DegronMD - P24723(PRKCH)

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:0000269|PubMed:10806212, ECO:0000269|PubMed:11112424, ECO:0000269|PubMed:11772428, ECO:0000269|PubMed:15489897, ECO:0000269|PubMed:17146445, ECO:0000269|PubMed:18780722, ECO:0000269|PubMed:19114660, ECO:0000269|PubMed:20558593, ECO:0000269|PubMed:21820409, ECO:0000269|PubMed:22304920}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.E660D	TCGA-BR-4257	STAD	TCGA	PVLTPIDE	DEG_SCF_FBW7_2	653:660	Mutation altering degron motif	0.6758
p.E660D	DO38683	STAD	ICGC	PVLTPIDE	DEG_SCF_FBW7_2	653:660	Mutation altering degron motif	0.6758
p.H662L	DO228299	LICA	ICGC	PVLTPIDE	DEG_SCF_FBW7_2	653:660	Mutation rewiring degron network	0.2778
p.E670K	SIDM00120	Prostate Carcinoma	GDSC	PVLTPIDE	DEG_SCF_FBW7_2	653:660	Mutation rewiring degron network	0.0556
p.E670K	DU-145	prostate	COSMIC	PVLTPIDE	DEG_SCF_FBW7_2	653:660	Mutation rewiring degron network	0.0556

DegronMD: protein-targeted degradation, mutation and drug response to degrons

PRKCH

UniProt ID: P24723

Entrez ID: 5583

Protein name: Protein kinase C eta type (EC 2.7.11.13) (PKC-L) (nPKC-eta)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for PRKCH in