ATP6V1G1 (UniProt O75348) encodes V-type proton ATPase subunit G 1, a 118 amino acid peripheral subunit (13.8 kDa) that is a component of the V1 peripheral complex of the vacuolar H+-ATPase (V-ATPase). The protein is also known as V-ATPase 13 kDa subunit 1 and Vacuolar proton pump subunit G 1.
V-ATPases are ATP-hydrolysis-driven proton pumps that acidify intracellular compartments across all eukaryotes.
Subunit G 1 is one of three G-subunit paralogs in humans (G1, G2, G3). G1 is ubiquitously expressed.
The V1 complex contains three peripheral stalks, each consisting of EG heterodimers.
PMID:33065002
The G subunit forms heterodimers with the E subunit, and these peripheral stalks link V1 to V0.
PMID:17360703
UniProt notes the G1 subunit has been directly identified by mass spectrometry in the V1 complex of the human V-ATPase structure.
[file:human/ATP6V1G1/ATP6V1G1-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"]
A key functional study showed that loss of ATP6V1G1 (identified in a genome-wide screen) impairs V-ATPase activity, leading to iron depletion and HIF1alpha stabilization.
PMID:28296633
This places intracellular iron homeostasis as a downstream consequence of V-ATPase activity (proton pump function needed for endosomal acidification and iron release from transferrin).
UniProt lists apical cell membrane in kidney, based on co-localization with other H+-ATPase subunits in TAL and DCT segments.
PMID:29993276
Also detected in lysosomal membrane (HDA, mass spec from lysosome-enriched fractions) and in cytosol (as component of unassembled V1 complex). Identification in extracellular exosomes is likely a contaminant in those datasets and is non-core.
A NAS annotation links V-ATPase (including ATP6V1G1) to regulation of macroautophagy. This is an indirect/downstream effect of lysosomal acidification — V-ATPase activity is required for lysosomal function and thus autophagy completion, but the G1 subunit does not directly regulate autophagy.
[PMID:22982048 "macroautophagy is responsible for the uptake of lipofuscin into the lysosomes" — here V-ATPase disruption is used to impair lysosomal activity]
Multiple high-throughput interactome datasets contribute generic protein binding annotations (GO:0005515) for ATP6V1G1. These should all be treated as over-annotations. The specific functional interaction is with ATP6V1E1/E2 (forming G-E peripheral stalks).
[file:human/ATP6V1G1/ATP6V1G1-uniprot.txt "O75348; P36543: ATP6V1E1; NbExp=3; IntAct=EBI-711802, EBI-348639; O75348; Q96A05: ATP6V1E2; NbExp=12; IntAct=EBI-711802, EBI-8650380"]
The ATPase binding annotation (PMID:17360703) reflects the G1/a (V0 subunit a) interaction documented in that paper — this is more informative than generic protein binding.
ATP6V1G1 is a structural peripheral stalk subunit of the V1 complex of the V-ATPase. Its core function is as part of the proton-transporting ATPase complex. Annotations to V1 domain membership, proton transmembrane transport, and lysosomal/endosomal membrane localization are all well-supported. The iron homeostasis and HIF pathway effects are downstream consequences of V-ATPase proton pump activity rather than direct molecular functions of the G1 subunit per se.
Falcon deep research has now completed (file:human/ATP6V1G1/ATP6V1G1-deep-research-falcon.md,
26 citations). It corroborates the G1 peripheral-stalk core above and adds isoform
and disease-context detail; no change to annotation calls.
Net: no change to calls — G1 is the ubiquitous EG peripheral-stalk (stator) V1
subunit supporting V-ATPase assembly and organellar acidification.