Protein SET

Protein SET (UniProt: Q01105) is a multifunctional 290-amino acid protein involved in apoptosis, transcription, nucleosome assembly, and histone chaperoning. It functions as a potent inhibitor of protein phosphatase 2A and histone acetyltransferases, thereby suppressing HAT-dependent transcription and affecting DNA methylation dynamics. SET also regulates cytotoxic T-lymphocyte-induced apoptosis through inhibition of the nuclease NME1.

SET is associated with intellectual developmental disorder, autosomal dominant 58 (MRD58, MIM 618106), which presents with developmental delay, intellectual disability, and language impairment (UniProt: Q01105). The protein's roles in transcriptional regulation and epigenetic modification position it within chromatin remodeling and cell cycle control pathways relevant to neuronal development and function.

In Alzheimer's disease, SET is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log₂ fold-change of −1.56 across one subcellular fraction (Chaparral AD proteomics). This reduction in a key transcriptional and epigenetic regulator may contribute to dysregulation of gene expression patterns observed in AD neuropathology.