Reviewed, UniProtKB/Swiss-Prot P09215 (KPCD_RAT)

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

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	673 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. Truncated isoform 2 is inactive.
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 PDK1, CDCP1, RAD9A and MUC1 By similarity.
Subcellular location	Cytoplasm. Membrane; Peripheral membrane protein.
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 Thr-505, within the activation loop. Autophosphorylated and/or phosphorylated. Although the Thr-505 phosphorylation occurs it is not a prerequisite for enzymatic activity. Ref.7 Ref.8
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 Direct protein sequencing
Gene Ontology (GO)
Biological process	aging Inferred from expression pattern. Source: RGD aspartate transport Inferred from mutant phenotype. Source: RGD cellular response to glucose starvation Inferred from expression pattern. Source: RGD cellular response to insulin stimulus Inferred from expression pattern. Source: RGD collagen metabolic process Inferred from mutant phenotype. Source: RGD induction of apoptosis Inferred from direct assay. Source: RGD intracellular signaling cascade Inferred from direct assay. Source: RGD positive regulation of MAP kinase activity Inferred from mutant phenotype. Source: RGD positive regulation of MAPKKK cascade Inferred from mutant phenotype. Source: RGD positive regulation of glucose import Inferred from mutant phenotype. Source: RGD protein amino acid autophosphorylation Inferred from direct assay. Source: RGD response to amino acid stimulus Inferred from expression pattern. Source: RGD response to drug Inferred from expression pattern. Source: RGD response to ethanol Inferred from expression pattern. Source: RGD response to glucose stimulus Inferred from expression pattern. Source: RGD response to heat Inferred from expression pattern. Source: RGD response to hydrogen peroxide Inferred from expression pattern. Source: RGD response to hypoxia Inferred from expression pattern. Source: RGD response to mechanical stimulus Inferred from expression pattern. Source: RGD response to organic cyclic substance Inferred from expression pattern. Source: RGD
Cellular component	extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Inferred from direct assay. Source: RGD mitochondrion Inferred from direct assay. Source: RGD nucleus Inferred from direct assay. Source: RGD
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium-independent protein kinase C activity Ref.6 Inferred from direct assay. Source: RGD diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: RGD zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: P09215-1)

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: P09215-2)

Also known as: PKC-delta-III;

The sequence of this isoform differs from the canonical sequence as follows:
     327-673: DNNGTYGKIW...VNPKYEQFLE → GESGSHIPLK...AALARYCLQN

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 673

673

Protein kinase C delta type

PRO_0000055696

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

43

1

Phosphothreonine By similarity

Modified residue

50

1

Phosphothreonine By similarity

Modified residue

130

1

Phosphoserine By similarity

Modified residue

299

1

Phosphoserine By similarity

Modified residue

311

1

Phosphotyrosine By similarity

Modified residue

332

1

Phosphotyrosine By similarity

Modified residue

372

1

Phosphotyrosine By similarity

Modified residue

505

1

Phosphothreonine Ref.7

Modified residue

643

1

Phosphoserine Probable

Modified residue

645

1

Phosphoserine By similarity

Modified residue

652

1

Phosphoserine By similarity

Modified residue

662

1

Phosphoserine Ref.8

Natural variations

Alternative sequence

327 – 673

347

DNNGT…EQFLE → GESGSHIPLKLPFPDRAREK NSSETWDKTTTGPMARSGRG ATGAALRTSPSRKYLAKAAL ARYCLQN in isoform 2.

VSP_004742

Experimental info

Mutagenesis

505

1

T → A: Decrease in the phosphorylation level. Ref.7

Sequence conflict

147

1

A → S AA sequence Ref.6

Sequence conflict

249

1

T → S in CAB75578. Ref.2

Sequence conflict

249

1

T → S in AAH76505. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

673

Helix Strand Turn

Details...

Beta strand

3 – 13

11

Beta strand

27 – 35

9

Helix

38 – 40

3

Beta strand

43 – 46

4

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 – 122

10

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PKC-delta-I) [UniParc]. Last modified July 1, 1989. Version 1. Checksum: D2C767E55863A23C	FASTA	673	77,520
	10 20 30 40 50 60 MAPFLRISFN SYELGSLQAE DDASQPFCAV KMKEALTTDR GKTLVQKKPT MYPEWKSTFD 70 80 90 100 110 120 AHIYEGRVIQ IVLMRAAEDP MSEVTVGVSV LAERCKKNNG KAEFWLDLQP QAKVLMCVQY 130 140 150 160 170 180 FLEDGDCKQS MRSEEEAMFP TMNRRGAIKQ AKIHYIKNHE FIATFFGQPT FCSVCKEFVW 190 200 210 220 230 240 GLNKQGYKCR QCNAAIHKKC IDKIIGRCTG TATNSRDTIF QKERFNIDMP HRFKVYNYMS 250 260 270 280 290 300 PTFCDHCGTL LWGLVKQGLK CEDCGMNVHH KCREKVANLC GINQKLLAEA LNQVTQKASR 310 320 330 340 350 360 KPETPETVGI YQGFEKKTAV SGNDIPDNNG TYGKIWEGSN RCRLENFTFQ KVLGKGSFGK 370 380 390 400 410 420 VLLAELKGKE RYFAIKYLKK DVVLIDDDVE CTMVEKRVLA LAWENPFLTH LICTFQTKDH 430 440 450 460 470 480 LFFVMEFLNG GDLMFHIQDK GRFELYRATF YAAEIICGLQ FLHGKGIIYR DLKLDNVMLD 490 500 510 520 530 540 KDGHIKIADF GMCKENIFGE NRASTFCGTP DYIAPEILQG LKYSFSVDWW SFGVLLYEML 550 560 570 580 590 600 IGQSPFHGDD EDELFESIRV DTPHYPRWIT KESKDIMEKL FERDPAKRLG VTGNIRLHPF 610 620 630 640 650 660 FKTINWNLLE KRKVEPPFKP KVKSPSDYSN FDPEFLNEKP QLSFSDKNLI DSMDQTAFKG 670 FSFVNPKYEQ FLE
	Isoform 2 (PKC-delta-III). Checksum: 88104F3B17991F6C	FASTA	393	44,305
	10 20 30 40 50 60 MAPFLRISFN SYELGSLQAE DDASQPFCAV KMKEALTTDR GKTLVQKKPT MYPEWKSTFD 70 80 90 100 110 120 AHIYEGRVIQ IVLMRAAEDP MSEVTVGVSV LAERCKKNNG KAEFWLDLQP QAKVLMCVQY 130 140 150 160 170 180 FLEDGDCKQS MRSEEEAMFP TMNRRGAIKQ AKIHYIKNHE FIATFFGQPT FCSVCKEFVW 190 200 210 220 230 240 GLNKQGYKCR QCNAAIHKKC IDKIIGRCTG TATNSRDTIF QKERFNIDMP HRFKVYNYMS 250 260 270 280 290 300 PTFCDHCGTL LWGLVKQGLK CEDCGMNVHH KCREKVANLC GINQKLLAEA LNQVTQKASR 310 320 330 340 350 360 KPETPETVGI YQGFEKKTAV SGNDIPGESG SHIPLKLPFP DRAREKNSSE TWDKTTTGPM 370 380 390 ARSGRGATGA ALRTSPSRKY LAKAALARYC LQN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The structure, expression, and properties of additional members of the protein kinase C family." Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y. J. Biol. Chem. 263:6927-6932(1988) [PubMed: 2834397] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain.
[2]	"Genomic structure and chromosomal localization of the rat PKCdelta-gene." Kurkinen K.M.A., Keinanen R.A., Karhu R., Koistinaho J. Gene 242:115-123(2000) [PubMed: 10721703] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: Wistar Kyoto.
[3]	"cDNA cloning of an alternative splicing variant of protein kinase C delta (PKC deltaIII), a new truncated form of PKCdelta, in rats." Ueyama T., Ren Y., Ohmori S., Sakai K., Tamaki N., Saito N. Biochem. Biophys. Res. Commun. 269:557-563(2000) [PubMed: 10708593] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[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] (ISOFORM 1). Tissue: Lung.
[5]	"Identification of three additional members of rat protein kinase C family: delta-, epsilon- and zeta-subspecies." Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y. FEBS Lett. 226:125-128(1987) [PubMed: 3691811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 123-286.
[6]	"Expression and characterization of protein kinase C-delta." Olivier A.R., Parker P.J. Eur. J. Biochem. 200:805-810(1991) [PubMed: 1915352] [Abstract] Cited for: PROTEIN SEQUENCE OF 142-153.
[7]	"The broad specificity of dominant inhibitory protein kinase C mutants infers a common step in phosphorylation." Garcia-Paramio P., Cabrerizo Y., Bornancin F., Parker P.J. Biochem. J. 333:631-636(1998) [PubMed: 9677322] [Abstract] Cited for: MUTAGENESIS OF THR-505, PHOSPHORYLATION AT THR-505.
[8]	"Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS." Moser K., White F.M. J. Proteome Res. 5:98-104(2006) [PubMed: 16396499] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-662, MASS SPECTROMETRY. Tissue: Liver.
[9]	"Crystal structure of the C2 domain from protein kinase C-delta." Pappa H., Murray-Rust J., Dekker L.V., Parker P.J., McDonald N.Q. Structure 6:885-894(1998) [PubMed: 9687370] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-123.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M18330 mRNA. Translation: AAA41871.1.
AJ230617 , AJ230618, AJ230619, AJ230620, AJ230621, AJ230622, AJ230623, AJ230624, AJ230625, AJ230626, AJ230627, AJ230628, AJ230629, AJ230630, AJ230631, AJ230632, AJ230633 Genomic DNA. Translation: CAB75578.1.
AF219629 mRNA. Translation: AAF32345.1.
BC076505 mRNA. Translation: AAH76505.1.

IPI

IPI00212816.
IPI00231534.

PIR

KIRTCD. A28163.

RefSeq

NP_579841.1.

UniGene

Rn.98279

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BDY	X-ray	2.20	A/B	1-123	[»]

SMR

P09215. Positions 231-280, 344-616.

ModBase

Search...

Protein-protein interaction databases

STRING

P09215.

PTM databases

PhosphoSite

P09215.

Proteomic databases

PRIDE

P09215.

Genome annotation databases

Ensembl

ENSRNOT00000022279; ENSRNOP00000022279; ENSRNOG00000016346; Rattus norvegicus. [Genome view]
ENSRNOT00000025858; ENSRNOP00000025858; ENSRNOG00000016346; Rattus norvegicus. [Genome view]
ENSRNOT00000051099; ENSRNOP00000050007; ENSRNOG00000016346; Rattus norvegicus. [Genome view]

GeneID

170538.

KEGG

rno:170538.

UCSC

AF219629. rat.

Organism-specific databases

CTD

170538.

RGD

67383. Prkcd.

Phylogenomic databases

HOVERGEN

P09215.

Enzyme and pathway databases

BRENDA

2.7.11.13. 248.

Gene expression databases

ArrayExpress

P09215.

Genevestigator

P09215.

GermOnline

ENSRNOG00000016346. Rattus norvegicus.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
IPR000008. C2_Ca-dep.
IPR020454. DAG/PE_bd.
IPR015745. PKC.
IPR017892. Pkinase_C.
IPR014376. Prot_kin_PKC_delta.
IPR002219. Prot_Kinase_C-like_PE/DAG_bd.
IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
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]

ProtoNet

Search...

Other Resources

NextBio

621024.

PMAP-CutDB

P09215.

Entry information

Entry name

KPCD_RAT

Accession

Primary (citable) accession number: P09215
Secondary accession number(s): Q6DG48, Q9JK29, Q9JL03

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	October 13, 2009
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)