Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTYQ0656)

DOT Name	Protein kinase C beta type (PRKCB)
Synonyms	PKC-B; PKC-beta; EC 2.7.11.13
Gene Name	PRKCB
UniProt ID	KPCB_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2I0E
EC Number	2.7.11.13
Pfam ID	PF00130 ; PF00168 ; PF00069 ; PF00433
Sequence	MADPAAGPPPSEGEESTVRFARKGALRQKNVHEVKNHKFTARFFKQPTFCSHCTDFIWGF GKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPASDDPRSKHKFKIHTYSSPTFCDHCGS LLYGLIHQGMKCDTCMMNVHKRCVMNVPSLCGTDHTERRGRIYIQAHIDRDVLIVLVRDA KNLVPMDPNGLSDPYVKLKLIPDPKSESKQKTKTIKCSLNPEWNETFRFQLKESDKDRRL SVEIWDWDLTSRNDFMGSLSFGISELQKASVDGWFKLLSQEEGEYFNVPVPPEGSEANEE LRQKFERAKISQGTKVPEEKTTNTVSKFDNNGNRDRMKLTDFNFLMVLGKGSFGKVMLSE RKGTDELYAVKILKKDVVIQDDDVECTMVEKRVLALPGKPPFLTQLHSCFQTMDRLYFVM EYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHI KIADFGMCKENIWDGVTTKTFCGTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAP FEGEDEDELFQSIMEHNVAYPKSMSKEAVAICKGLMTKHPGKRLGCGPEGERDIKEHAFF RYIDWEKLERKEIQPPYKPKARDKRDTSNFDKEFTRQPVELTPTDKLFIMNLDQNEFAGF SYTNPEFVINV
Function	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 (AR)-dependent transcription, by being recruited to AR 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. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1. 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. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4.
KEGG Pathway	EGFR tyrosine ki.se inhibitor resistance (hsa01521 ) MAPK sig.ling pathway (hsa04010 ) ErbB sig.ling pathway (hsa04012 ) Ras sig.ling pathway (hsa04014 ) Rap1 sig.ling pathway (hsa04015 ) Calcium sig.ling pathway (hsa04020 ) Chemokine sig.ling pathway (hsa04062 ) NF-kappa B sig.ling pathway (hsa04064 ) HIF-1 sig.ling pathway (hsa04066 ) Phosphatidylinositol sig.ling system (hsa04070 ) Sphingolipid sig.ling pathway (hsa04071 ) mTOR sig.ling pathway (hsa04150 ) Vascular smooth muscle contraction (hsa04270 ) Wnt sig.ling pathway (hsa04310 ) VEGF sig.ling pathway (hsa04370 ) Focal adhesion (hsa04510 ) Gap junction (hsa04540 ) Neutrophil extracellular trap formation (hsa04613 ) .tural killer cell mediated cytotoxicity (hsa04650 ) B cell receptor sig.ling pathway (hsa04662 ) Fc gamma R-mediated phagocytosis (hsa04666 ) Leukocyte transendothelial migration (hsa04670 ) Circadian entrainment (hsa04713 ) Long-term potentiation (hsa04720 ) Retrograde endocan.binoid sig.ling (hsa04723 ) Glutamatergic sy.pse (hsa04724 ) Cholinergic sy.pse (hsa04725 ) Serotonergic sy.pse (hsa04726 ) GABAergic sy.pse (hsa04727 ) Dopaminergic sy.pse (hsa04728 ) Long-term depression (hsa04730 ) Inflammatory mediator regulation of TRP channels (hsa04750 ) Insulin secretion (hsa04911 ) GnRH sig.ling pathway (hsa04912 ) Melanogenesis (hsa04916 ) Thyroid hormone synthesis (hsa04918 ) Thyroid hormone sig.ling pathway (hsa04919 ) Oxytocin sig.ling pathway (hsa04921 ) Aldosterone synthesis and secretion (hsa04925 ) Parathyroid hormone synthesis, secretion and action (hsa04928 ) GnRH secretion (hsa04929 ) Insulin resistance (hsa04931 ) AGE-RAGE sig.ling pathway in diabetic complications (hsa04933 ) Growth hormone synthesis, secretion and action (hsa04935 ) Aldosterone-regulated sodium reabsorption (hsa04960 ) Endocrine and other factor-regulated calcium reabsorption (hsa04961 ) Salivary secretion (hsa04970 ) Gastric acid secretion (hsa04971 ) Pancreatic secretion (hsa04972 ) Carbohydrate digestion and absorption (hsa04973 ) Spinocerebellar ataxia (hsa05017 ) Pathways of neurodegeneration - multiple diseases (hsa05022 ) Amphetamine addiction (hsa05031 ) Morphine addiction (hsa05032 ) Leishmaniasis (hsa05140 ) African trypanosomiasis (hsa05143 ) Amoebiasis (hsa05146 ) Hepatitis B (hsa05161 ) Human cytomegalovirus infection (hsa05163 ) Influenza A (hsa05164 ) Human immunodeficiency virus 1 infection (hsa05170 ) Coro.virus disease - COVID-19 (hsa05171 ) Pathways in cancer (hsa05200 ) Proteoglycans in cancer (hsa05205 ) MicroR.s in cancer (hsa05206 ) Chemical carcinogenesis - receptor activation (hsa05207 ) Glioma (hsa05214 ) Non-small cell lung cancer (hsa05223 ) Hepatocellular carcinoma (hsa05225 ) Choline metabolism in cancer (hsa05231 ) Diabetic cardiomyopathy (hsa05415 )
Reactome Pathway	Activation of NF-kappaB in B cells (R-HSA-1169091 ) Trafficking of GluR2-containing AMPA receptors (R-HSA-416993 ) G alpha (z) signalling events (R-HSA-418597 ) Depolymerization of the Nuclear Lamina (R-HSA-4419969 ) WNT5A-dependent internalization of FZD4 (R-HSA-5099900 ) VEGFR2 mediated cell proliferation (R-HSA-5218921 ) RHO GTPases Activate NADPH Oxidases (R-HSA-5668599 ) Response to elevated platelet cytosolic Ca2+ (R-HSA-76005 ) RUNX1 regulates transcription of genes involved in differentiation of myeloid cells (R-HSA-8939246 ) Disinhibition of SNARE formation (R-HSA-114516 )

Molecular Interaction Atlas (MIA) of This DOT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

34 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Protein kinase C beta type (PRKCB).	[1]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein kinase C beta type (PRKCB).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein kinase C beta type (PRKCB).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Protein kinase C beta type (PRKCB).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein kinase C beta type (PRKCB).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein kinase C beta type (PRKCB).	[7]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide decreases the expression of Protein kinase C beta type (PRKCB).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Protein kinase C beta type (PRKCB).	[9]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Protein kinase C beta type (PRKCB).	[4]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Protein kinase C beta type (PRKCB).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Protein kinase C beta type (PRKCB).	[9]
Aspirin	DM672AH	Approved	Aspirin affects the expression of Protein kinase C beta type (PRKCB).	[11]
Indomethacin	DMSC4A7	Approved	Indomethacin decreases the expression of Protein kinase C beta type (PRKCB).	[14]
Cocaine	DMSOX7I	Approved	Cocaine decreases the expression of Protein kinase C beta type (PRKCB).	[15]
Ursodeoxycholic acid	DMCUT21	Approved	Ursodeoxycholic acid increases the activity of Protein kinase C beta type (PRKCB).	[16]
Deoxycholic acid	DM3GYAL	Approved	Deoxycholic acid increases the activity of Protein kinase C beta type (PRKCB).	[16]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Protein kinase C beta type (PRKCB).	[9]
Tamibarotene	DM3G74J	Phase 3	Tamibarotene increases the expression of Protein kinase C beta type (PRKCB).	[2]
phorbol 12-myristate 13-acetate	DMJWD62	Phase 2	phorbol 12-myristate 13-acetate decreases the expression of Protein kinase C beta type (PRKCB).	[19]
Bryostatin-1	DM1JOXY	Phase 2	Bryostatin-1 decreases the expression of Protein kinase C beta type (PRKCB).	[20]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein kinase C beta type (PRKCB).	[22]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein kinase C beta type (PRKCB).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein kinase C beta type (PRKCB).	[24]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein kinase C beta type (PRKCB).	[26]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein kinase C beta type (PRKCB).	[27]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Protein kinase C beta type (PRKCB).	[28]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Protein kinase C beta type (PRKCB).	[29]
D-glucose	DMMG2TO	Investigative	D-glucose increases the activity of Protein kinase C beta type (PRKCB).	[30]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN affects the expression of Protein kinase C beta type (PRKCB).	[31]
Tributylstannanyl	DMHN7CB	Investigative	Tributylstannanyl increases the expression of Protein kinase C beta type (PRKCB).	[29]
Cycloheximide	DMGDA3C	Investigative	Cycloheximide decreases the expression of Protein kinase C beta type (PRKCB).	[32]
	DM9CEI5		increases the activity of Protein kinase C beta type (PRKCB).	[16]
Benzoquinone	DMNBA0G	Investigative	Benzoquinone increases the expression of Protein kinase C beta type (PRKCB).	[33]
NSC-1771	DMNXDGQ	Investigative	NSC-1771 decreases the activity of Protein kinase C beta type (PRKCB).	[34]
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⏷ Show the Full List of 34 Drug(s)

5 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein kinase C beta type (PRKCB).	[6]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the phosphorylation of Protein kinase C beta type (PRKCB).	[12]
Docetaxel	DMDI269	Approved	Docetaxel increases the phosphorylation of Protein kinase C beta type (PRKCB).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein kinase C beta type (PRKCB).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Protein kinase C beta type (PRKCB).	[25]
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2 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Nicotine	DMWX5CO	Approved	Nicotine affects the localization of Protein kinase C beta type (PRKCB).	[13]
DNCB	DMDTVYC	Phase 2	DNCB affects the localization of Protein kinase C beta type (PRKCB).	[18]
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References

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18	Role of PKC- in chemical allergen-induced CD86 expression and IL-8 release in THP-1 cells. Arch Toxicol. 2014 Feb;88(2):415-24. doi: 10.1007/s00204-013-1144-z. Epub 2013 Oct 18.
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27	Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
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