Q5PU49 (KPCD_CANFA) Reviewed, UniProtKB/Swiss-Prot
Last modified November 13, 2013. Version 88. History...
Names and origin
|Protein names||Recommended name:|
Protein kinase C delta type
Tyrosine-protein kinase PRKCD
|Organism||Canis familiaris (Dog) (Canis lupus familiaris) [Reference proteome]|
|Taxonomic identifier||9615 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Carnivora › Caniformia › Canidae › Canis ›|
|Sequence length||674 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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, is required for oxygen radical production by NADPH oxidase and acts as positive or negative regulator in platelet functional responses. 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. 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 By similarity. The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent fashion By similarity.
ATP + a protein = ADP + a phosphoprotein.
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-505 (activation loop of the kinase domain), Ser-643 (turn motif) and Ser-662 (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.
Interacts with PDPK1 (via N-terminus region), RAD9A, CDCP1, MUC1 and VASP By similarity.
Cytoplasm By similarity. Cytoplasm › perinuclear region By similarity. Nucleus By similarity. Endoplasmic reticulum By similarity. Mitochondrion By similarity. Membrane; Peripheral membrane protein By similarity.
The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor.
The C2 domain is a non-calcium binding domain. It binds proteins containing phosphotyrosine in a sequence-specific manner By similarity.
Autophosphorylated and/or phosphorylated at Thr-505, within the activation loop; phosphorylation at Thr-505 is not a prerequisite for enzymatic activity. Autophosphorylated at Ser-299 and Ser-302. Upon TNFSF10/TRAIL treatment, phosphorylated at Tyr-155; phosphorylation is required for its translocation to the endoplasmic reticulum and cleavage by caspase-3. Phosphorylated at Tyr-310, Tyr-332 and Tyr-565; phosphorylation of Tyr-310 and Tyr-565 following thrombin stimulation potentiates its kinase activity. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2 By similarity.
Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation By similarity.
Contains 1 AGC-kinase C-terminal domain.
Contains 1 C2 domain.
Contains 2 phorbol-ester/DAG-type zinc fingers.
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 674||674||Protein kinase C delta type||PRO_0000055693|
|Chain||1 – 328||328||Protein kinase C delta type regulatory subunit By similarity||PRO_0000421665|
|Chain||329 – 674||346||Protein kinase C delta type catalytic subunit By similarity||PRO_0000421666|
|Domain||1 – 90||90||C2|
|Domain||347 – 601||255||Protein kinase|
|Domain||602 – 673||72||AGC-kinase C-terminal|
|Zinc finger||158 – 208||51||Phorbol-ester/DAG-type 1|
|Zinc finger||230 – 280||51||Phorbol-ester/DAG-type 2|
|Nucleotide binding||353 – 361||9||ATP By similarity|
|Active site||471||1||Proton acceptor By similarity|
|Binding site||376||1||ATP By similarity|
|Site||48||1||Interaction with phosphotyrosine-containing peptide By similarity|
|Site||62||1||Interaction with phosphotyrosine-containing peptide By similarity|
|Site||67||1||Interaction with phosphotyrosine-containing peptide By similarity|
|Site||123||1||Interaction with phosphotyrosine-containing peptide By similarity|
|Site||328 – 329||2||Cleavage; by caspase-3 By similarity|
Amino acid modifications
|Modified residue||43||1||Phosphothreonine By similarity|
|Modified residue||64||1||Phosphotyrosine By similarity|
|Modified residue||130||1||Phosphoserine By similarity|
|Modified residue||155||1||Phosphotyrosine By similarity|
|Modified residue||218||1||Phosphothreonine By similarity|
|Modified residue||299||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||302||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||310||1||Phosphotyrosine; by SRC By similarity|
|Modified residue||332||1||Phosphotyrosine; by SRC By similarity|
|Modified residue||505||1||Phosphothreonine; by autocatalysis By similarity|
|Modified residue||565||1||Phosphotyrosine By similarity|
|Modified residue||643||1||Phosphoserine Probable|
|Modified residue||652||1||Phosphoserine By similarity|
|Modified residue||662||1||Phosphoserine By similarity|
|AY825360 mRNA. Translation: AAV80465.1.|
|RefSeq||NP_001008716.1. NM_001008716.1. |
3D structure databases
|SMR||Q5PU49. Positions 149-218, 227-283, 344-666. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
Family and domain databases
|InterPro||IPR000961. AGC-kinase_C. |
|Pfam||PF00130. C1_1. 2 hits. |
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
|PIRSF||PIRSF000551. PKC_delta. 1 hit. |
PIRSF501104. Protein_kin_C_delta. 1 hit.
|PRINTS||PR00008. DAGPEDOMAIN. |
|SMART||SM00109. C1. 2 hits. |
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
|SUPFAM||SSF49562. SSF49562. 1 hit. |
SSF56112. SSF56112. 1 hit.
|PROSITE||PS51285. AGC_KINASE_CTER. 1 hit. |
PS50004. C2. False negative.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 2 hits.
PS50081. ZF_DAG_PE_2. 2 hits.
|Accession||Primary (citable) accession number: Q5PU49|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families