Nomenclature
Short Name:
QIK
Full Name:
Serine-threonine-protein kinase SNF1-like kinase 2
Alias:
- DKFZp434K1115
- Salt-inducible serine/threonine kinase 2
- SIK2
- SN1L2
- SNF1LK2
- EC 2.7.11.1
- KIAA0781
- LOH11CR1I
- Salt-inducible kinase 2
Classification
Type:
Protein-serine/threonine kinase
Group:
CAMK
Family:
CAMKL
SubFamily:
QIK
Structure
Mol. Mass (Da):
103,915
# Amino Acids:
926
# mRNA Isoforms:
1
mRNA Isoforms:
103,915 Da (926 AA; Q9H0K1)
4D Structure:
nteracts with and phosphorylates TORC2/CRTC2.
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
Acetylated:
K53.
Serine phosphorylated:
S90, S179-, S343, S358+, S379, S486, S512, S534, S545, S576, S587, S590.
Threonine phosphorylated:
T25, T175+, T359, T484, T589.
Tyrosine phosphorylated:
Y65, Y283, Y700.
Ubiquitinated:
K144, K536, K692.
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:
88
907
41
937
7
74
14
75
5
47
2
60
30
304
136
446
73
753
39
640
35
364
108
920
11
116
48
261
67
684
34
995
55
566
14
485
12
124
98
127
8
81
22
95
69
713
166
586
3
28
24
27
6
59
9
55
7
68
16
64
10
99
25
88
35
355
260
2967
11
117
8
105
8
83
92
88
56
577
157
567
10
100
14
75
5
54
18
59
10
107
4
120
3
32
8
23
8
78
14
79
100
1028
78
1468
2
23
24
21
5
49
8
42
7
70
8
60
14
146
42
161
33
335
24
329
36
369
46
431
56
579
98
1013
91
934
104
816
12
128
61
113
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
95.3
95.4
100
-
-
98
-
-
90
-
-
-
84.8
87.5
91
-
-
-
90.9
94.4
91
43.2
56.8
-
-
-
-
45.3
58.6
-
45.5
59
78
-
-
74.5
31.5
45.2
69
-
-
-
29.7
40.1
-
37.5
49.4
-
23.8
38.2
-
-
-
-
-
-
-
-
-
-
-
-
-
24.2
37.5
-
-
-
-
-
-
-
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 | IRS1 - P35568 |
| 2 | CRTC2 - Q53ET0 |
| 3 | NUAK1 - O60285 |
| 4 | PPP2R1B - P30154 |
| 5 | VCP - P55072 |
| 6 | PPP2CA - P67775 |
| 7 | DOCK5 - Q9H7D0 |
| 8 | PPP2R2B - Q00005 |
Regulation
Activation:
Activated by phosphorylation on Thr-175 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39.
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
General Disease Association:
Cancer
Specific Cancer Types:
Ovarian cancer
Comments:
QIK was also shown to be activated by tumour suppressor LKB1 and to stimulate histone deacetylases export. SIK2 is a centrosome kinase required for bipolar mitotic spindle formation, and may be a potential target for therapy in ovarian cancer.
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: Clear cell renal cell carcinomas (cRCC) stage I (%CFC= +797, p<0.0001); and Skin melanomas - malignant (%CFC= -58, p<0.089). The COSMIC website notes an up-regulated expression score for QIK 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 69 for this protein kinase in human cancers was 1.2-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.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.07 % in 24751 diverse cancer specimens. This rate is only -6 % lower and is very similar to 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 1270 large intestine cancers tested; 0.23 % in 603 endometrium cancers tested; 0.2 % in 589 stomach cancers tested; 0.2 % in 273 cervix cancers tested; 0.14 % in 548 urinary tract cancers tested; 0.12 % in 833 ovary cancers tested; 0.11 % in 864 skin cancers tested; 0.1 % in 1512 liver cancers tested; 0.09 % in 1634 lung cancers tested; 0.07 % in 942 upper aerodigestive tract cancers tested; 0.06 % in 1459 pancreas cancers tested; 0.06 % in 1276 kidney cancers tested; 0.05 % in 881 prostate cancers tested; 0.05 % in 238 bone cancers tested; 0.03 % in 382 soft tissue cancers tested; 0.03 % in 2082 central nervous system cancers tested; 0.03 % in 2009 haematopoietic and lymphoid cancers tested; 0.03 % in 1316 breast cancers tested; 0.02 % in 441 autonomic ganglia cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: T878T (10).
Comments:
Only 7 deletions, no insertions or complex mutations are noted on the COSMIC website.