DegronMD - P05129(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 ARNTL/BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (By similarity). {ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319, ECO:0000269|PubMed:16377624}. View more >>

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GO - Cellular component (CC): View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.A650V	TCGA-AZ-5407	COAD	TCGA	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation rewiring degron network	0.1111
p.A650V	TCGA-DF-A2KU	UCEC	TCGA	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation rewiring degron network	0.1111
p.A650V	DO8432	COAD	ICGC	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation rewiring degron network	0.1111
p.A650V	DO223286	UCEC	ICGC	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation rewiring degron network	0.1111
p.R659L	TCGA-EE-A3AE	SKCM	TCGA	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation altering degron motif	0.8428
p.R659L	DO37802	SKCM	ICGC	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation altering degron motif	0.8428
p.D666N	TCGA-VS-A9UI	CESC	TCGA	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation altering degron motif	0.5821
p.D666N	DO219734	CESC	ICGC	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation altering degron motif	0.5821
p.R659C	DO233154	GACA	ICGC	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation altering degron motif	0.8301
p.F670L	DO233280	GACA	ICGC	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation rewiring degron network	0.2222
p.R649W	DO231900	LINC	ICGC	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation rewiring degron network	0.0833
p.R659H	SIDM00491	Thyroid Gland Carcinoma	GDSC	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation altering degron motif	0.8244
p.R659H	ACH-001443	Thyroid Cancer	CCLE	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation altering degron motif	0.8244
p.R659H	ASH-3	thyroid	COSMIC	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation altering degron motif	0.8244
p.A651V	ACH-001862	Bile Duct Cancer	CCLE	DRLVLASID	DEG_APCC_DBOX_1	658:666	Mutation rewiring degron network	0.1389

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PRKCG

UniProt ID: P05129

Entrez ID: 5582

Protein name: Protein kinase C gamma type (PKC-gamma) (EC 2.7.11.13)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PRKCG in