AP2S1 encodes sigma2-adaptin (AP17), the 142-residue small subunit of the heterotetrameric AP-2 clathrin adaptor complex, the principal cargo-selection module of clathrin-mediated endocytosis at the plasma membrane. AP-2 comprises two large adaptins (alpha, either AP2A1 or AP2A2, and beta2/AP2B1), a medium subunit (mu2/AP2M1) and sigma2, and it assembles in the cytosol from alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane, where it reads sorting signals in the cytoplasmic tails of transmembrane cargo and links them to the clathrin lattice. The complex has two non-overlapping cargo sites on different subunits: mu2 reads tyrosine-based YxxPhi signals, while acidic dileucine signals are read by the alpha/sigma2 pair. Sigma2's own contribution is structurally defined -- the two leucines of the motif insert into adjacent hydrophobic pockets built from sigma2 residues (A63, L65, V88, N92, V98, L103, with N97 contacting the L-1 position), and sigma2 Arg15 together with alpha Arg21 forms the basic patch that binds the acidic residue four positions upstream. Sigma2 thus sits on the cytoplasmic face of the plasma membrane in forming clathrin-coated pits, and its folded longin-like domain has no catalytic activity of its own. Loss of the subunit is incompatible with endocytosis and, in mouse, with embryonic development; in humans, heterozygous missense substitutions of Arg15 weaken recognition of the dileucine motif of the calcium-sensing receptor, reducing its internalization and desensitising cells to extracellular calcium, which manifests as familial hypocalciuric hypercalcaemia type 3. Sigma2 also serves as a binding surface during ordered assembly of the complex: the chaperones AAGAB and CCDC32 both engage the alpha/sigma2 hemicomplex, CCDC32 doing so through a dileucine motif that mimics cargo.
Definition: Binding to an acidic dileucine sorting signal, a short linear motif of the form [D/E]xxxL[L/I] found in the cytoplasmic tails of transmembrane cargo proteins, which directs their selection into vesicles by heterotetrameric adaptor protein complexes.
Justification: GO can express binding of the tyrosine-based endocytic signal (GO:0089710 endocytic targeting sequence binding, whose definition requires 'an essential tyrosine (Y)') but has no term for the other major sorting signal, the acidic dileucine motif. Verified by QuickGO term lookup and by keyword searches for 'dileucine' (0 hits), 'sorting motif binding', 'internalization signal binding' and 'leucine motif', none of which returns a suitable molecular function. The gap has a direct annotation cost: the AP-2 sigma and alpha subunits, the AP-1 and AP-3 sigma subunits, and the GGA proteins that read the related DxxLL motif all lack an informative molecular function and fall back on bare protein binding. For AP2S1 specifically it is the reason eight GO:0005515 IPI rows cannot be upgraded, and the reason the disease mechanism of FHH3 -- weakened recognition of the CaSR dileucine motif by sigma2 Arg15 -- cannot be stated in GO terms. A sibling of GO:0089710 under GO:0005515 would mirror the existing structure exactly.
Parent term: protein binding
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: One of seven bare protein-binding rows citing AAGAB (Q6PD74, alpha- and gamma-adaptin-binding protein p34), each from a proteome-scale interactome deposition. The pairing is real and heavily replicated (UniProt records NbExp=12 for the IntAct interaction), but the mechanistic follow-up shows it is not a sigma2 activity: sigma2 does not bind AAGAB on its own, and only joins it once the alpha subunit is present, as part of an alpha:sigma2:AAGAB assembly intermediate. Reason: GO:0005515 states nothing about what AP2S1 does, and here it cannot be upgraded. Resolving the partner shows the association is alpha-dependent rather than a direct sigma2 binding activity, so no 'AAGAB binding'-style informative function is warranted on this subunit. The reference-projection test confirms these are catalogue depositions rather than statements about sigma2: counting distinct gene-product entities per reference in QuickGO with full pagination gives 1570 (PMID:25416956), 2324 (PMID:28514442), 449 (PMID:29892012), 746 (PMID:32296183), 4757 (PMID:33961781), 1394 (PMID:35271311), 1815 (PMID:40205054). The informative molecular function that AP2S1 does have -- recognition of acidic dileucine sorting signals -- has no GO term to modify to; that gap is recorded under proposed_new_terms and knowledge_gaps rather than papered over with an ill-fitting id. Supporting Evidence: PMID:31353312 Interestingly, while the Ο2 subunit itself did not associate with AAGAB in co-IP, it interacted with AAGAB when the Ξ± subunit was co-expressed PMID:31353312 We observed that the Ο2 subunit interacted stoichiometrically with AAGAB and the Ξ± subunit |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: One of seven bare protein-binding rows citing AAGAB (Q6PD74, alpha- and gamma-adaptin-binding protein p34), each from a proteome-scale interactome deposition. The pairing is real and heavily replicated (UniProt records NbExp=12 for the IntAct interaction), but the mechanistic follow-up shows it is not a sigma2 activity: sigma2 does not bind AAGAB on its own, and only joins it once the alpha subunit is present, as part of an alpha:sigma2:AAGAB assembly intermediate. Reason: GO:0005515 states nothing about what AP2S1 does, and here it cannot be upgraded. Resolving the partner shows the association is alpha-dependent rather than a direct sigma2 binding activity, so no 'AAGAB binding'-style informative function is warranted on this subunit. The reference-projection test confirms these are catalogue depositions rather than statements about sigma2: counting distinct gene-product entities per reference in QuickGO with full pagination gives 1570 (PMID:25416956), 2324 (PMID:28514442), 449 (PMID:29892012), 746 (PMID:32296183), 4757 (PMID:33961781), 1394 (PMID:35271311), 1815 (PMID:40205054). The informative molecular function that AP2S1 does have -- recognition of acidic dileucine sorting signals -- has no GO term to modify to; that gap is recorded under proposed_new_terms and knowledge_gaps rather than papered over with an ill-fitting id. Supporting Evidence: PMID:31353312 Interestingly, while the Ο2 subunit itself did not associate with AAGAB in co-IP, it interacted with AAGAB when the Ξ± subunit was co-expressed PMID:31353312 We observed that the Ο2 subunit interacted stoichiometrically with AAGAB and the Ξ± subunit |
| GO:0005515 protein binding | IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m... | MARK AS OVER ANNOTATED | Summary: One of seven bare protein-binding rows citing AAGAB (Q6PD74, alpha- and gamma-adaptin-binding protein p34), each from a proteome-scale interactome deposition. The pairing is real and heavily replicated (UniProt records NbExp=12 for the IntAct interaction), but the mechanistic follow-up shows it is not a sigma2 activity: sigma2 does not bind AAGAB on its own, and only joins it once the alpha subunit is present, as part of an alpha:sigma2:AAGAB assembly intermediate. Reason: GO:0005515 states nothing about what AP2S1 does, and here it cannot be upgraded. Resolving the partner shows the association is alpha-dependent rather than a direct sigma2 binding activity, so no 'AAGAB binding'-style informative function is warranted on this subunit. The reference-projection test confirms these are catalogue depositions rather than statements about sigma2: counting distinct gene-product entities per reference in QuickGO with full pagination gives 1570 (PMID:25416956), 2324 (PMID:28514442), 449 (PMID:29892012), 746 (PMID:32296183), 4757 (PMID:33961781), 1394 (PMID:35271311), 1815 (PMID:40205054). The informative molecular function that AP2S1 does have -- recognition of acidic dileucine sorting signals -- has no GO term to modify to; that gap is recorded under proposed_new_terms and knowledge_gaps rather than papered over with an ill-fitting id. Supporting Evidence: PMID:31353312 Interestingly, while the Ο2 subunit itself did not associate with AAGAB in co-IP, it interacted with AAGAB when the Ξ± subunit was co-expressed PMID:31353312 We observed that the Ο2 subunit interacted stoichiometrically with AAGAB and the Ξ± subunit |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: One of seven bare protein-binding rows citing AAGAB (Q6PD74, alpha- and gamma-adaptin-binding protein p34), each from a proteome-scale interactome deposition. The pairing is real and heavily replicated (UniProt records NbExp=12 for the IntAct interaction), but the mechanistic follow-up shows it is not a sigma2 activity: sigma2 does not bind AAGAB on its own, and only joins it once the alpha subunit is present, as part of an alpha:sigma2:AAGAB assembly intermediate. Reason: GO:0005515 states nothing about what AP2S1 does, and here it cannot be upgraded. Resolving the partner shows the association is alpha-dependent rather than a direct sigma2 binding activity, so no 'AAGAB binding'-style informative function is warranted on this subunit. The reference-projection test confirms these are catalogue depositions rather than statements about sigma2: counting distinct gene-product entities per reference in QuickGO with full pagination gives 1570 (PMID:25416956), 2324 (PMID:28514442), 449 (PMID:29892012), 746 (PMID:32296183), 4757 (PMID:33961781), 1394 (PMID:35271311), 1815 (PMID:40205054). The informative molecular function that AP2S1 does have -- recognition of acidic dileucine sorting signals -- has no GO term to modify to; that gap is recorded under proposed_new_terms and knowledge_gaps rather than papered over with an ill-fitting id. Supporting Evidence: PMID:31353312 Interestingly, while the Ο2 subunit itself did not associate with AAGAB in co-IP, it interacted with AAGAB when the Ξ± subunit was co-expressed PMID:31353312 We observed that the Ο2 subunit interacted stoichiometrically with AAGAB and the Ξ± subunit |
| GO:0005515 protein binding | IPI PMID:33859415 A genome-wide atlas of co-essential modules assigns function... | MARK AS OVER ANNOTATED | Summary: The one interaction row that is not a screen projection: only two entities in all of GOA cite PMID:33859415 for GO:0005515, AP2S1 and CCDC32 (Q9BV29, formerly C15orf57). UniProt's curated SUBUNIT line, written from the full text, records the interaction as direct and as the route by which CCDC32 associates with AP-2, and a subsequent structural study shows CCDC32 engaging the alpha/sigma2 hemicomplex through a canonical dileucine cargo motif -- i.e. through sigma2's own cargo-binding site. Reason: The interaction is genuine and mechanistically important, but the term recorded is bare protein binding, which conveys none of that. The activity it stands for is sigma2's recognition of an acidic dileucine motif, and GO has no molecular function for that: the nearest term, GO:0089710 endocytic targeting sequence binding, is defined for a signal 'with an essential tyrosine (Y)', which is the YxxPhi motif read by the mu2 subunit, not the dileucine motif read by sigma2. With no correct replacement available, the honest call is to mark the bare term over-annotated and register the missing term, rather than MODIFY to an id whose definition excludes this ligand. Supporting Evidence: PMID:33859415 We also show that C15orf57 encodes a protein that binds the AP2 complex, localizes to clathrin-coated pits and enables efficient transferrin uptake. PMID:42234739 CCDC32 contains two other binding sites for the Ξ±/Ο2 core, a canonical dileucine cargo motif and an Ξ±-helical domain that mimics an intramolecular interaction in the Ξ± subunit. file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: One of seven bare protein-binding rows citing AAGAB (Q6PD74, alpha- and gamma-adaptin-binding protein p34), each from a proteome-scale interactome deposition. The pairing is real and heavily replicated (UniProt records NbExp=12 for the IntAct interaction), but the mechanistic follow-up shows it is not a sigma2 activity: sigma2 does not bind AAGAB on its own, and only joins it once the alpha subunit is present, as part of an alpha:sigma2:AAGAB assembly intermediate. Reason: GO:0005515 states nothing about what AP2S1 does, and here it cannot be upgraded. Resolving the partner shows the association is alpha-dependent rather than a direct sigma2 binding activity, so no 'AAGAB binding'-style informative function is warranted on this subunit. The reference-projection test confirms these are catalogue depositions rather than statements about sigma2: counting distinct gene-product entities per reference in QuickGO with full pagination gives 1570 (PMID:25416956), 2324 (PMID:28514442), 449 (PMID:29892012), 746 (PMID:32296183), 4757 (PMID:33961781), 1394 (PMID:35271311), 1815 (PMID:40205054). The informative molecular function that AP2S1 does have -- recognition of acidic dileucine sorting signals -- has no GO term to modify to; that gap is recorded under proposed_new_terms and knowledge_gaps rather than papered over with an ill-fitting id. Supporting Evidence: PMID:31353312 Interestingly, while the Ο2 subunit itself did not associate with AAGAB in co-IP, it interacted with AAGAB when the Ξ± subunit was co-expressed PMID:31353312 We observed that the Ο2 subunit interacted stoichiometrically with AAGAB and the Ξ± subunit |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | MARK AS OVER ANNOTATED | Summary: One of seven bare protein-binding rows citing AAGAB (Q6PD74, alpha- and gamma-adaptin-binding protein p34), each from a proteome-scale interactome deposition. The pairing is real and heavily replicated (UniProt records NbExp=12 for the IntAct interaction), but the mechanistic follow-up shows it is not a sigma2 activity: sigma2 does not bind AAGAB on its own, and only joins it once the alpha subunit is present, as part of an alpha:sigma2:AAGAB assembly intermediate. Reason: GO:0005515 states nothing about what AP2S1 does, and here it cannot be upgraded. Resolving the partner shows the association is alpha-dependent rather than a direct sigma2 binding activity, so no 'AAGAB binding'-style informative function is warranted on this subunit. The reference-projection test confirms these are catalogue depositions rather than statements about sigma2: counting distinct gene-product entities per reference in QuickGO with full pagination gives 1570 (PMID:25416956), 2324 (PMID:28514442), 449 (PMID:29892012), 746 (PMID:32296183), 4757 (PMID:33961781), 1394 (PMID:35271311), 1815 (PMID:40205054). The informative molecular function that AP2S1 does have -- recognition of acidic dileucine sorting signals -- has no GO term to modify to; that gap is recorded under proposed_new_terms and knowledge_gaps rather than papered over with an ill-fitting id. Supporting Evidence: PMID:31353312 Interestingly, while the Ο2 subunit itself did not associate with AAGAB in co-IP, it interacted with AAGAB when the Ξ± subunit was co-expressed PMID:31353312 We observed that the Ο2 subunit interacted stoichiometrically with AAGAB and the Ξ± subunit |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: One of seven bare protein-binding rows citing AAGAB (Q6PD74, alpha- and gamma-adaptin-binding protein p34), each from a proteome-scale interactome deposition. The pairing is real and heavily replicated (UniProt records NbExp=12 for the IntAct interaction), but the mechanistic follow-up shows it is not a sigma2 activity: sigma2 does not bind AAGAB on its own, and only joins it once the alpha subunit is present, as part of an alpha:sigma2:AAGAB assembly intermediate. Reason: GO:0005515 states nothing about what AP2S1 does, and here it cannot be upgraded. Resolving the partner shows the association is alpha-dependent rather than a direct sigma2 binding activity, so no 'AAGAB binding'-style informative function is warranted on this subunit. The reference-projection test confirms these are catalogue depositions rather than statements about sigma2: counting distinct gene-product entities per reference in QuickGO with full pagination gives 1570 (PMID:25416956), 2324 (PMID:28514442), 449 (PMID:29892012), 746 (PMID:32296183), 4757 (PMID:33961781), 1394 (PMID:35271311), 1815 (PMID:40205054). The informative molecular function that AP2S1 does have -- recognition of acidic dileucine sorting signals -- has no GO term to modify to; that gap is recorded under proposed_new_terms and knowledge_gaps rather than papered over with an ill-fitting id. Supporting Evidence: PMID:31353312 Interestingly, while the Ο2 subunit itself did not associate with AAGAB in co-IP, it interacted with AAGAB when the Ξ± subunit was co-expressed PMID:31353312 We observed that the Ο2 subunit interacted stoichiometrically with AAGAB and the Ξ± subunit |
| GO:0005829 cytosol | TAS Reactome:R-HSA-167537 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-167537), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-167597 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-167597), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-167601 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-167601), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182171 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-182171), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182186 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-182186), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-182198 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-182198), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-3928654 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-3928654), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5138433 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-5138433), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5138459 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-5138459), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8856808 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8856808), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8856813 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8856813), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8862280 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8862280), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8866277 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8866277), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8866283 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8866283), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867754 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8867754), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8867756 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8867756), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868071 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8868071), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868072 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8868072), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868230 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8868230), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868236 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8868236), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868648 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8868648), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868651 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8868651), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868658 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8868658), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868659 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8868659), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868660 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8868660), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8868661 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8868661), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8869438 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8869438), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871193 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8871193), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871194 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8871194), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8871196 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-8871196), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9681616 | KEEP AS NON CORE | Summary: One of thirty-one identical Reactome cytosol rows. The underlying biology is real -- AP-2 is assembled in the cytosol and cycles between a soluble pool and the membrane -- but this row is a participant-compartment assignment attached to a Reactome reaction (Reactome:R-HSA-9681616), not an observation about AP2S1. Reason: Keeping rather than removing, because the soluble cytosolic pool is genuine: AP-2 assembles in the cytosol from the alpha/sigma2 and beta2/mu2 hemicomplexes before being recruited to PtdIns(4,5)P2-containing membrane. Non-core, because the cytosol is where the complex waits rather than where AP2S1 does anything; the functionally informative locations are the clathrin-coated pit and the cytoplasmic face of the plasma membrane. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: PMID:31353312 The AP2 adaptor complex assembles in the cytosol PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt SubCell-to-GO mapping of the record's own 'Cell membrane' subcellular-location line. Correct and independently corroborated. Reason: AP-2 is a peripheral protein on the cytoplasmic face of the plasma membrane, recruited there by PtdIns(4,5)P2 and cargo motifs. The mapping reproduces a curated UniProt statement rather than inferring anything new. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB-SubCell:SL-0039 Β· UniProt SubCell: Cell membrane SUPPORTS TRANSFER UniProt controlled-vocabulary subcellular-location term 'Cell membrane', mapped 1:1 to GO:0005886. The record's own SUBCELLULAR LOCATION line carries it, so the mapping reproduces a curated statement rather than inferring a new one. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Plasma membrane transferred under GO_REF:0000024 with UniProtKB:P63010 as the source. P63010 is AP2B1, the beta-2 subunit of the same AP-2 complex -- a co-complex partner, not a sequence orthologue or paralogue of sigma2. UniProt uses ECO:0000250 with that accession as a complex-level 'inferred from' marker, and the conclusion it reaches is correct. Reason: The destination is right and is confirmed several other ways: the ComplexPortal NAS row places AP-2 on the cytoplasmic side of the plasma membrane, UniProt curates a coated-pit location from PubMed:33859415, and live imaging finds AP-2 at essentially all static clathrin spots. What is worth flagging is the shape of the inference rather than its outcome: an ISS whose source is a different subunit of the same complex is a complex-membership argument wearing sequence-similarity clothing. It is sound here because AP-2 is an obligate heterotetramer, but it is not the evidence the code implies. Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:P63010 Β· AP2B1 (Homo sapiens) SUPPORTS TRANSFER AP2B1_HUMAN, the beta-2 subunit of the same AP-2 complex -- not a sequence orthologue of sigma2 and not a paralogue of it. UniProt uses ECO:0000250 with this accession as a complex-level 'inferred from' marker rather than a similarity claim, so the transfer is sound about the destination (AP-2 works at the plasma membrane) while being weak as a sequence inference. The conclusion is independently confirmed by the ComplexPortal NAS row for the cytoplasmic face of the plasma membrane and by UniProt's own coated-pit location. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-177479 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-177479). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2130640 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-2130640). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2130725 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-2130725). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-392748 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-392748). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-392749 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-392749). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-445071 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-445071). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-445079 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-445079). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-555065 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-555065). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6784729 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-6784729). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6784735 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-6784735). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8855130 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8855130). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8855131 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8855131). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8866279 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8866279). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867754 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8867754). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8867756 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8867756). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868071 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8868071). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868072 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8868072). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868230 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8868230). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868236 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8868236). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868648 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8868648). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868651 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8868651). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-8868661 | ACCEPT | Summary: One of twenty-two Reactome plasma-membrane rows (Reactome:R-HSA-8868661). Unlike the cytosol and endolysosome rows, the compartment this one assigns is exactly where AP-2 works. Reason: The plasma membrane is where AP-2 is recruited, where it reads cargo motifs and where clathrin-coated pits form; GO's own structure already places the AP-2 adaptor complex there (GO:0005886 is among GO:0030122's ancestors). The row is redundant with twenty-one siblings and with the UniProt SubCell IEA and the ISS row, but redundancy is not error and the location is core. The reference-projection test settles what this row is. Querying QuickGO by reference and paginating fully, the Reactome reactions behind AP2S1's cellular-component rows assign the same compartment to every participant of the reaction -- R-HSA-8868658 alone reaches 104 gene products. 47 distinct Reactome reaction ids contribute AP2S1's 60 Reactome rows, and every one of those rows is a cellular-component row: Reactome supplies this gene no biological-process term at all. These are participant-compartment assignments imported wholesale, not per-gene author statements. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0006886 intracellular protein transport | IEA GO_REF:0000002 | ACCEPT | Summary: Intracellular protein transport, mapped from the family-wide clathrin small-chain signature IPR000804. Broad but true: clathrin-mediated endocytosis moves plasma-membrane proteins into the endosomal system. Reason: A generic InterPro2GO mapping from a signature shared by all AP-complex sigma subunits, so it cannot be more specific than the family's common role. It is correct for AP2S1 and sits above the AP-2-specific terms GO:0072583 and GO:0016192 that the record already carries, so no modification is warranted. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: InterPro:IPR000804 Β· InterPro IPR000804 Clathrin_sm-chain_CS SUPPORTS TRANSFER Clathrin adaptor small-chain signature (PROSITE PS00989 CLAT_ADAPTOR_S), matched by AP2S1 per its own DR lines. A family-wide signature shared with the AP-1, AP-3 and AP-4 sigma subunits, so terms mapped from it are necessarily family-level. Supporting Evidence: PMID:12086608 AP2 functions in clathrin-mediated endocytosis, the process whereby cargo enters the endosomal system from the plasma membrane. PMID:31671891 For efficient internalization, the cargo proteins need to be linked to the endocytic machinery via adaptor proteins such as the heterotetrameric endocytic adaptor complex AP-2 and a variety of mostly monomeric endocytic adaptors. |
| GO:0009898 cytoplasmic side of plasma membrane | NAS PMID:29184887 Weak Molecular Interactions in Clathrin-Mediated Endocytosis... | ACCEPT | Summary: Cytoplasmic side of the plasma membrane, a ComplexPortal statement applied to all fourteen AP-2 entities (four ComplexPortal complexes plus the five human and five mouse subunits). The most informative location term on the whole record. Reason: Exactly right and exactly specific: AP-2 is a peripheral complex on the cytoplasmic leaflet, reading cargo tails that project into the cytosol while holding PtdIns(4,5)P2 in the membrane. It is a complex-level statement rather than a sigma2-specific one -- fourteen entities share it -- but sigma2 is an obligate subunit and one of the two subunits that contact the dileucine motif, so the location is its own. Core. Supporting Evidence: PMID:29184887 The key stages in this step-wise process, from the starting point of cargo recognition, to the later stage of assembly of the clathrin coat, are dependent on weak interactions between a large network of proteins. PMID:19140243 The major recognition events are the two leucine residues binding in hydrophobic pockets on Ο2. file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane |
| GO:0015031 protein transport | IEA GO_REF:0000002 | ACCEPT | Summary: Protein transport from IPR016635 (AP complex small subunit). The broadest transport term on the record. Reason: Correct and harmless: it is a parent of the intracellular protein transport and vesicle-mediated transport terms already present. An IEA being broader than the literature-supported term is acceptable; the mapping is not wrong, only uninformative. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: InterPro:IPR016635 Β· InterPro IPR016635 AP_complex_ssu SUPPORTS TRANSFER AP complex small subunit (PIRSF015588), the family-level entry AP2S1 matches. Again family-level rather than AP-2-specific. Supporting Evidence: PMID:12086608 AP2 functions in clathrin-mediated endocytosis, the process whereby cargo enters the endosomal system from the plasma membrane. |
| GO:0016020 membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: The UniProt 'Membrane' subcellular-location keyword mapped to GO:0016020. True of a peripheral membrane protein, and the least informative location on the record. Reason: AP2S1 has no transmembrane segment; it reaches membranes as part of AP-2, which binds the cytoplasmic leaflet through PtdIns(4,5)P2 and cargo motifs. The term is correct but carries no information beyond the plasma-membrane, coated-pit and cytoplasmic-face terms already present, so it is kept as non-core rather than accepted as a statement of where AP2S1 acts. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB-SubCell:SL-0162 Β· UniProt SubCell: Membrane SUPPORTS TRANSFER UniProt controlled-vocabulary term 'Membrane', mapped 1:1 to GO:0016020. True of a peripheral membrane protein, but the least informative location the record supports. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane |
| GO:0016192 vesicle-mediated transport | IBA GO_REF:0000033 | ACCEPT | Summary: The family's single PAINT inference, and it is placed correctly. Node PTN000204281 is the only PTN node in PTHR11753, and its GO:0016192 IBD is seeded by sigma subunits of three different AP complexes: the AP-3 sigmas of budding yeast and Candida (Golgi-to-vacuole transport, IMP), the AP-1 sigmas of yeast, fission yeast, fly and mouse (endosome-to-Golgi retrieval and synaptic-vesicle budding, IDA/IMP), and the AP-2 sigmas of fly, worm, rat and human (clathrin-dependent endocytosis, IMP/IDA). Human AP2S1 is inside that clade -- UniProt assigns it to PTHR11753 -- and its cargo-binding surface is intact, so the inference transfers cleanly. Reason: Vesicle-mediated transport is true of AP2S1 and is core: the AP-2 heterotetramer it belongs to is the cargo-selection module of clathrin-mediated endocytosis, and cells lacking AP2S1 fail to internalise cargo at all. The term is broad, but that breadth is the right answer rather than a defect. The node's seeds do not agree on a pathway -- AP-3 seeds act between Golgi and vacuole, AP-1 seeds between endosome and Golgi, AP-2 seeds at the plasma membrane -- so their last common ancestor supports nothing more specific than vesicle-mediated transport, and GRANULARITY_MISMATCH (which applies only when donors agree and a finer term was available) does not. The more specific human-appropriate term GO:0072583 is separately annotated three times, so nothing is lost. There is no IRD or IKR anywhere in this family's PAINT slice, and no target-specific evidence of loss or divergence: the eight residues that build sigma2's dileucine-binding site are all present in P53680. Bookkeeping note, recorded rather than explained: the GOA/QuickGO WITH/FROM carries eleven gene donors while the current local PAINT slice lists ten seeds for this term, the extra one (FB:FBgn0043012) appearing in the same node's GO:0043231 seed list. Propagation Review Root cause: NO FAILURE CORE Sources checked: CGD:CAL0000182525 Β· APS3 (Candida albicans) SUPPORTS TRANSFER Resolves to Q59QC5, Candida albicans APS3, the AP-3 complex sigma subunit. Its experimental grounding is GO:0006896 Golgi-to-vacuole transport (IMP, PMID:20870878) -- a different vesicle pathway from AP-2, which is why the node sits at the vesicle-mediated-transport parent. FB:FBgn0039132 Β· AP-1sigma (Drosophila melanogaster) SUPPORTS TRANSFER Resolves to Drosophila AP-1sigma (four TrEMBL entries share the cross-reference; B8A403 carries the family IBA and a GO:0016192 NAS from PMID:11598180). An AP-1 subunit, so again a different pathway from the target's. FB:FBgn0043012 Β· AP-2sigma (Drosophila melanogaster) SUPPORTS TRANSFER Resolves to Q9VDC3, Drosophila AP-2sigma -- the fly orthologue of the target. It carries GO:0035615 clathrin-cargo adaptor activity by IMP (PMID:20226669), so the AP-2 branch of this node has its own experimental endocytic evidence. MGI:MGI:1098244 Β· Ap1s1 (Mus musculus) SUPPORTS TRANSFER Resolves to P61967, mouse Ap1s1 (AP-1 complex subunit sigma-1A), which carries GO:0042147 retrograde endosome-to-Golgi transport by IMP (PMID:24928897). MGI:MGI:1889383 Β· Ap1s2 (Mus musculus) SUPPORTS TRANSFER Resolves to Q9DB50, mouse Ap1s2, which carries GO:0016192 itself by IMP (PMID:24928897) plus GO:0016182 synaptic vesicle budding from endosome by IDA (PMID:20203623). One of the strongest direct experimental anchors for the transferred term. PANTHER:PTN000204281 SUPPORTS TRANSFER PTHR11753 ADAPTOR COMPLEXES SMALL SUBUNIT FAMILY IBD node (the family's only PTN node; seeded by AP-1, AP-2 and AP-3 sigma subunits from fungi, flies, nematodes, rodents and human). Human AP2S1 is inside the clade: UniProt assigns it to PTHR11753, and it is itself one of the node's seeds. PomBase:SPAP27G11.06c Β· vas2 (Schizosaccharomyces pombe) SUPPORTS TRANSFER Resolves to Q9P7N2, S. pombe vas2 (AP-1 complex subunit sigma-1), with GO:0042147 and GO:0099638 by IDA (PMID:19624755). Extends the node's experimental span to fission yeast. RGD:620188 Β· Ap2s1 (Rattus norvegicus) SUPPORTS TRANSFER Resolves to P62744, rat Ap2s1 -- the direct rodent orthologue, identical to the human protein over all 142 residues. It carries GO:0098884 postsynaptic neurotransmitter receptor internalization by IDA and EXP (PMID:17289840). SGD:S000003561 Β· APS3 (Saccharomyces cerevisiae) SUPPORTS TRANSFER Resolves to P47064, S. cerevisiae APS3 (AP-3 sigma), GO:0006896 by IMP (PMID:9335339). A fungal AP-3 seed, again in a non-endocytic pathway. SGD:S000004160 Β· APS1 (Saccharomyces cerevisiae) SUPPORTS TRANSFER Resolves to P35181, S. cerevisiae APS1 (AP-1 sigma-1), GO:0006896 by IMP (PMID:17003107). UniProtKB:P53680 Β· AP2S1 (Homo sapiens, the target) SUPPORTS TRANSFER The target itself. AP2S1's own GO:0048488 IDA and IMP (PMID:11102472) are among the descendant evidences the PAINT curator had in view when placing the IBD, so its appearance here is expected and is a marker that experimental grounding exists on the target, not a circular transfer. WB:WBGene00000157 Β· aps-2 (Caenorhabditis elegans) SUPPORTS TRANSFER Resolves to Q19123, C. elegans aps-2 (AP complex subunit sigma, 142 aa, PTHR11753), which carries GO:0072583 clathrin-dependent endocytosis by IMP (PMID:25303366). Not a UniProtKB accession, so not a key in PTHR11753-entries.csv; resolved instead through UniProt's own WormBase cross-reference line on Q19123. Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt DR PANTHER; PTHR11753; ADAPTOR COMPLEXES SMALL SUBUNIT FAMILY; 1. PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer PMID:31353312 the uptake of the cargo reporter was abolished in AAGAB KO cells or cells deficient in AP2S1, which encodes the Ο2 subunit of AP2 adaptor file:human/AP2S1/AP2S1-bioinformatics/RESULTS.md All eight positions match the literature: **True** |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000002 | ACCEPT | Summary: Vesicle-mediated transport from two InterPro entries, the family-wide IPR000804 and the AP-2-specific IPR027156. The same term the PAINT node assigns, reached independently by signature matching. Reason: Correct and core. That the AP-2-specific entry IPR027156 also maps to this term, alongside the family-wide one, means the annotation is not merely a family generalisation. Redundant with the IBA and NAS rows for the same term, which is fine. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR000804 Β· InterPro IPR000804 Clathrin_sm-chain_CS SUPPORTS TRANSFER Clathrin adaptor small-chain signature (PROSITE PS00989 CLAT_ADAPTOR_S), matched by AP2S1 per its own DR lines. A family-wide signature shared with the AP-1, AP-3 and AP-4 sigma subunits, so terms mapped from it are necessarily family-level. InterPro:IPR027156 Β· InterPro IPR027156 APS2 SUPPORTS TRANSFER APS2 -- the InterPro entry specific to the AP-2 sigma subunit, matched by AP2S1. Because it is subfamily-specific rather than family-wide, terms mapped from it (GO:0035615, GO:0072583) are AP-2-specific and not over-generalised. Supporting Evidence: PMID:12086608 AP2 functions in clathrin-mediated endocytosis, the process whereby cargo enters the endosomal system from the plasma membrane. PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0016192 vesicle-mediated transport | NAS PMID:15941406 Analysis of the AP-2 adaptor complex and cargo during clathr... | ACCEPT | Summary: Vesicle-mediated transport, ComplexPortal, from the live-imaging study of AP-2 and clathrin dynamics. Fourteen entities carry this reference for this term. Reason: Correct and core, and the same term the PAINT node assigns. Complex-level, as the projection count shows, but AP2S1 is an obligate part of the complex whose dynamics the paper measured. Supporting Evidence: PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots PMID:12086608 AP2 functions in clathrin-mediated endocytosis, the process whereby cargo enters the endosomal system from the plasma membrane. |
| GO:0030100 regulation of endocytosis | TAS PMID:10753805 Clathrin coat construction in endocytosis. | MODIFY | Summary: Regulation of endocytosis, a legacy UniProt TAS from a structural review of clathrin coat construction. Notably this reference projects to exactly one entity in all of GOA -- AP2S1 -- and the cached record is abstract-only, its abstract discussing the clathrin cage, the mu2 subunit and the alpha-appendage without mentioning the sigma subunit. Reason: GO:0030100 is defined as 'Any process that modulates the frequency, rate or extent of endocytosis'. AP-2 does not modulate clathrin-mediated endocytosis; it is the cargo-selection machinery that carries it out, and cargo uptake fails outright in cells deficient in AP2S1. Annotating core machinery as a regulator of its own process is a role conflation, and the correct term is the process itself. Proposing GO:0072583, which the record already carries from three better-grounded rows, so the modification loses no information and removes a misleading regulatory reading. MODIFY rather than REMOVE because the annotation is not false about the biology, only about the role: the cited review really is discussing AP-2 in endocytosis, and the curator's intent is recoverable as the process term. The two actions have the same net effect on the term set here, since GO:0072583 is already present three times; MODIFY is preferred because it records what the row was trying to say, which REMOVE would discard. If GOA would rather retire the row outright, the MISCITED mark on PMID:10753805 carries the same information. Proposed replacements: clathrin-dependent endocytosis Supporting Evidence: PMID:31353312 the uptake of the cargo reporter was abolished in AAGAB KO cells or cells deficient in AP2S1, which encodes the Ο2 subunit of AP2 adaptor PMID:23222959 AP2S1 mutations decreased the sensitivity of CaSR-expressing cells to extracellular calcium and reduced CaSR endocytosis |
| GO:0030117 membrane coat | IEA GO_REF:0000002 | ACCEPT | Summary: Membrane coat, from the family-wide clathrin small-chain signature. Reason: GO:0030117 is an ancestor of GO:0030122 AP-2 adaptor complex in GO's own structure, so this is the correct but less specific parent of a term the record already carries four times. A broader IEA sitting above a well-supported specific term needs no correction. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: InterPro:IPR000804 Β· InterPro IPR000804 Clathrin_sm-chain_CS SUPPORTS TRANSFER Clathrin adaptor small-chain signature (PROSITE PS00989 CLAT_ADAPTOR_S), matched by AP2S1 per its own DR lines. A family-wide signature shared with the AP-1, AP-3 and AP-4 sigma subunits, so terms mapped from it are necessarily family-level. Supporting Evidence: PMID:12086608 AP2 functions in clathrin-mediated endocytosis, the process whereby cargo enters the endosomal system from the plasma membrane. |
| GO:0030122 AP-2 adaptor complex | IEA GO_REF:0000120 | ACCEPT | Summary: AP-2 adaptor complex from ARBA rule ARBA00027293, with the mouse orthologue and the AP-2-specific InterPro entry also cited. The rule was fetched and its conditions read: the set that fires is FunFam 3.30.450.60:FF:000004 within Chordata, which AP2S1 satisfies exactly. Reason: The defining fact about this protein, reached here by a correctly-conditioned rule. GO:0030122's own definition names sigma2 as one of the four subunits, and the structural literature resolves AP2S1 within the 200 kDa AP-2 core. Core. The affinage record is cited here only for its definitional framing of what the gene encodes, which it states without mechanism; every mechanistic claim in this review is grounded on UniProt or a primary publication. Propagation Review Root cause: NO FAILURE CORE Sources checked: ARBA:ARBA00027293 Β· ARBA00027293 (GO:0030122 rule) SUPPORTS TRANSFER Fetched from the UniProt ARBA endpoint: the rule annotates GO:0030122 and the condition set that fires here is FunFam 3.30.450.60:FF:000004 within Chordata. AP2S1 carries exactly that FunFam assignment (DR FunFam; 3.30.450.60:FF:000004) and is a chordate protein, so the rule is correctly applied. UniProtKB:P62743 Β· Ap2s1 (Mus musculus) SUPPORTS TRANSFER Mouse Ap2s1, the orthologue used by the Ensembl Compara projection. Identical to human AP2S1 over all 142 residues (checked live in the bioinformatics analysis), so orthology-based transfer between them is as safe as it gets. ensembl:ENSMUSP00000083281 SUPPORTS TRANSFER The mouse Ensembl protein backing the same Compara projection; the protein-level identifier for the P62743 orthologue named alongside it. InterPro:IPR027156 Β· InterPro IPR027156 APS2 SUPPORTS TRANSFER APS2 -- the InterPro entry specific to the AP-2 sigma subunit, matched by AP2S1. Because it is subfamily-specific rather than family-wide, terms mapped from it (GO:0035615, GO:0072583) are AP-2-specific and not over-generalised. Supporting Evidence: PMID:12086608 AP2 functions in clathrin-mediated endocytosis, the process whereby cargo enters the endosomal system from the plasma membrane. file:human/AP2S1/AP2S1-uniprot.txt of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer file:human/AP2S1/AP2S1-deep-research-affinage.md AP2S1 encodes the Ο2 (AP17) subunit of the heterotetrameric AP2 clathrin adaptor complex, which links clathrin to the plasma membrane and recognizes tyrosine- and dileucine-based sorting motifs of cargo proteins during clathrin-mediated endocytosis |
| GO:0030122 AP-2 adaptor complex | NAS PMID:12086608 Molecular architecture and functional model of the endocytic... | ACCEPT | Summary: AP-2 adaptor complex, ComplexPortal, citing the 2.6 A structure of the AP2 core in which sigma2 is one of the four resolved chains. Reason: Directly supported: the cited structure contains sigma2 as a component of the crystallised 200 kDa core, so this is not a case where a complex-level reference fails to speak to the subunit. Core. Supporting Evidence: PMID:12086608 AP2 functions in clathrin-mediated endocytosis, the process whereby cargo enters the endosomal system from the plasma membrane. file:human/AP2S1/AP2S1-uniprot.txt of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type |
| GO:0030122 AP-2 adaptor complex | TAS PMID:10753805 Clathrin coat construction in endocytosis. | ACCEPT | Summary: AP-2 adaptor complex, the second of the three UniProt TAS terms from the Pearse 2000 review. Reason: Correct, whatever the provenance: sigma2 is one of the four chains of AP-2, established structurally and encoded in GO:0030122's own definition. The row adds nothing the ARBA, ComplexPortal and BHF-UCL rows do not already say, but it is not wrong. Supporting Evidence: PMID:12086608 AP2 functions in clathrin-mediated endocytosis, the process whereby cargo enters the endosomal system from the plasma membrane. file:human/AP2S1/AP2S1-uniprot.txt of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type |
| GO:0030122 AP-2 adaptor complex | TAS PMID:12121421 The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY... | ACCEPT | Summary: AP-2 adaptor complex, BHF-UCL, from Boll et al. 2002. This reference is a textbook projection: exactly five entities -- AP2A1, AP2A2, AP2B1, AP2M1 and AP2S1 -- each receive the identical triple GO:0030122 / GO:0035615 / GO:0072583 as TAS, although the paper's experiments are entirely on the mu2 subunit. Reason: One complex-level statement copied to five subunits is one statement, not five; but the statement is true of sigma2, which really is one of the four chains of AP-2, and much better evidence exists for that elsewhere on this record (the AP2 core structure, the ARBA/FunFam rule, ComplexPortal). Accepted on those grounds, with the projection noted so the row is not mistaken for independent support. Supporting Evidence: PMID:12121421 We show that 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 PMID:12086608 AP2 functions in clathrin-mediated endocytosis, the process whereby cargo enters the endosomal system from the plasma membrane. file:human/AP2S1/AP2S1-uniprot.txt of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type |
| GO:0030666 endocytic vesicle membrane | TAS Reactome:R-HSA-416639 | KEEP AS NON CORE | Summary: Reactome row from R-HSA-416639 'Trafficking of GluR2-containing AMPA receptors to extrasynaptic sites', placing AP2S1 on the endocytic vesicle membrane. Reason: Same reasoning as the clathrin-coated endocytic vesicle membrane row: GO:0030666 is an ancestor of GO:0030122, so complex membership entails it, and it is a parent of the more specific coated-vesicle term also present. True but uninformative, and one step removed from where sigma2 acts. Supporting Evidence: PMID:25898166 The three most abundant proteins in mammalian endocytic CCVs are clathrin and the two cargo-selecting, clathrin adaptors, CALM and AP2. PMID:42234739 AP-2 is composed of two large subunits (Ξ± and Ξ²2), a medium subunit (ΞΌ2), and a small subunit (Ο2) that assemble hierarchically from hemicomplexes (Ξ±/Ο2 and Ξ²2/ΞΌ2) before forming the final heterotetramer |
| GO:0030669 clathrin-coated endocytic vesicle membrane | TAS Reactome:R-HSA-5138459 | KEEP AS NON CORE | Summary: Reactome row from R-HSA-5138459 'WNT5A:FZD4 is endocytosed', placing AP2S1 on the clathrin-coated endocytic vesicle membrane. Reason: Kept, unlike the endolysosome rows, because GO's own structure entails it: GO:0030669 is an ancestor of GO:0030122 AP-2 adaptor complex, so a protein in AP-2 is in the coated endocytic vesicle membrane by construction. Proteomics agrees, finding AP2 among the three most abundant proteins of mammalian endocytic CCVs. Non-core because AP-2's functional residence is the forming coated pit rather than the budded vesicle, from which live imaging shows it is largely absent by the moment of scission -- a tension recorded as a knowledge gap rather than resolved here. Supporting Evidence: PMID:25898166 The three most abundant proteins in mammalian endocytic CCVs are clathrin and the two cargo-selecting, clathrin adaptors, CALM and AP2. PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots |
| GO:0035615 clathrin-cargo adaptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Clathrin-cargo adaptor activity mapped from IPR027156, the InterPro entry specific to the AP-2 sigma subunit rather than to the sigma family as a whole. Reason: The activity is a property of the assembled complex rather than of sigma2 alone -- bringing cargo together with clathrin needs the beta2 clathrin box and the alpha trunk as well -- so this is a contributory annotation in substance. It is nevertheless the best molecular function GO currently offers for this protein, and sigma2's contribution to it is direct and structurally resolved: the two leucines of an acidic dileucine motif bind pockets built from sigma2 residues. Accepted, with the caveat recorded in core_functions as contributes_to_molecular_function rather than molecular_function. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR027156 Β· InterPro IPR027156 APS2 SUPPORTS TRANSFER APS2 -- the InterPro entry specific to the AP-2 sigma subunit, matched by AP2S1. Because it is subfamily-specific rather than family-wide, terms mapped from it (GO:0035615, GO:0072583) are AP-2-specific and not over-generalised. Supporting Evidence: PMID:19140243 The major recognition events are the two leucine residues binding in hydrophobic pockets on Ο2. PMID:19140243 binds in two adjacent hydrophobic pockets on the small Ο2 subunit that are lined by a number of hydrophobic residues PMID:19140243 Mutation of a number of these to hydrophilic residues (Ο2L65S, Ο2V88D, Ο2V98S or Ο2L103S), or filling in the pocket by replacement of Ο2A63 or Ο2N92 with tryptophan, strongly inhibited binding of recombinant AP2 core complexes to different dileucine motifs |
| GO:0035615 clathrin-cargo adaptor activity | TAS PMID:12121421 The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY... | ACCEPT | Summary: Clathrin-cargo adaptor activity, BHF-UCL, from the same five-way projection. The cited paper maps the FDNPVY and YxxPhi sites on mu2 and says nothing about sigma2 -- so the row is right about the conclusion and silent about this subunit's contribution to it. Reason: Kept because the conclusion is correct and because the real evidence for sigma2's part in it is strong, just located in a different paper: the AP2-CD4 dileucine co-crystal shows the motif's two leucines binding pockets on sigma2, with six pocket mutations abolishing binding while PtdIns(4,5)P2 and YxxPhi binding are unaffected. That control is what makes the assignment subunit-specific rather than inherited from the complex. Graded as a contributory activity in core_functions, since generating a coated vesicle needs the whole adaptor. Supporting Evidence: PMID:12121421 We show that 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 PMID:19140243 The major recognition events are the two leucine residues binding in hydrophobic pockets on Ο2. PMID:19140243 Mutation of a number of these to hydrophilic residues (Ο2L65S, Ο2V88D, Ο2V98S or Ο2L103S), or filling in the pocket by replacement of Ο2A63 or Ο2N92 with tryptophan, strongly inhibited binding of recombinant AP2 core complexes to different dileucine motifs PMID:19140243 In contrast, the binding of wild-type and mutant AP2 cores to PtdIns4,5P2 and to YxxΞ¦ was unaffected |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-2130486 | REMOVE | Summary: One of five Reactome rows placing AP2S1 in the endolysosome membrane, from Reactome:R-HSA-2130486. Reading the cached Reactome entries shows what produced them: these are reactions in which a clathrin-coated-vesicle entity is relocated to a downstream compartment while keeping its full subunit roster -- 'Uncoating of clathrin-coated vesicles and fusion with endosomes' (R-HSA-2130486), 'PCSK9:LDLR:Clathrin-coated vesicle transport from plasma membrane to endolysosome' (R-HSA-6784729), 'VLDLR:PCSK9:Clathrin-coated vesicle translocates from the plasma membrane to lysosomal membrane' (R-HSA-8855130). The first of those is literally the step at which AP-2 leaves. Reason: Three independent lines say AP2S1 is not located in the endolysosome membrane. Ontology: GO's own closure places the AP-2 adaptor complex in the coated pit, the plasma membrane and the clathrin-coated endocytic vesicle -- GO:0005905, GO:0005886, GO:0045334, GO:0030669 and GO:0030666 are all ancestors of GO:0030122 -- while GO:0036020 is not, its ancestry running through lysosome and late-endosome membrane instead. UniProt: the record lists only cell membrane and coated pit, and explicitly notes that AP-2 disengages before internalization. Mechanism: AP-2 membrane recruitment requires PtdIns(4,5)P2, a plasma-membrane lipid, and Reactome's own R-HSA-8868648 has synaptojanin hydrolysing it to drive uncoating. This is a pathway-database compartment-inheritance artefact, not a curator judgement being overruled, and no experimental annotation is touched. (It is also not the same claim as the reported effect of AP2S1 knockdown on late-endosome-to-lysosome fusion: that paper localises APP, not AP2S1, to the late endosome, and postdates these rows.) Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt internalizing CCVs and to disengage from sites of endocytosis seconds file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-2130725 | REMOVE | Summary: One of five Reactome rows placing AP2S1 in the endolysosome membrane, from Reactome:R-HSA-2130725. Reading the cached Reactome entries shows what produced them: these are reactions in which a clathrin-coated-vesicle entity is relocated to a downstream compartment while keeping its full subunit roster -- 'Uncoating of clathrin-coated vesicles and fusion with endosomes' (R-HSA-2130486), 'PCSK9:LDLR:Clathrin-coated vesicle transport from plasma membrane to endolysosome' (R-HSA-6784729), 'VLDLR:PCSK9:Clathrin-coated vesicle translocates from the plasma membrane to lysosomal membrane' (R-HSA-8855130). The first of those is literally the step at which AP-2 leaves. Reason: Three independent lines say AP2S1 is not located in the endolysosome membrane. Ontology: GO's own closure places the AP-2 adaptor complex in the coated pit, the plasma membrane and the clathrin-coated endocytic vesicle -- GO:0005905, GO:0005886, GO:0045334, GO:0030669 and GO:0030666 are all ancestors of GO:0030122 -- while GO:0036020 is not, its ancestry running through lysosome and late-endosome membrane instead. UniProt: the record lists only cell membrane and coated pit, and explicitly notes that AP-2 disengages before internalization. Mechanism: AP-2 membrane recruitment requires PtdIns(4,5)P2, a plasma-membrane lipid, and Reactome's own R-HSA-8868648 has synaptojanin hydrolysing it to drive uncoating. This is a pathway-database compartment-inheritance artefact, not a curator judgement being overruled, and no experimental annotation is touched. (It is also not the same claim as the reported effect of AP2S1 knockdown on late-endosome-to-lysosome fusion: that paper localises APP, not AP2S1, to the late endosome, and postdates these rows.) Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt internalizing CCVs and to disengage from sites of endocytosis seconds file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-6784729 | REMOVE | Summary: One of five Reactome rows placing AP2S1 in the endolysosome membrane, from Reactome:R-HSA-6784729. Reading the cached Reactome entries shows what produced them: these are reactions in which a clathrin-coated-vesicle entity is relocated to a downstream compartment while keeping its full subunit roster -- 'Uncoating of clathrin-coated vesicles and fusion with endosomes' (R-HSA-2130486), 'PCSK9:LDLR:Clathrin-coated vesicle transport from plasma membrane to endolysosome' (R-HSA-6784729), 'VLDLR:PCSK9:Clathrin-coated vesicle translocates from the plasma membrane to lysosomal membrane' (R-HSA-8855130). The first of those is literally the step at which AP-2 leaves. Reason: Three independent lines say AP2S1 is not located in the endolysosome membrane. Ontology: GO's own closure places the AP-2 adaptor complex in the coated pit, the plasma membrane and the clathrin-coated endocytic vesicle -- GO:0005905, GO:0005886, GO:0045334, GO:0030669 and GO:0030666 are all ancestors of GO:0030122 -- while GO:0036020 is not, its ancestry running through lysosome and late-endosome membrane instead. UniProt: the record lists only cell membrane and coated pit, and explicitly notes that AP-2 disengages before internalization. Mechanism: AP-2 membrane recruitment requires PtdIns(4,5)P2, a plasma-membrane lipid, and Reactome's own R-HSA-8868648 has synaptojanin hydrolysing it to drive uncoating. This is a pathway-database compartment-inheritance artefact, not a curator judgement being overruled, and no experimental annotation is touched. (It is also not the same claim as the reported effect of AP2S1 knockdown on late-endosome-to-lysosome fusion: that paper localises APP, not AP2S1, to the late endosome, and postdates these rows.) Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt internalizing CCVs and to disengage from sites of endocytosis seconds file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-6784738 | REMOVE | Summary: One of five Reactome rows placing AP2S1 in the endolysosome membrane, from Reactome:R-HSA-6784738. Reading the cached Reactome entries shows what produced them: these are reactions in which a clathrin-coated-vesicle entity is relocated to a downstream compartment while keeping its full subunit roster -- 'Uncoating of clathrin-coated vesicles and fusion with endosomes' (R-HSA-2130486), 'PCSK9:LDLR:Clathrin-coated vesicle transport from plasma membrane to endolysosome' (R-HSA-6784729), 'VLDLR:PCSK9:Clathrin-coated vesicle translocates from the plasma membrane to lysosomal membrane' (R-HSA-8855130). The first of those is literally the step at which AP-2 leaves. Reason: Three independent lines say AP2S1 is not located in the endolysosome membrane. Ontology: GO's own closure places the AP-2 adaptor complex in the coated pit, the plasma membrane and the clathrin-coated endocytic vesicle -- GO:0005905, GO:0005886, GO:0045334, GO:0030669 and GO:0030666 are all ancestors of GO:0030122 -- while GO:0036020 is not, its ancestry running through lysosome and late-endosome membrane instead. UniProt: the record lists only cell membrane and coated pit, and explicitly notes that AP-2 disengages before internalization. Mechanism: AP-2 membrane recruitment requires PtdIns(4,5)P2, a plasma-membrane lipid, and Reactome's own R-HSA-8868648 has synaptojanin hydrolysing it to drive uncoating. This is a pathway-database compartment-inheritance artefact, not a curator judgement being overruled, and no experimental annotation is touched. (It is also not the same claim as the reported effect of AP2S1 knockdown on late-endosome-to-lysosome fusion: that paper localises APP, not AP2S1, to the late endosome, and postdates these rows.) Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt internalizing CCVs and to disengage from sites of endocytosis seconds file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots |
| GO:0036020 endolysosome membrane | TAS Reactome:R-HSA-8855130 | REMOVE | Summary: One of five Reactome rows placing AP2S1 in the endolysosome membrane, from Reactome:R-HSA-8855130. Reading the cached Reactome entries shows what produced them: these are reactions in which a clathrin-coated-vesicle entity is relocated to a downstream compartment while keeping its full subunit roster -- 'Uncoating of clathrin-coated vesicles and fusion with endosomes' (R-HSA-2130486), 'PCSK9:LDLR:Clathrin-coated vesicle transport from plasma membrane to endolysosome' (R-HSA-6784729), 'VLDLR:PCSK9:Clathrin-coated vesicle translocates from the plasma membrane to lysosomal membrane' (R-HSA-8855130). The first of those is literally the step at which AP-2 leaves. Reason: Three independent lines say AP2S1 is not located in the endolysosome membrane. Ontology: GO's own closure places the AP-2 adaptor complex in the coated pit, the plasma membrane and the clathrin-coated endocytic vesicle -- GO:0005905, GO:0005886, GO:0045334, GO:0030669 and GO:0030666 are all ancestors of GO:0030122 -- while GO:0036020 is not, its ancestry running through lysosome and late-endosome membrane instead. UniProt: the record lists only cell membrane and coated pit, and explicitly notes that AP-2 disengages before internalization. Mechanism: AP-2 membrane recruitment requires PtdIns(4,5)P2, a plasma-membrane lipid, and Reactome's own R-HSA-8868648 has synaptojanin hydrolysing it to drive uncoating. This is a pathway-database compartment-inheritance artefact, not a curator judgement being overruled, and no experimental annotation is touched. (It is also not the same claim as the reported effect of AP2S1 knockdown on late-endosome-to-lysosome fusion: that paper localises APP, not AP2S1, to the late endosome, and postdates these rows.) Supporting Evidence: file:human/AP2S1/AP2S1-uniprot.txt internalizing CCVs and to disengage from sites of endocytosis seconds file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots |
| GO:0045202 synapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synapse, projected from mouse Ap2s1 (P62743 / ENSMUSP00000083281) by Ensembl Compara orthology. Reason: The orthology step is about as safe as orthology gets -- human and mouse sigma2 are identical over all 142 residues, verified live in the bioinformatics analysis -- so the projection carries whatever the mouse annotation is worth. What it is worth is a generic neuronal compartment for a ubiquitously expressed adaptor subunit, i.e. a real but peripheral location, and one already covered more precisely by the presynapse and postsynapse rows. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:P62743 Β· Ap2s1 (Mus musculus) SUPPORTS TRANSFER Mouse Ap2s1, the orthologue used by the Ensembl Compara projection. Identical to human AP2S1 over all 142 residues (checked live in the bioinformatics analysis), so orthology-based transfer between them is as safe as it gets. ensembl:ENSMUSP00000083281 SUPPORTS TRANSFER The mouse Ensembl protein backing the same Compara projection; the protein-level identifier for the P62743 orthologue named alongside it. Supporting Evidence: file:human/AP2S1/AP2S1-bioinformatics/RESULTS.md Human, rat and mouse sigma2 identical over the full chain: **True** PMID:31671891 For efficient internalization, the cargo proteins need to be linked to the endocytic machinery via adaptor proteins such as the heterotetrameric endocytic adaptor complex AP-2 and a variety of mostly monomeric endocytic adaptors. PMID:38550987 Here, we show that multiple AP2 subunits regulate acoustically evoked behavior selection and habituation learning in zebrafish. |
| GO:0045334 clathrin-coated endocytic vesicle | NAS PMID:25898166 CALM regulates clathrin-coated vesicle size and maturation b... | ACCEPT | Summary: Clathrin-coated endocytic vesicle, ARUK-UCL, from the CALM/PICALM study whose own framing puts AP2 among the three most abundant CCV proteins. Eleven entities carry this reference for this term. Reason: Supported both ontologically and empirically. GO's own closure makes GO:0045334 an ancestor of GO:0030122, so a protein in AP-2 is in the clathrin-coated endocytic vesicle by construction; and CCV proteomics finds AP2 among its most abundant components. There is a genuine tension with live-imaging work reporting AP-2 to be largely excluded from the vesicles that actually internalise -- recorded as a knowledge gap rather than resolved by picking a side here. Supporting Evidence: PMID:25898166 The three most abundant proteins in mammalian endocytic CCVs are clathrin and the two cargo-selecting, clathrin adaptors, CALM and AP2. PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots |
| GO:0048268 clathrin coat assembly | TAS PMID:10753805 Clathrin coat construction in endocytosis. | KEEP AS NON CORE | Summary: Clathrin coat assembly, the third Pearse 2000 term. AP-2 does nucleate clathrin lattices, but the clathrin-engaging element of the complex is the beta2 hinge and its clathrin box, not sigma2. Reason: A real complex-level process, and sigma2 participates as an obligate subunit of the complex that performs it, so the row stays. It is not a core function of this protein: the division of labour within AP-2 puts clathrin binding on beta2 -- the peptide used to compete clathrin assembly in the classic experiment is a beta2 peptide -- while sigma2's own contribution is cargo-motif recognition. Marking it non-core keeps the subunit-level picture honest. Supporting Evidence: PMID:11102472 examined a DLL-containing peptide from the b2 subunit of AP-2 PMID:29184887 The key stages in this step-wise process, from the starting point of cargo recognition, to the later stage of assembly of the clathrin coat, are dependent on weak interactions between a large network of proteins. |
| GO:0048488 synaptic vesicle endocytosis | IDA PMID:11102472 A conserved clathrin assembly motif essential for synaptic v... | KEEP AS NON CORE | Summary: Synaptic vesicle endocytosis, SynGO, IDA. The direct assay behind it is in vitro clathrin assembly by AP-2 purified from bovine brain, competed by DLL-motif peptides. Reason: Not overruled: an experimental annotation made by a curator with the full text, and the underlying biology -- AP-2 in synaptic vesicle retrieval -- is not in doubt. But the assayed object is the intact complex and the motif peptide comes from beta2, so this speaks to AP-2 rather than to sigma2 specifically, and synaptic vesicle endocytosis is one neuronal instance of the general clathrin-dependent endocytosis function already annotated. Non-core for that reason, not because the evidence is weak. 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 PMID:11102472 examined a DLL-containing peptide from the b2 subunit of AP-2 |
| GO:0048488 synaptic vesicle endocytosis | IMP PMID:11102472 A conserved clathrin assembly motif essential for synaptic v... | KEEP AS NON CORE | Summary: Synaptic vesicle endocytosis, SynGO, IMP. The perturbation is peptide microinjection into squid giant presynaptic terminals, which reversibly blocked transmission and prevented coated-pit formation. Reason: The perturbation is pharmacological competition with a beta2-derived clathrin-assembly motif in an invertebrate synapse, not a manipulation of AP2S1. It establishes the complex's requirement in synaptic vesicle endocytosis, which is why the curator made the call, and it is left in place -- but as a tissue-specific, complex-level role rather than a core sigma2 function. 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 PMID:11102472 examined a DLL-containing peptide from the b2 subunit of AP-2 |
| GO:0048488 synaptic vesicle endocytosis | NAS PMID:11102472 A conserved clathrin assembly motif essential for synaptic v... | KEEP AS NON CORE | Summary: Synaptic vesicle endocytosis, SynGO, the non-experimental of the three rows from Morgan et al. 2000. Reason: Real for the AP-2 complex but tissue-specific, and the evidence is complex-level. The paper works with AP-2 purified from bovine brain and with a DLL-containing peptide taken from the beta2 subunit, microinjected into squid giant presynaptic terminals; sigma2 is never assayed on its own. Only four entities carry this reference for the term (AP2S1, AP2B1 human and rat, AP2M1), consistent with a complex-level call. Kept, because the curator read the full text and the complex-level claim is sound, but not as a core function of a ubiquitously expressed adaptor subunit. 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 PMID:11102472 examined a DLL-containing peptide from the b2 subunit of AP-2 |
| GO:0072583 clathrin-dependent endocytosis | IEA GO_REF:0000002 | ACCEPT | Summary: Clathrin-dependent endocytosis from the AP-2-specific InterPro entry IPR027156. The single most accurate process term on the record. Reason: Core. AP-2 is the principal cargo adaptor of clathrin-mediated endocytosis, and AP2S1 is required for it: cargo uptake is abolished in cells deficient in AP2S1. The mapping comes from the AP-2-specific signature, so it is not a family-level over-generalisation. Propagation Review Root cause: NO FAILURE CORE Sources checked: InterPro:IPR027156 Β· InterPro IPR027156 APS2 SUPPORTS TRANSFER APS2 -- the InterPro entry specific to the AP-2 sigma subunit, matched by AP2S1. Because it is subfamily-specific rather than family-wide, terms mapped from it (GO:0035615, GO:0072583) are AP-2-specific and not over-generalised. Supporting Evidence: PMID:31353312 the uptake of the cargo reporter was abolished in AAGAB KO cells or cells deficient in AP2S1, which encodes the Ο2 subunit of AP2 adaptor PMID:12086608 AP2 functions in clathrin-mediated endocytosis, the process whereby cargo enters the endosomal system from the plasma membrane. PMID:23222959 AP2S1 mutations decreased the sensitivity of CaSR-expressing cells to extracellular calcium and reduced CaSR endocytosis |
| GO:0072583 clathrin-dependent endocytosis | NAS PMID:29184887 Weak Molecular Interactions in Clathrin-Mediated Endocytosis... | ACCEPT | Summary: Clathrin-dependent endocytosis, ComplexPortal, from the review of weak interactions in CME. Reason: Core, and the process AP2S1 exists to serve. The complex-level character of the ComplexPortal projection does not weaken it: sigma2 is required for the process, and cargo uptake fails in AP2S1-deficient cells. Supporting Evidence: PMID:29184887 The key stages in this step-wise process, from the starting point of cargo recognition, to the later stage of assembly of the clathrin coat, are dependent on weak interactions between a large network of proteins. PMID:31353312 the uptake of the cargo reporter was abolished in AAGAB KO cells or cells deficient in AP2S1, which encodes the Ο2 subunit of AP2 adaptor |
| GO:0072583 clathrin-dependent endocytosis | TAS PMID:12121421 The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY... | ACCEPT | Summary: Clathrin-dependent endocytosis, BHF-UCL, the third term of the same five-way projection. Reason: Core and correct. Duplicated by the InterPro IEA and the ComplexPortal NAS rows, which is not a problem; the projection is noted only so that three rows for this term are not read as three independent lines of evidence. Supporting Evidence: PMID:12121421 We show that 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 PMID:31353312 the uptake of the cargo reporter was abolished in AAGAB KO cells or cells deficient in AP2S1, which encodes the Ο2 subunit of AP2 adaptor |
| GO:0098793 presynapse | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Presynapse, derived by the GOC term-relationship rule from AP2S1's GO:0048488 synaptic vesicle endocytosis annotation rather than from any observation of the protein. Reason: The inference itself is valid -- synaptic vesicle endocytosis happens at the presynaptic terminal -- but it inherits everything from its input, and that input is a SynGO annotation made from experiments on the intact AP-2 complex in squid giant synapse and on bovine brain AP-2, using a peptide from the beta2 subunit. AP2S1 is ubiquitously expressed with low tissue specificity, so a neuronal compartment is a real but peripheral location, not where this subunit is defined to act. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: GO:0048488 Β· GO:0048488 synaptic vesicle endocytosis (the input annotation) SUPPORTS TRANSFER The GOC term-relationship rule (GO_REF:0000108) infers the location from the process: synaptic vesicle endocytosis occurs at the presynapse, so a gene product annotated to it is placed there. The inference is only as good as its input, and its input here is the SynGO complex-level annotation from PMID:11102472. 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 PMID:11102472 examined a DLL-containing peptide from the b2 subunit of AP-2 |
| GO:0098794 postsynapse | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Postsynapse, derived by the same GOC rule from the GO:0098884 postsynaptic neurotransmitter receptor internalization row. Reason: Valid as an inference and grounded further upstream than it looks: the rat orthologue P62744 carries GO:0098884 by IDA and EXP from PMID:17289840, work on the AMPA receptor-AP-2 interaction. Still a tissue-specific location reached by rule rather than observation of the human protein, so non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: GO:0098884 Β· GO:0098884 postsynaptic neurotransmitter receptor internalization (the input annotation) SUPPORTS TRANSFER Same GOC rule, with GO:0098884 postsynaptic neurotransmitter receptor internalization as the input. That input is a ComplexPortal NAS row applied to all fourteen AP-2 entities, so the derived location inherits its complex-level character. Supporting Evidence: PMID:31671891 For efficient internalization, the cargo proteins need to be linked to the endocytic machinery via adaptor proteins such as the heterotetrameric endocytic adaptor complex AP-2 and a variety of mostly monomeric endocytic adaptors. |
| GO:0098884 postsynaptic neurotransmitter receptor internalization | NAS PMID:31671891 Endocytic Adaptor Proteins in Health and Disease: Lessons fr... | KEEP AS NON CORE | Summary: Postsynaptic neurotransmitter receptor internalization, ComplexPortal, from a review of endocytic adaptors in disease; fourteen AP-2 entities share it. Reason: Real, and better grounded than a review citation suggests: the rat orthologue carries this term by IDA and EXP from PMID:17289840, which mapped the determinants of the AMPA receptor-AP-2 interaction. But it is one tissue-specific instance of the general cargo-selection function of a ubiquitously expressed subunit (UniProt: low tissue specificity), so it belongs outside the core set. Supporting Evidence: PMID:31671891 For efficient internalization, the cargo proteins need to be linked to the endocytic machinery via adaptor proteins such as the heterotetrameric endocytic adaptor complex AP-2 and a variety of mostly monomeric endocytic adaptors. PMID:31353312 the uptake of the cargo reporter was abolished in AAGAB KO cells or cells deficient in AP2S1, which encodes the Ο2 subunit of AP2 adaptor |
| GO:0005905 clathrin-coated pit | IDA PMID:15941406 Analysis of the AP-2 adaptor complex and cargo during clathr... | NEW | Summary: The defining location of AP-2 is absent from GOA. AP-2 is the canonical marker of clathrin-coated pits: live imaging finds it at essentially every static clathrin spot on the plasma membrane, and UniProt curates 'Membrane, coated pit' for AP2S1 from PubMed:33859415 with a peripheral, cytoplasmic-side topology. Reason: GOA gives AP2S1 the plasma membrane 24 times, the cytosol 31 times and the clathrin-coated endocytic vesicle once, but never the coated pit -- the one structure AP-2 actually builds and occupies. GO's closure entails it (GO:0005905 is an ancestor of GO:0030122), which is precisely why the direct annotation is worth making explicit rather than leaving implicit behind a complex term. Coded IDA on the imaging evidence, which is of the AP-2 complex in live cells; the sigma2-specific attribution rests on AP-2 being an obligate heterotetramer, and UniProt makes the same attribution. A GOA curator may reasonably decline it as redundant-by-closure, and that objection is understood: the argument for making it anyway is that the coated pit is the structure AP-2 assembles and occupies, that UniProt curates it as an explicit subcellular location from experimental evidence, and that leaving the record's only direct locations as the plasma membrane and the cytosol misrepresents where the protein is concentrated. If the project prefers closure-implied terms to stay implicit, this is the row to drop; nothing else in the review depends on it. Supporting Evidence: PMID:15941406 while AP-2 is present in nearly all static clathrin spots, it is excluded from the disappearing population of clathrin spots file:human/AP2S1/AP2S1-uniprot.txt Membrane, coated pit {ECO:0000269|PubMed:33859415}; Peripheral membrane PMID:33859415 We also show that C15orf57 encodes a protein that binds the AP2 complex, localizes to clathrin-coated pits and enables efficient transferrin uptake. |
| GO:0055074 calcium ion homeostasis | IMP PMID:23222959 Mutations in AP2S1 cause familial hypocalciuric hypercalcemi... | NEW | Summary: The role that made this gene famous is missing from GOA entirely. Heterozygous Arg15 missense mutations in AP2S1 cause familial hypocalciuric hypercalcaemia type 3, with lifelong elevation of serum calcium; the mutations reduce CaSR endocytosis and desensitise CaSR-expressing cells to extracellular calcium, and a CRISPR knock-in mouse carrying p.Arg15Leu reproduces the hypercalcaemia and hypermagnesaemia. UniProt records the role in its FUNCTION line. Reason: Well replicated in humans and in mouse: Arg15 mutations were found in thirteen unrelated probands in the original series and seventeen more in the follow-up, all three alleles acting dominant-negatively on CaSR signal transduction, and the knock-in mouse shows the corresponding plasma chemistry. Coded IMP on the human genetic and cellular data rather than on the mouse, which is cited as a second reference. Deliberately not placed in core_functions: this is the organism-level consequence of sigma2's molecular job (selecting a dileucine-bearing GPCR into coated pits), not a second function of the protein. Supporting Evidence: PMID:23222959 missense mutations of AP2 Ο subunit (AP2S1) affecting Arg15, which forms key contacts with dileucine-based motifs of CCV cargo proteins, result in familial hypocalciuric hypercalcemia type 3 (FHH3), an extracellular calcium homeostasis disorder affecting the parathyroids, kidneys and bone PMID:23222959 AP2S1 mutations decreased the sensitivity of CaSR-expressing cells to extracellular calcium and reduced CaSR endocytosis file:human/AP2S1/AP2S1-uniprot.txt similarity). May also play a role in extracellular calcium homeostasis. PMID:26082470 All three FHH3-causing AP2Ο2 mutations impaired CaSR signal transduction in a dominant-negative manner. PMID:33729479 Co-immunoprecipitation studies showed that the AP2S1 p.Arg15Leu mutation impaired protein-protein interactions between AP2Ο2 and the other AP2 subunits, and also with the CaSR. |
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Download this section (compressed HTML)Q: Should GO create a molecular function for acidic dileucine ([D/E]xxxL[L/I]) sorting signal binding as a sibling of GO:0089710? Without it, the AP-2 alpha and sigma subunits, the AP-1 and AP-3 sigmas and the GGA proteins all fall back on bare protein binding, and the molecular mechanism of FHH3 has no GO expression.
Suggested experts: GO Ontology editors, Gene Ontology membrane-trafficking curators
Q: GO:0002031 G protein-coupled receptor internalization has negative regulation of GPCR signalling in its ancestry. Is that entailment intended? AP-2-mediated CaSR internalization sustains rather than terminates signalling, so the term cannot be used for the best-characterised cargo of AP2S1.
Suggested experts: GO Ontology editors, GPCR trafficking curators
Q: Should the five Reactome-derived GO:0036020 endolysosome membrane rows on AP2S1 be corrected at source? They arise because a clathrin-coated-vesicle entity keeps its full subunit roster while being relocated, including in a reaction named 'Uncoating of clathrin-coated vesicles and fusion with endosomes'. The same pattern will affect every AP-2 subunit and every clathrin chain.
Suggested experts: Reactome curators, GOA
Q: Does sigma2 Arg15 confer selectivity for particular dileucine motifs rather than general affinity? The CaSR motif RHQPLL has a non-acidic residue at L-4, and the FHH3 phenotype is far narrower than the endocytic defect expected from a general loss of dileucine recognition.
Suggested experts: AP complex structural biologists, Calcium homeostasis clinicians
Q: N92 is the one dileucine-pocket residue that distinguishes AP2S1 from every other human AP-1 to AP-4 sigma subunit, all of which carry D. Does it account for AP-2's reported tolerance of variation flanking the L[LI] pair compared with AP-1 and AP-3?
Suggested experts: AP complex structural biologists
Experiment: Measure, by surface plasmon resonance or liposome-binding assay, the affinity of recombinant wild-type and Arg15Cys/His/Leu AP2 cores for a panel of dileucine motifs systematically varied at the L-4 position (acidic E/D, the CaSR-like polar Q/H, and the basic R of GLUT4), with a TGN38 YxxPhi motif and PtdIns(4,5)P2 as internal specificity controls exactly as in the original structural study. A selectivity model predicts that the Arg15 mutants lose most affinity for non-acidic L-4 motifs while retaining it for acidic ones.
Hypothesis: Sigma2 Arg15 sets selectivity among dileucine motifs rather than global affinity, which is why FHH3 is a calcium disorder rather than a general endocytic disease.
Type: biophysical binding assay
Experiment: Make the reciprocal swap: sigma2 N92D in AP-2 cores and the corresponding D-to-N substitution in an AP-1 core, then compare binding across a matched motif panel. Pair with a cellular readout by knock-in of N92D at the endogenous AP2S1 locus and quantitative surface proteomics of dileucine-bearing cargo.
Hypothesis: N92, the single AP2-specific pocket residue, accounts for AP-2's broader dileucine tolerance relative to AP-1 and AP-3.
Type: structure-function mutagenesis
Experiment: Correlative live-cell TIRF and cryo-electron tomography of scission events in cells expressing endogenously tagged AP2S1 at known copy number, counting sigma2 molecules per vesicle immediately before and after scission. This would settle which of GO:0045334, GO:0030669 and GO:0005905 AP2S1 should carry.
Hypothesis: AP-2 is largely absent from the budded clathrin-coated vesicle, and its presence in CCV proteomes reflects co-purification of pits and partially uncoated carriers.
Type: quantitative imaging
Experiment: Repeat the APP and Abeta measurements in cells carrying a separation-of-function AP2S1 allele -- for example the pocket mutant V88D, which abolishes dileucine binding but leaves the subunit folded and complex-competent -- alongside full knockdown, and localise endogenous AP2S1 (not APP) relative to RAB9 and LAMP1. If the APP phenotype tracks dileucine-binding loss it is endocytic; if it survives V88D it is not.
Hypothesis: The reported effect of AP2S1 on APP degradation is an indirect consequence of impaired endocytosis rather than a distinct late-endosomal function.
Type: genetic separation of function
What is not known β curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: GO cannot express the one molecular activity that is specific to sigma2 rather than to the AP-2 complex: binding of the acidic dileucine sorting signal.
OPEN ONTOLOGY
What is known: Firmly established: the dileucine motif's two leucines bind adjacent hydrophobic pockets built from sigma2 residues; six pocket substitutions abolish or strongly reduce binding while leaving PtdIns(4,5)P2 and YxxPhi binding intact; sigma2 Arg15 with alpha Arg21 binds the L-4 residue; and all of these residues are present in the human protein. Equally firmly established on the ontology side: GO:0089710, the only endocytic-signal binding term, is defined for a signal with an essential tyrosine, which is the mu2 ligand.
Significance: Without the term, sigma2's function is representable in GO only as the complex-level GO:0035615 or as bare GO:0005515, and the molecular mechanism of a Mendelian disease (FHH3) has no GO expression. The same gap affects the alpha, AP-1 sigma, AP-3 sigma and GGA proteins.
What would resolve it: Create a sibling of GO:0089710 under GO:0005515 for acidic dileucine sorting signal binding, as set out in proposed_new_terms; then the eight protein-binding rows on this gene become candidates for MODIFY rather than over-annotation.
Provenance (the field's own admissions):
Gap: The obvious GO term for AP2S1's best-documented cargo function, GO:0002031 G protein-coupled receptor internalization, cannot be used because its ontological ancestry asserts a regulatory sign the data contradict.
OPEN ONTOLOGYBIOLOGY
What is known: Established: AP2S1 Arg15 mutants reduce CaSR internalization and shift the calcium concentration-response curve rightward, so loss of sigma2 function reduces CaSR signalling. Established on the ontology side: GO:0002031's is_a/part_of closure includes GO:0045744 negative regulation of G protein-coupled receptor signaling pathway and GO:0009968 negative regulation of signal transduction.
Significance: Annotating the term would propagate a claim that sigma2 negatively regulates GPCR signalling, when the human genetics show the opposite direction for this receptor -- consistent with work showing CaSR signals from internalized endosomal compartments, so that internalization sustains rather than terminates signalling. The row is therefore left unmade and recorded here.
What would resolve it: Either loosen the regulatory parentage of GO:0002031 so that receptor internalization does not entail negative regulation of the receptor's pathway, or determine experimentally whether CaSR is the exception among AP-2 GPCR cargo. Both are tractable.
Provenance (the field's own admissions):
Gap: Whether AP-2 is a genuine component of the budded clathrin-coated vesicle, or only of the coated pit, is unresolved, and the two best experiments disagree.
OPEN BIOLOGYCURATION
What is known: Established on one side: CCV proteomics places AP2 among the three most abundant proteins of mammalian endocytic clathrin-coated vesicles. Established on the other: quantitative live imaging of at least 80 clathrin spots per group finds AP-2 at nearly all static spots but excluded from the disappearing (internalizing) population, and UniProt records the same, noting that AP-2 disengages seconds before internalization.
Significance: Four cellular-component terms on this gene (GO:0045334, GO:0030669, GO:0030666, and by entailment part of GO:0030122's own placement in the ontology) depend on the answer. They are accepted or kept here on the ontology's own structure rather than on a resolution of the biology, and the distinction matters for any downstream use that reads AP-2 as a cargo-carrying vesicle protein.
What would resolve it: The two results are not strictly incompatible: proteomics measures a population purified over minutes, imaging measures individual events at the second scale, and residual AP-2 below the imaging threshold would satisfy both. A direct test would be single-vesicle correlative imaging of scission events with calibrated sigma2 copy number.
Provenance (the field's own admissions):
Gap: The reported endocytosis-independent role of AP2S1 in amyloid precursor protein turnover, acting through late-endosome-to-lysosome fusion, rests on a single laboratory and has no mechanistic link to sigma2's known activity.
OPEN BIOLOGY
What is known: Reported: AP2S1 knockdown or overexpression decreases or increases APP and Abeta; the effect is stated to be unrelated to endocytosis and to require VPS41; hippocampal AAV knockdown in APP/PS1 mice lowers APP and Abeta and improves cognition. Not reported: any localisation of AP2S1 itself to the late endosome, or any biochemical connection between the dileucine pocket and the fusion machinery.
Significance: If confirmed and shown to be direct, this would be a second, mechanistically separate function for the subunit and would warrant its own annotations. As it stands, an indirect consequence of perturbing a complex on which most membrane traffic depends is at least as likely. No annotation is made from it here.
What would resolve it: Independent replication, plus localisation of endogenous AP2S1 (not APP) to RAB9-positive late endosomes, and a separation-of-function allele that preserves endocytosis while losing the APP effect.
Provenance (the field's own admissions):
Gap: Why complete loss of AP2S1 is embryonic-lethal and blocks endocytosis generally, while the human Arg15 alleles produce only a narrow calcium-homeostasis disorder, is not explained.
OPEN BIOLOGY
What is known: Established: homozygous Ap2s1 loss-of-function mice die between E3.5 and E9.5 and homozygous Arg15Leu knock-ins die perinatally, while heterozygotes are haplosufficient; human Arg15 heterozygotes have lifelong hypercalcaemia and are otherwise largely asymptomatic. Established mechanistically: Arg15 contributes only to the basic L-4 patch, not to the leucine pockets themselves, and its double mutation with alpha Arg21 costs about an order of magnitude in affinity rather than abolishing binding.
Significance: The original authors proposed that Arg15 is specifically required for recognition of the CaSR motif. If true, the L-4 patch encodes motif selectivity rather than affinity alone, which would be a general result about how AP complexes discriminate between dileucine cargoes.
What would resolve it: Compare AP-2 Arg15 mutant binding across a panel of dileucine motifs differing at the L-4 position (the CaSR motif RHQPLL has a non-acidic L-4), and measure surface levels of several dileucine cargoes in Arg15 knock-in cells.
Provenance (the field's own admissions):
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