Disease relevance of ACCN1

• Localization of the 17q breakpoint of a constitutional 1;17 translocation in a patient with neuroblastoma within a 25-kb segment located between the ACCN1 and TLK2 genes and near the distal breakpoints of two microdeletions in neurofibromatosis type 1 patients [1].
• Thus, syntaxin 1A cannot inhibit Na(+) permeability in the absence of adequate plasma membrane ASIC2 expression, accounting for the observed functional expression of amiloride-sensitive currents in high grade glioma cells [2].
• Immunoreactivity to ASIC1a and ASIC2a subunits was found in small vestibular ganglion neurons and afferent fibers that run throughout the macula utricle and crista stroma [3].

High impact information on ACCN1

• Immunohistochemical experiments and functional measurements of unitary currents from the ASICs with the patch-clamp technique indicate that ASIC1 localizes to the plasma membrane of small-, medium-, and large-diameter cells, whereas ASIC2 and ASIC3 are preferentially in medium to large cells [4].
• Extending telomerically from the SRO, two additional genes-BLMH, encoding a hydrolase involved in bleomycin resistance, and ACCN1, encoding an amiloride-sensitive cation channel expressed in the CNS-were located in the deleted intervals of seven and three patients, respectively [5].
• Surface expression of ASIC2 inhibits the amiloride-sensitive current and migration of glioma cells [6].
• Thus, we used glycosylation studies to define the actual membrane topology of the ASIC2a subtype [7].
• Although ASIC1 was present in all of the high grade glial cells examined, ASIC2 mRNA was detected in less than half [2].

Biological context of ACCN1

• The PAC/BAC contig covers the region between the proximally located ACCN1 gene and the distally located TLK2 gene and SCYA chemokine gene cluster [1].
• The human degenerin MDEG, an amiloride-sensitive neuronal cation channel, is localized on chromosome 17q11.2-17q12 close to the microsatellite D17S798 [8].
• The ASIC2 promoter lacked a canonical TATA box, but contained one putative CCAAT box [9].
• To investigate the mechanisms involved in the regulation of ASIC2 gene expression, the human ASIC2 promoter region (-1551 to +117) was cloned and characterized [9].
• ASIC2a contributes to hearing in the cochlea, sour taste sensation, and visual transduction in the retina [10].

Anatomical context of ACCN1

• To investigate the subunit composition of native ASICs in peripheral and central neurons, we co-injected human as well as rodent ASIC2a and ASIC3 subunits in Xenopus oocytes [11].
• BNC1 has a unique pattern of expression with transcripts detected only in adult human brain and in spinal cord [12].
• Our previous studies suggested that differential regulation of ASIC2 expression occurs between high-grade glial-derived tumor cells and normal astrocytes [9].
• In human osteoblasts ASIC1, ASIC2, and ASIC3 mRNAs were shown [13].
• In bone, ASIC2 and ASIC3 were most abundant, while in chondrocytes it was ASIC1 [13].

Associations of ACCN1 with chemical compounds

• Purification and characterization of EDTA monooxygenase from the EDTA-degrading bacterium BNC1 [14].
• EDTA-degrading activities were detected in cell extracts of bacterium BNC1 when flavin mononucleotide (FMN), NADH, and O2 were present [14].
• Common radical initiators such as ACCN and triethylborane can be used [15].

Co-localisations of ACCN1

• Transfection of rat cortical neurons with constructs encoding green fluorescent protein- or hemagglutinin-tagged channels showed expression of ASIC1a and ASIC2a in punctate and clustering patterns in dendrites that co-localized with AKAP150 [16].

Other interactions of ACCN1

• RESULTS: In the Western blot, there was a significant three-fold increase in the mean relative optical density of the ASIC-3 55-kDa band (but not ASIC-1 or ASIC-2) in full-thickness inflamed intestine, as well as in separated muscle and mucosal layers [17].
• In contrast, the acid-gated Na(+) current associated with either the homomultimeric ASIC1a or ASIC2a channel was not influenced by wild type CFTR [18].
• The brain Na+ channel-1 (BNC1, also known as MDEG1 or ASIC2) is a member of the DEG/ENaC cation channel family [19].

Analytical, diagnostic and therapeutic context of ACCN1

• RT-PCR analyses demonstrated the presence of mRNA for either BNaC1 or BNaC2 in these tumors and in normal astrocytes [20].
• Peripheral axotomy markedly reduced ASIC2 expression in the axotomized dorsal root ganglion neurons [21].
• In situ hybridization and reverse transcription-polymerase chain reaction experiments showed that ASIC2a and ASIC2b transcripts were localized in taste cells [22].
• Immunohistochemical and immunoprecipitation studies revealed that both channels were expressed in a subset of taste cells and that some of the cells expressed ASIC2a/ASIC2b heteromeric assemblies [22].

References