Nomenclature
Short Name:
BCKDK
Full Name:
[3-methyl-2-oxobutanoate dehydrogenase [lipoamide]] kinase, mitochondrial
Alias:
- BCKD
- BCKDHKIN
- BCKD-kinase
- Branched-chain alpha-ketoacid dehydrogenase kinase
- EC 2.7.1.115
- EC 2.7.11.4
Classification
Type:
Protein-serine/threonine kinase
Group:
Atypical
Family:
PDHK
SubFamily:
NA
Specific Links
Structure
Mol. Mass (Da):
46,360
# Amino Acids:
412
# mRNA Isoforms:
3
mRNA Isoforms:
46,360 Da (412 AA; O14874); 41,090 Da (365 AA; O14874-3); 37,768 Da (335 AA; O14874-2)
4D Structure:
Monomer
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 159 | 404 | HATPase_c |
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:
K184, K192, K233, K245.
Serine phosphorylated:
S9, S31, S33, S47, S52.
Threonine phosphorylated:
T32, T35, T37.
Tyrosine phosphorylated:
Y77, Y93.
Ubiquitinated:
K48.
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
873
16
868
7
130
10
70
7
126
1
0
40
762
46
1444
40
745
14
706
9
169
44
256
18
335
19
513
40
754
21
995
29
551
10
475
11
215
43
149
14
261
14
203
40
763
94
648
4
69
12
14
4
79
7
24
7
135
9
56
11
202
7
117
5
100
97
34
12
234
7
150
10
192
49
86
33
629
56
604
7
127
8
86
6
116
12
48
6
117
2
17
5
89
7
56
4
84
8
26
100
1884
27
2924
5
87
15
22
8
142
7
51
6
119
7
54
6
104
14
65
59
1120
18
793
18
338
27
478
19
353
56
443
52
988
26
707
2
40
22
86
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
99.8
99.8
100
98.1
98.5
98
-
-
97
-
-
97
-
-
96
-
-
-
95.2
96.8
95
95.6
96.6
96
-
-
-
73.3
78.4
-
-
-
89
82.1
89.8
83
75.9
84.5
81
-
-
-
22.8
39.7
-
-
-
-
24.5
42.5
-
61.2
74.9
-
32.3
51.7
-
33.5
53.2
-
-
-
-
31.8
50.1
-
25.7
47.6
32
-
-
42
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
Binding Proteins
Examples of known interacting proteins
hiddentext
| No. | Name – UniProt ID |
|---|---|
| 1 | TRAF4 - Q9BUZ4 |
| 2 | SUMO1 - P63165 |
| 3 | CAB39L - Q9H9S4 |
| 4 | BCKDHB - P21953 |
| 5 | CAB39 - Q9Y376 |
| 6 | RNF219 - Q5W0B1 |
| 7 | FAM98B - Q52LJ0 |
| 8 | RTCD1 - O00442 |
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
General Disease Association:
Neurological disorders
Specific Diseases (Non-cancerous):
Branched-chain ketoacid dehydrogenase kinase deficiency (BCKDKD)
Comments:
The BCKDK gene is involved in branched-chain ketoacid dehydrogenase kinase deficiency, which is a metabolic disorder characterized by autism, epilepsy, intellectual disability, and reduced branched-chain amino acids. A diet enriched with branched amino acids can help to normalize plasma BCAA levels.
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 cell carcinomas (%CFC= +67, p<0.002); Cervical epithelial cancer (%CFC= +48, p<0.027); Classical Hodgkin lymphomas (%CFC= +91, p<0.0002); Large B-cell lymphomas (%CFC= +171, p<(0.0003); Lung adenocarcinomas (%CFC= +50, p<0.0001); and Skin melanomas - malignant (%CFC= +59, p<0.003). The COSMIC website notes an up-regulated expression score for BCKDK in diverse human cancers of 654, which is 1.4-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 75 for this protein kinase in human cancers was 1.3-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: 0.06 % in 25158 diverse cancer specimens. This rate is only -25 % 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: 0.37 % in 589 stomach cancers tested; 0.29 % in 1270 large intestine cancers tested; 0.24 % in 603 endometrium cancers tested.
Frequency of Mutated Sites:
None > 2 in 19,689 cancer specimens
Comments:
Only 3 deletions, and no insertions or complex mutations are noted on the COSMIC website.