DMPK
Domain
The coiled coil domain is required for homodimerization and regulates the enzymatic activity.
Function
Non-receptor serine/threonine protein kinase which is necessary for the maintenance of skeletal muscle structure and function. May play a role in myocyte differentiation and survival by regulating the integrity of the nuclear envelope and the expression of muscle-specific genes. May also phosphorylate PPP1R12A and inhibit the myosin phosphatase activity to regulate myosin phosphorylation. Also critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity probably through the regulation of cellular calcium homeostasis. Phosphorylates PLN, a regulator of calcium pumps and may regulate sarcoplasmic reticulum calcium uptake in myocytes. May also phosphorylate FXYD1/PLM which is able to induce chloride currents. May also play a role in synaptic plasticity.
Involvement in disease
Dystrophia myotonica 1
DM1
A muscular disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness and cardiac arrhythmias.
None
The disease is caused by variants affecting the gene represented in this entry. The causative mutation is a CTG expansion in the 3'-UTR of the DMPK gene. A length exceeding 50 CTG repeats is pathogenic, while normal individuals have 5 to 37 repeats. Intermediate alleles with 35-49 triplets are not disease-causing but show instability in intergenerational transmissions. Disease severity varies with the number of repeats: mildly affected persons have 50 to 150 repeats, patients with classic DM have 100 to 1,000 repeats, and those with congenital onset can have more than 2,000 repeats.
Post-translational modifications
Phosphorylated. Autophosphorylates. Phosphorylation by RAF1 may result in activation of DMPK.
Proteolytic processing of the C-terminus may remove the transmembrane domain and release the kinase from membranes stimulating its activity.
Sequence Similarities
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily.
Tissue Specificity
Most isoforms are expressed in many tissues including heart, skeletal muscle, liver and brain, except for isoform 2 which is only found in the heart and skeletal muscle, and isoform 14 which is only found in the brain, with high levels in the striatum, cerebellar cortex and pons.
Cellular localization
- Endoplasmic reticulum membrane
- Single-pass type IV membrane protein
- Cytoplasmic side
- Nucleus outer membrane
- Single-pass type IV membrane protein
- Cytoplasmic side
- Mitochondrion outer membrane
- Single-pass type IV membrane protein
- Sarcoplasmic reticulum membrane
- Cell membrane
- Cytoplasm
- Cytosol
- Localizes to sarcoplasmic reticulum membranes of cardiomyocytes.
- Isoform 1
- Mitochondrion membrane
- Isoform 3
- Mitochondrion membrane
Alternative names
DM1PK, MDPK, Myotonin-protein kinase, MT-PK, DM-kinase, DM1 protein kinase, DMPK, Myotonic dystrophy protein kinase, DMK