AP2M1
Description
The AP2M1 (adaptor related protein complex 2 subunit mu 1) is a protein-coding gene located on chromosome 3.
AP-2 complex subunit mu is a protein that in humans is encoded by the AP2M1 gene. This gene encodes a subunit of the heterotetrameric coat assembly protein complex 2 (AP2), which belongs to the adaptor complexes medium subunits family. The encoded protein is required for the activity of a vacuolar ATPase, which is responsible for proton pumping occurring in the acidification of endosomes and lysosomes. The encoded protein may also play an important role in regulating the intracellular trafficking and function of CTLA-4 protein. Two transcript variants encoding different isoforms have been found for this gene. AP2M1 has been shown to interact with CTLA-4 and Alpha-1B adrenergic receptor.
AP2M1, also known as AP-2 mu chain, Adaptin-mu2, Adaptor protein complex AP-2 subunit mu, Adaptor-related protein complex 2 subunit mu, Clathrin assembly protein complex 2 mu medium chain, Clathrin coat assembly protein AP50, Clathrin coat-associated protein AP50, HA2 50 kDa subunit, Plasma membrane adaptor AP-2 50 kDa protein, is a component of the adaptor protein complex 2 (AP-2). AP-2 complexes function in protein transport via transport vesicles in different membrane traffic pathways. They are vesicle coat components involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis, where cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs), destined for fusion with the early endosome. Clathrin serves as a mechanical scaffold but cannot bind directly to membrane components. AP complexes bind directly to both the clathrin lattice and the lipid and protein components of membranes, making them major clathrin adaptors contributing to CCV formation. AP-2 acts as a cargo receptor, selectively sorting membrane proteins involved in receptor-mediated endocytosis. It plays a role in recycling 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. It may also contribute to 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. The AP-2 mu subunit binds to transmembrane cargo proteins, recognizing Y-X-X-Phi motifs. This binding region is inaccessible in cytosolic AP-2 but becomes accessible through a conformational change following phosphorylation of the AP-2 mu subunit at Thr-156 in membrane-associated AP-2. This phosphorylation event appears to involve assembled clathrin, activating the AP-2 mu kinase AAK1. AP2M1 plays a role in the endocytosis of frizzled family members upon Wnt signaling.
AP2M1 is also known as AP50, CLAPM1, MRD60, mu2.
