ID KPCD_RAT Reviewed; 673 AA. AC P09215; Q6DG48; Q9JK29; Q9JL03; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 27-MAR-2024, entry version 224. DE RecName: Full=Protein kinase C delta type {ECO:0000305}; DE EC=2.7.11.13 {ECO:0000250|UniProtKB:Q05655}; 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|RGD:67383}; Synonyms=Pkcd; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=2834397; DOI=10.1016/s0021-9258(18)68732-0; RA Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y.; RT "The structure, expression, and properties of additional members of the RT protein kinase C family."; RL J. Biol. Chem. 263:6927-6932(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=Wistar Kyoto; RX PubMed=10721703; DOI=10.1016/s0378-1119(99)00539-9; RA Kurkinen K.M.A., Keinanen R.A., Karhu R., Koistinaho J.; RT "Genomic structure and chromosomal localization of the rat PKCdelta-gene."; RL Gene 242:115-123(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=10708593; DOI=10.1006/bbrc.2000.2331; RA Ueyama T., Ren Y., Ohmori S., Sakai K., Tamaki N., Saito N.; RT "cDNA cloning of an alternative splicing variant of protein kinase C delta RT (PKC deltaIII), a new truncated form of PKCdelta, in rats."; RL Biochem. Biophys. Res. Commun. 269:557-563(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE OF 123-286. RX PubMed=3691811; DOI=10.1016/0014-5793(87)80564-1; RA Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y.; RT "Identification of three additional members of rat protein kinase C family: RT delta-, epsilon- and zeta-subspecies."; RL FEBS Lett. 226:125-128(1987). RN [6] RP PROTEIN SEQUENCE OF 142-153. RX PubMed=1915352; DOI=10.1111/j.1432-1033.1991.tb16248.x; RA Olivier A.R., Parker P.J.; RT "Expression and characterization of protein kinase C-delta."; RL Eur. J. Biochem. 200:805-810(1991). RN [7] RP MUTAGENESIS OF THR-505, AND PHOSPHORYLATION AT THR-505. RX PubMed=9677322; DOI=10.1042/bj3330631; RA Garcia-Paramio P., Cabrerizo Y., Bornancin F., Parker P.J.; RT "The broad specificity of dominant inhibitory protein kinase C mutants RT infers a common step in phosphorylation."; RL Biochem. J. 333:631-636(1998). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY, CLEAVAGE BY CASPASE-3, AND ACTIVITY RP REGULATION. RX PubMed=12855683; DOI=10.1074/jbc.m305294200; RA Hamaguchi A., Suzuki E., Murayama K., Fujimura T., Hikita T., Iwabuchi K., RA Handa K., Withers D.A., Masters S.C., Fu H., Hakomori S.; RT "Sphingosine-dependent protein kinase-1, directed to 14-3-3, is identified RT as the kinase domain of protein kinase C delta."; RL J. Biol. Chem. 278:41557-41565(2003). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=16396499; DOI=10.1021/pr0503073; RA Moser K., White F.M.; RT "Phosphoproteomic analysis of rat liver by high capacity IMAC and LC- RT MS/MS."; RL J. Proteome Res. 5:98-104(2006). RN [10] RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT TYR-64 AND TYR-155. RX PubMed=17562707; DOI=10.1074/jbc.m703661200; RA DeVries-Seimon T.A., Ohm A.M., Humphries M.J., Reyland M.E.; RT "Induction of apoptosis is driven by nuclear retention of protein kinase C RT delta."; RL J. Biol. Chem. 282:22307-22314(2007). RN [11] RP PHOSPHORYLATION AT THR-505. RX PubMed=17569658; DOI=10.1074/jbc.m701676200; RA Rybin V.O., Guo J., Gertsberg Z., Elouardighi H., Steinberg S.F.; RT "Protein kinase Cepsilon (PKCepsilon) and Src control PKCdelta activation RT loop phosphorylation in cardiomyocytes."; RL J. Biol. Chem. 282:23631-23638(2007). RN [12] RP PHOSPHORYLATION AT TYR-311; TYR-332 AND THR-505. RX PubMed=18550549; DOI=10.1074/jbc.m802396200; RA Sumandea M.P., Rybin V.O., Hinken A.C., Wang C., Kobayashi T., Harleton E., RA Sievert G., Balke C.W., Feinmark S.J., Solaro R.J., Steinberg S.F.; RT "Tyrosine phosphorylation modifies protein kinase C delta-dependent RT phosphorylation of cardiac troponin I."; RL J. Biol. Chem. 283:22680-22689(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-311; SER-643 AND SER-662, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-123. RX PubMed=9687370; DOI=10.1016/s0969-2126(98)00090-2; RA Pappa H., Murray-Rust J., Dekker L.V., Parker P.J., McDonald N.Q.; RT "Crystal structure of the C2 domain from protein kinase C-delta."; RL Structure 6:885-894(1998). 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. Upon DNA damage, activates CC the promoter of the death-promoting transcription factor BCLAF1/Btf to CC trigger BCLAF1-mediated p53/TP53 gene transcription and apoptosis. In CC response to oxidative stress, interact with and activate CHUK/IKKA in CC the nucleus, causing the phosphorylation of p53/TP53. In the case of ER CC stress or DNA damage-induced apoptosis, can form a complex with the CC tyrosine-protein kinase ABL1 which trigger apoptosis independently of CC p53/TP53. In cytosol can trigger apoptosis by activating MAPK11 or CC MAPK14, inhibiting AKT1 and decreasing the level of X-linked inhibitor CC of apoptosis protein (XIAP), whereas in nucleus induces apoptosis via CC the activation of MAPK8 or MAPK9. Upon ionizing radiation treatment, is CC required for the activation of the apoptosis regulators BAX and BAK, CC which trigger the mitochondrial cell death pathway. Can phosphorylate CC MCL1 and target it for degradation which is sufficient to trigger for CC BAX activation and apoptosis. Is required for the control of cell cycle CC progression both at G1/S and G2/M phases. Mediates phorbol 12-myristate CC 13-acetate (PMA)-induced inhibition of cell cycle progression at G1/S CC phase by up-regulating the CDK inhibitor CDKN1A/p21 and inhibiting the CC cyclin CCNA2 promoter activity. In response to UV irradiation can CC phosphorylate CDK1, which is important for the G2/M DNA damage CC checkpoint activation. Can protect glioma cells from the apoptosis CC induced by TNFSF10/TRAIL, probably by inducing increased CC phosphorylation and subsequent activation of AKT1. Can also act as CC tumor suppressor upon mitogenic stimulation with PMA or TPA. In N- CC formyl-methionyl-leucyl-phenylalanine (fMLP)-treated cells, is required CC for 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. Involved in CC antifungal immunity by mediating phosphorylation and activation of CC CARD9 downstream of C-type lectin receptors activation, promoting CC interaction between CARD9 and BCL10, followed by activation of NF- CC kappa-B and MAP kinase p38 pathways (By similarity). May also play a CC role in the regulation of NADPH oxidase activity in eosinophil after CC stimulation with IL5, leukotriene B4 or PMA. In collagen-induced CC platelet aggregation, acts a negative regulator of filopodia formation CC and actin polymerization by interacting with and negatively regulating CC VASP phosphorylation. Downstream of PAR1, PAR4 and CD36/GP4 receptors, CC regulates differentially platelet dense granule secretion; acts as a CC positive regulator in PAR-mediated granule secretion, whereas it CC negatively regulates CD36/GP4-mediated granule release. Phosphorylates CC MUC1 in the C-terminal and regulates the interaction between MUC1 and CC beta-catenin (By similarity). The catalytic subunit phosphorylates 14- CC 3-3 proteins (YWHAB, YWHAZ and YWHAH) in a sphingosine-dependent CC fashion. Phosphorylates ELAVL1 in response to angiotensin-2 treatment CC (By 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:P28867, CC ECO:0000250|UniProtKB:Q05655}. CC -!- FUNCTION: Truncated isoform 2 is inactive. 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:0000250|UniProtKB:Q05655}; 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; Evidence={ECO:0000255|PROSITE- CC 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. {ECO:0000269|PubMed:12855683}. CC -!- SUBUNIT: Interacts with PDPK1 (via N-terminal region). Interacts with CC RAD9A (By similarity). Interacts with CDCP1. Interacts with MUC1. CC Interacts with VASP. Interacts with CAVIN3. Interacts with PRKD2 (via CC N-terminus and zing-finger domain 1 and 2) in response to oxidative CC 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:P28867, ECO:0000250|UniProtKB:Q05655}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17562707}. Nucleus CC {ECO:0000269|PubMed:17562707}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:17562707}. 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=P09215-1; Sequence=Displayed; CC Name=2; Synonyms=PKC-delta-III; CC IsoId=P09215-2; Sequence=VSP_004742; 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 (PubMed:9677322, PubMed:17569658). CC Autophosphorylated at Ser-299 (By similarity). Upon TNFSF10/TRAIL CC treatment, phosphorylated at Tyr-155; phosphorylation is required for CC its translocation to the endoplasmic reticulum and cleavage by caspase- CC 3 (PubMed:17562707). Phosphorylated at Tyr-311, Tyr-332 and Tyr-565; CC phosphorylation of Tyr-311 and Tyr-565 following thrombin or zymosan CC stimulation potentiates its kinase activity (PubMed:18550549). CC Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by CC the apoptotic C-terminal cleavage product of PKN2 (By similarity). CC Phosphorylated at Tyr-311 and Tyr-332 by SRC; phosphorylation leads to CC enhanced autophosphorylation at Thr-505 (PubMed:18550549). CC Phosphorylated at Tyr-311 through a SYK and SRC mechanism downstream of CC C-type lectin receptors activation, promoting its activation (By CC similarity). {ECO:0000250|UniProtKB:P28867, CC ECO:0000250|UniProtKB:Q05655, ECO:0000269|PubMed:17562707, CC ECO:0000269|PubMed:17569658, ECO:0000269|PubMed:18550549, CC ECO:0000269|PubMed:9677322}. 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:0000269|PubMed:12855683}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr CC protein kinase family. PKC subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M18330; AAA41871.1; -; mRNA. DR EMBL; AJ230617; CAB75578.1; -; Genomic_DNA. DR EMBL; AJ230618; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230619; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230620; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230621; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230622; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230623; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230624; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230625; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230626; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230627; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230628; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230629; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230630; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230631; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230632; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AJ230633; CAB75578.1; JOINED; Genomic_DNA. DR EMBL; AF219629; AAF32345.1; -; mRNA. DR EMBL; BC076505; AAH76505.1; -; mRNA. DR PIR; A28163; KIRTCD. DR RefSeq; NP_579841.1; NM_133307.1. DR PDB; 1BDY; X-ray; 2.20 A; A/B=1-123. DR PDB; 7KND; X-ray; 1.39 A; A=229-281. DR PDB; 7KNJ; X-ray; 1.57 A; A=229-281. DR PDB; 7KO6; X-ray; 1.80 A; A=229-281. DR PDB; 7L92; X-ray; 1.75 A; A/D/G/J/M/P/S/V=229-281. DR PDB; 7LCB; X-ray; 1.70 A; A=229-281. DR PDB; 7LEO; X-ray; 1.65 A; A/D=229-281. DR PDB; 7LF3; X-ray; 1.13 A; A=229-281. DR PDBsum; 1BDY; -. DR PDBsum; 7KND; -. DR PDBsum; 7KNJ; -. DR PDBsum; 7KO6; -. DR PDBsum; 7L92; -. DR PDBsum; 7LCB; -. DR PDBsum; 7LEO; -. DR PDBsum; 7LF3; -. DR AlphaFoldDB; P09215; -. DR SMR; P09215; -. DR BioGRID; 250924; 10. DR IntAct; P09215; 6. DR STRING; 10116.ENSRNOP00000025858; -. DR BindingDB; P09215; -. DR ChEMBL; CHEMBL3633; -. DR DrugCentral; P09215; -. DR GlyGen; P09215; 4 sites, 1 O-linked glycan (4 sites). DR iPTMnet; P09215; -. DR PhosphoSitePlus; P09215; -. DR jPOST; P09215; -. DR PaxDb; 10116-ENSRNOP00000025858; -. DR GeneID; 170538; -. DR KEGG; rno:170538; -. DR UCSC; RGD:67383; rat. [P09215-1] DR AGR; RGD:67383; -. DR CTD; 5580; -. DR RGD; 67383; Prkcd. DR eggNOG; KOG0694; Eukaryota. DR InParanoid; P09215; -. DR OrthoDB; 841660at2759; -. DR PhylomeDB; P09215; -. DR BRENDA; 2.7.11.13; 5301. DR Reactome; R-RNO-111465; Apoptotic cleavage of cellular proteins. DR Reactome; R-RNO-111933; Calmodulin induced events. DR Reactome; R-RNO-114508; Effects of PIP2 hydrolysis. DR Reactome; R-RNO-1250196; SHC1 events in ERBB2 signaling. DR Reactome; R-RNO-1489509; DAG and IP3 signaling. DR Reactome; R-RNO-2029485; Role of phospholipids in phagocytosis. DR Reactome; R-RNO-450520; HuR (ELAVL1) binds and stabilizes mRNA. DR Reactome; R-RNO-5218921; VEGFR2 mediated cell proliferation. DR Reactome; R-RNO-5607764; CLEC7A (Dectin-1) signaling. DR Reactome; R-RNO-5668599; RHO GTPases Activate NADPH Oxidases. DR Reactome; R-RNO-6798695; Neutrophil degranulation. DR Reactome; R-RNO-877300; Interferon gamma signaling. DR EvolutionaryTrace; P09215; -. DR PRO; PR:P09215; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005911; C:cell-cell junction; ISO:RGD. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0036019; C:endolysosome; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0016020; C:membrane; ISO:RGD. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0016363; C:nuclear matrix; ISO:RGD. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; ISO:RGD. DR GO; GO:0099524; C:postsynaptic cytosol; IDA:SynGO. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004697; F:diacylglycerol-dependent serine/threonine kinase activity; EXP:Reactome. DR GO; GO:0004699; F:diacylglycerol-dependent, calcium-independent serine/threonine kinase activity; IDA:RGD. DR GO; GO:0008047; F:enzyme activator activity; ISO:RGD. DR GO; GO:0019899; F:enzyme binding; ISO:RGD. DR GO; GO:0043560; F:insulin receptor substrate binding; ISO:RGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; ISO:RGD. DR GO; GO:0019901; F:protein kinase binding; IPI:RGD. DR GO; GO:0106310; F:protein serine kinase activity; ISS:UniProtKB. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD. DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:RHEA. DR GO; GO:0070976; F:TIR domain binding; IPI:BHF-UCL. DR GO; GO:0006915; P:apoptotic process; IMP:CACAO. DR GO; GO:0042100; P:B cell proliferation; ISO:RGD. DR GO; GO:0060326; P:cell chemotaxis; ISO:RGD. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:1904385; P:cellular response to angiotensin; ISS:UniProtKB. DR GO; GO:0042149; P:cellular response to glucose starvation; IEP:RGD. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:RGD. DR GO; GO:0071447; P:cellular response to hydroperoxide; ISO:RGD. DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD. DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:CACAO. DR GO; GO:0034644; P:cellular response to UV; ISS:UniProtKB. DR GO; GO:0090398; P:cellular senescence; ISO:RGD. DR GO; GO:0032963; P:collagen metabolic process; IMP:RGD. DR GO; GO:0070779; P:D-aspartate import across plasma membrane; IMP:RGD. DR GO; GO:0042742; P:defense response to bacterium; ISS:UniProtKB. DR GO; GO:0006974; P:DNA damage response; ISO:RGD. DR GO; GO:0016064; P:immunoglobulin mediated immune response; ISO:RGD. DR GO; GO:0035556; P:intracellular signal transduction; IDA:RGD. DR GO; GO:0030837; P:negative regulation of actin filament polymerization; ISS:UniProtKB. DR GO; GO:0051490; P:negative regulation of filopodium assembly; ISS: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; ISO:RGD. DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISO:RGD. DR GO; GO:0090331; P:negative regulation of platelet aggregation; ISS:UniProtKB. DR GO; GO:0042119; P:neutrophil activation; ISO:RGD. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; ISO:RGD. DR GO; GO:2000304; P:positive regulation of ceramide biosynthetic process; ISO:RGD. DR GO; GO:0046326; P:positive regulation of glucose import; IMP:RGD. DR GO; GO:2000753; P:positive regulation of glucosylceramide catabolic process; ISO:RGD. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:RGD. DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; ISO:RGD. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:RGD. DR GO; GO:2000755; P:positive regulation of sphingomyelin catabolic process; ISO:RGD. DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISS:UniProtKB. DR GO; GO:0043687; P:post-translational protein modification; ISO:RGD. DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISO:RGD. DR GO; GO:2000303; P:regulation of ceramide biosynthetic process; ISS:UniProtKB. DR GO; GO:0042325; P:regulation of phosphorylation; IDA:CACAO. DR GO; GO:0043200; P:response to amino acid; IEP:RGD. DR GO; GO:0045471; P:response to ethanol; IEP:RGD. DR GO; GO:0009749; P:response to glucose; IEP:RGD. DR GO; GO:0042542; P:response to hydrogen peroxide; IEP:RGD. DR GO; GO:0001666; P:response to hypoxia; IEP:RGD. DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD. DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD. DR GO; GO:0010243; P:response to organonitrogen compound; IEP:RGD. DR GO; GO:0006979; P:response to oxidative stress; IMP:RGD. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD. DR GO; GO:0023021; P:termination of signal transduction; ISO:RGD. 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; Direct protein sequencing; Kinase; Membrane; KW Metal-binding; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase; KW Tumor suppressor; Zinc; Zinc-finger. FT CHAIN 1..673 FT /note="Protein kinase C delta type" FT /id="PRO_0000055696" FT CHAIN 1..327 FT /note="Protein kinase C delta type regulatory subunit" FT /id="PRO_0000421671" FT CHAIN 328..673 FT /note="Protein kinase C delta type catalytic subunit" FT /id="PRO_0000421672" 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:0000305" FT MOD_RES 43 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:P28867" FT MOD_RES 50 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q05655" FT MOD_RES 64 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:17562707" 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:0000269|PubMed:17562707" 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:18550549, FT ECO:0007744|PubMed:22673903" FT MOD_RES 332 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:18550549" 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:17569658, FT ECO:0000269|PubMed:18550549, ECO:0000269|PubMed:9677322" 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:22673903" 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:16396499, FT ECO:0007744|PubMed:22673903" FT VAR_SEQ 327..673 FT /note="DNNGTYGKIWEGSNRCRLENFTFQKVLGKGSFGKVLLAELKGKERYFAIKYL FT KKDVVLIDDDVECTMVEKRVLALAWENPFLTHLICTFQTKDHLFFVMEFLNGGDLMFHI FT QDKGRFELYRATFYAAEIICGLQFLHGKGIIYRDLKLDNVMLDKDGHIKIADFGMCKEN FT IFGENRASTFCGTPDYIAPEILQGLKYSFSVDWWSFGVLLYEMLIGQSPFHGDDEDELF FT ESIRVDTPHYPRWITKESKDIMEKLFERDPAKRLGVTGNIRLHPFFKTINWNLLEKRKV FT EPPFKPKVKSPSDYSNFDPEFLNEKPQLSFSDKNLIDSMDQTAFKGFSFVNPKYEQFLE FT -> GESGSHIPLKLPFPDRAREKNSSETWDKTTTGPMARSGRGATGAALRTSPSRKYLA FT KAALARYCLQN (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10708593" FT /id="VSP_004742" FT MUTAGEN 505 FT /note="T->A: Decrease in the phosphorylation level." FT /evidence="ECO:0000269|PubMed:9677322" FT CONFLICT 147 FT /note="A -> S (in Ref. 6; AA sequence)" FT /evidence="ECO:0000305" FT CONFLICT 249 FT /note="T -> S (in Ref. 2; CAB75578 and 4; AAH76505)" FT /evidence="ECO:0000305" FT STRAND 3..13 FT /evidence="ECO:0007829|PDB:1BDY" FT STRAND 27..35 FT /evidence="ECO:0007829|PDB:1BDY" FT HELIX 38..40 FT /evidence="ECO:0007829|PDB:1BDY" FT STRAND 43..46 FT /evidence="ECO:0007829|PDB:1BDY" FT STRAND 58..62 FT /evidence="ECO:0007829|PDB:1BDY" FT STRAND 68..76 FT /evidence="ECO:0007829|PDB:1BDY" FT STRAND 79..87 FT /evidence="ECO:0007829|PDB:1BDY" FT HELIX 88..96 FT /evidence="ECO:0007829|PDB:1BDY" FT TURN 97..100 FT /evidence="ECO:0007829|PDB:1BDY" FT STRAND 101..107 FT /evidence="ECO:0007829|PDB:1BDY" FT STRAND 109..111 FT /evidence="ECO:0007829|PDB:1BDY" FT STRAND 113..122 FT /evidence="ECO:0007829|PDB:1BDY" FT STRAND 233..236 FT /evidence="ECO:0007829|PDB:7LF3" FT TURN 245..247 FT /evidence="ECO:0007829|PDB:7LF3" FT STRAND 253..255 FT /evidence="ECO:0007829|PDB:7LF3" FT STRAND 258..261 FT /evidence="ECO:0007829|PDB:7LF3" FT TURN 262..264 FT /evidence="ECO:0007829|PDB:7LF3" FT TURN 270..272 FT /evidence="ECO:0007829|PDB:7LF3" FT HELIX 273..275 FT /evidence="ECO:0007829|PDB:7LF3" SQ SEQUENCE 673 AA; 77520 MW; D2C767E55863A23C CRC64; MAPFLRISFN SYELGSLQAE DDASQPFCAV KMKEALTTDR GKTLVQKKPT MYPEWKSTFD AHIYEGRVIQ IVLMRAAEDP MSEVTVGVSV LAERCKKNNG KAEFWLDLQP QAKVLMCVQY FLEDGDCKQS MRSEEEAMFP TMNRRGAIKQ AKIHYIKNHE FIATFFGQPT FCSVCKEFVW GLNKQGYKCR QCNAAIHKKC IDKIIGRCTG TATNSRDTIF QKERFNIDMP HRFKVYNYMS PTFCDHCGTL LWGLVKQGLK CEDCGMNVHH KCREKVANLC GINQKLLAEA LNQVTQKASR KPETPETVGI YQGFEKKTAV SGNDIPDNNG TYGKIWEGSN RCRLENFTFQ KVLGKGSFGK VLLAELKGKE RYFAIKYLKK DVVLIDDDVE CTMVEKRVLA LAWENPFLTH LICTFQTKDH LFFVMEFLNG GDLMFHIQDK GRFELYRATF YAAEIICGLQ FLHGKGIIYR DLKLDNVMLD KDGHIKIADF GMCKENIFGE NRASTFCGTP DYIAPEILQG LKYSFSVDWW SFGVLLYEML IGQSPFHGDD EDELFESIRV DTPHYPRWIT KESKDIMEKL FERDPAKRLG VTGNIRLHPF FKTINWNLLE KRKVEPPFKP KVKSPSDYSN FDPEFLNEKP QLSFSDKNLI DSMDQTAFKG FSFVNPKYEQ FLE //