Protein kinase C eta type

UniProt P24723 Organism Homo sapiens Gene PKCL, PRKCH, PRKCL EC 2.7.11.13

Also known as: PKCL, PRKCH, PRKCL

Function

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.

Classification

Family (Pfam): PF00130 C1_1, PF00168 C2, PF00069 Pkinase, PF00433 Pkinase_C
InterPro: AGC-kinase_C, C1-like_sf, C2_dom, C2_domain_sf, DAG/PE-bd, Kinase-like_dom_sf, nPKC_eta, PKC_DAG/PE, PKC_eta, Pkinase_C, Prot_kin_PKC_delta, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
Functional cluster: Serine/Threonine Protein Kinases

Experimental structures · PDB · 4

2FK9 X-ray 1.75A
3TXO X-ray 2.05A
8FP1 X-ray 1.85A
8FP3 X-ray 2.30A

A predicted model is available from AlphaFold.

Gene Ontology · 26

Disease associations

obsolete susceptibility to ischemic stroke MONDO:0020671

Drugs targeting this protein · 5

GSK-690693 inhibitor
SOTRASTAURIN inhibitor
UCN-01 inhibitor
CEP-2563 DIHYDROCHLORIDE inhibitor
MIDOSTAURIN inhibitor

Related proteins · sequence + function similarity

Protein kinase C eta type 1.00
Protein kinase C eta type 1.00
Protein kinase C-like 1B 0.94
Protein kinase C epsilon type 0.94
Protein kinase C epsilon type 0.94
Protein kinase C 0.93
Protein kinase C epsilon type 0.93
Protein kinase C epsilon type 0.93
Calcium-independent protein kinase C 0.92
Protein kinase C-like 1 0.90
Protein kinase C delta type 0.90
Protein kinase C theta type 0.90

Co-cited proteins · studied together in the literature

Protein kinase C eta type 1 shared papers
PRKCH upstream open reading frame 2 2 shared papers
Occludin 1 shared papers
Protein kinase C epsilon type 2 shared papers
Diacylglycerol kinase theta 1 shared papers
Hexokinase-1 1 shared papers
Protein kinase C delta type 2 shared papers
eIF-2-alpha kinase GCN2 1 shared papers
Cyclic AMP-dependent transcription factor ATF-2 1 shared papers
Serine/threonine-protein kinase N1 1 shared papers
Serine/threonine-protein kinase N2 1 shared papers
Non-selective voltage-gated ion channel VDAC1 1 shared papers

Literature · 26 cited papers

Unraveling the hidden role of a uORF-encoded peptide as a kinase inhibitor of PKCs. Proc. Natl. Acad. Sci. U.S.A. · 2021
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Cell · 2012
Protein kinase C? activates NF-?B in response to camptothecin-induced DNA damage. Biochem. Biophys. Res. Commun. · 2011
Protein kinase C-eta and phospholipase D2 pathway regulates foam cell formation via regulator of G protein signaling 2. Mol. Pharmacol. · 2010
Translational control of protein kinase Ceta by two upstream open reading frames. Mol. Cell. Biol. · 2009
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
PKC eta regulates occludin phosphorylation and epithelial tight junction integrity. Proc. Natl. Acad. Sci. U.S.A. · 2009
PKC eta directs induction of IRF-4 expression and Ig kappa gene rearrangement in pre-BCR signaling pathway. Int. Immunol. · 2008
Patterns of somatic mutation in human cancer genomes. Nature · 2007
A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of cerebral infarction. Nat. Genet. · 2007
… and 14 more in the literature graph

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