Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PRKCG (P05129) - Overview - Molecular Target Synopsis

Protein


PRKCG, Protein kinase C gamma type
Enzyme Classification 2.7.11.13
UniProt P05129

Also Known as KPCG_HUMAN, PRKCG, PKCG

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. Interacts with GRIA4 (By similarity). Interacts with CDCP1. Interacts with TP53INP1 and p53/TP53. Interacts with ARNTL/BMAL1.

2E73
SOLUTION STRUCTURE OF THE PHORBOL ESTERS/DIACYLGLYCEROL BINDING DOMAIN OF PROTEIN KINASE C GAMMA
RCSB/PDB
Inspect Structure
See all 3D Structures for PRKCG

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PRKCG is active in the following subcellular-locations: cell junction, cell membrane, cell projection, cytoplasm, dendrite, perinuclear region, synapse, synaptosome.
GO terms: PRKCG is active in the following subcellular-locations: calyx of Held, cell-cell junction, cytosol, dendrite, nucleus, perinuclear region of cytoplasm, plasma membrane, postsynaptic cytosol, postsynaptic density, presynaptic cytosol, synaptic membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PRKCG has gain in 3 cell-lines, loss in 1 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: HT29, NCI_H322M, TK_10

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: CaR-1, UM-UC-1, HPAC

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

RNA Interference


PRKCG was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MDAMB157, MDAMB436. (see details)

3D Structures


For PRKCG there are:
2 structures (4 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PRKCG has been screened with 1446 compounds (2349 bioactivities), 195 compounds have bioactivities that show binding affinity of <= 500nM (288 bioactivities). (see details)