Reviewed, UniProtKB/Swiss-Prot Q05655 (KPCD_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein kinase C delta type
    EC=2.7.11.13
Alternative name(s):
    nPKC-delta

Gene names

Name:

PRKCD

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	676 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This is calcium-independent, phospholipid-dependent, serine- and threonine-specific enzyme. PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters. May play a role in antigen-dependent control of B-cell function. Phosphorylates MUC1 in the C-terminal and regulates the interaction between MUC1 and beta-catenin.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	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.
Subunit structure	Interacts with PDK1, RAD9A, CDCP1 and MUC1.
Subcellular location	CytoplasmBy similarity. Membrane; Peripheral membrane proteinBy similarity.
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	Phosphorylated on Thr-507, within the activation loop. Autophosphorylated and/or phosphorylated. Although the Thr-507 phosphorylation occurs it is not a prerequisite for enzymatic activity 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
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	Phorbol-ester binding 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
Gene Ontology (GO)
Biological process	intracellular signaling cascade Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Inferred from direct assay. Source: UniProtKB protein stabilization Non-traceable author statement. Source: UniProtKB senescence Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytosol Inferred from Experiment. Source: Reactome membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW enzyme activator activity Inferred from direct assay. Source: UniProtKB enzyme binding Inferred from physical interaction. Source: UniProtKB protein C-terminus binding Inferred from physical interaction. Source: UniProtKB protein kinase C activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FYN	P06241	3	EBI-704279,EBI-515315
GAP43	P17677	3	EBI-704279,EBI-1267511

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

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

Amino acid modifications

Modified residue

130

1

Phosphoserine

Modified residue

302

1

Phosphoserine

Modified residue

304

1

Phosphoserine

Modified residue

307

1

Phosphoserine

Modified residue

313

1

Phosphotyrosine

Modified residue

334

1

Phosphotyrosine

Modified residue

374

1

Phosphotyrosine

Modified residue

507

1

Phosphothreonine; by PDPK1 By similarity

Modified residue

645

1

Phosphoserine Potential

Modified residue

664

1

Phosphoserine

Natural variations

Natural variant

348

1

N → S: dbSNP rs33911937.

VAR_035347

Natural variant

375

1

F → S: dbSNP rs1056998.

VAR_006175

Natural variant

410

1

L → F: dbSNP rs34502209.

VAR_035348

Natural variant

483

1

R → W: dbSNP rs35891605.

VAR_046009

Natural variant

494

1

M → V

VAR_020610

Natural variant

593

1

V → M

VAR_006176

Experimental info

Sequence conflict

524

1

K → R in BAG36031. Ref.2

Sequence conflict

533

1

S → A Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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

Sequences

	Sequence		Length	Mass (Da)
	Q05655-1 [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

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: 8357834] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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. 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: 9427282] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 51-676.
[7]	"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: 7988719] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 432-533, VARIANT VAL-494.
[8]	"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: 11877440] [Abstract] Cited for: INTERACTION WITH MUC1, FUNCTION.
[9]	"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: 12628935] [Abstract] Cited for: INTERACTION WITH RAD9A.
[10]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664, MASS SPECTROMETRY. Tissue: Epithelium.
[11]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-313; TYR-334 AND TYR-374, MASS SPECTROMETRY.
[12]	"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: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, MASS SPECTROMETRY. Tissue: Platelet.
[13]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130; SER-302; SER-304; SER-307 AND SER-664, MASS SPECTROMETRY.
[14]	"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: 15851033] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-123 IN COMPLEX WITH PHOSPHOTYROSINE-CONTAINING PEPTIDE, INTERACTION WITH CDCP1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

PIR

S35704.

RefSeq

NP_006245.2.
NP_997704.1.

UniGene

Hs.155342

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum