General Information of the Protein
Protein ID
PT01364
Protein Name
Protein kinase C delta type
Secondarily
Protein Name
Tyrosine-protein kinase PRKCD
nPKC-delta
Sphingosine-dependent protein kinase-1
Gene Name
PRKCD
Secondarily
Gene Name
PKCD
Sequence
MAPFLRIAFNSYELGSLQAEDEANQPFCAVKMKEALSTERGKTLVQKKPTMYPEWKSTFDAHIYEGRVIQIVLMRAAEEPVSEVTVGVSVLAERCKKNNGKAEFWLDLQPQAKVLMSVQYFLEDVDCKQSMRSEDEAKFPTMNRRGAIKQAKIHYIKNHEFIATFFGQPTFCSVCKDFVWGLNKQGYKCRQCNAAIHKKCIDKIIGRCTGTAANSRDTIFQKERFNIDMPHRFKVHNYMSPTFCDHCGSLLWGLVKQGLKCEDCGMNVHHKCREKVANLCGINQKLLAEALNQVTQRASRRSDSASSEPVGIYQGFEKKTGVAGEDMQDNSGTYGKIWEGSSKCNINNFIFHKVLGKGSFGKVLLGELKGRGEYFAIKALKKDVVLIDDDVECTMVEKRVLTLAAENPFLTHLICTFQTKDHLFFVMEFLNGGDLMYHIQDKGRFELYRATFYAAEIMCGLQFLHSKGIIYRDLKLDNVLLDRDGHIKIADFGMCKENIFGESRASTFCGTPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDILEKLFEREPTKRLGVTGNIKIHPFFKTINWTLLEKRRLEPPFRPKVKSPRDYSNFDQEFLNEKARLSYSDKNLIDSMDQSAFAGFSFVNPKFEHLLED
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
AGC protein kinase group
>
AGC protein kinase PKC family
>
AGC protein kinase PKC delta subfamily
Function
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression as well as survival of several cancers, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses (PubMed:21810427, PubMed:21406692). Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction (By similarity). Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis (PubMed:21810427, PubMed:21406692). In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53 (PubMed:21810427, PubMed:21406692). In the case of ER stress or DNA damage-induced apoptosis, can form a complex with the tyrosine-protein kinase ABL1 which trigger apoptosis independently of p53/TP53 (PubMed:21810427, PubMed:21406692). In cytosol can trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is required for the activation of the apoptosis regulators BAX and BAK, which trigger the mitochondrial cell death pathway. Can phosphorylate MCL1 and target it for degradation which is sufficient to trigger for BAX activation and apoptosis. Is required for the control of cell cycle progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2 promoter activity. In response to UV irradiation can phosphorylate CDK1, which is important for the G2/M DNA damage checkpoint activation (By similarity). Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1 (PubMed:15774464). Is highly expressed in a number of cancer cells and promotes cell survival and resistance against chemotherapeutic drugs by inducing cyclin D1 (CCND1) and hyperphosphorylation of RB1, and via several pro-survival pathways, including NF-kappa-B, AKT1 and MAPK1/3 (ERK1/2). Involved in antifungal immunity by mediating phosphorylation and activation of CARD9 downstream of C-type lectin receptors activation, promoting interaction between CARD9 and BCL10, followed by activation of NF-kappa-B and MAP kinase p38 pathways (By similarity). Can also act as tumor suppressor upon mitogenic stimulation with PMA or TPA. In N-formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase activity, and regulates TNF-elicited superoxide anion production in neutrophils, by direct phosphorylation and activation of NCF1 or indirectly through MAPK1/3 (ERK1/2) signaling pathways (PubMed:19801500). May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA (PubMed:11748588). In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation (PubMed:16940418). Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates differentially platelet dense granule secretion; acts as a positive regulator in PAR-mediated granule secretion, whereas it negatively regulates CD36/GP4-mediated granule release (PubMed:19587372). Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin (PubMed:11877440). The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion (By similarity). Phosphorylates ELAVL1 in response to angiotensin-2 treatment (PubMed:18285462). Phosphorylates mitochondrial phospholipid scramblase 3 (PLSCR3), resulting in increased cardiolipin expression on the mitochondrial outer membrane which facilitates apoptosis (PubMed:12649167). Phosphorylates SMPD1 which induces SMPD1 secretion (PubMed:17303575).
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Uniprot ID
Primary ID:
Q05655

Secondarily ID:
B0KZ81
B2R834
Q15144
Q86XJ6
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Ensembl ID
ENSG00000163932
HGNC ID
HGNC:9399
Subcellular Location
Cytoplasm
Cytoplasm
Perinuclear region
Nucleus
Cell membrane
Mitochondrion
Endomembrane system
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000013 , Sf9
Compound ID Compound Name Compound Formula
CP0040070
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-[(4-hydroxybenzene)amido]cyclopentyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid
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C27H23NO10
 1
1
IC50 = 0.9 nM
   TI
   LI
   LO
   TS
CP0040333
2-{[2,6-dihydroxy-4-({[(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid
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C26H22N2O10
 1
1
IC50 = 5 nM
   TI
   LI
   LO
   TS
CP0398629
(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl 4-{[2-({[(2,2-dimethylpropanoyl)oxy]methoxy}carbonyl)-6-hydroxyphenyl]carbonyl}-3,5-dihydroxybenzoate
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C32H32N2O12
 1
1
IC50 = 10 nM
   TI
   LI
   LO
   TS
CP0495469
(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl 3,5-dihydroxy-4-{[2-hydroxy-6-(methoxycarbonyl)phenyl]carbonyl}benzoate
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C27H24N2O10
 1
1
IC50 = 18 nM
   TI
   LI
   LO
   TS
CP0372635
(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl 4-[(2-{[(acetyloxy)methoxy]carbonyl}-6-hydroxyphenyl)carbonyl]-3,5-dihydroxybenzoate
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C29H26N2O12
 1
1
IC50 = 24 nM
   TI
   LI
   LO
   TS
CP0038373
2-{[2,6-dihydroxy-4-({[(3R,4R)-3-[(4-hydroxybenzene)amido]azepan-4-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid
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C28H26N2O10
 1
1
IC50 = 32 nM
   TI
   LI
   LO
   TS
CP0405218
(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl 4-{[2-(ethoxycarbonyl)-6-hydroxyphenyl]carbonyl}-3,5-dihydroxybenzoate
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C28H26N2O10
 1
1
IC50 = 50 nM
   TI
   LI
   LO
   TS
CP0487436
(1R,2R)-2-[(4-hydroxybenzene)amido]cyclopentyl 3,5-dihydroxy-4-({2-hydroxy-6-[(propan-2-yloxy)carbonyl]phenyl}carbonyl)benzoate
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C30H29NO10
 1
1
IC50 = 50 nM
   TI
   LI
   LO
   TS
CP0391277
(1R,2R)-2-[(4-hydroxybenzene)amido]cyclopentyl 4-{[2-(ethoxycarbonyl)-6-hydroxyphenyl]carbonyl}-3,5-dihydroxybenzoate
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C29H27NO10
 1
1
IC50 = 67 nM
   TI
   LI
   LO
   TS
CP0405508
(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl 4-{[2-(butoxycarbonyl)-6-hydroxyphenyl]carbonyl}-3,5-dihydroxybenzoate
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C30H30N2O10
 1
1
IC50 = 80 nM
   TI
   LI
   LO
   TS
CP0419325
(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl 3,5-dihydroxy-4-({2-hydroxy-6-[(2-methylpropoxy)carbonyl]phenyl}carbonyl)benzoate
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C30H30N2O10
 1
1
IC50 = 200 nM
   TI
   LI
   LO
   TS
CP0405497
(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl 4-({2-[(cyclohexylmethoxy)carbonyl]-6-hydroxyphenyl}carbonyl)-3,5-dihydroxybenzoate
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C33H34N2O10
 1
1
IC50 = 310 nM
   TI
   LI
   LO
   TS
CP0410262
[(1S,3S,5Z,7R,8E,11S,12S,13E,15S,17R,21R,23R,25S)-25-acetyloxy-1,11,21-trihydroxy-17-[(1R)-1-hydroxyethyl]-5,13-bis(2-methoxy-2-oxoethylidene)-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.13,7.111,15]nonacos-8-en-12-yl] (2E,4E)-octa-2,4-dienoate
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C47H68O17
 1
1
Ki = 0.44 nM
   TI
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CP0450932
diheptan-3-yl 5-(hydroxymethyl)benzene-1,3-dicarboxylate
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C23H36O5
 1
1
Ki = 529 nM
   TI
   LI
   LO
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CP0498357
bis[[3-(trifluoromethyl)phenyl]methyl] 5-(hydroxymethyl)benzene-1,3-dicarboxylate
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C25H18F6O5
 1
1
Ki = 590 nM
   TI
   LI
   LO
   TS
CP0491085
dihexan-3-yl 5-(hydroxymethyl)benzene-1,3-dicarboxylate
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C21H32O5
 1
1
Ki = 915 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0040070
2-{[2,6-dihydroxy-4-({[(1R,2R)-2-[(4-hydroxybenzene)amido]cyclopentyl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid
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C27H23NO10
 2
1 IC50 = 0.9 nM
2 IC50 = 1 nM
CP0038373
2-{[2,6-dihydroxy-4-({[(3R,4R)-3-[(4-hydroxybenzene)amido]azepan-4-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid
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C28H26N2O10
 4
1 IC50 = 4 nM
2 IC50 = 20 nM
3 IC50 = 30 nM
4 IC50 = 32 nM
CP0040333
2-{[2,6-dihydroxy-4-({[(3R,4R)-4-[(4-hydroxybenzene)amido]pyrrolidin-3-yl]oxy}carbonyl)phenyl]carbonyl}-3-hydroxybenzoic acid
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C26H22N2O10
 1
1 IC50 = 5 nM
CP0645493
Tetradecanoic acid 9a-acetoxy-4a,7b-dihydroxy-3-hydroxymethyl-1,1,6,8-tetramethyl-5-oxo-1a,1b,4,4a,5,7a,7b,8,9,9a-decahydro-1H-cyclopropa[3,4]benzo[1,2-e]azulen-9-yl ester
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C36H56O8
 1
1 Ki = 0.8 nM
Clinical Information about the Protein
Target 1 ( Protein kinase C delta (PRKCD) )
Target Type Clinical trial Target
Disease 1 Target-related Disease  1
1 Human immunodeficiency virus infection [ICD-11: 1C62]
Investigative Drug(s) 1 Investigative Drug  1
1 PROSTRATIN Investigative
Human immunodeficiency virus infection
Target 2 ( PKC-delta messenger RNA (PRKCD mRNA) )
Target Type Literature-reported Target
Disease 1 Target-related Disease  1
1 Human immunodeficiency virus infection [ICD-11: 1C62]
Investigative Drug(s) 1 Investigative Drug  1
1 PROSTRATIN Investigative
Human immunodeficiency virus infection