Nomenclature
Short Name:
CDKL2
Full Name:
Cyclin-dependent kinase-like 2
Alias:
- EC 2.7.11.22
- Kinase CdkL2
- KKIAMRE
- P56
- Protein kinase p56 KKIAMRE
- Serine/threonine-protein kinase KKIAMRE
Classification
Type:
Protein-serine/threonine kinase
Group:
CMGC
Family:
CDKL
SubFamily:
NA
Structure
Mol. Mass (Da):
56,019
# Amino Acids:
493
# mRNA Isoforms:
1
mRNA Isoforms:
56,019 Da (493 AA; Q92772)
4D Structure:
NA
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 4 | 287 | 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
Acetylated:
K357, K360.
Serine phosphorylated:
S359.
Tyrosine phosphorylated:
Y15-, Y161+.
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:
69
1025
22
1254
0.6
9
11
8
2
33
7
28
17
255
81
366
20
291
24
236
0.4
6
46
10
11
169
29
411
39
580
26
1027
13
188
10
193
6
84
71
85
0.7
11
21
12
42
618
98
655
0.9
14
18
16
1.5
22
9
15
3
38
19
38
0.4
6
13
6
4
65
171
497
0.9
14
10
11
1.3
19
67
19
19
288
84
285
8
114
18
138
0.8
12
19
13
4
53
8
43
33
485
14
519
0.8
12
15
12
100
1488
50
3626
1.1
16
21
21
2
32
14
29
2
23
14
23
14
202
28
141
26
382
18
280
25
378
26
508
7
106
59
295
46
678
52
586
5
72
35
69
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
79.5
81.8
92
84
84.9
97
-
-
89
-
-
-
78.3
82.2
91
-
-
-
74.8
80.3
88
81.8
87
86
-
-
-
38.1
55.7
-
29.8
41.8
70
30.2
43.8
66
39.1
53.5
-
-
-
-
28
41.8
-
-
-
-
-
-
-
33.6
44.3
-
-
-
-
-
-
-
-
-
-
27.6
40.8
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | CBL - P22681 |
| 2 | PSMC4 - P43686 |
| 3 | PSMD6 - Q15008 |
| 4 | PSMD10 - O75832 |
| 5 | PAAF1 - Q9BRP4 |
| 6 | PSMD2 - Q13200 |
| 7 | TESC - Q96BS2 |
Regulation
Activation:
Likely that phosphorylation at Tyr-161 is required for catalytic activity based on homology with other CDK's.
Inhibition:
Likely that phosphorylation at Tyr-15 is inhibitory based on homology with other CDK's.
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
General Disease Association:
Cancer
Specific Cancer Types:
Breast cancer
Comments:
CDKL2 may be an oncoprotein (OP). CDKL2 has been identified as a novel potent promoter for epithelial-mesenchymal transition and breast cancer progression (PubMed: 25333262). CDKL2 stimulated primary tumour formation and metastasis in a breast cancer xenograft model. It is expressed at significantly higher levels mesenchymal human breast cancer cell lines than in epithelial lines, and its over-expression/amplification in human breast cancers is correlated with shorter disease-free survival.
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= -49, p<0.0002); Breast epithelial carcinomas (%CFC= -76, p<0.059); and Ovary adenocarcinomas (%CFC= -61, p<0.003). The COSMIC website notes an up-regulated expression score for CDKL2 in diverse human cancers of 372, which is 0.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 12 for this protein kinase in human cancers was 0.2-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 24846 diverse cancer specimens. This rate is only 25 % 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: 0.54 % in 1119 large intestine cancers tested; 0.37 % in 814 upper aerodigestive tract cancers tested; 0.33 % in 805 skin cancers tested; 0.14 % in 1619 lung cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: T383K (15).
Comments:
Thirteen deletions (8 at K74fs*5 deletionsframeshift in the kinase catalytic domain), 2 insertions and no complex mutations are noted on the COSMIC website.