ATP7B

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0140581 P-type monovalent copper transporter activity	IMP PMID:9837819 Functional characterization of missense mutations in ATP7B: ...	ACCEPT	Summary: IMP evidence from Forbes & Cox (1998) demonstrating that mutation of the CPC motif abolishes copper transport, directly establishing ATP7B as a P-type copper transporter. This is the strongest experimental evidence for this term. Reason: Core molecular function of ATP7B. The CPC motif mutagenesis study directly demonstrates copper transport activity. This is the best evidence code for this annotation. Supporting Evidence: PMID:9837819 Mutation of the CPC motif resulted in a nonfunctional protein, which demonstrates that this motif is essential for copper transport by ATP7B. PMID:22240481 Properties of ATP7B variants with pathogenic amino-acid substitution varied greatly even if substitutions were in the same functional domain. Some variants had complete loss of catalytic and transport activity, whereas others lost transport activity but retained phosphor-intermediate formation or had partial losses of activity. file:human/ATP7B/ATP7B-deep-research-falcon.md ATP7B encodes the Wilson disease copper transporter, a P1B-type (P-type) Cu(I)-transporting ATPase whose well-supported GO-relevant biology centers on: (i) ATP-driven Cu(I) export from the cytosol into the trans-Golgi network (TGN) lumen for metallation of secretory cuproproteins, and (ii) copper-induced trafficking to post-Golgi vesicles/pericanalicular compartments to enable cellular copper detoxification and biliary copper excretion in hepatocytes.
GO:0140581 P-type monovalent copper transporter activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference consistent with direct experimental evidence. Redundant with the IMP annotation from PMID:9837819. Reason: Redundant with the IMP evidence. IBA is consistent but adds no new information beyond the direct experimental demonstration.
GO:0140581 P-type monovalent copper transporter activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation redundant with IMP evidence. Reason: Redundant with IMP from PMID:9837819.
GO:0140581 P-type monovalent copper transporter activity	NAS PMID:12763797 Functional properties of the human copper-transporting ATPas...	ACCEPT	Summary: NAS from Tsivkovskii et al. (2002) on functional properties of ATP7B. Redundant with IMP evidence. Reason: Redundant with IMP from PMID:9837819.
GO:0140581 P-type monovalent copper transporter activity	TAS PMID:16472602 ATP7B mediates vesicular sequestration of copper: insight in...	ACCEPT	Summary: TAS from Cater et al. (2006) vesicular sequestration study. Redundant with IMP evidence. Reason: Redundant with IMP from PMID:9837819.
GO:0140581 P-type monovalent copper transporter activity	TAS Reactome:R-HSA-936895	ACCEPT	Summary: Reactome pathway annotation for ATP7B transporting Cu1+ to Golgi lumen. Redundant with IMP evidence. Reason: Redundant with IMP from PMID:9837819.
GO:0005375 copper ion transmembrane transporter activity	IEA GO_REF:0000117	MODIFY	Summary: Electronic annotation. This is a parent term of GO:0140581 (P-type monovalent copper transporter activity). The more specific term is preferred. Reason: Redundant with the more specific GO:0140581. The parent term adds no information beyond what the child term already captures. Proposed replacements: P-type monovalent copper transporter activity
GO:0005375 copper ion transmembrane transporter activity	IDA PMID:26004889 Functional characterization of new mutations in Wilson disea...	MODIFY	Summary: IDA from functional characterization of ATP7B mutations using yeast complementation assay. Correct but less specific than GO:0140581. Reason: The IDA evidence is strong but should use the more specific child term GO:0140581 (P-type monovalent copper transporter activity) since ATP7B is a P-type ATPase. Proposed replacements: P-type monovalent copper transporter activity
GO:0019829 ATPase-coupled monoatomic cation transmembrane transporter activity	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Electronic annotation. Parent term of GO:0140581. Reason: Overly general. Redundant with the more specific GO:0140581.
GO:0005507 copper ion binding	IDA PMID:12029094 Metallochaperone Atox1 transfers copper to the NH2-terminal ...	ACCEPT	Summary: IDA from Walker et al. (2002) demonstrating that ATOX1 transfers copper to ATP7B N-terminal domain in a saturable manner, and that copper binding stimulates catalytic activity. Reason: Directly demonstrated copper binding to the N-terminal HMA domains. Core to ATP7B function as each of the six HMA domains binds Cu(I). Supporting Evidence: PMID:12029094 We demonstrate that Atox1 transfers copper to the purified amino-terminal domain of WNDP (N-WNDP) in a dose-dependent and saturable manner.
GO:0005507 copper ion binding	IDA PMID:14709553 Binding of copper(I) by the Wilson disease protein and its c...	ACCEPT	Summary: IDA from Lutsenko group quantifying copper binding stoichiometry to ATP7B and its chaperone ATOX1. Reason: Provides additional quantitative evidence for copper binding. Confirms Cu(I) binding via six N-terminal HMA domains with CXXC motifs. Supporting Evidence: PMID:14709553 The WND and Menkes proteins are distinguished from other P-type ATPases by the presence of six soluble N-terminal metal-binding domains containing a conserved CXXC metal-binding motif.
GO:0005507 copper ion binding	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference consistent with IDA evidence. Reason: Redundant with IDA evidence.
GO:0005507 copper ion binding	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation redundant with IDA evidence. Reason: Redundant with IDA from PMID:12029094.
GO:0005524 ATP binding	IDA PMID:16567646 Solution structure of the N-domain of Wilson disease protein...	ACCEPT	Summary: IDA from Dmitriev & Bhattacharjee (2006) NMR solution structure of the N-domain, showing distinct nucleotide-binding environment. Reason: ATP binding is essential for the catalytic cycle of this P-type ATPase. The N-domain structure reveals the nucleotide-binding site. Supporting Evidence: PMID:16567646 the nucleotide coordination environment of ATP7B within this fold is different. The residues H1069, G1099, G1101, I1102, G1149, and N1150 conserved in the P(1B)-ATPase subfamily contribute to ATP binding.
GO:0005524 ATP binding	IDA PMID:15205462 The distinct functional properties of the nucleotide-binding...	KEEP AS NON CORE	Summary: IDA from Tsivkovskii et al. (2004) analyzing nucleotide-binding domain properties and Wilson disease mutations affecting ATP binding. Reason: Additional IDA evidence for ATP binding, confirms functional importance. Redundant with PMID:16567646.
GO:0005524 ATP binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: Electronic annotation redundant with IDA evidence. Reason: Redundant with IDA from PMID:16567646.
GO:0000166 nucleotide binding	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Overly general parent term of GO:0005524 (ATP binding). Reason: Redundant with the more specific GO:0005524 (ATP binding) which has IDA support.
GO:0016887 ATP hydrolysis activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: ATP hydrolysis is integral to the P-type ATPase catalytic cycle. However, this is implicit in the GO:0140581 (P-type monovalent copper transporter activity) annotation. Reason: While correct, the ATPase activity is part of the copper transport mechanism already captured by GO:0140581. Acceptable as supplementary.
GO:0046872 metal ion binding	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Overly general parent of GO:0005507 (copper ion binding). Reason: Too general. The specific copper ion binding term (GO:0005507) with IDA evidence is preferred.
GO:0005515 protein binding	IPI PMID:12968035 The copper toxicosis gene product Murr1 directly interacts w...	MARK AS OVER ANNOTATED	Summary: IPI for interaction with COMMD1/MURR1. The term "protein binding" is uninformative per curation guidelines. Reason: Per GO curation guidelines, "protein binding" (GO:0005515) is too vague and does not convey the specific biological role of the interaction. COMMD1 interaction is relevant to copper homeostasis and ATP7B stability/degradation, but a more specific MF term should be used if available. Supporting Evidence: PMID:12968035 the Wilson disease protein directly interacts with the human homologue of Murr1 in vitro and in vivo and that this interaction is mediated via the copper binding, amino terminus of this ATPase.
GO:0005515 protein binding	IPI PMID:17919502 Distinct Wilson's disease mutations in ATP7B are associated ...	MARK AS OVER ANNOTATED	Summary: IPI for interactions with COMMD1 and ATOX1. Uninformative term. Reason: "Protein binding" is uninformative. The ATOX1 interaction represents copper chaperone-mediated metal transfer, and COMMD1 interaction affects ATP7B stability. Supporting Evidence: PMID:17919502 Four WD patient-derived mutations in this region of ATP7B significantly increased its binding to COMMD1. Two of these mutations also resulted in mislocalization and increased degradation rate of ATP7B.
GO:0005515 protein binding	IPI PMID:16554302 Copper-dependent interaction of dynactin subunit p62 with th...	MARK AS OVER ANNOTATED	Summary: IPI for copper-dependent interaction with DCTN4 (dynactin p62). Uninformative term. Reason: "Protein binding" is uninformative. The DCTN4 interaction is copper-dependent and likely facilitates retrograde trafficking.
GO:0005515 protein binding	IPI PMID:16884690 Copper-dependent interaction of glutaredoxin with the N term...	MARK AS OVER ANNOTATED	Summary: IPI for copper-dependent interaction with glutaredoxin (GRX1). Uninformative term. Reason: "Protein binding" is uninformative. GRX1 interaction may facilitate copper binding by reducing disulfide bridges in HMA domains.
GO:0005515 protein binding	IPI PMID:16676348 A new hepatocytic isoform of PLZF lacking the BTB domain int...	MARK AS OVER ANNOTATED	Summary: IPI for interaction with ZBTB16/PLZF hepatocytic isoform. Uninformative term. Reason: "Protein binding" is uninformative. The PLZF interaction connects ATP7B to ERK signaling but the functional significance is less clear.
GO:0006825 copper ion transport	IDA PMID:26004889 Functional characterization of new mutations in Wilson disea...	ACCEPT	Summary: IDA from yeast complementation assay showing ATP7B variants affect copper transport. Reason: Core biological process of ATP7B. Directly demonstrated by functional assays. Supporting Evidence: PMID:26004889 Expression of human wild type ATP7B gene in ccc2Δ mutant yeast restored the growth deficiency and copper transport activity; however, expression of the mutant forms did not restore the copper transport functions and only partially supported the cell growth.
GO:0006825 copper ion transport	IGI PMID:26004889 Functional characterization of new mutations in Wilson disea...	KEEP AS NON CORE	Summary: IGI evidence from same study, likely from genetic interaction data in yeast. Reason: Redundant with IDA from same publication.
GO:0006825 copper ion transport	IMP PMID:9837819 Functional characterization of missense mutations in ATP7B: ...	KEEP AS NON CORE	Summary: IMP from CPC motif mutagenesis study showing loss of copper transport. Reason: Strong evidence but redundant with IDA from PMID:26004889 for the same term.
GO:0006825 copper ion transport	IGI PMID:12572677 Copper-induced trafficking of the cU-ATPases: a key mechanis...	KEEP AS NON CORE	Summary: IGI from Schaefer & Bhatt (2003) on copper-induced trafficking of Cu-ATPases. Reason: Redundant with other evidence for this term.
GO:0060003 copper ion export	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that ATP7B mediates copper ion export. This is the correct directional term - ATP7B exports copper out of the cytoplasm into the Golgi lumen and vesicles. Reason: Correct and important annotation. ATP7B mediates copper export from the cytoplasm into the TGN lumen (for ceruloplasmin biosynthesis) and into vesicles (for biliary excretion). Well supported by literature. Supporting Evidence: PMID:16472602 This report provides compelling evidence that the primary mechanism of biliary copper excretion involves ATP7B-mediated vesicular sequestration of copper rather than direct copper translocation across the canalicular membrane. PMID:12763797 Wilson's disease protein (WNDP) is a copper-transporting P(1)-type ATPase which plays a key role in normal distribution of copper in a number of tissues, particularly in the liver and the brain.
GO:0015677 copper ion import	IBA GO_REF:0000033	REMOVE	Summary: INCORRECT annotation. ATP7B mediates copper EXPORT (into Golgi/vesicles/bile), NOT import into the cell. Copper import into cells is performed by CTR1/SLC31A1. The IBA phylogenetic inference has incorrectly assigned the direction of transport. Reason: ATP7B is a copper exporter, not importer. It transports copper from the cytoplasm into the Golgi lumen and vesicles. Copper import into cells is mediated by CTR1 (SLC31A1). This is a fundamental error in the phylogenetic inference. Supporting Evidence: PMID:16472602 The Wilson protein (ATP7B) regulates levels of systemic copper by excreting excess copper into bile. PMID:12763797 Wilson's disease protein (WNDP) is a copper-transporting P(1)-type ATPase which plays a key role in normal distribution of copper in a number of tissues, particularly in the liver and the brain. file:human/ATP7B/ATP7B-deep-research-falcon.md The supported directionality is export from cytosol into TGN/vesicle lumen and ultimately bile, not import into cytosol. Copper uptake into cells is mediated by other proteins (e.g., CTR1), not ATP7B.
GO:0006878 intracellular copper ion homeostasis	IBA GO_REF:0000033	ACCEPT	Summary: ATP7B is central to intracellular copper homeostasis in hepatocytes, maintaining copper balance through biosynthetic copper loading and biliary excretion. Reason: Core biological process. ATP7B directly maintains copper homeostasis by exporting excess copper. Loss of function causes copper accumulation (Wilson disease). Supporting Evidence: PMID:16472602 The Wilson protein (ATP7B) regulates levels of systemic copper by excreting excess copper into bile.
GO:0006878 intracellular copper ion homeostasis	TAS PMID:16554302 Copper-dependent interaction of dynactin subunit p62 with th...	KEEP AS NON CORE	Summary: TAS from DCTN4 interaction study, which discusses ATP7B role in copper homeostasis. Reason: Redundant with IBA annotation for same term.
GO:1990880 cellular detoxification of copper ion	IDA PMID:16472602 ATP7B mediates vesicular sequestration of copper: insight in...	ACCEPT	Summary: IDA from Cater et al. (2006) demonstrating ATP7B mediates vesicular sequestration of excess copper for subsequent exocytosis. Reason: Directly demonstrated by immunofluorescence and copper accumulation studies in hepatoma cells. The vesicular sequestration mechanism specifically serves copper detoxification. Supporting Evidence: PMID:16472602 Expression of wild-type and mutant ATP7B caused Chinese hamster ovary cells to accumulate copper in vesicles, which subsequently undergo exocytosis, releasing copper across the plasma membrane.
GO:1990961 xenobiotic detoxification by transmembrane export across the plasma membrane	IC PMID:9837819 Functional characterization of missense mutations in ATP7B: ...	REMOVE	Summary: INCORRECT mechanism. ATP7B does NOT export copper directly across the plasma membrane. Per PMID:16472602, ATP7B mediates vesicular sequestration of copper, which subsequently undergoes exocytosis. Furthermore, copper is an essential element, not a xenobiotic. Reason: Two errors: (1) ATP7B uses vesicular sequestration, not direct plasma membrane export. Cater et al. (2006) explicitly showed ATP7B traffics to pericanalicular vesicles, NOT the canalicular membrane. (2) Copper is an endogenous essential metal, not a xenobiotic. The correct term is GO:1990880 (cellular detoxification of copper ion) which is already annotated with IDA evidence. Supporting Evidence: PMID:16472602 In HepG2 cells, elevated copper levels stimulated trafficking of ATP7B to pericanalicular vesicles and not to the canalicular membrane as previously reported. file:human/ATP7B/ATP7B-deep-research-falcon.md Evidence supports copper-stimulated redistribution toward apical/canalicular regions, but stable canalicular plasma membrane residence is variable across systems; some studies support vesicular sequestration/exocytosis without clear canalicular membrane labeling, while others report canalicular fractions and/or tight junction pools.
GO:0006812 monoatomic cation transport	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Overly general parent of copper ion transport. Reason: Too general. The specific copper ion transport term (GO:0006825) with IDA evidence is preferred.
GO:0034220 monoatomic ion transmembrane transport	TAS Reactome:R-HSA-936837	KEEP AS NON CORE	Summary: Reactome pathway annotation for ion transport by P-type ATPases. General term. Reason: Correct but overly general. Subsumed by more specific copper transport annotations.
GO:0046688 response to copper ion	IDA PMID:16472602 ATP7B mediates vesicular sequestration of copper: insight in...	ACCEPT	Summary: IDA showing ATP7B undergoes copper-responsive trafficking from TGN to pericanalicular vesicles in HepG2 cells. Reason: The copper-responsive trafficking of ATP7B is a well-established phenomenon central to its homeostatic function. Elevated copper triggers relocalization from TGN to vesicles. Supporting Evidence: PMID:16472602 In HepG2 cells, elevated copper levels stimulated trafficking of ATP7B to pericanalicular vesicles and not to the canalicular membrane as previously reported.
GO:0046688 response to copper ion	IDA PMID:16939419 Copper binding to the N-terminal metal-binding sites or the ...	KEEP AS NON CORE	Summary: IDA from Cater et al. (2006) showing copper-induced trafficking occurs even without N-terminal metal-binding sites or CPC motif. Reason: Provides mechanistic insight but redundant with PMID:16472602 IDA for the same term. Supporting Evidence: PMID:16939419 Copper binding to the N-terminal metal-binding sites or the CPC motif is not essential for copper-induced trafficking of the human Wilson protein (ATP7B).
GO:0046688 response to copper ion	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic annotation redundant with IDA evidence. Reason: Redundant with IDA from PMID:16472602.
GO:0046688 response to copper ion	IDA PMID:15269005 Signals regulating trafficking of Menkes (MNK; ATP7A) copper...	REMOVE	Summary: WRONG GENE. PMID:15269005 (Greenough et al. 2004) is about ATP7A (Menkes protein) trafficking in MDCK cells, NOT ATP7B. This annotation has been mis-attributed. Reason: PMID:15269005 studied ATP7A (Menkes), not ATP7B. The paper title explicitly states "Signals regulating trafficking of Menkes (MNK; ATP7A) copper-translocating P-type ATPase in polarized MDCK cells." This is a mis-annotation error.
GO:0032588 trans-Golgi network membrane	IDA PMID:9837819 Functional characterization of missense mutations in ATP7B: ...	ACCEPT	Summary: IDA from Forbes & Cox (1998) showing ATP7B localizes to TGN membrane under basal copper conditions. Reason: Well-established primary localization of ATP7B. The TGN is where ATP7B performs its biosynthetic role of loading copper into ceruloplasmin and other cuproenzymes. Supporting Evidence: PMID:9837819 Wilson disease is an autosomal recessive disorder of copper transport that causes hepatic and/or neurological disease resulting from copper accumulation in the liver and brain. The protein defective in this disorder is a putative copper-transporting P-type ATPase, ATP7B. file:human/ATP7B/ATP7B-deep-research-falcon.md At basal/low copper, ATP7B localizes predominantly to the trans-Golgi network (TGN), consistent with its biosynthetic role in delivering Cu into the secretory pathway.
GO:0032588 trans-Golgi network membrane	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: Electronic annotation redundant with IDA evidence. Reason: Redundant with IDA from PMID:9837819.
GO:0005802 trans-Golgi network	IDA PMID:16472602 ATP7B mediates vesicular sequestration of copper: insight in...	ACCEPT	Summary: IDA from Cater et al. (2006) showing ATP7B localizes to TGN in HepG2 hepatoma cells under basal conditions. Reason: Confirmed TGN localization using endogenous ATP7B in hepatoma cells, which is more physiologically relevant than overexpression systems. Supporting Evidence: PMID:16472602 Immunofluorescence microscopy was used to investigate the effect of copper concentration on the localization of endogenous ATP7B in HepG2 cells.
GO:0005802 trans-Golgi network	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Electronic annotation from Ensembl Compara orthology transfer. Reason: Redundant with IDA from PMID:16472602.
GO:0005802 trans-Golgi network	IDA PMID:15269005 Signals regulating trafficking of Menkes (MNK; ATP7A) copper...	REMOVE	Summary: WRONG GENE. PMID:15269005 is about ATP7A (Menkes), not ATP7B. Mis-attributed annotation. Reason: PMID:15269005 studied ATP7A trafficking in MDCK cells. While ATP7B does localize to TGN (confirmed by other papers), this specific evidence is incorrectly attributed.
GO:0005794 Golgi apparatus	IDA GO_REF:0000052	KEEP AS NON CORE	Summary: IDA from immunofluorescence curation. Less specific than TGN membrane. Reason: Correct but less specific than GO:0032588 (trans-Golgi network membrane). Acceptable as supporting evidence.
GO:0005794 Golgi apparatus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic annotation, less specific than TGN. Reason: Redundant with more specific TGN annotations.
GO:0000139 Golgi membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic annotation. Less specific than GO:0032588 (TGN membrane). Reason: Redundant with the more specific GO:0032588 (trans-Golgi network membrane) which has IDA support.
GO:0000139 Golgi membrane	TAS Reactome:R-HSA-936895	KEEP AS NON CORE	Summary: Reactome annotation. Less specific than TGN membrane. Reason: Redundant with more specific TGN membrane annotation.
GO:0031410 cytoplasmic vesicle	IDA PMID:16472602 ATP7B mediates vesicular sequestration of copper: insight in...	ACCEPT	Summary: IDA showing ATP7B traffics to pericanalicular cytoplasmic vesicles under elevated copper conditions. Reason: Copper-induced vesicular localization is essential for the biliary excretion function of ATP7B. Well demonstrated in HepG2 cells. Supporting Evidence: PMID:16472602 Mutation of an endocytic retrieval signal in ATP7B caused the protein to constitutively localize to vesicles and not to the plasma membrane, suggesting that a vesicular compartment(s) is the final trafficking destination for ATP7B. file:human/ATP7B/ATP7B-deep-research-falcon.md Upon copper elevation, ATP7B exits the TGN and redistributes to cytosolic vesicles/pericanalicular vesicles and subapical compartments in hepatocyte-derived polarized models; this trafficking is reversible upon copper chelation.
GO:0005770 late endosome	IDA PMID:15681833 The Wilson disease protein ATP7B resides in the late endosom...	KEEP AS NON CORE	Summary: IDA from Harada et al. (2005) reporting ATP7B co-localizes with Rab7 and NPC1 in late endosomes. This represents a minority view in the field; most groups report TGN as the primary compartment. Reason: While experimentally supported, this may represent a post-Golgi trafficking intermediate rather than the primary steady-state compartment. The TGN model is more widely accepted and consistent with the ceruloplasmin biosynthesis role. Supporting Evidence: PMID:15681833 We have confirmed that ATP7B is a late endosome-associated membrane protein.
GO:0005770 late endosome	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic annotation consistent with Harada study. Reason: See IDA late endosome annotation above.
GO:0048471 perinuclear region of cytoplasm	IDA PMID:16939419 Copper binding to the N-terminal metal-binding sites or the ...	KEEP AS NON CORE	Summary: IDA showing ATP7B at the perinuclear region, consistent with TGN localization. Reason: The TGN is perinuclear, so this is consistent but less informative than the TGN annotation. Acceptable as supporting.
GO:0005886 plasma membrane	IBA GO_REF:0000033	REMOVE	Summary: IBA phylogenetic inference. QUESTIONABLE for ATP7B. Unlike ATP7A which traffics to the basolateral plasma membrane, ATP7B traffics to pericanalicular vesicles, NOT the plasma membrane. Reason: ATP7B does not localize to the plasma membrane. Per PMID:16472602, ATP7B traffics to pericanalicular vesicles and NOT to the canalicular membrane. Mutation of the endocytic retrieval signal causes constitutive vesicular localization, not PM localization. The IBA inference likely transferred from ATP7A which does traffic to PM. Supporting Evidence: PMID:16472602 Mutation of an endocytic retrieval signal in ATP7B caused the protein to constitutively localize to vesicles and not to the plasma membrane, suggesting that a vesicular compartment(s) is the final trafficking destination for ATP7B. file:human/ATP7B/ATP7B-deep-research-falcon.md A cautious annotation should emphasize copper-induced apical/canalicular-associated trafficking and/or “TGN → pericanalicular vesicles” rather than constitutive “plasma membrane.”
GO:0005886 plasma membrane	TAS PMID:8298641 The Wilson disease gene is a copper transporting ATPase with...	REMOVE	Summary: TAS from the original 1993 Wilson disease gene cloning paper (Tanzi et al.). This predates the detailed trafficking studies and was based on the assumption that a transmembrane transporter must be at the PM. Reason: Outdated annotation from 1993 before ATP7B trafficking was understood. Subsequent studies (PMID:16472602, PMID:16939419) have definitively shown ATP7B traffics to TGN and vesicles, not the plasma membrane.
GO:0016323 basolateral plasma membrane	IDA PMID:15269005 Signals regulating trafficking of Menkes (MNK; ATP7A) copper...	REMOVE	Summary: WRONG GENE. PMID:15269005 is about ATP7A (Menkes protein) in polarized MDCK cells. ATP7A traffics to the basolateral membrane; ATP7B traffics to the apical/canalicular side via vesicular intermediates. Reason: Mis-attributed annotation. PMID:15269005 studied ATP7A (Menkes), not ATP7B. The paper explicitly describes "Menkes (MNK; ATP7A)" in the title. Basolateral PM is the correct localization for ATP7A but incorrect for ATP7B, which traffics to apical/pericanalicular vesicles.
GO:0016020 membrane	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Very generic membrane annotation. Reason: Too general. More specific membrane annotations (TGN membrane, cytoplasmic vesicle) are available with IDA support.
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	KEEP AS NON CORE	Summary: HDA from NK cell membrane proteome study. Identifies ATP7B as a membrane protein, which is correct but uninformative. Reason: Generic membrane annotation. The HDA from an NK cell proteomics study is not informative for ATP7B's specific subcellular localization.
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Electronic annotation mapping from UniProt subcellular location. May relate to isoform 2 which is cytoplasmic. Reason: This may refer to isoform 2 (P35670-2) which lacks transmembrane domains and is cytoplasmic. Acceptable as a general annotation but isoform-specificity should be noted.
GO:0005739 mitochondrion	IEA GO_REF:0000044	MARK AS OVER ANNOTATED	Summary: Electronic annotation from UniProt mapping. Based on the WND/140 kDa proteolytic fragment reported by one group (PMID:9600907). Not the primary localization of full-length ATP7B. Reason: The mitochondrial localization was reported for a 140 kDa N-terminally cleaved fragment, not full-length ATP7B. This finding (PMID:9600907) has not been widely reproduced and does not reflect the primary subcellular localization of the protein.
GO:0005739 mitochondrion	HTP PMID:34800366 Quantitative high-confidence human mitochondrial proteome an...	MARK AS OVER ANNOTATED	Summary: HTP from large-scale mitochondrial proteomics study. May represent contamination or the cleaved fragment. Reason: High-throughput proteomics can detect contaminating proteins or low-abundance fragments. The primary localization of ATP7B is TGN, not mitochondria. This HTP finding is inconsistent with the extensive cell biology literature.

Gene Description

Existing Annotations Review

Core Functions

ATP7B is an ATP-dependent P1B-type Cu(I) transporter that exports cytosolic copper into the trans-Golgi network lumen for secretory cuproenzyme metallation and traffics under elevated copper to vesicular/pericanalicular compartments for copper detoxification and biliary excretion.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

📚 Additional Documentation

Notes

📄 View Raw YAML