AP2M1 encodes the medium ΞΌ2 subunit of the heterotetrameric AP-2 clathrin adaptor complex. Its C-terminal domain recognizes cytoplasmic sorting signals in membrane cargo, especially tyrosine-based motifs, while its N-terminal region helps assemble the adaptor core. AP-2 cycles between the cytosol and coats on the cytoplasmic face of the plasma membrane, coupling cargo selection to clathrin-dependent internalization. Membrane-dependent rearrangement and phosphorylation of ΞΌ2 Thr156 coordinate cargo capture and accessory-protein recruitment. This machinery supports receptor turnover and synaptic membrane-protein retrieval. Pathogenic AP2M1 variants can impair endocytosis and cause developmental and epileptic encephalopathy.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002092 positive regulation of receptor internalization | IEA GO_REF:0000107 | ACCEPT | Summary: Promotes internalization by selecting cargo for AP-2 coated pits. Reason: The rat-derived electronic assertion agrees with the conserved cargo-recognition role and human-cell depletion/rescue evidence. The retained regulatory process describes ΞΌ2-dependent uptake efficiency, not a separate kinase or an independently reconstructed rat experiment. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. ensembl:ENSRNOP00000054900 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:31104773 Functional complementation of both the ΞΌ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2ΞΌ conditional knockout mice revealed a significant impairment of CME of transferrin. PMID:17035630 Mutating the PtdIns(4,5)P2 binding site of alpha, the phosphorylation site of mu2, or the YXXPhi binding site of mu2 impairs AP-2 function, as assayed by transferrin uptake. |
| GO:0005048 signal sequence receptor activity | IDA PMID:8918456 Sequence requirements for the recognition of tyrosine-based ... | ACCEPT | Summary: Recognizes tyrosine-based endocytic sorting signals. Reason: The cited primary abstract reports ΞΌ2 recognition of Yxx-hydrophobic peptides with sequence specificity. This fits the current GO definition of a short localization signal, which is not restricted to ER signal peptides. Reagent species is not resolved by the abstract; human ΞΌ2 motif-recognition evidence corroborates the conserved activity. Supporting Evidence: PMID:8918456 Both mu 2 and AP-2 are shown to interact with various sequences of the form tyrosine-polar-polar-hydrophobic (YppΓΈ) found on receptors that follow the clathrin pathway. PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. |
| GO:0005048 signal sequence receptor activity | IDA PMID:9171339 Regulatory interactions in the recognition of endocytic sort... | ACCEPT | Summary: Recognizes cargo sorting signals through ΞΌ2. Reason: The cited study explicitly analyzes ΞΌ2 interactions with endocytic sorting sequences. Preserve the source IDA annotation; the abstract establishes the recognition mechanism without resolving every reagent species. Human ΞΌ2 cargo-tail assays independently support the same established activity. Supporting Evidence: PMID:9171339 this binding is strengthened significantly when the AP-2 complex is present in clathrin coats PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. |
| GO:0005048 signal sequence receptor activity | IEA GO_REF:0000107 | ACCEPT | Summary: Retain conserved ΞΌ2 sorting-signal recognition. Reason: Rat-to-human transfer agrees with target-specific human ΞΌ2 cargo-tail and purified-domain experiments. The source transfer is preserved, while the exact donor experiment has not been reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. ensembl:ENSRNOP00000054900 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. PMID:33436498 a binding site for the clathrin adaptor AP2 ΞΌ2 in ACE2 overlaps with a phospho-dependent binding site for the SH2 domains of Src family tyrosine kinases. |
| GO:0005515 protein binding | IPI PMID:12032142 Subunit H of the V-ATPase binds to the medium chain of adapt... | KEEP AS NON CORE | Summary: Retain the mapped interaction with the regulatory V-ATPase H subunit. Reason: The source abstract explicitly maps binding between ΞΌ2 residues 1β145 and ATP6V1H residues 133β363. This is a supported accessory interaction; no sufficiently justified narrower function is assigned from the abstract alone. The regulatory H subunit is not itself the ATPase catalytic subunit, so its identity does not warrant ATPase binding or ATPase activity for ΞΌ2. Supporting Evidence: PMID:12032142 The interaction sites of V1H and mu2 were mapped to a central region in V1H from positions 133 to 363 |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P51116 remains unresolved. Reason: The human interactome abstract describes a broad interaction map; the exact pair assay and target construct were not inspected. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P63010 remains unresolved. Reason: The human interactome abstract describes a broad interaction map; the exact pair assay and target construct were not inspected. P63010 is the AP2B1 beta subunit; independent AP-2 architecture supports a plausible association but does not establish what this original experiment measured. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q59EK9 remains unresolved. Reason: The human interactome abstract describes a broad interaction map; the exact pair assay and target construct were not inspected. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q92609 remains unresolved. Reason: The human interactome abstract describes a broad interaction map; the exact pair assay and target construct were not inspected. |
| GO:0005515 protein binding | IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q9UHP6 remains unresolved. Reason: The human interactome abstract describes a broad interaction map; the exact pair assay and target construct were not inspected. |
| GO:0005515 protein binding | IPI PMID:19419997 The dyslexia-associated protein KIAA0319 interacts with adap... | MODIFY | Summary: Refine KIAA0319 binding to sorting-signal recognition. Reason: Actual source Methods identify human ΞΌ2 NM_004068 constructs. Tail mapping and the KIAA0319 Y995A mutant connect ΞΌ2 association with its internalization signal. The refinement describes signal recognition; lysate pull-down and yeast interaction tests are not mislabeled as purified binary binding. Proposed replacements: signal sequence receptor activity Supporting Evidence: PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. |
| GO:0005515 protein binding | IPI PMID:20029029 Regulation of epidermal growth factor receptor trafficking b... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P00533 remains unresolved. Reason: The abstract addresses HDAC6-dependent EGFR trafficking and a broader interaction survey; the AP2M1βEGFR supporting assay was not inspected. |
| GO:0005515 protein binding | IPI PMID:21653829 Protein interactome reveals converging molecular pathways am... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P51114 remains unresolved. Reason: The autism interactome abstract does not expose the exact target-pair experiment. |
| GO:0005515 protein binding | IPI PMID:22916011 Identification and targeting of an interaction between a tyr... | MODIFY | Summary: Refine HCV-core binding to recognition of its sorting motif. Reason: Actual source Methods use Human ORFeome AP2M1 constructs. Motif mutations, microfluidic binding and endogenous co-IP in infected Huh-7.5 cells support recognition of the core YxxΦ signal. Preserve the processed viral partner identifier and both recorded μ2 products; no viral-assembly BP is added. Proposed replacements: signal sequence receptor activity Supporting Evidence: PMID:22916011 Using microfluidics affinity analysis, protein-fragment complementation assays, and co-immunoprecipitations in infected cells, we show that this motif mediates core binding to AP2M1. |
| GO:0005515 protein binding | IPI PMID:23676497 Endocytosis of synaptic ADAM10 in neuronal plasticity and Al... | KEEP AS NON CORE | Summary: Retain the source-specific ADAM10/AP-2 association. Reason: The inspected human hippocampal co-IP detects ADAM10 with ΞΌ2 and the AP-2 alpha/beta subunits. The source row combines O14672, O94973, O95782 and P63010; a single new direct-binding mechanism should not be assigned to every listed pair. Preserve this positive complex association and express adaptor activity in the existing contributes_to annotation. Supporting Evidence: PMID:23676497 we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. |
| GO:0005515 protein binding | IPI PMID:23864651 The identification of novel proteins that interact with the ... | MODIFY | Summary: Specify binding to the GLP-1 G protein-coupled receptor. Reason: The human receptor/human fetal-brain interaction screen and reported CHO co-IP validation directly identify AP2M1 as a GLP1R interactor. The available cache contains abstract and Discussion rather than complete Methods/Results; the refinement rests on the named partner class, not an inferred interface. Intracellular GPCR binding does not imply ligand, agonist or antagonist activity. Proposed replacements: G protein-coupled receptor binding Supporting Evidence: PMID:23864651 A screen of a human fetal brain cDNA prey library with an unliganded human GLP-1R as bait in yeast revealed 38 novel interactor protein candidates. These interactions were confirmed in mammalian Chinese hamster ovarian cells by coimmunoprecipitation. |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P00533 remains unresolved. Reason: The EGFR network study is relevant, but its exact AP2M1 interaction evidence and validation table were not inspected. |
| GO:0005515 protein binding | IPI PMID:24189400 Perturbation of the mutated EGFR interactome identifies vuln... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P63010 remains unresolved. Reason: The EGFR network study is relevant, but its exact AP2M1 interaction evidence and validation table were not inspected. P63010 is the AP2B1 beta subunit; independent AP-2 architecture supports a plausible association but does not establish what this original experiment measured. |
| GO:0005515 protein binding | IPI PMID:24603492 TBC1D5 and the AP2 complex regulate ATG9 trafficking and ini... | KEEP AS NON CORE | Summary: Retain ATG9A association with AP-2. Reason: The inspected original Fig. 3 and Results show ATG9A co-precipitating the AP-2/clathrin machinery in human U2OS cells. They do not resolve a purified ΞΌ2-specific interface for this source row. Retain the positive association without borrowing the more specific motif mechanism from a different study. Supporting Evidence: PMID:24603492 ATG9 and TBC1D5 interact with clathrin and the AP2 complex. |
| GO:0005515 protein binding | IPI PMID:24603492 TBC1D5 and the AP2 complex regulate ATG9 trafficking and ini... | KEEP AS NON CORE | Summary: Retain TBC1D5 association with ΞΌ2. Reason: The inspected original Fig. 3 uses purified GST-AP2M1 to recover TBC1D5 from human HeLa lysate. Its additional purified-protein supplement was described but not independently inspected. This supports the pair without establishing a new molecular activity of ΞΌ2 or transferring TBC1D5's RabGAP function. Supporting Evidence: PMID:24603492 ATG9 and TBC1D5 interact with clathrin and the AP2 complex. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P63010 remains unresolved. Reason: The nuclear crosslinking study is not rejected from its title or compartment; the exact AP2M1 pair and crosslink evidence were not inspected. P63010 is the AP2B1 beta subunit; independent AP-2 architecture supports a plausible association but does not establish what this original experiment measured. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P51116 remains unresolved. Reason: The variant-interaction survey was read at abstract scope; the exact pair and variant conditions were not inspected. |
| GO:0005515 protein binding | IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q92609 remains unresolved. Reason: The variant-interaction survey was read at abstract scope; the exact pair and variant conditions were not inspected. |
| GO:0005515 protein binding | IPI PMID:31980649 Extensive rewiring of the EGFR network in colorectal cancer ... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P00533 remains unresolved. Reason: The KRAS-dependent EGFR network abstract does not resolve the precise AP2M1 pair experiment. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P0DPH9 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P35268 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P55081 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P62807 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q00013 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q03393 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q16778 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q1ED39 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q68CQ4 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q6ZUT1 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q86YD7 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q8N3F0 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records the AP2M1βMAB21L3 pair; its physiological role is unresolved. Reason: The primary HuRI portal interaction table explicitly records MAB21L3βAP2M1 in HI-III. Together with the original human ORFeome Y2H workflow, this supports the reported pair as an experimental interaction. It does not identify an endocytic sorting motif, cargo/adaptor mechanism, endogenous colocalization, or an isoform-specific interface. Retain as non-core rather than invent a specific molecular function. The indexed primary table at https://interactome-atlas.org/search/MAB21L3 lists this pair with score 0.823; sequence-level clone details were not retrieved. The score is not used to infer a physiological mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q8N9N8 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records the AP2M1βPRPF38A pair; its physiological role is unresolved. Reason: The primary HuRI portal interaction table explicitly records PRPF38AβAP2M1 in HI-III. Together with the original human ORFeome Y2H workflow, this supports the reported pair as an experimental interaction. It does not identify an endocytic sorting motif, cargo/adaptor mechanism, endogenous colocalization, or an isoform-specific interface. Retain as non-core rather than invent a specific molecular function. The indexed primary table at https://interactome-atlas.org/search/PRPF38A lists this pair with score 0.888; sequence-level clone details were not retrieved. The score is not used to infer a physiological mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q96EY4 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI records the AP2M1βEAF1 pair; its physiological role is unresolved. Reason: The primary HuRI portal interaction table explicitly records EAF1βAP2M1 in HI-III. Together with the original human ORFeome Y2H workflow, this supports the reported pair as an experimental interaction. It does not identify an endocytic sorting motif, cargo/adaptor mechanism, endogenous colocalization, or an isoform-specific interface. Retain as non-core rather than invent a specific molecular function. The EAF1βAP2M1 row was observed among neighboring-network interactions on the indexed MAB21L3 page (https://interactome-atlas.org/search/MAB21L3), with HI-III score 0.809. This is not a claim that an EAF1-specific portal page was inspected; sequence-level clone details were not retrieved. The score is not used to infer a physiological mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q96MH2 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q99633 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q99880 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q9BSU3 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q9BU76 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q9NZ81 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q9P0T4 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q9UHP6 remains unresolved. Reason: The recovered HuRI article describes the reference interaction map, but its body contains no AP2M1/Q96CW1 target row and does not include the pair-level supplementary tables. The original target-pair record and construct controls are therefore not available in the inspected material. A new source-specific molecular mechanism cannot be assigned from the paper-level assay description. |
| GO:0005515 protein binding | IPI PMID:33436498 Cytoplasmic short linear motifs in ACE2 and integrin Ξ²(3) li... | MODIFY | Summary: Specify recognition of the ATG9A sorting sequence. Reason: The inspected original Table 2/Fig. 3 measures binding of human Q96CW1 ΞΌ2 residues 160β435 to the ATG9A 4β14 YxxΞ¦ probe. This supports the specific signal-recognition refinement for this source, independently of the other ATG9A screen rows. Proposed replacements: signal sequence receptor activity Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33436498 Cytoplasmic short linear motifs in ACE2 and integrin Ξ²(3) li... | MODIFY | Summary: Specify recognition of the ACE2 endocytic sorting sequence. Reason: The inspected original Figs. 3β4 and Table 4 measure human ΞΌ2-domain binding to ACE2-tail peptides; Tyr781 phosphorylation inhibits it. This is a low-affinity biochemical motif interaction, not proof that the interaction is required for viral entry. Proposed replacements: signal sequence receptor activity Supporting Evidence: PMID:33436498 a binding site for the clathrin adaptor AP2 ΞΌ2 in ACE2 overlaps with a phospho-dependent binding site for the SH2 domains of Src family tyrosine kinases. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P63010 remains unresolved. Reason: The two-cell-line interactome combines context-dependent co-complex evidence; the exact AP2M1 pair record was not inspected. P63010 is the AP2B1 beta subunit; independent AP-2 architecture supports a plausible association but does not establish what this original experiment measured. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q59EK9 remains unresolved. Reason: The two-cell-line interactome combines context-dependent co-complex evidence; the exact AP2M1 pair record was not inspected. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q68CQ4 remains unresolved. Reason: The two-cell-line interactome combines context-dependent co-complex evidence; the exact AP2M1 pair record was not inspected. |
| GO:0005515 protein binding | IPI PMID:34799561 Large scale discovery of coronavirus-host factor protein int... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q7Z3C6 remains unresolved. Reason: The coronavirus motif-screen abstract does not establish the precise AP2M1βATG9A construct and assay used for this row. Independent targeted ATG9A motif evidence is considered separately and is not relabeled as this source's experiment. |
| GO:0005515 protein binding | IPI PMID:34964704 AP2M1 mediates autophagy-induced CLDN2 (claudin 2) degradati... | MODIFY | Summary: Specify CLDN2 sorting-sequence recognition. Reason: The inspected Fig. 7/Methods show endogenous human AP2M1 association with CLDN2 and loss of association after mutations in CLDN2 YxxΦ motifs. Human epithelial-cell depletion links this interaction to internalization. The evidence supports motif-dependent cargo recognition without a purified binary-interface claim. Proposed replacements: signal sequence receptor activity Supporting Evidence: PMID:34964704 Site-directed mutagenesis revealed that AP2M1 binds to CLDN2 tyrosine motifs (YXXЀ) (67-70 and 148-151). |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P63010 remains unresolved. Reason: The OpenCell abstract describes endogenous tagging and interaction mapping; the AP2M1βAP2B1 pair record was not inspected. P63010 is the AP2B1 beta subunit; independent AP-2 architecture supports a plausible association but does not establish what this original experiment measured. |
| GO:0005515 protein binding | IPI PMID:35384245 Physical and functional interactome atlas of human receptor ... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P00533 remains unresolved. Reason: The receptor-tyrosine-kinase atlas combines several assay types; the exact AP2M1βEGFR evidence was not inspected. |
| GO:0005515 protein binding | IPI PMID:37100772 Large-scale phage-based screening reveals extensive pan-vira... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P00533 remains unresolved. Reason: The pan-viral motif screen contains many interactions, but this exact AP2M1 partner peptide and its validation were not inspected. |
| GO:0005515 protein binding | IPI PMID:37100772 Large-scale phage-based screening reveals extensive pan-vira... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P18272 remains unresolved. Reason: The pan-viral motif screen contains many interactions, but this exact AP2M1 partner peptide and its validation were not inspected. |
| GO:0005515 protein binding | IPI PMID:37100772 Large-scale phage-based screening reveals extensive pan-vira... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q77IS8 remains unresolved. Reason: The pan-viral motif screen contains many interactions, but this exact AP2M1 partner peptide and its validation were not inspected. |
| GO:0005515 protein binding | IPI PMID:37100772 Large-scale phage-based screening reveals extensive pan-vira... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q7Z3C6 remains unresolved. Reason: The pan-viral motif screen contains many interactions, but this exact AP2M1 partner peptide and its validation were not inspected. Independent targeted ATG9A motif evidence is considered separately and is not relabeled as this source's experiment. |
| GO:0005515 protein binding | IPI PMID:37219487 Large-scale phosphomimetic screening identifies phospho-modu... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:Q7Z3C6 remains unresolved. Reason: The phosphomimetic-screen abstract does not resolve the AP2M1βATG9A peptide conditions or binding result. Independent targeted ATG9A motif evidence is considered separately and is not relabeled as this source's experiment. |
| GO:0005515 protein binding | IPI PMID:39251607 Systematic identification of post-transcriptional regulatory... | UNDECIDED | Summary: The source-specific interaction with UniProtKB:P51116 remains unresolved. Reason: The post-transcriptional regulatory-network abstract does not expose this AP2M1βFXR2 experiment or distinguish proximity from other interaction evidence. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-190519 | UNDECIDED | Summary: Destination-membrane localization is not resolved by the available event record. Reason: The R-HSA-190519 summary describes internalized annular gap-junction cargo and subsequent endo/lysosomal degradation. It does not expose a ΞΌ2-localization measurement or the compartmented molecular participants behind the TAS mapping. Keep that specific localization unresolved; cargo delivery is neither evidence of ΞΌ2 residence nor proof that no transient destination pool can exist. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-190829 | UNDECIDED | Summary: Destination-membrane localization is not resolved by the available event record. Reason: R-HSA-190829 describes lysosomal destruction of internalized gap-junction plaques. The exact AP2M1-bearing entity and primary localization evidence underlying the TAS assertion have not been recovered. Preserve uncertainty rather than infer either destination residence or its absence from a cargo summary. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the soluble cytosolic AP-2 pool. Reason: The actual PTN000242370 cytosol IBD was inspected. AP-2 structural and recruitment evidence independently establishes a cytosolic pool that engages the plasma membrane. Full target-to-node topology was not reconstructed; the donor list is not treated as a support score. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000242370 UNRESOLVED The actual PAINT node assertion was inspected in the local family export; full tree/MSA placement was not reconstructed. Target self-inclusion and donor count are not defects. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-167537 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-167537 places AP-2 recruitment at the cytoplasmic NefβCD4 complex. Retain the broad cytosolic ΞΌ2 pool in this adaptor-recruitment context. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-167537 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-167597 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-167597 describes internalization of the NefβCD4βAP2 complex. This is compatible with ΞΌ2 functioning on the cytoplasmic coat; it is not evidence that ΞΌ2 enters the vesicle lumen. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-167597 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-167601 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-167601 describes CD4 degradation. Retain the existing broad cytosolic AP2 annotation using established adaptor localization, while distinguishing ΞΌ2 from the cargo delivered for proteolysis. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-167601 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-167637 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-167637 follows Nef-driven CD28 uptake toward lysosomal degradation. ΞΌ2 participates from the cytoplasmic adaptor pool; the destination of CD28 is not automatically the location of ΞΌ2. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-167637 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182171 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-182171 concerns CD8 degradation after uptake. The accepted cytosolic ΞΌ2 annotation reflects its established adaptor pool, not a claim that it is the luminal lysosomal degradation substrate. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-182171 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182186 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-182186 describes Nef-dependent CD8 trafficking and explicitly leaves some downstream COPI interactions unresolved. The broad cytosolic AP2 location is retained without claiming those later interfaces have been reconstructed. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-182186 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182198 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-182198 describes CD8 endocytosis through the named AP2-containing complex. Retain ΞΌ2βs cytoplasmic coat/adaptor context. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-182198 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3928654 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-3928654 describes EPH/ephrin internalization with cytoplasmic partners and clathrin coats. The broad cytosolic ΞΌ2 annotation fits that adaptor role; EEA1-positive cargo arrival is a separate observation. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-3928654 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5138433 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-5138433 explicitly describes ΞΌ2 recognition of DVL2 DEP/YHEL elements during FZD4 uptake. This supports its cytoplasmic cargo-recognition role, with the modelβs uncertainty about beta-arrestin requirement preserved. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-5138433 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5138459 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-5138459 describes AP2-dependent WNT5AβFZD4 uptake and possible beta-arrestin dissociation. Retain the broad cytosolic ΞΌ2 location; beta-arrestin timing is not treated as direct ΞΌ2 dissociation evidence. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-5138459 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8856808 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8856808 describes recruitment of soluble AP2, opening of its core and cargo capture at the plasma membrane. These transitions directly fit an adaptor cycling from the cytosol to the coat. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8856808 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8856813 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8856813 identifies ΞΌ2 Thr156 as the AAK1 phosphorylation substrate. Retain the cytoplasmic AP2 pool in this regulatory event; AAK1 performs the phosphorylation. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8856813 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8862280 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8862280 describes FCHo/SGIP-dependent stabilization and opening of AP2 at nascent pits. The cytosolic annotation fits recruitment of the adaptor into that assembly, distinct from the F-BAR membrane interaction. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8862280 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8866277 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8866277 distinguishes direct cargo recognition by the AP2 core from accessory-protein recruitment by its ears. Retain the cytosolic ΞΌ2 location consistent with the coreβs cargo-recognition role. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8866277 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8866283 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8866283 recruits GPCRs through beta-arrestins and clathrin-coat components. ΞΌ2βs cytosolic AP2 location is retained without assigning it every beta-arrestin receptor interface. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8866283 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8867754 concerns staged BAR-protein recruitment to the AP2/clathrin pit. Retain the broad cytosolic adaptor pool; the curvature-recognition domains belong to the recruited BAR proteins. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8867754 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8867756 describes concurrent CLASP/cargo and AP2/clathrin assembly. Retain ΞΌ2βs cytosolic recruitment context while preserving the sourceβs caveat that these events need not be strictly sequential. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8867756 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8868071 recruits PIK3C2A through clathrin during pit maturation. The retained ΞΌ2 annotation is cytosolic coat/adaptor context; direct PIK3C2A recruitment by ΞΌ2 is not inferred. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8868071 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8868072 describes PIK3C2A lipid phosphorylation within a maturing coat. Retain the broad ΞΌ2 cytosolic context rather than interpret the reaction title as ΞΌ2 catalytic activity. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8868072 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8868230 describes SNX9-linked actin machinery at late pits, particularly under membrane tension. ΞΌ2 remains a cytoplasmic adaptor component; this record does not establish its own actin-nucleation mechanism. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8868230 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8868236 recruits dynamin through BAR and other coat partners. Retain the cytoplasmic AP2 context without claiming a ΞΌ2-specific dynamin interface from this summary. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8868236 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8868648 connects phosphoinositide turnover with coat disassembly and uncoating. This is compatible with AP2 exchange between membrane-bound and cytosolic pools; the exact ΞΌ2 release kinetics are not supplied. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8868648 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8868651 describes synaptojanin recruitment by endophilin, clathrin and AP2-associated machinery. Retain broad cytosolic ΞΌ2 localization while distinguishing the synaptojanin isoform/timing findings from ΞΌ2 itself. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8868651 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868658 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8868658 concerns HSPA8-mediated clathrin disassembly. Retain ΞΌ2βs independently established cytosolic pool, but this specific clathrinβHSPA8 mechanism is not recast as an isolated ΞΌ2 assay. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8868658 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868659 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8868659 recruits auxilins after fission, priming vesicles for endosomal fusion. The broad ΞΌ2 cytosolic annotation is consistent with coat recycling; auxilin-mediated uncoating does not itself locate ΞΌ2 on the destination membrane. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8868659 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868660 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8868660 describes HSPA8 recruitment and persistence on liberated clathrin. Retain the general ΞΌ2 cytosolic pool without transferring the measured HSPA8/clathrin stoichiometry to AP2. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8868660 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8868661 describes dynamin-dependent fission of an AP2/clathrin-coated pit. Retain ΞΌ2βs cytoplasmic adaptor context; dynamin is the GTPase that executes scission. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8868661 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8869438 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8869438 explicitly states that the timing and mechanism of coat-associated protein loss remain poorly understood. Retain cytosolic AP2 recycling without converting this broad model into a universal claim about ΞΌ2 release timing. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8869438 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871193 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8871193 links AAK1 displacement and ΞΌ2 dephosphorylation with weakened AP2βmembrane association. This directly fits regulated return toward a cytosolic pool; exact destination exclusion is not demonstrated. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8871193 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871194 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8871194 models RAB5/GAPVD1-dependent AP2 uncoating and membrane-lipid turnover. Retain the broad cytosolic adaptor location while preserving the predictive nature of the timing/model. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8871194 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871196 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-8871196 describes transient AP2/clathrin recruitment from soluble pools to PI(4,5)P2-rich plasma membrane. The source explicitly notes variable temporal order and abortive pits, supporting a dynamic cytosolic/membrane cycle. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-8871196 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9681616 | ACCEPT | Summary: Retain the cytosolic coat/adaptor pool in this pathway event. Reason: R-HSA-9681616 describes chlorpromazine perturbing AP2/clathrin relocation. Retain the broad cytosolic adaptor pool; pharmacological disruption is not a newly assigned physiological ΞΌ2 ligand function. Supporting Evidence: PMID:20603002 In the "locked" cytosolic form, AP2's binding sites for the two endocytic motifs, YxxPhi on the C-terminal domain of mu2 (C-mu2) and [ED]xxxL[LI] on sigma2, are blocked by parts of beta2. Reactome:R-HSA-9681616 |
| GO:0005886 plasma membrane | EXP PMID:31104773 A Recurrent Missense Variant in AP2M1 Impairs Clathrin-Media... | ACCEPT | Summary: ΞΌ2 localizes to the plasma membrane during coat formation. Reason: Actual source imaging shows ΞΌ2 recruitment in human HeLa cells; Arg170Trp preserves membrane/pit localization despite impaired uptake. The named mCherry rescue reagent is rat, distinct from human host-cell depletion and patient genetics. Preserve the source annotation without claiming all constructs are human. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Retain plasma-membrane localization. Reason: The HPA-derived cellular localization agrees with independently inspected ΞΌ2 recruitment and uptake experiments. The HPA image-level evidence was not separately reanalyzed, and this acceptance does not infer an integral membrane topology. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. |
| GO:0005886 plasma membrane | IDA PMID:14530274 The AP-2 complex is excluded from the dynamic population of ... | ACCEPT | Summary: Retain activity at plasma-membrane coated sites. Reason: The cited study images alpha/beta2 adaptors at the plasma membrane. Independent ΞΌ2 imaging confirms the location, while later work documents limitations of tagged adaptor dynamics. Preserve the location assertion without adopting the older kinetic interpretation as a universal exclusion of AP-2 from vesicles. Supporting Evidence: PMID:17035630 Mutating the PtdIns(4,5)P2 binding site of alpha, the phosphorylation site of mu2, or the YXXPhi binding site of mu2 impairs AP-2 function, as assayed by transferrin uptake. PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Retain peripheral plasma-membrane localization. Reason: The UniProt subcellular-location mapping matches independently inspected ΞΌ2 localization. AP2M1 acts on the cytoplasmic side as an adaptor subunit, rather than as a transmembrane receptor. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0039 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-167633 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-167633 event concerns Formation of Nef:Cd28:Clathrin-coated Pit Adapter Protein complex. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-167633 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-167637 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-167637 event concerns Internalization of Nef:CD28:Clathrin-Coated Pit Adapter Protein Complex. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-167637 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-177479 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-177479 event concerns Axonal transport of NGF:Trk complexes. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-177479 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-190519 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-190519 event concerns Internalization of gap junction plaques. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-190519 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-196017 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-196017 event concerns Dynamin is recruited to the gap junction plaque. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-196017 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-196026 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-196026 event concerns Dab2 is recruited to the junctional plaques. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-196026 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2130640 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-2130640 event concerns Recruitment of clathrin coated vesicle by Ii. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-2130640 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2130725 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-2130725 event concerns Internalization of MHC II:Ii clathrin coated vesicle. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-2130725 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-392748 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-392748 event concerns L1 binds to AP-2 Clathrin complex. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-392748 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-392749 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-392749 event concerns Transport of L1 into endosomes. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-392749 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-445071 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-445071 event concerns Reinsertion of L1 into the plasma membrane. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-445071 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-445079 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-445079 event concerns Phosphorylation of L1 by ERK. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-445079 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-555065 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-555065 event concerns Formation of clathrin coated vesicle. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-555065 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6784729 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-6784729 event concerns PCSK9:LDLR:Clathrin-coated vesicle transport from plasma membrane to endolysosome. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-6784729 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6784735 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-6784735 event concerns PCSK9:LDLR bind to Clathrin. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-6784735 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8855130 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8855130 event concerns VLDLR:PCSK9:Clathrin-coated vesicle translocates from the plasma membrane to lysosomal membrane. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8855130 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8855131 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8855131 event concerns VLDLR:PCSK9 binds Clathrin-coated vesicles. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8855131 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8866279 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8866279 event concerns Epsin family proteins bind ubiquitinated cargo. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8866279 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8867754 event concerns F- and N- BAR domain proteins bind the clathrin-coated pit. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8867754 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8867756 event concerns CLASP proteins and cargo are recruited to the nascent clathrin-coated pit. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8867756 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8868071 event concerns Clathrin recruits PIK3C2A. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8868071 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8868072 event concerns Clathrin-associated PIK3C2A phosphorylates PI(4)P to PI(3,4)P2. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8868072 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8868230 event concerns SNX9 recruits components of the actin polymerizing machinery. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8868230 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8868236 event concerns BAR domain proteins recruit dynamin. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8868236 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8868648 event concerns SYNJ hydrolyze PI(4,5)P2 to PI(4)P. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8868648 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8868651 event concerns Endophilins recruit synaptojanins to the clathrin-coated pit. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8868651 |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: Retain the plasma-membrane-associated AP-2 pool. Reason: The inspected Reactome:R-HSA-8868661 event concerns Dynamin-mediated GTP hydrolysis promotes vesicle scission. Its component-level plasma-membrane assignment agrees with independently observed ΞΌ2 recruitment to endocytic sites. This retains location, not a claim that ΞΌ2 performs every molecular reaction or accompanies cargo throughout later degradation. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. Reactome:R-HSA-8868661 |
| GO:0005905 clathrin-coated pit | IDA PMID:31104773 A Recurrent Missense Variant in AP2M1 Impairs Clathrin-Media... | ACCEPT | Summary: ΞΌ2 occupies clathrin-coated pits. Reason: Actual source imaging and quantitative coat analysis retain ΞΌ2 at clathrin-positive sites, including the disease-associated mutant that impairs uptake. Localization and functional impairment are distinct observations. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | ACCEPT | Summary: Retain intracellular protein transport through the AP-2 adaptor. Reason: The InterPro family mapping is broad, but human cargo-recognition and uptake evidence supports this existing transport assertion. It does not give ΞΌ2 every trafficking route of the wider adaptor family. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001392 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. InterPro:IPR018240 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. PMID:31104773 Functional complementation of both the ΞΌ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2ΞΌ conditional knockout mice revealed a significant impairment of CME of transferrin. |
| GO:0006896 Golgi to vacuole transport | IBA GO_REF:0000033 | UNDECIDED | Summary: The inherited Golgi-to-vacuole route remains unresolved. Reason: The exact PTN000055849 GO:0006896 IBD was inspected, together with a same-term IRD at PTN002575694. Full family topology/MSA are unavailable, so that loss cannot be assigned to AP2M1 from node order or taxon alone. The current term includes Golgi-to-lysosome transport; plasma-membrane cargo entry is not equivalent evidence. No donor-count, self-source or yeast-only objection is made. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN000055849 UNRESOLVED Actual PTN000055849 GO:0006896 IBD and same-term IRD at PTN002575694 were read, but topology linking the target to the loss branch is unresolved. Node order and taxon alone cannot assign a loss to AP2M1. |
| GO:0006900 vesicle budding from membrane | IMP PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: AP-2 contributes structurally to endocytic budding. Reason: The actual source includes ΞΌ2 depletion and rescue experiments: loss of ΞΌ2 strongly reduces coated-pit abundance and changes coat size. AP2M1 supplies cargo/coat structure; CALM supplies the directly characterized curvature-sensing amphipathic helix. This existing process assertion does not assign CALM's membrane-bending chemistry to ΞΌ2. Supporting Evidence: PMID:25898166 AP2 depletion (of ΞΌ2) resulted in an βΌ12-fold decrease in the number of endocytic CCPs/CCVs |
| GO:0008021 synaptic vesicle | IBA GO_REF:0000033 | ACCEPT | Summary: Retain the synaptic-vesicle retrieval context. Reason: The conserved AP-2 coat participates in reformation and sorting of synaptic-vesicle membrane. This is a transient active retrieval pool, not a claim that AP2M1 is an integral resident of every mature synaptic vesicle. The actual synaptic-vesicle IBD is available for row 134; the full topology and exact rat transfer experiment remain uninspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008307226 UNRESOLVED The actual PAINT node assertion was inspected in the local family export; full tree/MSA placement was not reconstructed. Target self-inclusion and donor count are not defects. Supporting Evidence: PMID:11102472 Microinjection of these peptides into squid giant presynaptic terminals reversibly blocked synaptic transmission and inhibited synaptic vesicle endocytosis by preventing coated pit formation at the plasma membrane. PMID:31671891 ΞΌ2-subunit also interacts with C2 domains as present in Synaptotagmin1 [11] or Otoferlin [12]. |
| GO:0008021 synaptic vesicle | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the synaptic-vesicle retrieval context. Reason: The conserved AP-2 coat participates in reformation and sorting of synaptic-vesicle membrane. This is a transient active retrieval pool, not a claim that AP2M1 is an integral resident of every mature synaptic vesicle. The actual synaptic-vesicle IBD is available for row 134; the full topology and exact rat transfer experiment remain uninspected. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. ensembl:ENSRNOP00000054900 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:11102472 Microinjection of these peptides into squid giant presynaptic terminals reversibly blocked synaptic transmission and inhibited synaptic vesicle endocytosis by preventing coated pit formation at the plasma membrane. PMID:31671891 ΞΌ2-subunit also interacts with C2 domains as present in Synaptotagmin1 [11] or Otoferlin [12]. |
| GO:0009898 cytoplasmic side of plasma membrane | NAS PMID:29184887 Weak Molecular Interactions in Clathrin-Mediated Endocytosis... | ACCEPT | Summary: AP2M1 acts at the cytoplasmic plasma-membrane surface. Reason: The inspected adaptor review places the AP-2 cargo-recognition machinery on the cytoplasmic side, consistent with ΞΌ2 cargo-tail recognition and peripherally recruited coat architecture. Supporting Evidence: PMID:29184887 It interacts directly with two types of internalization motifs (LL and (Y-X-X-Ξ¦) (Ξ¦ = hydrophobic residue) found within the cytoplasmic domains of integral membrane protein receptors via its Ο (LL) and ΞΌ2 (Y-X-X-Ξ¦) subunits PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Retain membrane association of the peripheral adaptor. Reason: The broad electronic membrane assignment agrees with direct ΞΌ2 imaging and membrane-dependent AP-2 opening. It does not imply a transmembrane segment or indiscriminate residence at all organelles. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0162 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:31104773 However, we found that AP-2ΞΌ WT and p.Arg170Trp variants colocalize with clathrin equally well in HeLa cells, suggesting that localization of the pathogenic AP-2ΞΌ variant in clathrin-coated pits is not altered. PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000002 | ACCEPT | Summary: AP2M1 participates in vesicle-mediated cargo transport. Reason: The broad family mapping is independently grounded by ΞΌ2 sorting-signal recognition and AP-2-dependent uptake. It is restricted here to the established adaptor role. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001392 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. InterPro:IPR018240 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. PMID:31104773 Functional complementation of both the ΞΌ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2ΞΌ conditional knockout mice revealed a significant impairment of CME of transferrin. |
| GO:0016192 vesicle-mediated transport | NAS PMID:15941406 Analysis of the AP-2 adaptor complex and cargo during clathr... | ACCEPT | Summary: Retain vesicle-mediated transport as an adaptor function. Reason: The cited paper discusses tagged AP-2 and cargo dynamics. Its early interpretation of AP-2 exclusion from internalizing carriers has construct-dependent limitations documented by later work. The broad transport function is independently well established, so the retained annotation does not require endorsing every kinetic conclusion. Supporting Evidence: PMID:17035630 Mutating the PtdIns(4,5)P2 binding site of alpha, the phosphorylation site of mu2, or the YXXPhi binding site of mu2 impairs AP-2 function, as assayed by transferrin uptake. PMID:31104773 Functional complementation of both the ΞΌ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2ΞΌ conditional knockout mice revealed a significant impairment of CME of transferrin. |
| GO:0030122 AP-2 adaptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: AP2M1 is the medium subunit of the AP-2 complex. Reason: Sequence, AP-2 structural studies and human tissue co-immunoprecipitation agree on the medium subunit's complex membership. The original reference and qualifier are retained; PAINT target self-inclusion is legitimate experimental grounding, not circularity. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000242370 UNRESOLVED The actual PAINT node assertion was inspected in the local family export; full tree/MSA placement was not reconstructed. Target self-inclusion and donor count are not defects. Supporting Evidence: PMID:12086608 We describe the structure of the 200 kDa AP2 "core" (alpha trunk, beta2 trunk, mu2, and sigma2) PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:23676497 we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. |
| GO:0030122 AP-2 adaptor complex | IDA PMID:23676497 Endocytosis of synaptic ADAM10 in neuronal plasticity and Al... | ACCEPT | Summary: AP2M1 is the medium subunit of the AP-2 complex. Reason: Sequence, AP-2 structural studies and human tissue co-immunoprecipitation agree on the medium subunit's complex membership. The original reference and qualifier are retained; PAINT target self-inclusion is legitimate experimental grounding, not circularity. Supporting Evidence: PMID:12086608 We describe the structure of the 200 kDa AP2 "core" (alpha trunk, beta2 trunk, mu2, and sigma2) PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:23676497 we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. |
| GO:0030122 AP-2 adaptor complex | IEA GO_REF:0000120 | ACCEPT | Summary: AP2M1 is the medium subunit of the AP-2 complex. Reason: Sequence, AP-2 structural studies and human tissue co-immunoprecipitation agree on the medium subunit's complex membership. The original reference and qualifier are retained; PAINT target self-inclusion is legitimate experimental grounding, not circularity. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00027293 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. ensembl:ENSRNOP00000054900 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:12086608 We describe the structure of the 200 kDa AP2 "core" (alpha trunk, beta2 trunk, mu2, and sigma2) PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:23676497 we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. |
| GO:0030122 AP-2 adaptor complex | NAS PMID:12086608 Molecular architecture and functional model of the endocytic... | ACCEPT | Summary: AP2M1 is the medium subunit of the AP-2 complex. Reason: Sequence, AP-2 structural studies and human tissue co-immunoprecipitation agree on the medium subunit's complex membership. The original reference and qualifier are retained; PAINT target self-inclusion is legitimate experimental grounding, not circularity. Supporting Evidence: PMID:12086608 We describe the structure of the 200 kDa AP2 "core" (alpha trunk, beta2 trunk, mu2, and sigma2) PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:23676497 we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. |
| GO:0030122 AP-2 adaptor complex | TAS PMID:12121421 The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY... | ACCEPT | Summary: AP2M1 is the medium subunit of the AP-2 complex. Reason: Sequence, AP-2 structural studies and human tissue co-immunoprecipitation agree on the medium subunit's complex membership. The original reference and qualifier are retained; PAINT target self-inclusion is legitimate experimental grounding, not circularity. Supporting Evidence: PMID:12086608 We describe the structure of the 200 kDa AP2 "core" (alpha trunk, beta2 trunk, mu2, and sigma2) PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:23676497 we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. |
| GO:0030131 clathrin adaptor complex | IEA GO_REF:0000002 | ACCEPT | Summary: Retain membership in the clathrin adaptor machinery. Reason: The family-level complex term is broader than AP-2 membership but correct. ΞΌ2 is a constituent of the heterotetramer, not an independently complete clathrin coat. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR001392 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. InterPro:IPR018240 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:12086608 We describe the structure of the 200 kDa AP2 "core" (alpha trunk, beta2 trunk, mu2, and sigma2) PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. |
| GO:0030666 endocytic vesicle membrane | TAS Reactome:R-HSA-416639 | ACCEPT | Summary: Retain the transient endocytic carrier membrane pool. Reason: The Reactome record describes constitutive AMPA-receptor recycling and does not itself resolve ΞΌ2 residence at every trafficking stage. Independent AP-2 structural/endocytic evidence supports transient peripheral association with forming endocytic carriers; no permanent recycling-endosome residence is inferred. Supporting Evidence: Reactome:R-HSA-416639 PMID:29184887 We have so far discussed how these interactions occur at the membrane, but in order for internalization to occur, the coated vesicle itself must form. This process of coat formation is driven by interactions between AP2 and its network of binding partners which bind to the appendage (or βearβ) domains of Ξ±2-adaptin and Ξ²2-adaptin. |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-5138459 | ACCEPT | Summary: Retain association with forming clathrin-coated endocytic carriers. Reason: The inspected WNT5A/FZD4 event explicitly depends on AP-2 during uptake. ΞΌ2 contributes to the coat-associated adaptor pool; this does not assert that the receptor, arrestin and AP-2 remain bound throughout all later traffic. Supporting Evidence: Reactome:R-HSA-5138459 PMID:29184887 We have so far discussed how these interactions occur at the membrane, but in order for internalization to occur, the coated vesicle itself must form. This process of coat formation is driven by interactions between AP2 and its network of binding partners which bind to the appendage (or βearβ) domains of Ξ±2-adaptin and Ξ²2-adaptin. |
| GO:0031623 receptor internalization | IEA GO_REF:0000117 | ACCEPT | Summary: Retain receptor internalization. Reason: Independent human-cell uptake and cargo-tail experiments support the automated process assignment, although the exact ARBA rule was not reconstructed. ΞΌ2 recognizes and organizes cargo within AP-2 rather than merely being consumed by internalization. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00087457 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. PMID:31104773 Functional complementation of both the ΞΌ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2ΞΌ conditional knockout mice revealed a significant impairment of CME of transferrin. |
| GO:0031623 receptor internalization | IMP PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: ΞΌ2 contributes to receptor uptake. Reason: The source's ΞΌ2-depletion and rescue controls directly establish AP-2-dependent transferrin uptake. CALM is the focal protein, but actual ΞΌ2 experiments were inspected, so the paper title is not a misattribution argument. Supporting Evidence: PMID:25898166 AP2 depletion (of ΞΌ2) resulted in an βΌ12-fold decrease in the number of endocytic CCPs/CCVs |
| GO:0035615 clathrin-cargo adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Retain ΞΌ2 contribution to clathrin-cargo adaptor activity. Reason: ΞΌ2 supplies cargo-signal recognition within the assembled AP-2 adaptor; other subunits supply additional membrane and clathrin contacts. The authored core explicitly uses contributes_to_molecular_function. Original qualifiers are preserved, including the two existing contributes_to rows; acceptance does not claim autonomous isolated-ΞΌ2 bridging. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000055849 UNRESOLVED The actual PAINT node assertion was inspected in the local family export; full tree/MSA placement was not reconstructed. Target self-inclusion and donor count are not defects. Supporting Evidence: PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:23676497 we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. PMID:12121421 recognition of the FDNPVY signal is mediated by a binding site in the mu2-subunit that is distinct from the site for the more general YppΓ sorting signal |
| GO:0035615 clathrin-cargo adaptor activity | IDA PMID:23676497 Endocytosis of synaptic ADAM10 in neuronal plasticity and Al... | ACCEPT | Summary: Retain ΞΌ2 contribution to clathrin-cargo adaptor activity. Reason: ΞΌ2 supplies cargo-signal recognition within the assembled AP-2 adaptor; other subunits supply additional membrane and clathrin contacts. The authored core explicitly uses contributes_to_molecular_function. Original qualifiers are preserved, including the two existing contributes_to rows; acceptance does not claim autonomous isolated-ΞΌ2 bridging. Supporting Evidence: PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:23676497 we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. PMID:12121421 recognition of the FDNPVY signal is mediated by a binding site in the mu2-subunit that is distinct from the site for the more general YppΓ sorting signal |
| GO:0035615 clathrin-cargo adaptor activity | TAS PMID:12121421 The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY... | ACCEPT | Summary: Retain ΞΌ2 contribution to clathrin-cargo adaptor activity. Reason: ΞΌ2 supplies cargo-signal recognition within the assembled AP-2 adaptor; other subunits supply additional membrane and clathrin contacts. The authored core explicitly uses contributes_to_molecular_function. Original qualifiers are preserved, including the two existing contributes_to rows; acceptance does not claim autonomous isolated-ΞΌ2 bridging. Supporting Evidence: PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:23676497 we identified the clathrin adaptor AP2 as an interacting partner of a previously uncharacterized atypical binding motif in the ADAM10 C-terminal domain. PMID:12121421 recognition of the FDNPVY signal is mediated by a binding site in the mu2-subunit that is distinct from the site for the more general YppΓ sorting signal |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-2130486 | UNDECIDED | Summary: Destination-membrane localization is not resolved by the available event record. Reason: The R-HSA-2130486 event is named uncoating and fusion, while its short summary states that MHC-II/Ii vesicles fuse with endosomes. This suggests a coat-to-destination mapping question, but does not establish when ΞΌ2 leaves in that exact model or exclude a transient destination pool. The source-specific endolysosome-membrane claim remains unresolved. |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-2130725 | UNDECIDED | Summary: Destination-membrane localization is not resolved by the available event record. Reason: R-HSA-2130725 describes MHC-II/Ii entry from the plasma membrane and conflicting dynamin-perturbation findings. Those experiments concern cargo uptake, not a ΞΌ2-specific measurement at the endolysosome. The original TAS localization remains unresolved without declaring the curated event incorrect. |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-6784729 | UNDECIDED | Summary: Destination-membrane localization is not resolved by the available event record. Reason: R-HSA-6784729 follows PCSK9βLDLR cargo through endosomes to lysosomal degradation. The accessible summary does not expose the AP2M1-containing entity or a destination-localization assay. Retain uncertainty; well-established plasma-membrane coat function does not by itself exclude other membrane pools. |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-6784738 | UNDECIDED | Summary: Destination-membrane localization is not resolved by the available event record. Reason: R-HSA-6784738 separates clathrin-dependent entry of PCSK9βLDLR from later lysosomal degradation. It does not establish ΞΌ2 persistence or absence at the destination; the exact compartment-mapping evidence needs inspection before a confident overannotation judgment. |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-8855130 | UNDECIDED | Summary: Destination-membrane localization is not resolved by the available event record. Reason: R-HSA-8855130 names a VLDLR/PCSK9/clathrin-coated vesicle moving toward lysosomal membrane. The summary retains a coat label but does not resolve the timing or identity of AP2M1-containing participants. Keep the specific TAS localization unresolved rather than turn a plausible general uncoating model into an inspected source result. |
| GO:0044325 transmembrane transporter binding | IPI PMID:23529131 Oestrogen promotes KCNQ1 potassium channel endocytosis and p... | ACCEPT | Summary: Retain binding to the membrane transporter KCNQ1. Reason: The inspected original Fig. 3 shows endogenous ΞΌ2 co-IP with KCNQ1 in human HT29cl.19A cells, enhanced by estrogen during uptake. Co-IP supports the existing partner-class term; it does not establish a purified binary interface or experimentally map a particular KCNQ1 sorting motif. Supporting Evidence: PMID:23529131 KCNQ1 was retrieved from the plasma membrane by a clathrin-mediated endocytosis, which involved the association between KCNQ1 and the clathrin adaptor, AP-2. |
| GO:0045334 clathrin-coated endocytic vesicle | NAS PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: Retain association with the clathrin-coated endocytic carrier. Reason: The actual study characterizes ΞΌ2-dependent coated-pit/vesicle production and uses ΞΌ2 depletion/rescue controls. The adaptor is a transient coat component, not a permanent luminal or integral membrane protein. Supporting Evidence: PMID:25898166 AP2 depletion (of ΞΌ2) resulted in an βΌ12-fold decrease in the number of endocytic CCPs/CCVs PMID:17035630 Mutating the PtdIns(4,5)P2 binding site of alpha, the phosphorylation site of mu2, or the YXXPhi binding site of mu2 impairs AP-2 function, as assayed by transferrin uptake. |
| GO:0048488 synaptic vesicle endocytosis | IDA PMID:11102472 A conserved clathrin assembly motif essential for synaptic v... | ACCEPT | Summary: Retain participation in synaptic-vesicle retrieval. Reason: The actual cited main paper uses bovine brain AP-2/clathrin assembly and squid presynaptic intervention to establish conserved complex-level coat function during retrieval. Preserve the curated human process assertion with this cross-species scope explicit; the experiments do not isolate a human ΞΌ2 catalytic step or transfer beta2 clathrin-binding chemistry to ΞΌ2. Supporting Evidence: PMID:11102472 Microinjection of these peptides into squid giant presynaptic terminals reversibly blocked synaptic transmission and inhibited synaptic vesicle endocytosis by preventing coated pit formation at the plasma membrane. PMID:31671891 ΞΌ2-subunit also interacts with C2 domains as present in Synaptotagmin1 [11] or Otoferlin [12]. |
| GO:0048488 synaptic vesicle endocytosis | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the conserved synaptic-vesicle endocytic role. Reason: The rat transfer agrees with the conserved AP-2 cargo-sorting/coat role and independent neuronal adaptor evidence. Exact donor experiments were not reconstructed; this does not imply that ΞΌ2 acts as dynamin or clathrin. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. ensembl:ENSRNOP00000054900 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:11102472 Microinjection of these peptides into squid giant presynaptic terminals reversibly blocked synaptic transmission and inhibited synaptic vesicle endocytosis by preventing coated pit formation at the plasma membrane. PMID:31671891 ΞΌ2-subunit also interacts with C2 domains as present in Synaptotagmin1 [11] or Otoferlin [12]. |
| GO:0048488 synaptic vesicle endocytosis | IMP PMID:11102472 A conserved clathrin assembly motif essential for synaptic v... | ACCEPT | Summary: Retain participation in synaptic-vesicle retrieval. Reason: The actual cited main paper uses bovine brain AP-2/clathrin assembly and squid presynaptic intervention to establish conserved complex-level coat function during retrieval. Preserve the curated human process assertion with this cross-species scope explicit; the experiments do not isolate a human ΞΌ2 catalytic step or transfer beta2 clathrin-binding chemistry to ΞΌ2. Supporting Evidence: PMID:11102472 Microinjection of these peptides into squid giant presynaptic terminals reversibly blocked synaptic transmission and inhibited synaptic vesicle endocytosis by preventing coated pit formation at the plasma membrane. PMID:31671891 ΞΌ2-subunit also interacts with C2 domains as present in Synaptotagmin1 [11] or Otoferlin [12]. |
| GO:0048488 synaptic vesicle endocytosis | NAS PMID:11102472 A conserved clathrin assembly motif essential for synaptic v... | ACCEPT | Summary: Retain participation in synaptic-vesicle retrieval. Reason: The actual cited main paper uses bovine brain AP-2/clathrin assembly and squid presynaptic intervention to establish conserved complex-level coat function during retrieval. Preserve the curated human process assertion with this cross-species scope explicit; the experiments do not isolate a human ΞΌ2 catalytic step or transfer beta2 clathrin-binding chemistry to ΞΌ2. Supporting Evidence: PMID:11102472 Microinjection of these peptides into squid giant presynaptic terminals reversibly blocked synaptic transmission and inhibited synaptic vesicle endocytosis by preventing coated pit formation at the plasma membrane. PMID:31671891 ΞΌ2-subunit also interacts with C2 domains as present in Synaptotagmin1 [11] or Otoferlin [12]. |
| GO:0050750 low-density lipoprotein particle receptor binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain LDL-receptor-tail binding as a secondary interaction context. Reason: PMID:12121421 directly reports μ2 binding to FDNPVY and YppΦ peptides at distinct sites. Preserve the rat-derived assertion without claiming that the human endogenous LDLR route depends solely on direct μ2 recognition rather than accessory adaptors. Abstract-level reagent species and exact donor provenance remain unresolved. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. ensembl:ENSRNOP00000054900 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:12121421 recognition of the FDNPVY signal is mediated by a binding site in the mu2-subunit that is distinct from the site for the more general Yppà sorting signal |
| GO:0050750 low-density lipoprotein particle receptor binding | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Retain LDL-receptor-tail binding as a secondary interaction context. Reason: PMID:12121421 directly reports μ2 binding to FDNPVY and YppΦ peptides at distinct sites. Preserve the rat-derived assertion without claiming that the human endogenous LDLR route depends solely on direct μ2 recognition rather than accessory adaptors. Abstract-level reagent species and exact donor provenance remain unresolved. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:12121421 recognition of the FDNPVY signal is mediated by a binding site in the mu2-subunit that is distinct from the site for the more general Yppà sorting signal |
| GO:0065003 protein-containing complex assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain the reported accessory contribution to complex assembly. Reason: The cited reconstitution study reports that removal of AP50 impairs V-ATPase reassembly and that AP-2 restores it. This supports the existing broad assembly context, with in-vitro and reagent-species limits explicit. It does not establish ATP hydrolysis by ΞΌ2 or a second principal enzyme function. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. ensembl:ENSRNOP00000054900 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:7989329 The addition of purified AP-2 containing the AP50 polypeptide restores the ability of the V1 subunits to assemble with the V0 sector |
| GO:0065003 protein-containing complex assembly | TAS PMID:7989329 Activity and in vitro reassembly of the coated vesicle (H+)-... | KEEP AS NON CORE | Summary: Retain the reported accessory contribution to complex assembly. Reason: The cited reconstitution study reports that removal of AP50 impairs V-ATPase reassembly and that AP-2 restores it. This supports the existing broad assembly context, with in-vitro and reagent-species limits explicit. It does not establish ATP hydrolysis by ΞΌ2 or a second principal enzyme function. Supporting Evidence: PMID:7989329 The addition of purified AP-2 containing the AP50 polypeptide restores the ability of the V1 subunits to assemble with the V0 sector |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | UNDECIDED | Summary: The extracellular-vesicle detection remains unresolved. Reason: The urinary-exosome proteomics abstract does not expose the target-specific peptide/detection table. Intracellular coat function does not exclude extracellular-vesicle cargo, but it cannot establish this source-specific observation either. Preserve the HDA annotation without inferring a false localization from the paper's general scope. |
| GO:0072583 clathrin-dependent endocytosis | IBA GO_REF:0000033 | ACCEPT | Summary: AP2M1 contributes to clathrin-dependent endocytosis. Reason: Cargo recognition, membrane-recruited AP-2 architecture and ΞΌ2-dependent uptake directly establish the conserved process. Human-cell evidence and species-limited recombinant/animal assays are distinguished in the notes. For the IBA, the actual endocytosis IBD is present and target self-support is valid; full topology was not reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000242371 UNRESOLVED The actual PAINT node assertion was inspected in the local family export; full tree/MSA placement was not reconstructed. Target self-inclusion and donor count are not defects. Supporting Evidence: PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:31104773 Functional complementation of both the ΞΌ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2ΞΌ conditional knockout mice revealed a significant impairment of CME of transferrin. |
| GO:0072583 clathrin-dependent endocytosis | IDA PMID:23676497 Endocytosis of synaptic ADAM10 in neuronal plasticity and Al... | ACCEPT | Summary: AP2M1 contributes to clathrin-dependent endocytosis. Reason: Cargo recognition, membrane-recruited AP-2 architecture and ΞΌ2-dependent uptake directly establish the conserved process. Human-cell evidence and species-limited recombinant/animal assays are distinguished in the notes. For the IBA, the actual endocytosis IBD is present and target self-support is valid; full topology was not reconstructed. Supporting Evidence: PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:31104773 Functional complementation of both the ΞΌ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2ΞΌ conditional knockout mice revealed a significant impairment of CME of transferrin. |
| GO:0072583 clathrin-dependent endocytosis | IDA PMID:31104773 A Recurrent Missense Variant in AP2M1 Impairs Clathrin-Media... | ACCEPT | Summary: AP2M1 contributes to clathrin-dependent endocytosis. Reason: Cargo recognition, membrane-recruited AP-2 architecture and ΞΌ2-dependent uptake directly establish the conserved process. Human-cell evidence and species-limited recombinant/animal assays are distinguished in the notes. For the IBA, the actual endocytosis IBD is present and target self-support is valid; full topology was not reconstructed. Supporting Evidence: PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:31104773 Functional complementation of both the ΞΌ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2ΞΌ conditional knockout mice revealed a significant impairment of CME of transferrin. |
| GO:0072583 clathrin-dependent endocytosis | NAS PMID:29184887 Weak Molecular Interactions in Clathrin-Mediated Endocytosis... | ACCEPT | Summary: AP2M1 contributes to clathrin-dependent endocytosis. Reason: Cargo recognition, membrane-recruited AP-2 architecture and ΞΌ2-dependent uptake directly establish the conserved process. Human-cell evidence and species-limited recombinant/animal assays are distinguished in the notes. For the IBA, the actual endocytosis IBD is present and target self-support is valid; full topology was not reconstructed. Supporting Evidence: PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:31104773 Functional complementation of both the ΞΌ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2ΞΌ conditional knockout mice revealed a significant impairment of CME of transferrin. |
| GO:0072583 clathrin-dependent endocytosis | TAS PMID:12121421 The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY... | ACCEPT | Summary: AP2M1 contributes to clathrin-dependent endocytosis. Reason: Cargo recognition, membrane-recruited AP-2 architecture and ΞΌ2-dependent uptake directly establish the conserved process. Human-cell evidence and species-limited recombinant/animal assays are distinguished in the notes. For the IBA, the actual endocytosis IBD is present and target self-support is valid; full topology was not reconstructed. Supporting Evidence: PMID:19419997 We also identify tyrosine-995 of KIAA0319 as a critical amino acid required for the interaction with AP-2 and subsequent internalization. PMID:20603002 The AP2 adaptor complex (alpha, beta2, sigma2, and mu2 subunits) crosslinks the endocytic clathrin scaffold to PtdIns4,5P(2)-containing membranes and transmembrane protein cargo. PMID:31104773 Functional complementation of both the ΞΌ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2ΞΌ conditional knockout mice revealed a significant impairment of CME of transferrin. |
| GO:0097494 regulation of vesicle size | IMP PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: AP-2 organization contributes to vesicle-size regulation. Reason: The actual source shows that ΞΌ2 depletion changes coated-structure abundance and size, with rescue controls. The existing process annotation is consistent with coat organization; the directly demonstrated curvature sensor in this paper is CALM, not ΞΌ2. Supporting Evidence: PMID:25898166 AP2 depletion (of ΞΌ2) resulted in an βΌ12-fold decrease in the number of endocytic CCPs/CCVs |
| GO:0098794 postsynapse | IEA GO_REF:0000108 | ACCEPT | Summary: Retain the postsynaptic cargo-retrieval compartment. Reason: The inferred location follows the established postsynaptic receptor-internalization role, supported by the inspected adaptor review. This is an endocytic machinery pool rather than a claim that ΞΌ2 is a postsynaptic signaling receptor or scaffold. Propagation Review Root cause: NO FAILURE CORE Sources checked: GO:0098884 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:31671891 Since AP-2 is not only involved in the sorting of synaptic vesicle proteins, but also regulates the surface expression of postsynaptic neurotransmitter receptors |
| GO:0098884 postsynaptic neurotransmitter receptor internalization | IBA GO_REF:0000033 | ACCEPT | Summary: Retain postsynaptic neurotransmitter-receptor internalization. Reason: The inspected AP-2 sections of the cited review explicitly discuss postsynaptic receptor surface regulation as a cargo-sorting role. This is direct adaptor participation, not an annotation inferred solely from seizures. The actual PAINT IBD for this process is present; the exact rat experiments and full family topology were not independently reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000242374 UNRESOLVED The actual PAINT node assertion was inspected in the local family export; full tree/MSA placement was not reconstructed. Target self-inclusion and donor count are not defects. Supporting Evidence: PMID:31671891 Since AP-2 is not only involved in the sorting of synaptic vesicle proteins, but also regulates the surface expression of postsynaptic neurotransmitter receptors |
| GO:0098884 postsynaptic neurotransmitter receptor internalization | IEA GO_REF:0000107 | ACCEPT | Summary: Retain postsynaptic neurotransmitter-receptor internalization. Reason: The inspected AP-2 sections of the cited review explicitly discuss postsynaptic receptor surface regulation as a cargo-sorting role. This is direct adaptor participation, not an annotation inferred solely from seizures. The actual PAINT IBD for this process is present; the exact rat experiments and full family topology were not independently reconstructed. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. ensembl:ENSRNOP00000054900 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:31671891 Since AP-2 is not only involved in the sorting of synaptic vesicle proteins, but also regulates the surface expression of postsynaptic neurotransmitter receptors |
| GO:0098884 postsynaptic neurotransmitter receptor internalization | NAS PMID:31671891 Endocytic Adaptor Proteins in Health and Disease: Lessons fr... | ACCEPT | Summary: Retain postsynaptic neurotransmitter-receptor internalization. Reason: The inspected AP-2 sections of the cited review explicitly discuss postsynaptic receptor surface regulation as a cargo-sorting role. This is direct adaptor participation, not an annotation inferred solely from seizures. The actual PAINT IBD for this process is present; the exact rat experiments and full family topology were not independently reconstructed. Supporting Evidence: PMID:31671891 Since AP-2 is not only involved in the sorting of synaptic vesicle proteins, but also regulates the surface expression of postsynaptic neurotransmitter receptors |
| GO:0098894 extrinsic component of presynaptic endocytic zone membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Retain the peripheral presynaptic endocytic coat pool. Reason: The conserved AP-2 complex retrieves synaptic membrane cargo from the cytoplasmic surface. The existing rat transfer fits this peripheral endocytic role; it does not imply an integral membrane or neurotransmitter-release activity. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. ensembl:ENSRNOP00000054900 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:11102472 Microinjection of these peptides into squid giant presynaptic terminals reversibly blocked synaptic transmission and inhibited synaptic vesicle endocytosis by preventing coated pit formation at the plasma membrane. PMID:31671891 ΞΌ2-subunit also interacts with C2 domains as present in Synaptotagmin1 [11] or Otoferlin [12]. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Retain glutamatergic-synapse localization as a neuronal context. Reason: The electronic rat transfer is biologically compatible with postsynaptic receptor trafficking, but this named synapse type is a context of a broadly expressed cargo adaptor rather than its defining location. Exact donor localization experiments were not independently reconstructed; no contradictory evidence or taxon restriction is claimed. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. ensembl:ENSRNOP00000054900 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:31671891 the internalization of AMPA-type glutamate receptors by Synaptotagmin3 in addition to AP-2 [76]. |
| GO:0099003 vesicle-mediated transport in synapse | IEA GO_REF:0000117 | ACCEPT | Summary: Retain synaptic vesicle-mediated transport. Reason: The broad automated process fits AP-2-mediated retrieval and sorting at synapses. The specific ARBA rule is not reconstructed, and acceptance does not give ΞΌ2 the fusion or neurotransmitter-release chemistry of its cargo. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00027531 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:11102472 Microinjection of these peptides into squid giant presynaptic terminals reversibly blocked synaptic transmission and inhibited synaptic vesicle endocytosis by preventing coated pit formation at the plasma membrane. PMID:31671891 ΞΌ2-subunit also interacts with C2 domains as present in Synaptotagmin1 [11] or Otoferlin [12]. |
| GO:1900244 positive regulation of synaptic vesicle endocytosis | IEA GO_REF:0000107 | ACCEPT | Summary: Retain promotion of synaptic-vesicle endocytosis. Reason: The rat-derived regulatory annotation is consistent with the conserved coat-assembly/cargo-sorting contribution to retrieval. It does not assign ΞΌ2 an enzymatic regulatory step or infer a new disease process from perturbation alone. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P84092 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. ensembl:ENSRNOP00000054900 UNRESOLVED The exact donor experiment or electronic mapping was not reconstructed. Separately inspected target evidence is described in the rationale; no failure is inferred from donor count. Supporting Evidence: PMID:11102472 Microinjection of these peptides into squid giant presynaptic terminals reversibly blocked synaptic transmission and inhibited synaptic vesicle endocytosis by preventing coated pit formation at the plasma membrane. PMID:31671891 ΞΌ2-subunit also interacts with C2 domains as present in Synaptotagmin1 [11] or Otoferlin [12]. |
| GO:1903077 negative regulation of protein localization to plasma membrane | IMP PMID:19581412 Quantitative proteomics identifies a Dab2/integrin module re... | ACCEPT | Summary: AP-2 reduces cargo residence at the plasma membrane by internalization. Reason: The actual source includes ΞΌ2 depletion and reports increased surface integrins. ΞΌ2 supplies the internalizing adaptor machinery; the study's focus on DAB2 does not negate its explicitly assayed AP-2 controls. This is the existing removal/localization process, not an inferred transcriptional repression mechanism. Supporting Evidence: PMID:19581412 AP2 or clathrin depletion significantly increases surface Ξ±1, Ξ±5, and Ξ²1. |
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Download this section (compressed HTML)Q: Which target-specific assay establishes AP2M1 residence on mature lysosomal or endolysosomal membranes, as distinct from its coat on carriers carrying cargo to those destinations?
Q: Where does human AP2M1 lie relative to the GO:0006896 IBD and same-term IRD in the complete PAINT tree, and is there target-specific retention or loss evidence?
Q: Which exact interaction experiments support the unresolved generic screen pairs, and which distinguish direct sorting-signal recognition from coassembly or indirect association?
Q: How do the two human AP2M1 isoforms differ in cargo recognition and regulation under endogenous expression, beyond both tested isoforms binding HCV core?
Q: Would a dedicated endocytic sorting-motif binding term better distinguish μ2 recognition of cytoplasmic YxxΦ cargo tails from other localization-signal recognition? The current GO:0005048 definition already covers short protein-localization signals, so the present source-specific term remains applicable.
Experiment: Compare matched human AP2M1 isoforms and cargo-site mutants in AP-2 reconstitution and endogenous rescue, measuring motif binding, coat recruitment and receptor uptake separately.
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