ATP7B

Summary: Human ATP7B supports copper delivery in a yeast complementation assay.

Reason: PMID:9837819 tests human ATP7B variants by complementation of yeast ccc2-dependent high-affinity iron uptake. This is an indirect functional readout of copper delivery, not purified copper flux, but it supports the core P-type copper transporter function. Independent ATP-dependent vesicle transport controls in PMID:22240481 corroborate that mechanism.

Summary: ATP7B belongs to the conserved P-type copper-transporter lineage.

Reason: Retain the PAINT inference of the conserved copper-transporting P-type ATPase activity. Human ATP7B catalytic and transport experiments independently support it; no target-specific loss or divergent function was found. The ancestral node was not reconstructed, and donor number or self-inclusion is not used against the IBA.

Summary: Electronic annotation captures the established ATP-dependent copper-transporter activity.

Reason: The combined electronic assignment agrees with the human ATP7B catalytic cycle and copper transport measured in PMID:22240481. It describes the principal molecular function, irrespective of the existence of stronger experimental rows.

Summary: ATP7B enzymatic properties and ATOX1-dependent regulation support copper transport.

Reason: The complete abstract of PMID:12763797 describes functional characterization of ATP7B and regulation by ATOX1. It supports the principal copper-transporting ATPase activity. This is the Lutsenko and colleagues 2003 source; the old author/year attribution should not be repeated.

Summary: ATP7B mediates vesicular copper sequestration in cellular experiments.

Reason: PMID:16472602 reports ATP7B-dependent copper sequestration in vesicles using wild-type and mutant ATP7B in CHO cells alongside endogenous HepG2 localization. Retain the transporter activity as core, without reclassifying those cell experiments as a homogeneous purified-protein flux assay.

Summary: Reactome assigns ATP7B the Golgi copper-transport reaction.

Reason: The complete Reactome R-HSA-936895 event assigns ATP7B the transport of cytosolic Cu(I) into the Golgi lumen. This is the same core P-type copper-transporting activity supported experimentally elsewhere.

Summary: The electronic copper-transporter annotation can be specified as P-type Cu(I) transport.

Reason: The ARBA-derived copper transmembrane transporter assertion is sound but general. Refine it to the established ATP-driven P-type Cu(I) mechanism, independently corroborated by human ATP7B expressed in Sf9 microsomal vesicles in PMID:22240481. This is a specificity correction of the existing assertion; it does not add a new activity or treat the ancestor as biologically false.

Proposed replacements: P-type monovalent copper transporter activity

Summary: Human ATP7B rescue in yeast supports its specific copper-transporter mechanism.

Reason: PMID:26004889 reports wild-type human ATP7B rescue and variant-dependent impairment in yeast ccc2 cells. Preserve the original IDA tuple and the yeast complementation boundary: the assay is not purified copper flux. The specific P-type Cu(I) activity is supported by the combined functional evidence, including the independent ATP-dependent vesicle assay in PMID:22240481.

Proposed replacements: P-type monovalent copper transporter activity

Summary: The ATPase-coupled cation-transporter inference can be specified to Cu(I).

Reason: The combined electronic inference correctly describes ATP-coupled cation transport, but the identified substrate and P-type mechanism permit the more specific Cu(I) transporter term. PMID:22240481 tests ATP-dependent copper accumulation in ATP7B-containing membrane vesicles with mock, low-temperature, vanadate and catalytic-mutant controls. No additional core activity is proposed.

Proposed replacements: P-type monovalent copper transporter activity

Summary: ATOX1 transfers copper to ATP7B amino-terminal metal-binding domains.

Reason: PMID:12029094 directly reports saturable copper transfer from recombinant ATOX1 to purified ATP7B amino-terminal metal-binding domains and stimulation of full-length ATP7B catalytic activity. Copper binding is integral to the transporter mechanism.

Summary: ATP7B metal-binding domains bind Cu(I) in thermodynamic measurements.

Reason: PMID:14709553 reports thermodynamic characterization of Cu(I) binding by Wilson protein metal-binding domains and its chaperone. Retain the substrate-binding function as core; no unsupported inference about an affinity difference is needed.

Summary: Copper binding is a conserved component of ATP7B function.

Reason: The PAINT copper-binding inference agrees with direct human ATP7B domain experiments. It is a phylogenetic assertion, not weakened by the number of donor entries or by the target also having direct experimental evidence.

Summary: Electronic copper binding agrees with the experimentally characterized substrate-binding domains.

Reason: Electronic copper binding is supported by the established substrate-coordinating domains and direct copper-binding studies. This is a core mechanistic property, not an additional distinct core activity.

Summary: The ATP7B nucleotide-binding domain has a characterized ATP-binding environment.

Reason: PMID:16567646 reports structural characterization of the ATP7B nucleotide-binding domain and its ATP-binding environment. ATP binding is required for the transport cycle and is core.

Summary: Recombinant ATP7B nucleotide-binding domains bind ATP.

Reason: PMID:15205462 measures ATP binding by a recombinant ATP7B nucleotide-binding domain and analyzes disease variants. Retain this direct core mechanistic evidence; duplication of an ATP-binding term across papers is allowed.

Summary: Domain-based ATP binding agrees with the ATP-dependent transport cycle.

Reason: The InterPro-associated ATP-binding inference agrees with the directly characterized nucleotide-binding domain and ATP-driven transport. An electronic source is not a reason to demote an otherwise core property.

Summary: The domain-based nucleotide-binding inference can specify the ATP substrate.

Reason: The InterPro-derived nucleotide-binding assertion can be refined to ATP binding in the transport cycle, independently supported by recombinant ATP7B N-domain measurements in PMID:15205462. That paper also reports little discrimination among ATP, ADP and AMP, so this refinement identifies a supported substrate rather than claiming exclusive ATP binding or disproving the broader nucleotide-binding property.

Proposed replacements: ATP binding

Summary: ATP hydrolysis drives the copper-transport cycle.

Reason: ATP hydrolysis is part of the established P-type pump catalytic cycle. Retain the broad enzymatic property as core while describing the coupled copper transporter, rather than an unrelated soluble ATPase, in the synthesis.

Summary: The domain-based metal-binding inference can identify copper as its substrate.

Reason: The InterPro-derived metal-ion-binding assertion is biologically correct but nonspecific. PMID:14709553 directly characterizes Cu(I) binding by ATP7B metal-binding domains, supporting copper ion binding as the appropriate refinement. The proposal does not imply that every domain has identical affinity or that other metal interactions have been excluded.

Proposed replacements: copper ion binding

Summary: ATP7B associates with MURR1/COMMD1 through its amino-terminal region.

Reason: Bare protein binding (GO:0005515) carries no functional information, so the row is removed; removal does not mean the interaction is false. The complete abstract of PMID:12968035 reports interaction of human MURR1/COMMD1 with Wilson protein and maps interaction to the ATP7B amino-terminal region. The association itself is supported. Interaction alone does not establish a distinct ATP7B adaptor, folding, or regulatory molecular function; the reported association is not rendered biologically incorrect by the breadth of the term.

Summary: ATP7B interacts with the copper donor ATOX1; the original cited assay remains uninspected.

Reason: Bare protein binding (GO:0005515) carries no functional information, so the row is removed; removal does not mean the interaction is false. The source tuple identifies ATOX1 (UniProtKB:O00244), distinct from MURR1/COMMD1. The complete cached abstract of PMID:12968035 describes COMMD1 interaction but does not expose the ATOX1 experiment, so that original source-specific assay has not been independently verified. The complete abstract of PMID:12029094 independently describes ATP7B–ATOX1 protein interactions and demonstrates recombinant ATOX1-mediated copper transfer to purified ATP7B amino-terminal domains, with effects on full-length ATP7B catalytic activity. The ATP7B–ATOX1 association is biologically supported, but bare protein binding does not describe the copper-transfer relationship it reflects, and that corroboration comes from PMID:12029094 rather than from the uninspected original assay. ATOX1 copper-chaperone activity does not establish a chaperone or adaptor activity of ATP7B.

Summary: Cell-based precipitation supports ATP7B association with COMMD1.

Reason: Bare protein binding (GO:0005515) carries no functional information, so the row is removed; removal does not mean the interaction is false. PMID:17919502 Methods and selected Results describe ATP7B-Flag and COMMD1-GST in human HEK293T/HepG2 cells, precipitation from cell lysates, and ATP7B residues 1–650. This supports the association, not a purified binary stoichiometry. The paper does not find COMMD1 necessary for ATP7B copper-induced redistribution under its tested conditions; do not assign an invented adaptor function.

Summary: ATP7B associates with dynactin subunit DCTN4 in a copper-dependent manner.

Reason: Bare protein binding (GO:0005515) carries no functional information, so the row is removed; removal does not mean the interaction is false. The complete abstract of PMID:16554302 reports a human liver two-hybrid screen, mammalian co-immunoprecipitation and a copper-dependent ATP7B N-terminal interaction with DCTN4/dynactin p62. The association itself is not disputed. The proposed link to trafficking does not itself demonstrate a distinct ATP7B motor-adaptor activity.

Summary: ATP7B associates with glutaredoxin 1 in copper-dependent interaction assays.

Reason: Bare protein binding (GO:0005515) carries no functional information, so the row is removed; removal does not mean the interaction is false. PMID:16884690 explicitly assays both ATP7A and ATP7B interactions with glutaredoxin 1 using two-hybrid and mammalian co-immunoprecipitation approaches. The copper- and cysteine-dependent association is not disputed; the paralog-inclusive title is not misattribution, and the proposed redox model does not make ATP7B a glutaredoxin enzyme.

Summary: An ATP7B C-terminal region associates with a hepatocytic PLZF isoform.

Reason: Bare protein binding (GO:0005515) carries no functional information, so the row is removed; removal does not mean the interaction is false. PMID:16676348 reports ATP7B C-terminal interaction with a hepatocytic PLZF isoform lacking its BTB domain, supported by two-hybrid, precipitation and colocalization. The association is not disputed, but it does not make ATP7B a transcription factor or justify assigning a specific adaptor activity from association and ERK readouts alone.

Summary: Human ATP7B mediates copper transport in the yeast model.

Reason: PMID:26004889 supports copper transport by human ATP7B in the yeast model. Copper movement is the direct work of this transporter and is core; preserve the original evidence code and assay limits.

Summary: Genetic experiments support the same core copper-transport process.

Reason: The same PMID:26004889 genetic-interaction assertion concerns the core copper-transport process. A different evidence code or duplicate term does not turn a core process into a non-core process; retain the yeast model boundary.

Summary: Human ATP7B restores a yeast copper-delivery defect.

Reason: PMID:9837819 uses ATP7B-mediated rescue of yeast ccc2 copper-delivery function. Although growth/iron uptake is an indirect assay, independent direct vesicular copper transport corroborates the underlying core process. Defer to the existing IMP assertion without relabeling it direct flux.

Summary: ATP7B copper transport is established, while the exact source-specific chimera experiment has bounded access.

Reason: PMID:12572677 discusses ATP7A/MNK metal-binding mutants and WND/ATP7B amino-terminal chimeras in the complete abstract. This does not establish a wrong-gene citation. Retain the curator-assigned IGI copper-transport assertion because ATP7B transport is independently established; disclose that the precise ATP7B genetic-interaction experiment in the full paper was not reread.

Summary: ATP7B transport contributes to removal of copper from cells.

Reason: The official GO definition covers directed copper movement out of a cell or organelle. ATP7B contributes copper transport to cellular elimination through its vesicular/exocytic route, supported by PMID:16472602. Retain the PAINT core process without converting vesicular excretion into a universal direct plasma-membrane pump assay.

Summary: ATP7B transports cytosolic copper into the Golgi and vesicular lumen.

Reason: The official GO:0015677 definition includes directed movement into an organelle. ATP7B pumps cytosolic copper into the Golgi/vesicle lumen, fitting this definition. The old import-versus-export rejection used an incorrect cell-only interpretation and is not grounds to reject the PAINT assertion.

Summary: ATP7B directly contributes to intracellular copper homeostasis.

Reason: ATP7B directly transports copper into the secretory/endosomal pathway and supports removal of excess cellular copper. This direct transport contribution supports the conserved intracellular copper-homeostasis IBA as core; no phylogenetic-loss argument was found.

Summary: ATP7B copper-homeostasis function is supported independently of the interaction study alone.

Reason: PMID:16554302 investigates an ATP7B interaction in copper-dependent trafficking, while independent catalytic and cellular studies establish ATP7B itself as a copper-homeostasis transporter. Retain the TAS core process with curatorial deference; the paper does not turn DCTN4 association into a new ATP7B activity.

Summary: ATP7B sequesters excess copper into vesicles for cellular elimination.

Reason: PMID:16472602 reports ATP7B-dependent sequestration of excess copper into vesicles followed by exocytosis. ATP7B performs the transport step in copper detoxification, satisfying direct participation rather than mere necessity.

Summary: The source-specific plasma-membrane xenobiotic-export inference remains unresolved.

Reason: GO:1990961 specifically requires detoxification by export across the plasma membrane to the cell exterior. The accessible PMID:9837819 abstract describes human ATP7B variant complementation in yeast and does not resolve that exact IC mechanism. Copper being essential does not exclude a xenobiotic role, but the source-specific plasma-membrane export inference remains unverified. No REMOVE or wrong-gene claim is warranted.

Summary: The electronic cation-transport process can specify copper movement across a membrane.

Reason: The InterPro-derived monoatomic-cation transport annotation captures a real ATP7B function. Direct ATP-dependent copper uptake into ATP7B-containing vesicles in PMID:22240481 supports the more informative copper ion transmembrane transport term. This specifies the transported ion and membrane step without adding a separate process assertion or asserting indiscriminate cation transport.

Proposed replacements: copper ion transmembrane transport

Summary: The broad Reactome P-type ion-transport annotation can specify its ATP7B copper step.

Reason: The original Reactome R-HSA-936837 annotation is pathway-level P-type ion transport. Its ATP7B event R-HSA-936895 explicitly transports cytosolic Cu(I) into the Golgi lumen, supporting refinement to copper ion transmembrane transport. The event supplies the specific substrate and membrane step; membership in the broad pathway alone is not treated as evidence for every P-type substrate.

Proposed replacements: copper ion transmembrane transport

Summary: ATP7B redistribution and transport respond to elevated copper.

Reason: PMID:16472602 directly reports copper-dependent redistribution and ATP7B-mediated handling of excess copper in cells. This is a core response in which the transporter performs the copper-sequestration step, not only a change in its expression.

Summary: ATP7B catalytic-state mutations alter copper-dependent trafficking.

Reason: PMID:16939419 reports copper-dependent ATP7B redistribution and catalytic-domain mutant effects. Its cached abstract/introduction/discussion support this response, but the cache omits Methods/Results despite full_text_available=true. Retain the core response while making that reading limit explicit.

Summary: The inferred copper response agrees with direct cellular observations.

Reason: The electronic response-to-copper inference is consistent with direct copper-induced trafficking and transport studies, including PMID:16472602 and PMID:16939419. It represents the core regulated copper-handling response.

Summary: ATP7B copper responsiveness is independently established; the original paper-specific target panel is unverified.

Reason: Retain the experimental response-to-copper assertion with explicit curatorial deference and independent ATP7B support from PMID:16472602 and PMID:16939419. The accessible PMID:15269005 abstract foregrounds ATP7A in polarized MDCK cells; its exact ATP7B experiment remains unverified, so it must not be described as directly checked or confidently misattributed. The biological response is independently established.

Summary: The ATP7B transport cycle operates at the trans-Golgi network membrane.

Reason: ATP7B TGN membrane localization is directly supported by independent human-cell work and the Golgi copper-transport reaction. Retain the curator-assigned PMID:9837819 location with that corroboration; the available yeast-complementation abstract does not itself verify the cited localization panel.

Summary: Electronic TGN membrane localization agrees with functional evidence.

Reason: The electronic TGN membrane location agrees with established ATP7B localization and its Golgi copper-delivery function. This is a core functional compartment, irrespective of the presence of another evidence code.

Summary: Endogenous ATP7B resides in the Golgi system before copper-induced redistribution.

Reason: PMID:16472602 follows endogenous ATP7B in HepG2 cells from its basal Golgi distribution to copper-induced pericanalicular vesicles. Retain the TGN as a core compartment without claiming that the complete paper or figure pixels were read.

Summary: Orthology-derived TGN localization is independently supported for human ATP7B.

Reason: The orthology-derived TGN location is independently supported on human ATP7B. Retain the core location without using donor count or source duplication to demote it.

Summary: Human ATP7B TGN localization is independently established; the original paper-specific target panel is unverified.

Reason: Retain the experimental TGN location with curatorial deference and independent human ATP7B localization support, including PMID:16472602 and selected PMID:17919502 Results. The exact ATP7B panel in PMID:15269005 was not recovered; the ATP7A-focused abstract cannot justify its old wrong-paralog REMOVE.

Summary: Curated Golgi immunofluorescence agrees with the established core compartment.

Reason: The curated immunofluorescence Golgi annotation is consistent with the well-supported human ATP7B TGN localization. Retain this core organelle location; the exact source image was not independently inspected.

Summary: Golgi apparatus localization supports the secretory copper-delivery role.

Reason: The UniProt-derived Golgi location agrees with the principal secretory-pathway function of ATP7B. This broad core location is not invalidated by the more specific TGN annotations.

Summary: ATP7B is a membrane transporter in the Golgi system.

Reason: ATP7B is an integral membrane copper pump in the Golgi/TGN system. Retain Golgi membrane as a core location and preserve the original machine-sourced term.

Summary: Reactome places ATP7B copper transport at Golgi membrane.

Reason: The complete Reactome R-HSA-936895 event places the ATP7B copper-transport reaction at Golgi membrane. This is direct functional context for a core location.

Summary: Copper-induced ATP7B vesicles participate in copper sequestration.

Reason: PMID:16472602 reports endogenous ATP7B in copper-induced pericanalicular vesicles and ATP7B-dependent vesicular copper accumulation. Cytoplasmic vesicles are a core compartment for this demonstrated detoxification route.

Summary: ATP7B localizes with late-endosome markers in the studied cellular models.

Reason: The complete cached Results of PMID:15681833 compare endogenous ATP7B and fluorescent constructs with late-endosome markers, including Rab7/NPC1, in several cellular models and use U18666A perturbation. Retain the directly observed late-endosomal location as a core trafficking compartment with model dependence; neither universal late-endosome residence nor direct lumenal copper flux was established by those imaging experiments alone.

Summary: The electronic late-endosome location has independent experimental support.

Reason: The electronic late-endosome location is independently supported by ATP7B localization experiments in PMID:15681833 and the curated UniProt location. Retain it without dismissing the original study as merely a minority view.

Summary: ATP7B can show a perinuclear distribution.

Reason: PMID:16939419 reports perinuclear ATP7B distributions and copper-dependent redistribution, including mutant effects. Perinuclear region is a supported coarse spatial description; retain it as non-core rather than treating it as a distinct functional compartment or generic cytosolic activity.

Summary: ATP7B has context-dependent plasma-membrane localization.

Reason: Do not reject the PAINT plasma-membrane location with a universal-absence claim. Indexed original PMID:38032054 Results/Figure 1 text and Methods report tagged ATP7B at the gp135-positive apical surface of polarized MDCK cells after copper exposure. Retain a context-dependent non-core location; this is not proof of constitutive human plasma-membrane residence or direct membrane copper flux.

Summary: Later ATP7B surface-localization evidence qualifies the historical TAS assertion.

Reason: Retain the plasma-membrane location using explicit independent later localization support from PMID:38032054, rather than claiming that the partial-clone PMID:8298641 abstract establishes a surface-localization assay. The source-specific 1993 TAS derivation is not reconstructed, but the location is not biologically excluded. Preserve a context-dependent non-core interpretation.

Summary: The original ATP7B basolateral-membrane experiment remains unresolved.

Reason: The exact ATP7B evidence behind the basolateral plasma-membrane IDA in PMID:15269005 remains unavailable. Its ATP7A-focused abstract is insufficient to claim misattribution. Later ATP7B apical localization and altered sorting of mutants do not, by themselves, verify wild-type basolateral residence in the original experiment.

Summary: The electronic membrane localization can specify a supported ATP7B compartment.

Reason: The combined electronic membrane assertion is sound but general. Independent ATP7B evidence, including the curated Golgi transport event R-HSA-936895, supports trans-Golgi network membrane as a specific compartment. This refinement does not imply exclusive or constitutive TGN residence; copper-responsive late-endosomal and other cellular locations remain represented separately.

Proposed replacements: trans-Golgi network membrane

Summary: The curated NK-cell membrane-proteome observation is retained as a contextual location.

Reason: PMID:19946888 describes a YTS NK-cell membrane proteomic survey. Retain its curated HDA membrane assertion with source-specific deference, while the exact ATP7B target table remains uninspected. This study does not independently establish TGN localization in the material read; the separately supported TGN annotation must not be substituted for its measured compartment. The broad high-throughput observation is retained as non-core context.

Summary: The cytoplasmic localization mapping has alternative-product context.

Reason: The immutable UniProt record distinguishes a cytoplasmic alternative isoform from the principal membrane-localized transporter. Retain the cytoplasm mapping with product context, without projecting soluble localization onto full-length canonical ATP7B or inventing another product.

Summary: Mitochondrial localization is reported for a 140-kDa ATP7B product.

Reason: The immutable UniProt record explicitly associates a 140-kDa Wilson-protein species with mitochondria. Independent primary consultation of PMID:9600907 Methods/Results/captions supports that processed-product context. Preserve a non-core mitochondrial location without inventing a splice-isoform identity, a precise cleavage site, or a new mitochondrial function. ORGANELLES check (2026-10-24), as a synthesis row - GO_REF:0000044 maps UniProt SL-0173, which the record gives for the WND/140 kDa chain from PMID:9600907 (immunofluorescence with mitochondrial markers, membrane fractionation and purified human mitochondria), so the feature the mapping assumes is present and the organelle claim stands for that product. Stays at the root - ATP7B has eight curated TM segments, but no cached study places the 140-kDa product in the inner or outer membrane (no mitoplast, protease protection or sub-mitochondrial fractionation), so membrane topology is the only line and no sub-compartment row is added.

Summary: MitoCoP high-confidence mitochondrial proteome entry; the ATP7B-specific call is in uncached supplementary tables.

Reason: The ATP7B entry, evidence category and product identity in the PMID:34800366 MitoCoP target supplement were not verified. Its fourth pool includes literature-selected proteins, so inclusion cannot be equated with an ATP7B measurement in every proteomic assay. The processed 140-kDa literature is relevant but does not resolve this exact HTP assertion; no contamination or full-length-localization claim is justified. ORGANELLES check (2026-10-24) - the cached PMID:34800366 text does not name ATP7B or P35670, so the entry cannot be verified here. It is kept as non-core in deference to the GOA curator, as for AMACR's MitoCoP row. Its claim, a mitochondrial pool of (processed) ATP7B, is the same claim the IEA row makes on independent support (PMID:9600907), so the two rows on this term carry consistent actions. The HTP assay could not resolve a sub-compartment in any case.