ATP7A

Summary: The broad nucleotide-binding mapping is compatible with ATP7A, but ATP binding is directly established by the purified human nucleotide-binding-domain NMR study in PMID:19917612.

Reason: The broad nucleotide-binding mapping is compatible with ATP7A, but ATP binding is directly established by the purified human nucleotide-binding-domain NMR study in PMID:19917612. Refine the nonspecific ligand class to ATP binding. This is a refinement of the existing source row, not a new function or a full-length transport measurement.

Proposed replacements: ATP binding

Summary: Retain the curator's mouse Q64430 transfer as a peripheral developmental consequence of copper delivery to vascular cuproenzymes.

Reason: Retain the curator's mouse Q64430 transfer as a peripheral developmental consequence of copper delivery to vascular cuproenzymes. Vascular abnormalities fit the established ATP7A phenotype, but this assessment has not reconstructed the donor's individual vessel-development experiment and does not make ATP7A a vascular structural protein or a separate developmental core.

Summary: The Q64430 ortholog assertion is compatible with copper-dependent vascular matrix maintenance and remodeling.

Reason: The Q64430 ortholog assertion is compatible with copper-dependent vascular matrix maintenance and remodeling. Retain the existing curated peripheral process with explicit donor deference; the exact remodeling assay was not reread and no direct remodeling enzyme activity is attributed to ATP7A.

Summary: The transferred regulation-of-oxidative-phosphorylation assertion needs its mouse donor experiment and causal context.

Reason: The transferred regulation-of-oxidative-phosphorylation assertion needs its mouse donor experiment and causal context. A bounded primary abstract lead reports respiratory-chain changes in copper-deficient mottled mice, but that is not enough to distinguish regulation by ATP7A from systemic copper deficiency or secondary metabolic compensation. Do not infer a mitochondrial ATP7A pump or remove an unread donor assertion.

Summary: PMID:10419525 directly reports recombinant human ATP7A and an in-vitro vesicle copper-transport assay, supporting the defining copper transporter activity.

Reason: PMID:10419525 directly reports recombinant human ATP7A and an in-vitro vesicle copper-transport assay, supporting the defining copper transporter activity. The complete abstract was read; full assay Methods and the listed erratum body were not read. The more specific monovalent P-type activity already exists in rows110-112, so no duplicate replacement is needed.

Summary: The automatic Q64430/ENSMUSP00000109186 ortholog transfer agrees with direct human copper-transport evidence in PMID:10419525.

Reason: The automatic Q64430/ENSMUSP00000109186 ortholog transfer agrees with direct human copper-transport evidence in PMID:10419525. Retain this correct parent of the specific P-type Cu(I) pump activity as part of the core mechanism, without treating the transfer itself as a new human assay.

Summary: The manually transferred mouse copper transporter function is conserved and independently established for human ATP7A by PMID:10419525.

Reason: The manually transferred mouse copper transporter function is conserved and independently established for human ATP7A by PMID:10419525. The original ISS source and donor are preserved; this is a core transport activity.

Summary: Copper binding is an experimentally grounded substrate-recognition component of ATP7A, supported by the human domain studies and the PAINT ancestral assertion at PTN000642961.

Reason: Copper binding is an experimentally grounded substrate-recognition component of ATP7A, supported by the human domain studies and the PAINT ancestral assertion at PTN000642961. The target Q04656 legitimately appears among the descendant evidence; this is not circular support. It is retained within the pump mechanism, not synthesized as a second core.

Summary: PMID:15670166 directly studies Cu(I) transfer from human HAH1/ATOX1 to ATP7A's second and fifth metal-binding domains by NMR.

Reason: PMID:15670166 directly studies Cu(I) transfer from human HAH1/ATOX1 to ATP7A's second and fifth metal-binding domains by NMR. This supports copper binding by the tested domains; it does not itself measure full-length membrane transport or establish a stable ATOX1 complex.

Summary: The ARBA/InterPro copper-binding mapping is consistent with experimentally characterized ATP7A CXXC domains.

Reason: The ARBA/InterPro copper-binding mapping is consistent with experimentally characterized ATP7A CXXC domains. Preserve the electronic provenance and retain the activity as a substrate-binding component of the copper pump.

Summary: ATP7A associates with PDZD11/AIPP1 through a C-terminal-tail-dependent interaction.

Reason: The PMID:16051599 abstract establishes the ATP7A-AIPP1/PDZD11 pair. A separate independent reading of original construct Methods, interaction/domain-analysis Results, Figures1-2 captions and targeted Discussion reports human ATP7A-tail binding to near-full-length AIPP1 prey and mammalian co-immunoprecipitation. Deleting the final15 ATP7A residues abolished the interaction, whereas dileucine-to-alanine substitution did not. The inspected experiments did not isolate or mutate the partner PDZ domain; binding to the terminal DTAL motif remains an interpretation consistent with the tail result. Retain the verified association as non-core without asserting the more specific GO:0030165 interface from a PDZ-containing partner alone. This does not deny the plausible PDZ mechanism; the SNX27 row has separate partner-domain deletion evidence.

Summary: PMID:16371425 reports ATP7A-SOD3 association and copper-dependent SOD3 activation.

Reason: PMID:16371425 reports ATP7A-SOD3 association and copper-dependent SOD3 activation. The independent primary consultation verifies mouse-cell co-immunoprecipitation, human ATP7A transfection in CHO-SOD3 cells, and human recombinant SOD3 pull-down from mouse lysate; the CHO-SOD3 construct species was not recovered. Retain the curated human pair with these mixed-species and assay limits, without claiming purified binary binding or ATP7A superoxide-dismutase catalysis.

Summary: ATP7A binding to GRX1 depends on copper and intact metal-binding motifs.

Reason: The complete PMID:16884690 abstract explicitly identifies GRX1 as an ATP7A and ATP7B partner and states that interaction requires copper and intact metal-binding motifs, using yeast two-hybrid and mammalian co-immunoprecipitation approaches. GO:0032767 is the specific copper-dependent protein-binding activity; its official definition cites this same paper. Refine the association without transferring GRX1 oxidoreductase chemistry to ATP7A. The full Methods and purified binary binding were not independently established.

Proposed replacements: copper-dependent protein binding

Summary: ATP7A associates with ATOX1 under copper-replete pull-down conditions.

Reason: PMID:21667063 selected construct Methods and Results/Figures1 and6 describe human ATP7A wild-type and mutant proteins in HEK293T cells and ATOX1 GST pull-downs whose recovery depends on copper. The Results distinguish this association from copper-independent COMMD1 binding. Refine the generic ATOX1 row to GO:0032767 on this source-specific evidence, rather than solely copying the same-partner annotation from PMID:10497213. The experiment does not assign a separate copper-chaperone core to ATP7A or establish purified binary binding.

Proposed replacements: copper-dependent protein binding

Summary: PMID:21667063 directly tests COMMD1 binding to wild-type and mutant human ATP7A, including ATP7A cytosolic regions and the COMMD1 COMM region.

Reason: PMID:21667063 directly tests COMMD1 binding to wild-type and mutant human ATP7A, including ATP7A cytosolic regions and the COMMD1 COMM region. The COMMD1 association is retained as non-core. Its copper dependence differs from ATOX1 in the reported assay, and improved ATP7A expression does not establish a new ATP7A regulatory enzyme activity.

Summary: The selected primary Results/Fig3A of PMID:23563491 show ATP7A C-terminal-tail pull-down of SNX27 and loss of recovery for SNX27 lacking its PDZ domain.

Reason: The selected primary Results/Fig3A of PMID:23563491 show ATP7A C-terminal-tail pull-down of SNX27 and loss of recovery for SNX27 lacking its PDZ domain. GO:0030165 PDZ domain binding is therefore a supported specific replacement for the generic binding row. These Results were read in the preserved staged XML alternate; the normal canonical record remains abstract-only, and no whole-paper or purified-binary-assay claim is made.

Proposed replacements: PDZ domain binding

Summary: The indexed primary Results/Fig2 of PMID:26199316 directly recover endogenous ATP7A with endogenous dopamine beta-hydroxylase in human SH-SY5Y cells, with antigen-peptide competition and transferrin-receptor controls.

Reason: The indexed primary Results/Fig2 of PMID:26199316 directly recover endogenous ATP7A with endogenous dopamine beta-hydroxylase in human SH-SY5Y cells, with antigen-peptide competition and transferrin-receptor controls. Retain the association as non-core; co-immunoprecipitation is not proof of purified binary binding, and ATP7A supplies copper rather than catalyzing dopamine hydroxylation.

Summary: PMID:19917612 studies the purified human ATP7A nucleotide-binding domain, residues1051-1231, expressed in E.coli and examined by solution NMR with ATP.

Reason: PMID:19917612 studies the purified human ATP7A nucleotide-binding domain, residues1051-1231, expressed in E.coli and examined by solution NMR with ATP. The selected construct Methods and ATP-binding Results support ATP binding as part of the pump's core catalytic mechanism, without claiming a full-length transport assay in this paper.

Summary: The P-type ATPase InterPro assignment agrees with the directly characterized human ATP-binding domain and the ATP-dependent copper-transport mechanism.

Reason: The P-type ATPase InterPro assignment agrees with the directly characterized human ATP-binding domain and the ATP-dependent copper-transport mechanism. Preserve this electronic source while retaining the activity as a core catalytic component.

Summary: ATP binding is correct for ATP7A and independently supported by PMID:19917612.

Reason: ATP binding is correct for ATP7A and independently supported by PMID:19917612. PMID:9817923 chiefly addresses the C-terminal trafficking signal in the available abstract; retain this TAS statement with curator deference and explicit independent ATP-binding support rather than presenting the trafficking paper as a direct nucleotide-binding assay.

Summary: Endosomal residence is compatible with ATP7A's observed recycling between the plasma membrane and trans-Golgi network.

Reason: Endosomal residence is compatible with ATP7A's observed recycling between the plasma membrane and trans-Golgi network. Retain the ARBA location as a non-core trafficking compartment; this does not turn ATP7A cargo into an endosome-organization factor.

Summary: PMID:8943055 reports ATP7A in TGN-associated and peripheral vesicles, including overlap with the cation-independent mannose-6-phosphate receptor in selected localization Results.

Reason: PMID:8943055 reports ATP7A in TGN-associated and peripheral vesicles, including overlap with the cation-independent mannose-6-phosphate receptor in selected localization Results. Retain late-endosomal localization with curator deference; the read panels do not warrant universal lysosomal localization or an additional endosomal function core.

Summary: PMID:9467005 explicitly distinguishes the major Golgi-localized product from an exon10-skipped product colocalizing with ER-resident BiP.

Reason: PMID:9467005 explicitly distinguishes the major Golgi-localized product from an exon10-skipped product colocalizing with ER-resident BiP. That transcript occurs at low levels in normal individuals as well as constitutively in the OHS family. Retain ER localization in this processed splice-product context; do not generalize it to the principal functional pump or invent an isoform field absent from the source row. ORGANELLES check (2026-11-04). Direct evidence with an ER marker (BiP colocalization), and the exon 10-skipped product is a natural low-level splice form (UniProt isoform 5, Q04656-5), so this is a real minor ER pool rather than mere biosynthetic transit; KEEP_AS_NON_CORE stands. The pool is ER retention of a variant lacking transmembrane domains 3 and 4 that cannot effect copper transport, so the ER is not where the copper-pump activity acts. The variant keeps six of the eight annotated helices and is very likely membrane-embedded, but the paper (abstract only in the cache) reports no assay resolving ER membrane from lumen, and inferred topology of a retained deletion form is a single line, so no ER-membrane sub-compartment row is added; the row stays at the root.

Summary: The UniProt ER mapping is consistent with the separately described isoform5/exon10-skipped product in PMID:9467005.

Reason: The UniProt ER mapping is consistent with the separately described isoform5/exon10-skipped product in PMID:9467005. Retain this location as non-core with product specificity rather than rejecting it because the principal ATP7A product is a TGN/plasma-membrane transporter. ORGANELLES check (2026-11-04). The SL-0095 keyword comes from the isoform-specific UniProt line for isoform 5, tagged ECO:0000269 with PubMed:9467005, so the electronic row restates the EXP row's real, isoform-restricted ER pool and keeps the same KEEP_AS_NON_CORE action; the mapping drops the isoform restriction, which is one more reason it is non-core. UniProt gives no ER sub-location, so the row stays at the root.

Summary: The immunofluorescence-curated Golgi annotation agrees with direct human localization in PMID:8943055 and PMID:9147644.

Reason: The immunofluorescence-curated Golgi annotation agrees with direct human localization in PMID:8943055 and PMID:9147644. Retain the correct parent location for the TGN copper-supply core; the exact original GO_REF imaging record was not independently reopened.

Summary: PMID:9467005 explicitly places the major ATP7A product in the perinuclear Golgi system and contrasts it with the exon10-skipped ER product.

Reason: PMID:9467005 explicitly places the major ATP7A product in the perinuclear Golgi system and contrasts it with the exon10-skipped ER product. Retain Golgi localization for the principal copper-pump activity while preserving all six products.

Summary: The combined ortholog/subcellular-location mapping agrees with direct human Golgi localization.

Reason: The combined ortholog/subcellular-location mapping agrees with direct human Golgi localization. Retain this parent of TGN localization without manufacturing a new Golgi-function process annotation.

Summary: The PTN001185001 PAINT inference agrees with ATP7A's established activity at the trans-Golgi network.

Reason: The PTN001185001 PAINT inference agrees with ATP7A's established activity at the trans-Golgi network. Target Q04656 among the descendant evidence is expected, not circular. Human localization and copper-dependent secretory-pathway enzyme activation independently support this core compartment.

Summary: PMID:12812980 examines ATP7A trafficking between the TGN and cell surface and supports this established location.

Reason: PMID:12812980 examines ATP7A trafficking between the TGN and cell surface and supports this established location. Retain the IDA annotation, while recognizing that ATP7A is the trafficked cargo rather than the machinery catalyzing its own endocytosis.

Summary: The selected localization Results and complete Methods of PMID:8943055 identify human ATP7A in the trans-Golgi region using marker comparisons.

Reason: The selected localization Results and complete Methods of PMID:8943055 identify human ATP7A in the trans-Golgi region using marker comparisons. Retain this central compartment for copper delivery to secretory-pathway cuproenzymes.

Summary: The ARBA and ortholog mapping is concordant with independently established human TGN localization.

Reason: The ARBA and ortholog mapping is concordant with independently established human TGN localization. Retain the core location with the original evidence/source objects unchanged.

Summary: The immutable UniProt record separately describes a cytosolic short product, isoform3 by name (Q04656-4), whereas the principal pump is multipass membrane-associated.

Reason: The immutable UniProt record separately describes a cytosolic short product, isoform3 by name (Q04656-4), whereas the principal pump is multipass membrane-associated. Retain the generic cytosol mapping as a product-dependent non-core location; do not infer that full-length ATP7A is normally soluble or silently assign this row to a specific isoform.

Summary: PMID:10484781 uses an exofacial tag and surface-antibody uptake to demonstrate ATP7A cycling through the plasma membrane under basal and elevated copper.

Reason: PMID:10484781 uses an exofacial tag and surface-antibody uptake to demonstrate ATP7A cycling through the plasma membrane under basal and elevated copper. This is a core location for cellular copper export, not a constitutive claim that all ATP7A molecules reside at the surface.

Summary: PMID:28389643 compares ATP7A trafficking and copper retention in human patient fibroblasts and mutant constructs.

Reason: PMID:28389643 compares ATP7A trafficking and copper retention in human patient fibroblasts and mutant constructs. Retain plasma-membrane localization as an established copper-responsive state. The selected Methods and abstract were read; individual mutant localization panels are not all independently verified here.

Summary: Plasma-membrane localization is directly established by independent human ATP7A studies, especially PMID:10484781 and PMID:12812980.

Reason: Plasma-membrane localization is directly established by independent human ATP7A studies, especially PMID:10484781 and PMID:12812980. The complete Results of PMID:9147644 read here primarily demonstrate Golgi/TGN localization; its plasma-membrane discussion is a proposed trafficking model. Retain the correct location through explicit curator deference and independent evidence, without claiming that this paper's read panels directly show the surface pool.

Summary: The ancestral PAINT plasma-membrane assertion at PTN001185001 agrees with direct human ATP7A surface-cycling and copper-efflux evidence.

Reason: The ancestral PAINT plasma-membrane assertion at PTN001185001 agrees with direct human ATP7A surface-cycling and copper-efflux evidence. The target's presence in the descendant list is valid. Retain this core active compartment.

Summary: PMID:12812980 explicitly investigates ATP7A internalization from the plasma membrane.

Reason: PMID:12812980 explicitly investigates ATP7A internalization from the plasma membrane. Retain this experimentally grounded copper-export compartment without inferring ATP7A itself has endocytic adaptor activity.

Summary: The combined ARBA, ortholog and UniProt location inference agrees with direct surface-antibody experiments on ATP7A.

Reason: The combined ARBA, ortholog and UniProt location inference agrees with direct surface-antibody experiments on ATP7A. Retain the core plasma-membrane location and the original electronic evidence provenance.

Summary: The complete R-HSA-936802 summary and official event identify the human ATP7A:PDZD11 catalyst at the plasma membrane, moving Cu(I) to the extracellular region.

Reason: The complete R-HSA-936802 summary and official event identify the human ATP7A:PDZD11 catalyst at the plasma membrane, moving Cu(I) to the extracellular region. Retain the event-grounded location; this does not require inventing a new protein-complex annotation.

Summary: The Q64430 catecholamine-process transfer is compatible with ATP7A-mediated copper delivery to dopamine beta-hydroxylase and the human ATP7A-DBH association in PMID:26199316.

Reason: The Q64430 catecholamine-process transfer is compatible with ATP7A-mediated copper delivery to dopamine beta-hydroxylase and the human ATP7A-DBH association in PMID:26199316. Retain the existing physiological process as non-core with ortholog deference, not as direct ATP7A catecholamine catalysis.

Summary: ATP7A transports copper ions across membranes.

Reason: The InterPro:IPR027256 monoatomic-cation-transport mapping is biologically compatible but does not identify ATP7A's substrate or membrane-translocation role. Refine this electronic parent to GO:0035434 copper ion transmembrane transport, supported independently by the human ATP7A vesicle transport and copper-responsive trafficking experiments in PMID:10419525. This refinement covers transport across secretory and cell-surface membranes without assigning an additional tissue process. Existing copper-specific annotations do not prevent refining this separate broad source row; no NEW row is added.

Proposed replacements: copper ion transmembrane transport

Summary: PMID:11092760 demonstrates copper-dependent rescue of tyrosinase activity by ATP7A in Menkes fibroblasts and dependence on the invariant phosphorylation-site residue.

Reason: PMID:11092760 demonstrates copper-dependent rescue of tyrosinase activity by ATP7A in Menkes fibroblasts and dependence on the invariant phosphorylation-site residue. This supports ATP7A-mediated copper transport into the secretory pathway. ATP7A is the copper transporter, not the melanogenic oxidase.

Summary: The PTN008451426 ancestral copper-homeostasis assignment matches the established human pump mechanism and cellular copper-retention phenotypes.

Reason: The PTN008451426 ancestral copper-homeostasis assignment matches the established human pump mechanism and cellular copper-retention phenotypes. The target is valid descendant evidence in PAINT. Retain the homeostatic process as core.

Summary: Mouse-ortholog electronic transfer of copper homeostasis is independently supported by human ATP7A transport and retention experiments.

Reason: Mouse-ortholog electronic transfer of copper homeostasis is independently supported by human ATP7A transport and retention experiments. Retain the original transfer provenance and the core biological role.

Summary: PMID:16397091 expresses human ATP7A in transgenic mice and reports altered tissue copper levels and distribution.

Reason: PMID:16397091 expresses human ATP7A in transgenic mice and reports altered tissue copper levels and distribution. This supports the human protein's copper-homeostatic capacity, while the organismal experiment is explicitly a mouse host rather than a human physiological trial.

Summary: PMID:28389643 measures abnormal copper accumulation/retention in human patient fibroblasts and evaluates ATP7A variants.

Reason: PMID:28389643 measures abnormal copper accumulation/retention in human patient fibroblasts and evaluates ATP7A variants. Retain the core copper-homeostasis process, separating measured cellular phenotypes from proposed structural explanations for particular mutations.

Summary: The mouse ISS assertion for mitochondrion organization has not been traced to the relevant donor experiment in this audit.

Reason: The mouse ISS assertion for mitochondrion organization has not been traced to the relevant donor experiment in this audit. ATP7A deficiency can cause secondary copper-dependent respiratory and ultrastructural changes, but that does not independently establish an ATP7A organization step or mitochondrial localization. Retain uncertainty rather than remove the unread curated transfer.

Summary: Retain the curated mouse locomotory-behavior transfer as a peripheral organismal consequence of ATP7A-dependent neuronal copper supply.

Reason: Retain the curated mouse locomotory-behavior transfer as a peripheral organismal consequence of ATP7A-dependent neuronal copper supply. The exact donor behavioral test was not reread; this is not a distinct motor enzyme activity or a claim that human behavior was directly assayed.

Summary: The Q64430 glycoprotein-biosynthesis transfer needs the donor's specific product, assay and ontology-propagation context.

Reason: The Q64430 glycoprotein-biosynthesis transfer needs the donor's specific product, assay and ontology-propagation context. ATP7A's established support of secretory cuproenzymes does not by itself establish general glycoprotein synthesis. Do not infer a glycosyltransferase function or remove an unread donor assertion.

Summary: Copper export directly lowers excess cellular copper and is a detoxification step performed by ATP7A itself.

Reason: Copper export directly lowers excess cellular copper and is a detoxification step performed by ATP7A itself. Retain the mouse-transferred copper-detoxification process as part of the principal transport role, supported independently by human copper-hyperaccumulation and transport-defective phenotypes.

Summary: The UniProt postsynaptic-density mapping concerns neuronal ATP7A distribution and is distinct from its broadly expressed TGN/plasma-membrane activity.

Reason: The UniProt postsynaptic-density mapping concerns neuronal ATP7A distribution and is distinct from its broadly expressed TGN/plasma-membrane activity. Retain the specialized non-core location with the record's orthology limits; no human postsynaptic fraction experiment was newly verified.

Summary: The P70705 rat-ortholog postsynaptic-density transfer is retained as a specialized neuronal location.

Reason: The P70705 rat-ortholog postsynaptic-density transfer is retained as a specialized neuronal location. It is not evidence that ATP7A is a structural postsynaptic scaffold, and the exact rat localization experiment was not reread.

Summary: GO:0015677 includes copper movement into an organelle, not only entry across the cell surface.

Reason: GO:0015677 includes copper movement into an organelle, not only entry across the cell surface. The PTN001185001 inference is therefore consistent with ATP7A delivering copper from cytosol into the secretory pathway. Retain the ancestral assertion without using the short donor list as a weakness.

Summary: The mouse copper-import transfer is compatible with organellar uptake into the TGN lumen and independent human secretory-pathway copper delivery in PMID:11092760.

Reason: The mouse copper-import transfer is compatible with organellar uptake into the TGN lumen and independent human secretory-pathway copper delivery in PMID:11092760. It does not assert that ATP7A imports extracellular copper into the cytosol.

Summary: Retain the broad membrane observation at the resolution of its original proteomics source.

Reason: The original HDA membrane annotation is retained with curatorial deference. The cached PMID:19946888 abstract describes the NK-cell membrane-proteomics study, but its ATP7A target entry and compartment-specific evidence were not inspected. Independent ATP7A imaging establishes TGN and plasma-membrane locations, already represented in their own reviewed rows. Those studies support membrane association but do not make this proteomics observation compartment-specific; retain it as non-core without replacement.

Summary: The electronic membrane mapping is correct for the principal multipass ATP7A pump but nonspecific.

Reason: The electronic membrane mapping is correct for the principal multipass ATP7A pump but nonspecific. Refine it to the independently established TGN and plasma-membrane locations, retaining copper-dependent cycling and the distinct short-product localization limits. This does not assign every alternative product to both compartments.

Proposed replacements: trans-Golgi network membrane plasma membrane

Summary: PMID:16397091 addresses human ATP7A expressed in a mouse tissue context and is curated for basolateral surface localization.

Reason: PMID:16397091 addresses human ATP7A expressed in a mouse tissue context and is curated for basolateral surface localization. Retain this physiologically relevant copper-export surface with curator deference; the precise basolateral panel was not independently read and the evidence is not re-described as a human-tissue IDA assay.

Summary: PMID:16371425 supports ATP7A-dependent SOD3 activation and association, but the exact copper handoff remains unresolved.

Reason: PMID:16371425 supports ATP7A-dependent SOD3 activation and association, but the exact copper handoff remains unresolved. GO:0016532 inherits molecular-carrier activity GO:0140104, whose comment distinguishes a carrier moving with cargo from a transporter facilitating its movement. The electronic mouse transfer therefore has a carrier-versus-membrane-pump mapping ambiguity; this is not a denial of SOD3 copper delivery or an assertion that the term is restricted to SOD1.

Summary: The manually transferred mouse SOD copper-chaperone annotation has the same unresolved ontology boundary: the primary evidence supports copper-dependent SOD3 activity/association, while GO:0016532 inherits a carrier convention not automatically established by ATP7A membrane transport.

Reason: The manually transferred mouse SOD copper-chaperone annotation has the same unresolved ontology boundary: the primary evidence supports copper-dependent SOD3 activity/association, while GO:0016532 inherits a carrier convention not automatically established by ATP7A membrane transport. Preserve the curated ISS assertion pending clarification rather than converting physiological copper provision into a confidently verified mobile-carrier MF or a new SOD enzyme activity.

Summary: ATP hydrolysis is the energy-coupling component of the P-type copper pump and is supported by its catalytic domain and ATP-dependent transport behavior.

Reason: ATP hydrolysis is the energy-coupling component of the P-type copper pump and is supported by its catalytic domain and ATP-dependent transport behavior. Retain the InterPro-derived activity within the principal transport mechanism, not as an independent soluble ATPase core.

Summary: The mouse radical-removal annotation can describe ATP7A's copper-cofactor contribution to SOD3 activation rather than ATP7A catalyzing dismutation.

Reason: The mouse radical-removal annotation can describe ATP7A's copper-cofactor contribution to SOD3 activation rather than ATP7A catalyzing dismutation. Retain the existing peripheral process with explicit ortholog and participation limits. This is not a proposal for a new antioxidant enzyme function.

Summary: ATP7A is a P-type monovalent copper pump.

Reason: The InterPro:IPR027256 ATPase-coupled cation-transporter parent is correct but insufficiently specific for ATP7A. Refine it to GO:0140581 P-type monovalent copper transporter activity, combining the original family mapping with the independently established human copper-pump mechanism and Cu(I)-binding domain evidence. This is a specificity refinement of a compatible electronic assertion; it does not change the original evidence tuple or introduce a NEW function. The existing Cu(I)-specific rows retain their own evidence.

Proposed replacements: P-type monovalent copper transporter activity

Summary: Retain the existing mouse Purkinje-cell differentiation transfer as a peripheral developmental role with explicit curator deference.

Reason: Retain the existing mouse Purkinje-cell differentiation transfer as a peripheral developmental role with explicit curator deference. ATP7A-dependent neuronal copper supply provides a coherent biological context, but the exact donor differentiation experiment has not been reconstructed and no human differentiation assay is claimed.

Summary: Retain the curated mouse pyramidal-neuron development transfer as a peripheral consequence of neuronal copper supply.

Reason: Retain the curated mouse pyramidal-neuron development transfer as a peripheral consequence of neuronal copper supply. The exact donor developmental assay has not been reconstructed; this is curator deference, not a newly established stage-specific human developmental mechanism.

Summary: Retain the existing mouse CNS-neuron-development transfer as a peripheral developmental role, with explicit curator deference and the established neuronal copper-supply context.

Reason: Retain the existing mouse CNS-neuron-development transfer as a peripheral developmental role, with explicit curator deference and the established neuronal copper-supply context. The defining activity remains copper transport; no new developmental term or direct human lineage assay is asserted.

Summary: PMID:9817923 reports the C-terminal dileucine-dependent localization/trafficking phenotype.

Reason: PMID:9817923 reports the C-terminal dileucine-dependent localization/trafficking phenotype. Retain the TGN transport-vesicle location with curator deference, as a trafficking compartment of ATP7A cargo rather than a distinct vesicle-biogenesis function.

Summary: The mouse extracellular-matrix-organization transfer is compatible with ATP7A supplying copper to secretory lysyl oxidase pathways and the connective-tissue phenotype of ATP7A deficiency.

Reason: The mouse extracellular-matrix-organization transfer is compatible with ATP7A supplying copper to secretory lysyl oxidase pathways and the connective-tissue phenotype of ATP7A deficiency. Retain the existing peripheral process; ATP7A is not the enzyme that oxidatively crosslinks matrix proteins, and the donor's exact matrix assay was not reread.

Summary: Retain the curated mouse collagen-fibril-organization role as a downstream consequence of copper supply to matrix-modifying cuproenzymes.

Reason: Retain the curated mouse collagen-fibril-organization role as a downstream consequence of copper supply to matrix-modifying cuproenzymes. This does not assign collagen synthesis or lysyl oxidase chemistry to ATP7A; the exact donor fibril experiment remains outside the bounded reading.

Summary: The UniProt axonal location is consistent with specialized neuronal ATP7A distribution.

Reason: The UniProt axonal location is consistent with specialized neuronal ATP7A distribution. Retain it as a non-core location, not as evidence of an axonal motor or cytoskeletal structural function.

Summary: Retain the rat P70705 axon-location transfer with its orthology provenance.

Reason: Retain the rat P70705 axon-location transfer with its orthology provenance. Independent mouse neuronal captions also describe ATP7A in Purkinje axons, but the exact rat donor assay was not reread and is not converted into direct human evidence.

Summary: The UniProt dendritic location is a specialized neuronal distribution of the copper transporter.

Reason: The UniProt dendritic location is a specialized neuronal distribution of the copper transporter. Retain it as non-core; no claim is made that ATP7A itself builds or transports along dendrites.

Summary: Retain the P70705 rat dendrite annotation as a conserved specialized location.

Reason: Retain the P70705 rat dendrite annotation as a conserved specialized location. The read mouse Purkinje-cell captions provide corroborating neuronal context, not a reconstruction of the rat donor source or a human direct-localization experiment.

Summary: The complete R-HSA-6803545 summary models ATP7A-mediated copper delivery to the phagosomal lumen; its cited functional context includes mouse RAW264.7 macrophages.

Reason: The complete R-HSA-6803545 summary models ATP7A-mediated copper delivery to the phagosomal lumen; its cited functional context includes mouse RAW264.7 macrophages. Retain the phagocytic-vesicle membrane location as a specialized non-core compartment. The historical event title says Cu2+, but its reaction entities and catalyst activity are Cu(I); no cache title or source object is rewritten.

Summary: Retain the mouse hair-follicle-morphogenesis transfer as a peripheral developmental consequence compatible with ATP7A-dependent copper and connective-tissue/pigmentation biology.

Reason: Retain the mouse hair-follicle-morphogenesis transfer as a peripheral developmental consequence compatible with ATP7A-dependent copper and connective-tissue/pigmentation biology. The exact follicle morphogenesis donor assay was not reread; abnormal hair alone is not presented as newly demonstrated human morphogenesis evidence.

Summary: ATP7A occupies cytoplasmic vesicles during copper-responsive cycling, but this broad compartment is less informative than its TGN and plasma-membrane activity sites.

Reason: ATP7A occupies cytoplasmic vesicles during copper-responsive cycling, but this broad compartment is less informative than its TGN and plasma-membrane activity sites. Retain the ortholog-derived location as non-core, without a redundant vesicle core location.

Summary: The combined ortholog/subcellular-location mapping is compatible with ATP7A endosomal recycling.

Reason: The combined ortholog/subcellular-location mapping is compatible with ATP7A endosomal recycling. Retain early-endosome membrane as a non-core trafficking location; the row is not an annotation to endosome organization.

Summary: Retain the mouse early-endosome membrane transfer in the ATP7A recycling pathway.

Reason: Retain the mouse early-endosome membrane transfer in the ATP7A recycling pathway. The date-only duplicate in raw GOA was already collapsed during seeding; preserve this single source assertion without inventing another row or upgrading the ISS evidence to human IDA.

Summary: The selected Methods and Results of PMID:27337370 explicitly use stabilized mouse ATP7A constructs for the dileucine trafficking experiments in human host cells; human cDNA stabilization is also described.

Reason: The selected Methods and Results of PMID:27337370 explicitly use stabilized mouse ATP7A constructs for the dileucine trafficking experiments in human host cells; human cDNA stabilization is also described. Retain the established human TGN-membrane location with curator deference and independent human localization evidence, while preserving this construct-species limit and the existing GO-CAM activity location.

Summary: The Q64430/ENSMUSP00000109186 TGN-membrane transfer agrees with the established location of the active human copper pump.

Reason: The Q64430/ENSMUSP00000109186 TGN-membrane transfer agrees with the established location of the active human copper pump. Retain the original electronic evidence and the core compartment.

Summary: The manual mouse TGN-membrane transfer is consistent with direct human Golgi/TGN evidence and the copper-supply mechanism.

Reason: The manual mouse TGN-membrane transfer is consistent with direct human Golgi/TGN evidence and the copper-supply mechanism. Preserve ISS provenance; no additional duplicate TGN annotation is needed.

Summary: PMID:31283225 characterizes the human ATP7A first metal-binding domain interacting with ATOX1 in a copper/platinum-dependent structural system.

Reason: PMID:31283225 characterizes the human ATP7A first metal-binding domain interacting with ATOX1 in a copper/platinum-dependent structural system. Retain the specific copper-dependent association as non-core, with domain and in-vitro limits; it does not establish an additional full-length drug-transport core.

Summary: PMID:10497213 explicitly tests interactions of HAH1/ATOX1 with Menkes and Wilson protein metal-binding domains.

Reason: PMID:10497213 explicitly tests interactions of HAH1/ATOX1 with Menkes and Wilson protein metal-binding domains. Retain the ATP7A interaction, but do not transfer the paper's Wilson-only reversibility/metallospecificity experiments to ATP7A or claim that all ATP7A partners are copper-dependent.

Summary: The electronic mouse/UniProt melanosome-membrane mapping is compatible with specialized copper delivery to the melanogenic pathway.

Reason: The electronic mouse/UniProt melanosome-membrane mapping is compatible with specialized copper delivery to the melanogenic pathway. Retain the location as non-core; the transporter is not itself tyrosinase, and this row does not establish every ATP7A product in melanosomes.

Summary: Retain the Q64430 melanosome-membrane transfer as a specialized compartment consistent with copper-dependent tyrosinase activation.

Reason: Retain the Q64430 melanosome-membrane transfer as a specialized compartment consistent with copper-dependent tyrosinase activation. Preserve the single seeded assertion after its raw date-only duplicate was removed; do not upgrade the donor localization to a new human IDA claim.

Summary: The specific mouse T-helper-cell differentiation assertion has not been connected to its primary donor experiment in this audit.

Reason: The specific mouse T-helper-cell differentiation assertion has not been connected to its primary donor experiment in this audit. General copper requirements, immune expression or macrophage phagosomal transport do not establish this distinct lymphocyte differentiation process. Preserve the curated source while leaving the biological transfer unresolved.

Summary: Retain the mouse epinephrine-metabolism transfer as a peripheral catecholamine role, plausibly mediated through copper-dependent dopamine beta-hydroxylase upstream of epinephrine.

Reason: Retain the mouse epinephrine-metabolism transfer as a peripheral catecholamine role, plausibly mediated through copper-dependent dopamine beta-hydroxylase upstream of epinephrine. The direct ATP7A-DBH association supports that route, but no ATP7A epinephrine-synthesizing enzyme activity or newly verified human flux assay is claimed.

Summary: The norepinephrine-metabolism assertion is consistent with ATP7A providing copper to dopamine beta-hydroxylase and the human interaction evidence in PMID:26199316.

Reason: The norepinephrine-metabolism assertion is consistent with ATP7A providing copper to dopamine beta-hydroxylase and the human interaction evidence in PMID:26199316. Retain the mouse-transferred process as non-core; DBH performs the hydroxylation chemistry.

Summary: Retain the mouse dopamine-metabolism transfer in the DBH/copper-supply context: dopamine is the substrate consumed by DBH during norepinephrine production.

Reason: Retain the mouse dopamine-metabolism transfer in the DBH/copper-supply context: dopamine is the substrate consumed by DBH during norepinephrine production. ATP7A's contribution is copper delivery, not dopamine transport or hydroxylase catalysis. The exact donor metabolite experiment was not reread.

Summary: The serotonin-metabolism ISS row requires its specific donor evidence.

Reason: The serotonin-metabolism ISS row requires its specific donor evidence. The established DBH/catecholamine mechanism does not automatically extend to serotonin, and the bounded primary reading did not establish an ATP7A-specific serotonin metabolic step. Do not remove the unread transfer or invent a cuproenzyme explanation.

Summary: The ortholog-derived neuron-projection location is consistent with ATP7A distribution in neuronal processes.

Reason: The ortholog-derived neuron-projection location is consistent with ATP7A distribution in neuronal processes. Retain the broad non-core compartment rather than making it an additional active-site core location.

Summary: Retain the mouse neuron-projection localization with its manual-transfer provenance.

Reason: Retain the mouse neuron-projection localization with its manual-transfer provenance. The neuron-specific distribution does not imply that ATP7A is a projection structural constituent or directly assembles neurites.

Summary: The electronic mouse neuronal-cell-body mapping is compatible with perinuclear neuronal ATP7A and the read mouse neuronal captions.

Reason: The electronic mouse neuronal-cell-body mapping is compatible with perinuclear neuronal ATP7A and the read mouse neuronal captions. Retain this specialized non-core location without representing the transfer as a human imaging experiment.

Summary: Retain the mouse neuronal-cell-body annotation as a conserved, specialized location of ATP7A.

Reason: Retain the mouse neuronal-cell-body annotation as a conserved, specialized location of ATP7A. The source-specific donor imaging was not reread; this is explicit curator deference with corroborating neuronal context.

Summary: Pigmentation is a well-supported downstream role of ATP7A copper supply: PMID:11092760 reports ATP7A-dependent tyrosinase activation and melanogenesis in Menkes fibroblasts.

Reason: Pigmentation is a well-supported downstream role of ATP7A copper supply: PMID:11092760 reports ATP7A-dependent tyrosinase activation and melanogenesis in Menkes fibroblasts. Retain the mouse-transferred pigmentation process as non-core, without making ATP7A a pigment biosynthetic enzyme.

Summary: Retain the curated mouse skin-development role as a peripheral copper-dependent developmental consequence, consistent with pigmentation and connective-tissue abnormalities.

Reason: Retain the curated mouse skin-development role as a peripheral copper-dependent developmental consequence, consistent with pigmentation and connective-tissue abnormalities. The exact skin-development donor assay was not reread; no separate developmental core or new process is proposed.

Summary: The Cu(II)-specific pump assertion conflicts with ATP7A monovalent copper transport.

Reason: The official GO:0043682 definition specifies a Cu(II)-transport reaction and its AmiGO relation table includes in-taxon Bacteria (https://amigo.geneontology.org/amigo/term/GO:0043682). ATP7A instead has the established Cu(I) P-type pump activity represented by GO:0140581 and RHEA:25792. This is rejection of a chemically incompatible source assertion, unlike refinement of compatible broad electronic parents. The Q64430 donor tuple remains unchanged and its historical assignment has not been reconstructed. Retain REMOVE on target chemistry and ontology scope; do not invent an additional pump assertion.

Summary: The generic metal-binding domain assignment is supported, but the human ATP7A domain studies establish copper binding specifically.

Reason: The generic metal-binding domain assignment is supported, but the human ATP7A domain studies establish copper binding specifically. Refine the broad metal-ion term to copper ion binding, retaining the domain-level evidence boundary and avoiding an inference that ATP7A transports arbitrary metals.

Proposed replacements: copper ion binding

Summary: PMID:11092760 shows ATP7A-dependent activation of tyrosinase and melanogenesis, with copper-chelation and catalytic-site controls.

Reason: PMID:11092760 shows ATP7A-dependent activation of tyrosinase and melanogenesis, with copper-chelation and catalytic-site controls. Retain positive regulation of melanin biosynthesis as a specialized consequence of copper delivery, not as ATP7A's core chemistry or direct tyrosinase catalysis.

Summary: Retain the mouse elastic-fiber-assembly transfer in the established connective-tissue/cuproenzyme context.

Reason: Retain the mouse elastic-fiber-assembly transfer in the established connective-tissue/cuproenzyme context. ATP7A can contribute copper supply to enzymes required for matrix crosslinking, but does not itself polymerize elastic fibers. The exact donor assembly experiment was not reread and no NEW process is proposed.

Summary: The mouse lung-alveolus-development assertion is retained as a peripheral developmental role compatible with copper-dependent connective-tissue maintenance.

Reason: The mouse lung-alveolus-development assertion is retained as a peripheral developmental role compatible with copper-dependent connective-tissue maintenance. The specific donor developmental experiment was not reread; no direct human alveolar assay or independent ATP7A morphogenetic mechanism is claimed.

Summary: PMID:10567439 directly examines human breast tissue and reports predominantly perinuclear ATP7A in nonlactating tissue with altered granular distribution during lactation.

Reason: PMID:10567439 directly examines human breast tissue and reports predominantly perinuclear ATP7A in nonlactating tissue with altered granular distribution during lactation. Retain the observed broad location as non-core; copper transfer into milk was proposed rather than directly measured in the read abstract.

Summary: PMID:16397091 examines human ATP7A transgene expression and localization in mouse tissues.

Reason: PMID:16397091 examines human ATP7A transgene expression and localization in mouse tissues. Retain the broad perinuclear location with curator deference and explicit host-species limits; it is not a separate organellar function.

Summary: PMID:8943055 directly describes perinuclear human ATP7A staining in the Golgi/TGN region.

Reason: PMID:8943055 directly describes perinuclear human ATP7A staining in the Golgi/TGN region. Retain this correct but broad location as non-core, while TGN membrane carries the informative activity compartment.

Summary: Retain the mouse neuron-projection-morphogenesis assertion as a peripheral effect of copper-dependent neuronal development.

Reason: Retain the mouse neuron-projection-morphogenesis assertion as a peripheral effect of copper-dependent neuronal development. The read mouse neuronal abstract/captions provide corroborating cytoskeletal and synaptic context but do not reconstruct this exact donor experiment; ATP7A is not assigned a neurite structural or motor activity.

Summary: The Q64430 cartilage-development transfer is retained as a peripheral connective-tissue role.

Reason: The Q64430 cartilage-development transfer is retained as a peripheral connective-tissue role. Copper delivery to secretory cuproenzymes provides a plausible conserved contribution, but the exact donor cartilage assay was not reread and no human chondrogenic mechanism is newly asserted.

Summary: The PTN008451426 PAINT copper-export assertion matches direct human ATP7A transport/efflux biology.

Reason: The PTN008451426 PAINT copper-export assertion matches direct human ATP7A transport/efflux biology. Q04656 among the descendant evidence is expected and valid. Retain export as a core process and preserve the ancestral node rather than treating the IBA as a pairwise similarity transfer.

Summary: PMID:10419525 directly compares recombinant human ATP7A transport and trafficking mutants and reports copper hyperaccumulation when surface trafficking is lost.

Reason: PMID:10419525 directly compares recombinant human ATP7A transport and trafficking mutants and reports copper hyperaccumulation when surface trafficking is lost. Retain copper export as a core process while distinguishing vesicle transport measurements from whole-cell efflux and acknowledging the unread full Methods/erratum.

Summary: The combined ARBA and mouse-ortholog export inference is independently supported by human ATP7A copper transport and copper-dependent surface cycling.

Reason: The combined ARBA and mouse-ortholog export inference is independently supported by human ATP7A copper transport and copper-dependent surface cycling. Retain the core process and original electronic provenance.

Summary: The manual mouse copper-export transfer is conserved and supported by direct human ATP7A experiments.

Reason: The manual mouse copper-export transfer is conserved and supported by direct human ATP7A experiments. This is the transporter performing the export step itself, not merely a substrate or a downstream marker.

Summary: The PTN000642961 ancestral monovalent P-type copper-pump activity is consistent with human ATP7A's Cu(I) substrate and ATP-coupled catalytic mechanism.

Reason: The PTN000642961 ancestral monovalent P-type copper-pump activity is consistent with human ATP7A's Cu(I) substrate and ATP-coupled catalytic mechanism. The target's own experimental contribution to PAINT is legitimate, and no target-specific loss is evident.

Summary: PMID:10419525 supports ATP-dependent copper-translocating activity of recombinant human ATP7A.

Reason: PMID:10419525 supports ATP-dependent copper-translocating activity of recombinant human ATP7A. Together with the Cu(I)-specific biochemical and curated catalytic record, it supports the defining P-type monovalent copper transporter activity. The source remains IDA; assay and erratum read limits are explicit.

Summary: The combined ARBA, ortholog, RHEA:25792 and EC:7.2.2.8 mapping describes the established Cu(I) P-type pump.

Reason: The combined ARBA, ortholog, RHEA:25792 and EC:7.2.2.8 mapping describes the established Cu(I) P-type pump. Retain this specific core activity; it is not interchangeable with the divalent Cu(II) term in row96.

Summary: PMID:31283225 directly characterizes Cu(I) handling by the human ATP7A first metal-binding domain in an ATOX1/platinum interaction system.

Reason: PMID:31283225 directly characterizes Cu(I) handling by the human ATP7A first metal-binding domain in an ATOX1/platinum interaction system. Retain cuprous-ion binding as a substrate-recognition component of the pump, without claiming that this domain study alone measures membrane flux.

Summary: PMID:14572476 experimentally characterizes the ATP7A second metal-binding domain and Cu(I) ligation.

Reason: PMID:14572476 experimentally characterizes the ATP7A second metal-binding domain and Cu(I) ligation. Retain the specific substrate-binding activity with domain-level scope; no complete-pump transport assay is inferred from the structural experiment.

Summary: PMID:15035611 determines apo and Cu(I)-bound structures of the human ATP7A second metal-binding domain expressed in E.coli.

Reason: PMID:15035611 determines apo and Cu(I)-bound structures of the human ATP7A second metal-binding domain expressed in E.coli. This directly supports cuprous-ion binding by the tested human domain, a component of the pump mechanism rather than a separate core.

Summary: The PMID:10419525 evidence for superoxide-removal regulation remains unresolved.

Reason: GO:2000121 concerns modulation of superoxide-radical removal. The complete PMID:10419525 cached abstract establishes human ATP7A copper transport and trafficking, but the relevant original superoxide experiment and listed erratum were not accessible in this assessment. The GO-CAM69ea894900001492 carries the same PMID and regulatory assertion; it records curatorial context, not an independent experimental verification. PMID:16371425 separately supports ATP7A-dependent SOD3 activation with the documented mixed-species assay limits, but it does not verify this original PMID:10419525 IDA assignment. Retain the source tuple and defer this row pending primary-evidence clarification. Abstract silence does not establish a miscitation, wrong-paper attribution or absence of an experiment from the full paper.