JPH2
Description
The JPH2 (junctophilin 2) is a protein-coding gene located on chromosome 20.
Junctophilin 2, also known as JPH2, is a protein encoded by the JPH2 gene in humans. Alternative splicing occurs at this locus, resulting in two distinct isoforms. JPH2 is a crucial component of junctional complexes between the plasma membrane and the endoplasmic/sarcoplasmic reticulum, found in all excitable cell types. It consists of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a cytoplasmic MORN domain that interacts with the plasma membrane. JPH2 belongs to the junctophilin gene family and is the primary isoform in cardiac tissue, also co-expressed with JPH1 in skeletal muscle. It plays a vital role in maintaining the spacing and geometry of the cardiac dyad, which is essential for calcium-induced calcium release by positioning L-type calcium channels on the plasma membrane close to ryanodine receptor type 2 on the sarcoplasmic reticulum. JPH2 also contains a nuclear localization signal and a DNA binding domain. During heart disease, stress-activated calpain cleaves JPH2, releasing an N-terminal fragment containing the nuclear localization signal and DNA binding domain. This fragment translocates to the nucleus and regulates gene transcription.
Junctophilin-2 (JPH2) acts as a membrane-binding protein, bridging the plasma membrane and sarcoplasmic reticulum. This role is crucial for normal excitation-contraction coupling in cardiomyocytes. JPH2 maintains the critical 12-15 nm gap between the sarcolemma and sarcoplasmic reticulum membranes within the cardiac dyads, enabling functional communication between the cell surface and intracellular calcium release channels. It further contributes to proper intracellular calcium signaling in cardiac myocytes by participating in ryanodine receptor-mediated calcium ion release. Additionally, JPH2 contributes to the formation of skeletal muscle triad junctions.
JPH2 is also known as CMD2E, CMH17, JP-2, JP2.
Associated Diseases
- Cardiomyopathy, familial hypertrophic, 17
- Familial isolated dilated cardiomyopathy
- Cardiomyopathy, dilated, 2E
