Nomenclature
Short Name:
MST4
Full Name:
Serine-threonine-protein kinase MST4
Alias:
- EC 2.7.11.1
- MASK
- RP6-213H19.1
- Serine/threonine protein kinase MST4
Classification
Type:
Protein-serine/threonine kinase
Group:
STE
Family:
STE20
SubFamily:
YSK
Structure
Mol. Mass (Da):
46,529
# Amino Acids:
416
# mRNA Isoforms:
3
mRNA Isoforms:
46,529 Da (416 AA; Q9P289); 39,658 Da (354 AA; Q9P289-3); 37,770 Da (339 AA; Q9P289-2)
4D Structure:
Homodimer. Interacts with PDCD10 and GOLGA2.
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 24 | 274 | Pkinase |
| 50 | 77 | Coiled-coil |
| 364 | 391 | Coiled-coil |
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:
S4, S34, S260, S300, S304, S306, S309, S325.
Threonine phosphorylated:
T170, T172+, T178+, T182-, T264, T320, T327, T328.
Tyrosine phosphorylated:
Y86, Y89, Y101.
Ubiquitinated:
K32, K40, K146, K175, K214, K233, K280, K401.
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:
24
1208
22
1152
0.2
11
6
9
3
169
11
90
21
1070
83
3218
18
919
19
578
1.3
65
46
37
2
105
22
76
100
5132
36
8484
16
821
7
526
0.4
23
68
27
1.1
54
24
42
13
648
92
616
3
177
23
143
0.5
26
3
35
1.1
59
10
73
0.7
37
12
52
6
328
166
1661
2
98
14
66
0.3
17
63
15
13
681
81
615
0.5
28
20
29
4
182
21
255
2
119
13
88
0.6
33
14
24
10
531
20
751
87
4448
57
8055
3
159
22
109
2
96
14
64
11
587
14
493
0.5
24
28
20
29
1494
18
703
17
864
26
1565
5
280
67
365
15
747
52
650
3
177
35
352
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
60.5
62
100
39.2
56.9
100
-
-
99
-
-
-
66.3
66.5
100
-
-
-
98.1
99.3
98
38.7
57
99
-
-
-
73.1
78.8
-
38.5
56.4
92
38.1
56
88
37.4
55.7
78
-
-
-
28.7
44
83
-
-
-
34.8
53.7
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
20.6
28.7
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | MOBKL3 - Q9Y3A3 |
| 2 | STRN - O43815 |
| 3 | PPP2CA - P67775 |
| 4 | CTTNBP2 - Q8WZ74 |
| 5 | SLMAP - Q14BN4 |
| 6 | STRN4 - Q9NRL3 |
| 7 | CTTNBP2NL - Q9P2B4 |
| 8 | FGFR1OP2 - Q9NVK5 |
| 9 | FAM40B - Q9ULQ0 |
| 10 | PPP2R1A - P30153 |
| 11 | RAF1 - P04049 |
Regulation
Activation:
Interaction with Golgi matrix protein GOLGA2 leads to autophosphorylation on Thr-178, possibly as a consequence of stabilization of dimer formation. May also be activated by C-terminal cleavage.
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
Known Upstream Kinases
For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET
predictions.
Based on in vitro and/or in vivo phosphorylation data
| Kinase Short Name | UniProt ID (Human) | Phosphosite Location | Phosphosite Sequence | Effect of Phosphorylation |
|---|
Known Downstream Substrates
For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET
predictions.
Based on in vitro and/or in vivo phosphorylation data
| Substrate Short Name | UniProt ID (Human) | Phosphosite Location | Phosphosite Sequence | Effect of Phosphorylation |
|---|
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:
Prostate cancer
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= +132, p<0.003); Breast epithelial carcinomas (%CFC= -53, p<0.096); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= -56, p<0.016); Ovary adenocarcinomas (%CFC= -85, p<0.002); Prostate cancer - metastatic (%CFC= -72, p<0.0001); Skin melanomas - malignant (%CFC= -88, p<0.0002); Uterine fibroids (%CFC= -56, p<0.002); Uterine leiomyomas from fibroids (%CFC= -51, p<0.104); and Vulvar intraepithelial neoplasia (%CFC= +63, p<0.097). The COSMIC website notes an up-regulated expression score for MST4 in diverse human cancers of 597, which is 1.3-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 65 for this protein kinase in human cancers was 1.1-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. MST4 phosphotransferase activity can also be increased through deleting the C-terminal. A conserved and catalytically important residue is K53.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 25411 diverse cancer specimens. This rate is very similar (+ 10% higher) 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: 0.44 % in 1093 large intestine cancers tested; 0.42 % in 805 skin cancers tested; 0.4 % in 602 endometrium cancers tested; 0.2 % in 1941 lung cancers tested.
Frequency of Mutated Sites:
None > 4 in 20,694 cancer specimens
Comments:
Only 2 deletions, and no insertions or complex mutations are noted on the COSMIC website.