Nomenclature
Short Name:
MAST3
Full Name:
Microtubule-associated serine-threonine-protein kinase 3
Alias:
- EC 2.7.11.1
- KIAA0561
- Microtubule associated serine/threonine kinase 3
Classification
Type:
Protein-serine/threonine kinase
Group:
AGC
Family:
MAST
SubFamily:
NA
Structure
Mol. Mass (Da):
143,137
# Amino Acids:
1309
# mRNA Isoforms:
1
mRNA Isoforms:
143,137 Da (1309 AA; O60307)
4D Structure:
NA
1D Structure:
Subfamily Alignment
Domain Distribution:
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
M1.
Methylated:
R878, R892.
Serine phosphorylated:
S39, S47, S66, S85, S88, S134, S135, S146, S153, S155, S157, S259, S277, S348, S672, S680, S698, S699, S709, S710, S711, S728, S747, S754, S760, S774, S782, S792, S793, S847, S880, S885, S889, S898, S912, S1060, S1063, S1201, S1203, S1215, S1223, S1257, S1262, S1273.
Threonine phosphorylated:
T37, T121, T164, T369, T665, T685.
Tyrosine phosphorylated:
Y176, Y524, Y546, Y557, Y708, Y977.
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:
51
887
16
1115
3
55
7
16
3
47
1
0
57
1005
43
532
46
814
10
547
11
186
45
389
23
409
16
574
100
1756
15
4657
41
727
7
441
7
120
42
55
7
122
11
68
36
634
92
586
6
108
12
18
4
74
6
47
8
146
8
59
4
76
8
50
3
59
97
24
7
118
5
119
2
43
40
29
26
459
53
454
15
269
7
139
11
199
9
107
3
58
2
22
6
98
5
68
6
106
7
47
66
1163
25
1599
6
109
12
14
3
45
5
27
3
61
5
15
6
113
14
83
9
161
6
43
49
869
15
695
8
142
54
272
57
997
26
806
2
40
22
35
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
88.9
89.7
97
88.7
89.6
97
-
-
92
-
-
-
92.8
95.2
94
-
-
-
88.6
91.5
90
52.1
62.4
90
-
-
-
52.1
62.2
-
71.5
78.8
78
67.2
74.8
77
45.2
54
71
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | PTEN - P60484 |
| 2 | CNTNAP4 - Q9C0A0 |
| 3 | YWHAH - Q04917 |
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
Disease Linkage
General Disease Association:
Gastrointestinal disorders
Specific Diseases (Non-cancerous):
Inflammatory bowel disease (IBD)
Comments:
Inflammatory bowel disease (IBD) is a gastrointestinal disease characterized by recurrent inflammation of the bowels, leading to gastrointestinal distress. The general term IBD encompasses the inflammatory disorders Crohn's disease and ulcerative colitis. IBD is thought to be caused by over-exaggerated inflammatory responses to commensal microbes found in the gastrointestinal tract. The occurence of IBD shows a strong familial component, indicating that genetic factors may be important contributors to the disease pathogenesis. In a genome-wide association study (GWAS), an intronic variant (rs273506) was mapped to the MAST3 gene that was found to be closely associated with the occurence of IBD. In addition, MAST3 expression was demonstrated in antigen-presenting cells and in lymphocytes, providing a potential mechanistic link between altered MAST3 expression and recurrent bowel inflammation. Furthermore, knockdown of MAST3 expression resulted in reduced Toll-like receptor-4 dependent NF-kappa-B activation, which is associated with IBD pathogenesis.
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: Barrett's esophagus epithelial metaplasia (%CFC= +92, p<0.0006); Breast epithelial cell carcinomas (%CFC= +54, p<0.047); Classical Hodgkin lymphomas (%CFC= -47, p<0.009); Large B-cell lymphomas (%CFC= +48, p<0.024); Pituitary adenomas (ACTH-secreting) (%CFC= -64); and Prostate cancer (%CFC= +107, p<0.062). The COSMIC website notes an up-regulated expression score for MAST3 in diverse human cancers of 351, which is 0.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 17 for this protein kinase in human cancers was 0.3-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: 0.05 % in 24892 diverse cancer specimens. This rate is only -31 % lower 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: 0.23 % in 1259 large intestine cancers tested; 0.2 % in 273 cervix cancers tested; 0.19 % in 603 endometrium cancers tested; 0.19 % in 589 stomach cancers tested; 0.16 % in 864 skin cancers tested; 0.12 % in 127 biliary tract cancers tested; 0.08 % in 548 urinary tract cancers tested; 0.06 % in 710 oesophagus cancers tested; 0.06 % in 1512 liver cancers tested; 0.05 % in 833 ovary cancers tested; 0.05 % in 1459 pancreas cancers tested; 0.04 % in 382 soft tissue cancers tested; 0.04 % in 1822 lung cancers tested; 0.04 % in 1276 kidney cancers tested; 0.03 % in 238 bone cancers tested; 0.03 % in 1305 breast cancers tested; 0.02 % in 942 upper aerodigestive tract cancers tested; 0.02 % in 2082 central nervous system cancers tested; 0.01 % in 881 prostate cancers tested; 0.01 % in 558 thyroid cancers tested.
Frequency of Mutated Sites:
None > 4 in 20,175 cancer specimens
Comments:
Only 4 deletions, 2 insertions, and no complex mutations are noted on the COSMIC website.