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MGP002429

UniProt Annotations

Entry Information
Gene Nameprotein kinase C, theta
Protein EntryKPCT_HUMAN
UniProt IDQ04759
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q04759-1; Sequence=Displayed; Name=2; IsoId=Q04759-2; Sequence=VSP_017294; Name=3; IsoId=Q04759-3; Sequence=VSP_054550; Note=No experimental confirmation available.;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
CofactorName=Mg(2+); Xref=ChEBI:CHEBI:18420;
DomainThe C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain.
Enzyme RegulationNovel 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.
FunctionCalcium-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:0000269|PubMed:11342610, ECO:0000269|PubMed:14988727, ECO:0000269|PubMed:15364919, ECO:0000269|PubMed:16252004, ECO:0000269|PubMed:16356855, ECO:0000269|PubMed:16709830, ECO:0000269|PubMed:19549985, ECO:0000269|PubMed:8657160}.
InteractionQ06187:BTK; NbExp=2; IntAct=EBI-374762, EBI-624835; P06241:FYN; NbExp=7; IntAct=EBI-374762, EBI-515315; O76003:GLRX3; NbExp=5; IntAct=EBI-374762, EBI-374781; Q00613:HSF1; NbExp=2; IntAct=EBI-374762, EBI-719620; P35570:Irs1 (xeno); NbExp=2; IntAct=EBI-374762, EBI-520230; P06239:LCK; NbExp=2; IntAct=EBI-374762, EBI-1348; Q8IVH8:MAP4K3; NbExp=4; IntAct=EBI-374762, EBI-1758170; Q05513:PRKCZ; NbExp=3; IntAct=EBI-374762, EBI-295351;
PtmAutophosphorylation at Thr-219 is required for targeting to the TCR and cellular function of PRKCQ upon antigen receptor ligation. Following TCR stimulation, phosphorylated at Tyr-90 and Ser-685. {ECO:0000269|PubMed:10652356, ECO:0000269|PubMed:11772397, ECO:0000269|PubMed:15364937, ECO:0000269|PubMed:16252004, ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:19369195, ECO:0000269|PubMed:19690332, ECO:0000269|PubMed:21406692, ECO:0000269|Ref.33}.
SimilarityBelongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. {ECO:0000305}.
SimilarityContains 1 AGC-kinase C-terminal domain. {ECO:0000305}.
SimilarityContains 1 C2 domain. {ECO:0000305}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
SimilarityContains 2 phorbol-ester/DAG-type zinc fingers. {ECO:0000255|PROSITE-ProRule:PRU00226}.
Subcellular LocationCytoplasm. 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.
SubunitInteracts with GLRX3 (via N-terminus). Interacts with ECT2. Part of a lipid raft complex composed at least of BCL10, CARD11, MALT1 and IKBKB. {ECO:0000269|PubMed:10636891, ECO:0000269|PubMed:15254234, ECO:0000269|PubMed:16356855}.
Tissue SpecificityExpressed in skeletal muscle, T-cells, megakaryoblastic cells and platelets. {ECO:0000269|PubMed:7686153}.
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