Relevance to Autism

Li et al., 2023 determined that a de novo splice-region variant in the SENP6 gene originally identified in an ASD proband from the Autism Sequencing Consortium in Satterstrom et al., 2020 was a non-canonical splicing variant; subsequent functional analysis by minigene splicing assays demonstrated that this variant resulted in skipping of exon 18. Additional de novo variants in the SENP6 gene, including a de novo frameshift variant, have been identified in ASD probands (Zhou et al., 2022; Trost et al., 2022).

Molecular Function

Ubiquitin-like molecules (UBLs), such as SUMO1, are structurally related to ubiquitin and can be ligated to target proteins in a similar manner as ubiquitin. However, covalent attachment of UBLs does not result in degradation of the modified proteins. SUMO1 modification is implicated in the targeting of RANGAP1 to the nuclear pore complex, as well as in stabilization of I-kappa-B-alpha (NFKBIA) from degradation by the 26S proteasome. Like ubiquitin, UBLs are synthesized as precursor proteins, with 1 or more amino acids following the C-terminal glycine-glycine residues of the mature UBL protein. Thus, the tail sequences of the UBL precursors need to be removed by UBL-specific proteases, such as SENP6, prior to their conjugation to target proteins. SENPs also display isopeptidase activity for deconjugation of SUMO-conjugated substrates

External Links

References