Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis (  , ). Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1 . Preferentially, may phosphorylate substrates on threonine residues (, ). Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes . Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes . Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity .
(Microbial infection) By regulating clathrin-mediated endocytosis, AAK1 plays a role in the entry of hepatitis C virus as well as for the lifecycle of other viruses such as Ebola and Dengue.
Subcellular locations: Cell membrane, Membrane, Clathrin-coated pit, Presynapse
Active when found in clathrin-coated pits at the plasma membrane. In neuronal cells, enriched at presynaptic terminals. In non-neuronal cells, enriched at leading edge of migrating cells.
Detected in brain, heart and liver. Isoform 1 is the predominant isoform in brain.