Disease relevance of JPH1

• Using adenovirus with small hairpin interference RNA (shRNA) against both JP1 and JP2 genes, we could achieve acute suppression of JPs in skeletal muscle fibers [1].
• We have studied up to 70 cases of sporadic colorectal cancer for allele loss at markers predominantly on the long arm of chromosome 10, including loci flanking the putative Cowden Disease/JP1 locus [2].
• Mutations at the putative Cowden Disease/JP1 locus may therefore be important in sporadic colorectal cancer and fine mapping of allele loss on 10q in sporadic colon cancers may help to refine the position of this gene [2].
• Rearrangement of TCR gamma chain gene involving JP1 suggests early thymocyte origin of peripheral T-cell lymphoma [3].

High impact information on JPH1

• Using preparative SDS-PAGE, in-gel tryptic digestion, high pressure liquid chromatography, and mass spectrometry-based peptide sequencing, we identified 7-diethylamino-3-(4'-maleimidylphenyl)-4-methylcoumarin-thioether adducts on three cysteine residues of JP1 (101, 402, and 627); the remaining five cysteines of JP1 were unlabeled [4].
• Junctophilin 1 (JP1), a 72-kDa protein localized at the skeletal muscle triad, is essential for stabilizing the close apposition of T-tubule and sarcoplasmic reticulum membranes to form junctions [4].
• Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50) [5].
• Uncoupling store-operated Ca2+ entry and altered Ca2+ release from sarcoplasmic reticulum through silencing of junctophilin genes [1].
• Junctophilin (JP) mediates the close contact between cell surface and intracellular membranes in muscle cells ensuring efficient excitation-contraction coupling [1].

Biological context of JPH1

• In this report we describe the primary structures, genomic organization, and tissue distribution of human JP subtypes [6].
• By cloning and analyzing human genomic DNA segments, the protein-coding sequence interrupted with four introns was defined in each JP gene [6].
• Genomic mapping demonstrated that JP genes do not cluster on the human genome [6].
• In most clones, rearrangements occurred on both chromosomes and involved the J2 segment, but only 2 and 4 out of the 49 described rearrangements involved the additional J gamma segments JP1 and JP2, respectively [7].
• Here we demonstrate that disruption of triad junction structure formed by the transverse tubular (TT) invagination of plasma membrane and terminal cisternae of sarcoplasmic reticulum (SR) by reduction of JP expression leads to defective Ca2+ homeostasis in muscle cells [1].

Anatomical context of JPH1

• In the human T-cell rearranging gamma (TRG gamma) locus, five joining (J) segments have been identified: J1, J2 and three additional segments JP, JP1 and JP2 [8].

Associations of JPH1 with chemical compounds

• Knockdown of JP also causes a reduction in SR Ca2+ storage and altered caffeine-induced Ca2+ release, suggesting an orthograde regulation of the TT membrane on the SR Ca2+ release machinery [1].
• Most rearrangements, if not all, involve the T cell receptor gamma C1 region (JP1, JP, J1 segments) in both tissues, confirming the accessibility of the C1 region in early stages of development [9].

Other interactions of JPH1

• Moreover, several human genetic diseases are caused by mutations at the ryanodine receptor and junctophilin subtype genes [10].

References