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Names & Taxonomy

Uniprot ID:: Q05655
Entry Name:: KPCD_HUMAN
Status:: reviewed
Protein Names:: Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)]
Gene Names:: PRKCD
Gene Names Primary:: PRKCD
Organism:: Homo sapiens (Human)

Structure

Length:: 676
Sequence:: MAPFLRIAFNSYELGSLQAEDEANQPFCAVKMKEALSTERGKTLVQKKPTMYPEWKSTFDAHIYEGRVIQIVLMRAAEEPVSEVTVGVSVLAERCKKNNGKAEFWLDLQPQAKVLMSVQYFLEDVDCKQSMRSEDEAKFPTMNRRGAIKQAKIHYIKNHEFIATFFGQPTFCSVCKDFVWGLNKQGYKCRQCNAAIHKKCIDKIIGRCTGTAANSRDTIFQKERFNIDMPHRFKVHNYMSPTFCDHCGSLLWGLVKQGLKCEDCGMNVHHKCREKVANLCGINQKLLAEALNQVTQRASRRSDSASSEPVGIYQGFEKKTGVAGEDMQDNSGTYGKIWEGSSKCNINNFIFHKVLGKGSFGKVLLGELKGRGEYFAIKALKKDVVLIDDDVECTMVEKRVLTLAAENPFLTHLICTFQTKDHLFFVMEFLNGGDLMYHIQDKGRFELYRATFYAAEIMCGLQFLHSKGIIYRDLKLDNVLLDRDGHIKIADFGMCKENIFGESRASTFCGTPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDILEKLFEREPTKRLGVTGNIKIHPFFKTINWTLLEKRRLEPPFRPKVKSPRDYSNFDQEFLNEKARLSYSDKNLIDSMDQSAFAGFSFVNPKFEHLLED
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cytoplasm

Function

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. Negatively regulates B cell proliferation and also has an important function in self-antigen induced B cell tolerance induction. Upon DNA damage, activates the promoter of the death-promoting transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In response to oxidative stress, interact with and activate CHUK/IKKA in the nucleus, causing the phosphorylation of p53/TP53. 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. 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. Can protect glioma cells from the apoptosis induced by TNFSF10/TRAIL, probably by inducing increased phosphorylation and subsequent activation of AKT1. 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). 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. May also play a role in the regulation of NADPH oxidase activity in eosinophil after stimulation with IL5, leukotriene B4 or PMA. In collagen-induced platelet aggregation, acts a negative regulator of filopodia formation and actin polymerization by interacting with and negatively regulating VASP phosphorylation. 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. Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin. 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).
Catalytic Activity:: ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:: ENZYME REGULATION: Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-507 (activation loop of the kinase domain), Ser-645 (turn motif) and Ser-664 (hydrophobic region), need to be phosphorylated for its full activation. Activated by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the pseudosubstrate motif in the regulatory subunit is released from the substrate recognition site of the catalytic subunit, which enables PRKCD to become constitutively activated. The catalytic subunit which displays properties of a sphingosine-dependent protein kinase is activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS), but not by ceramide or Sph-1-P and is strongly inhibited by phosphatidylserine (By similarity).
Active Site:: ACT_SITE 473 473 Proton acceptor.
Cross Reference Drug Bank:: DB05013 DB00675
Gene Ontology Go:: cell-cell junction
cytoplasm
cytosol
endoplasmic reticulum
extracellular exosome
nuclear matrix
nucleoplasm
nucleus
perinuclear region of cytoplasm
plasma membrane
ATP binding
calcium-independent protein kinase C activity
enzyme activator activity
enzyme binding
insulin receptor substrate binding
kinase binding
metal ion binding
non-membrane spanning protein tyrosine kinase activity
protein kinase activity
protein kinase binding
protein kinase C activity
protein serine/threonine kinase activity
activation of phospholipase C activity
activation of protein kinase activity
apoptotic process
B cell proliferation
blood coagulation
cell chemotaxis
cell cycle
cellular component disassembly involved in execution phase of apoptosis
cellular response to angiotensin
cellular response to hydrogen peroxide
cellular response to hydroperoxide
cellular senescence
cytokine-mediated signaling pathway
defense response to bacterium
epidermal growth factor receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
fibroblast growth factor receptor signaling pathway
gene expression
histone phosphorylation
immunoglobulin mediated immune response
innate immune response
interferon-gamma-mediated signaling pathway
interleukin-10 production
interleukin-12 production
intrinsic apoptotic signaling pathway in response to oxidative stress
negative regulation of actin filament polymerization
negative regulation of filopodium assembly
negative regulation of glial cell apoptotic process
negative regulation of inflammatory response
negative regulation of insulin receptor signaling pathway
negative regulation of MAP kinase activity
negative regulation of peptidyl-tyrosine phosphorylation
negative regulation of platelet aggregation
negative regulation of protein binding
neurotrophin TRK receptor signaling pathway
neutrophil activation
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
platelet activation
positive regulation of apoptotic signaling pathway
positive regulation of ceramide biosynthetic process
positive regulation of endodeoxyribonuclease activity
positive regulation of glucosylceramide catabolic process
positive regulation of phospholipid scramblase activity
positive regulation of protein dephosphorylation
positive regulation of protein import into nucleus
positive regulation of response to DNA damage stimulus
positive regulation of sphingomyelin catabolic process
positive regulation of superoxide anion generation
programmed cell death
protein phosphorylation
protein stabilization
regulation of actin cytoskeleton organization
regulation of mRNA stability
regulation of receptor activity
signal transduction
stimulatory C-type lectin receptor signaling pathway
termination of signal transduction
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Biological Process:: activation of phospholipase C activity
activation of protein kinase activity
apoptotic process
B cell proliferation
blood coagulation
cell chemotaxis
cell cycle
cellular component disassembly involved in execution phase of apoptosis
cellular response to angiotensin
cellular response to hydrogen peroxide
cellular response to hydroperoxide
cellular senescence
cytokine-mediated signaling pathway
defense response to bacterium
epidermal growth factor receptor signaling pathway
Fc-gamma receptor signaling pathway involved in phagocytosis
fibroblast growth factor receptor signaling pathway
gene expression
histone phosphorylation
immunoglobulin mediated immune response
innate immune response
interferon-gamma-mediated signaling pathway
interleukin-10 production
interleukin-12 production
intrinsic apoptotic signaling pathway in response to oxidative stress
negative regulation of actin filament polymerization
negative regulation of filopodium assembly
negative regulation of glial cell apoptotic process
negative regulation of inflammatory response
negative regulation of insulin receptor signaling pathway
negative regulation of MAP kinase activity
negative regulation of peptidyl-tyrosine phosphorylation
negative regulation of platelet aggregation
negative regulation of protein binding
neurotrophin TRK receptor signaling pathway
neutrophil activation
peptidyl-serine phosphorylation
peptidyl-threonine phosphorylation
platelet activation
positive regulation of apoptotic signaling pathway
positive regulation of ceramide biosynthetic process
positive regulation of endodeoxyribonuclease activity
positive regulation of glucosylceramide catabolic process
positive regulation of phospholipid scramblase activity
positive regulation of protein dephosphorylation
positive regulation of protein import into nucleus
positive regulation of response to DNA damage stimulus
positive regulation of sphingomyelin catabolic process
positive regulation of superoxide anion generation
programmed cell death
protein phosphorylation
protein stabilization
regulation of actin cytoskeleton organization
regulation of mRNA stability
regulation of receptor activity
signal transduction
stimulatory C-type lectin receptor signaling pathway
termination of signal transduction
vascular endothelial growth factor receptor signaling pathway
Gene Ontology Molecular Function:: ATP binding
calcium-independent protein kinase C activity
enzyme activator activity
enzyme binding
insulin receptor substrate binding
kinase binding
metal ion binding
non-membrane spanning protein tyrosine kinase activity
protein kinase activity
protein kinase binding
protein kinase C activity
protein serine/threonine kinase activity
Gene Ontology Cellular Component:: cell-cell junction
cytoplasm
cytosol
endoplasmic reticulum
extracellular exosome
nuclear matrix
nucleoplasm
nucleus
perinuclear region of cytoplasm
plasma membrane
Keywords:: 3D-structure
ATP-binding
Alternative splicing
Apoptosis
Cell cycle
Cell membrane
Complete proteome
Cytoplasm
Kinase
Membrane
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Serine/threonine-protein kinase
Transferase
Tumor suppressor
Zinc
Zinc-finger
Interacts With:: Q9NR28; P06241; P17677; C6GKH1; P24001-2; P19878; P11388; P04637; Q9H3D4

Names & Taxonomy

Structure

Subcellular location

Function

Publication