ATP6V0D1 encodes the ubiquitous d1 isoform of the V0 d subunit of the vacuolar H+-ATPase (V-ATPase). The protein is a peripheral component of the membrane-embedded V0 sector and helps couple the V1 ATP-hydrolysis motor to V0 proton translocation. ATP6V0D1-containing V-ATPase complexes acidify lysosomes, endosomes, phagosomes, synaptic vesicles, and other intracellular compartments, thereby supporting vesicle traffic, lysosomal degradation, nutrient-dependent mTORC1 signaling, and ion homeostasis.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016471 vacuolar proton-transporting V-type ATPase complex | IBA GO_REF:0000033 | ACCEPT | Summary: Supported core ATP6V0D1 annotation: vacuolar proton-transporting V-type ATPase complex. Reason: ATP6V0D1/d1 is a V0-sector d subunit of the V-ATPase. Biochemical, UniProt, and human V-ATPase structural evidence support V-ATPase complex membership and V0-domain placement as core annotations. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase) file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:18752060 These data indicate that the d subunit in man is centrally located within the pump and is thus important in its rotary mechanism PMID:33065002 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 file:human/ATP6V0D1/ATP6V0D1-deep-research-manual.md ATP6V0D1 encodes V-type proton ATPase subunit d 1, also called V-ATPase AC39/p39 |
| GO:0046961 proton-transporting ATPase activity, rotational mechanism | IBA GO_REF:0000033 | ACCEPT | Summary: ATP6V0D1 contributes to the assembled V-ATPase proton-pump activity: proton-transporting ATPase activity, rotational mechanism. Reason: The d1 subunit is not the independent catalytic ATPase, but the IBA annotation already uses the contributes_to qualifier. This accurately represents ATP6V0D1 as a V0 subunit contributing to the assembled V-ATPase rotary proton-pump activity. Supporting Evidence: PMID:18752060 human d1 and d2 are able to directly interact with the D and F subunits PMID:18752060 the d subunit in man is centrally located within the pump PMID:33065002 human V-ATPase in three rotational states |
| GO:0005769 early endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: early endosome. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the lysosomal surface, the site of mTORC1 activation PMID:28296633 V-ATPase, the key proton pump for endo-lysosomal acidification |
| GO:0007034 vacuolar transport | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Vacuolar transport is plausible as a downstream V-ATPase/endolysosomal trafficking context but is not the most specific ATP6V0D1 function. Reason: The conserved primary role is proton-pump complex function and compartment acidification. Vacuolar transport depends on acidic endolysosomal compartments, but this term is broader than the direct ATP6V0D1 mechanism. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:33065002 supporting intracellular membrane trafficking and protein degradation |
| GO:0007035 vacuolar acidification | IBA GO_REF:0000033 | ACCEPT | Summary: Core V-ATPase proton transport/acidification process: vacuolar acidification. Reason: ATP6V0D1 functions in the V-ATPase complex that translocates protons and acidifies intracellular compartments. This is the principal biological process supported for the d1 subunit. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase) file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:18752060 These data indicate that the d subunit in man is centrally located within the pump and is thus important in its rotary mechanism PMID:33065002 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 file:human/ATP6V0D1/ATP6V0D1-deep-research-manual.md ATP6V0D1 encodes V-type proton ATPase subunit d 1, also called V-ATPase AC39/p39 |
| GO:0033181 plasma membrane proton-transporting V-type ATPase complex | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Plasma membrane V-ATPase localization is supported in specialized cells but is not the dominant ATP6V0D1/d1 context. Reason: UniProt notes that V-ATPase can be targeted to the plasma membrane in some cell types. For ubiquitous ATP6V0D1/d1, the better-supported core locations are lysosomal and endosomal V-ATPase complexes. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt in some cell types, is targeted to the plasma membrane PMID:33065002 Plasma membrane V-ATPases carry out extracellular acidification in specialized organs |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the lysosomal surface, the site of mTORC1 activation PMID:28296633 V-ATPase, the key proton pump for endo-lysosomal acidification |
| GO:0016020 membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Membrane localization is true but too general for ATP6V0D1. Reason: ATP6V0D1 is a peripheral membrane-associated V0-sector subunit. The informative locations are the V-ATPase complex and lysosomal/endosomal membranes rather than the parent membrane term. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Membrane PMID:18752060 The vacuolar H+-ATPase d subunit is known to associate with the integral membrane V0 domain |
| GO:0016471 vacuolar proton-transporting V-type ATPase complex | IEA GO_REF:0000117 | ACCEPT | Summary: Supported core ATP6V0D1 annotation: vacuolar proton-transporting V-type ATPase complex. Reason: ATP6V0D1/d1 is a V0-sector d subunit of the V-ATPase. Biochemical, UniProt, and human V-ATPase structural evidence support V-ATPase complex membership and V0-domain placement as core annotations. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase) file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:18752060 These data indicate that the d subunit in man is centrally located within the pump and is thus important in its rotary mechanism PMID:33065002 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 file:human/ATP6V0D1/ATP6V0D1-deep-research-manual.md ATP6V0D1 encodes V-type proton ATPase subunit d 1, also called V-ATPase AC39/p39 |
| GO:0030665 clathrin-coated vesicle membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Context-specific vesicle membrane localization for V-ATPase: clathrin-coated vesicle membrane. Reason: V-ATPases acidify several specialized vesicle classes, including clathrin-coated and phagocytic vesicles. These locations are plausible and supported, but lysosomal/endosomal V-ATPase function is the primary ATP6V0D1 role. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Cytoplasmic vesicle, clathrin-coated vesicle membrane |
| GO:0030670 phagocytic vesicle membrane | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Context-specific vesicle membrane localization for V-ATPase: phagocytic vesicle membrane. Reason: V-ATPases acidify several specialized vesicle classes, including clathrin-coated and phagocytic vesicles. These locations are plausible and supported, but lysosomal/endosomal V-ATPase function is the primary ATP6V0D1 role. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Cytoplasmic vesicle, clathrin-coated vesicle membrane |
| GO:0033179 proton-transporting V-type ATPase, V0 domain | IEA GO_REF:0000120 | ACCEPT | Summary: Supported core ATP6V0D1 annotation: proton-transporting V-type ATPase, V0 domain. Reason: ATP6V0D1/d1 is a V0-sector d subunit of the V-ATPase. Biochemical, UniProt, and human V-ATPase structural evidence support V-ATPase complex membership and V0-domain placement as core annotations. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase) file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:18752060 These data indicate that the d subunit in man is centrally located within the pump and is thus important in its rotary mechanism PMID:33065002 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 file:human/ATP6V0D1/ATP6V0D1-deep-research-manual.md ATP6V0D1 encodes V-type proton ATPase subunit d 1, also called V-ATPase AC39/p39 |
| GO:0042592 homeostatic process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: Homeostatic process is overly broad for ATP6V0D1. Reason: The specific supported homeostatic roles are endolysosomal acidification, proton transmembrane transport, and context-specific iron/HIF regulation. The generic parent term loses the actual function. Proposed replacements: vacuolar acidification proton transmembrane transport intracellular iron ion homeostasis Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:28296633 disrupting the V-ATPase results in intracellular iron depletion |
| GO:0046961 proton-transporting ATPase activity, rotational mechanism | IEA GO_REF:0000120 | MODIFY | Summary: ATP6V0D1 contributes to the assembled V-ATPase proton-pump activity: proton-transporting ATPase activity, rotational mechanism. Reason: The term is biologically appropriate for ATP6V0D1-containing V-ATPase complexes, but the GOA qualifier should be changed from enables to contributes_to. The d1 subunit is not the independent catalytic ATPase; it contributes to the rotary V-ATPase mechanism that couples ATP hydrolysis in V1 to proton transfer through V0. Proposed replacements: proton-transporting ATPase activity, rotational mechanism Supporting Evidence: PMID:18752060 human d1 and d2 are able to directly interact with the D and F subunits PMID:18752060 the d subunit in man is centrally located within the pump PMID:33065002 human V-ATPase in three rotational states |
| GO:0098793 presynapse | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Presynapse is an inferred neuronal context from synaptic vesicle acidification, not core ATP6V0D1 biology. Reason: V-ATPases acidify synaptic vesicles, but the reviewed evidence for ATP6V0D1/d1 is broader endolysosomal V-ATPase function. Presynapse should remain a context-specific location. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:18752060 acidification of diverse intracellular compartments in eukaryotic cells, including endosomes, lysosomes, clathrin-coated and synaptic vesicles |
| GO:1902600 proton transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: Core V-ATPase proton transport/acidification process: proton transmembrane transport. Reason: ATP6V0D1 functions in the V-ATPase complex that translocates protons and acidifies intracellular compartments. This is the principal biological process supported for the d1 subunit. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase) file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:18752060 These data indicate that the d subunit in man is centrally located within the pump and is thus important in its rotary mechanism PMID:33065002 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 file:human/ATP6V0D1/ATP6V0D1-deep-research-manual.md ATP6V0D1 encodes V-type proton ATPase subunit d 1, also called V-ATPase AC39/p39 |
| GO:0005515 protein binding | IPI PMID:16713569 A protein-protein interaction network for human inherited at... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent ATP6V0D1 function. Reason: These interaction-map annotations are useful context but do not identify a specific ATP6V0D1 activity. Proposed replacements: vacuolar proton-transporting V-type ATPase complex proton-transporting ATPase activity, rotational mechanism Supporting Evidence: PMID:16713569 We identified 770 mostly novel protein-protein interactions using a stringent yeast two-hybrid screen PMID:32296183 The dataset, versioned HI-III-20 (Human Interactome obtained from screening Space III, published in 2020), contains 52,569 verified PPIs involving 8,275 proteins PMID:32814053 connects ∼5,000 human proteins via ∼30,000 candidate interactions |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent ATP6V0D1 function. Reason: These interaction-map annotations are useful context but do not identify a specific ATP6V0D1 activity. Proposed replacements: vacuolar proton-transporting V-type ATPase complex proton-transporting ATPase activity, rotational mechanism Supporting Evidence: PMID:16713569 We identified 770 mostly novel protein-protein interactions using a stringent yeast two-hybrid screen PMID:32296183 The dataset, versioned HI-III-20 (Human Interactome obtained from screening Space III, published in 2020), contains 52,569 verified PPIs involving 8,275 proteins PMID:32814053 connects ∼5,000 human proteins via ∼30,000 candidate interactions |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent ATP6V0D1 function. Reason: These interaction-map annotations are useful context but do not identify a specific ATP6V0D1 activity. Proposed replacements: vacuolar proton-transporting V-type ATPase complex proton-transporting ATPase activity, rotational mechanism Supporting Evidence: PMID:16713569 We identified 770 mostly novel protein-protein interactions using a stringent yeast two-hybrid screen PMID:32296183 The dataset, versioned HI-III-20 (Human Interactome obtained from screening Space III, published in 2020), contains 52,569 verified PPIs involving 8,275 proteins PMID:32814053 connects ∼5,000 human proteins via ∼30,000 candidate interactions |
| GO:0005769 early endosome | IEA GO_REF:0000107 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: early endosome. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the lysosomal surface, the site of mTORC1 activation PMID:28296633 V-ATPase, the key proton pump for endo-lysosomal acidification |
| GO:0015078 proton transmembrane transporter activity | IEA GO_REF:0000107 | ACCEPT | Summary: ATP6V0D1 contributes to the assembled V-ATPase proton-pump activity: proton transmembrane transporter activity. Reason: The d1 subunit is not the independent catalytic ATPase, but it is centrally positioned in the rotary V-ATPase mechanism and contributes to coupling ATP hydrolysis in V1 to proton transfer through V0. Supporting Evidence: PMID:18752060 human d1 and d2 are able to directly interact with the D and F subunits PMID:18752060 the d subunit in man is centrally located within the pump PMID:33065002 human V-ATPase in three rotational states |
| GO:0033176 proton-transporting V-type ATPase complex | IEA GO_REF:0000107 | ACCEPT | Summary: Supported core ATP6V0D1 annotation: proton-transporting V-type ATPase complex. Reason: ATP6V0D1/d1 is a V0-sector d subunit of the V-ATPase. Biochemical, UniProt, and human V-ATPase structural evidence support V-ATPase complex membership and V0-domain placement as core annotations. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase) file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:18752060 These data indicate that the d subunit in man is centrally located within the pump and is thus important in its rotary mechanism PMID:33065002 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 file:human/ATP6V0D1/ATP6V0D1-deep-research-manual.md ATP6V0D1 encodes V-type proton ATPase subunit d 1, also called V-ATPase AC39/p39 |
| GO:0097401 synaptic vesicle lumen acidification | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Synaptic vesicle lumen acidification is plausible for V-ATPase but context-specific for ATP6V0D1. Reason: The V-ATPase family acidifies synaptic vesicles, but ATP6V0D1/d1 is not uniquely a synaptic-vesicle factor. Keep as a non-core inferred location/process context. Supporting Evidence: PMID:18752060 acidification of diverse intracellular compartments in eukaryotic cells, including endosomes, lysosomes, clathrin-coated and synaptic vesicles |
| 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: Directly supported lysosomal amino-acid/mTORC1 signaling context: cellular response to amino acid stimulus. Reason: The mTORC1 work supports V-ATPase, including V0 d1, as part of lysosomal amino-acid sensing through Ragulator/Rag signaling. This is a real signaling output but secondary to the core proton-pump/acidification function. Supporting Evidence: PMID:22053050 the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1 PMID:22053050 Ragulator provides a physical and functional link between the v-ATPase and the Rag GTPases PMID:22053050 direct interaction between the V0 component d1 and p18 |
| 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: Directly supported lysosomal amino-acid/mTORC1 signaling context: guanyl nucleotide exchange factor activator activity. Reason: The mTORC1 work supports V-ATPase, including V0 d1, as part of lysosomal amino-acid sensing through Ragulator/Rag signaling. This is a real signaling output but secondary to the core proton-pump/acidification function. Supporting Evidence: PMID:22053050 the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1 PMID:22053050 Ragulator provides a physical and functional link between the v-ATPase and the Rag GTPases PMID:22053050 direct interaction between the V0 component d1 and p18 |
| GO:0005765 lysosomal membrane | IDA PMID:22053050 mTORC1 senses lysosomal amino acids through an inside-out me... | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the lysosomal surface, the site of mTORC1 activation PMID:28296633 V-ATPase, the key proton pump for endo-lysosomal acidification |
| GO:0046611 lysosomal proton-transporting V-type ATPase complex | IDA PMID:22053050 mTORC1 senses lysosomal amino acids through an inside-out me... | ACCEPT | Summary: Supported core ATP6V0D1 annotation: lysosomal proton-transporting V-type ATPase complex. Reason: ATP6V0D1/d1 is a V0-sector d subunit of the V-ATPase. Biochemical, UniProt, and human V-ATPase structural evidence support V-ATPase complex membership and V0-domain placement as core annotations. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase) file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:18752060 These data indicate that the d subunit in man is centrally located within the pump and is thus important in its rotary mechanism PMID:33065002 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 file:human/ATP6V0D1/ATP6V0D1-deep-research-manual.md ATP6V0D1 encodes V-type proton ATPase subunit d 1, also called V-ATPase AC39/p39 |
| 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: Directly supported lysosomal amino-acid/mTORC1 signaling context: positive regulation of TORC1 signaling. Reason: The mTORC1 work supports V-ATPase, including V0 d1, as part of lysosomal amino-acid sensing through Ragulator/Rag signaling. This is a real signaling output but secondary to the core proton-pump/acidification function. Supporting Evidence: PMID:22053050 the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1 PMID:22053050 Ragulator provides a physical and functional link between the v-ATPase and the Rag GTPases PMID:22053050 direct interaction between the V0 component d1 and p18 |
| GO:0000220 vacuolar proton-transporting V-type ATPase, V0 domain | ISS GO_REF:0000024 | ACCEPT | Summary: Supported core ATP6V0D1 annotation: vacuolar proton-transporting V-type ATPase, V0 domain. Reason: ATP6V0D1/d1 is a V0-sector d subunit of the V-ATPase. Biochemical, UniProt, and human V-ATPase structural evidence support V-ATPase complex membership and V0-domain placement as core annotations. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase) file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:18752060 These data indicate that the d subunit in man is centrally located within the pump and is thus important in its rotary mechanism PMID:33065002 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 file:human/ATP6V0D1/ATP6V0D1-deep-research-manual.md ATP6V0D1 encodes V-type proton ATPase subunit d 1, also called V-ATPase AC39/p39 |
| GO:0005515 protein binding | IPI PMID:30374053 TMEM9 promotes intestinal tumorigenesis through vacuolar-ATP... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent ATP6V0D1 function. Reason: TMEM9/ATP6AP2 interactions are V-ATPase assembly/signaling context; generic protein binding should not define ATP6V0D1 function. Proposed replacements: vacuolar proton-transporting V-type ATPase complex proton-transporting ATPase activity, rotational mechanism Supporting Evidence: PMID:30374053 TMEM9 binds to and facilitates assembly of vacuolar-ATPase (v-ATPase) |
| GO:0005515 protein binding | IPI PMID:29644770 TMEM55B contributes to lysosomal homeostasis and amino acid-... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent ATP6V0D1 function. Reason: TMEM55B interaction supports lysosomal V-ATPase/mTORC1 context, but protein binding remains too generic. Proposed replacements: vacuolar proton-transporting V-type ATPase complex proton-transporting ATPase activity, rotational mechanism Supporting Evidence: PMID:29644770 TMEM55B interacts with many proteins that participate in mTORC1 activation including components of the vacuolar-type proton ATPase (V-ATPase) |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9639286 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: Reactome:R-HSA-9645608 Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1 |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9640167 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: Reactome:R-HSA-9645608 Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1 |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9640168 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: Reactome:R-HSA-9645608 Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1 |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9640175 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: Reactome:R-HSA-9645608 Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1 |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9640195 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: Reactome:R-HSA-9645608 Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1 |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9645598 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: Reactome:R-HSA-9645608 Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1 |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9645608 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: Reactome:R-HSA-9645608 Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1 |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9646468 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: Reactome:R-HSA-9645608 Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the vacuolar H(+)-adenosine triphosphatase ATPase (v-ATPase) is necessary for amino acids to activate mTORC1 |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9858932 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the lysosomal surface, the site of mTORC1 activation PMID:28296633 V-ATPase, the key proton pump for endo-lysosomal acidification |
| GO:0006879 intracellular iron ion homeostasis | IMP PMID:28296633 The vacuolar-ATPase complex and assembly factors, TMEM199 an... | KEEP AS NON CORE | Summary: Supported but non-core ATP6V0D1 context: intracellular iron ion homeostasis. Reason: ATP6V0D1 disruption was identified in a V-ATPase/HIF screen and linked to intracellular iron depletion. This is a downstream consequence of endolysosomal V-ATPase function, not the primary evolved activity of the d1 subunit. Supporting Evidence: PMID:28296633 five V-ATPase subunits: ATP6AP1, ATP6V1A, ATP6V1G1, ATP6V0A2 and ATP6V0D1 PMID:28296633 disrupting the V-ATPase results in intracellular iron depletion |
| GO:0036295 cellular response to increased oxygen levels | IMP PMID:28296633 The vacuolar-ATPase complex and assembly factors, TMEM199 an... | MARK AS OVER ANNOTATED | Summary: The HIF/aerobic-response evidence is real but the GO term is an over-specific downstream readout for ATP6V0D1. Reason: PMID:28296633 shows ATP6V0D1/V-ATPase disruption stabilizes HIF1A in aerobic conditions via iron depletion. That supports iron/HIF homeostasis context, but not a direct ATP6V0D1 role in cellular response to increased oxygen levels. Proposed replacements: intracellular iron ion homeostasis Supporting Evidence: PMID:28296633 five V-ATPase subunits: ATP6AP1, ATP6V1A, ATP6V1G1, ATP6V0A2 and ATP6V0D1 PMID:28296633 disrupting the V-ATPase results in intracellular iron depletion |
| GO:0016241 regulation of macroautophagy | NAS PMID:22982048 Lipofuscin is formed independently of macroautophagy and lys... | MARK AS OVER ANNOTATED | Summary: Regulation of macroautophagy is over-annotated for ATP6V0D1 based on the cited lipofuscin study. Reason: The cited paper discusses macroautophagy and lysosomal uptake of lipofuscin but does not establish ATP6V0D1 as a specific macroautophagy regulator. In the PN context, ATP6V0D1 should be represented through lysosomal V-ATPase acidification rather than a broad macroautophagy-regulatory claim. Proposed replacements: vacuolar acidification Supporting Evidence: PMID:22982048 macroautophagy is responsible for the uptake of lipofuscin into the lysosomes file:human/ATP6V0D1/ATP6V0D1-notes.md The `regulation of macroautophagy` row from the lipofuscin paper is not strong direct evidence for ATP6V0D1 as a macroautophagy regulator |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Extracellular exosome detection is supported by high-throughput proteomics but is not core ATP6V0D1 function. Reason: ATP6V0D1 can be detected in exosome proteomics datasets, consistent with endomembrane origin and vesicle biology. These HDA rows should not drive functional interpretation. Supporting Evidence: PMID:19056867 LC-MS/MS to profile the proteome of human urinary exosomes PMID:19199708 we catalogued 491 proteins in the exosome fraction of human parotid saliva PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected |
| GO:0005515 protein binding | IPI PMID:20093472 Requirement of prorenin receptor and vacuolar H+-ATPase-medi... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent ATP6V0D1 function. Reason: The PRR/ATP6AP2 Wnt paper supports a V-ATPase signaling/adaptor context, not a specific ATP6V0D1 molecular function beyond V-ATPase complex function. Proposed replacements: vacuolar proton-transporting V-type ATPase complex proton-transporting ATPase activity, rotational mechanism Supporting Evidence: PMID:20093472 PRR functions in a renin-independent manner as an adaptor between Wnt receptors and the vacuolar H+-adenosine triphosphatase (V-ATPase) complex |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: Extracellular exosome detection is supported by high-throughput proteomics but is not core ATP6V0D1 function. Reason: ATP6V0D1 can be detected in exosome proteomics datasets, consistent with endomembrane origin and vesicle biology. These HDA rows should not drive functional interpretation. Supporting Evidence: PMID:19056867 LC-MS/MS to profile the proteome of human urinary exosomes PMID:19199708 we catalogued 491 proteins in the exosome fraction of human parotid saliva PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Extracellular exosome detection is supported by high-throughput proteomics but is not core ATP6V0D1 function. Reason: ATP6V0D1 can be detected in exosome proteomics datasets, consistent with endomembrane origin and vesicle biology. These HDA rows should not drive functional interpretation. Supporting Evidence: PMID:19056867 LC-MS/MS to profile the proteome of human urinary exosomes PMID:19199708 we catalogued 491 proteins in the exosome fraction of human parotid saliva PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected |
| GO:0005765 lysosomal membrane | HDA PMID:17897319 Integral and associated lysosomal membrane proteins. | ACCEPT | Summary: Supported endolysosomal V-ATPase location: lysosomal membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the lysosomal surface, the site of mTORC1 activation PMID:28296633 V-ATPase, the key proton pump for endo-lysosomal acidification |
| GO:0060271 cilium assembly | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cilium assembly is a supported V-ATPase/SNX10 trafficking context but not the core ATP6V0D1 function. Reason: The SNX10 study supports V-ATPase-dependent ciliogenesis and centrosomal targeting, but ATP6V0D1 is best curated primarily as a V-ATPase proton-pump subunit. Supporting Evidence: PMID:21844891 SNX10 interacts with V-ATPase complex and targets it to the centrosome PMID:21844891 Like SNX10, V-ATPase regulates ciliogenesis in vitro and in vivo |
| GO:0005813 centrosome | IDA PMID:21844891 A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and... | KEEP AS NON CORE | Summary: Centrosome colocalization is supported in the SNX10/V-ATPase ciliogenesis context but is not core. Reason: The cited paper places SNX10/V-ATPase at the centrosome during ciliogenesis. This is a context-specific colocalization rather than the primary ATP6V0D1 location. Supporting Evidence: PMID:21844891 SNX10 interacts with V-ATPase complex and targets it to the centrosome PMID:21844891 Like SNX10, V-ATPase regulates ciliogenesis in vitro and in vivo |
| GO:0030670 phagocytic vesicle membrane | TAS Reactome:R-HSA-1222516 | KEEP AS NON CORE | Summary: Context-specific vesicle membrane localization for V-ATPase: phagocytic vesicle membrane. Reason: V-ATPases acidify several specialized vesicle classes, including clathrin-coated and phagocytic vesicles. These locations are plausible and supported, but lysosomal/endosomal V-ATPase function is the primary ATP6V0D1 role. Supporting Evidence: Reactome:R-HSA-1222516 When pumping, ATP hydrolysis drives a 120 degree rotation of the rotor which leads to movement of three protons into the phagosome |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-1791184 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: endosome membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments Reactome:R-HSA-74723 The effect of the proton pump is to allow entry of [H+] ions into the lumen of the endosome |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-5252133 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: endosome membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: Reactome:R-HSA-5252133 Vacuolar-type H+-ATPases (V-ATPases) are proton pumps that acidify intracellular cargos file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the lysosomal surface, the site of mTORC1 activation PMID:28296633 V-ATPase, the key proton pump for endo-lysosomal acidification |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-74723 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: endosome membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: Reactome:R-HSA-74723 The effect of the proton pump is to allow entry of [H+] ions into the lumen of the endosome file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the lysosomal surface, the site of mTORC1 activation PMID:28296633 V-ATPase, the key proton pump for endo-lysosomal acidification |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-917841 | ACCEPT | Summary: Supported endolysosomal V-ATPase location: endosome membrane. Reason: ATP6V0D1-containing V-ATPase complexes function on lysosomal and endosomal membranes, where they acidify organelle lumens. These are core cellular locations for the d1 subunit. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Lysosome membrane PMID:22053050 the lysosomal surface, the site of mTORC1 activation PMID:28296633 V-ATPase, the key proton pump for endo-lysosomal acidification |
| GO:0005515 protein binding | IPI PMID:18752060 The d subunit plays a central role in human vacuolar H(+)-AT... | MARK AS OVER ANNOTATED | Summary: Protein binding is too generic to represent ATP6V0D1 function. Reason: PMID:18752060 provides meaningful evidence for d1 interaction with V1 D and F subunits, but the curatable function is V-ATPase rotary coupling/complex membership rather than generic protein binding. Proposed replacements: vacuolar proton-transporting V-type ATPase complex proton-transporting ATPase activity, rotational mechanism Supporting Evidence: PMID:18752060 human d1 and d2 are able to directly interact with the D and F subunits PMID:18752060 the d subunit in man is centrally located within the pump PMID:33065002 human V-ATPase in three rotational states |
| GO:0016020 membrane | IDA PMID:18752060 The d subunit plays a central role in human vacuolar H(+)-AT... | KEEP AS NON CORE | Summary: Membrane localization is true but too general for ATP6V0D1. Reason: ATP6V0D1 is a peripheral membrane-associated V0-sector subunit. The informative locations are the V-ATPase complex and lysosomal/endosomal membranes rather than the parent membrane term. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Membrane PMID:18752060 The vacuolar H+-ATPase d subunit is known to associate with the integral membrane V0 domain |
| GO:0016471 vacuolar proton-transporting V-type ATPase complex | IDA PMID:18752060 The d subunit plays a central role in human vacuolar H(+)-AT... | ACCEPT | Summary: Supported core ATP6V0D1 annotation: vacuolar proton-transporting V-type ATPase complex. Reason: ATP6V0D1/d1 is a V0-sector d subunit of the V-ATPase. Biochemical, UniProt, and human V-ATPase structural evidence support V-ATPase complex membership and V0-domain placement as core annotations. Supporting Evidence: file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase) file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments PMID:18752060 These data indicate that the d subunit in man is centrally located within the pump and is thus important in its rotary mechanism PMID:33065002 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 file:human/ATP6V0D1/ATP6V0D1-deep-research-manual.md ATP6V0D1 encodes V-type proton ATPase subunit d 1, also called V-ATPase AC39/p39 |
| GO:0016471 vacuolar proton-transporting V-type ATPase complex | NAS PMID:11118322 Structure of the VPATPD gene encoding subunit D of the human... | ACCEPT | Summary: Supported core ATP6V0D1 annotation: vacuolar proton-transporting V-type ATPase complex. Reason: ATP6V0D1/d1 is a V0-sector d subunit of the V-ATPase. Biochemical, UniProt, and human V-ATPase structural evidence support V-ATPase complex membership and V0-domain placement as core annotations. Supporting Evidence: PMID:11118322 Structure of the VPATPD gene encoding subunit D of the human vacuolar proton ATPase PMID:11118322 The encoded protein is 99.5% identical to mouse subunit D at the amino acid level file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase) file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments |
| GO:1902600 proton transmembrane transport | NAS PMID:11118322 Structure of the VPATPD gene encoding subunit D of the human... | ACCEPT | Summary: The original gene-structure citation is weak alone, but proton transport is supported by the full ATP6V0D1 evidence set. Reason: PMID:11118322 establishes VPATPD/ATP6V0D1 as the gene encoding human vacuolar proton ATPase subunit D; later biochemical and structural evidence supports the proton-transport annotation through V-ATPase complex function. Supporting Evidence: PMID:11118322 Structure of the VPATPD gene encoding subunit D of the human vacuolar proton ATPase PMID:11118322 The encoded protein is 99.5% identical to mouse subunit D at the amino acid level file:human/ATP6V0D1/ATP6V0D1-uniprot.txt Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase) file:human/ATP6V0D1/ATP6V0D1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments |
Loading supporting content…
Download this section (compressed HTML)Q: Should the ATP6V0D1 mTORC1 amino-acid sensing annotations remain as direct non-core V-ATPase signaling outputs, or should GO represent them primarily at the assembled V-ATPase/Ragulator complex level?
Q: Which ATP6V0D1-containing V-ATPase pools are most relevant to proteostasis phenotypes: lysosomal degradation, endosomal trafficking, autophagy-lysosome flux, or nutrient signaling through mTORC1?
Experiment: Deplete ATP6V0D1 in human cells and rescue with RNAi-resistant wild-type or V0-interaction-defective mutants while measuring lysosomal pH, EGFR/MHC-I lysosomal degradation, LC3 flux, and accumulation of undegraded protein cargo.
Hypothesis: ATP6V0D1 supports proteostasis phenotypes primarily through endolysosomal acidification rather than a direct macroautophagy-regulatory activity.
Type: loss-of-function rescue with lysosomal acidification and degradation assays
Experiment: Mutate ATP6V0D1 surfaces required for Ragulator p18 interaction and test amino-acid-stimulated mTORC1 lysosomal recruitment and S6K/4E-BP phosphorylation while monitoring V-ATPase assembly and organelle pH.
Hypothesis: The d1-p18/Ragulator interaction contributes to mTORC1 amino-acid sensing independently of bulk lysosomal pH changes.
Type: interaction-mutant signaling assay
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)