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. 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. ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein] ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein] Stimulated by clathrin. Interacts (via CBD domain) with clathrin (By similarity). Interacts with AP-2 complex (By similarity). Interacts with NUMB (By similarity). Interacts with alpha-adaptin (By similarity). Interacts with EPS15 isoform 2 (By similarity). Interacts with membrane-bound activated NOTCH1 but not with the inactive full-length form of NOTCH1 (By similarity). Preferentially interacts with monoubiquitinated activated NOTCH1 compared to the non-ubiquitinated form (By similarity). 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 (By similarity). Detected in brain (at protein level). Autophosphorylated. Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.