Nomenclature
Short Name:
NEK8
Full Name:
Serine-threonine-protein kinase Nek8
Alias:
- EC 2.7.11.1
- NEK12A
- NIMA-related kinase 12a
Classification
Type:
Protein-serine/threonine kinase
Group:
Other
Family:
NEK
SubFamily:
NA
Structure
Mol. Mass (Da):
74,806
# Amino Acids:
692
# mRNA Isoforms:
1
mRNA Isoforms:
74,806 Da (692 AA; Q86SG6)
4D Structure:
NA
1D Structure:
Subfamily Alignment
Domain Distribution:
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:
S151, S156, S158.
Threonine phosphorylated:
T131, T162.
Ubiquitinated:
K639.
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
2133
12
619
1.4
30
5
23
-
-
-
-
2
39
49
22
40
859
17
408
2
41
18
14
2
42
23
25
0.3
6
3
1
0.4
9
3
2
0.7
15
3
1
0.7
15
3
3
54
1148
15
596
-
-
-
-
0.3
7
3
3
0.4
9
3
2
2
33
10
12
3
63
11
37
0.6
12
3
1
0.8
17
3
15
36
770
49
311
0.3
7
3
1
1.3
27
3
4
-
-
-
-
0.5
10
3
4
0.7
15
3
2
38
806
35
712
1.1
23
3
1
1.3
28
3
10
0.5
11
3
1
-
-
-
-
62
1328
12
48
19
398
16
348
0.1
3
24
2
39
829
52
683
28
587
35
503
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
75.4
77
97
87.1
87.8
98
-
-
95
-
-
-
88.9
91.1
94
-
-
-
93.5
96.4
94
93.4
95.4
94
-
-
-
68.8
74
-
76.9
85.2
81
24.8
39.5
77
73.9
85.2
74
-
-
-
-
-
37
-
-
-
23.3
37.9
40
38.3
50.9
-
-
-
-
-
-
-
-
-
-
24.3
44.1
-
-
-
-
21.8
37.2
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Regulation
Activation:
NA
Inhibition:
NA
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
Disease Linkage
General Disease Association:
Cancer, nephrological, and immune disorders
Specific Diseases (Non-cancerous):
Kidney disease; Nephronophthisis 9 (NPHP9); Polycystic kidney disease (PKD); Renal-hepatic-pancreatic dysplasia; Renal-hepatic-pancreatic dysplasia 2; Renal-hepatic-pancreatic dysplasia 1; Infantile autosomal recessive medullary cystic kidney disease
Comments:
Kidney Disease is a rare disorder related to Cystic Kidney, and Polycystic Kidney Disease (PKD) where multiple cysts develop in the kidney, often leading to kidney failure. Nephronophthisis 9 (NPHP9) is a rare disorder affecting the kidneys of children leading to kidney failure through extensive cyst formation. In NPHP9 there is are independent mutations, L330F, H425Y, or A497P that will induce abnormal ciliary location, while not affecting ciliation, mitosis, or centriole number. Renal-Hepatic-Pancreatic Dysplasia affects kidney tissues, has a relation to hepatitis, and is often characterized by effects including renal dysplasia, pancreatic fibrosis, and hepatic dysgenesis. Infantile Autosomal Recessive Medullary Cystic Kidney Disease has also been called Immunologic Deficiency Syndrome, affects the kidney, and has a relation to cystic kidney and asphyxiating thoracic dystrophy disorders.
Specific Cancer Types:
Breast malignant phyllodes tumours; Jaw cancer
Comments:
NEK8 is linked to Breast Malignant Phyllodes tumours, which are rare disorders that has a relation to sarcoma and breast fibroadenomas.
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 human Ovary adenocarcinomas (%CFC= +89, p<0.009). The COSMIC website notes an up-regulated expression score for NEK8 in diverse human cancers of 472, which is close to the average score of 462 for the human protein kinases. The down-regulated expression score of 86 for this protein kinase in human cancers was 1.4-fold of the 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.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.08 % in 24726 diverse cancer specimens. This rate is very similar (+ 8% 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: 0.34 % in 1270 large intestine cancers tested; 0.29 % in 589 stomach cancers tested; 0.17 % in 603 endometrium cancers tested; 0.16 % in 273 cervix cancers tested; 0.14 % in 710 oesophagus cancers tested; 0.13 % in 548 urinary tract cancers tested; 0.13 % in 1634 lung cancers tested; 0.1 % in 833 ovary cancers tested; 0.1 % in 1316 breast cancers tested; 0.09 % in 1512 liver cancers tested; 0.06 % in 238 bone cancers tested; 0.05 % in 942 upper aerodigestive tract cancers tested; 0.05 % in 558 thyroid cancers tested; 0.05 % in 1459 pancreas cancers tested; 0.03 % in 441 autonomic ganglia cancers tested; 0.03 % in 2009 haematopoietic and lymphoid cancers tested; 0.02 % in 2103 central nervous system cancers tested; 0.01 % in 1276 kidney cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: T606N (4).
Comments:
Only 4 deletions, 4 insertions, and no complex mutations are noted on the COSMIC website.