Nomenclature
Short Name:
DYRK3
Full Name:
Dual-specificity tyrosine-phosphorylation regulated kinase 3
Alias:
- EC 2.7.12.1
- REDK
- Regulatory erythroid kinase
Classification
Type:
Protein-serine/threonine kinase
Group:
CMGC
Family:
DYRK
SubFamily:
Dyrk2
Structure
Mol. Mass (Da):
65714
# Amino Acids:
588
# mRNA Isoforms:
2
mRNA Isoforms:
65,714 Da (588 AA; O43781); 63,977 Da (568 AA; O43781-2)
4D Structure:
NA
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 209 | 522 | Pkinase |
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Tyrosine phosphorylated:
Y209, Y367+, Y369+, Y451.
Serine phosphorylated:
S350, S372, S453, S469, S537.
Threonine phosphorylated:
T351, T368+, T455, T456, T532.
Acetylated:
K481,K488.
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:
70
1295
22
1572
1.2
23
11
17
5
101
3
34
23
422
71
1156
34
625
21
484
100
1848
54
4564
8
148
29
350
41
749
21
1139
14
264
10
251
2
38
45
18
2
33
16
34
36
665
103
640
2
43
14
24
4
78
9
18
3
64
13
62
1.4
25
13
21
16
296
108
2778
2
41
10
10
3
50
45
35
21
386
79
370
2
35
12
32
2
32
14
28
3
50
4
39
26
476
10
220
2
32
12
18
36
669
45
805
2
35
17
25
4
82
10
48
4
66
10
29
3
59
14
49
28
513
30
275
99
1831
26
5789
13
234
65
463
42
767
52
677
22
400
35
545
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.5
99.5
99.5
98.8
99.5
99
-
-
93
-
-
96
85.7
88.8
95
-
-
-
89.6
93.5
90
90.8
94.2
91
-
-
-
58
70.8
-
59
71.9
73.5
65.3
77.9
70
63.4
76.7
65
-
-
-
39
51
-
-
-
-
40.5
52.5
-
54.8
68.4
-
-
-
-
-
-
-
-
-
-
22.3
37.8
-
26.5
41
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
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 |
|---|
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: Brain glioblastomas (%CFC= -82, p<0.03); and Malignant pleural mesotheliomas (MPM) tumours (%CFC= -51, p<0.044); The COSMIC website notes an up-regulated expression score for DYRK3 in diverse human cancers of 593, which is 1.3-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 15 for this protein kinase in human cancers was 0.3-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 24726 diverse cancer specimens. This rate is only 11 % 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: 1.13 % in 15 pituitary cancers tested; 0.52 % in 1270 large intestine cancers tested; 0.32 % in 589 stomach cancers tested; 0.2 % in 603 endometrium cancers tested.
Frequency of Mutated Sites:
None > 3 in 20,009 cancer specimens
Comments:
Only 7 deletion, 1 insertion and 1 complex mutation are noted on the COSMIC website.