Nomenclature
Short Name:
TSSK2
Full Name:
Testis-specific serine-threonine protein kinase 2
Alias:
- DGSG
- DiGeorge syndrome protein G
- ST2B
- STK22B
- Testis-specific kinase 2
- Testis-specific serine kinase 2; TSSK-2; TSK2
- EC 2.7.11.1
- FLJ38613
- Serine/threonine protein kinase 22B
- SPOGA2
Classification
Type:
Protein-serine/threonine kinase
Group:
CAMK
Family:
TSSK
SubFamily:
NA
Structure
Mol. Mass (Da):
40,939
# Amino Acids:
358
# mRNA Isoforms:
1
mRNA Isoforms:
40,939 Da (358 AA; Q96PF2)
4D Structure:
Binds to STK22A
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 12 | 272 | Pkinase |
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K35, K41.
Serine phosphorylated:
S258.
Threonine phosphorylated:
T174+.
Tyrosine phosphorylated:
Y12, Y23, Y87.
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:
54
682
29
1119
3
35
15
42
2
30
2
25
33
417
81
1324
21
260
25
220
3
33
81
107
16
200
31
502
100
1263
31
2049
21
269
17
237
5
62
73
96
3
33
21
33
48
605
153
587
1
13
24
5
2
30
12
30
5
69
15
64
1
12
15
8
4
45
109
23
3
42
11
36
3
42
77
28
20
249
109
305
3
33
13
27
2
22
17
23
2
21
4
2
46
577
11
421
2
22
13
17
69
875
46
1882
1.3
17
27
12
3
42
11
45
2
23
11
16
10
122
28
64
19
239
24
239
53
665
36
829
10
128
60
463
53
671
52
593
17
218
26
177
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
98.6
99.4
99
96.1
97.8
97
-
-
91
-
-
-
93.8
97.5
87
-
-
-
90.2
94.4
92
20.9
32.2
93
-
-
-
77.7
86
-
20.6
30.7
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
20.6
35
38
37.7
55.1
-
-
-
-
-
-
-
-
-
-
28.7
43.8
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Regulation
Activation:
Activated by phosphorylation on Thr-174, potentially by autophosphorylation.
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
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 |
|---|
| Staurosporine | IC50 < 25 nM | 5279 | 22037377 | |
| AT9283 | IC50 > 100 nM | 24905142 | 19143567 | |
| CHEMBL1650545 | IC50 > 100 nM | 53316611 | 1650545 | 21128646 |
| K-252a; Nocardiopsis sp. | IC50 > 150 nM | 3813 | 281948 | 22037377 |
| MK5108 | IC50 > 1 µM | 24748204 | 20053775 | |
| Silmitasertib | IC50 > 1 µM | 24748573 | 21174434 | |
| SNS314 | IC50 > 1 µM | 16047143 | 514582 | 18678489 |
| SU11652 | IC50 > 1 µM | 24906267 | 13485 | 22037377 |
| CHEMBL248757 | Ki > 1.526 µM | 44444843 | 248757 | 17935989 |
| Momelotinib | IC50 > 2 µM | 25062766 | 19295546 | |
| JNJ-28871063 | IC50 > 4 µM | 17747413 | 17975007 |
Disease Linkage
General Disease Association:
Immune disorder
Specific Diseases (Non-cancerous):
Digeorge syndrome
Comments:
Some single-nucleotide polymorphisms of the TSSK2 gene can be associated with human spermatogenesis impairment.
Comments:
TSSK2 levels are markedly reduced compare to most protein kinases in human cancers.
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 human Cervical cancer stage 1B (%CFC= +107, p<0.048). The COSMIC website notes an up-regulated expression score for TSSK2 in diverse human cancers of 18, which is 96% lower than the average score of 462 for the human protein kinases. The down-regulated expression score of 2 for this protein kinase in human cancers was 97% lower than 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: 0.06 % in 24726 diverse cancer specimens. This rate is only -22 % 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: 0.36 % in 864 skin cancers tested; 0.32 % in 603 endometrium cancers tested; 0.29 % in 1270 large intestine cancers tested; 0.19 % in 589 stomach cancers tested; 0.16 % in 881 prostate cancers tested; 0.1 % in 558 thyroid cancers tested; 0.1 % in 273 cervix cancers tested; 0.08 % in 710 oesophagus cancers tested; 0.06 % in 1316 breast cancers tested; 0.05 % in 1634 lung cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: D247N (3).
Comments:
Only 1 deletion, and no insertions or complex mutations are noted on the COSMIC website.