ATP6V1E1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:1902600 proton transmembrane transport	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference that ATP6V1E1 participates in proton transmembrane transport. Well-supported by the established role of V-ATPase as the primary proton pump in eukaryotic cells. Reason: Proton transmembrane transport is the core biological process of the V-ATPase, and subunit E1 is an indispensable structural component of the V1 sector required for complex function. Supporting Evidence: PMID:33065002 Vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases) are ATP-driven proton pumps comprised of a cytoplasmic V1 complex for ATP hydrolysis and a membrane-embedded Vo complex for proton transfer. They play important roles in acidification of intracellular vesicles, organelles, and the extracellular milieu in eukaryotes.
GO:0046961 proton-transporting ATPase activity, rotational mechanism	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic inference for rotational ATPase activity. The E subunit is a peripheral stalk component essential for maintaining the stator architecture during rotation. Reason: The proton-transporting ATPase activity via rotational mechanism is the core molecular function of the complex. Subunit E is required for complex stability and function. Supporting Evidence: PMID:33065002 Vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases) are ATP-driven proton pumps comprised of a cytoplasmic V1 complex for ATP hydrolysis and a membrane-embedded Vo complex for proton transfer.
GO:0005765 lysosomal membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular location vocabulary mapping. Supported by HDA proteomics evidence (PMID:17897319) and by the established biology of V-ATPase on lysosomes. Reason: Lysosomal membrane is the primary functional location of V-ATPase. Multiple evidence types support this localization.
GO:0016324 apical plasma membrane	IEA GO_REF:0000044	ACCEPT	Summary: UniProt subcellular location vocabulary mapping for apical plasma membrane. Confirmed by direct experimental evidence in kidney tubular epithelium (PMID:29993276). Reason: Apical membrane localization of V-ATPase in kidney tubular epithelium is experimentally confirmed (PMID:29993276) and is relevant to ATP6V1E1's function in renal acid-base homeostasis. Supporting Evidence: PMID:29993276 H(+)-ATPase B1 subunit localizes to thick ascending limb and distal convoluted tubule of rodent and human kidney.
GO:0030665 clathrin-coated vesicle membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular location vocabulary mapping based on ortholog data. V-ATPase acidifies clathrin-coated vesicles in the endocytic pathway. Reason: Consistent with V-ATPase biology but non-core relative to lysosomal function.
GO:0030672 synaptic vesicle membrane	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular location vocabulary mapping for synaptic vesicle membrane based on ortholog data. Reason: Synaptic vesicle context is non-core for this ubiquitously expressed subunit, though V-ATPase does acidify synaptic vesicles.
GO:0033178 proton-transporting two-sector ATPase complex, catalytic domain	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based annotation placing ATP6V1E1 in the catalytic domain of the two-sector ATPase complex. The V1 sector is the catalytic domain of V-ATPase. Reason: The V1 sector is the catalytic (ATP-hydrolyzing) domain of the two-sector V-ATPase. Subunit E is part of this domain.
GO:0046961 proton-transporting ATPase activity, rotational mechanism	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based annotation for rotational ATPase activity. Consistent with IBA annotation. Reason: Consistent with established V-ATPase biology.
GO:1902600 proton transmembrane transport	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based annotation for proton transmembrane transport. Reason: Consistent with IBA and TAS annotations.
GO:0005515 protein binding	IPI PMID:16169070 A human protein-protein interaction network: a resource for ...	MARK AS OVER ANNOTATED	Summary: Generic protein binding from a large-scale human protein-protein interaction network study. Not informative for the specific function of ATP6V1E1. Reason: Protein binding from a high-throughput interactome study is uninformative for understanding ATP6V1E1 core function.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	MARK AS OVER ANNOTATED	Summary: Generic protein binding from the OpenCell endogenous tagging study. High-throughput; not informative. Reason: Protein binding from high-throughput studies is uninformative for this V-ATPase subunit.
GO:0005765 lysosomal membrane	IDA PMID:22053050 mTORC1 senses lysosomal amino acids through an inside-out me...	ACCEPT	Summary: Direct experimental evidence from the Zoncu et al. (2011) mTORC1 study showing V-ATPase (including E1 subunit as part of V1 domain) is active at the lysosomal membrane. Reason: Core localization supported by IDA evidence. The lysosomal membrane is the primary site of V-ATPase activity. Supporting Evidence: PMID:22053050 the v-ATPase engages in extensive amino acid-sensitive interactions with the Ragulator, a scaffolding complex that anchors the Rag GTPases to the lysosome.
GO:0046611 lysosomal proton-transporting V-type ATPase complex	IDA PMID:22053050 mTORC1 senses lysosomal amino acids through an inside-out me...	ACCEPT	Summary: IDA from the Zoncu et al. (2011) study demonstrating V-ATPase complex on lysosomes; E1 subunit is part of this complex. Reason: Well-supported by multiple evidence types. Supporting Evidence: PMID:22053050 the v-ATPase engages in extensive amino acid-sensitive interactions with the Ragulator, a scaffolding complex that anchors the Rag GTPases to the lysosome.
GO:0071230 cellular response to amino acid stimulus	IDA PMID:22053050 mTORC1 senses lysosomal amino acids through an inside-out me...	KEEP AS NON CORE	Summary: The V-ATPase (with E1 as part of V1 domain) is required for mTORC1 activation in response to amino acids. This represents a genuine secondary function. Reason: The cellular response to amino acid stimulus is a genuine secondary function of V-ATPase supported by direct experimental evidence, but is not the primary proton-pumping role. Supporting Evidence: PMID:22053050 the v-ATPase engages in extensive amino acid-sensitive interactions with the Ragulator, a scaffolding complex that anchors the Rag GTPases to the lysosome. In a cell-free system, ATP hydrolysis by the v-ATPase was necessary for amino acids to regulate the v-ATPase-Ragulator interaction and promote mTORC1 translocation.
GO:0160124 guanyl nucleotide exchange factor activator activity	IDA PMID:22053050 mTORC1 senses lysosomal amino acids through an inside-out me...	KEEP AS NON CORE	Summary: The V-ATPase complex contributes to GEF activator activity in mTORC1 signaling. V-ATPase activity facilitates Ragulator-mediated GEF activation of Rag GTPases. Reason: This secondary function in mTORC1 signaling is genuine but not the primary role of V-ATPase or subunit E1. Supporting Evidence: PMID:22053050 amino acids activate the Rag guanosine triphosphatases (GTPases), which promote the translocation of mTORC1 to the lysosomal surface, the site of mTORC1 activation. We found that the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1.
GO:1904263 positive regulation of TORC1 signaling	IDA PMID:22053050 mTORC1 senses lysosomal amino acids through an inside-out me...	KEEP AS NON CORE	Summary: V-ATPase is required for mTORC1 activation by amino acids. Reason: Secondary function of V-ATPase in mTORC1 signaling; not the primary proton pump role.
GO:0016324 apical plasma membrane	EXP PMID:29993276 H(+)-ATPase B1 subunit localizes to thick ascending limb and...	ACCEPT	Summary: Experimental evidence showing V-ATPase subunit E1 at the apical membrane of kidney thick ascending limb and distal convoluted tubule epithelial cells. This is functionally relevant to renal acid excretion. Reason: Experimentally confirmed apical membrane localization in kidney is well-supported and biologically meaningful for renal acid-base homeostasis. Supporting Evidence: PMID:29993276 H(+)-ATPase B1 subunit localizes to thick ascending limb and distal convoluted tubule of rodent and human kidney.
GO:0000221 vacuolar proton-transporting V-type ATPase, V1 domain	IDA PMID:33065002 Structures of a Complete Human V-ATPase Reveal Mechanisms of...	ACCEPT	Summary: Direct experimental evidence from the cryo-EM structural study (Wang et al. 2020) confirming that E1 is a component of the V1 domain, present in three copies as part of EG peripheral stalk heterodimers. Reason: The cryo-EM structures directly confirmed the position of subunit E in the V1 domain. This is core complex membership. Supporting Evidence: PMID:33065002 Vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases) are ATP-driven proton pumps comprised of a cytoplasmic V1 complex for ATP hydrolysis and a membrane-embedded Vo complex for proton transfer.
GO:0016241 regulation of macroautophagy	NAS PMID:22982048 Lipofuscin is formed independently of macroautophagy and lys...	MARK AS OVER ANNOTATED	Summary: NAS annotation from Parkinson's UK curation. V-ATPase broadly supports macroautophagy through lysosomal acidification, which is required for autophagosome-lysosome fusion and degradation. Reason: Regulation of macroautophagy is an indirect, downstream consequence of V-ATPase lysosomal acidification, not a specific regulatory function of subunit E1. Overstates functional specificity.
GO:0070062 extracellular exosome	HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid...	MARK AS OVER ANNOTATED	Summary: High-throughput proteomics detection in parotid gland exosomes. Likely reflects membrane co-purification rather than a specific exosome function. Reason: Exosome detection by proteomics is likely artifactual for a lysosomal V-ATPase subunit. Not informative for core function.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	MARK AS OVER ANNOTATED	Summary: High-throughput proteomics detection in urinary exosomes. Reason: Same reasoning as parotid gland exosome annotation. Not informative.
GO:0005765 lysosomal membrane	HDA PMID:17897319 Integral and associated lysosomal membrane proteins.	ACCEPT	Summary: Lysosomal membrane proteomics study detected ATP6V1E1. Confirms lysosomal membrane localization. Reason: Direct proteomics evidence for lysosomal membrane localization is consistent with established V-ATPase biology.
GO:0051117 ATPase binding	IPI PMID:20717956 Rab11b and its effector Rip11 regulate the acidosis-induced ...	KEEP AS NON CORE	Summary: The E subunit of V-ATPase interacts with RAB11B, as shown in the study of acidosis-induced V-ATPase trafficking in salivary ducts (PMID:20717956). The ATPase binding annotation records this as the E subunit binding to an ATPase (itself being part of the V-ATPase). Reason: ATPase binding is a context-specific interaction of the E subunit with RAB11B in the context of regulated V-ATPase trafficking. This is a secondary, context-specific function.
GO:0005829 cytosol	TAS Reactome:R-HSA-1222516	KEEP AS NON CORE	Summary: Reactome TAS annotation. The V1 peripheral sector can dissociate from V0 and exist as a soluble cytoplasmic complex during regulated disassembly. Reason: V1 domain can be in cytosol during regulated disassembly; consistent with V-ATPase regulation biology.
GO:0005829 cytosol	TAS Reactome:R-HSA-5252133	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol. Reason: Consistent with V1 domain biology.
GO:0005829 cytosol	TAS Reactome:R-HSA-74723	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol. Reason: Consistent.
GO:0005829 cytosol	TAS Reactome:R-HSA-917841	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol. Reason: Consistent.
GO:0005829 cytosol	TAS Reactome:R-HSA-9639286	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol. Reason: Consistent.
GO:0005829 cytosol	TAS Reactome:R-HSA-9640167	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol. Reason: Consistent.
GO:0005829 cytosol	TAS Reactome:R-HSA-9640168	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol. Reason: Consistent.
GO:0005829 cytosol	TAS Reactome:R-HSA-9640175	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol. Reason: Consistent.
GO:0005829 cytosol	TAS Reactome:R-HSA-9640195	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol. Reason: Consistent.
GO:0005829 cytosol	TAS Reactome:R-HSA-9645598	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol. Reason: Consistent.
GO:0005829 cytosol	TAS Reactome:R-HSA-9645608	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol. Reason: Consistent.
GO:0005829 cytosol	TAS Reactome:R-HSA-9646468	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol. Reason: Consistent.
GO:0005829 cytosol	TAS Reactome:R-HSA-9858923	KEEP AS NON CORE	Summary: Reactome TAS annotation for cytosol in MITF/lysosome biogenesis context. Reason: Consistent; relevant to MITF-regulated expression of ATP6V1E1 for lysosome biogenesis.
GO:0005515 protein binding	IPI PMID:21784977 Zinc finger protein tristetraprolin interacts with CCL3 mRNA...	REMOVE	Summary: PMID:21784977 concerns tristetraprolin (ZFP36) binding to CCL3 mRNA and regulating tissue inflammation. There is no evident connection to ATP6V1E1 in this publication. This annotation appears to be a curation error. Reason: PMID:21784977 is about tristetraprolin/CCL3 mRNA regulation and does not contain evidence for ATP6V1E1 protein binding. This annotation is likely a curation error.
GO:0005515 protein binding	IPI PMID:11399750 Interaction between aldolase and vacuolar H+-ATPase: evidenc...	MARK AS OVER ANNOTATED	Summary: The interaction with ALDOC (aldolase) recorded in PMID:11399750 is a specific biochemically-validated interaction of the V-ATPase E subunit with aldolase. Generic protein binding is less informative than this specific interaction. Reason: The underlying biology (E subunit-aldolase interaction) is more informative than generic protein binding. The specific interaction couples glycolytic ATP supply to V-ATPase activity, which warrants a more precise annotation if a suitable GO term existed. Supporting Evidence: PMID:11399750 A screen for proteins that bind the V-ATPase E subunit using the yeast two-hybrid assay identified the cDNA clone coded for aldolase, an enzyme of the glycolytic pathway.
GO:0005768 endosome	ISS GO_REF:0000024	ACCEPT	Summary: Ortholog-based annotation for endosome localization. V-ATPase acidifies endosomes in the endocytic pathway. Reason: Endosome localization is consistent with V-ATPase biology and the more specific endosome membrane annotation.
GO:0005829 cytosol	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Ortholog-based annotation for cytosol localization. Reason: Consistent with V1 domain regulated disassembly biology.
GO:0016324 apical plasma membrane	ISS GO_REF:0000024	ACCEPT	Summary: Ortholog-based annotation for apical plasma membrane, consistent with the EXP evidence from PMID:29993276. Reason: Consistent with experimental evidence for kidney apical membrane localization.
GO:0016469 proton-transporting two-sector ATPase complex	TAS PMID:8250920 Cloning and tissue distribution of subunits C, D, and E of t...	ACCEPT	Summary: TAS from the original cloning paper (van Hille et al. 1993). Subunit E is part of the proton-transporting V-type ATPase complex. Reason: Historically supported complex membership confirmed by subsequent structural studies. Supporting Evidence: PMID:8250920 The vacuolar proton ATPase (V-ATPase) translocates protons into intracellular organelles or across the plasma membrane of specialised cells such as osteoclast and renal intercalated cells.
GO:1902600 proton transmembrane transport	TAS PMID:8250920 Cloning and tissue distribution of subunits C, D, and E of t...	ACCEPT	Summary: TAS from the original cloning paper. Reason: Historically supported core function.

Gene Description

Existing Annotations Review

Core Functions

Apical membrane V-ATPase function in kidney tubular epithelium (thick ascending limb and distal convoluted tubule). Contributes to urinary acidification and renal acid-base homeostasis.

Interaction with aldolase (ALDOC) providing a mechanism for coupling glycolytic ATP generation to V-ATPase proton pumping activity. Aldolase deficiency causes V1-V0 dissociation, implicating this interaction in V-ATPase assembly/regulation.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

📚 Additional Documentation

Notes

Pn Notes

📄 View Raw YAML