id: Q8NHE4 gene_symbol: ATP6V0E2 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- ATP6V0E2 encodes the "e2" form of the V-type proton ATPase (V-ATPase) subunit e, a small (81 aa, ~9.2 kDa) integral membrane protein with two transmembrane helices. It is one of two e-subunit paralogs in human (e1 = ATP6V0E1, e2 = ATP6V0E2) and is an accessory membrane component of the V0 proton-translocation sector of the V-ATPase. The V-ATPase is a rotary proton pump composed of a peripheral, cytoplasmic V1 sector that hydrolyzes ATP and a membrane-integral V0 sector that translocates protons across the membrane; together they acidify and maintain the pH of intracellular compartments including lysosomes, endosomes, the Golgi, secretory vesicles, synaptic vesicles, clathrin-coated vesicles and phagosomes, and in some cell types the plasma membrane. As a V0 subunit, e2 contributes to the assembly and proton-pumping function of the holoenzyme; yeast complementation studies show the e-subunit is essential for proper pump function. Unlike the ubiquitously expressed e1, ATP6V0E2 has a more restricted tissue distribution with high expression in heart, brain and kidney. alternative_products: - name: '1' id: Q8NHE4-1 - name: '2' id: Q8NHE4-2 sequence_note: VSP_027104 - name: '3' id: Q8NHE4-3 sequence_note: VSP_027105 - name: '4' id: Q8NHE4-4 sequence_note: VSP_044857 existing_annotations: - term: id: GO:1902600 label: proton transmembrane transport evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: >- Phylogenetically-inferred annotation that ATP6V0E2 is involved in proton transmembrane transport, consistent with its role as a V0-sector subunit of the V-ATPase proton pump. Strongly supported by the experimental yeast complementation data and the UniProt function description. action: ACCEPT reason: >- This is the core biological process of the V-ATPase to which e2 contributes. It is independently supported by experimental (IGI) and curatorial (ISS) evidence and by the UniProt FUNCTION statement. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- a membrane integral complex (V0) that translocates protons reference_section_type: DATABASE_ENTRY - reference_id: PMID:17350184 supporting_text: >- either form of the e-subunit is essential for proper proton pump function reference_section_type: ABSTRACT - term: id: GO:0000220 label: vacuolar proton-transporting V-type ATPase, V0 domain evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: >- ATP6V0E2 is a component of the V0 membrane domain of the vacuolar V-type ATPase. This is the core complex membership for an e-subunit and is well supported. action: ACCEPT reason: >- UniProt SUBUNIT explicitly places subunit e within the V0 proton translocation complex; the IBA assignment is consistent with this. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR. reference_section_type: DATABASE_ENTRY - term: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: contributes_to review: summary: >- As a V0 subunit, e2 contributes to (rather than independently enables) the rotational-mechanism proton-transporting ATPase activity of the holoenzyme. The contributes_to qualifier is the precise and correct usage for an accessory subunit of a multiprotein pump. action: ACCEPT reason: >- The rotational proton-pumping activity is a property of the assembled V1V0 holoenzyme; a single membrane subunit contributes to it. The contributes_to qualifier correctly captures this. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons reference_section_type: DATABASE_ENTRY - reference_id: PMID:17350184 supporting_text: >- either form of the e-subunit is essential for proper proton pump function reference_section_type: ABSTRACT - term: id: GO:0016020 label: membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: >- ATP6V0E2 is an integral, multi-pass membrane protein; localization to membrane is correct but very generic. action: KEEP_AS_NON_CORE reason: >- True but uninformative relative to more specific compartment terms (lysosomal/endosomal/vesicle membranes). Retained as a non-core, high-level localization statement. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane protein reference_section_type: DATABASE_ENTRY - term: id: GO:0030665 label: clathrin-coated vesicle membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: >- Localization to clathrin-coated vesicle membrane, transferred by similarity from an ortholog (Q5EB76) via UniProt subcellular location mapping. Consistent with V-ATPase distribution across the endomembrane system but not directly demonstrated for human e2. action: KEEP_AS_NON_CORE reason: >- Plausible compartment for V-ATPase but based on orthology transfer rather than direct human evidence; not the core function of the subunit. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- Cytoplasmic vesicle, clathrin-coated vesicle membrane {ECO:0000250|UniProtKB:Q5EB76} reference_section_type: DATABASE_ENTRY - term: id: GO:0030672 label: synaptic vesicle membrane evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: >- Localization to synaptic vesicle membrane inferred by automated/orthology methods. V-ATPases acidify synaptic vesicles, so this is biologically plausible, but it derives from ortholog transfer (rat Q5EB76) rather than direct human data. action: KEEP_AS_NON_CORE reason: >- Reasonable compartment annotation by analogy/orthology; not core and not directly demonstrated for human ATP6V0E2. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000250|UniProtKB:Q5EB76} reference_section_type: DATABASE_ENTRY - term: id: GO:0033179 label: proton-transporting V-type ATPase, V0 domain evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: part_of review: summary: >- InterPro-based assignment of e2 to the V0 domain of the V-type ATPase, via the e1/e2 subunit InterPro signatures. Consistent with the experimentally supported V0 membership. action: ACCEPT reason: >- Correct complex/domain membership supported by InterPro family signatures (IPR008389, IPR017385) and by the UniProt SUBUNIT description. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f reference_section_type: DATABASE_ENTRY - term: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: >- InterPro-based assignment of rotational proton-transporting ATPase activity with the enables qualifier. The activity assignment is correct at the family level, but enables is less precise than contributes_to for a single V0 subunit that cannot pump protons alone. action: ACCEPT reason: >- The molecular function is correct for the V-ATPase family. The enables qualifier is the GOA convention for complex subunits via InterPro; the IBA annotation already captures the more precise contributes_to. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- a membrane integral complex (V0) that translocates protons reference_section_type: DATABASE_ENTRY - term: id: GO:1902600 label: proton transmembrane transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: >- InterPro-based assignment of involvement in proton transmembrane transport. Consistent with the IBA/IGI annotations to the same process. action: ACCEPT reason: >- Core process of the V-ATPase, correctly inferred from InterPro family membership and corroborated by experimental evidence. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- a membrane integral complex (V0) that translocates protons reference_section_type: DATABASE_ENTRY - term: id: GO:0000220 label: vacuolar proton-transporting V-type ATPase, V0 domain evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: part_of review: summary: >- Curator-judged sequence-similarity transfer (from Q2KIB5) placing e2 in the vacuolar V0 domain. Duplicates the IBA assignment to the same term and is well supported. action: ACCEPT reason: >- Correct V0 domain membership supported by orthology and by the UniProt SUBUNIT description. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR reference_section_type: DATABASE_ENTRY - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9639286 qualifier: located_in review: summary: >- Reactome pathway-context annotation placing the V-ATPase (and thus e2) on the lysosomal membrane during amino-acid/mTORC1 signaling reactions. Localization is correct; the specific reaction context is mTORC1 signaling rather than an e2-specific role. action: KEEP_AS_NON_CORE reason: >- Lysosomal membrane is a major and correct V-ATPase location, but this annotation derives from a Reactome signaling reaction assigned to the whole complex, not to a unique e2 function. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2 reference_section_type: DATABASE_ENTRY - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9640167 qualifier: located_in review: summary: >- Reactome annotation to lysosomal membrane in the context of mTORC1 amino-acid sensing. Correct compartment, complex-level/reaction context. action: KEEP_AS_NON_CORE reason: >- Duplicate lysosomal membrane localization from a Reactome signaling reaction assigned to the V-ATPase complex; correct but non-core. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2 reference_section_type: DATABASE_ENTRY - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9640168 qualifier: located_in review: summary: >- Reactome lysosomal membrane localization from an mTORC1/Ragulator dissociation reaction. Correct compartment for the V-ATPase complex. action: KEEP_AS_NON_CORE reason: >- Correct but non-core; complex-level localization from a signaling reaction. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2 reference_section_type: DATABASE_ENTRY - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9640175 qualifier: located_in review: summary: >- Reactome lysosomal membrane localization (V-ATPase:Ragulator binding SLC38A9:Arginine reaction). Correct compartment, signaling context. action: KEEP_AS_NON_CORE reason: >- Correct but non-core; complex-level localization from a signaling reaction. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2 reference_section_type: DATABASE_ENTRY - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9640195 qualifier: located_in review: summary: >- Reactome lysosomal membrane localization (RRAGA,B GTP hydrolysis reaction). Correct compartment, signaling context. action: KEEP_AS_NON_CORE reason: >- Correct but non-core; complex-level localization from a signaling reaction. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2 reference_section_type: DATABASE_ENTRY - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9645598 qualifier: located_in review: summary: >- Reactome lysosomal membrane localization (RRAGC,D GTP hydrolysis reaction). Correct compartment, signaling context. action: KEEP_AS_NON_CORE reason: >- Correct but non-core; complex-level localization from a signaling reaction. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2 reference_section_type: DATABASE_ENTRY - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9645608 qualifier: located_in review: summary: >- Reactome lysosomal membrane localization (V-ATPase:Ragulator binding mTORC1 reaction). Correct compartment, signaling context. action: KEEP_AS_NON_CORE reason: >- Correct but non-core; complex-level localization from a signaling reaction. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2 reference_section_type: DATABASE_ENTRY - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9646468 qualifier: located_in review: summary: >- Reactome lysosomal membrane localization (mTORC1 binding RHEB:GTP reaction). Correct compartment, signaling context. action: KEEP_AS_NON_CORE reason: >- Correct but non-core; complex-level localization from a signaling reaction. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2 reference_section_type: DATABASE_ENTRY - term: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism evidence_type: IGI original_reference_id: PMID:17350184 qualifier: enables review: summary: >- Experimental genetic-interaction (yeast complementation) evidence that the human e-subunit restores proton pump function in an e-subunit-deficient yeast strain, supporting its contribution to rotational proton-transporting ATPase activity. The enables qualifier is acceptable per GOA convention, though contributes_to is more precise for a single subunit. action: ACCEPT reason: >- Direct functional evidence (yeast complementation, WITH ortholog Q3E7B6) that e2 is required for proper pump function; strongest support for the molecular function. supported_by: - reference_id: PMID:17350184 supporting_text: >- We show by complementation studies in a yeast strain deficient for the ortholog of this subunit, that either form of the e-subunit is essential for proper proton pump function. reference_section_type: ABSTRACT - term: id: GO:1902600 label: proton transmembrane transport evidence_type: IGI original_reference_id: PMID:17350184 qualifier: involved_in review: summary: >- Experimental genetic-interaction (yeast complementation) evidence that e2 is required for proton pump function, supporting involvement in proton transmembrane transport. action: ACCEPT reason: >- Core process supported by direct functional complementation data. supported_by: - reference_id: PMID:17350184 supporting_text: >- either form of the e-subunit is essential for proper proton pump function reference_section_type: ABSTRACT - term: id: GO:0016241 label: regulation of macroautophagy evidence_type: NAS original_reference_id: PMID:22982048 qualifier: involved_in review: summary: >- NAS annotation to regulation of macroautophagy citing a lipofuscin/autophagy study in senescent fibroblasts. That paper does not mention ATP6V0E2 and concerns general lysosomal/autophagy biology; assigning this process to this specific V0 subunit is an over-annotation. While V-ATPase-driven acidification is broadly upstream of autophagy, this subunit does not have a documented direct regulatory role in macroautophagy. action: MARK_AS_OVER_ANNOTATED reason: >- The cited reference does not address ATP6V0E2 and provides no assertion-level support for a macroautophagy-regulation role for this subunit; the process is several steps removed from the subunit's direct function. supported_by: - reference_id: PMID:22982048 supporting_text: >- Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts. reference_section_type: TITLE - term: id: GO:0030670 label: phagocytic vesicle membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-1222516 qualifier: located_in review: summary: >- Reactome annotation placing the V-ATPase on the phagosome membrane during intraphagosomal acidification. Correct compartment for the complex; not an e2-specific function. action: KEEP_AS_NON_CORE reason: >- Plausible V-ATPase compartment derived from a Reactome complex-level pathway reaction; non-core for this subunit. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments reference_section_type: DATABASE_ENTRY - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-5252133 qualifier: located_in review: summary: >- Reactome annotation placing the V-ATPase on the endosome membrane (ATP6AP1 binds V-ATPase reaction). Correct compartment for the complex. action: KEEP_AS_NON_CORE reason: >- Correct V-ATPase compartment from a Reactome complex-level reaction; non-core for this subunit. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments reference_section_type: DATABASE_ENTRY - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-74723 qualifier: located_in review: summary: >- Reactome annotation to endosome membrane in the context of endosome acidification. Correct compartment for the V-ATPase complex. action: KEEP_AS_NON_CORE reason: >- Correct but non-core; complex-level localization from a Reactome acidification reaction. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments reference_section_type: DATABASE_ENTRY - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-917841 qualifier: located_in review: summary: >- Reactome annotation to endosome membrane (acidification of Tf:TfR1 endosome). Correct compartment for the V-ATPase complex. action: KEEP_AS_NON_CORE reason: >- Correct but non-core; complex-level localization from a Reactome acidification reaction. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments reference_section_type: DATABASE_ENTRY - term: id: GO:0007035 label: vacuolar acidification evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: involved_in review: summary: >- Sequence-similarity transfer (from Q3E7B6) that e2 is involved in vacuolar acidification, the defining physiological output of V-ATPase proton transport. Well supported by the gene/protein name and the UniProt function. action: ACCEPT reason: >- Acidification of intracellular compartments is the direct downstream consequence of the proton transport that e2 contributes to; consistent with the lysosomal e2 alternative name and UniProt FUNCTION. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments reference_section_type: DATABASE_ENTRY - term: id: GO:0016020 label: membrane evidence_type: NAS original_reference_id: PMID:17350184 qualifier: located_in review: summary: >- Membrane localization stated in the cloning paper; correct but generic. action: KEEP_AS_NON_CORE reason: >- True high-level localization; superseded in informativeness by the specific compartment-membrane terms. supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane protein reference_section_type: DATABASE_ENTRY - term: id: GO:0042625 label: ATPase-coupled ion transmembrane transporter activity evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: enables review: summary: >- Generic ATPase-coupled ion transporter activity transferred by similarity. The more specific and accurate molecular function for this V-ATPase subunit is GO:0046961 (proton-transporting ATPase activity, rotational mechanism), which is already annotated. This broader term is redundant and less precise, and e2 contributes to rather than independently enables transporter activity. action: MODIFY reason: >- A more specific term that accurately captures the rotational proton-pumping mechanism of the V-ATPase is available and already used; the generic term should be replaced by it. proposed_replacement_terms: - id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- a membrane integral complex (V0) that translocates protons reference_section_type: DATABASE_ENTRY core_functions: - description: >- As an accessory membrane subunit (e2) of the V0 proton-translocation sector of the vacuolar H+-ATPase, ATP6V0E2 contributes to ATP-hydrolysis-driven, rotational-mechanism proton transport across endomembranes, thereby acidifying intracellular compartments such as lysosomes and endosomes. molecular_function: id: GO:0005198 label: structural molecule activity contributes_to_molecular_function: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism directly_involved_in: - id: GO:1902600 label: proton transmembrane transport - id: GO:0007035 label: vacuolar acidification locations: - id: GO:0005765 label: lysosomal membrane - id: GO:0010008 label: endosome membrane in_complex: id: GO:0000220 label: vacuolar proton-transporting V-type ATPase, V0 domain supported_by: - reference_id: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt supporting_text: >- Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons reference_section_type: DATABASE_ENTRY - reference_id: PMID:17350184 supporting_text: >- either form of the e-subunit is essential for proper proton pump function reference_section_type: ABSTRACT proposed_new_terms: [] suggested_questions: - question: >- Do the e1 (ATP6V0E1) and e2 (ATP6V0E2) subunits confer distinct compartment-specific or tissue-specific V-ATPase functions, given e2's restricted expression in heart, brain and kidney? - question: >- Is e2 incorporated into V-ATPase complexes with particular V0 a-subunit isoforms (ATP6V0A1-A4), as suggested by the multiple ComplexPortal variant complexes listing this subunit? suggested_experiments: - description: >- Targeted knockout/knockdown of ATP6V0E2 in cell types with high e2 expression (e.g., kidney or brain-derived cells) followed by ratiometric measurement of lysosomal/endosomal pH to test its specific contribution to compartment acidification relative to e1. - description: >- Affinity purification of assembled V-ATPase from e2-expressing tissues coupled to mass spectrometry and cryo-EM to define which V0 a-subunit variant complexes incorporate e2 versus e1. references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000024 title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:17350184 title: 'Molecular cloning and characterization of a novel form of the human vacuolar H+-ATPase e-subunit: an essential proton pump component.' findings: [] - id: PMID:22982048 title: Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts. findings: [] - id: Reactome:R-HSA-1222516 title: Intraphagosomal pH is lowered to 5 by V-ATPase findings: [] - id: Reactome:R-HSA-5252133 title: ATP6AP1 binds V-ATPase findings: [] - id: Reactome:R-HSA-74723 title: Endosome acidification findings: [] - id: Reactome:R-HSA-917841 title: Acidification of Tf:TfR1 containing endosome findings: [] - id: Reactome:R-HSA-9639286 title: RRAGC,D exchanges GTP for GDP findings: [] - id: Reactome:R-HSA-9640167 title: RRAGA,B exchanges GDP for GTP findings: [] - id: Reactome:R-HSA-9640168 title: v-ATPase:Ragulator:RRAGA,B:GTP:RRAGC,D:GDP:SLC38A9:Arginine dissociates yielding v-ATPase:Ragulator:RRAGA,B:GTP:RRAGC,D:GDP and SLC38A9:Arginine findings: [] - id: Reactome:R-HSA-9640175 title: v-ATPase:Ragulator:RagA,B:GDP:RagC,D:GDP binds SLC38A9:Arginine findings: [] - id: Reactome:R-HSA-9640195 title: RRAGA,B hydrolyzes GTP findings: [] - id: Reactome:R-HSA-9645598 title: RRAGC,D hydrolyzes GTP findings: [] - id: Reactome:R-HSA-9645608 title: v-ATPase:Ragulator:RRAGA,B:GTP:RRAGC,D:GDP binds mTORC1 findings: [] - id: Reactome:R-HSA-9646468 title: mTORC1 binds RHEB:GTP findings: []