AP2S1 Rabbit mAb

AP2S1 Rabbit mAb recognizes endogenous levels of total AP2S1 protein.

AP2S1 encodes the small (~17 kDa) sigma-1 subunit of the adaptor protein complex 2 (AP-2), a heterotetramer essential for clathrin-mediated endocytosis. This complex facilitates cargo selection and vesicle formation at the plasma membrane by bridging clathrin coats with membrane lipids and cargo proteins. AP2S1 has a beta-sandwich fold without enzymatic activity and plays a critical scaffolding role, recognizing sorting motifs such as YxxΦ and dileucine on cargo proteins to ensure selective internalization. AP2S1 also regulates intracellular trafficking by modulating late endosome–lysosome fusion, which influences degradation of proteins like amyloid precursor protein (APP). Silencing AP2S1 enhances this fusion, promoting APP clearance and reducing neurotoxic Aβ42 levels, through interaction with HOPS complex proteins (e.g., VPS41 and VPS16). This mechanism is implicated in Alzheimer’s disease pathology. Additionally, missense mutations at the conserved Arg15 residue of AP2S1 cause familial hypocalciuric hypercalcemia type 3 (FHH3), disrupting calcium-sensing receptor (CaSR) endocytosis and signaling. These mutations reduce adaptor affinity for CaSR dileucine motifs, impair receptor internalization, and alter calcium homeostasis, leading to benign hypercalcemia with low urinary calcium excretion.