Nomenclature
Short Name:
TNK1
Full Name:
Non-receptor tyrosine-protein kinase TNK1
Alias:
- CD38 negative kinase 1
- EC 2.7.10.2
Classification
Type:
Protein-tyrosine kinase
Group:
TK
Family:
Ack
SubFamily:
NA
Structure
Mol. Mass (Da):
72468
# Amino Acids:
666
# mRNA Isoforms:
2
mRNA Isoforms:
72,468 Da (666 AA; Q13470); 71,922 Da (661 AA; Q13470-2)
4D Structure:
Interacts with the SH3 domain of PLCG1 via its Pro-rich domain
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:
S60, S68, S94, S96, S255, S354, S468, S500, S502, S505, S508, S518, S519, S546, S550, S553, S582, S587, S659.
Threonine phosphorylated:
T209, T214, T248, T258, T514, T612.
Tyrosine phosphorylated:
Y77, Y235, Y277+, Y287, Y353, Y651, Y661.
Ubiquitinated:
K141, K260.
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
1118
29
1598
11
121
15
161
20
228
14
156
35
396
98
673
73
815
25
649
5
56
74
31
44
487
39
631
70
780
46
1421
48
533
17
405
14
159
107
126
11
128
36
150
53
591
219
695
13
148
36
131
6
67
15
78
16
177
32
201
4
43
16
41
7
81
289
89
14
156
25
141
8
89
101
94
48
536
109
514
7
79
30
118
8
90
34
87
16
178
24
140
12
131
24
144
14
160
29
191
51
565
61
671
10
116
38
82
13
144
25
152
12
139
25
116
26
289
28
172
34
375
24
309
64
713
36
717
34
383
60
982
65
732
57
689
13
150
35
118
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
98
98.2
99
96.1
97.3
99
-
-
85
-
-
-
74.4
78.5
85
-
-
-
82.7
87.5
83
30.4
41
83
-
-
-
-
-
-
21.2
34.9
-
21.1
34.3
-
39.6
55.2
-
-
-
-
21.4
31.6
-
23.7
33.8
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
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 | PLCG1 - P19174 |
Regulation
Activation:
NA
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 |
|---|
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:
Hodgkin lymphomas
Comments:
Phosphorylation of the TNK1 protein at several sites (Y77, Y235, Y277, Y287, and Y353) was observed in Hodgkin lymphoma (HL) cancer cell lines, indicating a possible role for the aberrant activity of the protein in the pathogenesis of this disease. In addition, a truncated form of TNK1 was identified in HL cancer cells, however the effect of the truncation on its phosphotransferase activity was unclear.
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: Brain glioblastomas (%CFC= +105, p<0.0002); Brain oligodendrogliomas (%CFC= +67, p<0.033); Ovary adenocarcinomas (%CFC= +49, p<0.05). The COSMIC website notes an up-regulated expression score for TNK1 in diverse human cancers of 325, which is 0.7-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 217 for this protein kinase in human cancers was 3.6-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.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.04 % in 24947 diverse cancer specimens. This rate is -52 % lower than the average rate of 0.075 % calculated for human protein kinases in general. Such a low frequency of mutation in human cancers is consistent with this protein kinase playing a role as a tumour requiring protein (TRP).
Mutation Rate in Specific Cancers:
Highest percent mutation rates per 100 amino acids length in human cancers: 0.3 % in 1093 large intestine cancers tested.
Frequency of Mutated Sites:
None > 2 in 20,230 cancer specimens
Comments:
Only 1 deletion, and no insertions or complex mutations are noted on the COSMIC website.