InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKCQ

Summary

InnateDB Protein

IDBP-51304.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PRKCQ

Protein Name

protein kinase C, theta

Synonyms

nPKC-theta; PRKCT;

Species

Homo sapiens

Ensembl Protein

ENSP00000263125

InnateDB Gene

IDBG-51302 (PRKCQ)

Protein Structure

UniProt Annotation

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 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. {ECO:0000269PubMed:11342610, ECO:0000269PubMed:14988727, ECO:0000269PubMed:15364919, ECO:0000269PubMed:16252004, ECO:0000269PubMed:16356855, ECO:0000269PubMed:16709830, ECO:0000269PubMed:19549985, ECO:0000269PubMed:8657160}.

Subcellular Localization

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.

Disease Associations

Tissue Specificity

Expressed in skeletal muscle, T-cells, megakaryoblastic cells and platelets. {ECO:0000269PubMed:7686153}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 46 experimentally validated interaction(s) in this database.
They are also associated with 11 interaction(s) predicted by orthology.

Experimentally validated
Total	46 [view]
Protein-Protein	45 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	11 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004697	protein kinase C activity
GO:0004713	protein tyrosine kinase activity
GO:0004842	ubiquitin-protein transferase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0046872	metal ion binding

Biological Process

GO:0001558	regulation of cell growth
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006509	membrane protein ectodomain proteolysis
GO:0006915	apoptotic process
GO:0006921	cellular component disassembly involved in execution phase of apoptosis
GO:0006954	inflammatory response
GO:0007411	axon guidance
GO:0007596	blood coagulation
GO:0007603	phototransduction, visible light
GO:0016056	rhodopsin mediated signaling pathway
GO:0016567	protein ubiquitination
GO:0022400	regulation of rhodopsin mediated signaling pathway
GO:0030168	platelet activation
GO:0032740	positive regulation of interleukin-17 production
GO:0032753	positive regulation of interleukin-4 production
GO:0035556	intracellular signal transduction
GO:0038095	Fc-epsilon receptor signaling pathway
GO:0042102	positive regulation of T cell proliferation
GO:0045086	positive regulation of interleukin-2 biosynthetic process
GO:0045087	innate immune response
GO:0046627	negative regulation of insulin receptor signaling pathway
GO:0050852	T cell receptor signaling pathway
GO:0050870	positive regulation of T cell activation
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0070233	negative regulation of T cell apoptotic process
GO:0090330	regulation of platelet aggregation
GO:2000318	positive regulation of T-helper 17 type immune response
GO:2000570	positive regulation of T-helper 2 cell activation

Cellular Component

GO:0001772	immunological synapse
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000008 C2 domain
IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002219 Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR014376 Protein kinase C, delta/epsilon/eta/theta types
IPR017892 Protein kinase, C-terminal
IPR020454 Diacylglycerol/phorbol-ester binding
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00168
PF00069
PF07714
PF00130
PF00433

PRINTS

PR00360
PR00109
PR00008

PIRSF

PIRSF000551

SMART

SM00239
SM00133
SM00109
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References