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Updated November 2019

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Nomenclature

Short Name:
CLK3
Full Name:
Dual specificity protein kinase CLK3
Alias:
  • CDC like kinase 3
  • EC 2.7.12.1
  • FLJ22858
  • PHCLK3
  • PHCLK3/152

Classification

Type:
Protein-serine/threonine kinase
Group:
CMGC
Family:
CLK
SubFamily:
NA
 
 

Specific Links

Entrez-Gene Entry: 1198
Entrez-Protein Entry: NP_003983
GeneCards Entry: CLK3
KinBASE Entry: CLK3
OMIM Entry: 602990
Pfam Entry: P49761
PhosphoNET Entry: P49761
Phosphosite Plus Entry: 2137
Protein Data Bank Entry: 1EU9
ScanSite Entry: P49761
Source Entry: CLK3
UCSD-Nature Entry: A000667
UniProt Entry: P49761
Kinexus Products: CLK3
CLKSelectide - CLK3 protein kinase substrate peptide - Powder PE-01BGW99

General Links

ClustalW2
GPS-Cuckoo
Human Protein Atlas
Kinase.com
Kinase Research
Kinasource
Kinomer
Netphorest
NetworKIN
Phosida
PhosphoElm
Protein Blast
ScanSite
String

Structure

Mol. Mass (Da):
58588
# Amino Acids:
490
# mRNA Isoforms:
4
mRNA Isoforms:
73,515 Da (638 AA; P49761); 58,588 Da (490 AA; P49761-1); 56,207 Da (467 AA; P49761-3); 18,971 Da (152 AA; P49761-2)
4D Structure:
NA
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
3D Image (rendered using PV Viewer):

PDB ID
2EU9

Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
304 620 Pkinase
 

Kinexus Products

Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
○ CLKSelectide - CLK3 protein kinase substrate peptide - Powder PE-01BGW99
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:

S157, S165, S175, S197, S199, S215, S224, S226, S265, S270, S271, S280, S281, S283.
Threonine phosphorylated:

T217, T314.
Tyrosine phosphorylated:

Y155, Y163, Y166, Y218, Y232.
Ubiquitinated:
K317, K460, K557, K573, K123.
 

Distribution

Based on gene microarray analysis from the NCBI
Human Tissue Distribution
% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:
% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:
  • adipose
    14

    1055

    16

    944

  • adrenal
    2

    185

    10

    92

  • bladder
    1.4

    110

    1

    0

  • brain
    6

    495

    86

    960

  • breast
    12

    890

    14

    726

  • cervix
    3

    204

    43

    364

  • colon
    6

    463

    19

    631

  • heart
    13

    991

    20

    1521

  • intestine
    9

    728

    10

    525

  • kidney
    3

    251

    44

    233

  • liver
    20

    1550

    43

    4167

  • lung
    10

    784

    105

    693

  • lymphnode
    2

    129

    12

    31

  • ovary
    2

    180

    9

    164

  • pancreas
    2

    136

    11

    69

  • pituitary
    1.4

    110

    8

    33

  • prostate
    2

    132

    104

    63

  • salivarygland
    3

    247

    7

    133

  • skeletalmuscle"
    8

    633

    88

    2124

  • skin
    9

    727

    56

    718

  • spinalcord
    2

    180

    10

    54

  • spleen
    3

    259

    12

    148

  • stomach
    2

    142

    10

    91

  • testis
    31

    2381

    48

    5754

  • thymus
    4

    323

    10

    224

  • thyroid
    18

    1358

    28

    1798

  • tonsil
    2

    189

    15

    127

  • trachea
    3

    246

    8

    183

  • uterus
    3

    267

    8

    184

  • reticulocytes"
    9

    669

    14

    157

  • t-lymphocytes
    15

    1125

    18

    710

  • b-lymphocytes
    100

    7705

    33

    9773

  • neutrophils
    0.9

    66

    56

    96

  • macrophages
    10

    780

    31

    707

  • sperm
    7

    563

    22

    589

 

Evolution

Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
  • tableheader
    100

    100

    100
  • tableheader
    76.7

    76.7

    100
  • tableheader
    98

    98.3

    98
  • tableheader
    -

    -

    99
  • tableheader
    -

    -

    100
  • tableheader
    59.4

    59.6

    99
  • tableheader
    -

    -

    -
  • tableheader
    88.9

    89.7

    88
  • tableheader
    76

    76.3

    99
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    65.8

    70.7

    84
  • tableheader
    53.3

    63.5

    77.5
  • tableheader
    51.1

    63.3

    -
  • tableheader
    -

    -

    -
  • tableheader
    34

    49.9

    -
  • tableheader
    43.3

    53.9

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    30.7

    44.5

    -
  • tableheader
    23.7

    41.8

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Binding Proteins

Examples of known interacting proteins
hiddentext
No. Name – UniProt ID
1 C1orf63 - Q9BUV0
2 YWHAG - P61981
 

Regulation

Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
 

Protein Kinase Specificity

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

Kinections GIF
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 #:
1
 

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
R547 Kd = 13 nM 6918852 22037378
Silmitasertib IC50 = 41 nM 24748573 21174434
Cdk1/2 Inhibitor III IC50 > 50 nM 5330812 261720 22037377
Flt-3 Inhibitor II IC50 > 150 nM 11601743 377193 22037377
Gö6976 IC50 > 150 nM 3501 302449 22037377
IDR E804 IC50 > 150 nM 6419764 1802727 22037377
IRAK-1-4 Inhibitor I IC50 > 150 nM 11983295 379787 22037377
A674563 Kd = 160 nM 11314340 379218 22037378
NVP-TAE684 Kd = 210 nM 16038120 509032 22037378
1;9-Pyrazoloanthrone IC50 > 250 nM 8515 7064 22037377
Gö6983 IC50 > 250 nM 3499 261491 22037377
GSK-3 Inhibitor XIII IC50 > 250 nM 6419766 359482 22037377
SureCN2579964 IC50 < 250 nM 24948986 22934575
Bosutinib Kd = 300 nM 5328940 288441 22037378
CHEMBL1082152 Kd = 310 nM 11560568 1082152 20138512
JNJ-7706621 Kd = 310 nM 5330790 191003 18183025
AT7519 Kd = 370 nM 11338033 22037378
SureCN2505235 IC50 < 400 nM 23649240 22934575
CHEMBL1551169 IC50 = 435 nM 46916176 1551169 21450467
NCGC00010037 Kd = 470 nM 3232621 19837585
AG-E-60384 IC50 = 500 nM 6419741 413188 22037377
BCP9000906 IC50 = 500 nM 5494425 21156 22037377
HDS029 IC50 = 500 nM 11566580 203644 22037377
Indirubin-3′-monoxime IC50 = 500 nM 5326739 22037377
WHI-P154 IC50 = 500 nM 3795 473773 22037377
BI2536 Kd = 630 nM 11364421 513909 22037378
Staurosporine Kd = 910 nM 5279 18183025
A 443654 IC50 < 1 µM 10172943 379300 19465931
Alvocidib Kd = 1 µM 9910986 428690 15711537
GSK-3b Inhibitor XI IC50 > 1 µM 10020713 272629 22037377
JAK3 Inhibitor VI IC50 > 1 µM 16760524 22037377
MK5108 IC50 > 1 µM 24748204 20053775
PKR Inhibitor IC50 > 1 µM 6490494 235641 22037377
ST078197 IC50 > 1 µM 1048845 210833 22037377
WZ3146 Kd > 1 µM 44607360 20033049
WZ4002 Kd > 1 µM 44607530 20033049
Hesperadin Kd < 1.25 µM 10142586 514409 19035792
CHEMBL1354134 IC50 = 1.32 µM 46916179 1354134 21450467
CHEMBL1474834 IC50 = 1.924 µM 44223970 1474834 21450467
Momelotinib IC50 > 2 µM 25062766 19295546
CHEMBL1357975 IC50 = 2.017 µM 44223965 1357975 21450467
Pelitinib Kd = 2.1 µM 6445562 607707 15711537
MLN8054 Kd = 2.3 µM 11712649 259084 18183025
SureCN7685369 Kd < 2.5 µM 9925594 526901 19035792
CHEMBL1725513 IC50 = 2.556 µM 46916177 1725513 21450467
BMS-690514 Kd = 3 µM 11349170 21531814
TG003 Kd = 3 µM 1893668 408982 19837585
CHEMBL1704879 IC50 = 3.019 µM 46916172 1704879 21450467
CHEMBL1552755 IC50 = 3.294 µM 44223955 1552755 21450467
CHEMBL1705549 IC50 = 3.527 µM 46916170 1705549 21450467
N-Benzoylstaurosporine Kd = 3.6 µM 56603681 608533 22037378
PHA-665752 Kd = 3.6 µM 10461815 450786 22037378
CHEMBL1436585 IC50 = 3.642 µM 46916178 1436585 21450467
CHEMBL566900 IC50 = 4.65 µM 44223977 566900 21450467
CHEMBL1396483 IC50 = 4.655 µM 44223971 1396483 21450467
CHEMBL1591577 IC50 = 4.949 µM 44223973 1591577 21450467
 

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: Large B-cell lymphomas (%CFC= +45, p<0.041); Large B-cell lymphomas (%CFC= +45, p<0.047); and Skin melanomas - malignant (%CFC= +66, p<0.0001). The COSMIC website notes an up-regulated expression score for CLK3 in diverse human cancers of 416, which is 0.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 99 for this protein kinase in human cancers was 1.7-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: 0.07 % in 24751 diverse cancer specimens. This rate is only -4 % lower and is very similar to 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: 0.59 % in 589 stomach cancers tested; 0.26 % in 1270 large intestine cancers tested; 0.24 % in 603 endometrium cancers tested; 0.23 % in 710 oesophagus cancers tested; 0.09 % in 1316 breast cancers tested.
Frequency of Mutated Sites:

None > 2 in 20,034 cancer specimens
Comments:
Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
CLK3
OMIM Entry:
602990
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