AP2A1

This gene encodes the alpha 1 adaptin subunit of the adaptor protein 2 (AP-2) complex found in clathrin coated vesicles. The AP-2 complex is a heterotetramer consisting of two large adaptins (alpha or beta), a medium adaptin (mu), and a small adaptin (sigma). The complex is part of the protein coat on the cytoplasmic face of coated vesicles which links clathrin to receptors in vesicles. Alternative splicing of this gene results in two transcript variants encoding two different isoforms. A third transcript variant has been described, but its full length nature has not been determined. [provided by RefSeq, Jul 2008]

Full Name

Adaptor Related Protein Complex 2 Alpha 1 Subunit

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 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity).

Biological Process

Antigen processing and presentation of exogenous peptide antigen via MHC class II Source: Reactome
Clathrin-dependent endocytosis Source: UniProtKB
Endocytosis Source: UniProtKB
Ephrin receptor signaling pathway Source: Reactome
Golgi to endosome transport Source: UniProtKB
Intracellular protein transport Source: UniProtKB
Low-density lipoprotein particle clearance Source: Reactome
Low-density lipoprotein particle receptor catabolic process Source: Reactome
Membrane organization Source: Reactome
Negative regulation of hyaluronan biosynthetic process Source: UniProtKB
Positive regulation of neuron projection development Source: Ensembl
Positive regulation of receptor-mediated endocytosis Source: Ensembl
Receptor-mediated endocytosis Source: GO_Central
Regulation of defense response to virus by virus Source: Reactome
Wnt signaling pathway, planar cell polarity pathway Source: Reactome

Cellular Location

Cell membrane; Coated pit. AP-2 appears to be excluded from internalizing CCVs and to disengage from sites of endocytosis seconds before internalization of the nascent CCV.