Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFJ8Q1)

DTT Name	Protein kinase C alpha (PRKCA)
Synonyms	Protein kinase C alpha type; PRKACA; PKCalpha; PKCA; PKC-alpha; PKC-A
Gene Name	PRKCA
DTT Type	Successful target	[1]
BioChemical Class	Kinase
UniProt ID	KPCA_HUMAN
TTD ID	T12808
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
EC Number	EC 2.7.11.13
Sequence	MADVFPGNDSTASQDVANRFARKGALRQKNVHEVKDHKFIARFFKQPTFCSHCTDFIWGF GKQGFQCQVCCFVVHKRCHEFVTFSCPGADKGPDTDDPRSKHKFKIHTYGSPTFCDHCGS LLYGLIHQGMKCDTCDMNVHKQCVINVPSLCGMDHTEKRGRIYLKAEVADEKLHVTVRDA KNLIPMDPNGLSDPYVKLKLIPDPKNESKQKTKTIRSTLNPQWNESFTFKLKPSDKDRRL SVEIWDWDRTTRNDFMGSLSFGVSELMKMPASGWYKLLNQEEGEYYNVPIPEGDEEGNME LRQKFEKAKLGPAGNKVISPSEDRKQPSNNLDRVKLTDFNFLMVLGKGSFGKVMLADRKG TEELYAIKILKKDVVIQDDDVECTMVEKRVLALLDKPPFLTQLHSCFQTVDRLYFVMEYV NGGDLMYHIQQVGKFKEPQAVFYAAEISIGLFFLHKRGIIYRDLKLDNVMLDSEGHIKIA DFGMCKEHMMDGVTTRTFCGTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDG EDEDELFQSIMEHNVSYPKSLSKEAVSVCKGLMTKHPAKRLGCGPEGERDVREHAFFRRI DWEKLENREIQPPFKPKVCGKGAENFDKFFTRGQPVLTPPDQLVIANIDQSDFEGFSYVN PQFVHPILQSAV
Function	Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42. Is highly expressed in a number of cancer cells where it can act as a tumor promoter and is implicated in malignant phenotypes of several tumors such as gliomas and breast cancers. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP.
KEGG Pathway	MAPK signaling pathway (hsa04010 ) ErbB signaling pathway (hsa04012 ) Ras signaling pathway (hsa04014 ) Rap1 signaling pathway (hsa04015 ) Calcium signaling pathway (hsa04020 ) HIF-1 signaling pathway (hsa04066 ) Phosphatidylinositol signaling system (hsa04070 ) Sphingolipid signaling pathway (hsa04071 ) mTOR signaling pathway (hsa04150 ) PI3K-Akt signaling pathway (hsa04151 ) Adrenergic signaling in cardiomyocytes (hsa04261 ) Vascular smooth muscle contraction (hsa04270 ) Wnt signaling pathway (hsa04310 ) VEGF signaling pathway (hsa04370 ) Focal adhesion (hsa04510 ) Tight junction (hsa04530 ) Gap junction (hsa04540 ) Natural killer cell mediated cytotoxicity (hsa04650 ) Fc epsilon RI signaling pathway (hsa04664 ) Fc gamma R-mediated phagocytosis (hsa04666 ) Leukocyte transendothelial migration (hsa04670 ) Circadian entrainment (hsa04713 ) Long-term potentiation (hsa04720 ) Retrograde endocannabinoid signaling (hsa04723 ) Glutamatergic synapse (hsa04724 ) Cholinergic synapse (hsa04725 ) Serotonergic synapse (hsa04726 ) GABAergic synapse (hsa04727 ) Dopaminergic synapse (hsa04728 ) Long-term depression (hsa04730 ) Inflammatory mediator regulation of TRP channels (hsa04750 ) Insulin secretion (hsa04911 ) GnRH signaling pathway (hsa04912 ) Melanogenesis (hsa04916 ) Thyroid hormone synthesis (hsa04918 ) Thyroid hormone signaling pathway (hsa04919 ) Oxytocin signaling pathway (hsa04921 ) Aldosterone-regulated sodium reabsorption (hsa04960 ) Endocrine and other factor-regulated calcium reabsorption (hsa04961 ) Salivary secretion (hsa04970 ) Gastric acid secretion (hsa04971 ) Pancreatic secretion (hsa04972 ) Amphetamine addiction (hsa05031 ) Morphine addiction (hsa05032 ) Vibrio cholerae infection (hsa05110 ) Pathogenic Escherichia coli infection (hsa05130 ) African trypanosomiasis (hsa05143 ) Amoebiasis (hsa05146 ) Hepatitis B (hsa05161 ) Influenza A (hsa05164 ) Pathways in cancer (hsa05200 ) Proteoglycans in cancer (hsa05205 ) MicroRNAs in cancer (hsa05206 ) Glioma (hsa05214 ) Non-small cell lung cancer (hsa05223 ) Choline metabolism in cancer (hsa05231 )
Reactome Pathway	Disinhibition of SNARE formation (R-HSA-114516 ) Regulation of KIT signaling (R-HSA-1433559 ) EGFR Transactivation by Gastrin (R-HSA-2179392 ) Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859 ) Syndecan interactions (R-HSA-3000170 ) Acetylcholine regulates insulin secretion (R-HSA-399997 ) Ca2+ pathway (R-HSA-4086398 ) Trafficking of GluR2-containing AMPA receptors (R-HSA-416993 ) G alpha (z) signalling events (R-HSA-418597 ) Depolymerisation of the Nuclear Lamina (R-HSA-4419969 ) HuR (ELAVL1) binds and stabilizes mRNA (R-HSA-450520 ) WNT5A-dependent internalization of FZD4 (R-HSA-5099900 ) VEGFR2 mediated cell proliferation (R-HSA-5218921 ) Response to elevated platelet cytosolic Ca2+ (R-HSA-76005 ) Calmodulin induced events (R-HSA-111933 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sodium phenylbutyrate	DMXLBCQ	Spinal muscular atrophy	8B61	Approved	[2]
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1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Sotrastaurin acetate	DME53YS	Renal transplantation	NE84	Phase 2	[1]
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1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID28460551-Compound-3	DMA1FRM	N. A.	N. A.	Patented	[3]
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5 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 3521	DMZFS69	N. A.	N. A.	Discontinued in Phase 2	[4]
Acteoside	DM0YHKB	Nephritis	GB40	Terminated	[5]
BALANOL	DMDLN9E	N. A.	N. A.	Terminated	[6]
LY-317644	DMM20PI	N. A.	N. A.	Terminated	[7]
RO-320432	DMFZ1YW	N. A.	N. A.	Terminated	[8]
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39 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(-)-Cercosporamide	DMJ249P	Discovery agent	N.A.	Investigative	[9]
1,2-dioctanoyl-sn-glycerol	DMEAB03	Discovery agent	N.A.	Investigative	[10]
2,3,3-Triphenyl-acrylonitrile	DM7H34U	Discovery agent	N.A.	Investigative	[11]
2-(4-Hydroxy-phenyl)-3,3-diphenyl-acrylonitrile	DMNGW1A	Discovery agent	N.A.	Investigative	[11]
3,3-Bis-(4-hydroxy-phenyl)-2-phenyl-acrylonitrile	DMO51QG	Discovery agent	N.A.	Investigative	[11]
3,3-Bis-(4-methoxy-phenyl)-2-phenyl-acrylonitrile	DMZPYN2	Discovery agent	N.A.	Investigative	[11]
3,4-di-(4-methoxyphenyl)-1H-pyrrole-2,5-dione	DMDO175	Discovery agent	N.A.	Investigative	[12]
3,4-diphenyl-1H-pyrrole-2,5-dione	DMPK6YT	Discovery agent	N.A.	Investigative	[12]
3-(1H-Indol-3-yl)-4-phenylamino-pyrrole-2,5-dione	DMP0RYB	Discovery agent	N.A.	Investigative	[13]
3-(4-Hydroxy-phenyl)-2,3-diphenyl-acrylonitrile	DME5238	Discovery agent	N.A.	Investigative	[11]
3-(4-methoxyphenyl)-4-phenyl-1H-pyrrole-2,5-dione	DMGC7RY	Discovery agent	N.A.	Investigative	[12]
3-(indole-3-yl)-4-phenyl-1H-pyrrole-2,5-dione	DM3EV9N	Discovery agent	N.A.	Investigative	[12]
4,5,6,7-tetrabromo-1H-benzo[d][1,2,3]triazole	DMN9YOB	Discovery agent	N.A.	Investigative	[14]
4-cycloheptyliden(4-hydroxyphenyl)methylphenol	DM4LIUC	Discovery agent	N.A.	Investigative	[11]
4-cyclohexyliden(4-hydroxyphenyl)methylphenol	DM8BLK2	Discovery agent	N.A.	Investigative	[11]
4-cyclopentyliden(4-hydroxyphenyl)methylphenol	DM7LN53	Discovery agent	N.A.	Investigative	[11]
4-[1-(4-hydroxyphenyl)-3-methyl-1-butenyl]phenol	DM8IYG1	Discovery agent	N.A.	Investigative	[11]
CALCEOLARIOSIDE A	DM6NPUM	Discovery agent	N.A.	Investigative	[5]
CALCEOLARIOSIDE B	DMEAUK5	Discovery agent	N.A.	Investigative	[5]
CI-1040	DMF3DZX	Discovery agent	N.A.	Investigative	[15]
Diheptan-3-yl 5-(hydroxymethyl)isophthalate	DMBAY7P	Discovery agent	N.A.	Investigative	[10]
Dihexan-3-yl 5-(hydroxymethyl)isophthalate	DM8TBQ9	Discovery agent	N.A.	Investigative	[10]
FORSYTHIASIDE	DMPC568	Discovery agent	N.A.	Investigative	[5]
Go 6983	DMKVTZN	Discovery agent	N.A.	Investigative	[16]
KN-62	DMLZ89P	Discovery agent	N.A.	Investigative	[15]
KT-5720	DM9J50F	Discovery agent	N.A.	Investigative	[15]
LEUCOSCEPTOSIDE A	DM6W27F	Discovery agent	N.A.	Investigative	[5]
LY-326449	DMN53M4	Discovery agent	N.A.	Investigative	[17]
Plantainoside D	DMWHNZ4	Discovery agent	N.A.	Investigative	[5]
PROSTRATIN	DM1HMJ5	Human immunodeficiency virus infection	1C62	Investigative	[18]
PUNICAFOLIN	DM7CWQY	Discovery agent	N.A.	Investigative	[19]
RO-316233	DMAGLPW	Discovery agent	N.A.	Investigative	[20]
Ro-32-0557	DMPVKEA	Discovery agent	N.A.	Investigative	[8]
Ro31-8220	DMDJLF0	Discovery agent	N.A.	Investigative	[15]
STAUROSPORINONE	DMU2H4K	Discovery agent	N.A.	Investigative	[15]
TANNIN	DMTFHRI	Discovery agent	N.A.	Investigative	[19]
[2,2':5',2'']Terthiophen-4-yl-methanol	DMRQC1F	Discovery agent	N.A.	Investigative	[21]
[2,2':5',2'']Terthiophene-4,5''-dicarbaldehyde	DMWDNLI	Discovery agent	N.A.	Investigative	[21]
[2,2':5',2'']Terthiophene-4-carbaldehyde	DM2S5EJ	Discovery agent	N.A.	Investigative	[21]
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⏷ Show the Full List of 39 Investigative Drug(s)

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