InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PRKCH

Summary

InnateDB Protein

IDBP-8481.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PRKCH

Protein Name

protein kinase C, eta

Synonyms

nPKC-eta; PKC-L; PKCL; PRKCL;

Species

Homo sapiens

Ensembl Protein

ENSP00000329127

InnateDB Gene

IDBG-8479 (PRKCH)

Protein Structure

UniProt Annotation

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. {ECO:0000269PubMed:10806212, ECO:0000269PubMed:11112424, ECO:0000269PubMed:11772428, ECO:0000269PubMed:15489897, ECO:0000269PubMed:17146445, ECO:0000269PubMed:18780722, ECO:0000269PubMed:19114660, ECO:0000269PubMed:20558593, ECO:0000269PubMed:21820409, ECO:0000269PubMed:22304920}.

Subcellular Localization

Cytoplasm {ECO:0000250}.

Disease Associations

Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. {ECO:0000269PubMed:17206144}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Tissue Specificity

Most abundant in lung, less in heart and skin. {ECO:0000269PubMed:1986216}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 14 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	14 [view]
Protein-Protein	14 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004697	protein kinase C activity
GO:0004699	calcium-independent protein kinase C activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0017160	Ral GTPase binding
GO:0019899	enzyme binding
GO:0046872	metal ion binding

Biological Process

GO:0006468	protein phosphorylation
GO:0007165	signal transduction
GO:0007596	blood coagulation
GO:0010744	positive regulation of macrophage derived foam cell differentiation
GO:0030168	platelet activation
GO:0034351	negative regulation of glial cell apoptotic process
GO:0035556	intracellular signal transduction
GO:0045618	positive regulation of keratinocyte differentiation
GO:0050861	positive regulation of B cell receptor signaling pathway
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0060252	positive regulation of glial cell proliferation
GO:0070528	protein kinase C signaling
GO:2000810	regulation of tight junction assembly

Cellular Component

GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane
GO:0005911	cell-cell junction
GO:0016020	membrane
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR000008 C2 domain
IPR000719 Protein kinase domain
IPR000961 AGC-kinase, C-terminal
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002219 Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR014376 Protein kinase C, delta/epsilon/eta/theta types
IPR017892 Protein kinase, C-terminal
IPR020454 Diacylglycerol/phorbol-ester binding
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00168
PF00069
PF07714
PF00130
PF00433

PRINTS

PR00360
PR00109
PR00008

PIRSF

PIRSF000551

SMART

SM00239
SM00133
SM00109
SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References