Asparagine synthetase (ASNS) (ASNS)

Asparagine synthetase (ASNS) is a cytoplasmic enzyme that catalyzes the ATP-dependent synthesis of asparagine from aspartate and glutamine, producing glutamate as a byproduct. It features two domains: an N-terminal glutaminase domain for glutamine hydrolysis to ammonia and a C-terminal synthetase domain for aspartate activation via β-aspartyl-AMP intermediate, connected by an intramolecular tunnel. Encoded by a single gene on chromosome 7q21.3 in humans, ASNS expression is low basally but upregulated by amino acid response (AAR) and unfolded protein response (UPR) pathways under stress. Elevated ASNS contributes to L-asparaginase resistance in leukemia, and deficiency causes neurological disorders.

Other names

asparagine synthetaseaspartate-ammonia ligaseASNSglutamine-dependent asparagine synthetase

Inhibition of asparagine synthesis leading to asparagine depletion and cell death in ASNS-dependent cancers; Competitive inhibition with ATP at synthetase active site