Nomenclature
Short Name:
VRK3
Full Name:
Serine-threonine-protein kinase VRK3
Alias:
- EC 2.7.11.1
- Vaccinia related kinase 3
- Vaccinia-related kinase 3
Classification
Type:
Protein-serine/threonine kinase
Group:
CK1
Family:
VRK
SubFamily:
NA
Structure
Mol. Mass (Da):
52,881
# Amino Acids:
474
# mRNA Isoforms:
3
mRNA Isoforms:
52,881 Da (474 AA; Q8IV63); 47,501 Da (424 AA; Q8IV63-3); 45,904 Da (412 AA; Q8IV63-2)
4D Structure:
NA
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 166 | 473 | Pkinase |
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:
S54, S55, S59, S66, S67, S71, S82, S83, S85, S90, S108, S115, S122, S129, S136.
Threonine phosphorylated:
T58, T70, T104, T112, T119, T126, T154, T156, T159.
Ubiquitinated:
K229, K275.
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:
58
1328
60
1358
6
129
21
95
6
140
17
101
15
345
209
981
29
666
60
574
2
57
138
39
3
77
69
72
60
1371
59
2764
34
778
24
610
7
166
131
118
8
191
44
129
40
911
226
668
6
131
50
77
3
76
12
48
6
127
35
98
4
82
36
71
7
165
242
99
13
291
26
775
4
90
137
76
22
497
236
486
7
151
32
102
8
183
38
107
5
126
20
94
30
697
26
393
11
261
32
188
55
1257
133
2199
6
136
53
76
9
211
26
172
5
120
26
81
9
210
56
169
38
880
42
694
36
824
66
1818
9
197
125
272
37
856
156
702
100
2303
87
3567
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
97.9
98.7
98
92.3
94.6
94
-
-
77
-
-
72
76.4
82.5
79
-
-
-
72.2
81.9
75
72.4
82.1
75.5
-
-
-
-
-
-
43
55.3
-
43.6
59.4
49
36.9
54.4
46
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | VRK1 - Q99986 |
| 2 | RAN - P62826 |
| 3 | TLR9 - Q9NR96 |
| 4 | TWF2 - Q6IBS0 |
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
Disease Linkage
General Disease Association:
Infectious disease
Specific Diseases (Non-cancerous):
Vaccinia
Comments:
Vaccinia is an infectious virus, typically affecting the skin and T cells. Symptoms of infection with this virus can include fever, rash, and body aches.
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: Barrett's esophagus epithelial metaplasia (%CFC= +80, p<0.0002); Clear cell renal cell carcinomas (cRCC) stage I (%CFC= -86, p<0.0001); Large B-cell lymphomas (%CFC= +59, p<0.006); Ovary adenocarcinomas (%CFC= +54, p<0.016); and Skin melanomas - malignant (%CFC= +116, p<0.0001). The COSMIC website notes an up-regulated expression score for VRK3 in diverse human cancers of 516, which is 1.1-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 364 for this protein kinase in human cancers was 6.1-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: 0.08 % in 24751 diverse cancer specimens. This rate is the same as 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: 0.39 % in 864 skin cancers tested; 0.31 % in 603 endometrium cancers tested; 0.29 % in 589 stomach cancers tested; 0.23 % in 273 cervix cancers tested; 0.23 % in 1270 large intestine cancers tested; 0.13 % in 1634 lung cancers tested; 0.12 % in 548 urinary tract cancers tested; 0.1 % in 1316 breast cancers tested; 0.09 % in 238 bone cancers tested; 0.08 % in 1512 liver cancers tested; 0.05 % in 833 ovary cancers tested; 0.04 % in 558 thyroid cancers tested; 0.03 % in 1276 kidney cancers tested; 0.02 % in 942 upper aerodigestive tract cancers tested; 0.02 % in 2009 haematopoietic and lymphoid cancers tested; 0.01 % in 1459 pancreas cancers tested.
Frequency of Mutated Sites:
None > 3 in 20,034 cancer specimens
Comments:
Only 1 deletion, 1 insertion, and 1 complex mutation are noted on the COSMIC website.