliferation
GO:0032946 positive regulation of mononuclear cell proliferation
GO:0033044 regulation of chromosome organization
GO:0033619 membrane protein proteolysis
GO:0034109 homotypic cell-cell adhesion
GO:0034110 regulation of homotypic cell-cell adhesion
GO:0035710 CD4-positive, alpha-beta T cell activation
GO:0035712 T-helper 2 cell activation
GO:0038093 Fc receptor signaling pathway
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0042035 regulation of cytokine biosynthetic process
GO:0042089 cytokine biosynthetic process
GO:0042094 interleukin-2 biosynthetic process
GO:0042098 T cell proliferation
GO:0042102 positive regulation of T cell proliferation
GO:0042107 cytokine metabolic process
GO:0042108 positive regulation of cytokine biosynthetic process
GO:0042110 T cell activation
GO:0042129 regulation of T cell proliferation
GO:0043434 response to peptide hormone
GO:0045076 regulation of interleukin-2 biosynthetic process
GO:0045086 positive regulation of interleukin-2 biosynthetic process
GO:0045785 positive regulation of cell adhesion
GO:0046626 regulation of insulin receptor signaling pathway
GO:0046627 negative regulation of insulin receptor signaling pathway
GO:0046631 alpha-beta T cell activation
GO:0046634 regulation of alpha-beta T cell activation
GO:0046635 positive regulation of alpha-beta T cell activation
GO:0046651 lymphocyte proliferation
GO:0048667 cell morphogenesis involved in neuron differentiation
GO:0050670 regulation of lymphocyte proliferation
GO:0050671 positive regulation of lymphocyte proliferation
GO:0050817 coagulation
GO:0050818 regulation of coagulation
GO:0050851 antigen receptor-mediated signaling pathway
GO:0050852 T cell receptor signaling pathway
GO:0050863 regulation of T cell activation
GO:0050865 regulation of cell activation
GO:0050867 positive regulation of cell activation
GO:0050870 positive regulation of T cell activation
GO:0050878 regulation of body fluid levels
GO:0051052 regulation of DNA metabolic process
GO:0051054 positive regulation of DNA metabolic process
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051091 positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051249 regulation of lymphocyte activation
GO:0051251 positive regulation of lymphocyte activation
GO:0051972 regulation of telomerase activity
GO:0051973 positive regulation of telomerase activity
GO:0060249 anatomical structure homeostasis
GO:0060326 cell chemotaxis
GO:0061041 regulation of wound healing
GO:0061564 axon development
GO:0070227 lymphocyte apoptotic process
GO:0070228 regulation of lymphocyte apoptotic process
GO:0070229 negative regulation of lymphocyte apoptotic process
GO:0070231 T cell apoptotic process
GO:0070232 regulation of T cell apoptotic process
GO:0070233 negative regulation of T cell apoptotic process
GO:0070486 leukocyte aggregation
GO:0070489 T cell aggregation
GO:0070527 platelet aggregation
GO:0070661 leukocyte proliferation
GO:0070663 regulation of leukocyte proliferation
GO:0070665 positive regulation of leukocyte proliferation
GO:0071375 cellular response to peptide hormone stimulus
GO:0071417 cellular response to organonitrogen compound
GO:0071593 lymphocyte aggregation
GO:0071887 leukocyte apoptotic process
GO:0071897 DNA biosynthetic process
GO:0072538 T-helper 17 type immune response
GO:0090330 regulation of platelet aggregation
GO:0097194 execution phase of apoptosis
GO:0097485 neuron projection guidance
GO:1900046 regulation of hemostasis
GO:1900076 regulation of cellular response to insulin stimulus
GO:1900077 negative regulation of cellular response to insulin stimulus
GO:1901652 response to peptide
GO:1901653 cellular response to peptide
GO:1903034 regulation of response to wounding
GO:1903037 regulation of leukocyte cell-cell adhesion
GO:1903039 positive regulation of leukocyte cell-cell adhesion
GO:1904353 regulation of telomere capping
GO:1904355 positive regulation of telomere capping
GO:1904356 regulation of telomere maintenance via telomere lengthening
GO:1904358 positive regulation of telomere maintenance via telomere lengthening
GO:2000106 regulation of leukocyte apoptotic process
GO:2000107 negative regulation of leukocyte apoptotic process
GO:2000278 regulation of DNA biosynthetic process
GO:2000316 regulation of T-helper 17 type immune response
GO:2000318 positive regulation of T-helper 17 type immune response
GO:2000514 regulation of CD4-positive, alpha-beta T cell activation
GO:2000516 positive regulation of CD4-positive, alpha-beta T cell activation
GO:2000569 regulation of T-helper 2 cell activation
GO:2000570 positive regulation of T-helper 2 cell activation
GO:2000573 positive regulation of DNA biosynthetic process
GO:2001252 positive regulation of chromosome organization
Molecular Function GO:0004674 protein serine/threonine kinase activity
GO:0004697 protein kinase C activity
Cellular Component GO:0001772 immunological synapse
> KEGG and Reactome Pathway
 
KEGG hsa04064 NF-kappa B signaling pathway
hsa04140 Regulation of autophagy
hsa04270 Vascular smooth muscle contraction
hsa04660 T cell receptor signaling pathway
hsa04750 Inflammatory mediator regulation of TRP channels
hsa04920 Adipocytokine signaling pathway
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-109581: Apoptosis
R-HSA-111465: Apoptotic cleavage of cellular proteins
R-HSA-75153: Apoptotic execution phase
R-HSA-422475: Axon guidance
R-HSA-1266738: Developmental Biology
R-HSA-202424: Downstream TCR signaling
R-HSA-114508: Effects of PIP2 hydrolysis
R-HSA-2871837: FCERI mediated NF-kB activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-416476: G alpha (q) signalling events
R-HSA-418597: G alpha (z) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-2514859: Inactivation, recovery and regulation of the phototransduction cascade
R-HSA-168249: Innate Immune System
R-HSA-373752: Netrin-1 signaling
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-5357801: Programmed Cell Death
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-202403: TCR signaling
R-HSA-2514856: The phototransduction cascade
R-HSA-2187338: Visual phototransduction
Summary
SymbolPRKCQ
Nameprotein kinase C, theta
Aliases PRKCT; nPKC-theta; Protein kinase C theta type
Chromosomal Location10p15
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between PRKCQ and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between PRKCQ and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
19201850LymphomaPromote immunity (infiltration; NK cell function)In the present work, we show that in vivo development of a MHC-I-deficient tumor (RMA-S) is much favored in PKCtheta(-/-) mice compared with wild-type mice. This is associated with a reduced recruitment of NK cells to the site of tumor development and a reduced activation status of recruited NK cells. This correlates with a reduced ex vivo and in vivo cytotoxic potential of NK cells isolated from PKCtheta(-/-) mice treated with polyinosinic:polycytidylic acid. Consistently, polinosinic:cytidilic acid treatment induces PKCtheta expression and activation of its enzymatic activity in NK cells in an indirect manner.
Summary
SymbolPRKCQ
Nameprotein kinase C, theta
Aliases PRKCT; nPKC-theta; Protein kinase C theta type
Chromosomal Location10p15
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of PRKCQ in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell logFC: -2.79; FDR: 0.03680 Resistant to T cell-mediated killing
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell logFC: -2.26; FDR: 0.02150 Resistant to T cell-mediated killing
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolPRKCQ
Nameprotein kinase C, theta
Aliases PRKCT; nPKC-theta; Protein kinase C theta type
Chromosomal Location10p15
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of PRKCQ in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.10.772
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.1450.804
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.0650.895
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1740.731
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.8650.527
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.7030.69
729033130MelanomaallAnti-PD-1 (nivolumab) 26231.380.0303
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15112.4280.0129
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3090.766
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.9240.259
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.7580.524
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 68230-0.2390.252
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of PRKCQ in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27733.72.711
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27593.73.40.31
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.85.9-1.11
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.516.7-4.21
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59200200.357
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38270001
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolPRKCQ
Nameprotein kinase C, theta
Aliases PRKCT; nPKC-theta; Protein kinase C theta type
Chromosomal Location10p15
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PRKCQ. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolPRKCQ
Nameprotein kinase C, theta
Aliases PRKCT; nPKC-theta; Protein kinase C theta type
Chromosomal Location10p15
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PRKCQ. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PRKCQ.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolPRKCQ
Nameprotein kinase C, theta
Aliases PRKCT; nPKC-theta; Protein kinase C theta type
Chromosomal Location10p15
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PRKCQ. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolPRKCQ
Nameprotein kinase C, theta
Aliases PRKCT; nPKC-theta; Protein kinase C theta type
Chromosomal Location10p15
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of PRKCQ expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolPRKCQ
Nameprotein kinase C, theta
Aliases PRKCT; nPKC-theta; Protein kinase C theta type
Chromosomal Location10p15
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between PRKCQ and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolPRKCQ
Nameprotein kinase C, theta
Aliases PRKCT; nPKC-theta; Protein kinase C theta type
Chromosomal Location10p15
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting PRKCQ collected from DrugBank database.
> Drugs from DrugBank database
 

  Details on drugs targeting PRKCQ.
ID Name Drug Type Targets #Targets
DB00675TamoxifenSmall MoleculeAR, EBP, ESR1, ESR2, ESRRG, KCNH2, NR1I2, PRKCA, PRKCB, PRKCD, PRK ......16
DB02010StaurosporineSmall MoleculeCDK2, CHRM1, CSK, GSK3B, ITK, LCK, MAPKAPK2, PDPK1, PIK3CG, PIM1, ......13
DB02482PhosphonothreonineSmall MoleculeAURKA, CDK7, MAPK1, MAPK12, PRKACA, PRKACB, PRKCQ, RHO, S100A119
DB04522DexfosfoserineSmall MoleculeCFTR, KCNC4, PDPK1, PIM1, PRKACA, PRKCQ, PYGL, PYGM, REG1A, RHO, S ......13