Nomenclature
Short Name:
caMLCK
Full Name:
Cardiac-MyBP-C-associated Ca/CaM kinase
Alias:
- caMLCK
- EC=2.7.11.18
- MGC126319
- MGC126320
- Myosin light chain kinase 3
- MYLK3
Classification
Type:
Protein-serine/threonine kinase
Group:
CAMK
Family:
MLCK
SubFamily:
NA
Structure
Mol. Mass (Da):
88,393
# Amino Acids:
819
# mRNA Isoforms:
2
mRNA Isoforms:
88,393 Da (819 AA; Q32MK0); 52,723 Da (478 AA; Q32MK0-4)
4D Structure:
NA
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 515 | 770 | Pkinase |
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:
S401, S408, S450, S536.
Threonine phosphorylated:
T537, T807.
Tyrosine phosphorylated:
Y804.
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:
100
1069
40
1113
0.7
7
12
7
2
20
1
0
6
63
132
179
47
505
45
298
0.5
5
73
6
0.7
7
55
8
99
1054
15
1292
29
310
10
316
4
42
57
44
0.7
8
12
6
57
606
87
404
0.5
5
12
4
0.8
9
6
9
1
16
9
11
0.8
9
27
11
1
11
31
18
2
19
6
14
15
158
69
122
41
434
153
299
3
35
8
46
1
12
10
9
0.8
9
2
8
2
25
6
25
0.9
10
8
10
47
507
86
468
0.7
8
15
9
1
11
6
5
1
12
6
7
16
174
28
159
28
300
18
216
26
282
41
539
0.5
5
65
3
60
645
130
590
7
79
74
76
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
32.5
40.4
99
94.5
95.9
94.5
-
-
76
-
-
-
45.3
53.3
72
-
-
-
69.2
76.5
72
37.2
50.6
71
-
-
-
49.4
58.1
-
21.7
29.8
54
-
-
61
-
-
-
-
-
-
-
-
45
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
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:
Derived from alignment of 45 peptides phosphorylated by recombinant MYLK3 in vitro tested in-house by Kinexus.
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 |
|---|
| Dovitinib | Kd = 2 nM | 57336746 | ||
| KW2449 | Kd = 4.3 nM | 11427553 | 1908397 | 22037378 |
| Lestaurtinib | Kd = 12 nM | 126565 | 22037378 | |
| Tozasertib | Kd = 15 nM | 5494449 | 572878 | 22037378 |
| Sunitinib | Kd = 23 nM | 5329102 | 535 | 22037378 |
| SU14813 | Kd = 42 nM | 10138259 | 1721885 | 22037378 |
| Nintedanib | Kd = 110 nM | 9809715 | 502835 | 22037378 |
| PD173955 | Kd = 140 nM | 447077 | 386051 | 22037378 |
| Staurosporine | Kd = 140 nM | 5279 | 22037378 | |
| PP242 | Kd = 360 nM | 25243800 | 22037378 | |
| A674563 | Kd = 400 nM | 11314340 | 379218 | 22037378 |
| Quizartinib | Kd = 410 nM | 24889392 | 576982 | 22037378 |
| WZ3146 | Kd > 1 µM | 44607360 | 20033049 | |
| WZ4002 | Kd > 1 µM | 44607530 | 20033049 | |
| AC1NS7CD | Kd = 1.7 µM | 5329665 | 295136 | 22037378 |
| Axitinib | Kd = 1.7 µM | 6450551 | 1289926 | 22037378 |
| SNS032 | Kd = 1.7 µM | 3025986 | 296468 | 22037378 |
| N-Benzoylstaurosporine | Kd = 2.3 µM | 56603681 | 608533 | 22037378 |
| Foretinib | Kd = 3 µM | 42642645 | 1230609 | 22037378 |
Disease Linkage
General Disease Association:
Inflammatory disorders
Specific Diseases (Non-cancerous):
Colitis
Comments:
Inhibition of MYLK3 can rescue inflammatory bowel cell characteristics in vitro, and MYLK3 overexpression has been positively linked with Colitis.
Gene Expression in Cancers:
The COSMIC website notes an up-regulated expression score for MYLK3 in diverse human cancers of 313, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than 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 24764 diverse cancer specimens. This rate is only 14 % 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 864 skin cancers tested; 0.29 % in 1296 large intestine cancers tested; 0.18 % in 603 endometrium cancers tested; 0.17 % in 710 oesophagus cancers tested; 0.17 % in 589 stomach cancers tested; 0.16 % in 548 urinary tract cancers tested; 0.13 % in 1634 lung cancers tested; 0.09 % in 833 ovary cancers tested; 0.09 % in 273 cervix cancers tested; 0.08 % in 881 prostate cancers tested; 0.06 % in 1276 kidney cancers tested; 0.05 % in 238 bone cancers tested; 0.04 % in 2081 central nervous system cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: V594A (3).
Comments:
Only 1 deletion, and no insertions or complex mutations are noted on the COSMIC website.