Nomenclature
Short Name:
NEK6
Full Name:
Serine-threonine-protein kinase Nek6
Alias:
- EC 2.7.11.1
- Kinase Nek6
- NIMA-related serine/threonine kinase
- Putative serine-threonine protein kinase
- SID6-1512
- NIMA
- NIMA (never in mitosis gene a)-related expressed kinase 6
- NIMA (never in mitosis gene a)-related kinase 6
- NIMA-related kinase 6
Classification
Type:
Protein-serine/threonine kinase
Group:
Other
Family:
NEK
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
35,714
# Amino Acids:
313
# mRNA Isoforms:
4
mRNA Isoforms:
39,844 Da (347 AA; Q9HC98-2); 38,460 Da (338 AA; Q9HC98-4); 37,823 Da (331 AA; Q9HC98-3); 35,714 Da (313 AA; Q9HC98)
4D Structure:
NA
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 45 | 305 | 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
Serine phosphorylated:
S37, S158, S165+, S198+, S199+, S206+, S215-.
Threonine phosphorylated:
T35, T181, T183, T201+, T202+, T210-.
Tyrosine phosphorylated:
Y108, Y152, Y212-, Y213-.
Ubiquitinated:
K49, K174.
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
1635
39
991
1.5
24
9
18
10
161
8
112
9
144
159
454
37
598
60
458
0.9
14
54
13
2
28
63
34
89
1458
20
3479
8
132
3
5
8
131
161
171
12
198
17
133
54
885
64
545
17
271
8
135
4
62
3
5
3
46
9
31
1.2
20
30
17
4
65
178
76
9
143
11
125
4
72
119
56
26
433
171
329
8
133
17
95
4
72
17
54
9
140
8
97
6
90
11
57
5
84
17
85
45
734
111
764
8
131
11
79
13
209
11
182
7
111
11
78
11
186
84
137
50
825
12
76
6
100
36
54
20
329
109
646
58
945
156
730
20
321
87
456
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
71.7
71.9
99
76.6
85.6
97
-
-
96
-
-
-
96.8
97.4
96
-
-
-
95.2
96.4
95
96.1
97.4
96
-
-
-
53.7
56.9
-
88.5
91.4
89
-
-
89
-
-
83.5
-
-
-
-
-
-
-
-
-
65.1
77.9
-
70.9
83
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | NEK9 - Q8TD19 |
| 2 | PIN1 - Q13526 |
| 3 | RPS6KB1 - P23443 |
| 4 | CDK7 - P50613 |
| 5 | NECAB2 - Q7Z6G3 |
| 6 | SMURF2 - Q9HAU4 |
| 7 | NCAPD2 - Q15021 |
| 8 | EML4 - Q9HC35 |
| 9 | EML2 - O95834 |
| 10 | EML3 - Q32P44 |
| 11 | WEE1 - P30291 |
| 12 | PCID2 - Q5JVF3 |
| 13 | NSF - P46459 |
Regulation
Activation:
Activated during M phase.
Inhibition:
Inhibition of activity results in apoptosis.
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
Comments:
NEK6 may be an oncoprotein (OP). NEK6 may contribute to tumorigenesis by suppressing p53/TP53-induced cancer cell senescence. NEK6 inhibition sensitizes human cancer cells towards premature senescence.
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: Brain glioblastomas (%CFC= -84, p<0.0002); Breast epithelial hyperplastic enlarged lobular units (HELU) (%CFC= +61, p<0.079); Clear cell renal cell carcinomas (cRCC) (%CFC= +82, p<0.021); Colon mucosal cell adenomas (%CFC= +100, p<0.0001); Large B-cell lymphomas (%CFC= +62, p<0.001); and Ovary adenocarcinomas (%CFC= +74, p<0.001). The COSMIC website notes an up-regulated expression score for NEK6 in diverse human cancers of 408, which is 0.9-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 74 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. K74M and K75M substitutions in NEK6 can lead to a loss of autophosphorylation and induction of apoptosis.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 24873 diverse cancer specimens. This rate is very similar (+ 4% higher) 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: 0.38 % in 590 stomach cancers tested; 0.34 % in 1305 large intestine cancers tested; 0.26 % in 864 skin cancers tested; 0.19 % in 1512 liver cancers tested; 0.18 % in 710 oesophagus cancers tested; 0.12 % in 273 cervix cancers tested; 0.11 % in 603 endometrium cancers tested; 0.1 % in 942 upper aerodigestive tract cancers tested; 0.1 % in 1326 breast cancers tested; 0.08 % in 834 ovary cancers tested; 0.08 % in 1637 lung cancers tested; 0.07 % in 885 prostate cancers tested; 0.06 % in 548 urinary tract cancers tested; 0.03 % in 1276 kidney cancers tested.
Frequency of Mutated Sites:
None > 3 in 20,156 cancer specimens
Comments:
Only 1 deletion, and no insertions or complex mutations are noted on the COSMIC website.