Summary: Human FCHO1 binds the endocytic scaffold EPS15 through its C-terminal mu-homology region.

Reason: PMID:19713939 Figure 5 shows EPS15 recovery with human FCHO1 muHD and competition by the EPS15 C-terminal fragment; the Methods identify the FCHO1 fragment as human and the cytosol as rat, consistent with the source partner A7BFV9. The Discussion explicitly identifies Ede1/EPS15 as scaffold/adaptor proteins. GO:0097110 scaffold protein binding therefore describes this positive pair more precisely than generic protein binding. This is a binding-class refinement, not a claim that the isolated assay proves FCHO1 recruits cargo, activates EPS15, or establishes binding of every natural FCHO1 product. The rat partner and existing source object remain unchanged. The official GO definition identifies binding to a scaffold protein and discusses their signaling-complex roles; EPS15 is explicitly characterized as an endocytic scaffold/adaptor in the original Discussion. This binding classification does not assign a signaling-scaffold activity to FCHO1.

Proposed replacements: scaffold protein binding

Summary: The human interactome screen supports FCHO1 binding to protein-tyrosine kinase PTK6.

Reason: PMID:25416956 Table S2G, worksheet row 4771, explicitly records PTK6 GeneID 5753 with FCHO1 GeneID 23149. Official UniProt metadata maps PTK6 to the source partner Q13882 and identifies it as a protein-tyrosine kinase. The original reports pairwise retesting of positive screen pairs. GO:1990782 protein tyrosine kinase binding is the supported specific binding class. This does not assign kinase activity to FCHO1, establish phosphorylation of FCHO1, or infer kinase activation/inhibition. No target-specific orthogonal validation is claimed from the dataset-wide controls or from the domain-pair analysis in Table S2F. The related 2019 variant-interaction study is not counted as an independent orthogonal confirmation of this pair.

Proposed replacements: protein tyrosine kinase binding

Summary: The human interactome screen supports a FCHO1–LGALS14 interaction without establishing a more specific FCHO1 molecular function.

Reason: PMID:25416956 Table S2G, worksheet row 9693, records FCHO1 GeneID 23149 with LGALS14 GeneID 56891, independently joined to source partner Q8TCE9 by official UniProt metadata. Retain this positive binary-screen evidence as non-core under the project binding exception. Binding a galectin does not establish carbohydrate binding, galectin-complex membership or an endocytic role for this pair. No more specific GO binding class was established from the saved assay evidence and bounded official term search; no physiological or product-specific mechanism is inferred.

Summary: The human interactome screen supports a FCHO1–EXOSC5 interaction without establishing exosome activity for FCHO1.

Reason: PMID:25416956 Table S2G, worksheet row 9694, records FCHO1 GeneID 23149 with EXOSC5 GeneID 56915, independently joined to source partner Q9NQT4. Retain the positive protein-binding observation as non-core. Identification of the partner as an RNA-exosome component does not show that FCHO1 binds the assembled complex, processes RNA, or has nuclease activity. The screen supplies a pairwise interaction, not those additional functions; dataset-wide orthogonal validation is not attributed to this particular pair.

Summary: The variant-interaction dataset retains the FCHO1–PTK6 pair and supports protein tyrosine kinase binding.

Reason: PMID:31515488 Supplementary Data 2, worksheet row 3437, joins FCHO1 GeneID 23149/O14526,E423G to PTK6 GeneID 5753 with Disruption=0. The original compares variant interactions with wild-type interactions in the Y2H framework. Together with the exact target/partner identities, this supports GO:1990782 protein tyrosine kinase binding. The non-disruption call is specific to the tested variant and interaction; it does not establish kinase regulation, phosphorylation, physiological localization, or equivalent activity of all natural splice products. The inspected Supplementary Data 6 has no FCHO1 PCA retest row. These are related Y2H measurements within an existing interactome framework, not two independent assay platforms; the later non-disruption result must not be counted as orthogonal validation of the 2014 pair.

Proposed replacements: protein tyrosine kinase binding

Summary: The tested FCHO1 variant retains the LGALS14 interaction in the variant-interaction dataset.

Reason: PMID:31515488 Supplementary Data 2, worksheet row 3438, records FCHO1 GeneID 23149/O14526,E423G with LGALS14 GeneID 56891 and Disruption=0. Retain the supported binding pair as non-core. The Y2H comparison with the wild-type pair does not establish carbohydrate binding by FCHO1, galectin-complex membership or a physiological function for the interaction. No target-specific PCA confirmation is claimed, and the source annotation is not rewritten to assert a natural isoform.

Summary: The tested FCHO1 variant retains the EXOSC5 interaction in the variant-interaction dataset.

Reason: PMID:31515488 Supplementary Data 2, worksheet row 3439, records FCHO1 GeneID 23149/O14526,E423G with EXOSC5 GeneID 56915 and Disruption=0. Retain this positive pair as non-core. Association with an RNA-exosome component does not itself establish binding to the assembled exosome, RNA metabolism or nuclease activity by FCHO1. The inspected Supplementary Data 6 contains no FCHO1 PCA retest row. The variant context is explained without changing the original source or assigning a natural product.

Summary: FCHO1 has a contextual HPA nucleoplasmic localization.

Reason: The actual HPA FCHO1 record reports enhanced nucleoplasm and cytosol localization with HPA041653 and HPA062981. Their distinct antigens match canonical residues 285–364 and 746–818. Three selected original composite images were inspected: both antibodies in MCF-7 and HPA062981 in PC-3. HPA reports nucleoplasm in all examined antibody/cell combinations, with cytosol in a subset. The images are consistent with those calls; no independent endogenous specificity control, isoform resolution or nuclear molecular function was established. The positive nuclear observation is retained without making it the principal endocytic site. The better-established plasma-membrane role does not disprove another pool.

Summary: The broad cytoplasm annotation is covered by the retained cytosol location.

Reason: GO:0005829 cytosol is a direct part_of child of GO:0005737 cytoplasm in the saved official ontology response. The positive cytosol observation in row 9 and modeled target pool in rows 10–17 provide the resolved compartment; no separately resolved non-cytosolic cytoplasmic pool is claimed by this broad IBA. The term is biologically compatible, not false. The exact positive IBD row and target family membership are present in the accepted PTHR23065 sources. Initial and single recovery requests for the target gene record, tree and family MSA timed out, so the target leaf path and alignment were not independently verified. That access limit is not evidence of functional divergence; target self-WITH is expected experimental grounding, not circularity.

Summary: FCHO1 occupies a cytosolic pool associated with its endocytic role.

Reason: The actual HPA FCHO1 record reports enhanced nucleoplasm and cytosol localization with HPA041653 and HPA062981. Their distinct antigens match canonical residues 285–364 and 746–818. Three selected original composite images were inspected: both antibodies in MCF-7 and HPA062981 in PC-3. HPA reports nucleoplasm in all examined antibody/cell combinations, with cytosol in a subset. The images are consistent with those calls; no independent endogenous specificity control, isoform resolution or nuclear molecular function was established. Cytosol is distinguished from nucleoplasm and from the plasma-membrane compartment. This positive target observation corroborates the cytosolic FCHO1 entities used in the Reactome recruitment and release model.

Summary: The Reactome source genuinely includes the cytosolic FCHO1 pool.

Reason: The actual nested source route reaches human FCHO1 entity 8862257, reference entity 229459, UniProt O14526 residues 1–889, assigned to GO:0005829 cytosol: 8856808 input 8862276; 8862276 hasComponent 8862270; 8862270 hasMember 8862272; 8862272 hasComponent 8862257. The event incorporates AP-2 and clathrin into an early coat containing the FCHO1/FCHO2 set. This is a pathway compartment model rather than an independent localization experiment. It is compatible with the actual HPA target cytosol observation and with recruitment of a peripheral endocytic protein to the membrane. Only this target route was expanded; unrelated branches were not exhaustively reviewed.

Summary: The Reactome source genuinely includes the cytosolic FCHO1 pool.

Reason: The actual nested source route reaches human FCHO1 entity 8862257, reference entity 229459, UniProt O14526 residues 1–889, assigned to GO:0005829 cytosol: 8856813 output 8856806; 8856806 hasComponent 8862270; 8862270 hasMember 8862272; 8862272 hasComponent 8862257. The event concerns AAK1 phosphorylation of AP-2. FCHO1 is a nested coat component, not the kinase. This is a pathway compartment model rather than an independent localization experiment. It is compatible with the actual HPA target cytosol observation and with recruitment of a peripheral endocytic protein to the membrane. Only this target route was expanded; unrelated branches were not exhaustively reviewed.

Summary: The Reactome source genuinely includes the cytosolic FCHO1 pool.

Reason: The actual nested source route reaches human FCHO1 entity 8862257, reference entity 229459, UniProt O14526 residues 1–889, assigned to GO:0005829 cytosol: 8862280 input 8862270; 8862270 hasMember 8862272; 8862272 hasComponent 8862257. The source explicitly recruits the cytosolic FCHO1/FCHO2 dimer set to a nascent plasma-membrane coat. This is a pathway compartment model rather than an independent localization experiment. It is compatible with the actual HPA target cytosol observation and with recruitment of a peripheral endocytic protein to the membrane. Only this target route was expanded; unrelated branches were not exhaustively reviewed.

Summary: The Reactome source genuinely includes the cytosolic FCHO1 pool.

Reason: The actual nested source route reaches human FCHO1 entity 8862257, reference entity 229459, UniProt O14526 residues 1–889, assigned to GO:0005829 cytosol: 8866283 input 8856806; 8856806 hasComponent 8862270; 8862270 hasMember 8862272; 8862272 hasComponent 8862257. Beta-arrestin-mediated GPCR recruitment contains the FCHO1-bearing coat; this does not establish FCHO1 binding to every modeled receptor. This is a pathway compartment model rather than an independent localization experiment. It is compatible with the actual HPA target cytosol observation and with recruitment of a peripheral endocytic protein to the membrane. Only this target route was expanded; unrelated branches were not exhaustively reviewed.

Summary: The Reactome source genuinely includes the cytosolic FCHO1 pool.

Reason: The actual nested source route reaches human FCHO1 entity 8862257, reference entity 229459, UniProt O14526 residues 1–889, assigned to GO:0005829 cytosol: 8867754 output 8862270; 8862270 hasMember 8862272; 8862272 hasComponent 8862257. The model releases the FCHO1/FCHO2 set into cytosol when later BAR proteins arrive. Its summation explicitly says that precise dissociation timing is unknown. This is a pathway compartment model rather than an independent localization experiment. It is compatible with the actual HPA target cytosol observation and with recruitment of a peripheral endocytic protein to the membrane. Only this target route was expanded; unrelated branches were not exhaustively reviewed.

Summary: The Reactome source genuinely includes the cytosolic FCHO1 pool.

Reason: The actual nested source route reaches human FCHO1 entity 8862257, reference entity 229459, UniProt O14526 residues 1–889, assigned to GO:0005829 cytosol: 8867756 input 8856806; 8856806 hasComponent 8862270; 8862270 hasMember 8862272; 8862272 hasComponent 8862257. The CLASP/cargo recruitment complex includes the FCHO1-bearing coat. The modeled ordering is not a uniquely resolved chronology. This is a pathway compartment model rather than an independent localization experiment. It is compatible with the actual HPA target cytosol observation and with recruitment of a peripheral endocytic protein to the membrane. Only this target route was expanded; unrelated branches were not exhaustively reviewed.

Summary: The Reactome source genuinely includes the cytosolic FCHO1 pool.

Reason: The actual nested source route reaches human FCHO1 entity 8862257, reference entity 229459, UniProt O14526 residues 1–889, assigned to GO:0005829 cytosol: 8868071 input 8867753; 8867753 hasComponent 8856806; 8856806 hasComponent 8862270; 8862270 hasMember 8862272; 8862272 hasComponent 8862257. PIK3C2A is recruited into a coat that contains FCHO1; lipid-kinase activity is not assigned to FCHO1. This is a pathway compartment model rather than an independent localization experiment. It is compatible with the actual HPA target cytosol observation and with recruitment of a peripheral endocytic protein to the membrane. Only this target route was expanded; unrelated branches were not exhaustively reviewed.

Summary: The Reactome source genuinely includes the cytosolic FCHO1 pool.

Reason: The actual nested source route reaches human FCHO1 entity 8862257, reference entity 229459, UniProt O14526 residues 1–889, assigned to GO:0005829 cytosol: 8868072 catalystActivity 8868073; 8868073 physicalEntity 8868051; 8868051 hasComponent 8867753; 8867753 hasComponent 8856806; 8856806 hasComponent 8862270; 8862270 hasMember 8862272; 8862272 hasComponent 8862257. The path passes through catalystActivity 8868073 and physicalEntity 8868051. FCHO1 is a component of that larger assembly, not the phosphoinositide kinase. This is a pathway compartment model rather than an independent localization experiment. It is compatible with the actual HPA target cytosol observation and with recruitment of a peripheral endocytic protein to the membrane. Only this target route was expanded; unrelated branches were not exhaustively reviewed.

Summary: FCHO1 acts at the plasma membrane.

Reason: Independent human FCHO1 evidence in PMID:22484487 shows membrane-associated puncta, PtdIns(4,5)P2-dependent F-BAR binding and an endocytic interaction hub. PMID:32098969 shows wild-type FCHO1 at plasma-membrane puncta and coordinated clathrin recruitment in human cells, with altered behavior of tested disease variants. These findings support participation without asserting that FCHO1 is universally required for every clathrin-mediated event. Plasma membrane includes associated peripheral proteins; it is retained as the core membrane location. The exact positive IBD row and target family membership are present in the accepted PTHR23065 sources. Initial and single recovery requests for the target gene record, tree and family MSA timed out, so the target leaf path and alignment were not independently verified. That access limit is not evidence of functional divergence; target self-WITH is expected experimental grounding, not circularity.

Summary: FCHO1 associates with the plasma membrane at endocytic coat sites.

Reason: The recovered 2010 supplement includes human FCHO1 constructs and surface-punctum localization, although several endogenous panels use a combined FCHo1/2 label. Independent 2012 human FCHO1 localization and 2020 wild-type-versus-variant imaging establish the same plasma-membrane claim. Acceptance rests on this convergent target-specific evidence, not an assumption that the editorial concern was resolved. The 2010 report has a verified 2025 Expression of Concern and subsequent Erratum; their bodies and affected-experiment/resolution scope were unavailable.

Summary: FCHO1 is associated with assembling clathrin-coated pits.

Reason: Independent human FCHO1 evidence in PMID:22484487 shows membrane-associated puncta, PtdIns(4,5)P2-dependent F-BAR binding and an endocytic interaction hub. PMID:32098969 shows wild-type FCHO1 at plasma-membrane puncta and coordinated clathrin recruitment in human cells, with altered behavior of tested disease variants. These findings support participation without asserting that FCHO1 is universally required for every clathrin-mediated event. Coated-pit association is distinguished from persistent residence on mature free coated vesicles. The exact positive IBD row and target family membership are present in the accepted PTHR23065 sources. Initial and single recovery requests for the target gene record, tree and family MSA timed out, so the target leaf path and alignment were not independently verified. That access limit is not evidence of functional divergence; target self-WITH is expected experimental grounding, not circularity.

Summary: FCHO1 is recruited to plasma-membrane clathrin-coated pits.

Reason: The original supplement Figure S2B follows tagged human FCHO1 with clathrin, and Figure S1D shows its overlap with FCHo2 puncta. Independent human FCHO1 localization in the 2012 study and coat-dynamics imaging in the 2020 study support this pit compartment directly. This is not a claim of residence on detached coated vesicles. The 2010 report has a verified 2025 Expression of Concern and subsequent Erratum; their bodies and affected-experiment/resolution scope were unavailable.

Summary: Human FCHO1 localizes to surface clathrin-coated pits.

Reason: The 2012 Results describe low-level GFP-FCHO1 puncta at the ventral surface that overlap AP-2 and remain distinct from APPL1- and EEA1-positive endosomes. Figure 1 and the domain analysis place full-length FCHO1 at clathrin foci; the human constructs are identified in Methods. The data support a coat-site location without assuming that every FCHO1 molecule is constitutively coat-bound.

Summary: FCHO1 localizes to clathrin-coated pits.

Reason: The actual current ARBA00028399 rule predicts the imported GO term and includes a Primates plus FunFam 1.20.1270.60:FF:000016 condition set. The official target record contains the corresponding Gene3D superfamily and FCHO1/F-BAR domain assignments, but the exact FunFam match and historical rule state were not independently reconstructed. Independent human FCHO1 evidence in PMID:22484487 shows membrane-associated puncta, PtdIns(4,5)P2-dependent F-BAR binding and an endocytic interaction hub. PMID:32098969 shows wild-type FCHO1 at plasma-membrane puncta and coordinated clathrin recruitment in human cells, with altered behavior of tested disease variants. These findings support participation without asserting that FCHO1 is universally required for every clathrin-mediated event. The combined annotation also names UniProt SL-0069 coated pit, present in the official target record. GO_REF:0000120 combines concordant electronic pipelines and does not constitute a second independent assay.

Summary: The inherited NOT annotation for mature clathrin-coated vesicles remains unresolved.

Reason: Preserve the negation. The recovered original reports FCHo1/2 depletion from purified coated-vesicle fractions, and Supplementary Figure S6E shows the combined FCHo1/2 blot with loading controls. However, the antibody Methods identify anti-FCHo2 Ra103 raised against the FCHO2 N-terminal region; this does not independently resolve the FCHO1-specific contribution to the combined signal. Positive pit localization does not by itself prove absence from mature vesicles. The 2010 report has a verified 2025 Expression of Concern and subsequent Erratum; their bodies and affected-experiment/resolution scope were unavailable. The evidence therefore remains compatible with the curator’s negative assignment, but does not settle its target-specific scope; no wrong-gene or retraction claim is made. UniProt O14526 independently records the curator statement that FCHO1 is present in forming pits but not mature coated vesicles. Its cited 2010 evidence overlaps this same source, so that statement is affirmative curated support rather than a separate target-resolved experiment that removes the remaining uncertainty.

Summary: FCHO1 binds the AP-2 adaptor complex through its central linker.

Reason: The 2012 study maps AP-2 association to human FCHO1 linker constructs, with the major determinant between residues 267 and 442. Figure 1c–d and the corresponding Results identify binding to the α-subunit appendage platform and loss of binding with its W840A substitution, with weaker β2-appendage association. Methods distinguish the human FCHO1 constructs from the mouse/rat appendage reagents. This directly supports AP-2-complex binding, without claiming that FCHO1 binds clathrin directly or that the same assay measured AP-2 activation.

Summary: FCHO1 contributes to clathrin coat assembly.

Reason: Independent human FCHO1 evidence in PMID:22484487 shows membrane-associated puncta, PtdIns(4,5)P2-dependent F-BAR binding and an endocytic interaction hub. PMID:32098969 shows wild-type FCHO1 at plasma-membrane puncta and coordinated clathrin recruitment in human cells, with altered behavior of tested disease variants. These findings support participation without asserting that FCHO1 is universally required for every clathrin-mediated event. The membrane-associated interaction hub and coordinated recruitment contribute to coat organization; this is not an assertion that FCHO1 itself polymerizes clathrin or is an obligatory nucleator in all cells. The exact positive IBD row and target family membership are present in the accepted PTHR23065 sources. Initial and single recovery requests for the target gene record, tree and family MSA timed out, so the target leaf path and alignment were not independently verified. That access limit is not evidence of functional divergence; target self-WITH is expected experimental grounding, not circularity.

Summary: FCHO1 contributes to clathrin coat assembly.

Reason: The actual current ARBA00089731 rule predicts the imported GO term and includes a Primates plus FunFam 1.20.1270.60:FF:000016 condition set. The official target record contains the corresponding Gene3D superfamily and FCHO1/F-BAR domain assignments, but the exact FunFam match and historical rule state were not independently reconstructed. Independent human FCHO1 evidence in PMID:22484487 shows membrane-associated puncta, PtdIns(4,5)P2-dependent F-BAR binding and an endocytic interaction hub. PMID:32098969 shows wild-type FCHO1 at plasma-membrane puncta and coordinated clathrin recruitment in human cells, with altered behavior of tested disease variants. These findings support participation without asserting that FCHO1 is universally required for every clathrin-mediated event.

Summary: FCHO1 contributes to assembly of endocytic clathrin coats.

Reason: The 2010 supplement contains FCHO1-specific knockdown and untagged-expression comparisons, in addition to combined FCHo1/2 manipulations and predominantly FCHo2 main-paper experiments. Independent 2012 domain interactions and 2020 wild-type-versus-variant coat dynamics support human FCHO1 as a membrane-associated organizer that helps assemble coats. The 2012 persistence of coats after FCHO1/2 depletion limits universal obligatory-nucleator wording, not this positive participation claim. The 2010 report has a verified 2025 Expression of Concern and subsequent Erratum; their bodies and affected-experiment/resolution scope were unavailable.

Summary: Human FCHO1 organizes productive clathrin-coated-pit formation.

Reason: The 2020 Results and Figure 3 compare wild-type human FCHO1 with patient-associated variants in FCHO1-deficient cells carrying endogenously tagged clathrin. Wild-type FCHO1 tracks productive coat formation, whereas the tested variants fail to show the same behavior. Together with its established membrane and coat-partner interactions, this demonstrates an organizing contribution rather than merely a downstream requirement. It does not establish universal dependence of all clathrin-mediated traffic on FCHO1.

Summary: FCHO1 supports T-cell-receptor signaling through context-dependent receptor trafficking.

Reason: Human FCHO1-deficient Jurkat cells in PMID:32098969 Figure 4 show impaired CD3:TCR internalization and receptor-triggered calcium responses, restored by wild-type FCHO1. Direct FCHO1–CD3 binding was not established. This supports the existing signaling annotation through endocytic organization, retained as a non-core cellular context. The independent 2019 patient study (PMID:30822429, main text discussing Figure E4A–B, Figure 1E–F and Figure E4C) adds impaired activation-induced proliferation and survival in the one patient with pre-transplant functional samples, P2; it does not independently reproduce the Jurkat trafficking mechanism. In activated P2 T-cell blasts, transferrin uptake was impaired but TCR/CD3 internalization was preserved. Patient cells, cargo and activation state therefore remain distinct from the Jurkat comparison; neither study establishes a universal cargo defect or a separate receptor-proximal catalytic activity.

Summary: FCHO1 positively supports activation of human T cells.

Reason: The 2020 study reports patient T-cell response abnormalities and FCHO1-dependent receptor trafficking/calcium responses in human Jurkat cells (Figures 4 and 6). PMID:30822429 adds functional evidence from pre-transplant patient P2 PBMCs: anti-CD3/CD28-induced proliferation was reduced, with more hypodiploid cells and fewer cycling cells, despite preserved induction of the measured activation markers. Its activated T-cell blasts had impaired transferrin uptake but preserved TCR/CD3 internalization. These observations strengthen the positive, context-dependent contribution to T-cell activation and expansion, without implying that every early activation readout fails or that the two studies measured the same trafficking phenotype. Retain the immune-cell role as non-core relative to membrane-associated endocytic organization, with no new activation-specific biochemical function.

Summary: FCHO1 participates in clathrin-dependent endocytosis.

Reason: Independent human FCHO1 evidence in PMID:22484487 shows membrane-associated puncta, PtdIns(4,5)P2-dependent F-BAR binding and an endocytic interaction hub. PMID:32098969 shows wild-type FCHO1 at plasma-membrane puncta and coordinated clathrin recruitment in human cells, with altered behavior of tested disease variants. These findings support participation without asserting that FCHO1 is universally required for every clathrin-mediated event. The target data support an endocytic contribution with cargo and cell-context differences; normal uptake in some deficient cells does not establish loss of this broader function. The exact positive IBD row and target family membership are present in the accepted PTHR23065 sources. Initial and single recovery requests for the target gene record, tree and family MSA timed out, so the target leaf path and alignment were not independently verified. That access limit is not evidence of functional divergence; target self-WITH is expected experimental grounding, not circularity.

Summary: FCHO1 participates in clathrin-dependent endocytosis.

Reason: The actual current ARBA00044606 rule predicts the imported GO term and includes a Primates plus FunFam 1.20.1270.60:FF:000016 condition set. The official target record contains the corresponding Gene3D superfamily and FCHO1/F-BAR domain assignments, but the exact FunFam match and historical rule state were not independently reconstructed. Independent human FCHO1 evidence in PMID:22484487 shows membrane-associated puncta, PtdIns(4,5)P2-dependent F-BAR binding and an endocytic interaction hub. PMID:32098969 shows wild-type FCHO1 at plasma-membrane puncta and coordinated clathrin recruitment in human cells, with altered behavior of tested disease variants. These findings support participation without asserting that FCHO1 is universally required for every clathrin-mediated event.

Summary: FCHO1 participates in clathrin-dependent endocytosis.

Reason: The 2010 supplement reports human FCHO1-specific perturbation and expression effects alongside combined FCHo1/2 experiments. Independent 2012 human FCHO1 membrane/coat interactions and 2020 receptor-internalization data support a physical organizing contribution to this pathway. Preserved uptake in other cargo and cell contexts limits claims of universal essentiality, not participation. The 2010 report has a verified 2025 Expression of Concern and subsequent Erratum; their bodies and affected-experiment/resolution scope were unavailable.

Summary: Human FCHO1 contributes to cargo-dependent clathrin-mediated endocytosis.

Reason: The 2020 study combines human FCHO1 coat-dynamics imaging with receptor-internalization comparisons and wild-type rescue. It also reports preserved transferrin uptake in patient fibroblasts, demonstrating that the dependency varies with cargo and cell context. FCHO1’s membrane and coat-partner organization supplies a direct structural contribution to the pathway; the annotation does not assert universal necessity or direct recognition of CD3.

Summary: A postsynaptic endocytic-zone location is a contextual ortholog inference.

Reason: The actual Ensembl response identifies one-to-one orthology from human ENSG00000130475 to rat ENSRNOG00000033912 / ENSRNOP00000049715; its ungapped target and source sequences match the captured official proteins. Rat D3ZIM5 has three SynGO source annotations to this term from PMID:35072626. That original study shows tagged FCHO1 at a subset of perisynaptic sites and transient recruitment in cultured rat hippocampal neurons (Figures 4 and 5, whose pixels were inspected). The stable-positioned site in the GO definition does not require every recruited protein to be permanently resident. FCHO1 was not among the endogenous knock-in controls or the later super-resolution component panel, and the plasmid species was not independently resolved. Preserve this bounded transfer without claiming direct human neuronal localization or a constitutive EZ component. PMID:41943152 provides separate rat presynaptic endocytosis context; it does not substitute for the postsynaptic localization experiment.

Summary: Human FCHO1 bridges membrane association and endocytic protein interactions to organize coat sites.

Reason: The synthesis combines human-target experiments rather than domain architecture alone. PMID:22484487 Results “The FCHO endocytic hub,” “The linker region” and “The μHD,” Figures 1–2 and Supplementary Figure S1k show PtdIns(4,5)P2-dependent FCHO1 membrane binding, central-linker AP-2 association and muHD association with EPS15/ITSN; domain-localization comparisons distinguish membrane association from coat-partner engagement. PMID:32098969 Figures 2–3 show that human FCHO1 wild type supports membrane-localized endocytic protein organization and coordinated clathrin-coat recruitment, whereas F-BAR or muHD disease variants disrupt different components of that behavior. Together these support GO:0043495 protein-membrane adaptor activity as an IC synthesis. This is not direct clathrin or CD3 binding, enzymatic activation, universal dependence of endocytosis on FCHO1, or a unique function of a natural splice product. Official typed is_a/part_of ancestry shows no ancestor/descendant relation between this term and the existing or replacement binding terms GO:0005515, GO:0035612, GO:0097110 and GO:1990782.