ATP7B is a P1B-type copper-transporting ATPase predominantly expressed in liver hepatocytes. Its two main physiological roles are:
ATP7B undergoes copper-responsive subcellular trafficking:
- Low copper: Resides at the TGN PMID:16939419
- High copper: Redistributes to cytoplasmic/pericanalicular vesicles PMID:16472602
- Copper removal: Returns to TGN [UniProt CC, PMID:10942420]
- Trafficking is coupled to catalytic cycle: acyl-phosphorylation required for anterograde trafficking, dephosphorylation for TGN retrieval PMID:16939419
There is a genuine controversy about the steady-state localization of ATP7B:
- TGN model (majority view): Most studies report TGN localization at basal copper, with copper-induced trafficking to vesicles [PMID:9837819, PMID:16472602, PMID:16939419, PMID:17919502]
- Late endosome model (Harada group): Harada et al. consistently report late endosome localization with Rab7 and NPC1 co-localization, arguing ATP7B is NOT a Golgi resident PMID:15681833
- Resolution: The late endosome data may represent a post-Golgi compartment that ATP7B traffics through. The TGN model is more widely accepted and consistent with ceruloplasmin biosynthesis role.
Key distinction: ATP7B primarily mediates copper excretion via vesicular sequestration, NOT direct translocation across the plasma membrane PMID:16472602. This is different from ATP7A which traffics to the basolateral plasma membrane PMID:15269005.
GO:0015677 copper ion import (IBA): This is WRONG for ATP7B. ATP7B mediates copper EXPORT (into bile/vesicles/Golgi lumen), not import into the cell. This appears to be a phylogenetic inference error.
GO:0005886 plasma membrane (IBA): Questionable. ATP7B does NOT primarily traffic to the plasma membrane. It traffics to pericanalicular VESICLES. This is a key distinction from ATP7A PMID:16472602.
GO:1990961 xenobiotic detoxification by transmembrane export across the plasma membrane (IC): The mechanism is vesicular sequestration, not direct plasma membrane export PMID:16472602.
GO:0005515 protein binding: Multiple uninformative "protein binding" annotations should be replaced with specific interaction terms.
GO:0016323 basolateral plasma membrane (IDA, PMID:15269005): This paper is about ATP7A (Menkes), NOT ATP7B! This is a mis-annotation.
GO:0005739 mitochondrion (IEA/HTP): Based on a proteolytic fragment (WND/140 kDa) reported by one group PMID:9600907. Not widely reproduced. Dubious for the full-length protein.
Redundant annotations: Many terms appear with multiple evidence codes (e.g., GO:0140581 appears 6 times).
Falcon deep research was added as ATP7B-deep-research-falcon.md and supports
the same core curation model: ATP7B is a P1B-type ATP-dependent Cu(I) transporter
whose central biology is copper export into the TGN and copper-induced
vesicular/pericanalicular trafficking for detoxification and biliary excretion
[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."].
The Falcon report also reinforces the key caveats already captured in the YAML:
ATP7B is not a copper importer [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."] and constitutive plasma membrane
annotation should be avoided in favor of condition-dependent TGN-to-vesicle or
apical/canalicular-associated trafficking [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.”"].