PRKCB - Protein kinase C beta type - human protein (Function)
 
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PRKCB »  Protein kinase C beta type
 
Gene name:  PRKCB
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. May participate in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis (By similarity). Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription.  
3
  • CuratedUniProtKB
GO molecular function 
Androgen receptor bindingdefinition[GO:0050681]  
1
  • IDAUniProtKB
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Calcium channel regulator activitydefinition[GO:0005246] silver  
  • IEAOrtholog Compara
Chromatin bindingdefinition[GO:0003682]  
1
  • IDAUniProtKB
Histone bindingdefinition[GO:0042393]  
1
  • IDAUniProtKB
Isoform  Beta-II   Histone kinase activity (H3-T6 specific)definition[GO:0035403]  
1
  • IDAUniProtKB
Ligand-dependent nuclear receptor transcription coactivator activitydefinition[GO:0030374]  
1
  • IMPUniProtKB
Protein bindingdefinition[GO:0005515]  
2
  • IPIUniProtKB
  • IPIIntAct
Protein kinase C activitydefinition[GO:0004697]  
  • IEAEC 2 GO
Protein kinase C bindingdefinition[GO:0005080]  
1
  • IPIUniProtKB
Zinc ion bindingdefinition[GO:0008270] silver  
  • IEAInterPro 2 GO
GO biological process 
Apoptotic processdefinition[GO:0006915]  
  • IEAUniProtKB KW
B cell activationdefinition[GO:0042113]  
  • ISSOrtholog Curator
B cell receptor signaling pathwaydefinition[GO:0050853]  
  • ISSOrtholog Curator
Calcium ion transportdefinition[GO:0006816] silver  
  • IEAOrtholog Compara
Cellular calcium ion homeostasisdefinition[GO:0006874] silver  
  • IEAOrtholog Compara
Cellular response to carbohydrate stimulusdefinition[GO:0071322] silver  
  • IEAOrtholog Compara
Isoform  Beta-II   Histone H3-T6 phosphorylationdefinition[GO:0035408]  
1
  • IDAUniProtKB
Intracellular signal transductiondefinition[GO:0035556] silver  
  • IEAInterPro 2 GO
Lipoprotein transportdefinition[GO:0042953]  
1
  • TASBHF-UCL
Negative regulation of glucose transportdefinition[GO:0010829]  
  • ISSOrtholog Curator
Negative regulation of insulin receptor signaling pathwaydefinition[GO:0046627]  
  • ISSOrtholog Curator
Positive regulation of angiogenesisdefinition[GO:0045766]  
  • ISSOrtholog Curator
Positive regulation of B cell receptor signaling pathwaydefinition[GO:0050861]  
  • ISSOrtholog Curator
Positive regulation of I-kappaB kinase/NF-kappaB signalingdefinition[GO:0043123]  
  • ISSOrtholog Curator
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
  • ISSOrtholog Curator
Positive regulation of vascular endothelial growth factor receptor signaling pathwaydefinition[GO:0030949]  
  • ISSOrtholog Curator
Protein phosphorylationdefinition[GO:0006468]  
1
  • TASPINC
Regulation of transcription from RNA polymerase II promoterdefinition[GO:0006357]  
1
  • IMPUniProtKB
Signal transductiondefinition[GO:0007165]  
1
  • NASPINC
Transcription, DNA-templateddefinition[GO:0006351]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.13: ATP + a protein ADP + a phosphoprotein.  
1
  • CuratedUniProtKB
It requires the following cofactor
Binds 3 calcium ions per subunit. The ions are bound to the C2 domain (By similarity).  
  • CuratedUniProtKB
It is regulated in the following manner
Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615).  
1
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
African trypanosomiasis  hsa05143+5579  
Aldosterone-regulated sodium reabsorption  hsa04960+5579  
Amoebiasis  hsa05146+5579  
B cell receptor signaling pathway  hsa04662+5579  
Calcium signaling pathway  hsa04020+5579  
Carbohydrate digestion and absorption  hsa04973+5579  
Chemokine signaling pathway  hsa04062+5579  
Cholinergic synapse  hsa04725+5579  
Dopaminergic synapse  hsa04728+5579  
Endocrine and other factor-regulated calcium reabsorption  hsa04961+5579  
ErbB signaling pathway  hsa04012+5579  
Fc epsilon RI signaling pathway  hsa04664+5579  
Fc gamma R-mediated phagocytosis  hsa04666+5579  
Focal adhesion  hsa04510+5579  
GABAergic synapse  hsa04727+5579  
Gap junction  hsa04540+5579  
Gastric acid secretion  hsa04971+5579  
Glioma  hsa05214+5579  
Glutamatergic synapse  hsa04724+5579  
GnRH signaling pathway  hsa04912+5579  
Influenza A  hsa05164+5579  
Leishmaniasis  hsa05140+5579  
Leukocyte transendothelial migration  hsa04670+5579  
Long-term depression  hsa04730+5579  
Long-term potentiation  hsa04720+5579  
MAPK signaling pathway  hsa04010+5579  
Melanogenesis  hsa04916+5579  
Natural killer cell mediated cytotoxicity  hsa04650+5579  
Non-small cell lung cancer  hsa05223+5579  
Pancreatic secretion  hsa04972+5579  
Pathways in cancer  hsa05200+5579  
Phosphatidylinositol signaling system  hsa04070+5579  
Salivary secretion  hsa04970+5579  
Tight junction  hsa04530+5579  
Vascular smooth muscle contraction  hsa04270+5579  
VEGF signaling pathway  hsa04370+5579  
Vibrio cholerae infection  hsa05110+5579  
Wnt signaling pathway  hsa04310+5579  
According to Reactome, this protein belongs to the following pathways:
Activation of NF-kappaB in B cells  REACT_118656  
Depolymerisation of the Nuclear Lamina  REACT_200828  
Disinhibition of SNARE formation  REACT_1178  
G alpha (z) signalling events  REACT_19333  
Response to elevated platelet cytosolic Ca2+  REACT_1280  
Trafficking of GluR2-containing AMPA receptors  REACT_18422  
WNT5A-dependent internalization of FZD4  REACT_172599  
 

Keywords

Biological process 
Adaptive immunity  definition   [KW-1064]
Apoptosis  definition   [KW-0053]
Immunity  definition   [KW-0391]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Chromatin regulator  definition   [KW-0156]
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PRKCB1
GenomeRNAi: 5579
PRO: PR:P05771
Chemistry
GuidetoPHARMACOLOGY: 1483