UniProt Accession

 KPCD_HUMAN; Q05655; B0KZ81; B2R834; Q15144; Q86XJ6 

Genbank Protein ID

 L07860; L07861; AK313216; CH471055; BC043350; Z22521; D10495; DQ516383 

Genbank Nucleotide ID

 AAA03176.1; AAA03175.1; BAG36031.1; EAW65279.1; AAH43350.1; CAA80249.1; BAA01381.1; ABF68960.1 

Protein Name

 Protein kinase C delta type 

Protein Synonyms/Alias

 Tyrosine-protein kinase PRKCD; nPKC-delta; Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit; Sphingosine-dependent protein kinase-1; SDK1 

Gene Name

 PRKCD 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
138	MRSEDEAKFPTMNRR	ubiquitination	[1]
184	DFVWGLNKQGYKCRQ	ubiquitination	[2, 3, 4]
222	SRDTIFQKERFNIDM	ubiquitination	[1]
319	IYQGFEKKTGVAGED	ubiquitination	[1]
336	DNSGTYGKIWEGSSK	ubiquitination	[1]
362	LGKGSFGKVLLGELK	ubiquitination	[2, 4]
496	IADFGMCKENIFGES	ubiquitination	[5]
613	INWTLLEKRRLEPPF	ubiquitination	[2, 4]
641	DQEFLNEKARLSYSD	ubiquitination	[1, 5]

Reference

 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [4] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 

Functional Description

 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. 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). 

Sequence Annotation

 DOMAIN 1 90 C2.
 DOMAIN 349 603 Protein kinase.
 DOMAIN 604 675 AGC-kinase C-terminal.
 ZN_FING 158 208 Phorbol-ester/DAG-type 1.
 ZN_FING 230 280 Phorbol-ester/DAG-type 2.
 NP_BIND 355 363 ATP (By similarity).
 ACT_SITE 473 473 Proton acceptor (By similarity).
 BINDING 378 378 ATP (By similarity).
 MOD_RES 43 43 Phosphothreonine (By similarity).
 MOD_RES 64 64 Phosphotyrosine (By similarity).
 MOD_RES 130 130 Phosphoserine.
 MOD_RES 155 155 Phosphotyrosine.
 MOD_RES 218 218 Phosphothreonine.
 MOD_RES 299 299 Phosphoserine; by autocatalysis.
 MOD_RES 302 302 Phosphoserine; by autocatalysis.
 MOD_RES 304 304 Phosphoserine; by autocatalysis.
 MOD_RES 307 307 Phosphoserine.
 MOD_RES 313 313 Phosphotyrosine.
 MOD_RES 334 334 Phosphotyrosine; by SRC (Probable).
 MOD_RES 374 374 Phosphotyrosine.
 MOD_RES 503 503 Phosphoserine.
 MOD_RES 507 507 Phosphothreonine; by autocatalysis
 MOD_RES 567 567 Phosphotyrosine.
 MOD_RES 645 645 Phosphoserine.
 MOD_RES 654 654 Phosphoserine.
 MOD_RES 658 658 Phosphoserine.
 MOD_RES 664 664 Phosphoserine.  

Keyword

 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell cycle; Cell membrane; Complete proteome; Cytoplasm; Endoplasmic reticulum; Kinase; Membrane; Metal-binding; Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase; Tumor suppressor; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 676 AA 

Protein Sequence

Gene Ontology

 GO:0005911; C:cell-cell junction; IEA:Compara.
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
 GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
 GO:0016363; C:nuclear matrix; IEA:Compara.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
 GO:0005886; C:plasma membrane; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004699; F:calcium-independent protein kinase C activity; TAS:BHF-UCL.
 GO:0008047; F:enzyme activator activity; IDA:UniProtKB.
 GO:0043560; F:insulin receptor substrate binding; ISS:BHF-UCL.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:EC.
 GO:0007202; P:activation of phospholipase C activity; TAS:Reactome.
 GO:0015810; P:aspartate transport; IEA:Compara.
 GO:0042100; P:B cell proliferation; IEA:Compara.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0006921; P:cellular component disassembly involved in execution phase of apoptosis; TAS:Reactome.
 GO:0042149; P:cellular response to glucose starvation; IEA:Compara.
 GO:0032869; P:cellular response to insulin stimulus; IEA:Compara.
 GO:0090398; P:cellular senescence; IMP:BHF-UCL.
 GO:0032963; P:collagen metabolic process; IEA:Compara.
 GO:0042742; P:defense response to bacterium; ISS:UniProtKB.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0010467; P:gene expression; TAS:Reactome.
 GO:0016064; P:immunoglobulin mediated immune response; IEA:Compara.
 GO:0006917; P:induction of apoptosis; IEA:Compara.
 GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
 GO:0032613; P:interleukin-10 production; IEA:Compara.
 GO:0032615; P:interleukin-12 production; IEA:Compara.
 GO:0035556; P:intracellular signal transduction; IEA:Compara.
 GO:0016071; P:mRNA metabolic process; TAS:Reactome.
 GO:0030837; P:negative regulation of actin filament polymerization; ISS:UniProtKB.
 GO:0051490; P:negative regulation of filopodium assembly; ISS:UniProtKB.
 GO:0034351; P:negative regulation of glial cell apoptotic process; IMP:UniProtKB.
 GO:0050728; P:negative regulation of inflammatory response; IC:BHF-UCL.
 GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:BHF-UCL.
 GO:0043407; P:negative regulation of MAP kinase activity; IMP:BHF-UCL.
 GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISS:BHF-UCL.
 GO:0090331; P:negative regulation of platelet aggregation; ISS:UniProtKB.
 GO:0032091; P:negative regulation of protein binding; TAS:BHF-UCL.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0042119; P:neutrophil activation; IDA:UniProtKB.
 GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:2000304; P:positive regulation of ceramide biosynthetic process; IMP:BHF-UCL.
 GO:0046326; P:positive regulation of glucose import; IEA:Compara.
 GO:2000753; P:positive regulation of glucosylceramide catabolic process; IMP:BHF-UCL.
 GO:0043406; P:positive regulation of MAP kinase activity; IEA:Compara.
 GO:1900163; P:positive regulation of phospholipid scramblase activity; IMP:UniProtKB.
 GO:0035307; P:positive regulation of protein dephosphorylation; IMP:BHF-UCL.
 GO:2001022; P:positive regulation of response to DNA damage stimulus; IMP:UniProtKB.
 GO:2000755; P:positive regulation of sphingomyelin catabolic process; IMP:BHF-UCL.
 GO:0032930; P:positive regulation of superoxide anion generation; IMP:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0050821; P:protein stabilization; NAS:UniProtKB.
 GO:0010469; P:regulation of receptor activity; TAS:BHF-UCL.
 GO:0043200; P:response to amino acid stimulus; IEA:Compara.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0045471; P:response to ethanol; IEA:Compara.
 GO:0009749; P:response to glucose stimulus; IEA:Compara.
 GO:0009408; P:response to heat; IEA:Compara.
 GO:0042542; P:response to hydrogen peroxide; IEA:Compara.
 GO:0001666; P:response to hypoxia; IEA:Compara.
 GO:0009612; P:response to mechanical stimulus; IEA:Compara.
 GO:0014070; P:response to organic cyclic compound; IEA:Compara.
 GO:0023021; P:termination of signal transduction; IMP:BHF-UCL. 

Interpro

 IPR000961; AGC-kinase_C.
 IPR000008; C2_Ca-dep.
 IPR008973; C2_Ca/lipid-bd_dom_CaLB.
 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_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00130; C1_1
 PF00069; Pkinase
 PF00433; Pkinase_C 

SMART

 SM00109; C1
 SM00239; C2
 SM00133; S_TK_X
 SM00220; S_TKc 

PROSITE

 PS51285; AGC_KINASE_CTER
 PS50004; C2
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS00479; ZF_DAG_PE_1
 PS50081; ZF_DAG_PE_2 

PRINTS

 PR00008; DAGPEDOMAIN.