KH domain-containing, RNA-binding, signal transduction-associated protein 1

KHDRBS1 is a KH domain-containing RNA-binding protein that functions as a signal transduction adapter and regulator of gene expression. It is recruited by receptor systems including T-cell, leptin, and insulin receptors, where it mediates signaling cascades through interactions with SH2/SH3 domain proteins (UniProt: Q07666). Additionally, KHDRBS1 regulates alternative splicing of neurologically relevant transcripts, including neurexins (NRXN1 and NRXN3), and cooperates with other splicing factors to control exon inclusion and mRNA stability.

The protein plays roles in the cell cycle, transcriptional regulation, and mRNA translation and export. KHDRBS1 binds RNA containing specific sequence motifs and coordinates with HNRNPA1 and KHDRBS2 to modulate splicing of anti-apoptotic factors and synaptic proteins (UniProt: Q07666). These functions position it within synaptic and neuronal homeostasis pathways.

KHDRBS1 is curated as downregulated in Alzheimer's Disease. In human post-mortem AD brain tissue compared to age-matched controls, KHDRBS1 showed decreased abundance with a mean log2 fold-change of −0.26 across subcellular fractions (Chaparral AD proteomics). This reduction may impair splicing regulation of synaptic proteins and signal transduction in AD pathology.