Q05655 (KPCD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	676 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. 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.22 Ref.25
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-terminus region), RAD9A, CDCP1, MUC1 and VASP. Ref.11 Ref.12 Ref.13 Ref.15 Ref.34
Subcellular location	Cytoplasm. Cytoplasm › perinuclear 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-terminus cleavage product of PKN2. Ref.11 Ref.14 Ref.16 Ref.17 Ref.25 Proteolytically cleaved into a catalytic subunit and a regulatory subunit by caspase-3 during apoptosis which results in kinase activation By similarity.
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 process	Apoptosis Cell cycle
Cellular component	Cell membrane Cytoplasm Endoplasmic reticulum Membrane Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Tumor suppressor
Domain	Repeat Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell proliferation Inferred from electronic annotation. Source: Compara activation of phospholipase C activity Traceable author statement. Source: Reactome aspartate transport Inferred from electronic annotation. Source: Compara cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cellular component disassembly involved in execution phase of apoptosis Traceable author statement. Source: Reactome cellular response to glucose starvation Inferred from electronic annotation. Source: Compara cellular response to insulin stimulus Inferred from electronic annotation. Source: Compara cellular senescence Inferred from mutant phenotype PubMed 15282327. Source: BHF-UCL collagen metabolic process Inferred from electronic annotation. Source: Compara 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: Compara induction of apoptosis Inferred from electronic annotation. Source: Compara interferon-gamma-mediated signaling pathway Traceable author statement. Source: Reactome interleukin-10 production Inferred from electronic annotation. Source: Compara interleukin-12 production Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: Compara 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 nerve growth factor 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 MAP kinase activity Inferred from electronic annotation. Source: Compara positive regulation of ceramide biosynthetic process Inferred from mutant phenotype PubMed 19279011. Source: BHF-UCL positive regulation of glucose import Inferred from electronic annotation. Source: Compara 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.25. Source: UniProtKB protein autophosphorylation Inferred from electronic annotation. Source: Compara protein stabilization Non-traceable author statement PubMed 16611985. Source: UniProtKB regulation of receptor activity Traceable author statement PubMed 14583092. Source: BHF-UCL response to amino acid stimulus Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to glucose stimulus Inferred from electronic annotation. Source: Compara response to heat Inferred from electronic annotation. Source: Compara response to hydrogen peroxide Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to mechanical stimulus Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara termination of signal transduction Inferred from mutant phenotype PubMed 19279008. Source: BHF-UCL
Cellular_component	cell-cell junction Inferred from electronic annotation. Source: Compara cytosol Inferred from direct assay PubMed 10770950Ref.14. Source: UniProtKB endoplasmic reticulum Inferred from direct assay Ref.14. Source: UniProtKB mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell nuclear matrix Inferred from electronic annotation. Source: Compara nucleoplasm Traceable author statement. Source: Reactome perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay PubMed 10770950PubMed 15632189. Source: UniProtKB
Molecular_function	ATP 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 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: EC
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FYN	P06241	4	EBI-704279,EBI-515315
GAP43	P17677	4	EBI-704279,EBI-1267511

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 676

676

Protein kinase C delta type

PRO_0000055694

Chain

1 – 329

329

Protein kinase C delta type regulatory subunit By similarity

PRO_0000421667

Chain

330 – 676

347

Protein kinase C delta type catalytic subunit By similarity

PRO_0000421668

Regions

Domain

1 – 90

90

C2

Domain

349 – 603

255

Protein kinase

Domain

604 – 675

72

AGC-kinase C-terminal

Zinc finger

158 – 208

51

Phorbol-ester/DAG-type 1

Zinc finger

230 – 280

51

Phorbol-ester/DAG-type 2

Nucleotide binding

355 – 363

9

ATP By similarity

Sites

Active site

473

1

Proton acceptor By similarity

Binding site

378

1

ATP By similarity

Site

48

1

Interaction with phosphotyrosine-containing peptide

Site

62

1

Interaction with phosphotyrosine-containing peptide

Site

67

1

Interaction with phosphotyrosine-containing peptide

Site

123

1

Interaction with phosphotyrosine-containing peptide

Site

329 – 330

2

Cleavage; by caspase-3 By similarity

Amino acid modifications

Modified residue

43

1

Phosphothreonine By similarity

Modified residue

64

1

Phosphotyrosine By similarity

Modified residue

130

1

Phosphoserine Ref.21

Modified residue

155

1

Phosphotyrosine Ref.14

Modified residue

218

1

Phosphothreonine Ref.23

Modified residue

299

1

Phosphoserine; by autocatalysis Ref.17 Ref.20

Modified residue

302

1

Phosphoserine; by autocatalysis Ref.17 Ref.21

Modified residue

304

1

Phosphoserine; by autocatalysis Ref.17 Ref.21 Ref.28 Ref.32

Modified residue

307

1

Phosphoserine Ref.21

Modified residue

313

1

Phosphotyrosine Ref.16 Ref.20 Ref.23 Ref.24

Modified residue

334

1

Phosphotyrosine; by SRC Probable

Modified residue

374

1

Phosphotyrosine Ref.28

Modified residue

503

1

Phosphoserine Ref.20

Modified residue

507

1

Phosphothreonine; by autocatalysis Probable

Modified residue

567

1

Phosphotyrosine Ref.16

Modified residue

645

1

Phosphoserine Ref.25 Ref.28 Ref.32

Modified residue

654

1

Phosphoserine Ref.20

Modified residue

658

1

Phosphoserine Ref.20

Modified residue

664

1

Phosphoserine Ref.20 Ref.21 Ref.23 Ref.24 Ref.28

Natural variations

Alternative sequence

328

1

Q → QGEAGSIAPLRFLFPLRPKK GDCPPFHCQVRQ in isoform 2.

VSP_043899

Natural variant

348

1

N → S.
Corresponds to variant rs33911937 [ dbSNP | Ensembl ].

VAR_035347

Natural variant

375

1

F → S. Ref.1
Corresponds to variant rs1056998 [ dbSNP | Ensembl ].

VAR_006175

Natural variant

410

1

L → F.
Corresponds to variant rs34502209 [ dbSNP | Ensembl ].

VAR_035348

Natural variant

483

1

R → W.
Corresponds to variant rs35891605 [ dbSNP | Ensembl ].

VAR_046009

Natural variant

494

1

M → V. Ref.8

VAR_020610

Natural variant

593

1

V → M. Ref.1

VAR_006176

Experimental info

Mutagenesis

299

1

S → A: Loss of phosphorylation. Ref.17

Mutagenesis

507

1

T → A: No effect on kinase activity. Ref.10

Sequence conflict

524

1

K → R in BAG36031. Ref.2

Sequence conflict

533

1

S → A no nucleotide entry Ref.8

Secondary structure

1

.

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676

Helix Strand Turn

Details...

Beta strand

1 – 13

13

Beta strand

20 – 23

4

Beta strand

27 – 38

12

Beta strand

41 – 45

5

Beta strand

58 – 62

5

Beta strand

68 – 76

9

Beta strand

79 – 87

9

Helix

88 – 96

9

Turn

97 – 100

4

Beta strand

101 – 107

7

Beta strand

109 – 111

3

Beta strand

113 – 123

11

Helix

156 – 158

3

Beta strand

161 – 164

4

Beta strand

173 – 175

3

Beta strand

181 – 183

3

Beta strand

186 – 189

4

Turn

190 – 192

3

Helix

200 – 202

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 2, 2008. Version 2. Checksum: 013F4314A2EE331A	FASTA	676	77,505
	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
	Isoform 2 (PKCdeltaVIII) [UniParc]. Checksum: F1380490CC52EF07	FASTA	707	80,953
	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 GVAGEDMQGE AGSIAPLRFL FPLRPKKGDC PPFHCQVRQD 370 380 390 400 410 420 NSGTYGKIWE GSSKCNINNF IFHKVLGKGS FGKVLLGELK GRGEYFAIKA LKKDVVLIDD 430 440 450 460 470 480 DVECTMVEKR VLTLAAENPF LTHLICTFQT KDHLFFVMEF LNGGDLMYHI QDKGRFELYR 490 500 510 520 530 540 ATFYAAEIMC GLQFLHSKGI IYRDLKLDNV LLDRDGHIKI ADFGMCKENI FGESRASTFC 550 560 570 580 590 600 GTPDYIAPEI LQGLKYTFSV DWWSFGVLLY EMLIGQSPFH GDDEDELFES IRVDTPHYPR 610 620 630 640 650 660 WITKESKDIL EKLFEREPTK RLGVTGNIKI HPFFKTINWT LLEKRRLEPP FRPKVKSPRD 670 680 690 700 YSNFDQEFLN EKARLSYSDK NLIDSMDQSA FAGFSFVNPK FEHLLED

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"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.
[23]	"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, MASS SPECTROMETRY.
[24]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[25]	"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.
[26]	"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.
[27]	"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.
[28]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[29]	"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.
[30]	"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].
[31]	"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.
[32]	"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, MASS SPECTROMETRY.
[33]	"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.
[34]	"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.
[35]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00329236.
IPI00887373.

PIR

S35704.

RefSeq

NP_006245.2. NM_006254.3.
NP_997704.1. NM_212539.1.

UniGene

Hs.155342.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YRK	X-ray	1.70	A	1-123	[»]
2YUU	NMR	-	A	149-218	[»]

ProteinModelPortal

Q05655.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29954N.

IntAct

Q05655. 10 interactions.

MINT

MINT-1346366.

STRING

9606.ENSP00000331602.

PTM databases

PhosphoSite

Q05655.

Polymorphism databases

DMDM

205371776.

Proteomic databases

PaxDb

Q05655.

PRIDE

Q05655.

Protocols and materials databases

DNASU

5580.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000330452; ENSP00000331602; ENSG00000163932.
ENST00000394729; ENSP00000378217; ENSG00000163932.

GeneID

5580.

KEGG

hsa:5580.

UCSC

uc003dgl.3. human.

Organism-specific databases

CTD

5580.

GeneCards

GC03P053190.

HGNC

HGNC:9399. PRKCD.

HPA

CAB010469.
CAB013225.
HPA001863.
HPA001890.

MIM

176977. gene.

neXtProt

NX_Q05655.

PharmGKB

PA33763.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233022.

HOVERGEN

HBG108317.

InParanoid

Q05655.

KO

K06068.

OMA

GEDEAKF.

OrthoDB

EOG4M91QX.

PhylomeDB

Q05655.

Enzyme and pathway databases

BRENDA

2.7.11.13. 2681.

Pathway_Interaction_DB

alphasynuclein_pathway. Alpha-synuclein signaling.
ceramidepathway. Ceramide signaling pathway.
endothelinpathway. Endothelins.
hedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.
ifngpathway. IFN-gamma pathway.
igf1_pathway. IGF1 pathway.
il6_7pathway. IL6-mediated signaling events.
lysophospholipid_pathway. LPA receptor mediated events.
pdgfrbpathway. PDGFR-beta signaling pathway.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.
syndecan_2_pathway. Syndecan-2-mediated signaling events.
syndecan_4_pathway. Syndecan-4-mediated signaling events.
txa2pathway. Thromboxane A2 receptor signaling.
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.

Reactome

REACT_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.

Gene expression databases

ArrayExpress

Q05655.

Bgee

Q05655.

CleanEx

HS_PRKCD.

Genevestigator

Q05655.

GermOnline

ENSG00000163932. Homo sapiens.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
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.
[Graphical view]

Pfam

PF00130. C1_1. 2 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

PIRSF

PIRSF000551. PKC_delta. 1 hit.

PRINTS

PR00008. DAGPEDOMAIN.

SMART

SM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 1 hit.
SSF56112. Kinase_like. 1 hit.

PROSITE

PS51285. AGC_KINASE_CTER. 1 hit.
PS50004. C2. False negative.
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]

ProtoNet

Search...

Other

BindingDB

Q05655.

ChEMBL

CHEMBL2996.

ChiTaRS

PRKCD. human.

EvolutionaryTrace

Q05655.

GenomeRNAi

5580.

NextBio

21638.

PMAP-CutDB

Q05655.

SOURCE

Search...

Entry information

Entry name

KPCD_HUMAN

Accession

Primary (citable) accession number: Q05655
Secondary accession number(s): B0KZ81 , B2R834, Q15144, Q86XJ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
Last sequence update:	September 2, 2008
Last modified:	May 1, 2013
This is version 149 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.