Annotated protein:AP-2 complex subunit alpha-2 (100 kDa coated vesicle protein C) (Adaptor protein complex AP-2 subunit alpha-2) (Adaptor-related protein complex 2 subunit alpha-2) (Alpha-adaptin C) (Alpha2-adaptin) (Clathrin assembly protein complex 2 alpha-C large chain) (Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit). Gene symbol: AP2A2. Taxonomy: Mus musculus (Mouse). Uniprot ID: P17427
antibody wiki:
SynGO gene info:SynGO data @ AP2A2
Ontology domain:Biological Process
SynGO term:synaptic vesicle endocytosis (GO:0048488)
Annotated paper:Lopez-Hernandez T, et al. "Clathrin-independent endocytic retrieval of SV proteins mediated by the clathrin adaptor AP-2 at mammalian central synapses" Elife. 2022 Jan 11;11:e71198 PMID:35014951
Figure(s):Figure 3
Annotation description:Figure 3: In hippocampal neurons from AP-2u (gene Ap2m1) knockout mice, the ablated expression of the AP-2 complex was shown to result in defective endocytosis of VGLUT1-labeled synaptic vesicles (SV).

While no comparable data is available for the alpha-adaptin subunits of the clathrin adaptor AP-2, it has been shown that;
- AP2A is involved in SV endocytosis in C.elegans (PMID:23482940) and Drosophila (PMID:9118220)
- AP2A1 and AP2A2 are both abundant in mammalian synaptic vesicles (PMID:33376223)

Taken together, we here annotate AP2A2 as involved in synaptic vesicle endocytosis
Evidence tracking, Biological System:Cultured neurons
Evidence tracking, Protein Targeting:Genetic transformation (eg; knockout, knockin, mutations)
Evidence tracking, Experiment Assay:Optical physiology
Non-tracable Author Statement (NAS):This annotation required some inference over additional information/literature, and is not solely based on observations made in the annotated paper by its original authors.
Annotator(s):Frank Koopmans (ORCID:0000-0002-4973-5732)
Guus Smit (ORCID:0000-0002-2286-1587)
Matthijs Verhage (ORCID:0000-0002-2514-0216)
Lab:Department of Functional Genomics, Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands
Additional literature:Figure 7: α-adaptin (ap2-a) mutants exhibit weak efects in synaptic vesicle protein localization.

Figure 8: Large vesicles accumulate at synapses in AP2 mutants. @ PMID:23482940

Figure 5: Drosophila-αAdaptin mutations impair the formation of endocytotic Synaptic Vesicles @ PMID:9118220

Dataset 1: AP2A1 and AP2A2 are among the top-most enriched synaptic vesicle proteins in a proteomic study of SV fractions prepared from rat brain @ PMID:33376223

structure of the 200 kDa AP2 "core" (α trunk, β2 trunk, μ2, and σ2) complexed with the polyphosphatidylinositol headgroup mimic inositolhexakisphosphate at 2.6 Å resolution. @ PMID:12086608
SynGO annotation ID:5521
Dataset release (version):20231201
View annotation as GO-CAM model:Gene Ontology