ATP6V1G2

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000221 vacuolar proton-transporting V-type ATPase, V1 domain	IBA GO_REF:0000033	ACCEPT	Summary: ATP6V1G2 is a G subunit of the peripheral (V1) sector of the V-ATPase; localization as part of the V1 domain is well supported by UniProt and structural biology of the EG peripheral stalk. Reason: The G subunit is a bona fide structural component of the V1 domain, forming EG peripheral stalks with the E subunit. This phylogenetic (IBA) annotation is consistent with the UniProt SUBUNIT description and the conserved V-ATPase architecture. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H.
GO:0030672 synaptic vesicle membrane	IBA GO_REF:0000033	ACCEPT	Summary: ATP6V1G2 is the brain/neuronal-enriched G-subunit isoform; as part of the V-ATPase it is active at the synaptic vesicle membrane, where the V1 sector docks onto V0 to acidify the vesicle lumen. Direct isoform-specific support comes from mass spectrometry of V-ATPase purified from rat-brain synaptic vesicles, where G2 was the predominant G subunit (~83% G2 vs ~17% G1). Reason: Consistent with the brain-enriched tissue specificity of this isoform and the established role of neuronal V-ATPase in synaptic vesicle acidification. The IBA transfer from neuronal G-subunit orthologs is appropriate, and proteomic data confirm that the G2 isoform (not merely the generic complex or the ubiquitous G1) is the major G subunit incorporated into synaptic-vesicle V-ATPase. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt TISSUE SPECIFICITY: Brain. file:human/ATP6V1G2/ATP6V1G2-deep-research-falcon.md Mass spectrometry analysis of V-ATPase purified from rat brain synaptic vesicles identified G2 as the predominant G subunit (with approximately 83% G2 and 17% G1), confirming its enrichment in neuronal vesicular compartments
GO:0097401 synaptic vesicle lumen acidification	IBA GO_REF:0000033	ACCEPT	Summary: As the neuronal V-ATPase G subunit, ATP6V1G2 is involved in acidifying the synaptic vesicle lumen, the proton gradient that drives neurotransmitter loading. Within the brain this isoform is expressed specifically in neurons, whereas non-neuronal cells (astrocytes/glia) use only G1, consistent with a neuron-restricted role in synaptic-vesicle acidification. Reason: This is the core neuronal biological process for the brain-enriched V1 G subunit, well supported by phylogenetic inference from orthologs and by the known function of neuronal V-ATPase. Falcon deep research corroborates the neuron-specific expression pattern that underlies the isoform-specificity of this annotation. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments. file:human/ATP6V1G2/ATP6V1G2-deep-research-falcon.md Within the brain, neurons express the unique G2 isoform in addition to G1, whereas non-neuronal cells such as astrocytes and glia express only the G1 isoform
GO:0016471 vacuolar proton-transporting V-type ATPase complex	IEA GO_REF:0000120	ACCEPT	Summary: ATP6V1G2 is a structural subunit of the vacuolar V-type ATPase holoenzyme. Reason: This is the defining complex membership for a V-ATPase G subunit and is directly supported by the UniProt FUNCTION/SUBUNIT descriptions, even though the source code is IEA. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Subunit of the V1 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.
GO:0030665 clathrin-coated vesicle membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Localization to the clathrin-coated vesicle membrane is inferred by similarity (UniProt SubCell mapping from the bovine ortholog Q0VCV6) and reflects general V-ATPase distribution rather than a defining function of this isoform. Reason: The annotation derives from UniProt subcellular-location mapping by similarity to an ortholog, not direct evidence for ATP6V1G2. It captures a plausible organelle-membrane localization but is not the core brain/synaptic role; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Cytoplasmic vesicle, clathrin-coated vesicle membrane {ECO:0000250\|UniProtKB:Q0VCV6}; Peripheral membrane protein.
GO:0042470 melanosome	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Melanosome localization is an organelle-membrane distribution detected by proteomics; it reflects V-ATPase presence on the melanosome membrane, not a melanosome-specific function. Reason: This IEA SubCell-mapped annotation duplicates the experimental melanosome evidence (PMID:17081065). It is a valid localization but peripheral to the core proton-pumping role; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt SUBCELLULAR LOCATION: Melanosome. Note=Highly enriched in late-stage melanosomes.
GO:0046961 proton-transporting ATPase activity, rotational mechanism	IEA GO_REF:0000120	ACCEPT	Summary: As part of the assembled V-ATPase, ATP6V1G2 contributes to rotary, ATP-hydrolysis-driven proton-transporting ATPase activity. This is a complex-level molecular function appropriately annotated to subunits per GO conventions. Reason: The G subunit does not itself hydrolyze ATP, but it is an essential peripheral-stalk component of the holoenzyme that enables rotary proton transport. GO annotates such subunit-level enabling of the complex activity; the annotation is well supported by the conserved V-ATPase mechanism. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons.
GO:1902600 proton transmembrane transport	IEA GO_REF:0000002	ACCEPT	Summary: ATP6V1G2 is involved in proton transmembrane transport as a subunit of the V-ATPase that translocates protons across organelle membranes. Reason: This is the core biological process of the V-ATPase and is directly supported by the UniProt FUNCTION description. The InterPro-based IEA is consistent with the well-established mechanism. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments.
GO:0005515 protein binding	IPI PMID:32296183 A reference map of the human binary protein interactome.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a high-throughput binary interactome screen is uninformative about molecular function and does not specify the biologically meaningful EG peripheral-stalk partnership. Reason: Per curation guidelines, generic GO:0005515 protein binding should be avoided in favor of a more informative MF term. The HuRI Y2H interaction does not by itself convey a specific function for ATP6V1G2. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome.
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a multimodal cell-map/interactome study is uninformative about molecular function. Reason: Generic protein binding should be avoided per curation guidelines. The interaction data do not define a specific molecular function for ATP6V1G2 beyond its established V-ATPase subunit role. Supporting Evidence: PMID:40205054 Multimodal cell maps as a foundation for structural and functional genomics.
GO:0030672 synaptic vesicle membrane	IEA GO_REF:0000107	ACCEPT	Summary: Synaptic vesicle membrane localization transferred from rodent orthologs; consistent with the brain-enriched isoform but redundant with the IBA annotation to the same term. Reason: The localization is well supported for the neuronal G subunit and matches the IBA annotation; the Ensembl Compara transfer is appropriate for this brain-enriched isoform. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt TISSUE SPECIFICITY: Brain.
GO:0097401 synaptic vesicle lumen acidification	IEA GO_REF:0000107	ACCEPT	Summary: Synaptic vesicle lumen acidification transferred from rodent orthologs; this is the core neuronal process for the brain-enriched V1 G subunit. Reason: Redundant with but consistent with the IBA annotation; well supported by the function of neuronal V-ATPase and the brain-enriched expression of this isoform. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments.
GO:0098850 extrinsic component of synaptic vesicle membrane	IEA GO_REF:0000107	ACCEPT	Summary: The peripheral V1 sector, including subunit G, attaches to the synaptic vesicle membrane as an extrinsic (peripheral) membrane component rather than being integral to it. Reason: Accurately describes how the cytosolic-facing V1 sector docks onto the membrane via V0; consistent with the UniProt "Peripheral membrane protein" designation and the EG peripheral-stalk architecture. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0042470 melanosome	EXP PMID:17081065 Proteomic and bioinformatic characterization of the biogenes...	KEEP AS NON CORE	Summary: ATP6V1G2 was detected by mass spectrometry in melanosome proteomes and is enriched in late-stage melanosomes, reflecting V-ATPase presence on this lysosome-related organelle membrane. Reason: This is genuine experimental localization evidence, but it represents organelle-membrane distribution of the V-ATPase rather than a melanosome-specific or defining function of this brain-enriched isoform; keep as non-core. Supporting Evidence: PMID:17081065 Comparative profiling and functional characterization of the melanosome proteomes identified approximately 1500 proteins in melanosomes of all stages. file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Note=Highly enriched in late-stage melanosomes. {ECO:0000269\|PubMed:17081065}.
GO:0000221 vacuolar proton-transporting V-type ATPase, V1 domain	ISS GO_REF:0000024	ACCEPT	Summary: ISS-based localization to the V1 domain, transferred from the bovine ortholog; consistent with the IBA annotation to the same term. Reason: The G subunit is a structural component of the V1 domain; this ISS transfer from the orthologous G subunit (Q0VCV6) is appropriate and consistent with the conserved architecture. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt three peripheral stalks each consisting of EG heterodimers.
GO:0016241 regulation of macroautophagy	NAS PMID:22982048 Lipofuscin is formed independently of macroautophagy and lys...	MARK AS OVER ANNOTATED	Summary: The cited paper is a general lipofuscin/autophagy study in senescent fibroblasts and provides no gene-specific evidence that ATP6V1G2 regulates macroautophagy. Reason: Any V-ATPase generically affects lysosomal/autophagic flux as a downstream consequence of organelle acidification, but this NAS annotation is not supported by gene-specific evidence and is an indirect over-annotation, not a core function of this subunit. Supporting Evidence: PMID:22982048 both the autophagosomes and the lysosomal system are not mandatory for the formation of lipofuscin, since that material accumulates in the cytosolic volume if autophagy or lysosomal activity is inhibited.
GO:0005829 cytosol	TAS Reactome:R-HSA-1222516	KEEP AS NON CORE	Summary: Cytosol localization from Reactome pathway participation (phagosomal acidification); reflects the peripheral/cytosolic-facing V1 sector and reaction-participant context rather than a defining stable location. Reason: The V1 sector faces the cytosol, so this is defensible, but it is a generic Reactome reaction-participant location and not the most informative compartment for this membrane-associated complex subunit; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0005829 cytosol	TAS Reactome:R-HSA-5252133	KEEP AS NON CORE	Summary: Cytosol localization from Reactome (ATP6AP1 binds V-ATPase); reflects the cytosolic-facing V1 sector in pathway context. Reason: Defensible but generic reaction-participant location; not the core compartment annotation for this membrane-associated subunit. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0005829 cytosol	TAS Reactome:R-HSA-74723	KEEP AS NON CORE	Summary: Cytosol localization from Reactome (endosome acidification); reflects the cytosolic-facing V1 sector in pathway context. Reason: Defensible but generic reaction-participant location; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0005829 cytosol	TAS Reactome:R-HSA-917841	KEEP AS NON CORE	Summary: Cytosol localization from Reactome (acidification of transferrin-containing endosome); reflects pathway participation of the V1 sector. Reason: Defensible but generic reaction-participant location; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0005829 cytosol	TAS Reactome:R-HSA-9639286	KEEP AS NON CORE	Summary: Cytosol localization from Reactome (mTORC1 amino-acid signaling pathway); reflects pathway participation of the V-ATPase. Reason: Defensible but generic reaction-participant location tied to mTORC1 signaling context; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0005829 cytosol	TAS Reactome:R-HSA-9640167	KEEP AS NON CORE	Summary: Cytosol localization from Reactome (mTORC1 amino-acid signaling pathway); reflects pathway participation. Reason: Defensible but generic reaction-participant location; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0005829 cytosol	TAS Reactome:R-HSA-9640168	KEEP AS NON CORE	Summary: Cytosol localization from Reactome (mTORC1 amino-acid signaling pathway); reflects pathway participation. Reason: Defensible but generic reaction-participant location; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0005829 cytosol	TAS Reactome:R-HSA-9640175	KEEP AS NON CORE	Summary: Cytosol localization from Reactome (mTORC1 amino-acid signaling pathway); reflects pathway participation. Reason: Defensible but generic reaction-participant location; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0005829 cytosol	TAS Reactome:R-HSA-9640195	KEEP AS NON CORE	Summary: Cytosol localization from Reactome (mTORC1 amino-acid signaling pathway); reflects pathway participation. Reason: Defensible but generic reaction-participant location; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0005829 cytosol	TAS Reactome:R-HSA-9645598	KEEP AS NON CORE	Summary: Cytosol localization from Reactome (mTORC1 amino-acid signaling pathway); reflects pathway participation. Reason: Defensible but generic reaction-participant location; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0005829 cytosol	TAS Reactome:R-HSA-9645608	KEEP AS NON CORE	Summary: Cytosol localization from Reactome (mTORC1 amino-acid signaling pathway); reflects pathway participation. Reason: Defensible but generic reaction-participant location; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.
GO:0005829 cytosol	TAS Reactome:R-HSA-9646468	KEEP AS NON CORE	Summary: Cytosol localization from Reactome (mTORC1 binds RHEB:GTP); reflects pathway participation. Reason: Defensible but generic reaction-participant location; keep as non-core. Supporting Evidence: file:human/ATP6V1G2/ATP6V1G2-uniprot.txt Peripheral membrane protein {ECO:0000305}.

Gene Description

Existing Annotations Review

Core Functions

In neurons, ATP6V1G2 contributes to acidification of the synaptic vesicle lumen, generating the proton-motive force required for neurotransmitter loading, as the brain-enriched V-ATPase G subunit docked onto the synaptic vesicle membrane.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

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Notes

Pn Notes

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