General Information of Drug Therapeutic Target (DTT) (ID: TT8QL1J)

DTT Name Protein kinase C theta (PRKCQ)
Synonyms Protein kinase C theta type; PRKCT; NPKC-theta
Gene Name PRKCQ
DTT Type
Clinical trial target
[1]
BioChemical Class
Kinase
UniProt ID
KPCT_HUMAN
TTD ID
T23995
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.7.11.13
Sequence
MSPFLRIGLSNFDCGSCQSCQGEAVNPYCAVLVKEYVESENGQMYIQKKPTMYPPWDSTF
DAHINKGRVMQIIVKGKNVDLISETTVELYSLAERCRKNNGKTEIWLELKPQGRMLMNAR
YFLEMSDTKDMNEFETEGFFALHQRRGAIKQAKVHHVKCHEFTATFFPQPTFCSVCHEFV
WGLNKQGYQCRQCNAAIHKKCIDKVIAKCTGSAINSRETMFHKERFKIDMPHRFKVYNYK
SPTFCEHCGTLLWGLARQGLKCDACGMNVHHRCQTKVANLCGINQKLMAEALAMIESTQQ
ARCLRDTEQIFREGPVEIGLPCSIKNEARPPCLPTPGKREPQGISWESPLDEVDKMCHLP
EPELNKERPSLQIKLKIEDFILHKMLGKGSFGKVFLAEFKKTNQFFAIKALKKDVVLMDD
DVECTMVEKRVLSLAWEHPFLTHMFCTFQTKENLFFVMEYLNGGDLMYHIQSCHKFDLSR
ATFYAAEIILGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKENMLGDAKTNTFC
GTPDYIAPEILLGQKYNHSVDWWSFGVLLYEMLIGQSPFHGQDEEELFHSIRMDNPFYPR
WLEKEAKDLLVKLFVREPEKRLGVRGDIRQHPLFREINWEELERKEIDPPFRPKVKSPFD
CSNFDKEFLNEKPRLSFADRALINSMDQNMFRNFSFMNPGMERLIS
Function
In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates in the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1. Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2.
KEGG Pathway
NF-kappa B signaling pathway (hsa04064 )
Vascular smooth muscle contraction (hsa04270 )
Tight junction (hsa04530 )
T cell receptor signaling pathway (hsa04660 )
Inflammatory mediator regulation of TRP channels (hsa04750 )
Adipocytokine signaling pathway (hsa04920 )
Measles (hsa05162 )
Reactome Pathway
Effects of PIP2 hydrolysis (R-HSA-114508 )
Inactivation, recovery and regulation of the phototransduction cascade (R-HSA-2514859 )
FCERI mediated NF-kB activation (R-HSA-2871837 )
G alpha (z) signalling events (R-HSA-418597 )
Apoptotic cleavage of cellular proteins (R-HSA-111465 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
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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3 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
CDE-6960 DMA0DKI Inflammation 1A00-CA43.1 Terminated [2]
LY-317644 DMM20PI N. A. N. A. Terminated [3]
RO-320432 DMFZ1YW N. A. N. A. Terminated [4]
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16 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
2,3,3-Triphenyl-acrylonitrile DM7H34U Discovery agent N.A. Investigative [5]
2-(4-Hydroxy-phenyl)-3,3-diphenyl-acrylonitrile DMNGW1A Discovery agent N.A. Investigative [5]
3,3-Bis-(4-hydroxy-phenyl)-2-phenyl-acrylonitrile DMO51QG Discovery agent N.A. Investigative [5]
3,3-Bis-(4-methoxy-phenyl)-2-phenyl-acrylonitrile DMZPYN2 Discovery agent N.A. Investigative [5]
3-(4-Hydroxy-phenyl)-2,3-diphenyl-acrylonitrile DME5238 Discovery agent N.A. Investigative [5]
4-cycloheptyliden(4-hydroxyphenyl)methylphenol DM4LIUC Discovery agent N.A. Investigative [5]
4-cyclohexyliden(4-hydroxyphenyl)methylphenol DM8BLK2 Discovery agent N.A. Investigative [5]
4-[1-(4-hydroxyphenyl)-3-methyl-1-butenyl]phenol DM8IYG1 Discovery agent N.A. Investigative [5]
L-serine-O-phosphate DMTJ1NH Discovery agent N.A. Investigative [6]
LY-326449 DMN53M4 Discovery agent N.A. Investigative [7]
Phosphonothreonine DMTFHPI Discovery agent N.A. Investigative [6]
RO-316233 DMAGLPW Discovery agent N.A. Investigative [8]
Ro-32-0557 DMPVKEA Discovery agent N.A. Investigative [4]
[2,2':5',2'']Terthiophen-4-yl-methanol DMRQC1F Discovery agent N.A. Investigative [9]
[2,2':5',2'']Terthiophene-4,5''-dicarbaldehyde DMWDNLI Discovery agent N.A. Investigative [9]
[2,2':5',2'']Terthiophene-4-carbaldehyde DM2S5EJ Discovery agent N.A. Investigative [9]
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⏷ Show the Full List of 16 Investigative Drug(s)

Molecular Expression Atlas (MEA) of This DTT

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DTT
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Breast cancer 2C82 Breast tissue 6.55E-09 0.05 0.16
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References

1 Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.
2 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800025002)
3 Synthesis of bisindolylmaleimide macrocycles, Bioorg. Med. Chem. Lett. 5(18):2093-2096 (1995).
4 Bisindolylmaleimide inhibitors of protein kinase C. Further conformational restriction of a tertiary amine side chain, Bioorg. Med. Chem. Lett. 4(11):1303-1308 (1994).
5 Multivariate analysis by the minimum spanning tree method of the structural determinants of diphenylethylenes and triphenylacrylonitriles implicate... J Med Chem. 1992 Feb 7;35(3):573-83.
6 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
7 (S)-13-[(dimethylamino)methyl]-10,11,14,15-tetrahydro-4,9:16, 21-dimetheno-1H, 13H-dibenzo[e,k]pyrrolo[3,4-h][1,4,13]oxadiazacyclohexadecene-1,3(2H... J Med Chem. 1996 Jul 5;39(14):2664-71.
8 Inhibitors of protein kinase C. 1. 2,3-Bisarylmaleimides. J Med Chem. 1992 Jan;35(1):177-84.
9 Novel protein kinase C inhibitors: synthesis and PKC inhibition of beta-substituted polythiophene derivatives. Bioorg Med Chem Lett. 1999 Aug 2;9(15):2279-82.