| Category | ATP6V1G3 summary | Evidence / notes |
|---|---|---|
| Gene name | **ATP6V1G3** (synonym: **ATP6G3**) | Matches the requested human gene encoding V-type proton ATPase subunit G3; one of three human G-subunit isoforms of the V-ATPase V1 domain (pqac-00000003, pqac-00000012) |
| Protein name | **V-type proton ATPase subunit G3**; **V-ATPase subunit G3**; **V-ATPase 13 kDa subunit 3** | G-subunit family member in the cytosolic V1 sector of the V-ATPase holoenzyme (pqac-00000003, pqac-00000012, pqac-00000013) |
| Organism | **Homo sapiens** | Human V-ATPase contains multiple subunit isoforms with tissue-dependent expression; ATP6V1G3 is the human kidney-enriched G isoform (pqac-00000004, pqac-00000012) |
| Isoform specificity | **G3 is the kidney-specific/enriched G-subunit isoform**; by contrast **G1 is ubiquitous** and **G2 is brain-specific** | Explicitly reported in V1G-targeting study; human V-ATPases also contain multiple isoforms in different tissues and organelles (pqac-00000004, pqac-00000003) |
| Tissue expression | Predominantly **kidney**; kidney-related expression signatures are also consistent with renal tumor transcriptomic studies and kidney cell-type markers | V1G-targeting work states ATP6V1G3 is uniquely expressed in kidney tissue; single-cell renal carcinoma profiling identifies ATP6V1G3 among marker genes for renal epithelial populations; chromophobe RCC studies place related V-ATPase lineage markers in distal nephron/intercalated cells (pqac-00000004, pqac-00000011) |
| Likely kidney cell context | Most consistent with **renal epithelial acid-handling/endocytic compartments**, especially **distal nephron/intercalated-cell lineage** and possibly proximal-tubule endolysosomal systems depending on V-ATPase subcomplex composition | Normal kidney lineage markers for chromophobe RCC map to distal nephron/intercalated cells; kidney V-ATPase biology strongly involves acid-secreting intercalated cells and proximal-tubule endocytic organelles, although ATP6V1G3 itself is not directly localized in those papers (pqac-00000005, pqac-00000011, pqac-00000013) |
| Subcellular localization | As a V1 subunit, ATP6V1G3 is expected on the **cytosolic/peripheral face of V-ATPase-positive membranes**, associated with **endosomes, lysosomes, Golgi/TGN, secretory vesicles**, and in specialized cells potentially **plasma membrane V-ATPases** | V-ATPases acidify endosomes, lysosomes, Golgi, secretory vesicles, and can localize to plasma membrane in specialized cells; G subunits belong to the peripheral V1 stalk on the cytosolic side rather than the transmembrane proton pore (pqac-00000000, pqac-00000003, pqac-00000012, pqac-00000013, pqac-00000014) |
| Primary biochemical function | **Does not itself catalyze proton transfer or ATP hydrolysis**; instead it supports the activity of the V-ATPase holoenzyme that uses **ATP hydrolysis in V1** to drive **proton translocation through V0** | Core V-ATPase function is ATP-driven proton pumping for organelle/plasma-membrane acidification; G subunits are structural/regulatory components of V1 rather than catalytic ATP-binding A/B subunits or V0 proton-path subunits (pqac-00000000, pqac-00000003, pqac-00000012, pqac-00000013, pqac-00000014) |
| Immediate substrate/process context | Functional output is **H+ transport** by the assembled V-ATPase; ATP6V1G3 contributes indirectly to movement of protons into organellar lumens or across plasma membrane in specialized acid-secreting cells | V-ATPase creates an electrochemical proton gradient needed for vesicle/organelle acidification and extracellular acidification in specialized epithelia and osteoclasts (pqac-00000000, pqac-00000012, pqac-00000013) |
| Structural role in V-ATPase | **Peripheral stalk subunit** of the V1 complex; human V1 contains **three copies of E and G** subunits forming the **three peripheral stalks** that connect the catalytic head to the membrane sector and stabilize the rotary machine during catalysis | Human V-ATPase structures show E/G pairs in PS-1, PS-2, and PS-3; G participates in long curved coiled-coil peripheral stalks that accommodate conformational changes during ATP hydrolysis-coupled rotation (pqac-00000003) |
| Role in rotational catalysis | Helps provide the **stator architecture** that counterbalances torque generated by the rotary central stalk/c-ring system, enabling efficient coupling of ATP hydrolysis to proton pumping | Reviews and structures identify V1 peripheral stalks as required for efficient rotational catalysis and coupling between V1 and V0 (pqac-00000002, pqac-00000003, pqac-00000012, pqac-00000013) |
| Complex membership | Part of the **V1 domain** of the **V-ATPase holoenzyme**; mammalian V1 contains subunits **A3B3CDE3FG3H** in general architecture | Rat and human structural papers define V1 composition and show isoform-specific assembly in mammalian tissues (pqac-00000001, pqac-00000003) |
| Key interacting proteins / complexes | Most direct partners are expected to be **V1 subunit E** within peripheral stalks and neighboring stator/collar components (**C, H, a-NTD**) in assembled V-ATPase; broader V-ATPase signaling interfaces involve **ATP6AP1**, **ATP6AP2/(pro)renin receptor**, Ragulator/mTOR machinery, and endolysosomal trafficking factors | Direct G3-specific interactors are not well defined in retrieved literature; structural work defines G within E/G peripheral stalks, while broader V-ATPase interactome includes signaling and assembly partners (pqac-00000003, pqac-00000006, pqac-00000012, pqac-00000013) |
| Evidence from other G-isoform studies | For **G1**, interaction with **RILP** and **RAB7** helps control V-ATPase localization/activation on late endosomes and lysosomes; these findings support a conserved trafficking-support role for G-family subunits, though they are **not direct proof for G3** | Important inferential evidence only; the direct study is on ATP6V1G1 in breast cancer cells (pqac-00000002) |
| Canonical biological processes | **Endosome/lysosome acidification**, **protein degradation**, **receptor-mediated endocytosis**, **vesicular trafficking**, **autophagy/lysosome function**, **secretory vesicle maturation**, **pH homeostasis** | Canonical V-ATPase functions are extensively reviewed and apply to any competent isoform-containing holoenzyme, including kidney-enriched assemblies containing G3 (pqac-00000000, pqac-00000012, pqac-00000013, pqac-00000014) |
| Signaling-related roles | V-ATPase acts as a **signaling hub/scaffold** in **mTORC1**, **Wnt**, **Notch**, nutrient sensing, lysosomal stress responses, and broader pH-sensitive signaling pathways | These are properties of the assembled V-ATPase complex rather than uniquely of ATP6V1G3, but they define pathway context for ATP6V1G3-containing complexes (pqac-00000000, pqac-00000003, pqac-00000012, pqac-00000014) |
| Kidney-relevant functional context | In kidney, V-ATPases support **acid-base homeostasis**, **distal nephron proton secretion**, and **proximal-tubule receptor-mediated endocytosis/endolysosomal function** | Kidney V-ATPase localization and function are established in review and proximal-tubule ATP6AP2 studies; ATP6V1G3 likely contributes where kidney-specific V1G isoform-containing complexes are used (pqac-00000000, pqac-00000005, pqac-00000013) |
| Recent developments (2023–2024) | Recent work emphasizes V-ATPase in **lysosome regeneration**, **lysosomal stress signaling**, **autophagy**, and **cancer biology**; however, **direct 2023–2024 ATP6V1G3-specific mechanistic studies are scarce** | Newer papers focus on whole-complex regulation and disease roles rather than the G3 isoform specifically; this is an important limitation for annotation confidence (pqac-00000012, pqac-00000014) |
| Disease / cancer associations | ATP6V1G3 expression is reported in **renal tumor datasets** and may be **downregulated in kidney renal clear cell carcinoma** relative to normal kidney in some analyses; broader V-ATPase dysregulation is linked to **cancer progression, metastasis, drug resistance, renal disease, osteopetrosis, and neurodegeneration** | Family-level associations are strong; ATP6V1G3-specific disease causality remains limited in current literature (pqac-00000008, pqac-00000010, pqac-00000011, pqac-00000012, pqac-00000014) |
| Pharmacology / therapeutic relevance | **V-ATPase is druggable**, and the **V1G subunit family** can be targeted pharmacologically; verucopeptin was reported to bind **ATP6V1G** and inhibit both **V-ATPase activity** and **mTORC1 signaling** in multidrug-resistant cancer models | The study does not establish G3-selective targeting, but it highlights the therapeutic relevance of the G-subunit family (pqac-00000004) |
| Major knowledge gap | **Very limited direct experimental literature on human ATP6V1G3**; most functional annotation is inferred from (i) shared G-subunit architecture, (ii) V-ATPase holoenzyme biology, and (iii) kidney-specific expression of G3 | This should be stated explicitly when interpreting function/localization/pathway claims (pqac-00000003, pqac-00000004, pqac-00000012) |
| Most useful references | Human V-ATPase structure and assembly: **Wang 2020**; mammalian brain structure: **Abbas 2020**; broad mechanistic review: **Eaton 2021**; V1G pharmacology and tissue specificity: **Wang 2020 Cell Chem Biol**; kidney/cancer expression resources: **Li 2020**, **Skala 2020**; lysosomal trafficking review: **Futai 2019** | These references provide the strongest basis for annotating ATP6V1G3 despite the lack of G3-specific mechanistic studies (pqac-00000000, pqac-00000001, pqac-00000003, pqac-00000004, pqac-00000008, pqac-00000011, pqac-00000013) |


*Table: This table consolidates the most relevant properties of human ATP6V1G3, combining direct evidence on V1G isoform specificity with broader structural and functional evidence from V-ATPase literature. It is useful for functional annotation because direct ATP6V1G3 studies are limited, so careful distinction between direct and inferred evidence is essential.*