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
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:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment

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
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:  
    14 14
 1055
 16
 944
 
 2 2
 185
 10
 92
 
 1.4 1.4
 110
 1
 0
 
 6 6
 495
 86
 960
 
 12 12
 890
 14
 726
 
 3 3
 204
 43
 364
 
 6 6
 463
 19
 631
 
 13 13
 991
 20
 1521
 
 9 9
 728
 10
 525
 
 3 3
 251
 44
 233
 
 20 20
 1550
 43
 4167
 
 10 10
 784
 105
 693
 
 2 2
 129
 12
 31
 
 2 2
 180
 9
 164
 
 2 2
 136
 11
 69
 
 1.4 1.4
 110
 8
 33
 
 2 2
 132
 104
 63
 
 3 3
 247
 7
 133
 
 8 8
 633
 88
 2124
 
 9 9
 727
 56
 718
 
 2 2
 180
 10
 54
 
 3 3
 259
 12
 148
 
 2 2
 142
 10
 91
 
 31 31
 2381
 48
 5754
 
 4 4
 323
 10
 224
 
 18 18
 1358
 28
 1798
 
 2 2
 189
 15
 127
 
 3 3
 246
 8
 183
 
 3 3
 267
 8
 184
 
 9 9
 669
 14
 157
 
 15 15
 1125
 18
 710
 
 100 100
 7705
 33
 9773
 
 0.9 0.9
 66
 56
 96
 
 10 10
 780
 31
 707
 
 7 7
 563
 22
 589
 
Evolution
Species Conservation
PhosphoNET % Identity:  
PhosphoNET % Similarity:  
  Homologene %
Identity:  
            PhosphoNET % Identity:  
PhosphoNET % Similarity:  
  Homologene %
Identity:  
    100 100
 100
 100
 76.7 76.7
 76.7
 100
 98 98
 98.3
 98
 - -
 -
 99
 - -
 -
 100
 59.4 59.4
 59.6
 99
 - -
 -
 -
 88.9 88.9
 89.7
 88
 76 76
 76.3
 99
 - -
 -
 -
 - -
 -
 -
 65.8 65.8
 70.7
 84
 53.3 53.3
 63.5
 77.5
 51.1 51.1
 63.3
 -
 - -
 -
 -
 34 34
 49.9
 -
 43.3 43.3
 53.9
 -
 - -
 -
 -
 - -
 -
 -
 - -
 -
 -
 - -
 -
 -
 - -
 -
 -
 30.7 30.7
 44.5
 -
 23.7 23.7
 41.8
 -
 - -
 -
 -
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
      
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 | 
|---|
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.
 

