Protein kinase C gamma type

UniProt P05129 Organism Homo sapiens Gene PKCG, PRKCG EC 2.7.11.13

Also known as: PKCG, PRKCG

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 BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (By similarity). Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking.

Classification

Family (Pfam): PF00130 C1_1, PF00168 C2, PF00069 Pkinase, PF00433 Pkinase_C
InterPro: AGC-kinase_C, C1-like_sf, C2_dom, C2_domain_sf, DAG/PE-bd, Kinase-like_dom_sf, PKC_DAG/PE, Pkinase_C, Prot_kinase_dom, Protein_kinase_ATP_BS, Protein_kinase_C_a/b/g, Ser/Thr_kinase_AS
Functional cluster: Serine/Threonine Protein Kinases

Experimental structures · PDB · 2

2E73 NMR
2UZP X-ray 2.00A

A predicted model is available from AlphaFold.

Gene Ontology · 39

Disease associations

spinocerebellar ataxia type 14 MONDO:0011540

Drugs targeting this protein · 5

GSK-690693 inhibitor
SOTRASTAURIN inhibitor
UCN-01 inhibitor
CEP-2563 DIHYDROCHLORIDE inhibitor
MIDOSTAURIN inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Tumor protein p53-inducible nuclear protein 1 1 shared papers
Protein kinase C zeta type 2 shared papers
Protein kinase C gamma type 1 shared papers
Protein kinase C beta type 1 shared papers
CUB domain-containing protein 1 1 shared papers
Protein kinase C beta type 2 shared papers
Protein-glutamine gamma-glutamyltransferase 6 1 shared papers
Kinesin-like protein KIF26B 1 shared papers
Transmembrane protein 240 1 shared papers
E3 ubiquitin-protein ligase TRIM52 1 shared papers
Protein kinase C delta type 1 shared papers
Protocadherin Fat 2 1 shared papers

Literature · 16 cited papers

PKC isoforms activate LRRK1 kinase by phosphorylating conserved residues (Ser1064, Ser1074 and Thr1075) within the CORB GTPase domain. Biochem. J. · 2022
Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia. Brain · 2017
Development and validation of a method for profiling post-translational modification activities using protein microarrays. PLoS ONE · 2010
A quantitative atlas of mitotic phosphorylation. Proc. Natl. Acad. Sci. U.S.A. · 2008
Protein kinase C as a stress sensor. Cell. Signal. · 2007
Protein kinase C delta regulates Ser46 phosphorylation of p53 tumor suppressor in the apoptotic response to DNA damage. J. Biol. Chem. · 2006
The C2 domain of PKCdelta is a phosphotyrosine binding domain. Cell · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
The DNA sequence and biology of human chromosome 19. Nature · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
Missense mutations in the regulatory domain of PKC gamma: a new mechanism for dominant nonepisodic cerebellar ataxia. Am. J. Hum. Genet. · 2003
Protein kinase C gamma (PKC gamma): function of neuron specific isotype. J. Biochem. · 2002
… and 4 more in the literature graph

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