Gene/Proteome Database (LMPD)

LMPD ID
LMP001139
Gene ID
Species
Mus musculus (Mouse)
Gene Name
protein kinase C, delta
Gene Symbol
Synonyms
AI385711; D14Ertd420e; PKC[d]; PKCdelta; Pkcd
Alternate Names
protein kinase C delta type; nPKC-delta; protein kinase C[d]; protein kinase C, delta V; protein kinase C, delta IV; tyrosine-protein kinase PRKCD; protein kinase C delta variant IX
Chromosome
14
Map Location
14 B|14 18.82 cM
EC Number
2.7.11.13

Proteins

protein kinase C delta type
Refseq ID NP_035233
Protein GI 6755082
UniProt ID P28867
mRNA ID NM_011103
Length 674
RefSeq Status VALIDATED
MAPFLRISFNSYELGSLQVEDEASQPFCAVKMKEALSTERGKTLVQKKPTMYPEWKTTFDAHIYEGRVIQIVLMRAAEDPVSEVTVGVSVLAERCKKNNGKAEFWLDLQPQAKVLMCVQYFLEDGDCKQSMRSEEEAKFPTMNRRGAIKQAKIHYIKNHEFIATFFGQPTFCSVCKEFVWGLNKQGYKCRQCNAAIHKKCIDKIIGRCTGTATNSRDTIFQKERFNIDMPHRFKVYNYMSPTFCDHCGSLLWGLVKQGLKCEDCGMNVHHKCREKVANLCGINQKLLAEALNQVTQRSSRKLDTTESVGIYQGFEKKPEVSGSDILDNNGTYGKIWEGSTRCTLENFTFQKVLGKGSFGKVLLAELKGKDKYFAIKCLKKDVVLIDDDVECTMVEKRVLALAWESPFLTHLICTFQTKDHLFFVMEFLNGGDLMFHIQDKGRFELYRATFYAAEIICGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKENIFGEGRASTFCGTPDYIAPEILQGLKYSFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDIMEKLFERDPDKRLGVTGNIRIHPFFKTINWSLLEKRKVEPPFKPKVKSPSDYSNFDPEFLNEKPQLSFSDKNLIDSMDQEAFHGFSFVNPKFEQFLDI
mat_peptide: 1..327 product: Protein kinase C delta type regulatory subunit (By similarity) inference: non-experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P28867.3) calculated_mol_wt: 37291 peptide sequence: MAPFLRISFNSYELGSLQVEDEASQPFCAVKMKEALSTERGKTLVQKKPTMYPEWKTTFDAHIYEGRVIQIVLMRAAEDPVSEVTVGVSVLAERCKKNNGKAEFWLDLQPQAKVLMCVQYFLEDGDCKQSMRSEEEAKFPTMNRRGAIKQAKIHYIKNHEFIATFFGQPTFCSVCKEFVWGLNKQGYKCRQCNAAIHKKCIDKIIGRCTGTATNSRDTIFQKERFNIDMPHRFKVYNYMSPTFCDHCGSLLWGLVKQGLKCEDCGMNVHHKCREKVANLCGINQKLLAEALNQVTQRSSRKLDTTESVGIYQGFEKKPEVSGSDILD mat_peptide: 328..674 product: Protein kinase C delta type catalytic subunit (By similarity) inference: non-experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (P28867.3) calculated_mol_wt: 40274 peptide sequence: NNGTYGKIWEGSTRCTLENFTFQKVLGKGSFGKVLLAELKGKDKYFAIKCLKKDVVLIDDDVECTMVEKRVLALAWESPFLTHLICTFQTKDHLFFVMEFLNGGDLMFHIQDKGRFELYRATFYAAEIICGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKENIFGEGRASTFCGTPDYIAPEILQGLKYSFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDIMEKLFERDPDKRLGVTGNIRIHPFFKTINWSLLEKRKVEPPFKPKVKSPSDYSNFDPEFLNEKPQLSFSDKNLIDSMDQEAFHGFSFVNPKFEQFLDI

Gene Information

Entrez Gene ID
Gene Name
protein kinase C, delta
Gene Symbol
Species
Mus musculus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005911 IDA:MGI C cell-cell junction
GO:0005737 IDA:MGI C cytoplasm
GO:0005829 IEA:Ensembl C cytosol
GO:0005783 ISS:UniProtKB C endoplasmic reticulum
GO:0070062 IEA:Ensembl C extracellular vesicular exosome
GO:0005739 IEA:UniProtKB-KW C mitochondrion
GO:0016363 IDA:MGI C nuclear matrix
GO:0005634 IDA:MGI C nucleus
GO:0005886 IEA:Ensembl C plasma membrane
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0008047 IEA:Ensembl F enzyme activator activity
GO:0043560 IPI:BHF-UCL F insulin receptor substrate binding
GO:0046872 IEA:UniProtKB-KW F metal ion binding
GO:0004715 IEA:UniProtKB-EC F non-membrane spanning protein tyrosine kinase activity
GO:0004697 IDA:UniProtKB F protein kinase C activity
GO:0042100 IMP:MGI P B cell proliferation
GO:0006915 IEA:UniProtKB-KW P apoptotic process
GO:0007049 IEA:UniProtKB-KW P cell cycle
GO:0090398 IEA:Ensembl P cellular senescence
GO:0042742 IMP:UniProtKB P defense response to bacterium
GO:0016064 IMP:MGI P immunoglobulin mediated immune response
GO:0032613 IMP:MGI P interleukin-10 production
GO:0032615 IMP:MGI P interleukin-12 production
GO:0035556 IEA:InterPro P intracellular signal transduction
GO:0043407 IEA:Ensembl P negative regulation of MAP kinase activity
GO:0030837 IMP:UniProtKB P negative regulation of actin filament polymerization
GO:0051490 IMP:UniProtKB P negative regulation of filopodium assembly
GO:0034351 ISS:UniProtKB P negative regulation of glial cell apoptotic process
GO:0046627 IMP:BHF-UCL P negative regulation of insulin receptor signaling pathway
GO:0050732 IMP:BHF-UCL P negative regulation of peptidyl-tyrosine phosphorylation
GO:0090331 IMP:UniProtKB P negative regulation of platelet aggregation
GO:0042119 IEA:Ensembl P neutrophil activation
GO:0018107 IEA:Ensembl P peptidyl-threonine phosphorylation
GO:2001235 IDA:MGI P positive regulation of apoptotic signaling pathway
GO:2000304 IEA:Ensembl P positive regulation of ceramide biosynthetic process
GO:2000753 IEA:Ensembl P positive regulation of glucosylceramide catabolic process
GO:1900163 IEA:Ensembl P positive regulation of phospholipid scramblase activity
GO:0035307 IEA:Ensembl P positive regulation of protein dephosphorylation
GO:2001022 IEA:Ensembl P positive regulation of response to DNA damage stimulus
GO:2000755 IEA:Ensembl P positive regulation of sphingomyelin catabolic process
GO:0032930 ISS:UniProtKB P positive regulation of superoxide anion generation
GO:0023021 IEA:Ensembl P termination of signal transduction

KEGG Pathway Links

KEGG Pathway ID Description
mmu04915 Estrogen signaling pathway
mmu04750 Inflammatory mediator regulation of TRP channels

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

Gene Name
protein kinase C, delta
Protein Entry
KPCD_MOUSE
UniProt ID
Species
Mouse

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=PKC-delta-I; IsoId=P28867-1; Sequence=Displayed; Name=2; Synonyms=PKC-delta-II; IsoId=P28867-2; Sequence=VSP_004741;
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.
Disruption Phenotype Mice are viable up to 1 year despite detection of auto-immune disease in these animals. They exhibit glomerulonephritis, splenomegaly and lymphadenopathy associated with B-cell expansion and defective B-cell tolerance to self- antigen. {ECO:0000269|PubMed:11976687}.
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). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
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. 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. 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. {ECO:0000269|PubMed:11976686, ECO:0000269|PubMed:11976687, ECO:0000269|PubMed:18025218, ECO:0000269|PubMed:19917613, ECO:0000269|PubMed:9705322}.
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). {ECO:0000250}.
Ptm Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation. {ECO:0000250}.
Similarity Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. {ECO:0000305}.
Similarity Contains 1 AGC-kinase C-terminal domain. {ECO:0000305}.
Similarity Contains 1 C2 domain. {ECO:0000305}.
Similarity Contains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
Similarity Contains 2 phorbol-ester/DAG-type zinc fingers. {ECO:0000255|PROSITE-ProRule:PRU00226}.
Subcellular Location Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear region {ECO:0000250}. Nucleus {ECO:0000250}. Endoplasmic reticulum {ECO:0000250}. Mitochondrion {ECO:0000250}. Membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}.
Subunit Interacts with PDPK1 (via N-terminal region), RAD9A, CDCP1, MUC1 and VASP. {ECO:0000250}.
Tissue Specificity Isoform 1 is highly expressed in developing pro- and pre-B-cells and moderately in mature T-cells. Isoform 2 is highly expressed in testis and ovary and at a lower level in thymocytes, brain and kidney.

Identical and Related Proteins

Unique RefSeq proteins for LMP001139 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
6755082 RefSeq NP_035233 674 protein kinase C delta type

Identical Sequences to LMP001139 proteins

Reference Database Accession Length Protein Name
GI:6755082 EMBL CAA42845.1 674 protein kinase [Mus musculus]
GI:6755082 GenBank AAF64316.1 674 protein kinase C delta [Mus musculus]
GI:6755082 GenBank AAF79208.1 674 PKC delta [Mus musculus]
GI:6755082 GenBank AAS57795.1 674 protein kinase C delta [Mus musculus]
GI:6755082 GenBank ABK42346.1 674 protein kinase C delta1 [synthetic construct]
GI:6755082 SwissProt P28867.3 674 RecName: Full=Protein kinase C delta type; AltName: Full=Tyrosine-protein kinase PRKCD; 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 [Mus musculus]

Related Sequences to LMP001139 proteins

Reference Database Accession Length Protein Name
GI:6755082 DBBJ BAE25785.1 674 unnamed protein product [Mus musculus]
GI:6755082 DBBJ BAE40604.1 674 unnamed protein product [Mus musculus]
GI:6755082 GenBank AAA73056.1 674 unnamed protein product [Mus musculus domesticus]
GI:6755082 GenBank EDL24758.1 678 protein kinase C, delta, isoform CRA_a, partial [Mus musculus]
GI:6755082 RefSeq XP_006518758.1 700 PREDICTED: protein kinase C delta type isoform X1 [Mus musculus]
GI:6755082 RefSeq XP_006518759.1 700 PREDICTED: protein kinase C delta type isoform X2 [Mus musculus]