Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Evidence
1:
Inferred from Physical InteractionIntAct
Myotonic dystrophy (DM) is caused by a CTG expansion in the 3'-untranslated region of a protein kinase gene (DMPK). Cardiovascular disease is one of the most prevalent causes of death in DM patients. Electrophysiological studies in cardiac muscles from DM patients and from DMPK(-/-) mice suggested that DMPK is critical to the modulation of cardiac contractility and to the maintenance of proper cardiac conduction activity. However, there are no data regarding the molecular signaling pathways involved in DM heart failure. Here we show that DMPK expression in cardiac myocytes is highly enriched in the sarcoplasmic reticulum (SR) where it colocalizes with the ryanodine receptor and phospholamban (PLN), a muscle-specific SR Ca(2+)-ATPase (SERCA2a) inhibitor. Coimmunoprecipitation studies showed that DMPK and PLN can physically associate. Furthermore, purified wild-type DMPK, but not a kinase-deficient mutant (K110A DMPK), phosphorylates PLN in vitro. Subsequent studies using the DMPK(-/-) mice demonstrated that PLN is hypo-phosphorylated in SR vesicles from DMPK(-/-) mice compared with wild-type mice both in vitro and in vivo. Finally, we show that Ca(2+) uptake in SR is impaired in ventricular homogenates from DMPK(-/-) mice. Together, our data suggest the existence of a novel regulatory DMPK pathway for cardiac contractility and provide a molecular mechanism for DM heart pathology.
Adrenergic receptor signaling pathway involved in heart processdefinition[GO:0086023]‹silver
A series of molecular signals beginning with a G-protein coupled adrenergic cell surface receptor combining with epinephrine or norepinephrine, which contributes to a circulatory system process carried out by the heart.
Fluorescence in situ hybridization (FISH) experiments were performed using genomic and complementary DNA probes in order to determine the location on human chromosomes for five genes expressed in cardiac and skeletal muscle sarcoplasmic reticulum. The chromosome location of each gene was determined in terms of both cytogenetic bands and fractional chromosome length. The ATP2A2 gene, expressing the SERCA2 isoform of the Ca2+ pump, maps to bands 12q23-q24.1, the phospholamban gene (PLN) to 6q22.1, the human skeletal muscle calsequestrin gene (CASQ1) to band 1q21, the cardiac calsequestrin gene (CASQ2) to bands 1p11-p13.3, and the cardiac calcium release channel gene (RYR2) to the interval between band 1q42.1 (distal) and band 1q43 (proximal).
Any process that modulates the frequency, rate or extent of the directed movement of calcium ions into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore.
Any process that modulates the frequency, rate or extent of cardiac muscle cell contraction.
IEAOrtholog Compara
Regulation of cardiac muscle contraction by regulation of the release of sequestered calcium iondefinition[GO:0010881]‹silver
Any process that modulates the frequency, rate or extent of cardiac muscle contraction via the regulation of the release of sequestered calcium ion by sarcoplasmic reticulum into cytosol. The sarcoplasmic reticulum is the endoplasmic reticulum of striated muscle, specialised for the sequestration of calcium ions that are released upon receipt of a signal relayed by the T tubules from the neuromuscular junction.
Any process that modulates the frequency, rate or extent of relaxation of muscle.
IEAOrtholog Compara
Regulation of ryanodine-sensitive calcium-release channel activitydefinition[GO:0060314]‹silver
Any process that modulates the activity of a ryanodine-sensitive calcium-release channel. The ryanodine-sensitive calcium-release channel catalyzes the transmembrane transfer of a calcium ion by a channel that opens when a ryanodine class ligand has been bound by the channel complex or one of its constituent parts.
IEAOrtholog Compara
Regulation of the force of heart contraction by cardiac conductiondefinition[GO:0086092]‹silver
A cardiac conduction process that modulates the extent of heart contraction, changing the force with which blood is propelled.
IEAOrtholog Compara
Pathways
According to KEGG, this protein belongs to the following pathways:
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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