Nomenclature
Short Name:
TLK1
Full Name:
Serine-threonine-protein kinase tousled-like 1
Alias:
- EC 2.7.11.1
- KIAA0137
- Kinase TLK1
- PKU-beta
- Tousled-like kinase 1
Classification
Type:
Protein-serine/threonine kinase
Group:
Other
Family:
TLK
SubFamily:
NA
Structure
Mol. Mass (Da):
86,700
# Amino Acids:
766
# mRNA Isoforms:
5
mRNA Isoforms:
89,023 Da (787 AA; Q9UKI8-2); 86,700 Da (766 AA; Q9UKI8); 81,927 Da (718 AA; Q9UKI8-5); 77,110 Da (670 AA; Q9UKI8-4); 63,994 Da (549 AA; Q9UKI8-3)
4D Structure:
Heterodimerizes with TLK2. Interacts with ASF1A and ASF1B
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 230 | 281 | Coiled-coil |
| 397 | 445 | Coiled-coil |
| 456 | 734 | Pkinase |
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:
S20, S22, S33, S93, S94, S97, S100, S103, S105, S133, S134, S138, S159, S170, S176, S188, S190, S563, S679, S741, S743-, S764+, S765.
Threonine phosphorylated:
T21, T38, T68, T89, T179, T192, T313.
Tyrosine phosphorylated:
Y717, Y738.
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:
55
1172
60
1125
2
53
23
70
3
71
3
112
18
394
201
1052
30
645
61
546
4
80
146
201
7
152
73
394
65
1400
48
2697
26
568
24
540
3
55
177
67
3
61
32
95
28
609
243
533
4
77
36
83
4
87
15
103
4
78
23
115
2
49
37
72
15
330
139
2010
3
54
14
43
2
42
165
42
23
496
246
528
5
97
20
124
4
86
26
126
4
84
14
71
4
82
14
113
4
84
20
155
33
702
122
683
3
55
39
64
2
53
14
51
3
56
14
65
2
51
84
47
35
755
30
756
100
2149
66
5471
9
197
124
560
32
678
161
593
6
119
87
178
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
97.3
97.3
100
93.5
93.7
100
-
-
99
-
-
-
99.4
99.7
99.5
-
-
-
98.1
99.2
98
-
-
98
-
-
-
91.5
92.8
-
94.1
95.8
96.5
-
-
-
83.2
89.4
88
-
-
-
-
-
-
46.4
61.2
-
37.9
50.8
-
-
-
-
-
-
-
-
-
-
-
-
-
35.7
35.7
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | ASF1A - Q9Y294 |
| 2 | ASF1B - Q9NVP2 |
| 3 | SNAP23 - O00161 |
| 4 | CHEK1 - O14757 |
| 5 | TLK2 - Q86UE8 |
| 6 | HIST1H1A - Q02539 |
Regulation
Activation:
NA
Inhibition:
Inactivated by phosphorylation at Ser-743, potentially by CHK.
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
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= +71, p<0.048); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= -65, p<0.012); Oral squamous cell carcinomas (OSCC) (%CFC= +84, p<0.007); and T-cell prolymphocytic leukemia (%CFC= -47, p<0.061). The COSMIC website notes an up-regulated expression score for TLK1 in diverse human cancers of 426, which is 0.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 178 for this protein kinase in human cancers was 3-fold of the average score of 60 for the human protein kinases.
Mutagenesis Experiments:
Insertional mutagenesis studies in mice support a role for this protein kinase in mouse cancer oncogenesis. TLK1 phosphotransferase activity can be abrogated with D607A, S743A, S743D or S743E mutations.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.06 % in 24812 diverse cancer specimens. This rate is only -26 % 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: 0.28 % in 602 endometrium cancers tested; 0.24 % in 1094 large intestine cancers tested; 0.19 % in 805 skin cancers tested; 0.1 % in 1620 lung cancers tested.
Frequency of Mutated Sites:
None > 3 in 20,095 cancer specimens
Comments:
Only 2 deletions, 2 insertions, and no complex mutations are noted on the COSMIC website.