id: Q96LB4 gene_symbol: ATP6V1G3 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- ATP6V1G3 (V-type proton ATPase subunit G 3) is the kidney-enriched isoform of the "G" subunit of the peripheral (V1) domain of the vacuolar H+-ATPase (V-ATPase). The V-ATPase is a multisubunit rotary enzyme in which the cytosolic V1 complex hydrolyzes ATP and the membrane-integral V0 complex translocates protons, together acidifying intracellular compartments (endosomes, lysosomes, secretory vesicles) and, in specialized cells, the extracellular/luminal space. The G subunit is a component of the peripheral stalk (stator), forming an E-G heterodimer that connects the catalytic V1 head to the membrane-embedded V0 a-subunit; this stator stalk holds the catalytic AB heterohexamer stationary against the torque of the central rotor. Of the three human G paralogs (G1/G2/G3), G3 expression is restricted to and enriched in the kidney, with additional detection in inner-ear epithelium, and assembles into the tissue-specific proton pump (with a4, B1, C2, d2) that drives apical proton secretion by renal collecting-duct intercalated cells for systemic acid-base homeostasis. G3 directly binds the V0 a-subunit (a4/a1), providing a physical link between the V1 and V0 domains required for pump assembly and regulation. alternative_products: - name: '1' id: Q96LB4-1 - name: '2' id: Q96LB4-2 sequence_note: Not described - name: '3' id: Q96LB4-3 sequence_note: VSP_036423 - name: '4' id: Q96LB4-4 sequence_note: VSP_036426 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: >- ATP6V1G3 is the G subunit of the peripheral V1 domain of the vacuolar H+-ATPase, assembling into the E-G peripheral stalk of the V1 complex. Membership in the V1 domain is a defining, core structural attribute of this gene product. action: ACCEPT reason: >- Accurate core cellular-component assignment; the G subunit is an integral structural component of the V1 peripheral stalk, consistent with the UniProt subunit description. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: three peripheral stalks each consisting of EG heterodimers - term: id: GO:0030672 label: synaptic vesicle membrane evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: >- This synaptic vesicle membrane localization is a phylogenetic (IBA) transfer reflecting the neuronal V-ATPase context of orthologs/paralogs. ATP6V1G3 is the kidney-enriched G isoform with no evidence of neuronal/synaptic vesicle function; the ubiquitous G1 isoform underlies the neuronal context. For G3 this is not a core localization. action: KEEP_AS_NON_CORE reason: >- Biologically plausible only as a generic V-ATPase property transferred across the family; not relevant to the kidney-specific function of G3, which is expressed in renal collecting-duct intercalated cells rather than neurons. The falcon deep research reinforces this isoform division of labour, noting that the brain-specific G2 (not G3) underlies the neuronal V-ATPase context. supported_by: - reference_id: PMID:17360703 supporting_text: in major organs of both mouse and man, G3 subunit expression is limited to the kidney - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: 'TISSUE SPECIFICITY: Kidney.' - reference_id: file:human/ATP6V1G3/ATP6V1G3-deep-research-falcon.md supporting_text: >- **G3 is the kidney-specific/enriched G-subunit isoform**; by contrast **G1 is ubiquitous** and **G2 is brain-specific** - 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 lumen acidification is an IBA transfer capturing the generic proton-pumping/acidification role of the V-ATPase G subunit family. The synaptic vesicle specialization is not relevant to the kidney-enriched G3 isoform, whose physiological context is renal acid secretion, not neurotransmission. action: KEEP_AS_NON_CORE reason: >- The underlying acidification activity is real and family-wide, but the synaptic-vesicle qualifier is not the core biological process for G3. Retained as non-core rather than removed because it reflects a true conserved V-ATPase function. The falcon deep research likewise frames the underlying proton-pumping/acidification output as a property of the assembled holoenzyme rather than of the G subunit itself. supported_by: - reference_id: PMID:17360703 supporting_text: in major organs of both mouse and man, G3 subunit expression is limited to the kidney - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments - reference_id: file:human/ATP6V1G3/ATP6V1G3-deep-research-falcon.md supporting_text: >- **Does not itself catalyze proton transfer or ATP hydrolysis**; instead it supports the activity of the V-ATPase holoenzyme - term: id: GO:0016471 label: vacuolar proton-transporting V-type ATPase complex evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: part_of review: summary: >- ATP6V1G3 is a bona fide subunit of the vacuolar H+-ATPase holoenzyme (V1+V0). Complex membership is supported by the UniProt subunit composition and by direct experimental demonstration that G3 binds the V0 a-subunit, confirming both are components of the same proton pump. action: ACCEPT reason: >- Core, well-supported cellular-component annotation; the G subunit is an integral part of the assembled V-ATPase complex. supported_by: - reference_id: PMID:17360703 supporting_text: This confirms that a4 and G3 are component subunits of the same proton pump - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: V-ATPase is a heteromultimeric enzyme made up of two complexes - term: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: enables review: summary: >- This molecular function describes the rotary ATP-hydrolysis-driven proton transport activity of the assembled V-ATPase. As a peripheral-stalk subunit, G3 contributes to (rather than independently enables) this activity, which is the central function of the holoenzyme. The annotation correctly captures the core molecular function of the complex to which G3 belongs. action: ACCEPT reason: >- Appropriate core molecular-function annotation for a V-ATPase subunit; the activity is enabled by the assembled complex of which G3 is a structural component. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons - term: id: GO:0051117 label: ATPase binding evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: enables review: summary: >- This IEA-derived ATPase binding annotation is the electronic counterpart of the experimentally supported G3-a interaction. The same binding function is directly demonstrated by the IPI annotation from PMID:17360703 (G3 binding the V0 a4/a1 subunit), so this annotation is accepted as a correct, if redundant, prediction. action: ACCEPT reason: >- Electronic prediction that is corroborated by the experimental IPI annotation to the same term; the specific G3-a-subunit binding is genuine and informative. supported_by: - reference_id: PMID:17360703 supporting_text: purified, immobilized full-length G3 to pull down the a4 subunit from human kidney membrane preparations - term: id: GO:1902600 label: proton transmembrane transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: >- Proton transmembrane transport is the central biological process of the V-ATPase to which G3 contributes as a peripheral-stalk subunit. This is a core, accurate process annotation reflecting the ATP-hydrolysis-driven translocation of protons across membranes. action: ACCEPT reason: >- Core biological-process annotation directly consistent with V-ATPase function and with the renal proton-secretion role of the G3-containing pump. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a membrane integral complex (V0) that translocates protons - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: >- Cytosolic localization reflects the peripheral (cytoplasmic) nature of the V1 domain and the pool of free/disassembled V1 subcomplex. While accurate, it is not the core functional location of the assembled membrane-bound pump and is captured redundantly across many electronic and Reactome annotations. action: KEEP_AS_NON_CORE reason: >- Real but non-core localization; the V1 G subunit is cytosolic when not assembled into the membrane holoenzyme, but the functionally important location is the membrane-associated V-ATPase. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005886 label: plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: >- Plasma membrane localization reflects the plasma-membrane-targeted V-ATPase of specialized acid-secreting cells. For the kidney-enriched G3, the relevant context is the apical plasma membrane of collecting-duct intercalated cells, where the tissue-specific pump mediates proton secretion. This is supported experimentally by the IDA annotation from PMID:17360703. action: ACCEPT reason: >- Plasma membrane is a functionally relevant location for the G3-containing tissue-specific V-ATPase in renal acid-handling cells; supported by both electronic and direct experimental evidence. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1222516 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation, one of many duplicate cytosol localizations from pathway reactions. Accurate for the peripheral V1 pool but non-core relative to the assembled membrane pump. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization derived from a Reactome pathway reaction; real but not the core functional location. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5252133 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation duplicating the V1 peripheral localization. Real but non-core. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization from a Reactome pathway reaction. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-74723 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation duplicating the V1 peripheral localization. Real but non-core. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization from a Reactome pathway reaction. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-917841 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation duplicating the V1 peripheral localization. Real but non-core. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization from a Reactome pathway reaction. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9639286 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation duplicating the V1 peripheral localization (mTORC1 amino-acid signaling context). Real but non-core. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization from a Reactome pathway reaction. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640167 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation duplicating the V1 peripheral localization (mTORC1 amino-acid signaling context). Real but non-core. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization from a Reactome pathway reaction. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640168 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation duplicating the V1 peripheral localization (mTORC1 amino-acid signaling context). Real but non-core. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization from a Reactome pathway reaction. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640175 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation duplicating the V1 peripheral localization (mTORC1 amino-acid signaling context). Real but non-core. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization from a Reactome pathway reaction. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640195 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation duplicating the V1 peripheral localization (mTORC1 amino-acid signaling context). Real but non-core. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization from a Reactome pathway reaction. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9645598 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation duplicating the V1 peripheral localization (mTORC1 amino-acid signaling context). Real but non-core. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization from a Reactome pathway reaction. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9645608 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation duplicating the V1 peripheral localization (mTORC1 amino-acid signaling context). Real but non-core. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization from a Reactome pathway reaction. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9646468 qualifier: located_in review: summary: >- Reactome TAS cytosol annotation duplicating the V1 peripheral localization (mTORC1 amino-acid signaling context). Real but non-core. action: KEEP_AS_NON_CORE reason: >- Duplicate cytosol localization from a Reactome pathway reaction. supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP - term: id: GO:0005829 label: cytosol evidence_type: IDA original_reference_id: PMID:17360703 qualifier: located_in review: summary: >- Direct experimental (IDA) cytosol localization of G3 from kidney, consistent with the peripheral V1 pool. Although experimentally observed, cytosol is not the core functional location of the assembled membrane-bound pump. action: KEEP_AS_NON_CORE reason: >- Experimentally observed but non-core localization; reflects the cytosolic pool of the V1 peripheral subunit rather than the functional membrane-associated holoenzyme. supported_by: - reference_id: PMID:17360703 supporting_text: in the kidney, C2, d2, and G3 as well. These subunits replace the ubiquitously expressed forms - term: id: GO:0005886 label: plasma membrane evidence_type: IDA original_reference_id: PMID:17360703 qualifier: located_in review: summary: >- Direct experimental (IDA) plasma membrane localization of G3 from kidney, consistent with the apical plasma-membrane V-ATPase of renal collecting-duct intercalated cells that mediates proton secretion. This is a functionally relevant location for the kidney-specific G3-containing pump. action: ACCEPT reason: >- Experimentally supported, functionally relevant plasma-membrane localization for the tissue-specific acid-secreting V-ATPase in kidney. supported_by: - reference_id: PMID:17360703 supporting_text: purified, immobilized full-length G3 to pull down the a4 subunit from human kidney membrane preparations - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment - term: id: GO:0051117 label: ATPase binding evidence_type: IPI original_reference_id: PMID:17360703 qualifier: enables review: summary: >- G3 directly and specifically binds the V0 a-subunit (a4/ATP6V0A4 and a1/ATP6V0A1), demonstrated by phage display, ELISA, and pull-down of a4 from kidney membranes by immobilized full-length G3. This G-a interaction physically links the V1 and V0 domains and is required for V-ATPase assembly and regulation. Because the binding partner is a specific named ATPase subunit (not a generic "protein binding"), this is an informative, core molecular-function annotation. The IPI WITH/FROM evidence cites UniProtKB:Q93050 (ATP6V0A1) and UniProtKB:Q9HBG4 (ATP6V0A4). action: ACCEPT reason: >- Specific, experimentally demonstrated interaction with a defined V-ATPase a-subunit; this is the mechanistically informative function of G3 (V1-V0 linkage), not an uninformative generic binding annotation. supported_by: - reference_id: PMID:17360703 supporting_text: identified a possible interaction between the G3 subunit and the a4 subunit of the H(+)-ATPase - reference_id: PMID:17360703 supporting_text: These interactions represent a novel link between the V(1) and V(0) domains in man, which is known to be required for H(+)-ATPase assembly and regulation core_functions: - description: >- Structural subunit of the peripheral stalk (stator) of the vacuolar H+-ATPase V1 domain, forming the E-G heterodimer that holds the catalytic AB head stationary and couples ATP hydrolysis to proton translocation by the holoenzyme. molecular_function: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism directly_involved_in: - id: GO:1902600 label: proton transmembrane transport in_complex: id: GO:0000221 label: vacuolar proton-transporting V-type ATPase, V1 domain supported_by: - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: three peripheral stalks each consisting of EG heterodimers - reference_id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons - description: >- Physically links the V1 and V0 domains by binding the membrane-embedded a-subunit (a4/a1), an interaction required for assembly and regulation of the kidney-specific proton pump that drives luminal acid secretion in renal intercalated cells. molecular_function: id: GO:0051117 label: ATPase binding directly_involved_in: - id: GO:1902600 label: proton transmembrane transport locations: - id: GO:0005886 label: plasma membrane supported_by: - reference_id: PMID:17360703 supporting_text: This confirms that a4 and G3 are component subunits of the same proton pump - reference_id: PMID:17360703 supporting_text: a novel link between the V(1) and V(0) domains in man, which is known to be required for H(+)-ATPase assembly and regulation proposed_new_terms: [] suggested_questions: - question: >- Does the kidney-specific G3-containing V-ATPase (with a4, B1, C2, d2) have distinct assembly, trafficking, or regulatory properties compared with the ubiquitous G1-containing pump in intercalated cells? - question: >- What is the functional significance of the inner-ear expression of G3, and does it contribute to endolymph acidification or other otic ion-handling processes? - question: >- Do isoform 3 (VSP_036423) and isoform 4 (VSP_036426), which alter the C-terminal coiled-coil region, retain the ability to form the E-G heterodimer and bind the a-subunit, or do they represent non-functional/regulatory variants? suggested_experiments: - description: Cryo-EM or crystallographic structure of the kidney-specific human V-ATPase containing G3, a4, B1, C2, and d2 to define how the G3 peripheral stalk engages the a4 subunit. - description: Conditional knockout or knock-in of Atp6v1g3 in mouse renal intercalated cells with assessment of urinary acidification and systemic acid-base balance to test the physiological requirement of the G3 isoform. - description: Co-immunoprecipitation and proximity-labeling in renal intercalated cells to map the full G3 interactome and confirm preferential incorporation of G3 into the tissue-specific pump over G1. references: - id: file:human/ATP6V1G3/ATP6V1G3-deep-research-falcon.md title: Falcon deep research report for ATP6V1G3 findings: - statement: >- Among the three human G-subunit isoforms, G3 is kidney-enriched, G1 is ubiquitous, and G2 is brain-specific - corroborating the kidney-restricted expression of G3 and supporting the KEEP_AS_NON_CORE treatment of the neuronal/synaptic-vesicle IBA annotations transferred across the G family. reference_section_type: RESULTS supporting_text: >- **G3 is the kidney-specific/enriched G-subunit isoform**; by contrast **G1 is ubiquitous** and **G2 is brain-specific** - statement: >- The report explicitly states that direct experimental literature on human ATP6V1G3 is very limited and that most functional/localization/signaling claims (cancer, mTORC1, Wnt/Notch, endolysosomal trafficking, RILP/RAB7) are inferred from the V-ATPase holoenzyme or other G isoforms (notably the G1-specific RILP/RAB7 study), not directly demonstrated for G3. These inferred, complex/family-level claims are therefore NOT attributed to G3 in this review. reference_section_type: RESULTS supporting_text: >- Very limited direct experimental literature on human ATP6V1G3 reference_review: relevance: MEDIUM correctness: UNVERIFIED review_notes: >- LLM-synthesized report (Edison/Falcon). Its cross-checkable, G3-attributable claims are limited to (i) kidney-enriched G3 vs ubiquitous G1 vs brain-specific G2 isoform specificity, which is consistent with PMID:17360703 and the UniProt "TISSUE SPECIFICITY: Kidney" record already cited here, and (ii) the structural role of the E-G peripheral stalk, consistent with UniProt. The report itself foregrounds that direct ATP6V1G3 experimental data are scarce and that its cancer (KIRC down-regulation), mTORC1/Wnt/Notch signaling, endolysosomal trafficking, and RILP/RAB7 claims are generalizations from the V-ATPase holoenzyme or the ATP6V1G1 paralog - these are explicitly NOT used to add or strengthen G3-specific annotations. Underlying PMIDs (Wang 2020, Eaton 2021, etc.) were not independently re-verified against cached full text, hence UNVERIFIED. - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees 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:17360703 title: V1 and V0 domains of the human H+-ATPase are linked by an interaction between the G and a subunits. findings: - statement: >- G3 subunit expression is limited to the kidney among major organs of mouse and man, with additional expression in human inner-ear epithelium; G3 assembles with other kidney-specific subunits (a4, C2, d2) plus B1 into a tissue-specific proton pump. reference_section_type: ABSTRACT supporting_text: in major organs of both mouse and man, G3 subunit expression is limited to the kidney - statement: >- G3 directly binds the V0 a4 subunit (pulled down from kidney membranes by immobilized full-length G3), confirming a4 and G3 are subunits of the same pump and providing a V1-V0 link required for assembly and regulation; similar G1/a1, G3/a1, and G1/a4 interactions occur. reference_section_type: ABSTRACT supporting_text: purified, immobilized full-length G3 to pull down the a4 subunit from human kidney membrane preparations - id: PMID:12384298 title: Molecular cloning and characterization of novel tissue-specific isoforms of the human vacuolar H(+)-ATPase C, G and d subunits, and their evaluation in autosomal recessive distal renal tubular acidosis. findings: - statement: >- ATP6V1G3 (G3) is a kidney-specific isoform of the V-ATPase G subunit, identified and characterized alongside tissue-specific C and d subunit isoforms. reference_section_type: ABSTRACT supporting_text: novel tissue-specific isoforms of the human vacuolar H(+)-ATPase C, G and d subunits - id: file:human/ATP6V1G3/ATP6V1G3-uniprot.txt title: UniProt entry Q96LB4 (VATG3_HUMAN), V-type proton ATPase subunit G 3 findings: - statement: >- G3 is a subunit of the V1 peripheral complex of the V-ATPase; the V1 complex includes three peripheral stalks each formed by an E-G heterodimer. reference_section_type: DATABASE_ENTRY supporting_text: three peripheral stalks each consisting of EG heterodimers - statement: >- The V-ATPase acidifies intracellular compartments and, in some cell types, is targeted to the plasma membrane to acidify the extracellular environment. reference_section_type: DATABASE_ENTRY supporting_text: is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment - statement: ATP6V1G3 tissue specificity is kidney. reference_section_type: DATABASE_ENTRY supporting_text: 'TISSUE SPECIFICITY: Kidney.' - 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: []