Nomenclature
Short Name:
PAK5
Full Name:
Serine-threonine-protein kinase PAK 7
Alias:
- EC 2.7.11.1
- PAK7
- PAK-7
- KIAA1264
- P21 protein (Cdc42/Rac)-activated kinase 7
- P21-activated kinase 7
- PAK 7
- PAK-5
Classification
Type:
Protein-serine/threonine kinase
Group:
STE
Family:
STE20
SubFamily:
PAKB
Specific Links
Structure
Mol. Mass (Da):
80,745
# Amino Acids:
719
# mRNA Isoforms:
1
mRNA Isoforms:
80,745 Da (719 AA; Q9P286)
4D Structure:
Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1
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.
hiddentext
Post-translation Modifications
For detailed information on phosphorylation of this kinase go to PhosphoNET
Acetylated:
K167.
Methylated:
R285.
Serine phosphorylated:
S183, S270, S271, S277, S286, S290, S345, S347, S573, S602+.
Threonine phosphorylated:
T281, T349, T606-.
Tyrosine phosphorylated:
Y159, Y182, Y272, Y350+, Y608-.
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:
46
432
29
818
4
37
15
28
1.2
11
2
5
48
445
77
503
35
329
25
298
0.6
6
74
7
8
76
31
191
48
445
27
524
28
261
17
224
1.4
13
73
12
1
9
21
9
51
472
152
481
0.9
8
24
8
2
17
10
15
2
14
15
7
4
40
15
17
0.9
8
109
9
1.3
12
10
8
1.2
11
77
11
26
241
109
283
2
14
13
7
1.2
11
16
13
2
16
4
14
2
15
9
22
1.4
13
12
18
43
402
42
479
1
9
27
8
2
15
9
12
2
14
10
19
6
54
28
50
34
317
24
324
100
932
36
1221
52
484
72
927
64
593
52
531
6
56
44
65
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
92.3
92.4
100
91.9
92.3
99
-
-
94
-
-
-
96.9
98.3
97
-
-
-
93.9
96.8
94
31.3
48.7
95
-
-
-
85.9
92.5
-
75.7
82.1
83
53.1
64.8
-
65
75.1
68
-
-
-
45.6
58.3
47
45.5
61.1
-
31.1
47
56
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
27.1
44.2
-
27.8
42.7
-
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | CDC42 - P60953 |
| 2 | BAD - Q92934 |
| 3 | TUBGCP4 - Q9UGJ1 |
| 4 | HIGD1A - Q9Y241 |
| 5 | CCDC13 - Q8IYE1 |
| 6 | AP2S1 - P53680 |
| 7 | CCDC59 - Q9P031 |
Regulation
Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
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
_Specificity_Predicted.gif)
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
Specific Cancer Types:
Ovarian cancer
Comments:
PAK5 is overexpressed in epithelial ovarian cancer (EOC), which is faced with an obstacle of paclitaxel resistance (PubMed: 23877225). Its expression was increased with EOC progression through the adenoma to carcinoma sequence, with the highest expression level of PAK5 in invasive and metastatic EOCs. Since PAK5 is correlated to human EOC, and its increased expression promotes EOC progression and induces EOC cell paclitaxel chemoresistance, PAK5 may be a useful target for therapeutic drug development.
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: Breast epithelial carcinomas (%CFC= -72, p<0.039); and Malignant pleural mesotheliomas (MPM) tumours (%CFC= -55, p<0.019). The COSMIC website notes an up-regulated expression score for PAK5 in diverse human cancers of 371, which is 0.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 0 for this protein kinase in human cancers was 100% lower than 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: 0.19 % in 25548 diverse cancer specimens. This rate is 2.6-fold 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: 1.67 % in 805 skin cancers tested; 0.71 % in 1093 large intestine cancers tested; 0.47 % in 1992 lung cancers tested; 0.35 % in 589 stomach cancers tested; 0.17 % in 1270 liver cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: S364L (6); P358H (5); M173I (5); A120V (5).
Comments:
Only 3 deletions, 1 complex mutation, and no insertions are noted on the COSMIC website.