Names & Taxonomy
- Uniprot ID:
- P05129
- Entry Name:
- KPCG_HUMAN
- Status:
- reviewed
- Protein Names:
- Protein kinase C gamma type (PKC-gamma) (EC 2.7.11.13)
- Gene Names:
- PRKCG PKCG
- Gene Names Primary:
- PRKCG
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 697
- Sequence:
- MAGLGPGVGDSEGGPRPLFCRKGALRQKVVHEVKSHKFTARFFKQPTFCSHCTDFIWGIGKQGLQCQVCSFVVHRRCHEFVTFECPGAGKGPQTDDPRNKHKFRLHSYSSPTFCDHCGSLLYGLVHQGMKCSCCEMNVHRRCVRSVPSLCGVDHTERRGRLQLEIRAPTADEIHVTVGEARNLIPMDPNGLSDPYVKLKLIPDPRNLTKQKTRTVKATLNPVWNETFVFNLKPGDVERRLSVEVWDWDRTSRNDFMGAMSFGVSELLKAPVDGWYKLLNQEEGEYYNVPVADADNCSLLQKFEACNYPLELYERVRMGPSSSPIPSPSPSPTDPKRCFFGASPGRLHISDFSFLMVLGKGSFGKVMLAERRGSDELYAIKILKKDVIVQDDDVDCTLVEKRVLALGGRGPGGRPHFLTQLHSTFQTPDRLYFVMEYVTGGDLMYHIQQLGKFKEPHAAFYAAEIAIGLFFLHNQGIIYRDLKLDNVMLDAEGHIKITDFGMCKENVFPGTTTRTFCGTPDYIAPEIIAYQPYGKSVDWWSFGVLLYEMLAGQPPFDGEDEEELFQAIMEQTVTYPKSLSREAVAICKGFLTKHPGKRLGSGPDGEPTIRAHGFFRWIDWERLERLEIPPPFRPRPCGRSGENFDKFFTRAAPALTPPDRLVLASIDQADFQGFTYVNPDFVHPDARSPTSPVPVPVM
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm
Function
- Function:
- Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/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 GRIA4/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 GRM5/MGLUR5 and phosphorylates GRIN1/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 be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. 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 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress (By similarity). Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component ARNTL/BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (By similarity).
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Cofactor:
- COFACTOR: Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
- Enzyme Regulation:
- ENZYME REGULATION: Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-514 (activation loop of the kinase domain), Thr-655 (turn motif) and Thr-674 (hydrophobic region), need to be phosphorylated for its full activation.
- Active Site:
- ACT_SITE 480 480 Proton acceptor.
- Cross Reference Drug Bank:
- DB00675
- Gene Ontology Go:
- cell-cell junction
cytosol
dendrite
intracellular
neuronal postsynaptic density
nucleus
perinuclear region of cytoplasm
plasma membrane
synaptic membrane
ATP binding
calcium-dependent protein kinase C activity
protein kinase activity
protein kinase C activity
protein serine/threonine/tyrosine kinase activity
zinc ion binding
activation of phospholipase C activity
blood coagulation
chemosensory behavior
epidermal growth factor receptor signaling pathway
fibroblast growth factor receptor signaling pathway
innate immune response
innervation
intracellular signal transduction
learning or memory
negative regulation of neuron apoptotic process
negative regulation of proteasomal protein catabolic process
negative regulation of protein catabolic process
negative regulation of protein ubiquitination
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
phosphorylation
platelet activation
positive regulation of mismatch repair
protein autophosphorylation
protein phosphorylation
regulation of circadian rhythm
regulation of phagocytosis
regulation of response to food
response to morphine
response to pain
rhythmic process
signal transduction
synaptic transmission - Gene Ontology Biological Process:
- activation of phospholipase C activity
blood coagulation
chemosensory behavior
epidermal growth factor receptor signaling pathway
fibroblast growth factor receptor signaling pathway
innate immune response
innervation
intracellular signal transduction
learning or memory
negative regulation of neuron apoptotic process
negative regulation of proteasomal protein catabolic process
negative regulation of protein catabolic process
negative regulation of protein ubiquitination
neurotrophin TRK receptor signaling pathway
peptidyl-serine phosphorylation
phosphorylation
platelet activation
positive regulation of mismatch repair
protein autophosphorylation
protein phosphorylation
regulation of circadian rhythm
regulation of phagocytosis
regulation of response to food
response to morphine
response to pain
rhythmic process
signal transduction
synaptic transmission - Gene Ontology Molecular Function:
- ATP binding
calcium-dependent protein kinase C activity
protein kinase activity
protein kinase C activity
protein serine/threonine/tyrosine kinase activity
zinc ion binding - Gene Ontology Cellular Component:
- cell-cell junction
cytosol
dendrite
intracellular
neuronal postsynaptic density
nucleus
perinuclear region of cytoplasm
plasma membrane
synaptic membrane - Keywords:
- 3D-structure
ATP-binding
Alternative splicing
Biological rhythms
Calcium
Cell junction
Cell membrane
Cell projection
Complete proteome
Cytoplasm
Disease mutation
Kinase
Membrane
Metal-binding
Neurodegeneration
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Spinocerebellar ataxia
Synapse
Synaptosome
Transferase
Ubl conjugation
Zinc
Zinc-finger