PRKCD - Protein kinase C delta type - human protein (Function)
 
Home Recent activites arrow-down favorite My favorites arrow-down favorite My labels arrow-down Downloads
Back to ...  
Publication View
Protein
Gene
References

 
PRKCD »  Protein kinase C delta type   [ EC 2.7.11.13 ]
 
Protein also known as:  Tyrosine-protein kinase PRKCD [EC 2.7.10.2]. Cleaved into:  Protein kinase C delta type catalytic subunit; Protein kinase C delta type regulatory subunit.
Gene name:  PRKCD
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 379 2
GENE REF ISO

Function

 show evidences
Overview 
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).  
6
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Calcium-independent protein kinase C activitydefinition[GO:0004699]  
1
  • TASBHF-UCL
Enzyme activator activitydefinition[GO:0008047]  
1
  • IDAUniProtKB
Enzyme bindingdefinition[GO:0019899]  
2
  • IPIBHF-UCL
  • IPIUniProtKB
Insulin receptor substrate bindingdefinition[GO:0043560]  
  • ISSOrtholog Curator
Metal ion bindingdefinition[GO:0046872]  
  • IEAUniProtKB KW
Non-membrane spanning protein tyrosine kinase activitydefinition[GO:0004715]  
  • IEAEC 2 GO
Protein bindingdefinition[GO:0005515]  
8
  • IPIIntAct
  • IPIUniProtKB
Protein C-terminus bindingdefinition[GO:0008022]  
1
  • IPIUniProtKB
Protein kinase C activitydefinition[GO:0004697]  
  • ISSOrtholog Curator
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • IDAUniProtKB
GO biological process 
Apoptotic processdefinition[GO:0006915]  
1
  • IDAUniProtKB
B cell proliferationdefinition[GO:0042100] silver  
  • IEAOrtholog Compara
Cell cycledefinition[GO:0007049]  
  • IEAUniProtKB KW
Cellular senescencedefinition[GO:0090398]  
1
  • IMPBHF-UCL
Defense response to bacteriumdefinition[GO:0042742]  
  • ISSOrtholog Curator
Immunoglobulin mediated immune responsedefinition[GO:0016064] silver  
  • IEAOrtholog Compara
Interleukin-10 productiondefinition[GO:0032613] silver  
  • IEAOrtholog Compara
Interleukin-12 productiondefinition[GO:0032615] silver  
  • IEAOrtholog Compara
Intracellular signal transductiondefinition[GO:0035556] silver  
  • IEAInterPro 2 GO
Negative regulation of actin filament polymerizationdefinition[GO:0030837]  
  • ISSOrtholog Curator
Negative regulation of filopodium assemblydefinition[GO:0051490]  
  • ISSOrtholog Curator
Negative regulation of glial cell apoptotic processdefinition[GO:0034351]  
1
  • IMPUniProtKB
Negative regulation of inflammatory responsedefinition[GO:0050728]  
1
  • ICBHF-UCL
Negative regulation of insulin receptor signaling pathwaydefinition[GO:0046627]  
1
  • TASBHF-UCL
  • ISSOrtholog Curator
Negative regulation of MAP kinase activitydefinition[GO:0043407]  
1
  • IMPBHF-UCL
Negative regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050732]  
1
  • ISSBHF-UCL
Negative regulation of platelet aggregationdefinition[GO:0090331]  
  • ISSOrtholog Curator
Negative regulation of protein bindingdefinition[GO:0032091]  
1
  • TASBHF-UCL
Neutrophil activationdefinition[GO:0042119]  
1
  • IDAUniProtKB
Peptidyl-threonine phosphorylationdefinition[GO:0018107]  
1
  • IDAUniProtKB
Positive regulation of apoptotic signaling pathwaydefinition[GO:2001235] silver  
  • IEAOrtholog Compara
Positive regulation of ceramide biosynthetic processdefinition[GO:2000304]  
1
  • IMPBHF-UCL
Positive regulation of glucosylceramide catabolic processdefinition[GO:2000753]  
1
  • IMPBHF-UCL
Positive regulation of phospholipid scramblase activitydefinition[GO:1900163]  
1
  • IMPUniProtKB
Positive regulation of protein dephosphorylationdefinition[GO:0035307]  
1
  • IMPBHF-UCL
Positive regulation of response to DNA damage stimulusdefinition[GO:2001022]  
1
  • IMPUniProtKB
Positive regulation of sphingomyelin catabolic processdefinition[GO:2000755]  
1
  • IMPBHF-UCL
Positive regulation of superoxide anion generationdefinition[GO:0032930]  
1
  • IMPUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Protein stabilizationdefinition[GO:0050821]  
1
  • NASUniProtKB
Regulation of receptor activitydefinition[GO:0010469]  
1
  • TASBHF-UCL
Termination of signal transductiondefinition[GO:0023021]  
1
  • IMPBHF-UCL
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.11.13: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
EC 2.7.10.2: ATP + a [protein]-L-tyrosine ADP + a [protein]-L-tyrosine phosphate.  
  • CuratedUniProtKB
It is regulated in the following manner
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).  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Chemokine signaling pathway  hsa04062+5580  
Fc epsilon RI signaling pathway  hsa04664+5580  
Fc gamma R-mediated phagocytosis  hsa04666+5580  
GnRH signaling pathway  hsa04912+5580  
Neurotrophin signaling pathway  hsa04722+5580  
Tight junction  hsa04530+5580  
Type II diabetes mellitus  hsa04930+5580  
Vascular smooth muscle contraction  hsa04270+5580  
According to Reactome, this protein belongs to the following pathways:
Apoptosis  REACT_578  
Disease  REACT_116125  
Gene Expression  REACT_71  
Hemostasis  REACT_604  
Immune System  REACT_6900  
Metabolism of RNA  REACT_21257  
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Apoptosis  definition   [KW-0053]
Cell cycle  definition   [KW-0131]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: PRKCD
GenomeRNAi: 5580
PRO: PR:Q05655
Chemistry
GuidetoPHARMACOLOGY: 1485