Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

PRKCE (Q02156) - Overview - Molecular Target Synopsis

Protein


PRKCE, Protein kinase C epsilon type
Enzyme Classification 2.7.11.13
UniProt Q02156

Also Known as KPCE_HUMAN, PRKCE, PKCE

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. Forms a ternary complex with TRIM63 and GN2BL1. Can form a complex with PDLIM5 and N-type calcium channel. Interacts with COPB1 and YWHAB (By similarity). Interacts with DGKQ and STAT3. Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner (PubMed:20353823).

5LIH
10 RESIDUE FRAGMENT OF
PKC EPSILON PSEUDO SUBSTRATE SEQUENCE
IN THE STRUCTURE OF
STRUCTURE OF A PEPTIDE-SUBSTRATE BOUND TO PKCIOTA CORE KINASE DOMAIN
RCSB/PDB
Inspect Structure
See all 3D Structures for PRKCE

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PRKCE is active in the following subcellular-locations: cell membrane, cytoplasm, cytoskeleton, nucleus, perinuclear region.
GO terms: PRKCE is active in the following subcellular-locations: cell periphery, cytoplasm, cytoskeleton, cytosol, endoplasmic reticulum, Golgi apparatus, mitochondrion, nucleus, perinuclear region of cytoplasm, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PRKCE has gain in 3 cell-lines, loss in 0 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SN12C, LOXIMVI, ACHN

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: LOX-IMVI, CAL-12T, WSU-FSCCL

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: CD20-positive B cell, GM12878, HMEC

(see details)

RNA Interference


PRKCE was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: OS25HAL, LM7. (see details)

3D Structures


For PRKCE there are:
2 structures (4 chains) solved
0 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PRKCE has been screened with 1331 compounds (1972 bioactivities), 314 compounds have bioactivities that show binding affinity of <= 500nM (453 bioactivities). (see details)