ACVR2A Knockout Cell Line (HEK293)

ACVR2A and ACVR2B are the two type II activin receptors — serine/threonine kinase receptors that bind activins, myostatin (GDF8), GDF11, BMPs, and other TGF-β superfamily ligands; upon ligand binding, the type II receptor recruits and phosphorylates type I receptors (ALK4/ACVR1B, ALK5, ALK7), which then phosphorylate SMAD2/3 (activin/myostatin branch) to regulate gene expression. ACVR2A and ACVR2B share substantial ligand and functional overlap, with myostatin/GDF11-mediated muscle growth suppression being a major shared function. This ligand-trap axis is the basis of several clinically important therapeutics. The choice between knockout and overexpression depends on whether you are studying ACVR2A-specific activin/myostatin signaling. This ACVR2A Knockout in HEK293 is a workhorse mechanistic platform — HEK293 supports systematic structure-function studies of ACVR2A-mediated SMAD2/3 signaling. Overexpression is useful for studying ACVR2A gain-of-function effects. Important consideration: ACVR2A and ACVR2B share substantial ligand binding and functional overlap — single ACVR2A knockout may show modest phenotypes if ACVR2B compensates. This product complements the parallel ACVR2A Knockout in HAP1 and the ACVR2A & ACVR2B Double Knockout in HEK293 (both also available) for systematic paralog dissection. Rescue with wild-type or kinase-dead ACVR2A is the standard specificity control. The knockout is a critical specificity tool for ⭐⭐ sotatercept (Winrevair, FDA-approved 2024 ActRIIA-Fc ligand trap for pulmonary arterial hypertension), luspatercept (Reblozyl, ActRIIB-Fc trap for anemia in MDS/β-thalassemia), bimagrumab (anti-ActRII antibody for muscle/metabolic disease), and emerging activin/myostatin pathway-targeted therapeutics.

Primary applications: • Activin/myostatin SMAD signaling: activin A, myostatin (GDF8), GDF11-induced phospho-SMAD2/3 analysis in ACVR2A-null cells. • Ligand trap specificity: critical genetic control for ⭐⭐ sotatercept (Winrevair), luspatercept (Reblozyl), bimagrumab. • ACVR2A/2B paralog dissection: parallel analysis with ACVR2A KO in HAP1 and the double KO in HEK293 (both available) for systematic paralog studies. • Muscle growth signaling: in heterologous muscle-relevant contexts, myostatin-mediated muscle growth suppression analysis. EDITGENE recommends this HEK293-based model for systematic activin/myostatin type II receptor research and ligand-trap drug development.

Yes. ACVR2A rescue experiments are well-established for activin receptor research: • Construct design: use a codon-modified ACVR2A sequence with a small intracellular C-terminal tag (FLAG, HA). ACVR2A has extracellular ligand-binding domain, single transmembrane span, and intracellular serine/threonine kinase domain — preserve all elements. • Surface localization validation: confirm plasma membrane localization before ligand binding studies. • Kinase-dead rescue: K219R mutation in the ATP-binding lysine abolishes catalytic activity. • Ligand-binding-deficient rescue: extracellular domain mutations disrupt activin/myostatin binding. • Functional readout: rescue should restore activin/myostatin-induced phospho-SMAD2/3 signaling. HEK293 transduces efficiently with lentivirus and supports stable rescue line generation.