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Non-Floating Harbour Syndrome (FLHS) neurodevelopmental disorder (NDD) is a recently described disorder caused by mutations in certain regions of the SRCAP gene. We generated two iPSC lines that contain truncating mutation on both alleles at the 3′-end of SRCAP using CRISPR/Cas9 technology. Both cell lines are pluripotent, differentiate into the 3 germ layers and contain no genomic aberrations or off-target modifications. The cell lines form part of a human disease model to investigate the effects of truncating mutations in different regions of SRCAP.
The spatio-temporal reduction and oxidation of protein thiols is an essential mechanism in signal transduction inall kingdoms of life. Thioredoxin (Trx) family proteins efficiently catalyze thiol-disulfide exchange reactions andthe proteins are widely recognized for their importance in the operation of thiol switches. Trx family proteinshave a broad and at the same time very distinct substrate specificity–a prerequisite for redox switching. Despiteof multiple efforts, the true nature for this specificity is still under debate. Here, we comprehensively compare theclassification/clustering of various redoxins from all domains of life based on their similarity in amino acidsequence, tertiary structure, and their electrostatic properties. We correlate these similarities to the existence ofcommon interaction partners, identified in various previous studies and suggested by proteomic screenings. Theseanalyses confirm that primary and tertiary structure similarity, and thereby all common classification systems, donot correlate to the target specificity of the proteins as thiol-disulfide oxidoreductases. Instead, a number ofexamples clearly demonstrate the importance of electrostatic similarity for their target specificity, independent oftheir belonging to the Trx or glutaredoxin subfamilies