Q04759

Background

Protein Name
Protein kinase C theta type
Gene Name
PRKCQ
Organism
Homo sapiens

Annotations

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.

Mapping Statistics

Site Maximum Consensus Site Population Minimum Consensus Site Population Median Consensus Site Population
MPP 16 15 15.0
AAS 2 2 2.0
ATP 33 1 14.0
DFG 4 4 4.0
DRS 13 3 9.0
PDIG 22 4 16.0
PIF 20 12 20.0

Mapping Results

PDB ID Maximum Consensus Site Population
MPP site AAS site MT3 site LBP site ATP site DEF site DFG site CMP site PMP site EDI site DRS site PDIG site PIF site
Total Druggable Structures per Site 2 0 0 0 5 0 0 0 0 0 0 4 2
2JED 16 0 0 0 18 0 0 0 0 0 12 21 0
5F9E 16 0 0 0 20 0 4 0 0 0 9 22 20
4RA5 15 0 0 0 23 0 0 0 0 0 0 22 20
4Q9Z 15 0 0 0 33 0 0 0 0 0 13 19 0
1XJD 0 2 0 0 23 0 4 0 0 0 3 15 12