Gene/Proteome Database (LMPD)
LMPD ID
LMP012917
Gene ID
Species
Rattus norvegicus (Rat)
Gene Name
protein kinase C, delta
Gene Symbol
Synonyms
Pkcd;
Alternate Names
protein kinase C delta type; nPKC-delta;
Chromosome
16
Map Location
16p16
EC Number
2.7.11.13
Summary
mediates mitochondrial-dependent apoptosis [RGD, Feb 2006]
Orthologs
Proteins
| protein kinase C delta type | |
|---|---|
| Refseq ID | NP_579841 |
| Protein GI | 18959250 |
| UniProt ID | P09215 |
| mRNA ID | NM_133307 |
| Length | 673 |
| MAPFLRISFNSYELGSLQAEDDASQPFCAVKMKEALTTDRGKTLVQKKPTMYPEWKSTFDAHIYEGRVIQIVLMRAAEDPMSEVTVGVSVLAERCKKNNGKAEFWLDLQPQAKVLMCVQYFLEDGDCKQSMRSEEEAMFPTMNRRGAIKQAKIHYIKNHEFIATFFGQPTFCSVCKEFVWGLNKQGYKCRQCNAAIHKKCIDKIIGRCTGTATNSRDTIFQKERFNIDMPHRFKVYNYMSPTFCDHCGTLLWGLVKQGLKCEDCGMNVHHKCREKVANLCGINQKLLAEALNQVTQKASRKPETPETVGIYQGFEKKTAVSGNDIPDNNGTYGKIWEGSNRCRLENFTFQKVLGKGSFGKVLLAELKGKERYFAIKYLKKDVVLIDDDVECTMVEKRVLALAWENPFLTHLICTFQTKDHLFFVMEFLNGGDLMFHIQDKGRFELYRATFYAAEIICGLQFLHGKGIIYRDLKLDNVMLDKDGHIKIADFGMCKENIFGENRASTFCGTPDYIAPEILQGLKYSFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDIMEKLFERDPAKRLGVTGNIRLHPFFKTINWNLLEKRKVEPPFKPKVKSPSDYSNFDPEFLNEKPQLSFSDKNLIDSMDQTAFKGFSFVNPKYEQFLE | |
Gene Information
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005737 | IDA:RGD | C | cytoplasm |
| GO:0005829 | IDA:RGD | C | cytosol |
| GO:0005783 | ISS:UniProtKB | C | endoplasmic reticulum |
| GO:0016020 | IDA:RGD | C | membrane |
| GO:0005739 | IDA:RGD | C | mitochondrion |
| GO:0005634 | IDA:RGD | C | nucleus |
| GO:0005886 | IDA:RGD | C | plasma membrane |
| GO:0005524 | IEA:UniProtKB-KW | F | ATP binding |
| GO:0070976 | IPI:BHF-UCL | F | TIR domain binding |
| GO:0004699 | IDA:RGD | F | calcium-independent protein kinase C activity |
| GO:0046872 | IEA:UniProtKB-KW | F | metal ion binding |
| GO:0004697 | ISS:UniProtKB | F | protein kinase C activity |
| GO:0019901 | IPI:RGD | F | protein kinase binding |
| GO:0007568 | IEP:RGD | P | aging |
| GO:0006915 | IEA:UniProtKB-KW | P | apoptotic process |
| GO:0015810 | IMP:RGD | P | aspartate transport |
| GO:0007049 | IEA:UniProtKB-KW | P | cell cycle |
| GO:0042149 | IEP:RGD | P | cellular response to glucose starvation |
| GO:0032869 | IEP:RGD | P | cellular response to insulin stimulus |
| GO:0032963 | IMP:RGD | P | collagen metabolic process |
| GO:0042742 | ISS:UniProtKB | P | defense response to bacterium |
| GO:0035556 | IDA:RGD | P | intracellular signal transduction |
| GO:0030837 | ISS:UniProtKB | P | negative regulation of actin filament polymerization |
| GO:0051490 | ISS:UniProtKB | P | negative regulation of filopodium assembly |
| GO:0034351 | ISS:UniProtKB | P | negative regulation of glial cell apoptotic process |
| GO:0090331 | ISS:UniProtKB | P | negative regulation of platelet aggregation |
| GO:0043406 | IMP:RGD | P | positive regulation of MAP kinase activity |
| GO:0043410 | IMP:RGD | P | positive regulation of MAPK cascade |
| GO:0043065 | IMP:RGD | P | positive regulation of apoptotic process |
| GO:0046326 | IMP:RGD | P | positive regulation of glucose import |
| GO:0032930 | ISS:UniProtKB | P | positive regulation of superoxide anion generation |
| GO:0046777 | IDA:RGD | P | protein autophosphorylation |
| GO:0006468 | IDA:RGD | P | protein phosphorylation |
| GO:0043200 | IEP:RGD | P | response to amino acid |
| GO:0042493 | IEP:RGD | P | response to drug |
| GO:0045471 | IEP:RGD | P | response to ethanol |
| GO:0009749 | IEP:RGD | P | response to glucose |
| GO:0009408 | IEP:RGD | P | response to heat |
| GO:0042542 | IEP:RGD | P | response to hydrogen peroxide |
| GO:0001666 | IEP:RGD | P | response to hypoxia |
| GO:0009612 | IEP:RGD | P | response to mechanical stimulus |
| GO:0014070 | IEP:RGD | P | response to organic cyclic compound |
| GO:0010243 | IEP:RGD | P | response to organonitrogen compound |
| GO:0006979 | IMP:RGD | P | response to oxidative stress |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| ko04062 | Chemokine signaling pathway |
| rno04062 | Chemokine signaling pathway |
| ko04915 | Estrogen signaling pathway |
| rno04915 | Estrogen signaling pathway |
| ko04664 | Fc epsilon RI signaling pathway |
| rno04664 | Fc epsilon RI signaling pathway |
| ko04666 | Fc gamma R-mediated phagocytosis |
| rno04666 | Fc gamma R-mediated phagocytosis |
| ko04912 | GnRH signaling pathway |
| rno04912 | GnRH signaling pathway |
| ko04750 | Inflammatory mediator regulation of TRP channels |
| rno04750 | Inflammatory mediator regulation of TRP channels |
| ko04722 | Neurotrophin signaling pathway |
| rno04722 | Neurotrophin signaling pathway |
| ko04530 | Tight junction |
| rno04530 | Tight junction |
| ko04930 | Type II diabetes mellitus |
| rno04930 | Type II diabetes mellitus |
| ko04270 | Vascular smooth muscle contraction |
| rno04270 | Vascular smooth muscle contraction |
Domain Information
InterPro Annotations
| Accession | Description |
|---|---|
| IPR000961 | AGC-kinase, C-terminal |
| IPR000008 | C2 domain |
| IPR020454 | Diacylglycerol/phorbol-ester binding |
| IPR027436 | Protein kinase C, delta |
| IPR014376 | Protein kinase C, delta/epsilon/eta/theta types |
| IPR002219 | Protein kinase C-like, phorbol ester/diacylglycerol-binding domain |
| IPR000719 | Protein kinase domain |
| IPR017441 | Protein kinase, ATP binding site |
| IPR017892 | Protein kinase, C-terminal |
| IPR011009 | Protein kinase-like domain |
| IPR008271 | Serine/threonine-protein kinase, active site |
| IPR002290 | Serine/threonine/dual specificity protein kinase, catalytic domain |
UniProt Annotations
Entry Information
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=PKC-delta-I; IsoId=P09215-1; Sequence=Displayed; Name=2; Synonyms=PKC-delta-III; IsoId=P09215-2; Sequence=VSP_004742; |
| Catalytic Activity | ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE- ProRule:PRU10027}. |
| Catalytic Activity | ATP + a protein = ADP + a phosphoprotein. |
| Domain | The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor. |
| Domain | The C2 domain is a non-calcium binding domain. It binds proteins containing phosphotyrosine in a sequence-specific manner (By similarity) |
| Enzyme Regulation | 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 |
| 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, 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) |
| Function | Truncated isoform 2 is inactive. |
| Ptm | 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. {ECO:0000250, ECO:0000269|PubMed:12855683, ECO:0000269|PubMed:16396499, ECO:0000269|PubMed:17562707, ECO:0000269|PubMed:17569658, ECO:0000269|PubMed:18550549, ECO:0000269|PubMed:9677322}. |
| Ptm | Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation |
| Similarity | Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily |
| Similarity | Contains 1 AGC-kinase C-terminal domain |
| Similarity | Contains 1 C2 domain |
| Similarity | Contains 1 protein kinase domain |
| Similarity | Contains 2 phorbol-ester/DAG-type zinc fingers |
| Subcellular Location | Cytoplasm . Nucleus . Cytoplasm, perinuclear region . Endoplasmic reticulum {ECO:0000250}. Mitochondrion . Membrane ; Peripheral membrane protein . |
| Subunit | Interacts with PDPK1 (via N-terminal region), RAD9A, CDCP1, MUC1 and VASP |
Identical and Related Proteins
Unique RefSeq proteins for LMP012917 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 18959250 | RefSeq | NP_579841 | 673 | protein kinase C delta type |
Identical Sequences to LMP012917 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:18959250 | GenBank | AAA41871.1 | 673 | protein kinase C delta subspecies [Rattus sp.] |
| GI:18959250 | SwissProt | P09215.1 | 673 | RecName: Full=Protein kinase C delta type; AltName: Full=nPKC-delta; Contains: RecName: Full=Protein kinase C delta type regulatory subunit; Contains: RecName: Full=Protein kinase C delta type catalytic subunit; AltName: Full=Sphingosine-dependent protein kinase-1; Short=SDK1 [Rattus norvegicus] |
Related Sequences to LMP012917 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:18959250 | GenBank | AAA41871.1 | 673 | protein kinase C delta subspecies [Rattus sp.] |
| GI:18959250 | GenBank | AAH76505.1 | 673 | Prkcd protein [Rattus norvegicus] |
| GI:18959250 | SwissProt | P09215.1 | 673 | RecName: Full=Protein kinase C delta type; AltName: Full=nPKC-delta; Contains: RecName: Full=Protein kinase C delta type regulatory subunit; Contains: RecName: Full=Protein kinase C delta type catalytic subunit; AltName: Full=Sphingosine-dependent protein kinase-1; Short=SDK1 [Rattus norvegicus] |