Nomenclature
Short Name:
BRSK1
Full Name:
BR serine/threonine-protein kinase 1
Alias:
- BR serine/threonine kinase 1
- EC 2.7.11.1
- KIAA1811
- SAD1
- SAD1 kinase
- SAD1A
Classification
Type:
Protein-serine/threonine kinase
Group:
CAMK
Family:
CAMKL
SubFamily:
BRSK
Structure
Mol. Mass (Da):
86,753
# Amino Acids:
794
# mRNA Isoforms:
3
mRNA Isoforms:
86,753 Da (794 AA; Q8TDC3-2); 85,087 Da (778 AA; Q8TDC3); 38,782 Da (343 AA; Q8TDC3-3)
4D Structure:
NA
1D Structure:
Subfamily Alignment
Domain Distribution:
Kinexus Products
Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
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Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:
S193-, S275, S399, S404, S413, S427, S432, S443, S447, S508, S515, S563, S587.
Threonine phosphorylated:
T189+, T417, T583, T772.
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
1782
9
1707
19
338
6
513
-
-
-
-
77
1381
30
2893
37
658
10
450
0.8
14
9
10
5
96
13
56
45
809
7
893
2
30
3
5
47
837
7
891
27
474
7
716
46
819
13
594
25
437
2
356
18
317
5
490
34
598
7
728
8
138
7
175
17
304
11
532
24
427
5
552
55
982
5
1328
27
478
28
217
83
1483
7
2236
19
345
5
391
-
-
-
-
43
772
7
985
27
488
7
458
36
636
21
610
5
81
5
50
22
389
5
512
6
114
5
169
-
-
-
-
59
1043
12
59
38
680
13
2173
0.2
4
12
0
45
793
26
415
14
244
22
153
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
0
0
99
-
-
-
-
-
99
-
-
-
98.1
98.2
98
-
-
-
94.8
95.4
99
29.2
44.5
99
-
-
-
32.1
33.3
-
28.3
43.9
-
-
-
84
25.1
38.5
81
-
-
-
48.5
62.5
53
-
-
-
25.7
37.9
34
-
-
-
-
-
-
-
-
-
-
-
-
27
41.9
-
22.2
34.2
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
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| No. | Name – UniProt ID |
|---|---|
| 1 | CDC25C - P30307 |
| 2 | CDC25B - P30305 |
| 3 | WEE1 - P30291 |
| 4 | NUAK1 - O60285 |
Regulation
Activation:
Activated by phosphorylation on Thr-205 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39
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 |
|---|
| AMPKa1 (PRKAA1) | Q13131 | T183 | SDGEFLRTSCGSPNY | + |
| BRSK1 | Q8TDC3 | S193 | LLETSCGSPHYACPE | - |
| BRSK1 | Q8TDC3 | T189 | VGDSLLETSCGSPHY | + |
| Cdc25B | P30305 | S375 | ARVLRSKSLCHDEIE | |
| Cdc25C | P30307 | S216 | SGLYRSPSMPENLNR | ? |
| MAPT/TAU | P10636 | S579 | NVKSKIGSTENLKHQ | |
| MAPT/TAU | P10636 | T529 | TPGSRSRTPSLPTPP | |
| TUBG1 | P23258 | S131 | READGSDSLEGFVLC | + |
| TUBG2 | Q9NRH3 | S131 | READGSDSLEGFVLC | + |
| Wee1 | P30291 | S642 | KKMNRSVSLTIY___ | - |
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:
Menopause
Specific Diseases (Non-cancerous):
Premature ovarian failure (POF); age at natural menopause (AANM)
Comments:
The rs12611091 SNP in BRSK1 can lead to premature ovarian failure, which is a rare condition.
Mutagenesis Experiments:
Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis. BRSK1's phosphotransferase activity was lost with the K59A, and G327A mutations.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.1 % in 24433 diverse cancer specimens. This rate is only 35 % 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: 0.33 % in 1229 large intestine cancers tested; 0.21 % in 710 oesophagus cancers tested; 0.18 % in 555 stomach cancers tested; 0.16 % in 864 skin cancers tested; 0.14 % in 548 urinary tract cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: R303W (5).
Comments:
Twelve R379fs*9 deletions, 9 other deletions, 9 R379fs*54 insertions mutations, and no complex mutations.