Tchem PRKCH Protein kinase C eta type

Protein Summary

Description

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. Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. It is a calcium-independent and phospholipids-dependent protein kinase. It is predominantly expressed in epithelial tissues and has been shown to reside specifically in the cell nucleus. This protein kinase can regulate keratinocyte differentiation by activating the MAP kinase MAPK13 (p38delta)-activated protein kinase cascade that targets CCAAT/enhancer-binding protein alpha (CEBPA). It is also found to mediate the transcription activation of the transglutaminase 1 (TGM1) gene. Mutations in this gene are associated with susceptibility to cerebral infarction. [provided by RefSeq, Sep 2015]

Uniprot Accession IDs

• P24723
• B4DJN5
• Q16246
• Q8NE03

Gene Name

• PRKCH

Ensembl ID

• ENST00000332981
• ENSP00000329127
• ENSG00000027075
• ENST00000555082
• ENSP00000450981

Symbol

• PKCL
• PRKCL
• PKCL
• PKC-L
• PRKCL
• nPKC-eta

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
molecular function	0.99
PubMedID	0.97
drug perturbation	0.87
trait	0.86

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Protein Kinase C Eta Type

Protein / Transfer/carrier Protein / Protein Kinase C Eta Type

Protein / Calcium-binding Protein / Intracellular Calcium-sensing Protein / Calmodulin / Protein Kinase C Eta Type

Protein / Calcium-binding Protein / Annexin / Protein Kinase C Eta Type

DTO Classes

Protein / Kinase / Protein Kinase / Agc Group / Pkc Family / Pkc Eta Subfamily / Protein Kinase C Eta Type

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 77.6   (req: < 5)

Gene RIFs: 57   (req: <= 3)

Antibodies: 246   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 77.6   (req: >= 5)

Gene RIFs: 57   (req: > 3)

Antibodies: 246   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 98

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0