id: O75348 gene_symbol: ATP6V1G1 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- ATP6V1G1 encodes V-type proton ATPase subunit G 1 (118 amino acids, 13.8 kDa), a peripheral stalk component of the V1 catalytic domain of the vacuolar-type H+-ATPase (V-ATPase). The V-ATPase is a large multi-subunit complex that couples ATP hydrolysis to proton translocation across membranes, thereby acidifying lysosomes, endosomes, and other intracellular compartments. The V1 domain (peripheral, cytosolic) contains subunits A-H and is responsible for ATP hydrolysis; it couples to the membrane-embedded V0 domain through three peripheral EG heterodimeric stalks that act as the stator. Subunit G 1 forms these EG heterodimers with subunit E (ATP6V1E1 or ATP6V1E2), directly contacts the V0 subunit a, and is essential for maintaining V1-V0 connectivity. ATP6V1G1 is ubiquitously expressed; humans also have two paralogous G subunits (G2, G3) with more restricted expression. The protein is present at lysosomal and endosomal membranes as part of the assembled holoenzyme, at the apical plasma membrane in kidney tubular epithelial cells (thick ascending limb and distal convoluted tubule), and in the cytosol as part of the free, disassembled V1 complex. V-ATPase-mediated acidification of endosomes is required for efficient iron release from transferrin; consistent with this, genetic disruption of ATP6V1G1 causes intracellular iron depletion, impaired prolyl hydroxylase (PHD) activity, and consequent HIF1alpha stabilization. existing_annotations: - term: id: GO:0000221 label: vacuolar proton-transporting V-type ATPase, V1 domain evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: ATP6V1G1 is a bona fide V1 domain subunit, confirmed by cryo-EM structure. action: ACCEPT reason: The V1 domain membership is experimentally established by mass spectrometry and cryo-EM (PMID:33065002). The IBA annotation is consistent with experimental data and reflects true V1 component status. supported_by: - reference_id: file:human/ATP6V1G1/ATP6V1G1-uniprot.txt supporting_text: "Subunit of the V1 complex of vacuolar(H+)-ATPase" - term: id: GO:0030672 label: synaptic vesicle membrane evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: Synaptic vesicle membrane activity inferred by phylogenetic transfer; reflects V-ATPase role at synaptic vesicles in neurons, not core function of this ubiquitous subunit. action: KEEP_AS_NON_CORE reason: While V-ATPases acidify synaptic vesicles in neurons, this annotation describes a non-core context for a ubiquitously expressed subunit. The specific activity is an indirect consequence of V1 participation in the overall proton pump complex rather than a dedicated synaptic function of G1. - term: id: GO:0097401 label: synaptic vesicle lumen acidification evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Synaptic vesicle acidification inferred by phylogenetic transfer; non-core for this ubiquitously expressed peripheral stalk subunit. action: KEEP_AS_NON_CORE reason: Synaptic vesicle lumen acidification is a neuron-specific downstream process. This ubiquitous G1 subunit contributes to V-ATPase activity generally; synaptic vesicle context is non-core. - term: id: GO:0016324 label: apical plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: IEA from UniProt subcellular location vocabulary mapping; supported by experimental co-localization in kidney tubular cells. action: ACCEPT reason: This IEA annotation is backed by experimental co-localization data showing H+-ATPase subunits including G1 at the apical membrane of kidney TAL and DCT (PMID:29993276). supported_by: - reference_id: PMID:29993276 supporting_text: the H+-ATPase B1 subunit colocalized with other H+-ATPase subunits in the TAL and DCT - term: id: GO:0016471 label: vacuolar proton-transporting V-type ATPase complex evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: part_of review: summary: Computationally inferred V-ATPase complex membership; correct and supported by structural evidence. action: ACCEPT reason: ATP6V1G1 is a component of the assembled V-ATPase holoenzyme. IEA annotation is consistent with cryo-EM structural data (PMID:33065002). - term: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables review: summary: IEA annotation for rotational mechanism ATPase activity; correct at the complex level. action: ACCEPT reason: The V-ATPase employs a rotational mechanism for proton translocation. As a peripheral stalk subunit, G1 contributes to this activity as part of the stator apparatus. The annotation is appropriate with contributes_to semantics implied. - term: id: GO:0051117 label: ATPase binding evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: enables review: summary: IEA ARBA prediction for ATPase binding; reflects known G1 interaction with V0 subunit a documented experimentally. action: ACCEPT reason: The G1 subunit directly interacts with V0 subunit a, constituting genuine ATPase binding within the V-ATPase complex (PMID:17360703). - term: id: GO:1902600 label: proton transmembrane transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: IEA from InterPro; proton transmembrane transport is the core function of the V-ATPase complex. action: ACCEPT reason: Proton transmembrane transport is the core biological process driven by the V-ATPase. As a structural component of the complex, G1 is rightly annotated as involved in this process. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:16169070 qualifier: enables review: summary: Generic protein binding from high-throughput proteome-wide interaction dataset; uninformative over-annotation. action: MARK_AS_OVER_ANNOTATED reason: This IPI annotation comes from a large-scale interactome screen. Protein binding in isolation is uninformative about G1 molecular function. The meaningful interaction is with ATP6V1E1/E2 (EG peripheral stalk) and V0 subunit a. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:21516116 qualifier: enables review: summary: Generic protein binding from high-throughput interaction screen; uninformative. action: MARK_AS_OVER_ANNOTATED reason: High-throughput interactome dataset; protein binding alone does not reflect the specific structural role of G1 in the V-ATPase. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:25416956 qualifier: enables review: summary: Generic protein binding from proteome-scale interactome network; uninformative. action: MARK_AS_OVER_ANNOTATED reason: High-throughput interactome dataset; does not reflect specific function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:30021884 qualifier: enables review: summary: Generic protein binding from crosslinking mass spectrometry dataset; uninformative over-annotation. action: MARK_AS_OVER_ANNOTATED reason: High-throughput dataset; uninformative for characterizing G1 function. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:31515488 qualifier: enables review: summary: Generic protein binding from population genetics interactome study; uninformative. action: MARK_AS_OVER_ANNOTATED reason: High-throughput interactome dataset; does not reflect specific molecular function of G1. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 qualifier: enables review: summary: Generic protein binding from binary interactome reference map; uninformative. action: MARK_AS_OVER_ANNOTATED reason: High-throughput interactome dataset; protein binding is an over-annotation for a subunit whose specific interactions (with E subunit and V0 subunit a) are known. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35271311 qualifier: enables review: summary: Generic protein binding from OpenCell endogenous tagging study; uninformative. action: MARK_AS_OVER_ANNOTATED reason: High-throughput dataset; protein binding does not describe the specific EG peripheral stalk assembly function. - term: id: GO:0005765 label: lysosomal membrane evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: IEA Ensembl Compara transfer; lysosomal membrane localization is consistent with HDA mass spectrometry data. action: ACCEPT reason: Lysosomal membrane localization is supported by mass spectrometry identification in lysosome-enriched fractions (PMID:17897319) and is expected for an assembled V-ATPase subunit. - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: IEA Ensembl Compara transfer; cytosolic localization reflects the regulated disassembly state where free V1 complex is in the cytoplasm. action: KEEP_AS_NON_CORE reason: Cytosolic localization is a real state (free V1 complex released from membranes under regulated disassembly) but is not the primary functional location. - term: id: GO:0005886 label: plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: IEA transfer; plasma membrane localization is supported by experimental evidence from kidney tubular cells (apical plasma membrane) and by the G/a subunit interaction study. action: ACCEPT reason: Plasma membrane localization is experimentally supported both by kidney apical membrane co-localization (PMID:29993276) and by the G1/a interaction study (PMID:17360703). The IEA is consistent with experimental findings. - term: id: GO:0015078 label: proton transmembrane transporter activity evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: contributes_to review: summary: IEA Ensembl Compara transfer; proton transmembrane transporter activity is a core V-ATPase function. action: ACCEPT reason: Proton transmembrane transporter activity is the direct molecular function of the V-ATPase complex. The contributes_to qualifier is appropriate for a structural subunit. - term: id: GO:0033176 label: proton-transporting V-type ATPase complex evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: part_of review: summary: IEA transfer for V-ATPase complex membership; correct at the whole-complex level, but the more specific V1 domain annotation is preferred. action: ACCEPT reason: ATP6V1G1 is a component of the entire V-ATPase holoenzyme as well as the V1 sub-complex. This whole-complex annotation is appropriate as a broader complement to the V1 domain annotation. - term: id: GO:0033180 label: proton-transporting V-type ATPase, V1 domain evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: part_of review: summary: IEA Ensembl Compara transfer; V1 domain membership is experimentally confirmed. action: ACCEPT reason: V1 domain membership is established by cryo-EM and mass spectrometry (PMID:33065002). This IEA is consistent with experimental evidence. - term: id: GO:0097401 label: synaptic vesicle lumen acidification evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: IEA Ensembl Compara transfer for synaptic vesicle lumen acidification; non-core neuronal context annotation. action: KEEP_AS_NON_CORE reason: Neuronal synaptic vesicle acidification is a non-core context for this ubiquitously expressed subunit. - term: id: GO:0098850 label: extrinsic component of synaptic vesicle membrane evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: is_active_in review: summary: IEA Ensembl Compara transfer; V1 domain is extrinsic to synaptic vesicle membranes in neurons. Non-core context. action: KEEP_AS_NON_CORE reason: The V1 peripheral complex is extrinsic to vesicle membranes in neurons. This is a non-core neuronal context for a ubiquitous subunit. - term: id: GO:0016324 label: apical plasma membrane evidence_type: EXP original_reference_id: PMID:29993276 qualifier: located_in review: summary: Experimental co-localization of G1 with other H+-ATPase subunits at the apical plasma membrane in kidney TAL and DCT. Strongly supported. action: ACCEPT reason: Direct experimental evidence from kidney sections showing co-localization of H+-ATPase subunits including G1 at the apical plasma membrane in thick ascending limb and distal convoluted tubule. supported_by: - reference_id: PMID:29993276 supporting_text: the H+-ATPase B1 subunit colocalized with other H+-ATPase subunits in the TAL and DCT - term: id: GO:0000221 label: vacuolar proton-transporting V-type ATPase, V1 domain evidence_type: IDA original_reference_id: PMID:33065002 qualifier: part_of review: summary: Direct experimental identification of G1 in the human V-ATPase V1 complex by cryo-EM structure determination. action: ACCEPT reason: High-quality cryo-EM structures of the complete human V-ATPase directly identified all V1 subunits including G1 by mass spectrometry. This is the strongest possible evidence for V1 domain membership. supported_by: - reference_id: file:human/ATP6V1G1/ATP6V1G1-uniprot.txt supporting_text: "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" - term: id: GO:0006879 label: intracellular iron ion homeostasis evidence_type: IMP original_reference_id: PMID:28296633 qualifier: involved_in review: summary: IMP annotation based on a genetic screen; loss of ATP6V1G1 disrupts V-ATPase proton pumping, which impairs endosomal acidification and iron release from transferrin. This is an indirect downstream consequence of impaired proton transport, not a direct iron homeostasis function. action: MARK_AS_OVER_ANNOTATED reason: The iron homeostasis effect observed upon ATP6V1G1 knockdown is an indirect consequence of disrupted V-ATPase activity impairing endosomal acidification and therefore transferrin-mediated iron delivery. The primary molecular function is proton transport; iron homeostasis is a secondary, downstream effect. Annotating the peripheral stalk subunit to iron homeostasis overstates its direct role. supported_by: - reference_id: PMID:28296633 supporting_text: disrupting the V-ATPase results in intracellular iron depletion, thereby impairing PHD activity and leading to HIF activation - reference_id: PMID:28296633 supporting_text: 'principally relating to mutagenesis of genes encoding five V-ATPase subunits: ATP6AP1, ATP6V1A, ATP6V1G1, ATP6V0A2 and ATP6V0D1' - term: id: GO:0036295 label: cellular response to increased oxygen levels evidence_type: IMP original_reference_id: PMID:28296633 qualifier: involved_in review: summary: IMP annotation; HIF1alpha stabilization upon ATP6V1G1 loss is an indirect consequence of iron depletion downstream of V-ATPase disruption. Not a direct oxygen-sensing function. action: MARK_AS_OVER_ANNOTATED reason: The cellular response to increased oxygen levels (HIF pathway) effect is downstream of iron depletion, which is itself downstream of impaired endosomal acidification. This is two steps removed from the primary proton pump function of G1. Annotating a structural peripheral stalk subunit to oxygen response conflates the primary molecular function with a distal phenotypic consequence. supported_by: - reference_id: PMID:28296633 supporting_text: disrupting the V-ATPase results in intracellular iron depletion, thereby impairing PHD activity and leading to HIF activation - term: id: GO:0016241 label: regulation of macroautophagy evidence_type: NAS original_reference_id: PMID:22982048 qualifier: involved_in review: summary: NAS annotation linking V-ATPase disruption to macroautophagy; the cited paper uses V-ATPase inhibition as a tool to block lysosomal function, not as direct evidence that G1 regulates macroautophagy. action: MARK_AS_OVER_ANNOTATED reason: The cited paper (PMID:22982048) uses V-ATPase disruption as a tool to impair lysosomal activity and does not demonstrate that ATP6V1G1 specifically regulates macroautophagy. V-ATPase activity is required for lysosomal acidification, which is needed for autophagy completion, but this generic consequence of proton pump disruption does not justify annotating the G1 structural subunit to regulation of macroautophagy. - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: HDA from urinary exosome proteomics; likely contamination of exosome fraction with non-exosomal V-ATPase; not considered a core localization. action: KEEP_AS_NON_CORE reason: Extracellular exosome identification from urinary proteomics (PMID:19056867) is likely a contaminant in the exosome-enriched fraction rather than genuine exosomal loading. Not a core localization for this cytosolic V1 peripheral stalk subunit. - term: id: GO:0005765 label: lysosomal membrane evidence_type: HDA original_reference_id: PMID:17897319 qualifier: located_in review: summary: HDA from lysosomal membrane proteomics; directly supports lysosomal membrane localization as part of the assembled V-ATPase holoenzyme. action: ACCEPT reason: Mass spectrometry identification in lysosome-enriched fractions (PMID:17897319) directly supports lysosomal membrane localization, consistent with the role of the assembled V-ATPase holoenzyme at the lysosomal membrane. supported_by: - reference_id: PMID:17897319 supporting_text: Integral and associated lysosomal membrane proteins - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1222516 qualifier: located_in review: summary: Reactome TAS annotation; cytosolic location reflects regulated disassembly state of free V1 complex. action: KEEP_AS_NON_CORE reason: The cytosolic V1 complex is a real regulated state (disassembled from V0 under nutrient deprivation), but not the primary functional localization. Multiple Reactome entries support this non-core annotation. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5252133 qualifier: located_in review: summary: Reactome TAS annotation for cytosol; same rationale as above. action: KEEP_AS_NON_CORE reason: Cytosolic localization in regulated disassembly context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-74723 qualifier: located_in review: summary: Reactome TAS annotation for cytosol; non-core regulated disassembly state. action: KEEP_AS_NON_CORE reason: Cytosolic localization in regulated disassembly context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-917841 qualifier: located_in review: summary: Reactome TAS annotation for cytosol; non-core. action: KEEP_AS_NON_CORE reason: Cytosolic localization in regulated disassembly context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9639286 qualifier: located_in review: summary: Reactome TAS annotation for cytosol in mTORC1 signaling context; non-core. action: KEEP_AS_NON_CORE reason: Cytosolic localization context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640167 qualifier: located_in review: summary: Reactome TAS annotation for cytosol; non-core. action: KEEP_AS_NON_CORE reason: Cytosolic localization in Rag GTPase/mTORC1 signaling context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640168 qualifier: located_in review: summary: Reactome TAS annotation for cytosol; non-core. action: KEEP_AS_NON_CORE reason: Cytosolic localization context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640175 qualifier: located_in review: summary: Reactome TAS annotation for cytosol; non-core. action: KEEP_AS_NON_CORE reason: Cytosolic localization context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640195 qualifier: located_in review: summary: Reactome TAS annotation for cytosol; non-core. action: KEEP_AS_NON_CORE reason: Cytosolic localization context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9645598 qualifier: located_in review: summary: Reactome TAS annotation for cytosol; non-core. action: KEEP_AS_NON_CORE reason: Cytosolic localization context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9645608 qualifier: located_in review: summary: Reactome TAS annotation for cytosol; non-core. action: KEEP_AS_NON_CORE reason: Cytosolic localization context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9646468 qualifier: located_in review: summary: Reactome TAS annotation for cytosol; non-core. action: KEEP_AS_NON_CORE reason: Cytosolic localization context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9858924 qualifier: located_in review: summary: Reactome TAS annotation for cytosol; non-core. action: KEEP_AS_NON_CORE reason: Cytosolic localization context; non-core. - term: id: GO:0005829 label: cytosol evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: ISS manual ortholog transfer for cytosol localization; consistent with regulated disassembly producing free cytosolic V1 complex. action: KEEP_AS_NON_CORE reason: Cytosolic localization reflects the regulated disassembly state; non-core. - term: id: GO:0005886 label: plasma membrane evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: ISS manual ortholog transfer for plasma membrane localization; consistent with experimental evidence showing G1 at apical plasma membrane in kidney and at plasma membrane in the G1/a interaction study. action: ACCEPT reason: Plasma membrane localization is well supported experimentally (PMID:17360703, PMID:29993276). ISS is consistent with these experimental findings. - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:17360703 qualifier: located_in review: summary: Experimental plasma membrane localization from study demonstrating G1/a subunit interaction; the study demonstrated G1 at plasma membrane in the context of V0 subunit a interaction. action: ACCEPT reason: The experimental evidence from PMID:17360703 demonstrates that G1 localizes at the plasma membrane as part of its interaction with V0 subunit a, which directly supports plasma membrane localization. supported_by: - reference_id: PMID:17360703 supporting_text: V1 and V0 domains of the human H+-ATPase are linked by an interaction between the G and a subunits - term: id: GO:0051117 label: ATPase binding evidence_type: IPI original_reference_id: PMID:17360703 qualifier: enables review: summary: Experimental IPI evidence for ATPase binding; reflects direct G1 interaction with V0 subunit a, a V-ATPase component. action: ACCEPT reason: PMID:17360703 experimentally demonstrated direct interaction between G1 and V0 subunit a (ATP6V0A1, ATP6V0A4), supporting ATPase binding annotation as a meaningful specific interaction. supported_by: - reference_id: PMID:17360703 supporting_text: V1 and V0 domains of the human H+-ATPase are linked by an interaction between the G and a subunits 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:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:16169070 title: 'A human protein-protein interaction network: a resource for annotating the proteome.' findings: [] - id: PMID:17360703 title: V1 and V0 domains of the human H+-ATPase are linked by an interaction between the G and a subunits. findings: - statement: G1/a1, G3/a1, and G1/a4 interactions demonstrated experimentally; G and a subunit interaction is a novel link between V1 and V0 required for H+-ATPase assembly and regulation. - id: PMID:17897319 title: Integral and associated lysosomal membrane proteins. findings: - statement: Mass spectrometry identification of ATP6V1G1 in lysosome-enriched fractions supports lysosomal membrane localization. - id: PMID:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. findings: - statement: Identification in urinary exosome fraction; likely contamination rather than genuine exosomal loading. - id: PMID:21516116 title: Next-generation sequencing to generate interactome datasets. findings: [] - id: PMID:22982048 title: Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts. findings: - statement: V-ATPase disruption used as a tool to impair lysosomal activity; does not directly implicate ATP6V1G1 in macroautophagy regulation. - id: PMID:25416956 title: A proteome-scale map of the human interactome network. findings: [] - id: PMID:28296633 title: The vacuolar-ATPase complex and assembly factors, TMEM199 and CCDC115, control HIF1alpha prolyl hydroxylation by regulating cellular iron levels. findings: - statement: ATP6V1G1 identified in genome-wide screen for HIF1alpha regulators; mechanism is indirect via iron depletion from impaired endosomal acidification leading to reduced PHD activity and HIF activation. - id: PMID:29993276 title: H(+)-ATPase B1 subunit localizes to thick ascending limb and distal convoluted tubule of rodent and human kidney. findings: - statement: H+-ATPase B1 subunit co-localizes with other H+-ATPase subunits at apical plasma membrane in kidney TAL and DCT. - id: PMID:30021884 title: Histone Interaction Landscapes Visualized by Crosslinking Mass Spectrometry in Intact Cell Nuclei. findings: [] - id: PMID:31515488 title: Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations. findings: [] - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: [] - id: PMID:33065002 title: Structures of a Complete Human V-ATPase Reveal Mechanisms of Its Assembly. findings: - statement: Cryo-EM structures of complete human V-ATPase directly identify all V1 subunits; V1 complex contains three peripheral EG heterodimeric stalks. - id: PMID:35271311 title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.' 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: [] - id: Reactome:R-HSA-9858924 title: MITF-M-dependent ATP6V1G1gene expression findings: [] core_functions: - description: >- ATP6V1G1 is a structural peripheral stalk subunit of the V1 domain of the V-ATPase, forming EG heterodimers with subunit E (ATP6V1E1/E2) that serve as the stator connecting the V1 catalytic hexameric ring to the V0 proton channel. It directly contacts the V0 subunit a, and the G-a interaction is required for V1-V0 assembly and integrity. As part of the assembled holoenzyme, ATP6V1G1 contributes to ATP-hydrolysis-driven proton transport across lysosomal, endosomal, and (in kidney tubular cells) apical plasma membranes. contributes_to_molecular_function: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism molecular_function: id: GO:0005198 label: structural molecule activity directly_involved_in: - id: GO:1902600 label: proton transmembrane transport locations: - id: GO:0005765 label: lysosomal membrane - id: GO:0010008 label: endosome membrane - id: GO:0016324 label: apical plasma membrane supported_by: - reference_id: file:human/ATP6V1G1/ATP6V1G1-uniprot.txt supporting_text: "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" - reference_id: PMID:17360703 supporting_text: V1 and V0 domains of the human H+-ATPase are linked by an interaction between the G and a subunits suggested_questions: - question: Are the three human G subunit paralogs (G1, G2, G3) fully interchangeable in the peripheral stalk, or does G1 have distinct V-ATPase assembly or localization properties compared with G2 and G3? experts: - Blake-Palmer KG - Karet FE - question: Does regulated disassembly of V1 from V0 under nutrient deprivation preferentially affect V-ATPase complexes containing a particular G subunit paralog, and what determines the cytosolic versus membrane-bound distribution of G1? experts: - Forgac M suggested_experiments: - hypothesis: G1, G2, and G3 are functionally non-equivalent peripheral stalk subunits with distinct V1-V0 coupling properties. description: >- Generate G1/G2/G3 paralog-specific knockout cell lines and perform functional complementation with each paralog individually to assess whether loss of G1 can be rescued by G2 or G3 with equal efficiency in lysosomal acidification and iron homeostasis assays. experiment_type: genetic complementation and lysosomal pH measurement - hypothesis: Post-translational modifications of G1 regulate V-ATPase assembly state (V1-V0 association vs. disassembly). description: >- Apply proximity labeling (BioID/APEX2) from G1 in nutrient-replete versus nutrient-deprived conditions to identify regulated binding partners in assembled versus disassembled states, and map G1 phosphorylation sites by quantitative phosphoproteomics. experiment_type: proximity labeling proteomics and phosphoproteomics