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

PRKCH (P24723) - Overview - Molecular Target Synopsis

Protein


PRKCH, Protein kinase C eta type
Enzyme Classification 2.7.11.13
UniProt P24723

Also Known as KPCL_HUMAN, PRKCH, PKCL, PRKCL

Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in the regulation of cell differentiation in keratinocytes and pre-B cell receptor, mediates regulation of epithelial tight junction integrity and foam cell formation, and is required for glioblastoma proliferation and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and activates the tyrosine kinase FYN, which in turn blocks epidermal growth factor receptor (EGFR) signaling and leads to keratinocyte growth arrest and differentiation. Associates with the cyclin CCNE1-CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1 dephosphorylation and thereby G1 arrest in keratinocytes. In association with RALA activates actin depolymerization, which is necessary for keratinocyte differentiation. In the pre-B cell receptor signaling, functions downstream of BLNK by up-regulating IRF4, which in turn activates L chain gene rearrangement. Regulates epithelial tight junctions (TJs) by phosphorylating occludin (OCLN) on threonine residues, which is necessary for the assembly and maintenance of TJs. In association with PLD2 and via TLR4 signaling, is involved in lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell formation. Upon PMA stimulation, mediates glioblastoma cell proliferation by activating the mTOR pathway, the PI3K/AKT pathway and the ERK1-dependent phosphorylation of ELK1. Involved in the protection of glioblastoma cells from irradiation-induced apoptosis by preventing caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates NF-kappa-B upstream signaling by activating IKBKB, and confers protection against DNA damage-induced apoptosis. Promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Phosphorylates ATF2 which promotes its nuclear retention and transcriptional activity and negatively regulates its mitochondrial localization. Interacts with FYN and RALA (By similarity). Interacts with DGKQ.

3TXO
PKC ETA KINASE IN COMPLEX WITH A NAPHTHYRIDINE
RCSB/PDB
Inspect Structure
See all 3D Structures for PRKCH

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: PRKCH is active in the following subcellular-locations: cytoplasm.
GO terms: PRKCH is active in the following subcellular-locations: cytoplasm, cytosol, extracellular exosome, plasma membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project PRKCH has gain in 5 cell-lines, loss in 1 cell-lines and no signal in 999 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MOLT_4, CCRF_CEM, NCI_H322M

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H1781, SCC-3, Jurkat, Clone E6-1

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: HUVEC, GM12878, MCF-7

(see details)

RNA Interference


PRKCH was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: SUM44, DU4475. (see details)

3D Structures


For PRKCH there are:
2 structures (2 chains) solved
1 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


PRKCH has been screened with 1433 compounds (2380 bioactivities), 285 compounds have bioactivities that show binding affinity of <= 500nM (405 bioactivities). (see details)