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FLASH GENE

Symbol

PRKCE

contributors: mct/pgu - updated : 01-07-2017

HGNC name	protein kinase C, epsilon
HGNC id	9401

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	2p21      Physical location : 45.879.042 - 46.415.128
Synonym name	nPKC-epsilon
Synonym symbol(s)	PKCE, MGC125656, MGC125657, nPKC-epsilon
EC.number	2.7.11.1, 2.7.11.13

DNA

TYPE	functioning gene
STRUCTURE	536.09 kb     15 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005400 15 - 5537 NP_005391 - 737 - 2001 11179977

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Lymphoid/Immune lymph node       highly Nervous brain       highly Reproductive male system testis     highly

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two zinc dependent phorbol-ester and DAG binding domains
	one C2 domain for binding to acidic phospholipids in a calcium independent manner

HOMOLOGY

interspecies

homolog to murine Prkce

Homologene

FAMILY	protein kinase superfamily
	Ser/Thr family of proteine kinase
	PKC subfamily

CATEGORY

signaling , receptor membrane serine/threonine

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	playing a pivotal role in endothelial cell cytoprotection against apoptosis
	epsilon inhibits human CYP11B2 gene expression through ERK1/2 signaling pathway and JUNB
	can induce distinctly different signaling from the Golgi and from the plasma membrane
	role in regulating insulin inositide-dependent PLCG1 signalling in skeletal muscle differentiation
	regulates BCL2 induction through activation of the transcription factor CREB1 (
	role in contraction-stimulated SLC2A4 traffic in muscle cells
	is likely a major signaling molecule that is involved in EDN1 induced positive inotropic effect in ventricular myocytes
	regulates the N-ethylmaleimide-sensitive factor (NSF), an ATPase critical for membrane fusion events, and thereby promotes the trafficking of GABA(A) receptors
	transforming oncogene and plays a pivotal role in numerous cellular processes including proliferation, invasion and differentiation
	is the critical upstream molecule for EDN1-initiated contractility changes
	EDN1 affects systolic Ca2+, and myofilament Ca2+ sensitivity and PRKCE is the upstream kinase involved in all of these intracellular regulatory processes

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

sensory transduction/olfaction

a component

INTERACTION

DNA

RNA

small molecule

protein	forms a signaling complex and acts co-operatively with AKT1 to protect vascular endothelial cells against apoptosis through induction of the anti-apoptotic protein BCL2 and inhibition of caspase-3 cleavage
	activates AKT1 via DNA-dependent protein kinase (DNA-PK)to mediate its antiapoptotic function
	interacts with NLRP5 in cumulus cells under physiological conditions (since PRKCE is known to collaborate with antiapoptotic signalling pathways, this suggests a novel mechanism for the function of NLRP5 in follicular maturation)
	scaffold protein linking PLCG1 to the EGFR module, and acting as negative allosteric modulator of EGF receptor signalling
	CTNND1 is a key effector of a RAS-PKCE oncogenic signaling axis
	specific PRKCE activation directly stimulated MME activity, leading to degradation of a monomeric form of APP peptide and decreased APP neuronal toxicity
	PDLIM5 could selectively recruit PRKCE to its specific substrate in neurons
	CYP1B1 may play an important role in preventing ubiquitin-proteasome-mediated XIAP degradation through the activation of PRKCE signaling in cancer cells

cell & other

REGULATION

activated by

EDN1 (is activated early and robustly following EDN1 stimulation and thus mediates multiple intracellular changes underlying the acute actions of EDN1 on myocardium)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   amplification     in thyroid carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive breast is a tractable therapeutic target for triple negative breast cancer (TNBC) neurology neurodegenerative alzheimer PRKCE activation may have therapeutic efficacy for AD by reducing neurotoxic APP accumulation as well as having direct anti-apoptotic and synaptogenic effects

ANIMAL & CELL MODELS

activation of two novel PKC isoforms (Prkcd and Prkce) and a classical PKC isoform (Prkca) during the development of steatohepatitis in mice fed the methionine- and choline-deficient (MCD) diet