P09215 (KPCD_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified June 11, 2014. Version 163. History...
Names and origin
|Protein names||Recommended name:|
Protein kinase C delta type
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||673 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein 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.
Truncated isoform 2 is inactive.
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. Ref.8
Interacts with PDPK1 (via N-terminal region), RAD9A, CDCP1, MUC1 and VASP 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. 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-311, Tyr-332 and Tyr-565; phosphorylation of Tyr-311 and Tyr-565 following thrombin stimulation potentiates its kinase activity. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2 By similarity. Phosphorylated at Tyr-311 and Tyr-332 by SRC; phosphorylation leads to enhanced autophosphorylation at Thr-505. Ref.7 Ref.10 Ref.11 Ref.12
Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation. Ref.8
Contains 1 AGC-kinase C-terminal domain.
Contains 1 C2 domain.
Contains 2 phorbol-ester/DAG-type zinc fingers.
Contains 1 protein kinase domain.
|This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]|
|Isoform 1 (identifier: P09215-1) |
Also known as: PKC-delta-I;
This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
|Isoform 2 (identifier: P09215-2) |
Also known as: PKC-delta-III;
The sequence of this isoform differs from the canonical sequence as follows:
327-673: DNNGTYGKIW...VNPKYEQFLE → GESGSHIPLK...AALARYCLQN
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 673||673||Protein kinase C delta type||PRO_0000055696|
|Chain||1 – 327||327||Protein kinase C delta type regulatory subunit||PRO_0000421671|
|Chain||328 – 673||346||Protein kinase C delta type catalytic subunit||PRO_0000421672|
|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||327 – 328||2||Cleavage; by caspase-3 Probable|
Amino acid modifications
|Modified residue||43||1||Phosphothreonine By similarity|
|Modified residue||64||1||Phosphotyrosine Ref.10|
|Modified residue||130||1||Phosphoserine By similarity|
|Modified residue||155||1||Phosphotyrosine Ref.10|
|Modified residue||218||1||Phosphothreonine By similarity|
|Modified residue||299||1||Phosphoserine; by autocatalysis By similarity|
|Modified residue||311||1||Phosphotyrosine; by SRC Ref.12|
|Modified residue||332||1||Phosphotyrosine; by SRC Ref.12|
|Modified residue||372||1||Phosphotyrosine By similarity|
|Modified residue||505||1||Phosphothreonine; by autocatalysis Ref.7 Ref.11 Ref.12|
|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 Ref.9|
|Alternative sequence||327 – 673||347||DNNGT…EQFLE → GESGSHIPLKLPFPDRAREK NSSETWDKTTTGPMARSGRG ATGAALRTSPSRKYLAKAAL ARYCLQN in isoform 2.||VSP_004742|
|Mutagenesis||505||1||T → A: Decrease in the phosphorylation level. Ref.7|
|Sequence conflict||147||1||A → S AA sequence Ref.6|
|Sequence conflict||249||1||T → S in CAB75578. Ref.2|
|Sequence conflict||249||1||T → S in AAH76505. Ref.4|
Helix Strand Turn
|Beta strand||3 – 13||11|
|Beta strand||27 – 35||9|
|Helix||38 – 40||3|
|Beta strand||43 – 46||4|
|Beta strand||58 – 62||5|
|Beta strand||68 – 76||9|
|Beta strand||79 – 87||9|
|Helix||88 – 96||9|
|Turn||97 – 100||4|
|Beta strand||101 – 107||7|
|Beta strand||109 – 111||3|
|Beta strand||113 – 122||10|
|||"The structure, expression, and properties of additional members of the protein kinase C family."|
Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y.
J. Biol. Chem. 263:6927-6932(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
|||"Genomic structure and chromosomal localization of the rat PKCdelta-gene."|
Kurkinen K.M.A., Keinanen R.A., Karhu R., Koistinaho J.
Gene 242:115-123(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: Wistar Kyoto.
|||"cDNA cloning of an alternative splicing variant of protein kinase C delta (PKC deltaIII), a new truncated form of PKCdelta, in rats."|
Ueyama T., Ren Y., Ohmori S., Sakai K., Tamaki N., Saito N.
Biochem. Biophys. Res. Commun. 269:557-563(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
|||"Identification of three additional members of rat protein kinase C family: delta-, epsilon- and zeta-subspecies."|
Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y.
FEBS Lett. 226:125-128(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 123-286.
|||"Expression and characterization of protein kinase C-delta."|
Olivier A.R., Parker P.J.
Eur. J. Biochem. 200:805-810(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 142-153.
|||"The broad specificity of dominant inhibitory protein kinase C mutants infers a common step in phosphorylation."|
Garcia-Paramio P., Cabrerizo Y., Bornancin F., Parker P.J.
Biochem. J. 333:631-636(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF THR-505, PHOSPHORYLATION AT THR-505.
|||"Sphingosine-dependent protein kinase-1, directed to 14-3-3, is identified as the kinase domain of protein kinase C delta."|
Hamaguchi A., Suzuki E., Murayama K., Fujimura T., Hikita T., Iwabuchi K., Handa K., Withers D.A., Masters S.C., Fu H., Hakomori S.
J. Biol. Chem. 278:41557-41565(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, CLEAVAGE BY CASPASE-3, ENZYME REGULATION.
|||"Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS."|
Moser K., White F.M.
J. Proteome Res. 5:98-104(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
|||"Induction of apoptosis is driven by nuclear retention of protein kinase C delta."|
DeVries-Seimon T.A., Ohm A.M., Humphries M.J., Reyland M.E.
J. Biol. Chem. 282:22307-22314(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-64 AND TYR-155.
|||"Protein kinase Cepsilon (PKCepsilon) and Src control PKCdelta activation loop phosphorylation in cardiomyocytes."|
Rybin V.O., Guo J., Gertsberg Z., Elouardighi H., Steinberg S.F.
J. Biol. Chem. 282:23631-23638(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-505.
|||"Tyrosine phosphorylation modifies protein kinase C delta-dependent phosphorylation of cardiac troponin I."|
Sumandea M.P., Rybin V.O., Hinken A.C., Wang C., Kobayashi T., Harleton E., Sievert G., Balke C.W., Feinmark S.J., Solaro R.J., Steinberg S.F.
J. Biol. Chem. 283:22680-22689(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-311; TYR-332 AND THR-505.
|||"Crystal structure of the C2 domain from protein kinase C-delta."|
Pappa H., Murray-Rust J., Dekker L.V., Parker P.J., McDonald N.Q.
Structure 6:885-894(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-123.
|+||Additional computationally mapped references.|
|M18330 mRNA. Translation: AAA41871.1.|
AJ230617 AJ230633 Genomic DNA. Translation: CAB75578.1.
AF219629 mRNA. Translation: AAF32345.1.
BC076505 mRNA. Translation: AAH76505.1.
|PIR||KIRTCD. A28163. |
|RefSeq||NP_579841.1. NM_133307.1. [P09215-1]|
3D structure databases
|SMR||P09215. Positions 1-123, 149-218, 227-283, 343-666. |
Protein-protein interaction databases
|BioGrid||250924. 8 interactions.|
|IntAct||P09215. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|UCSC||RGD:67383. rat. [P09215-1]|
|RGD||67383. Prkcd. |
Enzyme and pathway databases
|BRENDA||184.108.40.206. 5301. |
Gene expression databases
Family and domain databases
|Gene3D||220.127.116.11. 1 hit. |
|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. |
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: P09215|
Secondary accession number(s): Q6DG48, Q9JK29, Q9JL03
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|