PRKCG (protein kinase C gamma)

Gene

• Entrez ID: 5582
• Gene name: Protein kinase C gamma
• Gene symbol: PRKCG
• Synonyms: PKC-gamma, PKCC, PKCG, PKCI(3), PKCgamma, SCA14
• Chromosome: 19
• Chromosome location: 19q13.42
• Summary: Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play distinct roles in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase is expressed solely in the brain and spinal cord and its localization is restricted to neurons. It has been demonstrated that several neuronal functions, including long term potentiation (LTP) and long term depression (LTD), specifically require this kinase. Knockout studies in mice also suggest that this kinase may be involved in neuropathic pain development. Defects in this protein have been associated with neurodegenerative disorder spinocerebellar ataxia-14 (SCA14). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs78437096	T>A,C,G	Benign, pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs121918511	C>T	Pathogenic	Coding sequence variant, missense variant
rs121918512	T>C	Pathogenic	Coding sequence variant, missense variant
rs121918513	G>A	Pathogenic	Coding sequence variant, missense variant
rs121918514	G>A	Pathogenic	Coding sequence variant, missense variant
rs121918515	A>G	Pathogenic	Coding sequence variant, missense variant
rs121918516	T>C	Pathogenic	Coding sequence variant, missense variant
rs121918517	A>C,G	Pathogenic, uncertain-significance	Coding sequence variant, missense variant
rs121918518	C>G	Pathogenic	Coding sequence variant, missense variant
rs386134157	A>G	Pathogenic	Missense variant, coding sequence variant
rs386134158	G>C	Pathogenic	Missense variant, coding sequence variant
rs386134159	G>T	Pathogenic	Missense variant, coding sequence variant
rs386134160	T>A,C	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs386134161	ACACAA>-	Pathogenic	Coding sequence variant, inframe deletion
rs386134162	G>A	Pathogenic	Missense variant, coding sequence variant
rs386134163	C>T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs386134164	G>A,C	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs386134165	G>A	Pathogenic	Missense variant, coding sequence variant
rs386134166	T>A,C	Pathogenic	Missense variant, coding sequence variant
rs386134167	G>A	Pathogenic, uncertain-significance	Missense variant, coding sequence variant
rs386134168	T>A,C	Pathogenic	Missense variant, coding sequence variant
rs386134169	C>A	Pathogenic	Missense variant, coding sequence variant
rs386134170	GC>TT	Pathogenic	Missense variant, coding sequence variant
rs386134171	G>A	Pathogenic	Missense variant, coding sequence variant
rs387906679	G>T	Pathogenic	Coding sequence variant, missense variant
rs797045900	T>A	Likely-pathogenic	Missense variant, coding sequence variant
rs1303074743	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs1406338491	G>A,T	Likely-pathogenic	Splice donor variant
rs1555806333	G>A	Likely-pathogenic	Coding sequence variant, missense variant
rs1555808841	GTAATCTCACCCGCCGCCACTAGGTGTCCCCAACGTCCCCTCCGCCGTGCCGGCGGCAGCCCCACTTCACCCCCAACTTCACCACCCCCTGTCCCATTCTAG>-	Pathogenic	Stop lost, terminator codon variant, splice donor variant, inframe indel, intron variant, 3 prime UTR variant, splice acceptor variant
rs1599938631	G>A	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant
rs1599943097	C>A	Likely-pathogenic	Coding sequence variant, missense variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT017708	hsa-miR-335-5p	Microarray	18185580

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004672	Function	Protein kinase activity	IDA	15808853
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004697	Function	Protein kinase C activity	TAS	3755548
GO:0004698	Function	Calcium-dependent protein kinase C activity	IEA
GO:0004712	Function	Protein serine/threonine/tyrosine kinase activity	IDA	22797923
GO:0005515	Function	Protein binding	IPI	22939624, 31980649, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005829	Component	Cytosol	ISS
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	ISS
GO:0005911	Component	Cell-cell junction	IEA
GO:0006468	Process	Protein phosphorylation	TAS	3755548
GO:0007268	Process	Chemical synaptic transmission	IEA
GO:0007611	Process	Learning or memory	IEA
GO:0007635	Process	Chemosensory behavior	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0014069	Component	Postsynaptic density	IEA
GO:0016310	Process	Phosphorylation	IDA	15808853
GO:0018105	Process	Peptidyl-serine phosphorylation	IBA	21873635
GO:0030168	Process	Platelet activation	TAS
GO:0030425	Component	Dendrite	ISS
GO:0031397	Process	Negative regulation of protein ubiquitination	IDA	15808853
GO:0032095	Process	Regulation of response to food	ISS
GO:0032425	Process	Positive regulation of mismatch repair	IDA	15808853
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0042177	Process	Negative regulation of protein catabolic process	IDA	15808853
GO:0042752	Process	Regulation of circadian rhythm	ISS
GO:0043278	Process	Response to morphine	ISS
GO:0043524	Process	Negative regulation of neuron apoptotic process	ISS
GO:0044305	Component	Calyx of Held	IEA
GO:0046777	Process	Protein autophosphorylation	IEA
GO:0048265	Process	Response to pain	ISS
GO:0048471	Component	Perinuclear region of cytoplasm	ISS
GO:0048511	Process	Rhythmic process	IEA
GO:0050764	Process	Regulation of phagocytosis	IEA
GO:0060384	Process	Innervation	IEA
GO:0097060	Component	Synaptic membrane	IEA
GO:0099171	Process	Presynaptic modulation of chemical synaptic transmission	IEA
GO:0099523	Component	Presynaptic cytosol	IEA
GO:0099524	Component	Postsynaptic cytosol	IEA
GO:1901799	Process	Negative regulation of proteasomal protein catabolic process	ISS
GO:1990911	Process	Response to psychosocial stress	IEA
GO:2000300	Process	Regulation of synaptic vesicle exocytosis	IEA

Other IDs

• MIM: 176980
• HGNC: 9402
• e!Ensembl: ENSG00000126583

Protein

• UniProt ID: P05129
• Protein name: Protein kinase C gamma type (PKC-gamma) (EC 2.7.11.13)
• Protein 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).
• PDB: 2E73, 2UZP
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00130	C1_1	36 → 88	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00130	C1_1	101 → 153	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00168	C2	171 → 277	C2 domain	Domain
  PF00069	Pkinase	351 → 613	Protein kinase domain	Domain
  PF00433	Pkinase_C	639 → 675	Protein kinase C terminal domain	Family

• Sequence:

  MAGLGPGVGDSEGGPRPLFCRKGALRQKVVHEVKSHKFTARFFKQPTFCSHCTDFIWGIG
  KQGLQCQVCSFVVHRRCHEFVTFECPGAGKGPQTDDPRNKHKFRLHSYSSPTFCDHCGSL
  LYGLVHQGMKCSCCEMNVHRRCVRSVPSLCGVDHTERRGRLQLEIRAPTADEIHVTVGEA
  RNLIPMDPNGLSDPYVKLKLIPDPRNLTKQKTRTVKATLNPVWNETFVFNLKPGDVERRL
  SVEVWDWDRTSRNDFMGAMSFGVSELLKAPVDGWYKLLNQEEGEYYNVPVADADNCSLLQ
  KFEACNYPLELYERVRMGPSSSPIPSPSPSPTDPKRCFFGASPGRLHISDFSFLMVLGKG
  SFGKVMLAERRGSDELYAIKILKKDVIVQDDDVDCTLVEKRVLALGGRGPGGRPHFLTQL
  HSTFQTPDRLYFVMEYVTGGDLMYHIQQLGKFKEPHAAFYAAEIAIGLFFLHNQGIIYRD
  LKLDNVMLDAEGHIKITDFGMCKENVFPGTTTRTFCGTPDYIAPEIIAYQPYGKSVDWWS
  FGVLLYEMLAGQPPFDGEDEEELFQAIMEQTVTYPKSLSREAVAICKGFLTKHPGKRLGS
  GPDGEPTIRAHGFFRWIDWERLERLEIPPPFRPRPCGRSGENFDKFFTRAAPALTPPDRL
  VLASIDQADFQGFTYVNPDFVHPDARSPTSPVPVPVM

• Sequence length: 697