PRKCQ - Protein kinase C theta type - human protein (Function)
 
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PRKCQ »  Protein kinase C theta type   [ EC 2.7.11.13 ]
 
Protein also known as:  nPKC-theta.
Gene name:  PRKCQ
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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 to 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.  
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  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Metal ion bindingdefinition[GO:0046872]  
  • IEAUniProtKB KW
Protein bindingdefinition[GO:0005515]  
8
  • IPIIntAct
  • IPIUniProtKB
Protein kinase C activitydefinition[GO:0004697]  
  • IEAEC 2 GO
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • NASUniProtKB
GO biological process 
Inflammatory responsedefinition[GO:0006954]  
  • IEAUniProtKB KW
Intracellular signal transductiondefinition[GO:0035556]  
1
  • NASUniProtKB
Membrane protein ectodomain proteolysisdefinition[GO:0006509]  
  • ISSOrtholog Curator
Negative regulation of insulin receptor signaling pathwaydefinition[GO:0046627]  
1
  • IMPUniProtKB
Negative regulation of T cell apoptotic processdefinition[GO:0070233]  
2
  • IMPUniProtKB
Positive regulation of interleukin-17 productiondefinition[GO:0032740]  
  • ISSOrtholog Curator
Positive regulation of interleukin-2 biosynthetic processdefinition[GO:0045086] silver  
  • IEAOrtholog Compara
Positive regulation of interleukin-4 productiondefinition[GO:0032753]  
  • ISSOrtholog Curator
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
1
  • IDAUniProtKB
Positive regulation of T cell activationdefinition[GO:0050870]  
  • ISSOrtholog Curator
Positive regulation of T cell proliferationdefinition[GO:0042102] silver  
  • IEAOrtholog Compara
Positive regulation of T-helper 17 type immune responsedefinition[GO:2000318]  
  • ISSOrtholog Curator
Positive regulation of T-helper 2 cell activationdefinition[GO:2000570]  
  • ISSOrtholog Curator
Regulation of cell growthdefinition[GO:0001558]  
1
  • NASUniProtKB
Regulation of platelet aggregationdefinition[GO:0090330]  
  • ISSOrtholog Curator
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
  • ISSOrtholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.13: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
Magnesium.  
  • CuratedUniProtKB
It is regulated in the following manner
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-538 (activation loop of the kinase domain), Ser-676 (turn motif) and Ser-695 (hydrophobic region), need to be phosphorylated for its full activation.  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Adipocytokine signaling pathway  hsa04920+5588  
Measles  hsa05162+5588  
T cell receptor signaling pathway  hsa04660+5588  
Tight junction  hsa04530+5588  
Vascular smooth muscle contraction  hsa04270+5588  
According to Reactome, this protein belongs to the following pathways:
Apoptosis  REACT_578  
Developmental Biology  REACT_111045  
Disease  REACT_116125  
Hemostasis  REACT_604  
Immune System  REACT_6900  
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Immunity  definition   [KW-0391]
Inflammatory response  definition   [KW-0395]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PRKCQ
GenomeRNAi: 5588
PRO: PR:Q04759
Chemistry
GuidetoPHARMACOLOGY: 1488