PRKCE (protein kinase C epsilon)

Gene

• Entrez ID: 5581
• Gene name: Protein kinase C epsilon
• Gene symbol: PRKCE
• Synonyms: PKCE, nPKC-epsilon
• Chromosome: 2
• Chromosome location: 2p21
• Summary: Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the 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 family members 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 a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This kinase has been shown to be involved in many different cellular functions, such as neuron channel activation, apoptosis, cardioprotection from ischemia, heat shock response, as well as insulin exocytosis. Knockout studies in mice suggest that this kinase is important for lipopolysaccharide (LPS)-mediated signaling in activated macrophages and may also play a role in controlling anxiety-like behavior. [provided by RefSeq, Jul 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003667	hsa-miR-205-5p	immunoblot, qRT-PCR	19244118
MIRT007205	hsa-miR-1-3p	Luciferase reporter assay	23226300
MIRT007286	hsa-miR-31-5p	Luciferase reporter assay	23364795
MIRT027937	hsa-miR-96-5p	Sequencing	20371350
MIRT030913	hsa-miR-21-5p	Microarray	18591254
MIRT043664	hsa-miR-342-3p	CLASH	23622248
MIRT052955	hsa-miR-107	Luciferase reporter assay, qRT-PCR, Western blot	22158047
MIRT438113	hsa-miR-146a-5p	Luciferase reporter assay	23457043
MIRT438113	hsa-miR-146a-5p	qRT-PCR, Luciferase reporter assay, Western blot	25308712

Transcription factors

Transcription factor	Regulation	Reference
PAX5	Unknown	9190940
SP1	Repression	24825907
STAT1	Repression	24825907

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002281	Process	Macrophage activation involved in immune response	IEA
GO:0003785	Function	Actin monomer binding	ISS
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	15695813
GO:0004697	Function	Protein kinase C activity	IDA	18556656
GO:0004698	Function	Calcium-dependent protein kinase C activity	IEA
GO:0004699	Function	Calcium-independent protein kinase C activity	IEA
GO:0005515	Function	Protein binding	IPI	16810323, 19662078, 20353823, 21625473, 22939624, 24996056, 28934384, 31980649, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IDA	15632189
GO:0005739	Component	Mitochondrion	IEA
GO:0005783	Component	Endoplasmic reticulum	IDA	18556656
GO:0005794	Component	Golgi apparatus	ISS
GO:0005829	Component	Cytosol	IDA	17603037
GO:0005829	Component	Cytosol	TAS
GO:0005886	Component	Plasma membrane	IDA	15632189, 17603037
GO:0005886	Component	Plasma membrane	TAS
GO:0006468	Process	Protein phosphorylation	IDA	18556656
GO:0006915	Process	Apoptotic process	TAS	10438519
GO:0007049	Process	Cell cycle	IEA
GO:0007155	Process	Cell adhesion	IEA
GO:0007165	Process	Signal transduction	TAS	1382605
GO:0008047	Function	Enzyme activator activity	IMP	18556656
GO:0010634	Process	Positive regulation of epithelial cell migration	IMP	17603037
GO:0010763	Process	Positive regulation of fibroblast migration	ISS
GO:0010811	Process	Positive regulation of cell-substrate adhesion	IEA
GO:0018105	Process	Peptidyl-serine phosphorylation	IBA	21873635
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	15695813
GO:0019899	Function	Enzyme binding	IDA	18556656
GO:0019899	Function	Enzyme binding	IPI	15632189
GO:0030168	Process	Platelet activation	TAS
GO:0030546	Function	Signaling receptor activator activity	IEA
GO:0030838	Process	Positive regulation of actin filament polymerization	ISS
GO:0031397	Process	Negative regulation of protein ubiquitination	IEA
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	ISS
GO:0032024	Process	Positive regulation of insulin secretion	IEA
GO:0032230	Process	Positive regulation of synaptic transmission, GABAergic	IEA
GO:0032467	Process	Positive regulation of cytokinesis	IMP	18604201
GO:0035276	Function	Ethanol binding	IEA
GO:0035556	Process	Intracellular signal transduction	IBA	21873635
GO:0035641	Process	Locomotory exploration behavior	IEA
GO:0035669	Process	TRAM-dependent toll-like receptor 4 signaling pathway	ISS
GO:0038096	Process	Fc-gamma receptor signaling pathway involved in phagocytosis	TAS
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IEA
GO:0043231	Component	Intracellular membrane-bounded organelle	IDA
GO:0043278	Process	Response to morphine	IEA
GO:0043410	Process	Positive regulation of MAPK cascade	IEA
GO:0045111	Component	Intermediate filament cytoskeleton	IDA
GO:0046872	Function	Metal ion binding	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	ISS
GO:0050730	Process	Regulation of peptidyl-tyrosine phosphorylation	IEA
GO:0050790	Process	Regulation of catalytic activity	IEA
GO:0050996	Process	Positive regulation of lipid catabolic process	IEA
GO:0051279	Process	Regulation of release of sequestered calcium ion into cytosol	IEA
GO:0051301	Process	Cell division	IEA
GO:0061178	Process	Regulation of insulin secretion involved in cellular response to glucose stimulus	IEA
GO:0070257	Process	Positive regulation of mucus secretion	IEA
GO:0071361	Process	Cellular response to ethanol	IEA
GO:0071380	Process	Cellular response to prostaglandin E stimulus	IEA
GO:0071456	Process	Cellular response to hypoxia	IEA
GO:0071889	Function	14-3-3 protein binding	IEA
GO:0071944	Component	Cell periphery	ISS
GO:0090303	Process	Positive regulation of wound healing	IMP	17603037
GO:1903078	Process	Positive regulation of protein localization to plasma membrane	TAS	22732145
GO:2000650	Process	Negative regulation of sodium ion transmembrane transporter activity	TAS	19193863
GO:2001031	Process	Positive regulation of cellular glucuronidation	IMP	18556656

Other IDs

• MIM: 176975
• HGNC: 9401
• e!Ensembl: ENSG00000171132

Protein

• UniProt ID: Q02156
• Protein name: Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon)
• Protein function: Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. In HeLa cells, contributes to hepatocyte growth factor (HGF)-induced cell migration, and in human corneal epithelial cells, plays a critical role in wound healing after activation by HGF. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). In prostate cancer cells, interacts with and phosphorylates STAT3, which increases DNA-binding and transcriptional activity of STAT3 and seems to be essential for prostate cancer cell invasion. Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1. Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (PubMed:19542546).
• PDB: 2WH0, 5LIH
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00168	C2	6 → 119	C2 domain	Domain
  PF00130	C1_1	170 → 223	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00130	C1_1	243 → 295	Phorbol esters/diacylglycerol binding domain (C1 domain)	Domain
  PF00069	Pkinase	408 → 668	Protein kinase domain	Domain
  PF00433	Pkinase_C	689 → 730	Protein kinase C terminal domain	Family

• Sequence:

  MVVFNGLLKIKICEAVSLKPTAWSLRHAVGPRPQTFLLDPYIALNVDDSRIGQTATKQKT
  NSPAWHDEFVTDVCNGRKIELAVFHDAPIGYDDFVANCTIQFEELLQNGSRHFEDWIDLE
  PEGRVYVIIDLSGSSGEAPKDNEERVFRERMRPRKRQGAVRRRVHQVNGHKFMATYLRQP
  TYCSHCRDFIWGVIGKQGYQCQVCTCVVHKRCHELIITKCAGLKKQETPDQVGSQRFSVN
  MPHKFGIHNYKVPTFCDHCGSLLWGLLRQGLQCKVCKMNVHRRCETNVAPNCGVDARGIA
  KVLADLGVTPDKITNSGQRRKKLIAGAESPQPASGSSPSEEDRSKSAPTSPCDQEIKELE
  NNIRKALSFDNRGEEHRAASSPDGQLMSPGENGEVRQGQAKRLGLDEFNFIKVLGKGSFG
  KVMLAELKGKDEVYAVKVLKKDVILQDDDVDCTMTEKRILALARKHPYLTQLYCCFQTKD
  RLFFVMEYVNGGDLMFQIQRSRKFDEPRSRFYAAEVTSALMFLHQHGVIYRDLKLDNILL
  DAEGHCKLADFGMCKEGILNGVTTTTFCGTPDYIAPEILQELEYGPSVDWWALGVLMYEM
  MAGQPPFEADNEDDLFESILHDDVLYPVWLSKEAVSILKAFMTKNPHKRLGCVASQNGED
  AIKQHPFFKEIDWVLLEQKKIKPPFKPRIKTKRDVNNFDQDFTREEPVLTLVDEAIVKQI
  NQEEFKGFSYFGEDLMP

• Sequence length: 737