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Q05655 (KPCD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 162. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein kinase C delta type

EC=2.7.11.13
Alternative name(s):
Tyrosine-protein kinase PRKCD
EC=2.7.10.2
nPKC-delta

Cleaved into the following 2 chains:

  1. Protein kinase C delta type regulatory subunit
  2. Protein kinase C delta type catalytic subunit
    Alternative name(s):
    Sphingosine-dependent protein kinase-1
    Short name=SDK1
Gene names
Name:PRKCD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length676 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.9 Ref.12 Ref.14 Ref.15 Ref.23 Ref.26

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

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.

Subunit structure

Interacts with PDPK1 (via N-terminal region), RAD9A, CDCP1, MUC1 and VASP. Ref.11 Ref.12 Ref.13 Ref.15 Ref.36

Subcellular location

Cytoplasm. Cytoplasmperinuclear region. Nucleus. Endoplasmic reticulum. Mitochondrion. Cell membrane; Peripheral membrane protein Ref.14 Ref.17 Ref.18.

Domain

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.

Post-translational modification

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. Ref.11 Ref.14 Ref.16 Ref.17 Ref.26

Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation By similarity.

Involvement in disease

Immunodeficiency, common variable, 9 (CVID9) [MIM:615559]: A primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen. The defect results from a failure of B-cell differentiation and impaired secretion of immunoglobulins; the numbers of circulating B-cells is usually in the normal range, but can be low. CVID9 patients have B-cell deficiency and severe autoimmunity.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.35

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 C2 domain.

Contains 2 phorbol-ester/DAG-type zinc fingers.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
   Cellular componentCell membrane
Cytoplasm
Endoplasmic reticulum
Membrane
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseTumor suppressor
   DomainRepeat
Zinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell proliferation

Inferred from electronic annotation. Source: Ensembl

Fc-gamma receptor signaling pathway involved in phagocytosis

Traceable author statement. Source: Reactome

RNA metabolic process

Traceable author statement. Source: Reactome

activation of phospholipase C activity

Traceable author statement. Source: Reactome

apoptotic process

Inferred from direct assay PubMed 10770950. Source: UniProtKB

blood coagulation

Traceable author statement. Source: Reactome

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cellular component disassembly involved in execution phase of apoptosis

Traceable author statement. Source: Reactome

cellular senescence

Inferred from mutant phenotype PubMed 15282327. Source: BHF-UCL

cytokine-mediated signaling pathway

Traceable author statement. Source: Reactome

defense response to bacterium

Inferred from sequence or structural similarity. Source: UniProtKB

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

gene expression

Traceable author statement. Source: Reactome

immunoglobulin mediated immune response

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

interferon-gamma-mediated signaling pathway

Traceable author statement. Source: Reactome

interleukin-10 production

Inferred from electronic annotation. Source: Ensembl

interleukin-12 production

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

mRNA metabolic process

Traceable author statement. Source: Reactome

negative regulation of MAP kinase activity

Inferred from mutant phenotype PubMed 19279008. Source: BHF-UCL

negative regulation of actin filament polymerization

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of filopodium assembly

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of glial cell apoptotic process

Inferred from mutant phenotype Ref.14. Source: UniProtKB

negative regulation of inflammatory response

Inferred by curator PubMed 19279008. Source: BHF-UCL

negative regulation of insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of peptidyl-tyrosine phosphorylation

Inferred from sequence or structural similarity PubMed 14583092. Source: BHF-UCL

negative regulation of platelet aggregation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of protein binding

Traceable author statement PubMed 14583092. Source: BHF-UCL

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

neutrophil activation

Inferred from direct assay PubMed 10770950. Source: UniProtKB

peptidyl-threonine phosphorylation

Inferred from direct assay PubMed 10770950. Source: UniProtKB

platelet activation

Traceable author statement. Source: Reactome

positive regulation of apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of ceramide biosynthetic process

Inferred from mutant phenotype PubMed 19279011. Source: BHF-UCL

positive regulation of glucosylceramide catabolic process

Inferred from mutant phenotype PubMed 19279011. Source: BHF-UCL

positive regulation of phospholipid scramblase activity

Inferred from mutant phenotype PubMed 10770950. Source: UniProtKB

positive regulation of protein dephosphorylation

Inferred from mutant phenotype PubMed 19279008. Source: BHF-UCL

positive regulation of response to DNA damage stimulus

Inferred from mutant phenotype PubMed 17938203. Source: UniProtKB

positive regulation of sphingomyelin catabolic process

Inferred from mutant phenotype PubMed 19279011. Source: BHF-UCL

positive regulation of superoxide anion generation

Inferred from mutant phenotype Ref.26. Source: UniProtKB

protein phosphorylation

Inferred from direct assay PubMed 16611985. Source: UniProtKB

protein stabilization

Non-traceable author statement PubMed 16611985. Source: UniProtKB

regulation of receptor activity

Traceable author statement PubMed 14583092. Source: BHF-UCL

signal transduction

Traceable author statement. Source: Reactome

termination of signal transduction

Inferred from mutant phenotype PubMed 19279008. Source: BHF-UCL

   Cellular_componentcell-cell junction

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 15632189PubMed 16611985. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 10770950Ref.14. Source: UniProtKB

endoplasmic reticulum

Inferred from direct assay Ref.14. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867PubMed 23376485. Source: UniProt

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nuclear matrix

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 15632189Ref.14PubMed 16611985. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay PubMed 10770950PubMed 15632189. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calcium-independent protein kinase C activity

Traceable author statement PubMed 14583092. Source: BHF-UCL

enzyme activator activity

Inferred from direct assay PubMed 16611985. Source: UniProtKB

enzyme binding

Inferred from physical interaction PubMed 16611985. Source: UniProtKB

insulin receptor substrate binding

Inferred from sequence or structural similarity. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

non-membrane spanning protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein C-terminus binding

Inferred from physical interaction PubMed 16611985. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10948194Ref.13Ref.15. Source: UniProtKB

protein kinase C activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay PubMed 10770950. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q05655-1)

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: Q05655-2)

Also known as: PKCdeltaVIII;

The sequence of this isoform differs from the canonical sequence as follows:
     328-328: Q → QGEAGSIAPLRFLFPLRPKKGDCPPFHCQVRQ
Note: Antiapoptotic isoform, resistant to caspase-3 cleavage.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 676676Protein kinase C delta type
PRO_0000055694
Chain1 – 329329Protein kinase C delta type regulatory subunit By similarity
PRO_0000421667
Chain330 – 676347Protein kinase C delta type catalytic subunit By similarity
PRO_0000421668

Regions

Domain1 – 9090C2
Domain349 – 603255Protein kinase
Domain604 – 67572AGC-kinase C-terminal
Zinc finger158 – 20851Phorbol-ester/DAG-type 1
Zinc finger230 – 28051Phorbol-ester/DAG-type 2
Nucleotide binding355 – 3639ATP By similarity

Sites

Active site4731Proton acceptor By similarity
Binding site3781ATP By similarity
Site481Interaction with phosphotyrosine-containing peptide
Site621Interaction with phosphotyrosine-containing peptide
Site671Interaction with phosphotyrosine-containing peptide
Site1231Interaction with phosphotyrosine-containing peptide
Site329 – 3302Cleavage; by caspase-3 By similarity

Amino acid modifications

Modified residue431Phosphothreonine By similarity
Modified residue641Phosphotyrosine By similarity
Modified residue1301Phosphoserine Ref.21
Modified residue1551Phosphotyrosine Ref.14
Modified residue2181Phosphothreonine Ref.24
Modified residue2991Phosphoserine; by autocatalysis Ref.17 Ref.20
Modified residue3021Phosphoserine; by autocatalysis Ref.17 Ref.21
Modified residue3041Phosphoserine; by autocatalysis Ref.17 Ref.21 Ref.29 Ref.33
Modified residue3071Phosphoserine Ref.21
Modified residue3131Phosphotyrosine Ref.16 Ref.20 Ref.24 Ref.25
Modified residue3341Phosphotyrosine; by SRC Probable
Modified residue3741Phosphotyrosine Ref.29
Modified residue5031Phosphoserine Ref.20
Modified residue5071Phosphothreonine; by autocatalysis Probable
Modified residue5671Phosphotyrosine Ref.16
Modified residue6451Phosphoserine Ref.26 Ref.29 Ref.33
Modified residue6541Phosphoserine Ref.20
Modified residue6581Phosphoserine Ref.20
Modified residue6641Phosphoserine Ref.20 Ref.21 Ref.24 Ref.25 Ref.29

Natural variations

Alternative sequence3281Q → QGEAGSIAPLRFLFPLRPKK GDCPPFHCQVRQ in isoform 2.
VSP_043899
Natural variant3481N → S.
Corresponds to variant rs33911937 [ dbSNP | Ensembl ].
VAR_035347
Natural variant3751F → S. Ref.1
Corresponds to variant rs1056998 [ dbSNP | Ensembl ].
VAR_006175
Natural variant4101L → F.
Corresponds to variant rs34502209 [ dbSNP | Ensembl ].
VAR_035348
Natural variant4831R → W.
Corresponds to variant rs35891605 [ dbSNP | Ensembl ].
VAR_046009
Natural variant4941M → V. Ref.8
VAR_020610
Natural variant5931V → M. Ref.1
VAR_006176

Experimental info

Mutagenesis2991S → A: Loss of phosphorylation. Ref.17
Mutagenesis5071T → A: No effect on kinase activity. Ref.10
Sequence conflict5241K → R in BAG36031. Ref.2
Sequence conflict5331S → A no nucleotide entry Ref.8

Secondary structure

.................................. 676
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 2, 2008. Version 2.
Checksum: 013F4314A2EE331A

FASTA67677,505
        10         20         30         40         50         60 
MAPFLRIAFN SYELGSLQAE DEANQPFCAV KMKEALSTER GKTLVQKKPT MYPEWKSTFD 

        70         80         90        100        110        120 
AHIYEGRVIQ IVLMRAAEEP VSEVTVGVSV LAERCKKNNG KAEFWLDLQP QAKVLMSVQY 

       130        140        150        160        170        180 
FLEDVDCKQS MRSEDEAKFP TMNRRGAIKQ AKIHYIKNHE FIATFFGQPT FCSVCKDFVW 

       190        200        210        220        230        240 
GLNKQGYKCR QCNAAIHKKC IDKIIGRCTG TAANSRDTIF QKERFNIDMP HRFKVHNYMS 

       250        260        270        280        290        300 
PTFCDHCGSL LWGLVKQGLK CEDCGMNVHH KCREKVANLC GINQKLLAEA LNQVTQRASR 

       310        320        330        340        350        360 
RSDSASSEPV GIYQGFEKKT GVAGEDMQDN SGTYGKIWEG SSKCNINNFI FHKVLGKGSF 

       370        380        390        400        410        420 
GKVLLGELKG RGEYFAIKAL KKDVVLIDDD VECTMVEKRV LTLAAENPFL THLICTFQTK 

       430        440        450        460        470        480 
DHLFFVMEFL NGGDLMYHIQ DKGRFELYRA TFYAAEIMCG LQFLHSKGII YRDLKLDNVL 

       490        500        510        520        530        540 
LDRDGHIKIA DFGMCKENIF GESRASTFCG TPDYIAPEIL QGLKYTFSVD WWSFGVLLYE 

       550        560        570        580        590        600 
MLIGQSPFHG DDEDELFESI RVDTPHYPRW ITKESKDILE KLFEREPTKR LGVTGNIKIH 

       610        620        630        640        650        660 
PFFKTINWTL LEKRRLEPPF RPKVKSPRDY SNFDQEFLNE KARLSYSDKN LIDSMDQSAF 

       670 
AGFSFVNPKF EHLLED 

« Hide

Isoform 2 (PKCdeltaVIII) [UniParc].

Checksum: F1380490CC52EF07
Show »

FASTA70780,953

References

« Hide 'large scale' references
[1]"Molecular and biochemical characterization of a recombinant human PKC-delta family member."
Aris J.P., Basta P.V., Holmes W.D., Ballas L.M., Moomaw C., Rankl N.B., Blobel G., Loomis C.R., Burns D.J.
Biochim. Biophys. Acta 1174:171-181(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS SER-375 AND MET-593.
Tissue: Liver.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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).
Tissue: Skin.
[5]"Partial cDNA Sequence of human protein kinase C delta."
Hug H.
Submitted (MAR-1993) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-365 (ISOFORM 1).
Tissue: Hippocampus.
[6]"Functional analyses of mammalian protein kinase C isozymes in budding yeast and mammalian fibroblasts."
Nomoto S., Watanabe Y., Ninomiya-Tsuji J., Yang L.-X., Kikuchi K., Hagiwara M., Hidaka H., Matsumoto K., Irie K.
Genes Cells 2:601-614(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 51-676 (ISOFORM 1).
[7]"Identification of a novel antiapoptotic human protein kinase C delta isoform, PKCdeltaVIII in NT2 cells."
Jiang K., Apostolatos A.H., Ghansah T., Watson J.E., Vickers T., Cooper D.R., Epling-Burnette P.K., Patel N.A.
Biochemistry 47:787-797(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 224-371 (ISOFORM 2).
[8]"Identification of multiple, novel, protein kinase C-related gene products."
Palmer R.H., Ridden J., Parker P.J.
FEBS Lett. 356:5-8(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 432-533 (ISOFORM 1), VARIANT VAL-494.
[9]"Regulation of human eosinophil NADPH oxidase activity: a central role for PKCdelta."
Bankers-Fulbright J.L., Kita H., Gleich G.J., O'Grady S.M.
J. Cell. Physiol. 189:306-315(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Phosphorylation of the protein kinase C-theta activation loop and hydrophobic motif regulates its kinase activity, but only activation loop phosphorylation is critical to in vivo nuclear-factor-kappaB induction."
Liu Y., Graham C., Li A., Fisher R.J., Shaw S.
Biochem. J. 361:255-265(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF THR-507.
[11]"Regulation of both PDK1 and the phosphorylation of PKC-zeta and -delta by a C-terminal PRK2 fragment."
Hodgkinson C.P., Sale G.J.
Biochemistry 41:561-569(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PDPK1, PHOSPHORYLATION.
[12]"Protein kinase C delta regulates function of the DF3/MUC1 carcinoma antigen in beta-catenin signaling."
Ren J., Li Y., Kufe D.
J. Biol. Chem. 277:17616-17622(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MUC1, FUNCTION.
[13]"Protein kinase Cdelta is responsible for constitutive and DNA damage-induced phosphorylation of Rad9."
Yoshida K., Wang H.-G., Miki Y., Kufe D.
EMBO J. 22:1431-1441(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RAD9A.
[14]"Roles of tyrosine phosphorylation and cleavage of protein kinase Cdelta in its protective effect against tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis."
Okhrimenko H., Lu W., Xiang C., Ju D., Blumberg P.M., Gomel R., Kazimirsky G., Brodie C.
J. Biol. Chem. 280:23643-23652(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-155.
[15]"PKCdelta regulates collagen-induced platelet aggregation through inhibition of VASP-mediated filopodia formation."
Pula G., Schuh K., Nakayama K., Nakayama K.I., Walter U., Poole A.W.
Blood 108:4035-4044(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PLATELET AGGREGATION, INTERACTION WITH VASP.
[16]"Coincident regulation of PKCdelta in human platelets by phosphorylation of Tyr311 and Tyr565 and phospholipase C signalling."
Hall K.J., Jones M.L., Poole A.W.
Biochem. J. 406:501-509(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-313 AND TYR-567.
[17]"Novel phosphorylation site markers of protein kinase C delta activation."
Durgan J., Michael N., Totty N., Parker P.J.
FEBS Lett. 581:3377-3381(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT SER-299; SER-302 AND SER-304, MUTAGENESIS OF SER-299.
[18]"The localization of protein kinase Cdelta in different subcellular sites affects its proapoptotic and antiapoptotic functions and the activation of distinct downstream signaling pathways."
Gomel R., Xiang C., Finniss S., Lee H.K., Lu W., Okhrimenko H., Brodie C.
Mol. Cancer Res. 5:627-639(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[19]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[20]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299; TYR-313; SER-503; SER-654; SER-658 AND SER-664, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130; SER-302; SER-304; SER-307 AND SER-664, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[22]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"Lyn, PKC-delta, SHIP-1 interactions regulate GPVI-mediated platelet-dense granule secretion."
Chari R., Kim S., Murugappan S., Sanjay A., Daniel J.L., Kunapuli S.P.
Blood 114:3056-3063(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PLATELET RESPONSE.
[24]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-218; TYR-313 AND SER-664, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-313 AND SER-664, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[26]"Regulation of TNF-induced oxygen radical production in human neutrophils: role of delta-PKC."
Kilpatrick L.E., Sun S., Li H., Vary T.C., Korchak H.M.
J. Leukoc. Biol. 87:153-164(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF NCF1, PHOSPHORYLATION AT THR-507 AND SER-645.
[27]"Protein kinase C delta (PKC delta): activation mechanisms and functions."
Kikkawa U., Matsuzaki H., Yamamoto T.
J. Biochem. 132:831-839(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[28]"Diverse functions of protein kinase C isoforms in platelet activation and thrombus formation."
Harper M.T., Poole A.W.
J. Thromb. Haemost. 8:454-462(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[29]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304; TYR-374; SER-645 AND SER-664, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[30]"Two faces of protein kinase Cdelta: the contrasting roles of PKCdelta in cell survival and cell death."
Basu A., Pal D.
ScientificWorldJournal 10:2272-2284(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[31]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[32]"PKC-delta and PKC-epsilon: Foes of the same family or strangers?"
Duquesnes N., Lezoualc'h F., Crozatier B.
J. Mol. Cell. Cardiol. 51:665-673(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[33]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304 AND SER-645, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[34]"Protein kinase cdelta in apoptosis: a brief overview."
Zhao M., Xia L., Chen G.Q.
Arch. Immunol. Ther. Exp. 60:361-372(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[35]"B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C delta."
Salzer E., Santos-Valente E., Klaver S., Ban S.A., Emminger W., Prengemann N.K., Garncarz W., Mullauer L., Kain R., Boztug H., Heitger A., Arbeiter K., Eitelberger F., Seidel M.G., Holter W., Pollak A., Pickl W.F., Forster-Waldl E., Boztug K.
Blood 121:3112-3116(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CVID9.
[36]"The C2 domain of PKCdelta is a phosphotyrosine binding domain."
Benes C.H., Wu N., Elia A.E.H., Dharia T., Cantley L.C., Soltoff S.P.
Cell 121:271-280(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-123 IN COMPLEX WITH PHOSPHOTYROSINE-CONTAINING PEPTIDE, INTERACTION WITH CDCP1.
[37]"Solution structure of the first phorbol esters/diacylglycerol binding domain of human protein kinase C, delta."
RIKEN structural genomics initiative (RSGI)
Submitted (APR-2008) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 149-218.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L07860 mRNA. Translation: AAA03176.1.
L07861 mRNA. Translation: AAA03175.1.
AK313216 mRNA. Translation: BAG36031.1.
CH471055 Genomic DNA. Translation: EAW65279.1.
BC043350 mRNA. Translation: AAH43350.1.
Z22521 mRNA. Translation: CAA80249.1.
D10495 mRNA. Translation: BAA01381.1.
DQ516383 mRNA. Translation: ABF68960.1.
CCDSCCDS2870.1. [Q05655-1]
PIRS35704.
RefSeqNP_006245.2. NM_006254.3. [Q05655-1]
NP_997704.1. NM_212539.1. [Q05655-1]
XP_006713321.1. XM_006713258.1. [Q05655-1]
XP_006713322.1. XM_006713259.1. [Q05655-1]
UniGeneHs.155342.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1YRKX-ray1.70A1-123[»]
2YUUNMR-A149-218[»]
ProteinModelPortalQ05655.
SMRQ05655. Positions 1-123, 149-668.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111566. 114 interactions.
DIPDIP-29954N.
IntActQ05655. 19 interactions.
MINTMINT-1346366.
STRING9606.ENSP00000331602.

Chemistry

BindingDBQ05655.
ChEMBLCHEMBL2996.
GuidetoPHARMACOLOGY1485.

PTM databases

PhosphoSiteQ05655.

Polymorphism databases

DMDM205371776.

Proteomic databases

MaxQBQ05655.
PaxDbQ05655.
PRIDEQ05655.

Protocols and materials databases

DNASU5580.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330452; ENSP00000331602; ENSG00000163932. [Q05655-1]
ENST00000394729; ENSP00000378217; ENSG00000163932. [Q05655-1]
ENST00000608339; ENSP00000476782; ENSG00000273482. [Q05655-1]
ENST00000608438; ENSP00000477082; ENSG00000273482. [Q05655-1]
GeneID5580.
KEGGhsa:5580.
UCSCuc003dgl.3. human. [Q05655-1]

Organism-specific databases

CTD5580.
GeneCardsGC03P053190.
HGNCHGNC:9399. PRKCD.
HPACAB010469.
CAB013225.
HPA001863.
HPA001890.
MIM176977. gene.
615559. phenotype.
neXtProtNX_Q05655.
Orphanet3261. Autoimmune lymphoproliferative syndrome.
300345. Autosomal recessive systemic lupus erythematosus.
1572. Common variable immunodeficiency.
PharmGKBPA33763.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233022.
HOVERGENHBG108317.
InParanoidQ05655.
KOK06068.
OMAGEDEAKF.
OrthoDBEOG77M8QM.
PhylomeDBQ05655.
TreeFamTF102004.

Enzyme and pathway databases

BRENDA2.7.11.13. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_21257. Metabolism of RNA.
REACT_578. Apoptosis.
REACT_604. Hemostasis.
REACT_6900. Immune System.
REACT_71. Gene Expression.
SignaLinkQ05655.

Gene expression databases

ArrayExpressQ05655.
BgeeQ05655.
CleanExHS_PRKCD.
GenevestigatorQ05655.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR027436. PKC_delta.
IPR017892. Pkinase_C.
IPR014376. Prot_kin_PKC_delta.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00130. C1_1. 2 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000551. PKC_delta. 1 hit.
PIRSF501104. Protein_kin_C_delta. 1 hit.
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPRKCD. human.
EvolutionaryTraceQ05655.
GeneWikiPRKCD.
GenomeRNAi5580.
NextBio21638.
PMAP-CutDBQ05655.
PROQ05655.
SOURCESearch...

Entry information

Entry nameKPCD_HUMAN
AccessionPrimary (citable) accession number: Q05655
Secondary accession number(s): B0KZ81 expand/collapse secondary AC list , B2R834, Q15144, Q86XJ6
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: September 2, 2008
Last modified: July 9, 2014
This is version 162 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM