Nomenclature
Short Name:
PDHK2
Full Name:
[Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial
Alias:
- EC 2.7.11.2
- Kinase Pyruvate dehydrogenase kinase 2
- PDK2
- Pyruvate dehydrogenase [lipoamide] kinase isozyme 2, mitochondrial precursor
Classification
Type:
Protein-serine/threonine kinase
Group:
Atypical
Family:
PDHK
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
46,154
# Amino Acids:
407
# mRNA Isoforms:
2
mRNA Isoforms:
46,154 Da (407 AA; Q15119); 38,864 Da (343 AA; Q15119-2)
4D Structure:
NA
1D Structure:
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 240 | 363 | HATPase_c |
| 135 | 364 | Histidine kinase |
| 29 | 193 | BCDHK |
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:
S285.
Threonine phosphorylated:
T118.
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:
99
926
29
1172
14
134
17
107
38
360
12
476
45
421
97
489
78
728
25
656
3
32
78
44
42
393
35
611
81
759
47
640
50
468
17
400
38
357
99
381
19
174
35
225
65
605
198
803
11
106
34
209
12
108
15
102
11
107
21
114
20
192
16
115
9
82
209
98
21
193
23
234
51
481
107
444
50
466
109
498
19
175
29
177
12
116
33
166
69
650
22
1918
14
128
23
144
11
106
29
133
100
937
59
1409
28
258
37
1016
65
610
23
2109
19
182
23
192
58
540
28
121
58
540
24
516
60
565
36
574
18
173
66
415
71
669
57
614
6
52
35
40
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.8
99.8
100
-
-
-
-
-
98
-
-
100
88
88.9
99
-
-
-
97.3
98.8
97.5
97.5
98.8
97.5
-
-
-
-
-
-
68.9
84.6
93
74.7
87.2
75
73.1
86.8
73
-
-
-
54.2
71.2
59
-
-
-
48.9
66.3
52
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
20.6
43
-
-
-
-
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 | PDHX - O00330 |
| 2 | DLAT - P10515 |
| 3 | CTTN - Q14247 |
| 4 | PDK1 - Q15118 |
| 5 | AKT1 - P31749 |
| 6 | PDHA1 - P08559 |
| 7 | SGK1 - O00141 |
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 |
|---|
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
Gene Expression in Cancers:
The COSMIC website notes an up-regulated expression score for PDHK2 in diverse human cancers of 478, which is close to the average score of 462 for the human protein kinases. The down-regulated expression score of 111 for this protein kinase in human cancers was 1.9-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: 0.05 % in 24772 diverse cancer specimens. This rate is only -33 % 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: 0.22 % in 548 urinary tract cancers tested; 0.2 % in 864 skin cancers tested; 0.2 % in 603 endometrium cancers tested; 0.19 % in 1270 large intestine cancers tested; 0.1 % in 710 oesophagus cancers tested; 0.09 % in 273 cervix cancers tested; 0.09 % in 1634 lung cancers tested; 0.07 % in 1512 liver cancers tested; 0.06 % in 881 prostate cancers tested; 0.04 % in 2103 central nervous system cancers tested; 0.04 % in 1276 kidney cancers tested; 0.02 % in 1316 breast cancers tested.
Frequency of Mutated Sites:
None > 3 in 20,055 cancer specimens
Comments:
Only 2 deletions, 1 insertion, and no complex mutations are noted on the COSMIC website.