Nomenclature
Short Name:
RIOK1
Full Name:
Serine-threonine-protein kinase RIO1
Alias:
- AD034
- RIO kinase 1
- BA288G3.1
- EC 2.7.11.1
- FLJ30006
- Kinase RIOK1
Classification
Type:
Protein-serine/threonine kinase
Group:
Atypical
Family:
RIO
SubFamily:
RIO1
Structure
Mol. Mass (Da):
65,583
# Amino Acids:
568
# mRNA Isoforms:
1
mRNA Isoforms:
65,583 Da (568 AA; Q9BRS2)
4D Structure:
NA
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
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:
S21, S22, S24, S89, S102, S204, S225.
Threonine phosphorylated:
T107, T175, T468, T470, T494, T509.
Tyrosine phosphorylated:
Y83, Y223, Y440, Y466.
Ubiquitinated:
K81, K218, K299.
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:
17
1506
9
1105
0.6
54
4
2
2
166
15
103
5
409
51
1020
10
909
13
592
1
86
9
14
0.8
73
13
19
18
1569
28
3839
0.6
51
3
1
1.2
110
48
57
1
89
24
71
5
414
30
564
3
227
15
130
2
185
3
11
1.3
119
24
87
0.6
52
5
18
0.7
64
87
54
1.2
105
18
81
1.3
118
52
95
12
1049
31
646
1.1
97
24
73
2
144
24
110
2
145
15
99
3
284
18
174
2
178
24
134
14
1202
38
2128
2
215
18
129
1.4
120
18
80
2
157
18
101
0.6
56
14
34
11
937
24
430
100
8830
11
8765
0.1
12
12
8
11
987
26
747
1.2
109
40
114
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
98.8
98.9
99
94.5
96.8
95
-
-
89
-
-
-
89.6
94.9
89
-
-
-
80.3
88
80.5
81.5
89.8
82
-
-
-
73.1
81
-
75.2
84.2
77
70.4
80.6
79
69.7
82.2
71
-
-
-
47
64.3
56
-
-
-
-
-
58
50.2
66
-
41
60.7
-
-
-
-
-
-
49.5
-
-
53
32
49.3
48
-
-
50
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | GAR1 - Q9NY12 |
| 2 | MRTO4 - Q9UKD2 |
| 3 | BYSL - Q13895 |
| 4 | CSNK2A2 - P19784 |
| 5 | CSNK2A1 - P68400 |
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
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 |
|---|
| Lestaurtinib | Kd = 9 nM | 126565 | 19654408 | |
| Sunitinib | Kd = 35 nM | 5329102 | 535 | 18183025 |
| Staurosporine | Kd = 130 nM | 5279 | 18183025 | |
| Tozasertib | Kd = 360 nM | 5494449 | 572878 | 18183025 |
| Dovitinib | Kd = 420 nM | 57336746 | 18183025 | |
| PHA-665752 | Kd = 470 nM | 10461815 | 450786 | 22037378 |
| SU14813 | Kd = 590 nM | 10138259 | 1721885 | 18183025 |
| A674563 | Kd = 620 nM | 11314340 | 379218 | 22037378 |
| JNJ-7706621 | Kd = 1.1 µM | 5330790 | 191003 | 18183025 |
| BI2536 | Kd = 2.2 µM | 11364421 | 513909 | 22037378 |
| Ruxolitinib | Kd = 2.5 µM | 25126798 | 1789941 | 22037378 |
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: Colon mucosal cell adenomas (%CFC= +55, p<0.0001); Large B-cell lymphomas (%CFC= +83, p<0.007); Ovary adenocarcinomas (%CFC= +72, p<0.009); and Prostate cancer - metastatic (%CFC= +57, p<0.0002). The COSMIC website notes an up-regulated expression score for RIOK1 in diverse human cancers of 653, which is 1.4-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 111 for this protein kinase in human cancers was 1.9-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: 0.05 % in 24726 diverse cancer specimens. This rate is only -28 % 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: 0.24 % in 864 skin cancers tested; 0.24 % in 1270 large intestine cancers tested; 0.15 % in 603 endometrium cancers tested; 0.13 % in 273 cervix cancers tested; 0.11 % in 833 ovary cancers tested; 0.09 % in 589 stomach cancers tested; 0.09 % in 558 thyroid cancers tested; 0.08 % in 1512 liver cancers tested; 0.07 % in 1276 kidney cancers tested; 0.05 % in 1634 lung cancers tested; 0.05 % in 1459 pancreas cancers tested; 0.04 % in 942 upper aerodigestive tract cancers tested; 0.03 % in 548 urinary tract cancers tested; 0.03 % in 1316 breast cancers tested; 0.02 % in 881 prostate cancers tested; 0.02 % in 2009 haematopoietic and lymphoid cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: V76A (4).
Comments:
Only 1 deletion and 2 insertions and no complex mutations are noted on the COSMIC website.