Nomenclature
Short Name:
PAK6
Full Name:
Serine-threonine-protein kinase PAK 6
Alias:
- EC 2.7.11.1
- PAK5
Classification
Type:
Protein-serine/threonine kinase
Group:
STE
Family:
STE20
SubFamily:
PAKB
Specific Links
Structure
Mol. Mass (Da):
74869
# Amino Acids:
681
# mRNA Isoforms:
2
mRNA Isoforms:
74,869 Da (681 AA; Q9NQU5); 69,777 Da (636 AA; Q9NQU5-2)
4D Structure:
Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1 By similarity. Interacts with the androgen receptor.
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
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
Serine phosphorylated:
S83, S104, S113, S132, S135, S165+, S179, S207, S246, S248, S308, S327, S328, S346, S347, S360, S560+.
Threonine phosphorylated:
T69, T99, T326, T339, T354, T371, T564-.
Tyrosine phosphorylated:
Y81, Y129, Y144, Y365, Y566-.
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:
65
961
22
1228
4
57
12
38
20
293
11
622
31
461
76
440
41
612
24
538
5
67
46
33
0.9
14
28
8
21
313
28
464
8
123
13
145
10
152
44
568
6
88
25
213
41
612
93
569
10
141
22
390
0.7
10
9
11
2
32
12
26
5
79
12
38
8
118
91
360
13
196
19
503
2
36
50
55
58
853
82
699
10
150
21
409
5
81
23
183
23
333
12
821
14
202
19
475
9
126
21
316
47
691
51
709
6
85
26
186
12
181
19
419
6
90
19
187
8
125
14
50
30
437
18
314
100
1477
26
2444
6
94
59
357
55
811
52
701
17
251
35
252
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
52.7
60.8
99
98.5
99
98.5
-
-
93
-
-
-
66.4
67.7
94
-
-
-
92.5
95.6
93
30.7
48.5
93
-
-
-
62.3
69.9
-
75.9
82.4
78
46.7
61.7
66
52.5
64.5
69.5
-
-
-
44.4
57.6
-
44.9
57.6
-
29.8
47.3
45
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
25.6
43.1
-
28.1
41.6
-
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 | AR - P10275 |
| 2 | CDC42 - P60953 |
| 3 | AKT1 - P31749 |
| 4 | ESR1 - P03372 |
| 5 | PTEN - P60484 |
| 6 | YWHAQ - P27348 |
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 |
|---|
Disease Linkage
General Disease Association:
Cancer, inflammatory disorders
Specific Diseases (Non-cancerous):
La Crosse encephalitis
Comments:
La Crosse Encephalitis is characterized by inflammation in the brain inducing seizures, headaches, fever, coma, and paralysis.
Specific Cancer Types:
Prostate cancer
Comments:
PAK6 suppresses tumour progression through regulation of androgen receptor homeostasis.
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= -64, p<0.003); Bladder carcinomas (%CFC= +52, p<0.023); Breast epithelial carcinomas (%CFC= -54, p<0.021); Oral squamous cell carcinomas (OSCC) (%CFC= -54, p<0.03); Ovary adenocarcinomas (%CFC= +174, p<0.003); Pituitary adenomas (aldosterone-secreting) (%CFC= +115, p<0.012); Skin fibrosarcomas (%CFC= -85); Skin melanomas (%CFC= -73, p<0.023); Skin melanomas - malignant (%CFC= -64, p<0.006); and Vulvar intraepithelial neoplasia (%CFC= +87, p<0.001). The COSMIC website notes an up-regulated expression score for PAK6 in diverse human cancers of 351, which is 0.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 13 for this protein kinase in human cancers was 0.2-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. Activation of PAK6 through MAP2K6 can be inhibited through the three mutations S165A, S560A, and Y566F.
Mutation Rate in All Cancers:
Percent mutation rates per 100 amino acids length in human cancers: 0.06 % in 25387 diverse cancer specimens. This rate is only -22 % lower 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: 0.3 % in 589 stomach cancers tested; 0.27 % in 805 skin cancers tested; 0.22 % in 1119 large intestine cancers tested; 0.08 % in 1941 lung cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: R675Q (5).
Comments:
Only 4 deletions, 2 insertions, and no complex mutations are noted on the COSMIC website.