a calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase. Expressed in the brain and spinal cord where its localization is restricted to neurons. Several neuronal functions, including long term potentiation and depression (LTP<D) specifically require this kinase. Knockout studies in mice also suggest that this kinase may be involved in neuropathic pain development. Defects have been associated with neurodegenerative disorder spinocerebellar ataxia-14. Plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GLUR4 and NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor MGLUR5 and phosphorylates NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contributes to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43, resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress. Phosphorylates p53 and promotes p53-dependent apoptosis in response to DNA damage. Interacts with GRIA4. Interacts with CDCP1. Interacts with TP53INP1 and p53. Expressed in Purkinje cells of the cerebellar cortex. Note: This description may include information from UniProtKB.
Protein type: EC 220.127.116.11; Protein kinase, Ser/Thr (non-receptor); Kinase, protein; Protein kinase, AGC; AGC group; PKC family; Alpha subfamily
Cellular Component: perinuclear region of cytoplasm; dendrite; plasma membrane; cell junction; cytosol; nucleus
Molecular Function: protein kinase C activity; zinc ion binding; protein serine/threonine/tyrosine kinase activity; calcium-dependent protein kinase C activity; ATP binding; protein kinase activity
Biological Process: cell death; epidermal growth factor receptor signaling pathway; platelet activation; positive regulation of mismatch repair; fibroblast growth factor receptor signaling pathway; nerve growth factor receptor signaling pathway; protein amino acid autophosphorylation; response to morphine; response to pain; signal transduction; protein amino acid phosphorylation; synaptic transmission; learning and/or memory; phospholipase C activation; chemosensory behavior; innate immune response; negative regulation of protein ubiquitination; negative regulation of neuron apoptosis; blood coagulation; negative regulation of protein catabolic process; phosphorylation
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.