Protein: Protein kinase C theta type (EC 2.7.11.13) (nPKC-theta) (Q04759)
Organism: Homo sapiens (Human)
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. Phosphorylates CCDC88A/GIV and inhibits its guanine nucleotide exchange factor activity.
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.
Sequence: MSPFLRIGLSNFDCGSCQSCQGEAVNPYCAVLVKEYVESENGQMYIQKKPTMYPPWDSTFDAHINKGRVMQIIVKGKNVDLISETTVELYSLAERCRKNNGKTEIWLELKPQGRMLMNARYFLEMSDTKDMNEFETEGFFALHQRRGAIKQAKVHHVKCHEFTATFFPQPTFCSVCHEFVWGLNKQGYQCRQCNAAIHKKCIDKVIAKCTGSAINSRETMFHKERFKIDMPHRFKVYNYKSPTFCEHCGTLLWGLARQGLKCDACGMNVHHRCQTKVANLCGINQKLMAEALAMIESTQQARCLRDTEQIFREGPVEIGLPCSIKNEARPPCLPTPGKREPQGISWESPLDEVDKMCHLPEPELNKERPSLQIKLKIEDFILHKMLGKGSFGKVFLAEFKKTNQFFAIKALKKDVVLMDDDVECTMVEKRVLSLAWEHPFLTHMFCTFQTKENLFFVMEYLNGGDLMYHIQSCHKFDLSRATFYAAEIILGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKENMLGDAKTNTFCGTPDYIAPEILLGQKYNHSVDWWSFGVLLYEMLIGQSPFHGQDEEELFHSIRMDNPFYPRWLEKEAKDLLVKLFVREPEKRLGVRGDIRQHPLFREINWEELERKEIDPPFRPKVKSPFDCSNFDKEFLNEKPRLSFADRALINSMDQNMFRNFSFMNPGMERLIS
InterPro domains: - IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [377-683]
- IPR035892: C2 domain superfamily (homologous_superfamily) [1-130]
- IPR046349: C1-like domain superfamily (homologous_superfamily) [143-285]
- IPR027264: Protein kinase C, theta (family) [1-706]
- IPR020454: Diacylglycerol/phorbol-ester binding (domain) [157-282]
- IPR000008: C2 domain (domain) [1-107]
- IPR000961: AGC-kinase, C-terminal (domain) [635-706]
- IPR008271: Serine/threonine-protein kinase, active site (active_site) [500-512]
- IPR002219: Protein kinase C-like, phorbol ester/diacylglycerol-binding domain (domain) [159-283]
- IPR017892: Protein kinase, C-terminal (domain) [655-696]
- IPR034668: Novel protein kinase C theta, catalytic domain (domain) [374-704]
- IPR017441: Protein kinase, ATP binding site (binding_site) [386-409]
- IPR000719: Protein kinase domain (domain) [380-634]
- IPR014376: Protein kinase C, delta/epsilon/eta/theta types (family) [1-706]
Interaction partners: - Caspase recruitment domain-containing protein 11
- T-cell-specific surface glycoprotein CD28
- Inhibitor of nuclear factor kappa-B kinase subunit beta
- B-cell lymphoma/leukemia 10
- 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1
- Inhibitor of nuclear factor kappa-B kinase subunit alpha
- NF-kappa-B essential modulator
- Mitogen-activated protein kinase kinase kinase 7
- Nuclear factor NF-kappa-B p105 subunit
- Caspase recruitment domain-containing protein 10
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016740 (transferase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0004672 (protein kinase activity), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0016773 (phosphotransferase activity, alcohol group as acceptor), GO:0004674 (protein serine/threonine kinase activity), GO:0016301 (kinase activity), GO:0004697 (protein kinase C activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0002376 (immune system process), GO:0023052 (signaling), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0019222 (regulation of metabolic process), GO:0048584 (positive regulation of response to stimulus), GO:0006955 (immune response), GO:0051240 (positive regulation of multicellular organismal process), GO:0002684 (positive regulation of immune system process), GO:0006807 (nitrogen compound metabolic process), GO:0002682 (regulation of immune system process), GO:0051239 (regulation of multicellular organismal process), GO:0071704 (organic substance metabolic process), GO:0044237 (cellular metabolic process), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0065009 (regulation of molecular function), GO:0002253 (activation of immune response), GO:0007154 (cell communication), GO:0007165 (signal transduction), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:0002764 (immune response-regulating signaling pathway), GO:0044093 (positive regulation of molecular function), GO:1901564 (organonitrogen compound metabolic process), GO:0035556 (intracellular signal transduction), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0019538 (protein metabolic process), GO:0030155 (regulation of cell adhesion), GO:0060255 (regulation of macromolecule metabolic process), GO:0002694 (regulation of leukocyte activation), GO:0045785 (positive regulation of cell adhesion), GO:0001817 (regulation of cytokine production), GO:0043170 (macromolecule metabolic process), GO:0050867 (positive regulation of cell activation), GO:0006793 (phosphorus metabolic process), GO:0002696 (positive regulation of leukocyte activation), GO:0050776 (regulation of immune response), GO:0002757 (immune response-activating signaling pathway), GO:0050778 (positive regulation of immune response), GO:0007166 (cell surface receptor signaling pathway), GO:0001819 (positive regulation of cytokine production), GO:0050865 (regulation of cell activation), GO:0031295 (T cell costimulation), GO:0008284 (positive regulation of cell population proliferation), GO:0002768 (immune response-regulating cell surface receptor signaling pathway), GO:0022409 (positive regulation of cell-cell adhesion), GO:0022407 (regulation of cell-cell adhesion), GO:0010543 (regulation of platelet activation), GO:0010628 (positive regulation of gene expression), GO:0006796 (phosphate-containing compound metabolic process), GO:0010468 (regulation of gene expression), GO:0036211 (protein modification process), GO:0002429 (immune response-activating cell surface receptor signaling pathway), GO:0043412 (macromolecule modification), GO:0051251 (positive regulation of lymphocyte activation), GO:0032753 (positive regulation of interleukin-4 production), GO:0002821 (positive regulation of adaptive immune response), GO:0070665 (positive regulation of leukocyte proliferation), GO:0007264 (small GTPase mediated signal transduction), GO:0051249 (regulation of lymphocyte activation), GO:0050870 (positive regulation of T cell activation), GO:0038093 (Fc receptor signaling pathway), GO:0050863 (regulation of T cell activation), GO:0032944 (regulation of mononuclear cell proliferation), GO:0006468 (protein phosphorylation), GO:0050851 (antigen receptor-mediated signaling pathway), GO:0016310 (phosphorylation), GO:0032946 (positive regulation of mononuclear cell proliferation), GO:1903037 (regulation of leukocyte cell-cell adhesion), GO:1903039 (positive regulation of leukocyte cell-cell adhesion), GO:0033619 (membrane protein proteolysis), GO:0034110 (regulation of homotypic cell-cell adhesion), GO:0042102 (positive regulation of T cell proliferation), GO:0046635 (positive regulation of alpha-beta T cell activation), GO:0046634 (regulation of alpha-beta T cell activation), GO:0050852 (T cell receptor signaling pathway), GO:0042129 (regulation of T cell proliferation), GO:0018105 (peptidyl-serine phosphorylation), GO:0018107 (peptidyl-threonine phosphorylation), GO:0018209 (peptidyl-serine modification)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0031974 (membrane-enclosed lumen), GO:0005829 (cytosol), GO:0071944 (cell periphery), GO:0005615 (extracellular space), GO:0005737 (cytoplasm), GO:0012505 (endomembrane system), GO:0005654 (nucleoplasm), GO:0005576 (extracellular region), GO:0030141 (secretory granule), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0005768 (endosome), GO:0043230 (extracellular organelle), GO:0005773 (vacuole), GO:0043233 (organelle lumen), GO:0005783 (endoplasmic reticulum), GO:0070062 (extracellular exosome), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0036019 (endolysosome), GO:0060205 (cytoplasmic vesicle lumen), GO:0000323 (lytic vacuole), GO:0031983 (vesicle lumen), GO:0099503 (secretory vesicle), GO:0043231 (intracellular membrane-bounded organelle), GO:0034774 (secretory granule lumen), GO:0065010 (extracellular membrane-bounded organelle), GO:0042582 (azurophil granule), GO:0005775 (vacuolar lumen), GO:0031982 (vesicle), GO:0070013 (intracellular organelle lumen), GO:0005764 (lysosome), GO:0035578 (azurophil granule lumen), GO:1903561 (extracellular vesicle), GO:0097708 (intracellular vesicle), GO:0005634 (nucleus), GO:0031981 (nuclear lumen), GO:0005766 (primary lysosome)