Gene/Proteome Database (LMPD)

LMPD ID
LMP002945
Gene ID
5580
Species
Homo sapiens (Human)
Gene Name
protein kinase C, delta
Gene Symbol
PRKCD
Synonyms
ALPS3; CVID9; MAY1; PKCD; nPKC-delta
Alternate Names
protein kinase C delta type; protein kinase C delta VIII; tyrosine-protein kinase PRKCD
Chromosome
3
Map Location
3p21.31
EC Number
2.7.11.13
Summary
Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and the second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play distinct roles in cells. The protein encoded by this gene is one of the PKC family members. Studies both in human and mice demonstrate that this kinase is involved in B cell signaling and in the regulation of growth, apoptosis, and differentiation of a variety of cell types. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]
Orthologs
View orthologs and multiple alignments for PRKCD

Proteins

protein kinase C delta type
Refseq ID NP_006245
Protein GI 31377782
UniProt ID Q05655
mRNA ID NM_006254
Length 676
RefSeq Status REVIEWED
MAPFLRIAFNSYELGSLQAEDEANQPFCAVKMKEALSTERGKTLVQKKPTMYPEWKSTFDAHIYEGRVIQIVLMRAAEEPVSEVTVGVSVLAERCKKNNGKAEFWLDLQPQAKVLMSVQYFLEDVDCKQSMRSEDEAKFPTMNRRGAIKQAKIHYIKNHEFIATFFGQPTFCSVCKDFVWGLNKQGYKCRQCNAAIHKKCIDKIIGRCTGTAANSRDTIFQKERFNIDMPHRFKVHNYMSPTFCDHCGSLLWGLVKQGLKCEDCGMNVHHKCREKVANLCGINQKLLAEALNQVTQRASRRSDSASSEPVGIYQGFEKKTGVAGEDMQDNSGTYGKIWEGSSKCNINNFIFHKVLGKGSFGKVLLGELKGRGEYFAIKALKKDVVLIDDDVECTMVEKRVLTLAAENPFLTHLICTFQTKDHLFFVMEFLNGGDLMYHIQDKGRFELYRATFYAAEIMCGLQFLHSKGIIYRDLKLDNVLLDRDGHIKIADFGMCKENIFGESRASTFCGTPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRWITKESKDILEKLFEREPTKRLGVTGNIKIHPFFKTINWTLLEKRRLEPPFRPKVKSPRDYSNFDQEFLNEKARLSYSDKNLIDSMDQSAFAGFSFVNPKFEHLLED
protein kinase C delta type
Refseq ID NP_997704
Protein GI 47157325
UniProt ID Q05655
mRNA ID NM_212539
Length 676
RefSeq Status REVIEWED
Protein sequence is identical to GI:31377782 (mRNA isoform)

Gene Information

Entrez Gene ID
5580
Gene Name
protein kinase C, delta
Gene Symbol
PRKCD
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0005911 IEA:Ensembl C cell-cell junction
GO:0005737 IDA:UniProtKB C cytoplasm
GO:0005829 IDA:UniProtKB C cytosol
GO:0005783 IDA:UniProtKB C endoplasmic reticulum
GO:0070062 IDA:UniProt C extracellular vesicular exosome
GO:0005739 IEA:UniProtKB-KW C mitochondrion
GO:0016363 IEA:Ensembl C nuclear matrix
GO:0005654 TAS:Reactome C nucleoplasm
GO:0005634 IDA:UniProtKB C nucleus
GO:0005886 IDA:UniProtKB C plasma membrane
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0004699 TAS:BHF-UCL F calcium-independent protein kinase C activity
GO:0008047 IDA:UniProtKB F enzyme activator activity
GO:0019899 IPI:UniProtKB F enzyme binding
GO:0043560 ISS: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 ISS:UniProtKB F protein kinase C activity
GO:0004674 IDA:UniProtKB F protein serine/threonine kinase activity
GO:0042100 IEA:Ensembl P B cell proliferation
GO:0038096 TAS:Reactome P Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0016070 TAS:Reactome P RNA metabolic process
GO:0007202 TAS:Reactome P activation of phospholipase C activity
GO:0006915 IDA:UniProtKB P apoptotic process
GO:0007596 TAS:Reactome P blood coagulation
GO:0007049 IEA:UniProtKB-KW P cell cycle
GO:0006921 TAS:Reactome P cellular component disassembly involved in execution phase of apoptosis
GO:0090398 IMP:BHF-UCL P cellular senescence
GO:0019221 TAS:Reactome P cytokine-mediated signaling pathway
GO:0042742 ISS:UniProtKB P defense response to bacterium
GO:0007173 TAS:Reactome P epidermal growth factor receptor signaling pathway
GO:0008543 TAS:Reactome P fibroblast growth factor receptor signaling pathway
GO:0010467 TAS:Reactome P gene expression
GO:0016064 IEA:Ensembl P immunoglobulin mediated immune response
GO:0045087 TAS:Reactome P innate immune response
GO:0060333 TAS:Reactome P interferon-gamma-mediated signaling pathway
GO:0032613 IEA:Ensembl P interleukin-10 production
GO:0032615 IEA:Ensembl P interleukin-12 production
GO:0008631 TAS:ParkinsonsUK-UCL P intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0016071 TAS:Reactome P mRNA metabolic process
GO:0043407 IMP:BHF-UCL P negative regulation of MAP kinase activity
GO:0030837 ISS:UniProtKB P negative regulation of actin filament polymerization
GO:0051490 ISS:UniProtKB P negative regulation of filopodium assembly
GO:0034351 IMP:UniProtKB P negative regulation of glial cell apoptotic process
GO:0050728 IC:BHF-UCL P negative regulation of inflammatory response
GO:0046627 ISS:BHF-UCL P negative regulation of insulin receptor signaling pathway
GO:0050732 ISS:BHF-UCL P negative regulation of peptidyl-tyrosine phosphorylation
GO:0090331 ISS:UniProtKB P negative regulation of platelet aggregation
GO:0032091 TAS:BHF-UCL P negative regulation of protein binding
GO:0048011 TAS:Reactome P neurotrophin TRK receptor signaling pathway
GO:0042119 IDA:UniProtKB P neutrophil activation
GO:0018107 IDA:UniProtKB P peptidyl-threonine phosphorylation
GO:0030168 TAS:Reactome P platelet activation
GO:2001235 IEA:Ensembl P positive regulation of apoptotic signaling pathway
GO:2000304 IMP:BHF-UCL P positive regulation of ceramide biosynthetic process
GO:2000753 IMP:BHF-UCL P positive regulation of glucosylceramide catabolic process
GO:1900163 IMP:UniProtKB P positive regulation of phospholipid scramblase activity
GO:0035307 IMP:BHF-UCL P positive regulation of protein dephosphorylation
GO:2001022 IMP:UniProtKB P positive regulation of response to DNA damage stimulus
GO:2000755 IMP:BHF-UCL P positive regulation of sphingomyelin catabolic process
GO:0032930 IMP:UniProtKB P positive regulation of superoxide anion generation
GO:0006468 IDA:UniProtKB P protein phosphorylation
GO:0050821 NAS:UniProtKB P protein stabilization
GO:0010469 TAS:BHF-UCL P regulation of receptor activity
GO:0007165 TAS:Reactome P signal transduction
GO:0023021 IMP:BHF-UCL P termination of signal transduction

KEGG Pathway Links

KEGG Pathway ID Description
hsa04915 Estrogen signaling pathway
hsa04750 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_HUMAN
UniProt ID
Q05655
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q05655-1; Sequence=Displayed; Name=2; Synonyms=PKCdeltaVIII; IsoId=Q05655-2; Sequence=VSP_043899; Note=Antiapoptotic isoform, resistant to caspase-3 cleavage.;
Catalytic Activity ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO
Catalytic Activity ATP + a protein = ADP + a phosphoprotein.
Disease Immunodeficiency, common variable, 9 (CVID9) [MIM
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.
Enzyme Regulation 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).
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 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).
Interaction Q9NR28:DIABLO; NbExp=4; IntAct=EBI-704279, EBI-517508; P06241:FYN; NbExp=5; IntAct=EBI-704279, EBI-515315; P17677:GAP43; NbExp=4; IntAct=EBI-704279, EBI-1267511; C6GKH1:IL32; NbExp=3; IntAct=EBI-704279, EBI-9547476; P24001-2:IL32; NbExp=3; IntAct=EBI-704279, EBI-8800907;
Ptm Autophosphorylated and/or phosphorylated at Thr-507, within the activation loop; phosphorylation at Thr-507 is not a prerequisite for enzymatic activity. Autophosphorylated at Ser- 299, Ser-302 and Ser-304. 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-313, Tyr-334 and Tyr-567; phosphorylation of Tyr-313 and Tyr-567 following thrombin stimulation potentiates its kinase activity. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. {ECO
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. Cytoplasm, perinuclear region. Nucleus. Endoplasmic reticulum. Mitochondrion. Cell membrane; Peripheral membrane protein.
Subunit Interacts with PDPK1 (via N-terminal region), RAD9A, CDCP1, MUC1 and VASP. {ECO
Web Resource Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PRKCDID42901ch3p21.html";

Identical and Related Proteins

Unique RefSeq proteins for LMP002945 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
31377782 RefSeq NP_006245 676 protein kinase C delta type

Identical Sequences to LMP002945 proteins

Reference Database Accession Length Protein Name
GI:31377782 GenBank ADM03573.1 676 Sequence 168 from patent US 7727958
GI:31377782 GenBank AGV86231.1 676 Sequence 168 from patent US 8524673
GI:31377782 GenBank AHD71057.1 676 Sequence 4525 from patent US 8586006
GI:31377782 GenBank AHD71058.1 676 Sequence 4526 from patent US 8586006
GI:31377782 RefSeq XP_006713321.1 676 PREDICTED: protein kinase C delta type isoform X2 [Homo sapiens]
GI:31377782 RefSeq XP_006713322.1 676 PREDICTED: protein kinase C delta type isoform X3 [Homo sapiens]

Related Sequences to LMP002945 proteins

Reference Database Accession Length Protein Name
GI:31377782 DBBJ BAG36031.1 676 unnamed protein product [Homo sapiens]
GI:31377782 GenBank ACM86077.1 684 Sequence 11575 from patent US 6812339
GI:31377782 GenBank JAA06636.1 676 protein kinase C, delta [Pan troglodytes]
GI:31377782 GenBank JAA06637.1 676 protein kinase C, delta [Pan troglodytes]
GI:31377782 RefSeq XP_004034353.1 676 PREDICTED: protein kinase C delta type [Gorilla gorilla gorilla]
GI:31377782 RefSeq XP_006713320.1 692 PREDICTED: protein kinase C delta type isoform X1 [Homo sapiens]