Adaptor protein complex 2 (AP-2) (AP-2)

The Adaptor protein complex 2 (AP-2) is a heterotetrameric protein assembly that serves as a central hub for clathrin-mediated endocytosis at the plasma membrane [1]. It is composed of four distinct subunits: alpha (AP2A1 or AP2A2), beta (AP2B1), mu (AP2M1), and sigma (AP2S1), which coordinately recognize cargo motifs and recruit clathrin to initiate vesicle formation [2]. AP-2 is vital for the internalization of various receptors, including G protein-coupled receptors and receptor tyrosine kinases, thereby regulating cellular signaling and nutrient uptake [3]. In disease contexts, AP-2 is frequently hijacked by viruses such as HIV-1 and SARS-CoV-2 to facilitate cellular entry, and its dysfunction is implicated in cancers and neurodegenerative conditions [4]. Therapeutic strategies often target the regulation of AP-2, specifically through the inhibition of AP2-associated protein kinase 1 (AAK1) by drugs like baricitinib, to block viral infection or modulate receptor trafficking [5].

Other names

AP2 complexClathrin-associated adaptor protein complex 2Plasma membrane adaptor complexAP2Heterotetrameric AP-2 adaptor complex

Inhibition of AP-2 regulatory kinases such as AAK1 to prevent subunit phosphorylation, or direct interference with clathrin-binding domains to disrupt vesicle assembly.