Nomenclature
Short Name:
SBK1
Full Name:
SH3-binding kinase
Alias:
- BG683070
- EC 2.7.11.1
- Serine/threonine-protein kinase SBK1
- SBK.
Classification
Type:
Protein-serine/threonine kinase
Group:
Other
Family:
NKF1
SubFamily:
NA
Structure
Mol. Mass (Da):
46,252
# Amino Acids:
424
# mRNA Isoforms:
1
mRNA Isoforms:
46,252 Da (424 AA; Q52WX2)
4D Structure:
NA
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 53 | 318 | Pkinase |
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:
S47.
Threonine phosphorylated:
T50, T63-.
Tyrosine phosphorylated:
Y53.
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:
46
1397
12
996
1.4
43
2
7
-
-
-
-
7
210
54
223
28
838
18
425
0.3
9
18
7
0.3
10
20
7
100
3037
7
4205
-
-
-
-
1.4
41
52
81
9
279
4
343
32
973
16
476
-
-
-
-
-
-
-
-
4
126
4
94
1.4
41
10
19
5
148
88
85
-
-
-
-
12
371
36
174
15
453
56
282
9
282
4
233
10
303
4
235
-
-
-
-
-
-
-
-
21
625
4
261
37
1129
36
1474
-
-
-
-
-
-
-
-
-
-
-
-
3
100
28
88
57
1719
12
32
75
2289
16
3957
16
474
57
639
23
704
52
616
3
104
31
88
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
26.6
36
99
80.7
81.4
-
-
-
94
-
-
-
76.7
78.5
98
-
-
-
94.3
95
95
94.8
95.5
96
-
-
-
73.1
80.4
-
72.2
80.7
80
33.7
48.6
76
48.6
62
68
-
-
-
-
-
37
30.4
47.2
-
-
-
29
32.1
49.8
-
-
-
-
-
-
-
-
-
-
24.3
39.2
-
-
-
-
-
-
-
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:
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 |
|---|
| Staurosporine | Kd = 3.2 nM | 5279 | 22037378 | |
| NVP-TAE684 | Kd = 21 nM | 16038120 | 509032 | 22037378 |
| R406 | Kd = 93 nM | 11984591 | 22037378 | |
| Nintedanib | Kd = 110 nM | 9809715 | 502835 | 22037378 |
| Aurora A Inhibitor 23 (DF) | Kd < 200 nM | 21992004 | ||
| Lestaurtinib | Kd = 200 nM | 126565 | 22037378 | |
| Sunitinib | Kd = 200 nM | 5329102 | 535 | 22037378 |
| Gefitinib | Kd = 560 nM | 123631 | 939 | 22037378 |
| KW2449 | Kd = 580 nM | 11427553 | 1908397 | 22037378 |
| SU14813 | Kd = 620 nM | 10138259 | 1721885 | 22037378 |
| TG101348 | Kd = 790 nM | 16722836 | 1287853 | 22037378 |
| Aurora A Inhibitor 1 (DF) | Kd = 1 µM | 21992004 | ||
| Aurora A Inhibitor 29 (DF) | Kd = 1 µM | 21992004 | ||
| WZ3146 | Kd > 1 µM | 44607360 | 20033049 | |
| WZ4002 | Kd > 1 µM | 44607530 | 20033049 | |
| Dasatinib | Kd = 1.2 µM | 11153014 | 1421 | 22037378 |
| Erlotinib | Kd = 1.2 µM | 176870 | 553 | 22037378 |
| Crizotinib | Kd = 1.3 µM | 11626560 | 601719 | 22037378 |
| Ruxolitinib | Kd = 1.3 µM | 25126798 | 1789941 | 22037378 |
| Dovitinib | Kd = 1.5 µM | 57336746 | 22037378 | |
| JNJ-28312141 | Kd = 3.1 µM | 22037378 | ||
| Afatinib | Kd = 4.8 µM | 10184653 | 1173655 | 22037378 |
Disease Linkage
General Disease Association:
Cancer
Specific Cancer Types:
Esophagus squamous cell carcinomas
Comments:
SBK1 might be an oncoprotein (OP). SBK1 expression has been observed to be dysregulated in ovarian and several human cancer types. Significantly elevated SBK1 expression has been observed in ovarian cancer cell lines. The elevated expression of SBK1 was shown to protect the cancer cells from apoptosis induced by viral infection, thus the SBK1 protein is thought to act as an anti-apoptosis factor that promotes cancer cell survival. Therefore, the SBK1 protein appears to have an oncogenic role in ovarian cancer. A missense mutation in the SBK1 gene (K92E) was observed in human ovarian mucinous carcinoma specimens, potentially reflecting a gain-of-function in the SBK1 protein. Interestingly, the significant down-regulation of SBK1 expression has been observed in esophagus squamous cell carcinoma and stomach adenocarinoma, potentially reflecting a cell context-dependent role for the SBK1 protein.
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: Breast epithelial carcinomas (%CFC= -71, p<0.004); Breast epithelial hyperplastic enlarged lobular units (HELU) (%CFC= +47, p<0.071); Ovary adenocarcinomas (%CFC= +191, p<0.0001); and Prostate cancer (%CFC= +88, p<0.0005).
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 24433 diverse cancer specimens. This rate is only -10 % 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: 0.55 % in 864 skin cancers tested; 0.3 % in 1270 large intestine cancers tested; 0.16 % in 589 stomach cancers tested; 0.14 % in 1634 lung cancers tested; 0.13 % in 710 oesophagus cancers tested; 0.1 % in 238 bone cancers tested; 0.09 % in 548 urinary tract cancers tested; 0.08 % in 603 endometrium cancers tested; 0.06 % in 1276 kidney cancers tested; 0.05 % in 942 upper aerodigestive tract cancers tested; 0.04 % in 558 thyroid cancers tested; 0.03 % in 2103 central nervous system cancers tested; 0.03 % in 1459 pancreas cancers tested.
Frequency of Mutated Sites:
None > 3 in 20,075 cancer specimens
Comments:
Only 2 deletions, and no insertions or complex mutations are noted on the COSMIC website.