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Names & Taxonomy

Uniprot ID:: Q04759
Entry Name:: KPCT_HUMAN
Status:: reviewed
Protein Names:: Protein kinase C theta type (EC 2.7.11.13) (nPKC-theta)
Gene Names:: PRKCQ PRKCT
Gene Names Primary:: PRKCQ
Organism:: Homo sapiens (Human)

Structure

Length:: 706
Sequence:: MSPFLRIGLSNFDCGSCQSCQGEAVNPYCAVLVKEYVESENGQMYIQKKPTMYPPWDSTFDAHINKGRVMQIIVKGKNVDLISETTVELYSLAERCRKNNGKTEIWLELKPQGRMLMNARYFLEMSDTKDMNEFETEGFFALHQRRGAIKQAKVHHVKCHEFTATFFPQPTFCSVCHEFVWGLNKQGYQCRQCNAAIHKKCIDKVIAKCTGSAINSRETMFHKERFKIDMPHRFKVYNYKSPTFCEHCGTLLWGLARQGLKCDACGMNVHHRCQTKVANLCGINQKLMAEALAMIESTQQARCLRDTEQIFREGPVEIGLPCSIKNEARPPCLPTPGKREPQGISWESPLDEVDKMCHLPEPELNKERPSLQIKLKIEDFILHKMLGKGSFGKVFLAEFKKTNQFFAIKALKKDVVLMDDDVECTMVEKRVLSLAWEHPFLTHMFCTFQTKENLFFVMEYLNGGDLMYHIQSCHKFDLSRATFYAAEIILGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKENMLGDAKTNTFCGTPDYIAPEILLGQKYNHSVDWWSFGVLLYEMLIGQSPFHGQDEEELFHSIRMDNPFYPRWLEKEAKDLLVKLFVREPEKRLGVRGDIRQHPLFREINWEELERKEIDPPFRPKVKSPFDCSNFDKEFLNEKPRLSFADRALINSMDQNMFRNFSFMNPGMERLIS
Proteomes:: UP000005640

Subcellular location

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.

Function

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.
Catalytic Activity:: ATP + a protein = ADP + a phosphoprotein.
Cofactor:: COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation:: ENZYME REGULATION: 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.
Active Site:: ACT_SITE 504 504 Proton acceptor.
Cross Reference Drug Bank:: DB00675
Gene Ontology Go:: cytosol
immunological synapse
intracellular
neuromuscular junction
nucleus
plasma membrane
sarcolemma
ATP binding
metal ion binding
protein kinase C activity
protein serine/threonine kinase activity
ubiquitin-protein transferase activity
aging
apoptotic process
axon guidance
blood coagulation
cell chemotaxis
cellular component disassembly involved in execution phase of apoptosis
Fc-epsilon receptor signaling pathway
inflammatory response
innate immune response
intracellular signal transduction
membrane protein ectodomain proteolysis
negative regulation of insulin receptor signaling pathway
negative regulation of T cell apoptotic process
peptidyl-serine phosphorylation
phototransduction, visible light
platelet activation
positive regulation of filopodium assembly
positive regulation of interleukin-17 production
positive regulation of interleukin-2 biosynthetic process
positive regulation of interleukin-4 production
positive regulation of NF-kappaB import into nucleus
positive regulation of NF-kappaB transcription factor activity
positive regulation of protein secretion
positive regulation of stress fiber assembly
positive regulation of T cell activation
positive regulation of T cell proliferation
positive regulation of T-helper 17 type immune response
positive regulation of T-helper 2 cell activation
positive regulation of telomerase activity
positive regulation of telomere capping
positive regulation of telomere maintenance via telomerase
programmed cell death
protein ubiquitination
regulation of cell growth
regulation of G2/M transition of mitotic cell cycle
regulation of platelet aggregation
regulation of rhodopsin mediated signaling pathway
regulation of transcription, DNA-templated
regulation of vasoconstriction
respiratory burst
response to glucose
response to heat
response to hypoxia
response to insulin
response to organic cyclic compound
rhodopsin mediated signaling pathway
T cell receptor signaling pathway
tissue regeneration
Gene Ontology Biological Process:: aging
apoptotic process
axon guidance
blood coagulation
cell chemotaxis
cellular component disassembly involved in execution phase of apoptosis
Fc-epsilon receptor signaling pathway
inflammatory response
innate immune response
intracellular signal transduction
membrane protein ectodomain proteolysis
negative regulation of insulin receptor signaling pathway
negative regulation of T cell apoptotic process
peptidyl-serine phosphorylation
phototransduction, visible light
platelet activation
positive regulation of filopodium assembly
positive regulation of interleukin-17 production
positive regulation of interleukin-2 biosynthetic process
positive regulation of interleukin-4 production
positive regulation of NF-kappaB import into nucleus
positive regulation of NF-kappaB transcription factor activity
positive regulation of protein secretion
positive regulation of stress fiber assembly
positive regulation of T cell activation
positive regulation of T cell proliferation
positive regulation of telomerase activity
positive regulation of telomere capping
positive regulation of telomere maintenance via telomerase
positive regulation of T-helper 17 type immune response
positive regulation of T-helper 2 cell activation
programmed cell death
protein ubiquitination
regulation of cell growth
regulation of G2/M transition of mitotic cell cycle
regulation of platelet aggregation
regulation of rhodopsin mediated signaling pathway
regulation of transcription, DNA-templated
regulation of vasoconstriction
respiratory burst
response to glucose
response to heat
response to hypoxia
response to insulin
response to organic cyclic compound
rhodopsin mediated signaling pathway
T cell receptor signaling pathway
tissue regeneration
Gene Ontology Molecular Function:: ATP binding
metal ion binding
protein kinase C activity
protein serine/threonine kinase activity
ubiquitin-protein transferase activity
Gene Ontology Cellular Component:: cytosol
immunological synapse
intracellular
neuromuscular junction
nucleus
plasma membrane
sarcolemma
Keywords:: 3D-structure
ATP-binding
Alternative splicing
Cell membrane
Complete proteome
Cytoplasm
Immunity
Inflammatory response
Kinase
Magnesium
Membrane
Metal-binding
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Transferase
Zinc
Zinc-finger
Interacts With:: Q06187; P06241; O76003; Q00613; P35570; P06239; Q8IVH8; Q05513

Names & Taxonomy

Structure

Subcellular location

Function

Publication