KinaseNET

Nomenclature

Short Name:

PKD1

Full Name:

Protein kinase C, mu type

Alias:

EC 2.7.11.13
PKC-mu
PKD
PRKCM
PRKD1
Protein kinase D1; Protein kinase C, mu type; Protein kinase D;
Kinase PKD1
KPCD1
NPKC-mu
PKCM

Classification

Type:

Protein-serine/threonine kinase

Group:

CAMK

Family:

PKD

SubFamily:

Specific Links

Entrez-Gene Entry:	5587
Entrez-Protein Entry:	NP_002733
GeneCards Entry:	PKD
KinBASE Entry:	PKD1
OMIM Entry:	605435
Pfam Entry:	Q15139
PhosphoNET Entry:	Q15139
Phosphosite Plus Entry:	1763
ScanSite Entry:	Q15139
Source Entry:	PRKD1
UCSD-Nature Entry:	A001930
UniProt Entry:	Q15139
Kinexus Products:	PKD1 Protein-serine kinase C mu (Protein kinase D) S205 phosphosite-specific antibody AB-PK770 Protein-serine kinase C mu (Protein kinase D) S738+S742 phosphosite-specific antibody AB-PK771 CREB1 (123-135) KinSub - cyclic-AMP response element binding protein-1 (K123-R135, human) peptide; Crebtide protein kinase substrate peptide - Powder PE-01ACP95 PKCMSubtide - PKD1 (PRKCM) protein kinase substrate peptide - Powder PE-01BIV90 Protein-serine kinase C mu (Protein kinase D) (G735-G745, human) pS738+pS742 phosphopeptide - Powder PE-04AOZ95 Protein-serine kinase C mu (Protein kinase D) (R202-S208, human) pS205 phosphopeptide - Powder PE-04APA99

General Links

Structure

Mol. Mass (Da):

101704

# Amino Acids:

912

# mRNA Isoforms:

mRNA Isoforms:

101,704 Da (912 AA; Q15139)

4D Structure:

Interacts (via N-terminus) with ADAP1/CENTA1. Interacts with Src

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

Subfamily Alignment

Domain Distribution:

Start	End	Domain
140	196	C1
271	320	C1
422	541	PH
583	839	Pkinase

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.

hiddentext

○	Protein-serine kinase C mu (Protein kinase D) S205 phosphosite-specific antibody AB-PK770
○	Protein-serine kinase C mu (Protein kinase D) S738+S742 phosphosite-specific antibody AB-PK771
○	CREB1 (123-135) KinSub - cyclic-AMP response element binding protein-1 (K123-R135, human) peptide; Crebtide protein kinase substrate peptide - Powder PE-01ACP95
○	PKCMSubtide - PKD1 (PRKCM) protein kinase substrate peptide - Powder PE-01BIV90
○	Protein-serine kinase C mu (Protein kinase D) (G735-G745, human) pS738+pS742 phosphopeptide - Powder PE-04AOZ95
○	Protein-serine kinase C mu (Protein kinase D) (R202-S208, human) pS205 phosphopeptide - Powder PE-04APA99

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Acetylated:

K612.

Serine phosphorylated:

S205-, S208-, S219-, S223-, S225, S235, S237, S239, S247, S249+, S345, S379, S397-, S401, S412, S421, S448, S460, S473, S548, S549, S738+, S742+, S890, S892, S910+.

Threonine phosphorylated:

T210, T217, T224, T395+, T422, T746-.

Tyrosine phosphorylated:

Y95+, Y432, Y443, Y463+, Y502, Y749-, .

Ubiquitinated:

K292, K737.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

100

590

29

788
8

50

15

29
17

103

19

166
32

187

98

327
88

518

25

472
56

329

82

1432
25

145

31

348
76

446

47

871
54

320

17

259
18

106

90

121
7

40

37

92
89

526

170

533
10

58

41

177
14

83

12

72
8

45

15

33
9

55

15

61
15

88

129

140
9

52

28

79
5

32

98

31
62

363

109

405
18

106

30

94
11

65

33

187
11

65

29

116
21

124

28

127
10

61

30

149
90

530

64

940
5

28

44

76
13

74

28

169
17

98

28

114
13

78

28

55
42

248

24

247
60

355

36

367
34

202

67

415
90

532

57

515
24

144

35

133

Evolution

Species Conservation

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

100

100

100
99.4

99.5

99.5
98.9

99.3

99
-

-

97
-

-

99
92

93.9

97
-

-

-
92.5

95

93.5
93.1

95.4

94
-

-

-
81.3

86.3

-
-

-

90
-

-

84
80.1

86.7

83
-

-

-
20.1

32

-
-

-

-
43.7

56.2

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
20.2

34.4

-
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	PRKCE - Q02156
2	HDAC5 - Q9UQL6
3	CDH1 - P12830
4	BTK - Q06187
5	MT2A - P02795
6	EGFR - P00533
7	HDAC7 - Q8WUI4
8	KIDINS220 - Q9ULH0
9	IGF1R - P08069
10	C1QBP - Q07021
11	PPP1R14A - Q96A00
12	YWHAZ - P63104
13	COX19 - Q49B96
14	ADAP1 - O75689

Regulation

Activation:

Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds DAG with high affinity and appears to play the dominant role in mediating translocation to the cell membrane and trans-Golgi network. Phorbol-ester/DAG-type domain 2 binds phorbol ester with higher affinity. Phosphorylation at Tyr-95 increases phosphotransferase activity and induces interaction with PKC-delta.Phosphorylation at Ser-249 and Tyr-463 increases phosphotransferase activity. Phosphorylation at Ser-738 and Ser-742 increases phosphotransferase activity and induces interaction with ASK1, JNK1 and IKKb. Phosphorylation at Ser-910 increases phosphotransferase activity and prolongs kinase activation.

Inhibition:

Autophosphorylation of Ser-742 and phosphorylation of Ser-738 by PKC relieves auto-inhibition by the PH domain. Phosphorylation at Ser-205, Ser-208, Ser-219 and Ser-223 induces binding of 14-3-3 beta and tau to inhibit PKC-mu phosphotransferase activity. Phosphorylation at Ser-397 induces interaction with 14-3-3 beta.

Synthesis:

Degradation:

Known Upstream Kinases

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Kinase Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

SRC	P12931	Y95	KFPECGFYGMYDKIL	+
PKD1	Q15139	S205	GVRRRRLSNVSLTGV	-
p38d	O15264	S205	GVRRRRLSNVSLTGV	-
p38d	O15264	S208	RRRLSNVSLTGVSTI	-
p38d	O15264	S249	GREKRSNSQSYIGRP	+
PKCa	P17252	S249	GREKRSNSQSYIGRP	+
p38d	O15264	S397	EDANRTISPSTSNNI	-
p38d	O15264	S401	RTISPSTSNNIPLMR
ABL	P00519	Y432	KEGWMVHYTSKDTLR
SRC	P12931	Y432	KEGWMVHYTSKDTLR
ABL	P00519	Y463	NDTGSRYYKEIPLSE	+
SRC	P12931	Y463	NDTGSRYYKEIPLSE	+
ABL	P00519	Y502	TTANVVYYVGENVVN
SRC	P12931	Y502	TTANVVYYVGENVVN
PKCh	P24723	S738	ARIIGEKSFRRSVVG	+
PKCd	Q05655	S738	ARIIGEKSFRRSVVG	+
PKCe	Q02156	S738	ARIIGEKSFRRSVVG	+
PKD1	Q15139	S738	ARIIGEKSFRRSVVG	+
PKD3	O94806	S738	ARIIGEKSFRRSVVG	+
PKCz	Q05513	S738	ARIIGEKSFRRSVVG	+
PKCa	P17252	S738	ARIIGEKSFRRSVVG	+
PKCh	P24723	S742	GEKSFRRSVVGTPAY	+
PKCd	Q05655	S742	GEKSFRRSVVGTPAY	+
PKCe	Q02156	S742	GEKSFRRSVVGTPAY	+
PKD1	Q15139	S742	GEKSFRRSVVGTPAY	+
PKD3	O94806	S742	GEKSFRRSVVGTPAY	+
PKCz	Q05513	S742	GEKSFRRSVVGTPAY	+
p38d	O15264	S742	GEKSFRRSVVGTPAY	+
PKCa	P17252	S742	GEKSFRRSVVGTPAY	+
PKD1	Q15139	S910	KALGERVSIL_____	+

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.

Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name	UniProt ID (Human)	Phosphosite Location	Phosphosite Sequence	Effect of Phosphorylation

Akt1 (PKBa)	P31749	S473	RPHFPQFSYSASGTA	+
Akt1 (PKBa)	P31749	T308	KDGATMKTFCGTPEY	+
AP-2 alpha	P05549	S258	GVLRRAKSKNGGRSL
AP-2 alpha	P05549	S326	EFLNRQHSDPNEQVT
Cofilin 1	P23528	S2	______ASGVAVSDG
COL4A3BP	Q9Y5P4	S132	SSLRRHGSMVSLVSG	-
Cortactin	Q14247	S298	EKLAKHESQQDYSKG
Cortactin	Q14247	S348	EAVTSKTSNIRANFE
CREB1	P16220	S133	EILSRRPSYRKILND	+
CREB1	P16220	S98	KDLKRLFSGTQISTI
CTNNB1	P35222	T112	EGMQIPSTQFDAAHP
CTNNB1	P35222	T120	QFDAAHPTNVQRLAE
HDAC5	Q9UQL6	S259	FPLRKTASEPNLKVR
HDAC5	Q9UQL6	S498	RPLSRTQSSPLPQSP
HDAC7	Q8WUI4	S155	FPLRKTVSEPNLKLR
HDAC7	Q8WUI4	S358	WPLSRTRSEPLPPSA
HDAC7	Q8WUI4	S486	RPLSRAQSSPAAPAS
HPK1 (MAP4K1)	Q92918	S171	ATLARRLSFIGTPYW	+
HSP27	P04792	S82	RALSRQLSSGVSEIR	?
Jun (c-Jun)	P05412	S63	KNSDLLTSPDVGLLK	+
Kidins220	Q9ULH0	S924	RTITRQMSFDLTKLL
MARK2	Q7KZI7	S400	HKVQRSVSANPKQRR	?
PIK4CB	Q9UBF8	S294	SNLKRTASNPKVENE	+
PIP5K2A	P48426	T376	KAAHAAKTVKHGAGA	-
PKD1 (PRKCM)	Q15139	S205	GVRRRRLSNVSLTGV	-
PKD1 (PRKCM)	Q15139	S738	ARIIGEKSFRRSVVG	+
PKD1 (PRKCM)	Q15139	S742	GEKSFRRSVVGTPAY	+
PKD1 (PRKCM)	Q15139	S910	KALGERVSIL_____	+
PPP1R14A (CPI 17)	Q96A00	T38	QKRHARVTVKYDRRE	-
PTRH2	Q9Y3E5	S5	___MPSKSLVMEYLA
PTRH2	Q9Y3E5	S87	GKVAAQCSHAAVSAY
Rin1	Q13671	S351	RPLLRSMSAAFCSLL	-
SSH1	Q8WYL5	S978	SPLKRSHSLAKLGSL	-
TLR5	O60602	S805	YQLMKHQSIRGFVQK
TNNI3	P19429	S22	PAPIRRRSSNYRAYA
TNNI3	P19429	S23	APIRRRSSNYRAYAT
VR1	Q8NER1	S117	LRLYDRRSIFEAVAQ
EGFR	P00533	T678	RHIVRKRTLRRLLQE	-
EGFR	P00533	T693	RELVEPLTPSGEAPN	-

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Matrix Type:

Experimentally derived from alignment of 68 known protein substrate phosphosites and 25 peptides phosphorylated by recombinant PKD1 in vitro tested in-house by Kinexus.

Domain #:

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's

Based on in vitro and/or in vivo phosphorylation data

Compound Name	KD, Ki or IC50 (nM)	PubChem ID	ChEMBL ID	PubMed ID

Staurosporine	IC50 = 80 pM	5279		12166950
Ophiocordin	Ki = 5.3 nM	5287736	60254	16134928
TTT-3002	IC50 < 6 nM
Kinome_3681	IC50 = 6.2 nM	10029385	362558	15267232
BX517	IC50 = 10 nM	11161844	228654
Ro-31-8220	IC50 = 10 nM	5083	6291
Lestaurtinib	Kd = 14 nM	126565		22037378
Ro-32-0432	IC50 = 17.2 nM	127757	26501
JAK3 Inhibitor VI	IC50 < 25 nM	16760524		22037377
PKR Inhibitor	IC50 < 25 nM	6490494	235641	22037377
SB218078	IC50 < 25 nM	447446	289422	22037377
AT9283	IC50 < 30 nM	24905142		19143567
K-252a; Nocardiopsis sp.	IC50 = 33 nM	3813	281948
Gö6976	IC50 < 40 nM	3501	302449
Novartis 12a (PKD1)	IC50 < 40 nM
Staurosporine aglycone	IC50 < 40 nM	3035817	281948
Wyeth PDK1 Inhibitor Compound 1	IC50 < 40 nM
BCP9000906	IC50 > 50 nM	5494425	21156	22037377
BMS-690514	Kd < 50 nM	11349170		21531814
Cdk1/2 Inhibitor III	IC50 > 50 nM	5330812	261720	22037377
N-Benzoylstaurosporine	IC50 = 50 nM	56603681	608533
SU11652	IC50 > 50 nM	24906267	13485	22037377
7-hydroxystaurosporine	IC50 > 60 nM	72271	1236539
A 443654	IC50 < 60 nM	10172943	379300
SureCN3470757	IC50 < 60 nM	11588244	375236
HG-9-91-01	IC50 < 80 nM
NVP-TAE684	Kd = 80 nM	16038120	509032	22037378
Hypothemycin	IC50 = 100 nM	5477775	471474
Momelotinib	IC50 < 100 nM	25062766		19295546
1;9-Pyrazoloanthrone	IC50 > 150 nM	8515	7064	22037377
Gö6976	IC50 > 150 nM	3501	302449	22037377
PP1 Analog II; 1NM-PP1	IC50 > 150 nM	5154691	573578	22037377
Bisindolylmaleimide IV	IC50 = 190 nM	2399	266487	8151612
Syk Inhibitor IV	IC50 = 200 nM	10200390
Bosutinib	IC50 > 250 nM	5328940	288441	22037377
Syk Inhibitor II	IC50 > 250 nM	16760670		22037377
Arcyriaflavin A	IC50 = 310 nM	5327723	268368	8151612
Sunitinib	Kd = 310 nM	5329102	535	18183025
BI2536	Kd = 320 nM	11364421	513909	22037378
KT5720	IC50 < 400 nM	3844	608532
ALX-270-403-M001	IC50 = 500 nM			22037377
IPA-3	IC50 < 500 nM	521106	472940
SB220025	IC50 = 500 nM	5164	274064	22037377
SU9516	IC50 = 500 nM	5289419	258805	22037377
Alvocidib	Kd = 520 nM	9910986	428690	18183025
Aurora A Inhibitor 23 (DF)	Kd < 600 nM			21992004
BX795	IC50 < 600 nM	10077147	577784
GSK1838705A	Kd = 650 nM	25182616	464552	22037378
SureCN4875304	IC50 = 650 nM	46871765		20472445
PP121	IC50 < 750 nM	24905142		18849971
1-Naphthyl PP1	IC50 < 800 nM	4877
A-83-01	IC50 < 800 nM	16218924	1170377
K00596a	IC50 < 800 nM	9549298	200027
Neratinib	Kd = 820 nM	9915743	180022	22037378
Crizotinib	Kd = 990 nM	11626560	601719	22037378
Nintedanib	Kd = 990 nM	9809715	502835	22037378
AG-E-60384	IC50 > 1 µM	6419741	413188	22037377
Amgen TBK 1 inhibitor (Compound II)	IC50 = 1 µM
Bisindolylmaleimide I	IC50 < 1 µM	2396	7463
Dovitinib	IC50 > 1 µM	57336746		22037377
Fasudil	IC50 > 1 µM	3547	38380	22037377
Flt-3 Inhibitor II	IC50 > 1 µM	11601743	377193	22037377
FR180204	IC50 > 1 µM	11493598	259551	22037377
Gö6983	IC50 > 1 µM	3499	261491	22037377
GSK650394A	IC50 = 1 µM	25022668	558642
Icotinib	IC50 > 1 µM	22024915		22112293
JNK Inhibitor; Negative Control	IC50 > 1 µM	11665831		22037377
LY364947	IC50 > 1 µM	447966	261454	22037377
MK5108	IC50 > 1 µM	24748204		20053775
MRT67307	IC50 = 1 µM	44464263
NU6140	IC50 > 1 µM	10202471	1802728	22037377
PD0332991	IC50 = 1 µM	5330286	189963
PD169316	IC50 > 1 µM	4712	17331	22037377
Pyrimidylpyrrole, 11e	Ki = 1 µM	11634725	583042	19827834
Silmitasertib	IC50 > 1 µM	24748573		21174434
SNS314	IC50 > 1 µM	16047143	514582	18678489
SU11274	IC50 > 1 µM	9549297	261641	22037377
TG003	IC50 = 1 µM	1893668	408982
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
AC1NS7CD	Kd = 1.2 µM	5329665	295136	22037378
AST-487	Kd = 1.2 µM	11409972	574738	18183025
KW2449	Kd = 1.2 µM	11427553	1908397	22037378
SNS032	Kd = 1.2 µM	3025986	296468	18183025
SU14813	Kd = 2.4 µM	10138259	1721885	18183025
IRAK-4 kinase inhibitor b	IC50 > 3 µM
KIN 112	IC50 > 3 µM
R406	IC50 > 3 µM	11984591
Ruboxistaurin	IC50 > 3 µM	153999	91829
Gefitinib	Kd = 3.5 µM	123631	939	22037378
GSK690693	Kd = 3.5 µM	16725726	494089	22037378
EGCG (Epigallocatechin Gallate)	IC50 < 4 µM	65064	297453
JNJ-28871063	IC50 > 4 µM	17747413		17975007
Quercetagetin	IC50 < 4 µM	5281680	413552
GSK461364A	IC50 > 4.5 µM	15983966	1908394
GW441756 hydrochloride	IC50 > 4.5 µM	16219400

Disease Linkage

Gene Expression in Cancers:

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in the following types of human cancers: Gastric cancer (%CFC= -53, p<0.056); Ovary adenocarcinomas (%CFC= -50, p<0.047); and Prostate cancer (%CFC= -45, p<0.098). The COSMIC website notes an up-regulated expression score for PKD1 in diverse human cancers of 404, which is 0.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 28 for this protein kinase in human cancers was 0.5-fold of the average score of 60 for the human protein kinases.

Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.

Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.12 % in 25481 diverse cancer specimens. This rate is 1.64-fold higher than the average rate of 0.075 % calculated for human protein kinases in general.

Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.66 % in 1119 large intestine cancers tested; 0.46 % in 575 stomach cancers tested; 0.34 % in 805 skin cancers tested; 0.31 % in 602 endometrium cancers tested; 0.25 % in 1943 lung cancers tested; 0.22 % in 605 oesophagus cancers tested; 0.16 % in 1270 liver cancers tested.

Frequency of Mutated Sites:

None > 6 in 20,765 cancer specimens

Comments:

Only 2 deletions, 5 insertions and no complex mutations are noted on the COSMIC website.

COSMIC Entry:

PRKD1

OMIM Entry:

605435

Nomenclature

Short Name:

Full Name:

Alias:

Classification

Type:

Group:

Family:

SubFamily:

Specific Links

General Links

Structure

Mol. Mass (Da):

# Amino Acids:

# mRNA Isoforms:

mRNA Isoforms:

4D Structure:

1D Structure:

Subfamily Alignment

Domain Distribution:

Kinexus Products

hiddentext

Post-translation Modifications

Acetylated:

Serine phosphorylated:

Threonine phosphorylated:

Tyrosine phosphorylated:

Ubiquitinated:

Distribution

Human Tissue Distribution

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

% Max Expression: Mean Expression: Number of Samples: Standard Deviation:

Evolution

Species Conservation

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

PhosphoNET % Identity: PhosphoNET % Similarity: Homologene %Identity:

Binding Proteins

hiddentext

Regulation

Activation:

Inhibition:

Synthesis:

Degradation:

Known Upstream Kinases

Based on in vitro and/or in vivo phosphorylation data

Known Downstream Substrates

Based on in vitro and/or in vivo phosphorylation data

Protein Kinase Specificity

Matrix Type:

Domain #:

Inhibitors

Based on in vitro and/or in vivo phosphorylation data

Disease Linkage

Gene Expression in Cancers:

Mutagenesis Experiments:

Mutation Rate in All Cancers:

Mutation Rate in Specific Cancers:

Frequency of Mutated Sites:

Comments:

COSMIC Entry:

OMIM Entry:

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:

PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity: