Myotonin-protein kinase

1WT6, 2VD5176013400ENSG00000104936ENSMUSG00000030409Q09013P54265NM_001288766NM_004409NM_001190490NM_001190491NM_032418NP_001275695NP_004400NP_001275693.1NP_001275694.1NP_001275695.1NP_001177419NP_001177420NP_115794Myotonin-protein kinase (MT-PK) also known as myotonic dystrophy protein kinase (MDPK) or dystrophia myotonica protein kinase (DMK) is an enzyme that in humans is encoded by the DMPK gene.1wt6: Coiled-Coil domain of DMPK Myotonin-protein kinase (MT-PK) also known as myotonic dystrophy protein kinase (MDPK) or dystrophia myotonica protein kinase (DMK) is an enzyme that in humans is encoded by the DMPK gene. The dmpk gene product is a Ser/Thr protein kinase homologous to the MRCK p21-activated kinases and the Rho family of kinases. Data obtained by using antibodies that detect specific isoforms of DMPK indicate that the most abundant isoform of DMPK is an 80-kDa protein expressed almost exclusively in smooth, skeletal, and cardiac muscles. This kinase exists both as a membrane-associated and as a soluble form in human left ventricular samples. The different C termini of DMPK that arise from alternative splicing determine its localization to the endoplasmic reticulum, mitochondria, or cytosol in transfected COS-1 cells. Among the substrates for DMPK proposed by in vitro studies are phospholemman, the dihydropyridine receptor, and the myosin phosphatase targeting subunit. However, an in vivo demonstration of the phosphorylation of these substrates by DMPK remains to be established, and a link between these substrates and the clinical manifestations of myotonic dystrophy (DM) is unclear. Myotonin-protein kinase 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. Although the specific function of this protein is unknown, it appears to play an important role in muscle, heart, and brain cells. This protein may be involved in communication within cells. It also appears to regulate the production and function of important structures inside muscle cells by interacting with other proteins. For example, myotonic dystrophy protein kinase has been shown to turn off (inhibit) part of a muscle protein called myosin phosphatase. Myosin phosphatase is an enzyme that plays a role in muscle tensing (contraction) and relaxation. Dystrophia myotonica protein kinase (DMPK) is a serine/threonine kinase composed of a kinase domain and a coiled-coil domain involved in the multimerization. The crystal structure of the kinase domain of DMPK bound to the inhibitor bisindolylmaleimide VIII (BIM-8) revealed a dimeric enzyme associated by a conserved dimerization domain. The affinity of dimerisation suggested that the kinase domain alone is insufficient for dimerisation in vivo and that the coiled-coil domains are required for stable dimer formation. The kinase domain is in an active conformation, with a fully ordered and correctly positioned aC helix, and catalytic residues in a conformation competent for catalysis. The conserved hydrophobic motif at the C-terminal extension of the kinase domain is bound to the N-terminal lobe of the kinase domain, despite being unphosphorylated. The 3' untranslated region of this gene contains 5-37 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. As the DMPK repeat is replicated, the hairpin loop that is formed leads to repeat expansion (a) or contractions (b). Myotonic dystrophy (DM) 1 is an autosomal dominant neuromuscular disorder affecting approximately 1 in 8000 individuals. Affected individuals display a wide range of symptoms including myotonia, skeletal muscle weakness and wasting, cardiac conduction abnormalities, and cataracts. Despite cloning of the locus, the complex disease phenotype of DM has proven difficult to interpret, and the exact role of DMPK in the pathogenesis of DM remains unclear. Myotonic dystrophy protein kinase has been shown to interact with HSPB2 and RAC1.