KinaseNET

Nomenclature

Short Name:

CLK1

Full Name:

Dual specificity protein kinase CLK1

Alias:

CDC like kinase 1
CDC-like kinase 1
CLK
EC 2.7.1.112
EC 2.7.12.1

Classification

Type:

Protein-serine/threonine kinase

Group:

CMGC

Family:

CLK

SubFamily:

Specific Links

Entrez-Gene Entry:	1195
Entrez-Protein Entry:	NP_004062
GeneCards Entry:	CLK
KinBASE Entry:	CLK1
OMIM Entry:	601951
Pfam Entry:	P49759
PhosphoNET Entry:	P49759
Phosphosite Plus Entry:	2136
Protein Data Bank Entry:	1Z57
ScanSite Entry:	P49759
Source Entry:	CLK1
UCSD-Nature Entry:	A000665
UniProt Entry:	P49759
Kinexus Products:	CLK1 Dual specificity protein kinase CLK1 S337 phosphosite-specific antibody AB-PK583 Dual specificity protein kinase CLK1 S337+T338 phosphosite-specific antibody AB-PK584 Dual specificity protein kinase CLK1 (E334-S341, human) pS337+pT338 phosphopeptide - Powder PE-04AHQ99 Dual specificity protein kinase CLK1 (E334-V340, human) pS337 phosphopeptide - Powder PE-04AKA95 Dual specificity protein kinase CLK1 (E334-P348, human) pS337+pT338+pS341+pT342+pY345 phosphopeptide - Powder PE-04ASV90

General Links

Structure

Mol. Mass (Da):

57291

# Amino Acids:

484

# mRNA Isoforms:

mRNA Isoforms:

61,757 Da (526 AA; P49759-3); 57,291 Da (484 AA; P49759); 16,570 Da (136 AA; P49759-2)

4D Structure:

Interacts with PPIG.

1D Structure:

Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence

3D Image (rendered using PV Viewer):

PDB ID

2VAG

Subfamily Alignment

Domain Distribution:

Start	End	Domain
161	477	Pkinase

Kinexus Products

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

hiddentext

○	Dual specificity protein kinase CLK1 S337 phosphosite-specific antibody AB-PK583
○	Dual specificity protein kinase CLK1 S337+T338 phosphosite-specific antibody AB-PK584
○	Dual specificity protein kinase CLK1 (E334-S341, human) pS337+pT338 phosphopeptide - Powder PE-04AHQ99
○	Dual specificity protein kinase CLK1 (E334-V340, human) pS337 phosphopeptide - Powder PE-04AKA95
○	Dual specificity protein kinase CLK1 (E334-P348, human) pS337+pT338+pS341+pT342+pY345 phosphopeptide - Powder PE-04ASV90

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET

Serine phosphorylated:

S24, S34, S36, S37, S54, S59, S61, S101, S102, S104, S122, S140, S328, S337+, S341-.

Threonine phosphorylated:

T123, T138+, T330+, T338+, T342-.

Tyrosine phosphorylated:

Y56, Y76, Y80, Y345-.

Distribution

Based on gene microarray analysis from the NCBI

Human Tissue Distribution

% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:

10

796

16

700
1.4

113

12

101
28

2336

13

1832
12

1003

58

1629
13

1043

14

902
13

1086

45

2367
8

673

23

682
10

867

33

964
10

825

10

809
2

139

58

97
13

1084

29

1835
13

1090

130

1519
33

2769

24

3594
3

228

12

145
17

1397

27

2093
3

239

9

88
3

263

197

599
9

781

22

919
6

537

61

879
11

929

56

929
16

1352

26

1614
25

2081

27

2869
33

2756

14

2685
6

511

22

640
29

2428

26

3097
19

1595

38

1339
15

1264

27

1831
26

2133

22

2621
25

2112

22

2668
0.2

13

14

12
13

1088

18

209
100

8290

21

12254
2

153

56

243
12

996

26

745
3

222

22

313

Evolution

Species Conservation

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

100

100

100
99.8

100

99
97.9

98.8

98
-

-

-
-

-

-
78.7

86.8

92
-

-

-
89

93.6

90
50

65.9

91
-

-

-
86.6

91.7

-
22.4

39.2

76
68

79.1

71
53.8

68.3

-
-

-

-
31.9

42.7

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
-

-

-
37.8

56.2

-
27.5

45

35
-

-

-

For a wider analysis go to PhosphoNET Evolution in PhosphoNET

Binding Proteins

Examples of known interacting proteins

hiddentext

No.	Name – UniProt ID
1	PTPN1 - P18031
2	PPIG - Q13427
3	MBP - P02686
4	SFRS6 - Q13247
5	LUC7L3 - O95232
6	UBL5 - Q9BZL1
7	PRPF4 - O43172
8	SFRS3 - P84103
9	NCOR1 - O75376
10	BCLAF1 - Q9NYF8
11	SAFB - Q15424
12	SLU7 - O95391
13	PIAS4 - Q8N2W9
14	SRPK2 - P78362

Regulation

Activation:

Inhibition:

Synthesis:

Degradation:

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

Abl1	P00519	T735	DTEWRSVTLPRDLQS	+
Abl1 iso2	P00519-2	T754	DTEWRSVTLPRDLQS	+
PTP1B	P18031	S50	RNRYRDVSPFDHSRI	+

Protein Kinase Specificity

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

Matrix Type:

Predicted from the application of the Kinexus Kinase Substrate Predictor Version 2.0 algorithm, which was trained with over 10,000 kinase-protein substrate pairs and 8,000 kinase-peptide substrate pairs.

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

A674563	Kd = 1.4 nM	11314340	379218	22037378
Nintedanib	Kd = 8.8 nM	9809715	502835	22037378
Lestaurtinib	Kd = 9.6 nM	126565		22037378
Hesperadin	Kd < 10 nM	10142586	514409	19035792
CHEMBL1591577	IC50 = 11 nM	44223973	1591577	21450467
NVP-TAE684	Kd = 12 nM	16038120	509032	22037378
CHEMBL1515144	IC50 = 14 nM	44968186	1515144	21450467
CHEMBL1082152	Kd = 16 nM	11560568	1082152	20138512
CHEMBL1474834	Kd = 18 nM	44223970	1474834	21450467
TG003	Kd = 19 nM	1893668	408982	19837585
GSK1838705A	Kd = 21 nM	25182616	464552	22037378
NCGC00010428	IC50 = 22 nM	3233012		21450467
Sunitinib	Kd = 22 nM	5329102	535	18183025
Cdk1/2 Inhibitor III	IC50 < 25 nM	5330812	261720	22037377
JAK3 Inhibitor VI	IC50 < 25 nM	16760524		22037377
K-252a; Nocardiopsis sp.	IC50 < 25 nM	3813	281948	22037377
Staurosporine	Kd = 27 nM	5279		15711537
CHEMBL1396483	IC50 = 28 nM	44223971	1396483	21450467
NCGC00010037	Kd = 37 nM	3232621		19837585
CHEMBL1435542	Kd = 50 nM	44223952	1435542	21450467
KW2449	Kd = 64 nM	11427553	1908397	22037378
R547	Kd = 66 nM	6918852		22037378
CHEMBL1396654	IC50 = 69 nM	44223953	1396654	21450467
CHEMBL1436585	Kd = 72 nM	46916178	1436585	21450467
CHEMBL1476499	IC50 = 86 nM	44223974	1476499	21450467
CHEMBL1552755	IC50 = 90 nM	44223955	1552755	21450467
AST-487	Kd = 110 nM	11409972	574738	18183025
CHEMBL566900	IC50 = 111 nM	44223977	566900	21450467
CHEMBL1704879	IC50 = 128 nM	46916172	1704879	21450467
CHEMBL1357975	IC50 = 130 nM	44223965	1357975	21450467
BML-275	IC50 > 150 nM	11524144	478629	22037377
PKR Inhibitor	IC50 > 150 nM	6490494	235641	22037377
CHEMBL1551169	IC50 = 173 nM	46916176	1551169	21450467
CHEMBL1705549	IC50 = 176 nM	46916170	1705549	21450467
CHEMBL1725513	IC50 = 192 nM	46916177	1725513	21450467
CHEMBL1354134	IC50 = 227 nM	46916179	1354134	21450467
IDR E804	IC50 > 250 nM	6419764	1802727	22037377
PKCb Inhibitor	IC50 > 250 nM	6419755	366266	22037377
SB218078	IC50 > 250 nM	447446	289422	22037377
SU11652	IC50 > 250 nM	24906267	13485	22037377
N-Benzoylstaurosporine	Kd = 350 nM	56603681	608533	18183025
SU14813	Kd = 360 nM	10138259	1721885	18183025
LKB1(AAK1 dual inhibitor)	Kd < 400 nM	44588117	516312	19035792
SureCN7685369	Kd < 400 nM	9925594	526901	19035792
AC1NS7CD	Kd = 410 nM	5329665	295136	22037378
SNS032	Kd = 410 nM	3025986	296468	18183025
Aloisine A	IC50 = 500 nM	5326843	75680	22037377
Gö6983	IC50 = 500 nM	3499	261491	22037377
IRAK-1-4 Inhibitor I	IC50 = 500 nM	11983295	379787	22037377
Enzastaurin	Kd = 510 nM	176167	300138	22037378
Foretinib	Kd = 550 nM	42642645	1230609	22037378
CHEMBL1734733	IC50 = 598 nM	46916182	1734733	21450467
Bosutinib	Kd = 600 nM	5328940	288441	22037378
Tandutinib	Kd = 630 nM	3038522	124660	18183025
JNJ-7706621	Kd = 660 nM	5330790	191003	18183025
PHA-665752	Kd = 730 nM	10461815	450786	22037378
Momelotinib	IC50 < 750 nM	25062766		19295546
PP242	Kd = 910 nM	25243800		22037378
Ruboxistaurin	Kd = 910 nM	153999	91829	18183025
BI2536	Kd = 940 nM	11364421	513909	22037378
AT7519	Kd = 990 nM	11338033		22037378
A 443654	IC50 < 1 µM	10172943	379300	19465931
Bisindolylmaleimide I	IC50 > 1 µM	2396	7463	22037377
Pelitinib	Kd = 1 µM	6445562	607707	15711537
Purvalanol A	IC50 > 1 µM	456214	23327	22037377
WZ3146	Kd > 1 µM	44607360		20033049
WZ4002	Kd > 1 µM	44607530		20033049
R406	Kd = 1.2 µM	11984591		22037378
Roscovitine	Kd = 1.2 µM	160355	14762	18183025
Alvocidib	Kd = 1.7 µM	9910986	428690	18183025
Nilotinib	Kd = 2.1 µM	644241	255863	22037378
TG101348	Kd = 2.5 µM	16722836	1287853	22037378
BMS-690514	Kd = 3 µM	11349170		21531814
SureCN4875304	IC50 > 3.5 µM	46871765		20472445
CHEMBL573339	Kd = 3.9 µM	9884685	573339	18183025
PI-103	Kd = 3.9 µM	16739368	538346	18183025

Disease Linkage

General Disease Association:

Facial disorders

Specific Diseases (Non-cancerous):

3mc syndrome 2

Comments:

CLK1 regulates the alternative splicing of tissue factor pre-mRNA in endothelial cells and adenovirus E1A pre-mRNA. A small molecule inhibitor of CLK1 significantly reduces influenza virus replication.

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: Bladder carcinomas (%CFC= +54, p<0.041); Cervical cancer stage 2A (%CFC= +61, p<0.008); Ovary adenocarcinomas (%CFC= -74, p<0.0001); Skin fibrosarcomas (%CFC= -63); and Skin melanomas - malignant (%CFC= -61, p<0.001). The COSMIC website notes an up-regulated expression score for CLK1 in diverse human cancers of 354, which is 0.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 24 for this protein kinase in human cancers was 0.4-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: 0.09 % in 24751 diverse cancer specimens. This rate is only 17 % 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: 0.38 % in 273 cervix cancers tested; 0.34 % in 603 endometrium cancers tested; 0.24 % in 864 skin cancers tested; 0.23 % in 1270 large intestine cancers tested; 0.18 % in 589 stomach cancers tested; 0.15 % in 1512 liver cancers tested; 0.13 % in 1634 lung cancers tested.

Frequency of Mutated Sites:

None > 3 in 20,034 cancer specimens

Comments:

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

COSMIC Entry:

CLK1

OMIM Entry:

601951

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:

3D Image (rendered using PV Viewer):

PDB ID

Subfamily Alignment

Domain Distribution:

Kinexus Products

hiddentext

Post-translation Modifications

Serine phosphorylated:

Threonine phosphorylated:

Tyrosine phosphorylated:

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 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

General Disease Association:

Specific Diseases (Non-cancerous):

Comments:

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: