Gene Ontology annotation through association of InterPro records with GO terms

InterPro-derived V0-domain and proton-pump terms are mostly correct, but independent enables activity is over-stated for a single subunit.

Annotation inferences using phylogenetic trees

IBA supports conserved V-ATPase complex membership and contributes_to proton-pump activity.

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

UniProt subcellular-location mappings for endosome and plasma membrane are compatible with the reviewed literature.

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

HPA plasma-membrane localization is retained as non-core context.

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

Orthology-transferred acrosomal/perinuclear locations are retained as non-core context.

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

Automated V0-domain annotation is consistent with ATP6V0A2 subunit identity.

PMID:16415858

V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway.

ATP6V0A2/a2 is targeted to early endosomes, binds ARNO/PSCD2 in an acidification-dependent manner, and supports endocytic degradative trafficking.

PMID:17897319

Integral and associated lysosomal membrane proteins.

Lysosomal membrane proteomics detected vacuolar ATPase-associated polypeptides in purified lysosomal membranes.

PMID:2247090

Cloning of a cDNA for a T cell produced molecule with a putative immune regulatory role.

The old T-cell cDNA study supports only a broad putative immune-regulatory context and is not sufficient for a core immune-response function.

PMID:22982048

Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts.

The lipofuscin study does not establish ATP6V0A2-specific regulation of macroautophagy.

PMID:28296633

The vacuolar-ATPase complex and assembly factors, TMEM199 and CCDC115, control HIF1α prolyl hydroxylation by regulating cellular iron levels.

ATP6V0A2 appeared in a V-ATPase/HIF screen; V-ATPase disruption affected intracellular iron and PHD-dependent HIF regulation.

PMID:32001091

Structure and Roles of V-type ATPases.

V-ATPase review supports ATP-driven organelle acidification and differentially localized mammalian isoforms.

PMID:33065002

Structures of a Complete Human V-ATPase Reveal Mechanisms of Its Assembly.

Human V-ATPase structures support the V1 ATP-hydrolysis and Vo proton-transfer architecture and endosome/lysosome pH homeostasis.

Reactome:R-HSA-1222516

Intraphagosomal pH is lowered to 5 by V-ATPase

Reactome supports phagosomal V-ATPase acidification context.

Reactome:R-HSA-5252133

ATP6AP1 binds V-ATPase

Reactome supports V-ATPase acidification of intracellular cargos and ATP6AP1/V-ATPase context.

Reactome:R-HSA-74723

Endosome acidification

Reactome supports endosome lumen acidification by proton pump activity.

Reactome:R-HSA-917841

Acidification of Tf:TfR1 containing endosome

Reactome supports transferrin-receptor endosome acidification by V-type proton pumping ATPase.

file:human/ATP6V0A2/ATP6V0A2-uniprot.txt

UniProtKB ATP6V0A2 record Q9Y487

Curates ATP6V0A2 as a V0 V-ATPase a-subunit involved in organelle acidification, endosomal pH sensing, Golgi pH/glycosylation, and iron/HIF effects.

file:human/ATP6V0A2/ATP6V0A2-deep-research-manual.md

Manual deep research fallback for ATP6V0A2

Falcon deep research timed out and the configured fallback failed with quota error; this manual file summarizes the local UniProt, publication, Reactome, and PN evidence used for review.

file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv

Proteostasis PN projected annotations for ATP6V0A2

Projects ATP6V0A2 to lysosomal lumen acidification and lysosomal proton-transporting V-type ATPase V0 domain, both requiring gene-level review.

file:projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Proteostasis PN mapping scrutiny report

Flags lysosomal acidification mapping as requiring manual gene-level review before changing gene reviews.