InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKCG

Summary

InnateDB Protein

IDBP-67843.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PRKCG

Protein Name

protein kinase C, gamma

Synonyms

PKC-gamma; PKCC; PKCG; SCA14;

Species

Homo sapiens

Ensembl Protein

ENSP00000263431

InnateDB Gene

IDBG-67841 (PRKCG)

Protein Structure

UniProt Annotation

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. {ECO:0000250, ECO:0000269PubMed:16377624}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear region {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cell junction, synapse, synaptosome {ECO:0000250}. Cell projection, dendrite {ECO:0000250}. Note=Translocates to synaptic membranes on stimulation. {ECO:0000250}.

Disease Associations

Spinocerebellar ataxia 14 (SCA14) [MIM:605361]: Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA14 is an autosomal dominant cerebellar ataxia (ADCA). {ECO:0000269PubMed:12644968}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in Purkinje cells of the cerebellar cortex. {ECO:0000269PubMed:12644968}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 41 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.

Experimentally validated
Total	41 [view]
Protein-Protein	41 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	8 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004697	protein kinase C activity
GO:0004698	calcium-dependent protein kinase C activity
GO:0004712	protein serine/threonine/tyrosine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008270	zinc ion binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0006468	protein phosphorylation
GO:0006950	response to stress
GO:0007165	signal transduction
GO:0007173	epidermal growth factor receptor signaling pathway
GO:0007202	activation of phospholipase C activity
GO:0007268	synaptic transmission
GO:0007596	blood coagulation
GO:0007611	learning or memory
GO:0007635	chemosensory behavior
GO:0008219	cell death
GO:0008543	fibroblast growth factor receptor signaling pathway
GO:0016310	phosphorylation
GO:0030168	platelet activation
GO:0031397	negative regulation of protein ubiquitination
GO:0032425	positive regulation of mismatch repair
GO:0035556	intracellular signal transduction
GO:0042177	negative regulation of protein catabolic process
GO:0043278	response to morphine
GO:0043524	negative regulation of neuron apoptotic process
GO:0045087	innate immune response
GO:0046777	protein autophosphorylation
GO:0048011	neurotrophin TRK receptor signaling pathway
GO:0048265	response to pain
GO:0060384	innervation

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005911	cell-cell junction
GO:0030054	cell junction
GO:0030425	dendrite
GO:0043005	neuron projection
GO:0048471	perinuclear region of cytoplasm
GO:0097060	synaptic membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000008 C2 domain
IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002219 Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR014375 Protein kinase C, alpha/beta/gamma types
IPR017892 Protein kinase, C-terminal
IPR020454 Diacylglycerol/phorbol-ester binding
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00168
PF00069
PF07714
PF00130
PF00433

PRINTS

PR00360
PR00109
PR00008

PIRSF

PIRSF000550

SMART

SM00239
SM00133
SM00109
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References