Nomenclature
Short Name:
NEK7
Full Name:
Serine-threonine-protein kinase Nek7
Alias:
- EC 2.7.11.1
- Kinase Nek7
- NIMA (never in mitosis gene a)-related kinase 7
- NIMA-related serine/threonine kinase NEK7
Classification
Type:
Protein-serine/threonine kinase
Group:
Other
Family:
NEK
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
34,551
# Amino Acids:
302
# mRNA Isoforms:
2
mRNA Isoforms:
34,551 Da (302 AA; Q8TDX7); 13,402 Da (119 AA; Q8TDX7-2)
4D Structure:
NA
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 34 | 294 | Pkinase |
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:
M1.
Serine phosphorylated:
S5, S147, S187+, S188+, S195+, S204-, S245.
Threonine phosphorylated:
T30, T170, T172, T190+, T191+, T199-, T286.
Tyrosine phosphorylated:
Y97-, Y201-, Y202-, Y244-, Y287, Y289.
Ubiquitinated:
K163, K293.
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:
25
982
16
690
5
208
12
182
11
436
1
0
14
565
50
491
25
996
14
906
5
210
37
114
15
578
19
537
16
638
24
828
21
806
10
778
4
157
49
118
2
77
18
86
22
869
99
756
6
224
14
71
5
213
11
318
3
127
15
173
11
441
10
211
4
145
103
152
4
173
10
247
15
606
45
455
24
959
58
829
5
203
14
232
5
207
13
228
5
197
2
1
7
263
12
317
3
115
14
123
19
756
30
754
4
142
17
85
3
133
10
135
5
206
10
280
0.9
35
14
38
14
537
18
64
100
3929
29
5598
8
324
56
500
36
1422
26
615
1.3
50
22
65
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
57.4
64.6
100
99.3
99.7
99
-
-
99
-
-
-
99.3
99.7
99
-
-
-
97.7
99.3
98
77
85.9
98
-
-
-
47.8
54
-
98
98.3
98
95
96.7
95
87.1
93.4
89
-
-
-
-
-
-
-
-
-
68.9
80.8
75
78.2
85.1
-
-
-
-
-
-
-
-
-
-
-
-
-
20
35.4
-
-
-
-
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 | NEK9 - Q8TD19 |
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 |
|---|
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 |
|---|
| R406 | Kd = 11 nM | 11984591 | 22037378 | |
| 7-hydroxystaurosporine | IC50 > 100 nM | 72271 | 1236539 | |
| AT9283 | IC50 > 100 nM | 24905142 | 19143567 | |
| TG101348 | Kd = 160 nM | 16722836 | 1287853 | 22037378 |
| KW2449 | Kd = 210 nM | 11427553 | 1908397 | 22037378 |
| A 443654 | IC50 > 900 nM | 10172943 | 379300 | |
| BI-D1870 | IC50 > 900 nM | 25023738 | 573107 | |
| Gö6976 | IC50 > 900 nM | 3501 | 302449 | |
| Ro-31-8220 | IC50 > 900 nM | 5083 | 6291 | |
| Ruboxistaurin | IC50 > 900 nM | 153999 | 91829 | |
| MK5108 | IC50 > 1 µM | 24748204 | 20053775 | |
| Silmitasertib | IC50 > 1 µM | 24748573 | 21174434 | |
| SNS314 | IC50 > 1 µM | 16047143 | 514582 | 18678489 |
| WZ3146 | Kd > 1 µM | 44607360 | 20033049 | |
| WZ4002 | Kd > 1 µM | 44607530 | 20033049 | |
| NVP-TAE684 | Kd = 2.3 µM | 16038120 | 509032 | 22037378 |
| Lestaurtinib | Kd = 3.2 µM | 126565 | 18183025 | |
| SU14813 | Kd = 3.2 µM | 10138259 | 1721885 | 18183025 |
| JNJ-28871063 | IC50 > 4 µM | 17747413 | 17975007 | |
| Sunitinib | Kd = 4.1 µM | 5329102 | 535 | 18183025 |
| Staurosporine | Kd = 4.5 µM | 5279 | 18183025 | |
| Ruxolitinib | Kd = 4.9 µM | 25126798 | 1789941 | 22037378 |
Disease Linkage
General Disease Association:
Cancer
Specific Cancer Types:
Gall bladder carcinomas
Comments:
NEK7 has been significantly associated with certain clinicopathologic indices in gallbladder carcinomas. The high level expression of Nek7, FoxM1 and Plk1 was significantly associated with shorter overall survival time in 76 specimens of gallbladder carcinomas, pericarcinomas and normal tissues (PubMEd: 23359173).
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= +166, p<0.0002); Lung adenocarcinomas (%CFC= -45, p<0.0001); Malignant pleural mesotheliomas (MPM) tumours (%CFC= +132, p<0.011); Oral squamous cell carcinomas (OSCC) (%CFC= +68, p<0.007); Ovary adenocarcinomas (%CFC= -69, p<0.0004); and Skin melanomas - malignant (%CFC= -52, p<0.012). The COSMIC website notes an up-regulated expression score for NEK7 in diverse human cancers of 523, which is 1.1-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 49 for this protein kinase in human cancers was 0.8-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: 0.09 % in 24751 diverse cancer specimens. This rate is only 14 % 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: 0.55 % in 603 endometrium cancers tested; 0.5 % in 1270 large intestine cancers tested; 0.28 % in 589 stomach cancers tested; 0.2 % in 833 ovary cancers tested; 0.15 % in 864 skin cancers tested; 0.13 % in 1276 kidney cancers tested; 0.12 % in 548 urinary tract cancers tested; 0.12 % in 273 cervix cancers tested; 0.11 % in 881 prostate cancers tested; 0.06 % in 1634 lung cancers tested; 0.05 % in 1459 pancreas cancers tested; 0.04 % in 942 upper aerodigestive tract cancers tested; 0.04 % in 1512 liver cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: I162V (4).
Comments:
Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.