InterPro domain: IPR043532

This entry represents the N-terminal domain of heterotetrameric clathrin-associated adaptor protein complex 2 (AP-2) medium mu2 subunit. Mu2 is ubiquitously expressed in mammals. In higher eukaryotes, AP-2 plays a critical role in clathrin-mediated endocytosis from the plasma membrane in different cells. The membrane-anchored cargo molecules can be linked to the outer lattice of CCVs by AP-2. Those cargo molecules interact with adaptors through short sorting signals in their cytosolic segments. Tyrosine-based endocytotic signals are one of the most important sorting signals. They are of the form Y-X-X-Phi, where Y is tyrosine, X is any amino acid and Phi is a bulky hydrophobic residue that can be Leu, Ile, Met, Phe, or Val. These kinds of sorting signals can be recognized by the C-terminal domain of AP-2 mu2 subunit, also known as Y-X-X-Phi signal-binding domain that contains two hydrophobic pockets, one for the tyrosine-binding and one for the bulky hydrophobic residue-binding. Since the Y-X-X-Phi binding site is buried in the core structure of AP-2, a phosphorylation induced conformational change is required when the cargo molecules binds to AP-2 [ 1 , 2 ].

1. A structural explanation for the recognition of tyrosine-based endocytotic signals. Science 282, 1327-32
2. Study of the interaction of the medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28. Biochem. J. 359, 427-34