Names & Taxonomy
- Uniprot ID:
- P24723
- Entry Name:
- KPCL_HUMAN
- Status:
- reviewed
- Protein Names:
- Protein kinase C eta type (EC 2.7.11.13) (PKC-L) (nPKC-eta)
- Gene Names:
- PRKCH PKCL PRKCL
- Gene Names Primary:
- PRKCH
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 683
- Sequence:
- MSSGTMKFNGYLRVRIGEAVGLQPTRWSLRHSLFKKGHQLLDPYLTVSVDQVRVGQTSTKQKTNKPTYNEEFCANVTDGGHLELAVFHETPLGYDHFVANCTLQFQELLRTTGASDTFEGWVDLEPEGKVFVVITLTGSFTEATLQRDRIFKHFTRKRQRAMRRRVHQINGHKFMATYLRQPTYCSHCREFIWGVFGKQGYQCQVCTCVVHKRCHHLIVTACTCQNNINKVDSKIAEQRFGINIPHKFSIHNYKVPTFCDHCGSLLWGIMRQGLQCKICKMNVHIRCQANVAPNCGVNAVELAKTLAGMGLQPGNISPTSKLVSRSTLRRQGKESSKEGNGIGVNSSNRLGIDNFEFIRVLGKGSFGKVMLARVKETGDLYAVKVLKKDVILQDDDVECTMTEKRILSLARNHPFLTQLFCCFQTPDRLFFVMEFVNGGDLMFHIQKSRRFDEARARFYAAEIISALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKEGICNGVTTATFCGTPDYIAPEILQEMLYGPAVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDEVVYPTWLHEDATGILKSFMTKNPTMRLGSLTQGGEHAILRHPFFKEIDWAQLNHRQIEPPFRPRIKSREDVSNFDPDFIKEEPVLTPIDEGHLPMINQDEFRNFSYVSPELQP
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Cytoplasm
Function
- 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.
- Catalytic Activity:
- ATP + a protein = ADP + a phosphoprotein.
- Enzyme Regulation:
- ENZYME REGULATION: Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-513 (activation loop of the kinase domain), Thr-656 (turn motif) and Ser-675 (hydrophobic region), need to be phosphorylated for its full activation.
- Active Site:
- ACT_SITE 479 479 Proton acceptor.
- Gene Ontology Go:
- cell-cell junction
cytoplasm
cytosol
extracellular exosome
plasma membrane
ATP binding
calcium-independent protein kinase C activity
enzyme binding
metal ion binding
protein kinase C activity
blood coagulation
intracellular signal transduction
negative regulation of glial cell apoptotic process
peptidyl-serine phosphorylation
platelet activation
positive regulation of B cell receptor signaling pathway
positive regulation of glial cell proliferation
positive regulation of keratinocyte differentiation
positive regulation of macrophage derived foam cell differentiation
positive regulation of NF-kappaB transcription factor activity
protein kinase C signaling
protein phosphorylation
regulation of bicellular tight junction assembly
signal transduction - Gene Ontology Biological Process:
- blood coagulation
intracellular signal transduction
negative regulation of glial cell apoptotic process
peptidyl-serine phosphorylation
platelet activation
positive regulation of B cell receptor signaling pathway
positive regulation of glial cell proliferation
positive regulation of keratinocyte differentiation
positive regulation of macrophage derived foam cell differentiation
positive regulation of NF-kappaB transcription factor activity
protein kinase C signaling
protein phosphorylation
regulation of bicellular tight junction assembly
signal transduction - Gene Ontology Molecular Function:
- ATP binding
calcium-independent protein kinase C activity
enzyme binding
metal ion binding
protein kinase C activity - Gene Ontology Cellular Component:
- cell-cell junction
cytoplasm
cytosol
extracellular exosome
plasma membrane - Keywords:
- 3D-structure
ATP-binding
Alternative splicing
Complete proteome
Cytoplasm
Differentiation
Kinase
Metal-binding
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Transferase
Zinc
Zinc-finger