Bifunctional glutamate/proline--tRNA ligase

EPRS1 (bifunctional glutamate/proline–tRNA ligase) is a multifunctional aminoacyl-tRNA synthetase that catalyzes the attachment of L-glutamate and L-proline to their cognate tRNAs as part of the aminoacyl-tRNA synthetase multienzyme complex (UniProt: P07814). Beyond canonical protein synthesis, EPRS1 undergoes phosphorylation upon interferon-gamma stimulation and translocates to form the GAIT complex, which represses translation of inflammatory mRNAs; it also functions in mTORC1signaling to regulate fatty acid uptake and metabolism (UniProt: P07814). UniProt disease associations include hypomyelinating leukodystrophy type 15, an autosomal recessive disorder with early-onset motor and cognitive impairment (UniProt: P07814).

EPRS1 is tagged as downregulated in Alzheimer's disease. Chaparral AD proteomics analysis of human post-mortem AD brain tissue versus age-matched controls using TMT-labeled four-fraction differential proteomics demonstrated reduced EPRS1 abundance, with a mean log2 fold-change of −0.31 (Chaparral AD proteomics). The functional significance of decreased EPRS1 in AD pathogenesis remains to be determined, though its roles in translation control and cellular metabolism suggest potential relevance to neurodegenerative processes.