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FUNCTION Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 beta subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins; at least some clathrin-associated sorting proteins (CLASPs) are recognized by their [DE]-X(1,2)-F-X-X-[FL]-X-X-X-R motif. The AP-2 beta subunit binds to clathrin heavy chain, promoting clathrin lattice assembly; clathrin displaces at least some CLASPs from AP2B1 which probably then can be positioned for further coat assembly.SUBUNIT Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1) (PubMed:12086608, PubMed:19140243). Interacts with EPN1 (PubMed:10944104, PubMed:16516836). Interacts with EPS15; clathrin competes with EPS15 (PubMed:10944104, PubMed:16903783). Interacts with SNAP91; clathrin competes with SNAP91 (PubMed:10944104, PubMed:16516836, PubMed:16903783). Interacts with CLTC; clathrin competes with EPS15, SNAP91 and PIP5K1C (PubMed:10944104). Interacts with LDLRAP1 (PubMed:15728179, PubMed:16516836, PubMed:16903783). Interacts with AMPH and BIN1 (PubMed:16516836, PubMed:16903783). Interacts with ARF6 (GDP-bound) (PubMed:17719203). Interacts (dephosphorylated at Tyr-737) with ARRB1; phosphorylation of AP2B1 at Tyr-737 disrupts the interaction (PubMed:11777907, PubMed:16516836, PubMed:16903783, PubMed:17456551). Interacts with SLC2A8 (PubMed:16723738). Interacts with SCYL1 and SCYL2 (PubMed:16903783). Interacts with TGFBR1 and TGFBR2 (PubMed:12429842). Interacts with PIP5K1C; clathrin competes with PIP5K1C (By similarity). Interacts with DENND1B, but not with DENND1A, nor DENND1C (PubMed:20154091). Interacts with FCHO1 (PubMed:22484487). Interacts with RFTN1 (PubMed:27022195). Interacts with KIAA1107 (PubMed:29262337). Together with AP2A1 or AP2A2 and AP2M1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497).INTERACTION AP-2 appears to be excluded from internalizing CCVs and to disengage from sites of endocytosis seconds before internalization of the nascent CCV.ALTERNATIVE PRODUCTS Expressed in the brain (at protein level).PTM Phosphorylation at Tyr-737 by SRC occurs at the plasma membrane in clathrin-coated vesicles (CCVs).MISCELLANEOUS Highly expressed in the testis, spleen, thymus, prostate, ovary, blood leukocyte and brain, but not in the heart, placenta, lung, liver, skeletal muscle, kidney and pancreas. Testis expression is restricted to germ cells and is about 3-fold higher in adults than in embryos.SIMILARITY Belongs to the adaptor complexes large subunit family.
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