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AP2M1

Function

Component of the adaptor protein complex 2 (AP-2) (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). 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 (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). 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 (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis (PubMed:16581796). AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). 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 (By similarity). AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway (PubMed:19033387). During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs (By similarity). The surface region interacting with to the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at Thr-156 in membrane-associated AP-2 (PubMed:11877457). The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 (PubMed:11877457). Plays a role in endocytosis of frizzled family members upon Wnt signaling (By similarity).

Involvement in disease

Intellectual developmental disorder, autosomal dominant 60, with seizures

MRD60

An autosomal dominant disorder characterized by global developmental delay apparent in the first six months of life, followed by onset of seizures between 21 months and 4 years. Disease features include moderate-to-severe intellectual disability, poor speech, delayed walking, and ataxia.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

Phosphorylation at Thr-156 increases the affinity of the AP-2 complex for cargo membrane proteins during the initial stages of endocytosis.

Sequence similarities

Belongs to the adaptor complexes medium subunit family.

Tissue specificity

Expressed in the brain (at protein level).

Cellular localization

  • Cell membrane
  • Membrane
  • Coated pit
  • Peripheral membrane protein
  • Cytoplasmic side
  • AP-2 appears to be excluded from internalizing CCVs and to disengage from sites of endocytosis seconds before internalization of the nascent CCV.

Alternative names

  • AP-2 complex subunit mu
  • 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
  • CLAPM1
  • KIAA0109
  • AP2M1

Target type

Proteins

Molecular weight

49655Da