ATP6V0E2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:1902600 proton transmembrane transport	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt a membrane integral complex (V0) that translocates protons PMID:17350184 either form of the e-subunit is essential for proper proton pump function
GO:0000220 vacuolar proton-transporting V-type ATPase, V0 domain	IBA GO_REF:0000033	ACCEPT	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. Reason: UniProt SUBUNIT explicitly places subunit e within the V0 proton translocation complex; the IBA assignment is consistent with this. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt 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.
GO:0046961 proton-transporting ATPase activity, rotational mechanism	IBA GO_REF:0000033	ACCEPT	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. 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. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons PMID:17350184 either form of the e-subunit is essential for proper proton pump function
GO:0016020 membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: ATP6V0E2 is an integral, multi-pass membrane protein; localization to membrane is correct but very generic. Reason: True but uninformative relative to more specific compartment terms (lysosomal/endosomal/vesicle membranes). Retained as a non-core, high-level localization statement. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane protein
GO:0030665 clathrin-coated vesicle membrane	IEA GO_REF:0000044	KEEP AS NON CORE	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. Reason: Plausible compartment for V-ATPase but based on orthology transfer rather than direct human evidence; not the core function of the subunit. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt Cytoplasmic vesicle, clathrin-coated vesicle membrane {ECO:0000250\|UniProtKB:Q5EB76}
GO:0030672 synaptic vesicle membrane	IEA GO_REF:0000120	KEEP AS NON CORE	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. Reason: Reasonable compartment annotation by analogy/orthology; not core and not directly demonstrated for human ATP6V0E2. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000250\|UniProtKB:Q5EB76}
GO:0033179 proton-transporting V-type ATPase, V0 domain	IEA GO_REF:0000002	ACCEPT	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. Reason: Correct complex/domain membership supported by InterPro family signatures (IPR008389, IPR017385) and by the UniProt SUBUNIT description. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt 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
GO:0046961 proton-transporting ATPase activity, rotational mechanism	IEA GO_REF:0000002	ACCEPT	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. 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. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt a membrane integral complex (V0) that translocates protons
GO:1902600 proton transmembrane transport	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based assignment of involvement in proton transmembrane transport. Consistent with the IBA/IGI annotations to the same process. Reason: Core process of the V-ATPase, correctly inferred from InterPro family membership and corroborated by experimental evidence. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt a membrane integral complex (V0) that translocates protons
GO:0000220 vacuolar proton-transporting V-type ATPase, V0 domain	ISS GO_REF:0000024	ACCEPT	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. Reason: Correct V0 domain membership supported by orthology and by the UniProt SUBUNIT description. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-9639286	KEEP AS NON CORE	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. 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. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-9640167	KEEP AS NON CORE	Summary: Reactome annotation to lysosomal membrane in the context of mTORC1 amino-acid sensing. Correct compartment, complex-level/reaction context. Reason: Duplicate lysosomal membrane localization from a Reactome signaling reaction assigned to the V-ATPase complex; correct but non-core. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-9640168	KEEP AS NON CORE	Summary: Reactome lysosomal membrane localization from an mTORC1/Ragulator dissociation reaction. Correct compartment for the V-ATPase complex. Reason: Correct but non-core; complex-level localization from a signaling reaction. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-9640175	KEEP AS NON CORE	Summary: Reactome lysosomal membrane localization (V-ATPase:Ragulator binding SLC38A9:Arginine reaction). Correct compartment, signaling context. Reason: Correct but non-core; complex-level localization from a signaling reaction. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-9640195	KEEP AS NON CORE	Summary: Reactome lysosomal membrane localization (RRAGA,B GTP hydrolysis reaction). Correct compartment, signaling context. Reason: Correct but non-core; complex-level localization from a signaling reaction. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-9645598	KEEP AS NON CORE	Summary: Reactome lysosomal membrane localization (RRAGC,D GTP hydrolysis reaction). Correct compartment, signaling context. Reason: Correct but non-core; complex-level localization from a signaling reaction. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-9645608	KEEP AS NON CORE	Summary: Reactome lysosomal membrane localization (V-ATPase:Ragulator binding mTORC1 reaction). Correct compartment, signaling context. Reason: Correct but non-core; complex-level localization from a signaling reaction. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2
GO:0005765 lysosomal membrane	TAS Reactome:R-HSA-9646468	KEEP AS NON CORE	Summary: Reactome lysosomal membrane localization (mTORC1 binding RHEB:GTP reaction). Correct compartment, signaling context. Reason: Correct but non-core; complex-level localization from a signaling reaction. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt AltName: Full=Lysosomal 9 kDa H(+)-transporting ATPase V0 subunit e2
GO:0046961 proton-transporting ATPase activity, rotational mechanism	IGI PMID:17350184 Molecular cloning and characterization of a novel form of th...	ACCEPT	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. Reason: Direct functional evidence (yeast complementation, WITH ortholog Q3E7B6) that e2 is required for proper pump function; strongest support for the molecular function. Supporting Evidence: PMID:17350184 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.
GO:1902600 proton transmembrane transport	IGI PMID:17350184 Molecular cloning and characterization of a novel form of th...	ACCEPT	Summary: Experimental genetic-interaction (yeast complementation) evidence that e2 is required for proton pump function, supporting involvement in proton transmembrane transport. Reason: Core process supported by direct functional complementation data. Supporting Evidence: PMID:17350184 either form of the e-subunit is essential for proper proton pump function
GO:0016241 regulation of macroautophagy	NAS PMID:22982048 Lipofuscin is formed independently of macroautophagy and lys...	MARK AS OVER ANNOTATED	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. 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. Supporting Evidence: PMID:22982048 Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts.
GO:0030670 phagocytic vesicle membrane	TAS Reactome:R-HSA-1222516	KEEP AS NON CORE	Summary: Reactome annotation placing the V-ATPase on the phagosome membrane during intraphagosomal acidification. Correct compartment for the complex; not an e2-specific function. Reason: Plausible V-ATPase compartment derived from a Reactome complex-level pathway reaction; non-core for this subunit. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments
GO:0010008 endosome membrane	TAS Reactome:R-HSA-5252133	KEEP AS NON CORE	Summary: Reactome annotation placing the V-ATPase on the endosome membrane (ATP6AP1 binds V-ATPase reaction). Correct compartment for the complex. Reason: Correct V-ATPase compartment from a Reactome complex-level reaction; non-core for this subunit. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments
GO:0010008 endosome membrane	TAS Reactome:R-HSA-74723	KEEP AS NON CORE	Summary: Reactome annotation to endosome membrane in the context of endosome acidification. Correct compartment for the V-ATPase complex. Reason: Correct but non-core; complex-level localization from a Reactome acidification reaction. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments
GO:0010008 endosome membrane	TAS Reactome:R-HSA-917841	KEEP AS NON CORE	Summary: Reactome annotation to endosome membrane (acidification of Tf:TfR1 endosome). Correct compartment for the V-ATPase complex. Reason: Correct but non-core; complex-level localization from a Reactome acidification reaction. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments
GO:0007035 vacuolar acidification	ISS GO_REF:0000024	ACCEPT	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. 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. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments
GO:0016020 membrane	NAS PMID:17350184 Molecular cloning and characterization of a novel form of th...	KEEP AS NON CORE	Summary: Membrane localization stated in the cloning paper; correct but generic. Reason: True high-level localization; superseded in informativeness by the specific compartment-membrane terms. Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane protein
GO:0042625 ATPase-coupled ion transmembrane transporter activity	ISS GO_REF:0000024	MODIFY	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. 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 replacements: proton-transporting ATPase activity, rotational mechanism Supporting Evidence: file:human/ATP6V0E2/ATP6V0E2-uniprot.txt a membrane integral complex (V0) that translocates protons

Gene Description

Existing Annotations Review

Core Functions

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.

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