Alternative Splice Variants Encoding Unstable Protein Domains Exist in the Human Brain

Intrinsically Disordered Loops Inserted into the Structural Domains of Human Proteins

“…As reported by Homma et al, 31 alternative splicing (AS) sometimes introduces insertion loops into pre-existing domains. The three examples of insertion loops presented are rather short (nine, 11, and 32 residues) and are derived from extra exons (see Homma et al, Figure 4).…”

Alternative splicing in human transcriptome: Functional and structural influence on proteins

“…6). Homma et al (2004) found cases of AS that may produce AS isoforms less stable than other isoforms derived from the same gene in human brain cDNAs. We quantified here such putative unstable AS products, and found that the number of those products exceeded that of the stable products.…”

“…Wen et al (2004) searched public databases for human alternative splice variants to compile products of "very short alternative splicing (VSAS)," products resulted from AS of segments less than 50 nucleotides long, and proposed that VSAS may alter the 3D structure of proteins. Homma et al (2004) studied protein 3D structures of AS products in human brain and concluded that most of the alternative splice junctions coincided with domain junctions and that small proportion of cases were found that the junction resided within protein domain. These studies were informative, yet they were carried out using a limited number of AS products.…”

Comparative Genomics and Evolution of Alternative Splicing: The Pessimists′ Science

“…It avoids disrupting domains and instead tends to shuffle entire domains [110][111][112] and transmembrane segments 113 as opposed to a random control, reviewed in ref 114. A recent study using full-length mouse cDNAs demonstrated that among alternatively spliced genes, about 6% encode cytoplasmic and membrane-bound protein isoforms, 4% encode cytoplasmic and secreted isoforms, and 4% encode membrane-bound and secreted isoforms.…”