ID:KPCG_HUMAN DESCRIPTION: RecName: Full=Protein kinase C gamma type; Short=PKC-gamma; EC=2.7.11.13; 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Binds 3 calcium ions per subunit. The ions are bound to the C2 domain. 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. SUBUNIT: Interacts with GRIA4 (By similarity). Interacts with CDCP1. Interacts with TP53INP1 and p53/TP53. SUBCELLULAR LOCATION: Cytoplasm (By similarity). Cytoplasm, perinuclear region (By similarity). Cell membrane; Peripheral membrane protein (By similarity). Cell junction, synapse, synaptosome (By similarity). Cell projection, dendrite (By similarity). Note=Translocates to synaptic membranes on stimulation (By similarity). TISSUE SPECIFICITY: Expressed in Purkinje cells of the cerebellar cortex. PTM: Autophosphorylation on Thr-674 appears to regulate motor functions of junctophilins, JPH3 and JPH4 (By similarity). DISEASE: Defects in PRKCG are the cause of spinocerebellar ataxia type 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). SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. SIMILARITY: Contains 1 AGC-kinase C-terminal domain. SIMILARITY: Contains 1 C2 domain. SIMILARITY: Contains 2 phorbol-ester/DAG-type zinc fingers. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=Mutations of the PRKCG gene; Note=Retina International's Scientific Newsletter; URL="http://www.retina-international.org/files/sci-news/prkcgmut.htm"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PRKCG";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P05129
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006468 protein phosphorylation GO:0007268 chemical synaptic transmission GO:0007611 learning or memory GO:0007635 chemosensory behavior GO:0016310 phosphorylation GO:0018105 peptidyl-serine phosphorylation GO:0030168 platelet activation GO:0031397 negative regulation of protein ubiquitination GO:0032095 regulation of response to food GO:0032425 positive regulation of mismatch repair GO:0035556 intracellular signal transduction GO:0042177 negative regulation of protein catabolic process GO:0042752 regulation of circadian rhythm GO:0043278 response to morphine GO:0043524 negative regulation of neuron apoptotic process GO:0046777 protein autophosphorylation GO:0048265 response to pain GO:0048511 rhythmic process GO:0050764 regulation of phagocytosis GO:0060384 innervation GO:1901799 negative regulation of proteasomal protein catabolic process GO:1990911 response to psychosocial stress
AK296412 - Homo sapiens cDNA FLJ54490 complete cds, highly similar to Protein kinase C gamma type (EC 2.7.11.13). AK302958 - Homo sapiens cDNA FLJ52648 complete cds, highly similar to Protein kinase C gamma type (EC 2.7.11.13). AK296434 - Homo sapiens cDNA FLJ60619 complete cds, highly similar to Protein kinase C gamma type (EC 2.7.11.13). AK312302 - Homo sapiens cDNA, FLJ92607, highly similar to Homo sapiens protein kinase C, gamma (PRKCG), mRNA. M13977 - Human (clone lambda-hPKC-gamma6) protein kinase C-gamma (PRKCG) mRNA, 5' end cds. AF345987 - Homo sapiens protein kinase C gamma (PKCG) mRNA, complete cds. AX589157 - Sequence 5 from Patent WO02083727. BC047876 - Homo sapiens protein kinase C, gamma, mRNA (cDNA clone MGC:57564 IMAGE:5764695), complete cds. AB209671 - Homo sapiens mRNA for protein kinase C, gamma variant protein. AB527732 - Synthetic construct DNA, clone: pF1KB6274, Homo sapiens PRKCG gene for protein kinase C, gamma, without stop codon, in Flexi system. CU690520 - Synthetic construct Homo sapiens gateway clone IMAGE:100021455 5' read PRKCG mRNA. KJ905288 - Synthetic construct Homo sapiens clone ccsbBroadEn_14791 PRKCG gene, encodes complete protein. AK303741 - Homo sapiens cDNA FLJ50347 complete cds, highly similar to Protein kinase C gamma type (EC 2.7.11.13). Z15114 - H.sapiens mRNA for protein kinase C gamma (partial). AX589158 - Sequence 6 from Patent WO02083727. JD139242 - Sequence 120266 from Patent EP1572962. JD116386 - Sequence 97410 from Patent EP1572962. JD123047 - Sequence 104071 from Patent EP1572962. JD457730 - Sequence 438754 from Patent EP1572962. JD123623 - Sequence 104647 from Patent EP1572962. JD247150 - Sequence 228174 from Patent EP1572962. JD415850 - Sequence 396874 from Patent EP1572962. JD325614 - Sequence 306638 from Patent EP1572962. JD525825 - Sequence 506849 from Patent EP1572962. JD254067 - Sequence 235091 from Patent EP1572962. JD254442 - Sequence 235466 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_keratinocytePathway - Keratinocyte Differentiation
Reactome (by CSHL, EBI, and GO)
Protein P05129 (Reactome details) participates in the following event(s):
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
