Reviewed, UniProtKB/Swiss-Prot P28867 (KPCD_MOUSE)

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
Synonyms:	Pkcd

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	674 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 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Three specific sites; Thr-505 (activation loop of the kinase domain), Ser-643 (turn motif) and Ser-662 (hydrophobic region), need to be phosphorylated for its full activation.
Subunit structure	Interacts with RAD9A, CDCP1, PDK1 and MUC1 By similarity.
Subcellular location	CytoplasmBy similarity. Membrane; Peripheral membrane proteinBy similarity.
Tissue specificity	Isoform 1 is highly expressed in developing pro- and pre-B-cells and moderately in mature T-cells. Isoform 2 is highly expressed in testis and ovary and at a lower level in thymocytes, brain and kidney.
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 By similarity.
Post-translational modification	Phosphorylated on residue Thr-505, within the activation loop. Autophosphorylated and/or phosphorylated. Although the Thr-505 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	Alternative splicing
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	B cell proliferation Inferred from mutant phenotype. Source: MGI immunoglobulin mediated immune response Inferred from mutant phenotype. Source: MGI interleukin-10 production Inferred from mutant phenotype. Source: MGI interleukin-12 production Inferred from mutant phenotype. Source: MGI
Molecular function	protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TRIM41	Q8WV44-2	1	EBI-1551324,EBI-726015	From a different organism.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P28867-1)

Also known as: PKC-delta-I;

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: P28867-2)

Also known as: PKC-delta-II;

The sequence of this isoform differs from the canonical sequence as follows:
     326-326: L → LGEAGSHISLKLSFPSRAKEKDSSETC

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 674

674

Protein kinase C delta type

Regions

Domain

1 – 90

90

C2

Domain

347 – 601

255

Protein kinase

Domain

602 – 673

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

353 – 361

9

ATP By similarity

Sites

Active site

471

1

Proton acceptor By similarity

Binding site

376

1

ATP By similarity

Site

48

1

Interaction with phosphotyrosine-containing peptide By similarity

Site

62

1

Interaction with phosphotyrosine-containing peptide By similarity

Site

67

1

Interaction with phosphotyrosine-containing peptide By similarity

Site

123

1

Interaction with phosphotyrosine-containing peptide By similarity

Amino acid modifications

Modified residue

311

1

Phosphotyrosine

Modified residue

332

1

Phosphotyrosine By similarity

Modified residue

372

1

Phosphotyrosine By similarity

Modified residue

505

1

Phosphothreonine; by PDPK1 By similarity

Modified residue

643

1

Phosphoserine Probable

Modified residue

662

1

Phosphoserine By similarity

Natural variations

Alternative sequence

326

1

L → LGEAGSHISLKLSFPSRAKE KDSSETC in isoform 2.

Experimental info

Sequence conflict

214

1

N → I in BAA36408. Ref.4

Sequence conflict

226

1

N → S in BAA36408. Ref.4

Sequence conflict

319

1

E → D in AAA73056. Ref.1

Sequence conflict

330

1

G → W in AAA73056. Ref.1

Sequence conflict

337

1

E → V in AAA73056. Ref.1

Sequence conflict

501

1

G → D in AAA73056. Ref.1

Sequence conflict

503

1

A → P in AAA73056. Ref.1

Sequence conflict

513

1

I → S in AAA73056. Ref.1

Sequence conflict

518 – 520

3

LQG → PARA in BAA36408. Ref.4

Sequence conflict

538

1

E → R in BAA36408. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

674

Helix Strand Turn

Details...

Beta strand

233 – 236

4

Turn

245 – 247

3

Beta strand

253 – 256

4

Beta strand

258 – 261

4

Turn

262 – 264

3

Helix

270 – 275

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PKC-delta-I) [UniParc]. Last modified March 27, 2002. Version 3. Checksum: 6E9F753348F03D59	FASTA	674	77,547
	10 20 30 40 50 60 MAPFLRISFN SYELGSLQVE DEASQPFCAV KMKEALSTER GKTLVQKKPT MYPEWKTTFD 70 80 90 100 110 120 AHIYEGRVIQ IVLMRAAEDP VSEVTVGVSV LAERCKKNNG KAEFWLDLQP QAKVLMCVQY 130 140 150 160 170 180 FLEDGDCKQS MRSEEEAKFP TMNRRGAIKQ AKIHYIKNHE FIATFFGQPT FCSVCKEFVW 190 200 210 220 230 240 GLNKQGYKCR QCNAAIHKKC IDKIIGRCTG TATNSRDTIF QKERFNIDMP HRFKVYNYMS 250 260 270 280 290 300 PTFCDHCGSL LWGLVKQGLK CEDCGMNVHH KCREKVANLC GINQKLLAEA LNQVTQRSSR 310 320 330 340 350 360 KLDTTESVGI YQGFEKKPEV SGSDILDNNG TYGKIWEGST RCTLENFTFQ KVLGKGSFGK 370 380 390 400 410 420 VLLAELKGKD KYFAIKCLKK DVVLIDDDVE CTMVEKRVLA LAWESPFLTH LICTFQTKDH 430 440 450 460 470 480 LFFVMEFLNG GDLMFHIQDK GRFELYRATF YAAEIICGLQ FLHSKGIIYR DLKLDNVMLD 490 500 510 520 530 540 RDGHIKIADF GMCKENIFGE GRASTFCGTP DYIAPEILQG LKYSFSVDWW SFGVLLYEML 550 560 570 580 590 600 IGQSPFHGDD EDELFESIRV DTPHYPRWIT KESKDIMEKL FERDPDKRLG VTGNIRIHPF 610 620 630 640 650 660 FKTINWSLLE KRKVEPPFKP KVKSPSDYSN FDPEFLNEKP QLSFSDKNLI DSMDQEAFHG 670 FSFVNPKFEQ FLDI
	Isoform 2 (PKC-delta-II) [UniParc]. Checksum: CFB6D8A58220C962		700	80,294
	10 20 30 40 50 60 MAPFLRISFN SYELGSLQVE DEASQPFCAV KMKEALSTER GKTLVQKKPT MYPEWKTTFD 70 80 90 100 110 120 AHIYEGRVIQ IVLMRAAEDP VSEVTVGVSV LAERCKKNNG KAEFWLDLQP QAKVLMCVQY 130 140 150 160 170 180 FLEDGDCKQS MRSEEEAKFP TMNRRGAIKQ AKIHYIKNHE FIATFFGQPT FCSVCKEFVW 190 200 210 220 230 240 GLNKQGYKCR QCNAAIHKKC IDKIIGRCTG TATNSRDTIF QKERFNIDMP HRFKVYNYMS 250 260 270 280 290 300 PTFCDHCGSL LWGLVKQGLK CEDCGMNVHH KCREKVANLC GINQKLLAEA LNQVTQRSSR 310 320 330 340 350 360 KLDTTESVGI YQGFEKKPEV SGSDILGEAG SHISLKLSFP SRAKEKDSSE TCDNNGTYGK 370 380 390 400 410 420 IWEGSTRCTL ENFTFQKVLG KGSFGKVLLA ELKGKDKYFA IKCLKKDVVL IDDDVECTMV 430 440 450 460 470 480 EKRVLALAWE SPFLTHLICT FQTKDHLFFV MEFLNGGDLM FHIQDKGRFE LYRATFYAAE 490 500 510 520 530 540 IICGLQFLHS KGIIYRDLKL DNVMLDRDGH IKIADFGMCK ENIFGEGRAS TFCGTPDYIA 550 560 570 580 590 600 PEILQGLKYS FSVDWWSFGV LLYEMLIGQS PFHGDDEDEL FESIRVDTPH YPRWITKESK 610 620 630 640 650 660 DIMEKLFERD PDKRLGVTGN IRIHPFFKTI NWSLLEKRKV EPPFKPKVKS PSDYSNFDPE 670 680 690 700 FLNEKPQLSF SDKNLIDSMD QEAFHGFSFV NPKFEQFLDI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mouse protein kinase C-delta, the major isoform expressed in mouse hemopoietic cells: sequence of the cDNA, expression patterns, and characterization of the protein." Mischak H., Bodenteich A., Kolch W., Goodnight J., Hofer F., Mushinski J.F. Biochemistry 30:7925-7931(1991) [PubMed: 1868068] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Structure and properties of a ubiquitously expressed protein kinase C, nPKC delta." Mizuno K., Kubo K., Saido T.C., Akita Y., Osada S., Kuroki T., Ohno S., Suzuki K. Eur. J. Biochem. 202:931-940(1991) [PubMed: 1765103] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Strain: ICR. Tissue: Brain.
[3]	"Intron/exon structure of the murine protein kinase C delta gene." Wheeler D.L., Gillis M.E., Verma A.K. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). Strain: 129/SvJ.
[4]	"Novel protein kinase C delta isoform insensitive to caspase-3." Sakurai Y., Onishi Y., Tanimoto Y., Kizaki H. Biol. Pharm. Bull. 24:973-977(2001) [PubMed: 11558579] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[5]	"Protein kinase Cdelta controls self-antigen-induced B-cell tolerance." Mecklenbraeuker I., Saijo K., Zheng N.Y., Leitges M., Tarakhovsky A. Nature 416:860-865(2002) [PubMed: 11976686] [Abstract] Cited for: FUNCTION.
[6]	"Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1." Le Good J.A., Ziegler W.H., Parekh D.B., Alessi D.R., Cohen P., Parker P.J. Science 281:2042-2045(1998) [PubMed: 9748166] [Abstract] Cited for: PHOSPHORYLATION AT THR-505.
[7]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed: 17947660] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-311, MASS SPECTROMETRY. Tissue: Mast cell.
[8]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed: 18034455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-311, MASS SPECTROMETRY. Tissue: Brain.
[9]	"Crystal structure of the cys2 activator-binding domain of protein kinase C delta in complex with phorbol ester." Zhang G., Kazanietz M.G., Blumberg P.M., Hurley J.H. Cell 81:917-924(1995) [PubMed: 7781068] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 231-280 IN COMPLEX WITH PHORBOL ESTER AND ZINC IONS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M69042 mRNA. Translation: AAA73056.1.
X60304 mRNA. Translation: CAA42845.1.
AF274044 Genomic DNA. Translation: AAF79208.1.
AF251036 mRNA. Translation: AAF64316.1.
AB011812 mRNA. Translation: BAA36408.1.

PIR

KIMSCD. A40281.

RefSeq

NP_035233.1.

UniGene

Mm.2314

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1PTQ	X-ray	1.95	A	231-280	[»]
1PTR	X-ray	2.20	A	231-280	[»]

SMR

P28867. Positions 1-123, 344-616.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:1169N.

IntAct

P28867.

PTM databases

PhosphoSite

P28867.

Genome annotation databases

Ensembl

ENSMUSG00000021948. Mus musculus. [Contig view]

GeneID

18753.

KEGG

mmu:18753.

Organism-specific databases

MGI

MGI:97598. Prkcd.

Phylogenomic databases

HOGENOM

P28867.

HOVERGEN

P28867.

Gene expression databases

ArrayExpress

P28867.

CleanEx

MM_PRKCD.

GermOnline

ENSMUSG00000021948. Mus musculus.

Family and domain databases

InterPro

IPR000008. C2_Ca-dep.
IPR002219. DAG_PE_bd.
IPR015745. PKC.
IPR000961. Pkinase_C.
IPR014376. Prot_kin_PKC_delta.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_bd_CS.
IPR017442. Se/Thr_pkinase-rel.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]

PANTHER

PTHR22985:SF86. PKC. 1 hit.

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.

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

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

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]

BLOCKS

Search...

Other Resources

LinkHub

P28867.

SOURCE

Search...

ProtoNet

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Entry information

Entry name

KPCD_MOUSE

Accession

Primary (citable) accession number: P28867
Secondary accession number(s): Q91V85, Q9Z333

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	March 27, 2002
Last modified:	September 2, 2008
This is version 92 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)