Nomenclature
Short Name:
NuaK2
Full Name:
SNF1/AMP activated protein kinase
Alias:
- DKFZp434J037
- EC 2.7.11.1
- FLJ90349
- NUAK family, SNF1-like kinase, 2
- SNARK
Classification
Type:
Protein-serine/threonine kinase
Group:
CAMK
Family:
CAMKL
SubFamily:
NuaK
Structure
Mol. Mass (Da):
69,612
# Amino Acids:
628
# mRNA Isoforms:
1
mRNA Isoforms:
69,612 Da (628 AA; Q9H093)
4D Structure:
NA
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 53 | 303 | Pkinase |
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:
S30, S142, S435, S462, S523, S544, S547, S553, S573.
Threonine phosphorylated:
T58, T208+.
Tyrosine phosphorylated:
Y131, Y138, Y140, Y267+.
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:
100
1039
16
1229
8
85
8
42
5
55
7
57
29
297
50
574
45
465
14
436
8
80
37
23
19
197
15
57
37
387
21
507
64
670
10
554
34
351
33
200
8
87
18
71
82
854
69
676
14
141
18
47
7
70
6
45
10
107
15
63
6
63
7
37
9
95
80
46
10
102
12
45
7
76
43
44
72
747
56
733
7
70
14
49
19
199
16
108
6
61
8
44
7
71
12
50
9
91
14
55
81
845
32
772
16
167
21
110
11
115
12
51
6
67
12
51
43
449
14
118
96
997
18
533
99
1032
15
745
62
642
17
239
96
995
26
845
13
135
22
145
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
53.8
65.9
98
82
84.5
97
-
-
91
-
-
90
86.6
90.1
88
-
-
-
85.4
89.5
87
85.7
90.9
86.5
-
-
-
68.7
75.8
-
28.8
43.4
69
51.4
64
63
22.5
33.4
65
-
-
-
-
-
-
-
-
-
22.1
34.4
-
-
-
-
-
-
-
-
-
-
-
-
-
29.4
46.5
-
25.9
44.7
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | SMAD2 - Q15796 |
| 2 | ACVR1 - Q04771 |
| 3 | NUAK1 - O60285 |
| 4 | CDC37 - Q16543 |
Regulation
Activation:
Activated by phosphorylation on Thr-208 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:
Melanomas
Comments:
The Nuak2 gene is an emerging oncogene that affects tumour growth, migration, and clinical outcome of human melanoma.
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= -55, p<0.034); Bladder carcinomas (%CFC= -45, p<0.037); Breast epithelial hyperplastic enlarged lobular units (HELU) (%CFC= +115, p<0.027); Cervical epithelial cancer (%CFC= +147, p<0.001); Classical Hodgkin lymphomas (%CFC= -59, p<0.007); Clear cell renal cell carcinomas (cRCC) (%CFC= -45, p<0.054); Oral squamous cell carcinomas (OSCC) (%CFC= -57, p<0.062); Ovary adenocarcinomas (%CFC= +130, p<0.003); Papillary thyroid carcinomas (PTC) (%CFC= -51, p<0.001); Prostate cancer (%CFC= +70, p<0.029); Skin fibrosarcomas (%CFC= -55); Skin melanomas (%CFC= -47, p<0.062); Skin melanomas - malignant (%CFC= -59, p<0.006); Skin squamous cell carcinomas (%CFC= +86, p<0.039); and Vulvar intraepithelial neoplasia (%CFC= +95, p<0.027). The COSMIC website notes an up-regulated expression score for NuaK2 in diverse human cancers of 474, which is close to the average score of 462 for the human protein kinases. The down-regulated expression score of 2 for this protein kinase in human cancers was 97% lower than 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. A K81R substitution is associated with loss of autophosphorylation, phosphotransferase activity and anti-apoptotic activity.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.07 % in 24782 diverse cancer specimens. This rate is only -5 % 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: 0.5 % in 864 skin cancers tested; 0.24 % in 1270 large intestine cancers tested; 0.18 % in 603 endometrium cancers tested; 0.13 % in 238 bone cancers tested; 0.12 % in 548 urinary tract cancers tested; 0.12 % in 273 cervix cancers tested; 0.11 % in 710 oesophagus cancers tested; 0.11 % in 1276 kidney cancers tested; 0.1 % in 1316 breast cancers tested; 0.08 % in 833 ovary cancers tested; 0.07 % in 1512 liver cancers tested; 0.06 % in 1634 lung cancers tested; 0.04 % in 881 prostate cancers tested; 0.04 % in 1459 pancreas cancers tested; 0.03 % in 589 stomach cancers tested; 0.02 % in 2009 haematopoietic and lymphoid cancers tested; 0.01 % in 2103 central nervous system cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: E424K (3).
Comments:
Only 5 deletions, 1 insertion and no complex mutations are noted on the COSMIC website.