Nomenclature
Short Name:
DMPK1
Full Name:
Myotonin-protein kinase
Alias:
- Myotonic dystrophy protein kinase
- MDPK
- DM-kinase
- DMK
- DMPK
- MT-PK
Classification
Type:
Protein-serine/threonine kinase
Group:
AGC
Family:
DMPK
SubFamily:
GEK
Specific Links
Structure
Mol. Mass (Da):
70371
# Amino Acids:
639
# mRNA Isoforms:
12
mRNA Isoforms:
70,371 Da (639 AA; Q09013-1); 70,014 Da (634 AA; Q09013-6); 69,950 Da (630 AA; Q09013-16); 69,592 Da (625 AA; Q09013-15); 69,385 Da (629 AA; Q09013); 69,028 Da (624 AA; Q09013-11); 67,263 Da (609 AA; Q09013-7); 65,076 Da (589 AA; Q09013-5); 60,790 Da (545 AA; Q09013-8); 59,804 Da (535 AA; Q09013-10); 59,446 Da (530 AA; Q09013-12); 59,334 Da (540 AA; Q09013-2)
4D Structure:
Homodimer.
1D Structure:
3D Image (rendered using PV Viewer):
PDB ID
Subfamily Alignment
Domain Distribution:
| Start | End | Domain |
|---|---|---|
| 71 | 339 | Pkinase |
| 350 | 425 | Pkinase_C |
| 469 | 544 | Coiled-coil |
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
Threonine phosphorylated:
T533, T536+.
Ubiquitinated:
K75, K197.
Serine phosphorylated:
S2.
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:
51
515
42
726
9
90
20
99
15
153
15
191
31
312
127
499
74
755
30
562
46
472
119
1803
14
145
43
400
68
696
53
684
28
284
24
236
7
72
101
91
5
55
40
155
62
627
243
595
6
61
48
143
6
57
15
80
19
191
31
431
17
172
22
202
12
124
131
118
7
68
26
138
17
173
130
189
34
349
162
397
12
119
28
169
7
76
34
152
14
141
34
144
7
74
26
130
8
82
28
187
50
507
78
563
4
42
51
89
11
108
26
204
12
120
26
153
10
103
42
54
38
392
30
456
100
1019
51
1326
46
472
91
889
62
627
88
601
13
130
48
195
Evolution
Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
100
100
100
22.7
28.5
100
87.4
89.1
97
-
-
91
-
-
83
81.1
85
90
-
-
-
78.2
83.4
86
22.1
27.7
87
-
-
-
22.2
28.2
-
21.9
27.7
-
-
-
55
22.3
28.5
-
-
-
-
22.2
28.6
-
-
-
-
24.1
35.3
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
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 | HSPB2 - Q16082 |
| 2 | PPP1R12A - O14974 |
| 3 | RAF1 - P04049 |
| 4 | ATXN1 - P54253 |
Regulation
Activation:
Activated in response to G protein second messengers. Proteolytic processing of the C-terminus may remove the transmembrane domain and release the kinase from membranes stimulating its activity. Phosphorylation by RAF1 may result in activation of DMPK.
Inhibition:
Maintained in an inactive conformation by the negative autoregulatory C-terminal coiled-coil region.
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
Matrix Type:
Experimentally derived from alignment of 1 known protein substrate phosphosites and 29 peptides phosphorylated by recombinant DMPK1 in vitro tested in-house by Kinexus.
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:
Musculoskeletal disorders
Specific Diseases (Non-cancerous):
Myotonic dystrophy Type 1 (DM1); Myotonic dystrophy; Myotonia; Myotonic dystrophy Type 2; Congenital myotonic dystrophy
Comments:
DMPK1 is involved in dystrophia myotonica 1 (DM1), which is a muscular disorder characterized by several features such as myotonia, muscle wasting in the distal extremities, and hypogonadism. K100A mutation leads to loss of kinase activity and CTG expansion in the 3'-UTR of the DMPK gene are associated with this disease.
Gene Expression in Cancers:
The COSMIC website notes an up-regulated expression score for DMPK1 in diverse human cancers of 468, which is close to 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 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 24939 diverse cancer specimens. This rate is only -36 % 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: 0.25 % in 1270 large intestine cancers tested; 0.21 % in 589 stomach cancers tested; 0.18 % in 864 skin cancers tested; 0.18 % in 603 endometrium cancers tested; 0.17 % in 273 cervix cancers tested.
Frequency of Mutated Sites:
None > 2 in 20,223 cancer specimens
Comments:
Only 4 deletions, no insertions or complex mutations are noted on the COSMIC website.