Nomenclature
Short Name:
PDHK4
Full Name:
Pyruvate dehydrogenase [lipoamide]] kinase isozyme 4, mitochondrial
Alias:
- Pyruvate dehydrogenase kinase isoform 4
- PDK4
Classification
Type:
Protein-serine/threonine kinase
Group:
Atypical
Family:
PDHK
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
46,469
# Amino Acids:
411
# mRNA Isoforms:
1
mRNA Isoforms:
46,469 Da (411 AA; Q16654)
4D Structure:
NA
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 243 | 368 | HATPase_c |
| 138 | 368 | Histidine kinase |
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:
S10, S13, S368, S369, S381.
Ubiquitinated:
K111, K122.
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:
50
1031
30
904
9
192
12
243
87
1771
11
996
14
278
112
644
57
1161
30
775
2
45
59
96
9
184
39
295
29
583
41
672
36
739
10
646
36
725
85
969
14
294
30
551
37
754
133
820
12
244
22
279
7
137
9
88
10
201
17
235
31
632
18
805
6
121
202
223
11
230
18
236
100
2042
78
3301
37
761
107
713
23
461
26
637
16
328
28
424
29
590
20
685
8
154
18
137
4
91
26
95
47
950
74
924
17
337
25
471
26
538
18
526
19
395
18
440
4
81
28
77
21
439
18
338
12
254
31
344
25
515
76
869
43
877
83
818
83
1704
48
4042
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.7
100
100
98
99.5
98
-
-
93
-
-
97
58.2
74
94
-
-
-
92.7
96.8
93
92.2
96.3
93
-
-
-
70.3
74.4
-
77.7
88.1
80
72
85.4
-
64.7
82.7
73
-
-
-
50.6
68.5
-
-
-
-
47.6
65.9
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
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 | DLAT - P10515 |
| 2 | PDHA1 - P08559 |
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 |
|---|
Disease Linkage
Comments:
Studies in transgenic PDHK4 knockout mice subjected to a high-saturated fat diet that induces hyperglycemia, hyperinsulinaemia, glucose intolerance, hepatic steatosis and obesity, showed that PDHK4 is an attractive candidate for drug discovery for the treatment of type 2 diabetes. Cells that lack insulin (or are insensitive to insulin) often overexpress PDHK4.
Gene Expression in Cancers:
The COSMIC website notes an up-regulated expression score for PDHK4 in diverse human cancers of 329, which is 0.7-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: 0.08 % in 24751 diverse cancer specimens. This rate is very similar (+ 9% 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: 0.54 % in 864 skin cancers tested; 0.44 % in 603 endometrium cancers tested; 0.29 % in 1270 large intestine cancers tested; 0.16 % in 1512 liver cancers tested; 0.14 % in 710 oesophagus cancers tested; 0.12 % in 589 stomach cancers tested; 0.09 % in 273 cervix cancers tested; 0.07 % in 1316 breast cancers tested; 0.06 % in 1276 kidney cancers tested; 0.05 % in 2009 haematopoietic and lymphoid cancers tested; 0.05 % in 1459 pancreas cancers tested.
Frequency of Mutated Sites:
Most frequent mutations with the number of reports indicated in brackets: R124Q (3); R124* (3).
Comments:
Only 2 deletions, and no insertions or complex mutations are noted on the COSMIC website.