JPH2

JPH2 (Junctophilin 2) is a Protein Coding gene encodes the protein which is a component of junctional complexes and is composed of a C-terminal hydrophobic segment spanning the endoplasmic/sarcoplasmic reticulum membrane and a remaining cytoplasmic domain that shows specific affinity for the plasma membrane. Diseases associated with JPH2 include Cardiomyopathy, Familial Hypertrophic, 17 and Lung Abscess.

JPH2

Junctophilin-2
Membrane-binding protein that provides a structural bridge between the plasma membrane and the sarcoplasmic reticulum and is required for normal excitation-contraction coupling in cardiomyocytes (PubMed:20095964).
Provides a structural foundation for functional cross-talk between the cell surface and intracellular Ca(2+) release channels by maintaining the 12-15 nm gap between the sarcolemma and the sarcoplasmic reticulum membranes in the cardiac dyads (By similarity).
Necessary for proper intracellular Ca(2+) signaling in cardiac myocytes via its involvement in ryanodine receptor-mediated calcium ion release (By similarity).
Contributes to the construction of skeletal muscle triad junctions (By similarity).
Junctophilin-2 N-terminal fragment
Transcription repressor required to safeguard against the deleterious effects of cardiac stress. Generated following cleavage of the Junctophilin-2 chain by calpain in response to cardiac stress in cardiomyocytes. Following cleavage and release from the membrane, translocates to the nucleus, binds DNA and represses expression of genes implicated in cell growth and differentiation, hypertrophy, inflammation and fibrosis. Modifies the transcription profile and thereby attenuates pathological remodeling in response to cardiac stress. Probably acts by competing with MEF2 transcription factors and TATA-binding proteins.

Calcium ion homeostasisManual Assertion Based On ExperimentIDA:UniProtKB
Calcium ion transport into cytosolManual Assertion Based On ExperimentTAS:BHF-UCL
Negative regulation of transcription by RNA polymerase IIISS:UniProtKB
Negative regulation of transcription, DNA-templatedISS:UniProtKB
Positive regulation of ryanodine-sensitive calcium-release channel activityManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of cardiac muscle tissue developmentIEA:Ensembl
Regulation of ryanodine-sensitive calcium-release channel activityManual Assertion Based On ExperimentTAS:BHF-UCL

Junctophilin-2: Cell membrane; Sarcoplasmic reticulum membrane; Endoplasmic reticulum membrane. The transmembrane domain is anchored in sarcoplasmic reticulum membrane, while the N-terminal part associates with the plasma membrane. In heart cells, it predominantly associates along Z lines within myocytes. In skeletal muscle, it is specifically localized at the junction of A and I bands.
Junctophilin-2 N-terminal fragment: Nucleus. Accumulates in the nucleus of stressed hearts.

Cardiomyopathy, familial hypertrophic 17 (CMH17):
A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.

Cytoplasmic: 1-674
Helical: 675-695

Phosphorylation on Ser-165, probably by PKC, affects RYR1-mediated calcium ion release, interaction with TRPC3, and skeletal muscle myotubule development.
Proteolytically cleaved by calpain in response to cardiac stress. The major cleavage site takes place at the C-terminus and leads to the release of the Junctophilin-2 N-terminal fragment chain (JP2NT).