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Details on Person UniProt:P24723 PRKCH

Class:IdReferenceGeneProduct:58209
_chainChangeLogchain:1-683 added on Fri February 6 2015
_displayNameUniProt:P24723 PRKCH
_timestamp2025-02-21 19:49:20
chainchain:1-683
checksum0A29806CE31912F2
commentFUNCTION 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 L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)ACTIVITY 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. Inhibited by PRKCH upstream open reading frame 2 (PubMed:34593629).SUBUNIT Interacts with FYN (By similarity). Interacts with RALA (By similarity). Interacts with DGKQ (PubMed:15632189). Interacts with PRKCH upstream open reading frame 2; the interaction leads to inhibition of kinase activity (PubMed:34593629).INTERACTION Most abundant in lung, less in heart and skin.INDUCTION By stress conditions caused by amino acid starvation (at protein level).DOMAIN The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain.DISEASE Disease susceptibility is associated with variants affecting the gene represented in this entry.SIMILARITY Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
descriptionrecommendedName: Protein kinase C eta type ecNumber evidence="24"2.7.11.13 alternativeName: PKC-L alternativeName: nPKC-eta
geneNamePRKCH
PKCL
PRKCL
identifierP24723
isSequenceChangedFALSE
keyword3D-structure
Alternative splicing
ATP-binding
Cytoplasm
Differentiation
Kinase
Metal-binding
Nucleotide-binding
Phosphoprotein
Proteomics identification
Reference proteome
Repeat
Serine/threonine-protein kinase
Transferase
Zinc
Zinc-finger
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
namePRKCH
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8993708] ENSEMBL:ENSG00000027075 PRKCH [Homo sapiens]
secondaryIdentifierKPCL_HUMAN
B4DJN5
Q16246
Q8NE03
sequenceLength683
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:8971988] UniProt:P24723-1 PRKCH [Homo sapiens]
[ReferenceIsoform:8971989] UniProt:P24723-2 PRKCH [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:58208] PRKCH [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:9750060] p-PRKCH [cytosol] [Homo sapiens]
(referenceSequence)[ModifiedResidue:9750049] O-phospho-L-serine at 32
[ModifiedResidue:9750052] O-phospho-L-serine at 28
[ModifiedResidue:9750073] L-serine residue at 28
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