Nomenclature
Short Name:
OSR1
Full Name:
Oxidative-stress responsive 1
Alias:
- OXSR1
Classification
Type:
Protein-serine/threonine kinase
Group:
STE
Family:
STE20
SubFamily:
FRAY
Specific Links
Structure
Mol. Mass (Da):
58,022
# Amino Acids:
527
# mRNA Isoforms:
1
mRNA Isoforms:
58,022 Da (527 AA; O95747)
4D Structure:
Binds to and phosphorylates PAK1. Interacts with chloride channel proteins SLC12A6 isoform 2, SLC12A1 and SLC12A2 but not with SLC12A4 and SLC12A7, possibly establishing sensor/signaling modules that initiate the cellular response to environmental stress. Binds to and phosphorylates RELL1, RELL2 AND RELT
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 17 | 291 | Pkinase |
Kinexus Products
Click on entries below for direct links to relevant products from Kinexus for this protein kinase.
hiddentext
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K42, K46.
Serine phosphorylated:
S263, S269, S312, S324, S325+, S339, S347, S355, S359, S369, S425, S427, S435, S510.
Threonine phosphorylated:
T185+, T189, T310, T331, T430.
Ubiquitinated:
K52.
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:
64
830
16
793
11
147
10
29
47
609
18
697
71
931
67
1504
68
891
14
823
10
133
37
39
41
541
19
615
74
969
41
1662
49
638
10
539
24
307
62
450
15
190
31
254
61
792
112
697
19
250
29
290
11
142
9
38
9
124
11
48
11
148
8
43
29
377
118
2357
23
295
25
426
35
463
60
522
57
748
56
721
26
337
27
446
24
312
29
374
30
390
19
437
29
380
25
424
28
365
27
452
57
750
46
735
28
360
31
373
17
224
25
345
27
357
25
457
15
193
14
66
100
1306
18
769
100
1305
27
3332
14
185
55
239
94
1225
26
732
13
173
13
104
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.6
99.6
100
29.7
48.3
99
-
-
97
-
-
95
97.1
97.9
97
-
-
-
95.8
97.5
96
71
81
96
-
-
-
86.5
90.3
-
87.4
90.8
88
30.1
46.6
87
80.4
89.1
-
-
-
-
24
40.9
58
46.2
56.5
-
-
-
59
-
-
-
-
-
-
-
-
-
-
-
-
-
-
49
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Regulation
Activation:
Activated by phosphorylation at Thr-185 (in the kinase activation loop) and Ser-325.
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 |
|---|
| PAK1 | Q13153 | T84 | LPSDFEHTIHVGFDA | - |
| SLC12A2 (NKCC1) | P55011 | T203 | HQHYYYDTHTNTYYL | + |
| SLC12A2 (NKCC1) | P55011 | T207 | YYDTHTNTYYLRTFG | + |
| SLC12A2 (NKCC1) | P55011 | T212 | TNTYYLRTFGHNTMD | + |
| SLC12A2 (NKCC1) | P55011 | T217 | LRTFGHNTMDAVPRI | + |
| SLC12A2 (NKCC1) | P55011 | T230 | RIDHYRHTAAQLGEK | + |
| SLC12A3 | P55017 | T46 | SSHPSHLTHSSTFCM | |
| SLC12A3 | P55017 | T55 | SSTFCMRTFGYNTID | |
| SLC12A3 | P55017 | T60 | MRTFGYNTIDVVPTY |
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 |
|---|
| NVP-TAE684 | Kd = 48 nM | 16038120 | 509032 | 22037378 |
| Staurosporine | IC50 > 50 nM | 5279 | 22037377 | |
| TTT-3002 | IC50 < 60 nM | |||
| Sunitinib | Kd = 530 nM | 5329102 | 535 | 19654408 |
| Cdk1/2 Inhibitor III | IC50 > 1 µM | 5330812 | 261720 | 22037377 |
| HG-9-91-01 | IC50 = 1 µM | |||
| Staurosporine aglycone | IC50 < 1 µM | 3035817 | 281948 | |
| WZ3146 | Kd > 1 µM | 44607360 | 20033049 | |
| WZ4002 | Kd > 1 µM | 44607530 | 20033049 | |
| Nintedanib | Kd = 1.3 µM | 9809715 | 502835 | 22037378 |
| SU14813 | Kd = 1.6 µM | 10138259 | 1721885 | 22037378 |
| KW2449 | Kd = 1.7 µM | 11427553 | 1908397 | 22037378 |
| Ruxolitinib | Kd = 2.7 µM | 25126798 | 1789941 | 22037378 |
| R406 | Kd = 3.1 µM | 11984591 | 22037378 | |
| PLX4720 | Kd = 3.9 µM | 24180719 | 1230020 | 22037378 |
| GSK1838705A | Kd = 4.2 µM | 25182616 | 464552 | 22037378 |
| Amgen TBK 1 inhibitor (Compound II) | IC50 > 4.5 µM | |||
| BI2536 | IC50 > 4.5 µM | 11364421 | 513909 | |
| KIN 112 | IC50 > 4.5 µM |
Disease Linkage
General Disease Association:
Cancer
Specific Cancer Types:
Gastric cancer
Comments:
In gastric cancer, OSR1 is believed to be methylated in the promoter region inducing down-regulation of gene transcription, leading to disease.
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= +54, p<0.0002); Brain glioblastomas (%CFC= -45, p<0.004); Breast epithelial hyperplastic enlarged lobular units (HELU) (%CFC= +102, p<0.038); Cervical cancer (%CFC= +104, p<0.005); Oral squamous cell carcinomas (OSCC) (%CFC= -59, p<0.015); Skin squamous cell carcinomas (%CFC= +55, p<0.069); and Vulvar intraepithelial neoplasia (%CFC= +67, p<0.0008). The COSMIC website notes an up-regulated expression score for OSR1 in diverse human cancers of 436, which is close to the average score of 462 for the human protein kinases. The down-regulated expression score of 199 for this protein kinase in human cancers was 3.3-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. A K46A mutation can lead to the inhibition of autophosphorylation and abrogate phosphotransferase activity. A K36M mutation was noted to prevent phosphorylation of RELT, RELL1, and RELL2 by the kinase in cell lysates.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.05 % in 24704 diverse cancer specimens. This rate is only -29 % 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 273 cervix cancers tested; 0.27 % in 1270 large intestine cancers tested; 0.25 % in 603 endometrium cancers tested; 0.18 % in 864 skin cancers tested; 0.16 % in 589 stomach cancers tested; 0.15 % in 127 biliary tract cancers tested; 0.08 % in 710 oesophagus cancers tested; 0.08 % in 1634 lung cancers tested; 0.06 % in 1512 liver 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 2060 central nervous system cancers tested; 0.01 % in 2009 haematopoietic and lymphoid cancers tested; 0.01 % in 1459 pancreas cancers tested; 0.01 % in 1276 kidney cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: P433S (2).
Comments:
Only 3 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.