ID KPCD_MOUSE Reviewed; 674 AA.
AC P28867; Q91V85; Q9Z333;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 27-MAR-2002, sequence version 3.
DT 27-MAR-2024, entry version 227.
DE RecName: Full=Protein kinase C delta type {ECO:0000305};
DE EC=2.7.11.13 {ECO:0000269|PubMed:22265677};
DE AltName: Full=Tyrosine-protein kinase PRKCD;
DE EC=2.7.10.2;
DE AltName: Full=nPKC-delta;
DE Contains:
DE RecName: Full=Protein kinase C delta type regulatory subunit;
DE Contains:
DE RecName: Full=Protein kinase C delta type catalytic subunit;
DE AltName: Full=Sphingosine-dependent protein kinase-1;
DE Short=SDK1;
GN Name=Prkcd {ECO:0000312|MGI:MGI:97598}; Synonyms=Pkcd;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1868068; DOI=10.1021/bi00246a008;
RA Mischak H., Bodenteich A., Kolch W., Goodnight J., Hofer F.,
RA Mushinski J.F.;
RT "Mouse protein kinase C-delta, the major isoform expressed in mouse
RT hemopoietic cells: sequence of the cDNA, expression patterns, and
RT characterization of the protein.";
RL Biochemistry 30:7925-7931(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=ICR; TISSUE=Brain;
RX PubMed=1765103; DOI=10.1111/j.1432-1033.1991.tb16453.x;
RA Mizuno K., Kubo K., Saido T.C., Akita Y., Osada S., Kuroki T., Ohno S.,
RA Suzuki K.;
RT "Structure and properties of a ubiquitously expressed protein kinase C,
RT nPKC delta.";
RL Eur. J. Biochem. 202:931-940(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC STRAIN=129/SvJ;
RA Wheeler D.L., Gillis M.E., Verma A.K.;
RT "Intron/exon structure of the murine protein kinase C delta gene.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=11558579; DOI=10.1248/bpb.24.973;
RA Sakurai Y., Onishi Y., Tanimoto Y., Kizaki H.;
RT "Novel protein kinase C delta isoform insensitive to caspase-3.";
RL Biol. Pharm. Bull. 24:973-977(2001).
RN [5]
RP INTERACTION WITH CAVIN3.
RX PubMed=9054438;
RA Izumi Y., Hirai S., Tamai Y., Fujise-Matsuoka A., Nishimura Y., Ohno S.;
RT "A protein kinase Cdelta-binding protein SRBC whose expression is induced
RT by serum starvation.";
RL J. Biol. Chem. 272:7381-7389(1997).
RN [6]
RP FUNCTION.
RX PubMed=9705322; DOI=10.1074/jbc.273.34.21834;
RA Megidish T., Cooper J., Zhang L., Fu H., Hakomori S.;
RT "A novel sphingosine-dependent protein kinase (SDK1) specifically
RT phosphorylates certain isoforms of 14-3-3 protein.";
RL J. Biol. Chem. 273:21834-21845(1998).
RN [7]
RP FUNCTION.
RX PubMed=11976686; DOI=10.1038/416860a;
RA Mecklenbraeuker I., Saijo K., Zheng N.Y., Leitges M., Tarakhovsky A.;
RT "Protein kinase Cdelta controls self-antigen-induced B-cell tolerance.";
RL Nature 416:860-865(2002).
RN [8]
RP PHOSPHORYLATION AT THR-505.
RX PubMed=9748166; DOI=10.1126/science.281.5385.2042;
RA Le Good J.A., Ziegler W.H., Parekh D.B., Alessi D.R., Cohen P.,
RA Parker P.J.;
RT "Protein kinase C isotypes controlled by phosphoinositide 3-kinase through
RT the protein kinase PDK1.";
RL Science 281:2042-2045(1998).
RN [9]
RP DISRUPTION PHENOTYPE, FUNCTION IN B CELL PROLIFERATION, AND FUNCTION IN
RP B-CELL IMMUNE RESPONSES.
RX PubMed=11976687; DOI=10.1038/416865a;
RA Miyamoto A., Nakayama K., Imaki H., Hirose S., Jiang Y., Abe M.,
RA Tsukiyama T., Nagahama H., Ohno S., Hatakeyama S., Nakayama K.I.;
RT "Increased proliferation of B cells and auto-immunity in mice lacking
RT protein kinase Cdelta.";
RL Nature 416:865-869(2002).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-311, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [11]
RP FUNCTION, AND PHOSPHORYLATION AT THR-505.
RX PubMed=18025218; DOI=10.4049/jimmunol.179.11.7720;
RA Cheng N., He R., Tian J., Dinauer M.C., Ye R.D.;
RT "A critical role of protein kinase C delta activation loop phosphorylation
RT in formyl-methionyl-leucyl-phenylalanine-induced phosphorylation of
RT p47(phox) and rapid activation of nicotinamide adenine dinucleotide
RT phosphate oxidase.";
RL J. Immunol. 179:7720-7728(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-311, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-43; TYR-311 AND SER-662, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-311, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-311; THR-505; SER-643 AND
RP SER-662, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF CDK1.
RX PubMed=19917613; DOI=10.1074/jbc.m109.055392;
RA LaGory E.L., Sitailo L.A., Denning M.F.;
RT "The protein kinase Cdelta catalytic fragment is critical for maintenance
RT of the G2/M DNA damage checkpoint.";
RL J. Biol. Chem. 285:1879-1887(2010).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF CARD9, CATALYTIC ACTIVITY, AND
RP PHOSPHORYLATION AT TYR-311.
RX PubMed=22265677; DOI=10.1016/j.immuni.2011.11.015;
RA Strasser D., Neumann K., Bergmann H., Marakalala M.J., Guler R.,
RA Rojowska A., Hopfner K.P., Brombacher F., Urlaub H., Baier G., Brown G.D.,
RA Leitges M., Ruland J.;
RT "Syk kinase-coupled C-type lectin receptors engage protein kinase C-delta
RT to elicit Card9 adaptor-mediated innate immunity.";
RL Immunity 36:32-42(2012).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 231-280 IN COMPLEX WITH PHORBOL
RP ESTER AND ZINC IONS.
RX PubMed=7781068; DOI=10.1016/0092-8674(95)90011-x;
RA Zhang G., Kazanietz M.G., Blumberg P.M., Hurley J.H.;
RT "Crystal structure of the cys2 activator-binding domain of protein kinase C
RT delta in complex with phorbol ester.";
RL Cell 81:917-924(1995).
CC -!- FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that plays contrasting roles
CC in cell death and cell survival by functioning as a pro-apoptotic
CC protein during DNA damage-induced apoptosis, but acting as an anti-
CC apoptotic protein during cytokine receptor-initiated cell death, is
CC involved in tumor suppression, is required for oxygen radical
CC production by NADPH oxidase and acts as a positive or negative
CC regulator in platelet functional responses. Negatively regulates B cell
CC proliferation and also has an important function in self-antigen
CC induced B cell tolerance induction (PubMed:11976686, PubMed:11976687).
CC Upon DNA damage, activates the promoter of the death-promoting
CC transcription factor BCLAF1/Btf to trigger BCLAF1-mediated p53/TP53
CC gene transcription and apoptosis. In response to oxidative stress,
CC interact with and activate CHUK/IKKA in the nucleus, causing the
CC phosphorylation of p53/TP53. In the case of ER stress or DNA damage-
CC induced apoptosis, can form a complex with the tyrosine-protein kinase
CC ABL1 which trigger apoptosis independently of p53/TP53. In cytosol can
CC trigger apoptosis by activating MAPK11 or MAPK14, inhibiting AKT1 and
CC decreasing the level of X-linked inhibitor of apoptosis protein (XIAP),
CC whereas in nucleus induces apoptosis via the activation of MAPK8 or
CC MAPK9. Upon ionizing radiation treatment, is required for the
CC activation of the apoptosis regulators BAX and BAK, which trigger the
CC mitochondrial cell death pathway. Can phosphorylate MCL1 and target it
CC for degradation which is sufficient to trigger for BAX activation and
CC apoptosis. Is required for the control of cell cycle progression both
CC at G1/S and G2/M phases. Mediates phorbol 12-myristate 13-acetate
CC (PMA)-induced inhibition of cell cycle progression at G1/S phase by up-
CC regulating the CDK inhibitor CDKN1A/p21 and inhibiting the cyclin CCNA2
CC promoter activity. In response to UV irradiation can phosphorylate
CC CDK1, which is important for the G2/M DNA damage checkpoint activation
CC (PubMed:19917613). Can protect glioma cells from the apoptosis induced
CC by TNFSF10/TRAIL, probably by inducing increased phosphorylation and
CC subsequent activation of AKT1. Can also act as tumor suppressor upon
CC mitogenic stimulation with PMA or TPA (By similarity). In N-formyl-
CC methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required for
CC NCF1 (p47-phox) phosphorylation and activation of NADPH oxidase
CC activity, and regulates TNF-elicited superoxide anion production in
CC neutrophils, by direct phosphorylation and activation of NCF1 or
CC indirectly through MAPK1/3 (ERK1/2) signaling pathways
CC (PubMed:18025218). Involved in antifungal immunity by mediating
CC phosphorylation and activation of CARD9 downstream of C-type lectin
CC receptors activation, promoting interaction between CARD9 and BCL10,
CC followed by activation of NF-kappa-B and MAP kinase p38 pathways
CC (PubMed:22265677). May also play a role in the regulation of NADPH
CC oxidase activity in eosinophil after stimulation with IL5, leukotriene
CC B4 or PMA. In collagen-induced platelet aggregation, acts a negative
CC regulator of filopodia formation and actin polymerization by
CC interacting with and negatively regulating VASP phosphorylation.
CC Downstream of PAR1, PAR4 and CD36/GP4 receptors, regulates
CC differentially platelet dense granule secretion; acts as a positive
CC regulator in PAR-mediated granule secretion, whereas it negatively
CC regulates CD36/GP4-mediated granule release. Phosphorylates MUC1 in the
CC C-terminal and regulates the interaction between MUC1 and beta-catenin.
CC The catalytic subunit phosphorylates 14-3-3 proteins (YWHAB, YWHAZ and
CC YWHAH) in a sphingosine-dependent fashion (PubMed:9705322).
CC Phosphorylates ELAVL1 in response to angiotensin-2 treatment (By
CC similarity). Phosphorylates mitochondrial phospholipid scramblase 3
CC (PLSCR3), resulting in increased cardiolipin expression on the
CC mitochondrial outer membrane which facilitates apoptosis (By
CC similarity). Phosphorylates SMPD1 which induces SMPD1 secretion (By
CC similarity). {ECO:0000250|UniProtKB:Q05655,
CC ECO:0000269|PubMed:11976686, ECO:0000269|PubMed:11976687,
CC ECO:0000269|PubMed:18025218, ECO:0000269|PubMed:19917613,
CC ECO:0000269|PubMed:9705322}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13; Evidence={ECO:0000269|PubMed:22265677};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10027};
CC -!- ACTIVITY REGULATION: Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are
CC calcium-insensitive, but activated by diacylglycerol (DAG) and
CC phosphatidylserine. Three specific sites; Thr-505 (activation loop of
CC the kinase domain), Ser-643 (turn motif) and Ser-662 (hydrophobic
CC region), need to be phosphorylated for its full activation. Activated
CC by caspase-3 (CASP3) cleavage during apoptosis. After cleavage, the
CC pseudosubstrate motif in the regulatory subunit is released from the
CC substrate recognition site of the catalytic subunit, which enables
CC PRKCD to become constitutively activated. The catalytic subunit which
CC displays properties of a sphingosine-dependent protein kinase is
CC activated by D-erythro-sphingosine (Sph) or N,N-dimethyl-D-
CC erythrosphingosine (DMS) or N,N,N-trimethyl-D-erythrosphingosine (TMS),
CC but not by ceramide or Sph-1-P and is strongly inhibited by
CC phosphatidylserine (By similarity). {ECO:0000250|UniProtKB:Q05655}.
CC -!- SUBUNIT: Interacts with PDPK1 (via N-terminal region) (By similarity).
CC Interacts with RAD9A (By similarity). Interacts with CDCP1 (By
CC similarity). Interacts with MUC1 (By similarity). Interacts with VASP
CC (By similarity). Interacts with CAVIN3 (PubMed:9054438). Interacts with
CC PRKD2 (via N-terminus and zing-finger domain 1 and 2) in response to
CC oxidative stress; the interaction is independent of PRKD2 tyrosine
CC phosphorylation (By similarity). Interacts with PLSC3; interaction is
CC enhanced by UV irradiation (By similarity).
CC {ECO:0000250|UniProtKB:Q05655, ECO:0000269|PubMed:9054438}.
CC -!- INTERACTION:
CC P28867; P23242: Gja1; NbExp=4; IntAct=EBI-1551324, EBI-298630;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q05655}.
CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q05655}. Nucleus
CC {ECO:0000250|UniProtKB:Q05655}. Cell membrane
CC {ECO:0000250|UniProtKB:Q05655}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q05655}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q05655}. Endomembrane system
CC {ECO:0000250|UniProtKB:Q05655}. Note=Translocates to the mitochondria
CC upon apoptotic stimulation. Upon activation, translocates to the plasma
CC membrane followed by partial location to the endolysosomes.
CC {ECO:0000250|UniProtKB:Q05655}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=PKC-delta-I;
CC IsoId=P28867-1; Sequence=Displayed;
CC Name=2; Synonyms=PKC-delta-II;
CC IsoId=P28867-2; Sequence=VSP_004741;
CC -!- TISSUE SPECIFICITY: Isoform 1 is highly expressed in developing
CC pro- and pre-B-cells and moderately in mature T-cells. Isoform 2 is
CC highly expressed in testis and ovary and at a lower level in
CC thymocytes, brain and kidney.
CC -!- DOMAIN: The C1 domain, containing the phorbol ester/DAG-type region 1
CC (C1A) and 2 (C1B), is the diacylglycerol sensor.
CC -!- DOMAIN: The C2 domain is a non-calcium binding domain. It binds
CC proteins containing phosphotyrosine in a sequence-specific manner (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylated and/or phosphorylated at Thr-505, within the
CC activation loop; phosphorylation at Thr-505 is not a prerequisite for
CC enzymatic activity (By similarity). Autophosphorylated at Ser-299 (By
CC similarity). Upon TNFSF10/TRAIL treatment, phosphorylated at Tyr-155;
CC phosphorylation is required for its translocation to the endoplasmic
CC reticulum and cleavage by caspase-3 (By similarity). Phosphorylated at
CC Tyr-311, Tyr-332 and Tyr-565; phosphorylation of Tyr-311 and Tyr-565
CC following thrombin or zymosan stimulation potentiates its kinase
CC activity (By similarity). Phosphorylated by protein kinase PDPK1;
CC phosphorylation is inhibited by the apoptotic C-terminal cleavage
CC product of PKN2 (By similarity). Phosphorylated at Tyr-311 through a
CC SYK and SRC mechanism downstream of C-type lectin receptors activation,
CC promoting its activation (PubMed:22265677).
CC {ECO:0000250|UniProtKB:Q05655, ECO:0000269|PubMed:22265677}.
CC -!- PTM: Proteolytically cleaved into a catalytic subunit and a regulatory
CC subunit by caspase-3 during apoptosis which results in kinase
CC activation. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are viable up to 1 year despite detection of
CC auto-immune disease in these animals. They exhibit glomerulonephritis,
CC splenomegaly and lymphadenopathy associated with B-cell expansion and
CC defective B-cell tolerance to self-antigen.
CC {ECO:0000269|PubMed:11976687}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
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DR EMBL; M69042; AAA73056.1; -; mRNA.
DR EMBL; X60304; CAA42845.1; -; mRNA.
DR EMBL; AF274044; AAF79208.1; -; Genomic_DNA.
DR EMBL; AF251036; AAF64316.1; -; mRNA.
DR EMBL; AB011812; BAA36408.1; -; mRNA.
DR CCDS; CCDS26895.1; -. [P28867-1]
DR CCDS; CCDS79285.1; -. [P28867-2]
DR PIR; A40281; KIMSCD.
DR RefSeq; NP_035233.1; NM_011103.3. [P28867-1]
DR RefSeq; XP_006518758.1; XM_006518695.2. [P28867-2]
DR RefSeq; XP_017171407.1; XM_017315918.1. [P28867-2]
DR PDB; 1PTQ; X-ray; 1.95 A; A=231-280.
DR PDB; 1PTR; X-ray; 2.20 A; A=231-280.
DR PDB; 3UEJ; X-ray; 1.30 A; A/B=231-280.
DR PDB; 3UEY; X-ray; 1.30 A; A/B=231-280.
DR PDB; 3UFF; X-ray; 1.30 A; A/B=231-280.
DR PDB; 3UGD; X-ray; 1.45 A; A/B=231-280.
DR PDB; 3UGI; X-ray; 1.36 A; A/B=231-280.
DR PDB; 3UGL; X-ray; 1.36 A; A/B=231-280.
DR PDBsum; 1PTQ; -.
DR PDBsum; 1PTR; -.
DR PDBsum; 3UEJ; -.
DR PDBsum; 3UEY; -.
DR PDBsum; 3UFF; -.
DR PDBsum; 3UGD; -.
DR PDBsum; 3UGI; -.
DR PDBsum; 3UGL; -.
DR AlphaFoldDB; P28867; -.
DR SMR; P28867; -.
DR BioGRID; 202197; 18.
DR CORUM; P28867; -.
DR DIP; DIP-1169N; -.
DR IntAct; P28867; 6.
DR MINT; P28867; -.
DR STRING; 10090.ENSMUSP00000107830; -.
DR BindingDB; P28867; -.
DR ChEMBL; CHEMBL2560; -.
DR iPTMnet; P28867; -.
DR PhosphoSitePlus; P28867; -.
DR SwissPalm; P28867; -.
DR EPD; P28867; -.
DR jPOST; P28867; -.
DR MaxQB; P28867; -.
DR PaxDb; 10090-ENSMUSP00000107830; -.
DR PeptideAtlas; P28867; -.
DR ProteomicsDB; 263646; -. [P28867-1]
DR ProteomicsDB; 263647; -. [P28867-2]
DR Pumba; P28867; -.
DR Antibodypedia; 664; 1509 antibodies from 45 providers.
DR DNASU; 18753; -.
DR Ensembl; ENSMUST00000022521.13; ENSMUSP00000022521.7; ENSMUSG00000021948.18. [P28867-2]
DR Ensembl; ENSMUST00000112210.11; ENSMUSP00000107829.4; ENSMUSG00000021948.18. [P28867-1]
DR Ensembl; ENSMUST00000112211.9; ENSMUSP00000107830.3; ENSMUSG00000021948.18. [P28867-2]
DR GeneID; 18753; -.
DR KEGG; mmu:18753; -.
DR UCSC; uc007sve.2; mouse. [P28867-1]
DR UCSC; uc007svg.2; mouse. [P28867-2]
DR AGR; MGI:97598; -.
DR CTD; 5580; -.
DR MGI; MGI:97598; Prkcd.
DR VEuPathDB; HostDB:ENSMUSG00000021948; -.
DR eggNOG; KOG0694; Eukaryota.
DR GeneTree; ENSGT00940000155327; -.
DR InParanoid; P28867; -.
DR OMA; FKTINWI; -.
DR OrthoDB; 841660at2759; -.
DR PhylomeDB; P28867; -.
DR TreeFam; TF102004; -.
DR BRENDA; 2.7.11.13; 3474.
DR Reactome; R-MMU-111465; Apoptotic cleavage of cellular proteins.
DR Reactome; R-MMU-111933; Calmodulin induced events.
DR Reactome; R-MMU-114508; Effects of PIP2 hydrolysis.
DR Reactome; R-MMU-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-MMU-1489509; DAG and IP3 signaling.
DR Reactome; R-MMU-2029485; Role of phospholipids in phagocytosis.
DR Reactome; R-MMU-450520; HuR (ELAVL1) binds and stabilizes mRNA.
DR Reactome; R-MMU-5218921; VEGFR2 mediated cell proliferation.
DR Reactome; R-MMU-5607764; CLEC7A (Dectin-1) signaling.
DR Reactome; R-MMU-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR Reactome; R-MMU-877300; Interferon gamma signaling.
DR BioGRID-ORCS; 18753; 3 hits in 80 CRISPR screens.
DR ChiTaRS; Prkcd; mouse.
DR EvolutionaryTrace; P28867; -.
DR PRO; PR:P28867; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P28867; Protein.
DR Bgee; ENSMUSG00000021948; Expressed in lateral geniculate body and 281 other cell types or tissues.
DR ExpressionAtlas; P28867; baseline and differential.
DR Genevisible; P28867; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0036019; C:endolysosome; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005739; C:mitochondrion; ISS:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0099524; C:postsynaptic cytosol; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004697; F:diacylglycerol-dependent serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0004699; F:diacylglycerol-dependent, calcium-independent serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0008047; F:enzyme activator activity; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0043560; F:insulin receptor substrate binding; IPI:BHF-UCL.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; ISS:UniProtKB.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0070976; F:TIR domain binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0042100; P:B cell proliferation; IMP:MGI.
DR GO; GO:0060326; P:cell chemotaxis; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:1904385; P:cellular response to angiotensin; ISS:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0071447; P:cellular response to hydroperoxide; ISO:MGI.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:MGI.
DR GO; GO:0034644; P:cellular response to UV; ISS:UniProtKB.
DR GO; GO:0090398; P:cellular senescence; ISO:MGI.
DR GO; GO:0032963; P:collagen metabolic process; ISO:MGI.
DR GO; GO:0070779; P:D-aspartate import across plasma membrane; ISO:MGI.
DR GO; GO:0042742; P:defense response to bacterium; IMP:UniProtKB.
DR GO; GO:0006974; P:DNA damage response; ISO:MGI.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0030837; P:negative regulation of actin filament polymerization; IMP:UniProtKB.
DR GO; GO:0051490; P:negative regulation of filopodium assembly; IMP:UniProtKB.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0090331; P:negative regulation of platelet aggregation; IMP:UniProtKB.
DR GO; GO:0042119; P:neutrophil activation; ISO:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IDA:MGI.
DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; ISO:MGI.
DR GO; GO:0046326; P:positive regulation of glucose import; ISO:MGI.
DR GO; GO:2000753; P:positive regulation of glucosylceramide catabolic process; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; ISO:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:MGI.
DR GO; GO:2000755; P:positive regulation of sphingomyelin catabolic process; ISO:MGI.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISS:UniProtKB.
DR GO; GO:0043687; P:post-translational protein modification; ISO:MGI.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:MGI.
DR GO; GO:2000303; P:regulation of ceramide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0042325; P:regulation of phosphorylation; ISO:MGI.
DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
DR GO; GO:0023021; P:termination of signal transduction; ISO:MGI.
DR CDD; cd20834; C1_nPKC_theta-like_rpt1; 1.
DR CDD; cd20837; C1_nPKC_theta-like_rpt2; 1.
DR Gene3D; 3.30.60.20; -; 2.
DR Gene3D; 2.60.40.150; C2 domain; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR027436; PKC_delta.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR014376; Prot_kin_PKC_delta.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24356:SF427; PROTEIN KINASE C DELTA TYPE; 1.
DR PANTHER; PTHR24356; SERINE/THREONINE-PROTEIN KINASE; 1.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF21494; PKC_C2; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000551; PKC_delta; 1.
DR PIRSF; PIRSF501104; Protein_kin_C_delta; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 2.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR SUPFAM; SSF57889; Cysteine-rich domain; 2.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell cycle;
KW Cell membrane; Cytoplasm; Kinase; Membrane; Metal-binding; Mitochondrion;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Tumor suppressor; Zinc;
KW Zinc-finger.
FT CHAIN 1..674
FT /note="Protein kinase C delta type"
FT /id="PRO_0000055695"
FT CHAIN 1..327
FT /note="Protein kinase C delta type regulatory subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000421669"
FT CHAIN 328..674
FT /note="Protein kinase C delta type catalytic subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000421670"
FT DOMAIN 1..106
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 347..601
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 602..673
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 158..208
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 230..280
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ACT_SITE 471
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 353..361
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 376
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 48
FT /note="Interaction with phosphotyrosine-containing peptide"
FT /evidence="ECO:0000250"
FT SITE 62
FT /note="Interaction with phosphotyrosine-containing peptide"
FT /evidence="ECO:0000250"
FT SITE 67
FT /note="Interaction with phosphotyrosine-containing peptide"
FT /evidence="ECO:0000250"
FT SITE 123
FT /note="Interaction with phosphotyrosine-containing peptide"
FT /evidence="ECO:0000250"
FT SITE 327..328
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 43
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 50
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 64
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P09215"
FT MOD_RES 130
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 141
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 155
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 218
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 299
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 311
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000269|PubMed:22265677,
FT ECO:0007744|PubMed:17947660, ECO:0007744|PubMed:18034455,
FT ECO:0007744|PubMed:19131326, ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 332
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P09215"
FT MOD_RES 372
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 449
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 504
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 505
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:18025218,
FT ECO:0000269|PubMed:9748166, ECO:0007744|PubMed:21183079"
FT MOD_RES 565
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 643
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 652
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q05655"
FT MOD_RES 662
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT VAR_SEQ 326
FT /note="L -> LGEAGSHISLKLSFPSRAKEKDSSETC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11558579"
FT /id="VSP_004741"
FT CONFLICT 214
FT /note="N -> I (in Ref. 4; BAA36408)"
FT /evidence="ECO:0000305"
FT CONFLICT 226
FT /note="N -> S (in Ref. 4; BAA36408)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="E -> D (in Ref. 1; AAA73056)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="G -> W (in Ref. 1; AAA73056)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="E -> V (in Ref. 1; AAA73056)"
FT /evidence="ECO:0000305"
FT CONFLICT 501
FT /note="G -> D (in Ref. 1; AAA73056)"
FT /evidence="ECO:0000305"
FT CONFLICT 503
FT /note="A -> P (in Ref. 1; AAA73056)"
FT /evidence="ECO:0000305"
FT CONFLICT 513
FT /note="I -> S (in Ref. 1; AAA73056)"
FT /evidence="ECO:0000305"
FT CONFLICT 518..520
FT /note="LQG -> PARA (in Ref. 4; BAA36408)"
FT /evidence="ECO:0000305"
FT CONFLICT 538
FT /note="E -> R (in Ref. 4; BAA36408)"
FT /evidence="ECO:0000305"
FT STRAND 233..236
FT /evidence="ECO:0007829|PDB:3UFF"
FT TURN 245..247
FT /evidence="ECO:0007829|PDB:3UFF"
FT STRAND 253..256
FT /evidence="ECO:0007829|PDB:3UFF"
FT STRAND 258..261
FT /evidence="ECO:0007829|PDB:3UFF"
FT TURN 262..264
FT /evidence="ECO:0007829|PDB:3UFF"
FT HELIX 270..273
FT /evidence="ECO:0007829|PDB:3UFF"
FT STRAND 278..280
FT /evidence="ECO:0007829|PDB:3UFF"
SQ SEQUENCE 674 AA; 77547 MW; 6E9F753348F03D59 CRC64;
MAPFLRISFN SYELGSLQVE DEASQPFCAV KMKEALSTER GKTLVQKKPT MYPEWKTTFD
AHIYEGRVIQ IVLMRAAEDP VSEVTVGVSV LAERCKKNNG KAEFWLDLQP QAKVLMCVQY
FLEDGDCKQS MRSEEEAKFP TMNRRGAIKQ AKIHYIKNHE FIATFFGQPT FCSVCKEFVW
GLNKQGYKCR QCNAAIHKKC IDKIIGRCTG TATNSRDTIF QKERFNIDMP HRFKVYNYMS
PTFCDHCGSL LWGLVKQGLK CEDCGMNVHH KCREKVANLC GINQKLLAEA LNQVTQRSSR
KLDTTESVGI YQGFEKKPEV SGSDILDNNG TYGKIWEGST RCTLENFTFQ KVLGKGSFGK
VLLAELKGKD KYFAIKCLKK DVVLIDDDVE CTMVEKRVLA LAWESPFLTH LICTFQTKDH
LFFVMEFLNG GDLMFHIQDK GRFELYRATF YAAEIICGLQ FLHSKGIIYR DLKLDNVMLD
RDGHIKIADF GMCKENIFGE GRASTFCGTP DYIAPEILQG LKYSFSVDWW SFGVLLYEML
IGQSPFHGDD EDELFESIRV DTPHYPRWIT KESKDIMEKL FERDPDKRLG VTGNIRIHPF
FKTINWSLLE KRKVEPPFKP KVKSPSDYSN FDPEFLNEKP QLSFSDKNLI DSMDQEAFHG
FSFVNPKFEQ FLDI
//
