DMPK

The protein encoded by this gene is a serine-threonine kinase that is closely related to other kinases that interact with members of the Rho family of small GTPases. Substrates for this enzyme include myogenin, the beta-subunit of the L-type calcium channels, and phospholemman. The 3' untranslated region of this gene contains 5-38 copies of a CTG trinucleotide repeat. Expansion of this unstable motif to 50-5,000 copies causes myotonic dystrophy type I, which increases in severity with increasing repeat element copy number. Repeat expansion is associated with condensation of local chromatin structure that disrupts the expression of genes in this region. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Jul 2016]

Full Name

DM1 Protein Kinase

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.

Biological Process

Cellular calcium ion homeostasis Source: UniProtKB
Intracellular signal transduction Source: GO_Central
Muscle cell apoptotic process Source: UniProtKB
Nuclear envelope organization Source: UniProtKB
Peptidyl-serine phosphorylation Source: GO_Central
Protein phosphorylation Source: UniProtKB
Regulation of heart contraction Source: UniProtKB
Regulation of myotube differentiation Source: UniProtKB
Regulation of skeletal muscle contraction by calcium ion signaling Source: GO_Central

Cellular Location

Cell membrane; Cytosol; Endoplasmic reticulum membrane; Mitochondrion outer membrane; Nucleus outer membrane; Sarcoplasmic reticulum membrane. Localizes to sarcoplasmic reticulum membranes of cardiomyocytes.
Isoform 1&1: Mitochondrion membrane

Involvement in disease

Dystrophia myotonica 1 (DM1):
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. A muscular disorder characterized by myotonia, muscle wasting in the distal extremities, cataract, hypogonadism, defective endocrine functions, male baldness and cardiac arrhythmias.

Topology

Cytoplasmic: 1-590
Helical: 591-611
Lumenal: 612-629

PTM

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.