Nomenclature
Short Name:
NEK11
Full Name:
Serine-threonine-protein kinase Nek11
Alias:
- BC009414
- FLJ23495
Classification
Type:
Protein-serine/threonine kinase
Group:
Other
Family:
NEK
SubFamily:
NA
Structure
Mol. Mass (Da):
74,162
# Amino Acids:
645
# mRNA Isoforms:
4
mRNA Isoforms:
74,192 Da (645 AA; Q8NG66); 68,880 Da (599 AA; Q8NG66-4); 55,519 Da (482 AA; Q8NG66-3); 54,007 Da (470 AA; Q8NG66-2)
4D Structure:
NA
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 29 | 287 | Pkinase |
| 346 | 385 | Coiled-coil |
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K312.
Serine phosphorylated:
S47, S273+.
Tyrosine phosphorylated:
Y44.
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:
59
1269
28
1066
4
77
10
96
3
67
13
64
8
176
98
358
28
608
28
355
1.4
30
55
22
1
22
35
27
17
360
26
570
8
184
10
152
4
89
45
56
3
74
24
105
33
725
98
620
3
67
24
53
4
87
6
49
3
70
21
79
2
46
17
38
3
55
94
49
3
61
18
62
4
84
49
61
22
487
102
352
6
133
20
78
2
48
21
49
3
56
14
64
5
117
18
106
3
57
20
67
29
633
66
639
3
68
27
77
6
131
18
84
3
67
18
66
10
221
14
64
30
655
30
339
100
2167
31
5250
7
162
69
394
37
808
78
687
17
372
57
335
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
72.4
72.5
99
94.1
95.9
95
-
-
81
-
-
-
69
75.4
85
-
-
-
72.5
81
77
57.8
67.9
75
-
-
-
67.9
78.2
-
27.1
46.7
71
20.7
38.9
62
23.5
42.9
55.5
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
23.1
41.4
-
-
-
-
-
-
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Regulation
Activation:
Autorepressed by intramolecular binding of the C-terminus which dissociates following phosphorylation by NEK2 isoform 1 in G1/S-arrested cells. NEK2 isoform 2 is largely not present in the nucleolus, and does not appear to phosphorylate NEK11. Activated in response to DNA damage.
Inhibition:
Inhibited by zinc.
Synthesis:
NA
Degradation:
NA
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 |
|---|
| AT9283 | IC50 > 100 nM | 24905142 | 19143567 | |
| Dasatinib | IC50 > 150 nM | 11153014 | 1421 | 22037377 |
| R406 | Kd = 170 nM | 11984591 | 22037378 | |
| PLX4720 | Kd = 190 nM | 24180719 | 1230020 | 22037378 |
| Staurosporine | IC50 > 250 nM | 5279 | 22037377 | |
| Vemurafenib | IC50 = 317 nM | 42611257 | 1229517 | 20823850 |
| Bosutinib | Kd = 650 nM | 5328940 | 288441 | 22037378 |
| MK5108 | IC50 > 1 µM | 24748204 | 20053775 | |
| Purvalanol A | IC50 > 1 µM | 456214 | 23327 | 22037377 |
| SB218078 | IC50 > 1 µM | 447446 | 289422 | 22037377 |
| Silmitasertib | IC50 > 1 µM | 24748573 | 21174434 | |
| SNS314 | IC50 > 1 µM | 16047143 | 514582 | 18678489 |
| SureCN2505235 | IC50 = 1 µM | 5353854 | 101797 | 22934575 |
| WZ3146 | Kd > 1 µM | 44607360 | 20033049 | |
| WZ4002 | Kd > 1 µM | 44607530 | 20033049 | |
| TG101348 | Kd = 1.2 µM | 16722836 | 1287853 | 22037378 |
| CHEMBL248757 | Ki > 1.549 µM | 44444843 | 248757 | 17935989 |
| PD173955 | Kd = 3 µM | 447077 | 386051 | 22037378 |
| JNJ-28871063 | IC50 > 4 µM | 17747413 | 17975007 | |
| SureCN2579964 | IC50 < 4 µM | 24948986 | 22934575 |
Disease Linkage
Comments:
NEK11 may be a tumour requiring protein (TRP), since it displays extremely low rates of mutation in human cancers.
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: Cervical epithelial cancer (%CFC= +46, p<0.009); Prostate cancer - metastatic (%CFC= -45, p<0.0006); and T-cell prolymphocytic leukemia (%CFC= +98, p<0.006).
Mutagenesis Experiments:
Insertional mutagenesis studies in mice have not yet revealed 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: 0.03 % in 24433 diverse cancer specimens. This rate is -65 % lower than the average rate of 0.075 % calculated for human protein kinases in general. Such a low frequency of mutation in human cancers is consistent with this protein kinase playing a role as a tumour requiring protein (TRP).
Mutation Rate in Specific Cancers:
Highest percent mutation rates per 100 amino acids length in human cancers: 0.36 % in 864 skin cancers tested; 0.28 % in 603 endometrium cancers tested; 0.23 % in 1420 large intestine cancers tested; 0.22 % in 1635 lung cancers tested; 0.2 % in 548 urinary tract cancers tested; 0.16 % in 589 stomach cancers tested; 0.12 % in 1512 liver cancers tested; 0.08 % in 1316 breast cancers tested; 0.07 % in 942 upper aerodigestive tract cancers tested; 0.07 % in 441 autonomic ganglia cancers tested; 0.04 % in 710 oesophagus cancers tested; 0.02 % in 833 ovary cancers tested; 0.02 % in 2009 haematopoietic and lymphoid cancers tested; 0.02 % in 1276 kidney cancers tested; 0.01 % in 2082 central nervous system cancers tested; 0.01 % in 1459 pancreas cancers tested.
Frequency of Mutated Sites:
None > 4 in 20,160 cancer specimens
Comments:
Only 2 deletions, and no insertions or complex mutations are noted on the COSMIC website.