Disease relevance of ASPH

• Role of the aspartyl-asparaginyl-beta-hydroxylase gene in neuroblastoma cell motility [1].
• Ablation of junctin is associated with aberrant Ca homeostasis, which leads to fatal arrhythmias [2].
• Long-term isoproterenol infusion also induced premature ventricular contractions and atrioventricular heart block in junctin-null mice [2].
• We found that HAAH gene expression was undetectable during bile duct proliferation in both human disease and rat models as compared with cholangiocarcinoma [3].
• We previously reported overexpression of the HAAH gene in human hepatocellular carcinomas and cholangiocarcinomas (L. Lavaissiere et al., J. Clin. Investig., 98: 1313-1323, 1996) [3].

High impact information on ASPH

• RNA interference to deplete cells of endogenous junctate, knocked down both agonist-activated calcium release from intracellular stores and calcium entry via TRPC3 [4].
• Junctate, an integral calcium binding protein of endo(sarco)plasmic reticulum membrane, (a) induces and/or stabilizes peripheral couplings between the ER and the plasma membrane, and (b) forms a supramolecular complex with the InsP(3)R and the canonical transient receptor potential protein (TRPC) 3 calcium entry channel [4].
• These results demonstrate that junctate is a new protein involved in calcium homeostasis in eukaryotic cells [4].
• Alternative splicing of the locus AbetaH-J-J generates three functionally distinct proteins: an enzyme, AbetaH (aspartyl-beta-hydroxylase), a structural protein of the sarcoplasmic reticulum membrane (junctin), and an integral membrane calcium binding protein (junctate) [5].
• Junctin and junctate are two important proteins involved in calcium regulation in eukaryotic cells [5].

Biological context of ASPH

• Human junctin was cloned from an adult cardiac cDNA library [6].
• Sequence analysis demonstrates greater than 97% homology between the predicted amino acid sequences of human, rabbit, and canine junctin in the putative transmembrane domain and subsequent initial 61 amino acid portion of the putative luminal domain [6].

Anatomical context of ASPH

• Canine junctin is a 26-kDa transmembrane protein found in the sarcoplasmic reticulum (SR) membrane in cardiac and skeletal muscle [6].
• In addition, Northern blot analysis demonstrates that the expression of junctin increases markedly in postnatal rabbit myocardium [6].
• Screening a cDNA library from human skeletal muscle and cardiac muscle with a cDNA probe derived from junctin led to the isolation of two groups of cDNA clones [7].
• The essential physiological effects of junctin and its potential regulatory roles in sarcoplasmic reticulum Ca cycling and Ca-dependent cardiac functions, such as myocyte contractility and automaticity, are unknown [2].

Associations of ASPH with chemical compounds

• Furthermore, the previously described increase in SR Ca(2+) release with development is associated with the increased expression of junctin [6].

Physical interactions of ASPH

• Junctin is a calsequestrin binding protein detected in junctional sarcoplasmic reticulum of striated muscles [8].

Regulatory relationships of ASPH

• From these results, we propose a model in which calsequestrin, the DIDS-binding 30-kDa protein, and junctin form a ternary complex that regulates the RyR Ca(2+) release channel through interactions with triadin [9].

Other interactions of ASPH

• In addition, calsequestrin activates purified RyRs lacking triadin and junctin [10].
• Junctin is one of the components of the ryanodine receptor Ca release channel complex in sarcoplasmic reticulum [11].
• A human junctin isoform (isoform 1, 225 aa) was also identified and characterized [8].
• Myocyte enhancer factor 2 activates promoter sequences of the human AbetaH-J-J locus, encoding aspartyl-beta-hydroxylase, junctin, and junctate [5].

Analytical, diagnostic and therapeutic context of ASPH

• Rabbit junctin was cloned by RT-PCR [6].
• Molecular cloning of junctin from human and developing rabbit heart [6].
• Fluorescence in situ hybridization analysis revealed that the genetic loci of junctin and junctate map to the same cytogenetic band on human chromosome 8 [7].
• The gene copy number of human junctin and hASPH was investigated by genomic Southern blot analysis using various restriction enzymes and a common DNA probe [8].

References