ATP6V0B encodes the human V-type proton ATPase V0 proteolipid subunit c''. It is a small multi-pass membrane component of the proton-translocating V0 sector, where it forms part of the c-ring rotor/pore with an essential conserved Glu98 residue required for H+ transport. ATP6V0B-containing V-ATPase complexes acidify lysosomes, endosomes, Golgi-derived compartments and other vesicles, thereby supporting endolysosomal pH homeostasis, membrane trafficking, protein degradation, autophagic flux and lysosome-associated nutrient signaling. In specialized cell contexts, V-ATPase complexes can also function at the plasma membrane to acidify the extracellular or phagosomal environment.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0016020 membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Accept membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0006811 monoatomic ion transport | IEA GO_REF:0000043 | MODIFY | Summary: The annotation is directionally correct but too broad for ATP6V0B. Reason: ATP6V0B is not a generic ion-transport factor; it contributes to V-ATPase-driven proton transmembrane transport. Replace the broad monoatomic ion transport term with the established proton transport process term already supported elsewhere in GOA. Proposed replacements: proton transmembrane transport 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0015078 proton transmembrane transporter activity | IEA GO_REF:0000120 | MODIFY | Summary: The proton-transporter concept is correct, but the more precise complex activity is V-type ATPase rotational proton pumping. Reason: ATP6V0B contributes as the c'' proteolipid in the V0 rotor rather than acting as an independent transporter. A complex-level term, proton-transporting ATPase activity, rotational mechanism, is the better molecular-function target; in GPAD/GAF this should be treated conservatively as a contribution to the V-ATPase complex activity. Proposed replacements: proton-transporting ATPase activity, rotational mechanism 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. PMID:9653649 hATP6F is a hydrophobic protein with five putative transmembrane segments, having 61% amino acid identity and 83% similarity to the yeast protein, except in the N-terminus, and contains a conserved glutamic acid residue (Glu98) that is essential for H(+)-transporting activity. |
| GO:0030665 clathrin-coated vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Accept clathrin-coated vesicle membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000043 | KEEP AS NON CORE | Summary: Keep this localization as a valid but non-core or context-specific site for V-ATPase complexes. Reason: ATP6V0B is a membrane V-ATPase subunit and V-ATPases can act in vesicular or specialized plasma/phagosomal compartments. For ATP6V0B's core annotation, however, lysosomal/endosomal/Golgi V0-domain component and acidification terms are more informative than this broad or context-specific location. 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. 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:0033177 proton-transporting two-sector ATPase complex, proton-transporting domain | IEA GO_REF:0000002 | ACCEPT | Summary: This component annotation is consistent with ATP6V0B being the c'' proteolipid subunit of the V0 proton-translocating sector of V-ATPase. Reason: ATP6V0B is experimentally identified as a five-transmembrane human V-ATPase proteolipid with conserved Glu98 required for H+ transport, and human V-ATPase structures place V0 subunits in the membrane-embedded proton-transfer module. The component annotation is therefore part of the core molecular role of ATP6V0B. 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. PMID:9653649 hATP6F is a hydrophobic protein with five putative transmembrane segments, having 61% amino acid identity and 83% similarity to the yeast protein, except in the N-terminus, and contains a conserved glutamic acid residue (Glu98) that is essential for H(+)-transporting activity. |
| GO:0033179 proton-transporting V-type ATPase, V0 domain | IEA GO_REF:0000002 | ACCEPT | Summary: This component annotation is consistent with ATP6V0B being the c'' proteolipid subunit of the V0 proton-translocating sector of V-ATPase. Reason: ATP6V0B is experimentally identified as a five-transmembrane human V-ATPase proteolipid with conserved Glu98 required for H+ transport, and human V-ATPase structures place V0 subunits in the membrane-embedded proton-transfer module. The component annotation is therefore part of the core molecular role of ATP6V0B. 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. PMID:9653649 hATP6F is a hydrophobic protein with five putative transmembrane segments, having 61% amino acid identity and 83% similarity to the yeast protein, except in the N-terminus, and contains a conserved glutamic acid residue (Glu98) that is essential for H(+)-transporting activity. |
| GO:0046961 proton-transporting ATPase activity, rotational mechanism | IEA GO_REF:0000002 | ACCEPT | Summary: Accept the V-type ATPase rotational proton-pump activity as the complex activity to which ATP6V0B contributes. Reason: ATP6V0B is not the ATP-hydrolytic catalytic subunit, but it is an essential V0 c-ring proteolipid required for proton translocation by the rotary V-ATPase. This is the correct complex-level molecular function for the ATP6V0B-containing V-ATPase machinery. 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. PMID:9653649 hATP6F is a hydrophobic protein with five putative transmembrane segments, having 61% amino acid identity and 83% similarity to the yeast protein, except in the N-terminus, and contains a conserved glutamic acid residue (Glu98) that is essential for H(+)-transporting activity. |
| GO:1902600 proton transmembrane transport | IEA GO_REF:0000120 | ACCEPT | Summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. Reason: The ATP6V0B-containing V0 sector contributes to proton transfer by V-ATPase. Human V-ATPases maintain acidic endosomes and lysosomes and support membrane trafficking and protein degradation, so proton transport and organelle lumen acidification annotations reflect the core biological consequence of this subunit's role in the pump. 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. PMID:33065002 Vesicular and organellar V-ATPases are essential in establishing and maintaining the pH homeostasis of endosomes and lysosomes and in supporting intracellular membrane trafficking and protein degradation PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0005515 protein binding | IPI PMID:23864651 The identification of novel proteins that interact with the ... | REMOVE | Summary: Remove the generic protein binding annotation from the GLP-1R interaction screen. Reason: GO:0005515 is uninformative for ATP6V0B and the supporting study is a receptor-interactome screen rather than evidence for ATP6V0B's core V-ATPase function. No specific ATP6V0B molecular activity should be inferred from this interaction record. Supporting Evidence: PMID:23864651 A screen of a human fetal brain cDNA prey library with an unliganded human GLP-1R as bait in yeast revealed 38 novel interactor protein candidates. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Remove the generic protein binding annotation from the high-throughput binary interactome map. Reason: GO:0005515 is deliberately avoided in this curation workflow because it does not describe ATP6V0B's mechanistic role. This single REMOVE entry represents the multiple HuRI-derived GOA protein-binding interaction records from PMID:32296183; the HuRI study is a large-scale interaction map, useful as interaction evidence but not sufficient to replace the established V-ATPase c'' subunit function with a generic binding term. Supporting Evidence: 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 |
| GO:0005768 endosome | IEA GO_REF:0000107 | ACCEPT | Summary: Accept endosome as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Accept membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0033176 proton-transporting V-type ATPase complex | IEA GO_REF:0000107 | ACCEPT | Summary: This component annotation is consistent with ATP6V0B being the c'' proteolipid subunit of the V0 proton-translocating sector of V-ATPase. Reason: ATP6V0B is experimentally identified as a five-transmembrane human V-ATPase proteolipid with conserved Glu98 required for H+ transport, and human V-ATPase structures place V0 subunits in the membrane-embedded proton-transfer module. The component annotation is therefore part of the core molecular role of ATP6V0B. 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. PMID:9653649 hATP6F is a hydrophobic protein with five putative transmembrane segments, having 61% amino acid identity and 83% similarity to the yeast protein, except in the N-terminus, and contains a conserved glutamic acid residue (Glu98) that is essential for H(+)-transporting activity. |
| GO:0000139 Golgi membrane | NAS PMID:32001091 Structure and Roles of V-type ATPases. | ACCEPT | Summary: Accept Golgi membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0005765 lysosomal membrane | NAS PMID:32001091 Structure and Roles of V-type ATPases. | ACCEPT | Summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0005886 plasma membrane | NAS PMID:32001091 Structure and Roles of V-type ATPases. | KEEP AS NON CORE | Summary: Keep this localization as a valid but non-core or context-specific site for V-ATPase complexes. Reason: ATP6V0B is a membrane V-ATPase subunit and V-ATPases can act in vesicular or specialized plasma/phagosomal compartments. For ATP6V0B's core annotation, however, lysosomal/endosomal/Golgi V0-domain component and acidification terms are more informative than this broad or context-specific location. 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. 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:0007035 vacuolar acidification | NAS PMID:32001091 Structure and Roles of V-type ATPases. | ACCEPT | Summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. Reason: The ATP6V0B-containing V0 sector contributes to proton transfer by V-ATPase. Human V-ATPases maintain acidic endosomes and lysosomes and support membrane trafficking and protein degradation, so proton transport and organelle lumen acidification annotations reflect the core biological consequence of this subunit's role in the pump. 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. PMID:33065002 Vesicular and organellar V-ATPases are essential in establishing and maintaining the pH homeostasis of endosomes and lysosomes and in supporting intracellular membrane trafficking and protein degradation PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0007042 lysosomal lumen acidification | NAS PMID:32001091 Structure and Roles of V-type ATPases. | ACCEPT | Summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. Reason: The ATP6V0B-containing V0 sector contributes to proton transfer by V-ATPase. Human V-ATPases maintain acidic endosomes and lysosomes and support membrane trafficking and protein degradation, so proton transport and organelle lumen acidification annotations reflect the core biological consequence of this subunit's role in the pump. 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. PMID:33065002 Vesicular and organellar V-ATPases are essential in establishing and maintaining the pH homeostasis of endosomes and lysosomes and in supporting intracellular membrane trafficking and protein degradation PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0007042 lysosomal lumen acidification | NAS PMID:33065002 Structures of a Complete Human V-ATPase Reveal Mechanisms of... | ACCEPT | Summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. Reason: The ATP6V0B-containing V0 sector contributes to proton transfer by V-ATPase. Human V-ATPases maintain acidic endosomes and lysosomes and support membrane trafficking and protein degradation, so proton transport and organelle lumen acidification annotations reflect the core biological consequence of this subunit's role in the pump. 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. PMID:33065002 Vesicular and organellar V-ATPases are essential in establishing and maintaining the pH homeostasis of endosomes and lysosomes and in supporting intracellular membrane trafficking and protein degradation PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0010008 endosome membrane | NAS PMID:32001091 Structure and Roles of V-type ATPases. | ACCEPT | Summary: Accept endosome membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0016020 membrane | IDA PMID:33065002 Structures of a Complete Human V-ATPase Reveal Mechanisms of... | ACCEPT | Summary: Accept membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0033176 proton-transporting V-type ATPase complex | NAS PMID:33065002 Structures of a Complete Human V-ATPase Reveal Mechanisms of... | ACCEPT | Summary: This component annotation is consistent with ATP6V0B being the c'' proteolipid subunit of the V0 proton-translocating sector of V-ATPase. Reason: ATP6V0B is experimentally identified as a five-transmembrane human V-ATPase proteolipid with conserved Glu98 required for H+ transport, and human V-ATPase structures place V0 subunits in the membrane-embedded proton-transfer module. The component annotation is therefore part of the core molecular role of ATP6V0B. 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. PMID:9653649 hATP6F is a hydrophobic protein with five putative transmembrane segments, having 61% amino acid identity and 83% similarity to the yeast protein, except in the N-terminus, and contains a conserved glutamic acid residue (Glu98) that is essential for H(+)-transporting activity. |
| GO:0048388 endosomal lumen acidification | NAS PMID:32001091 Structure and Roles of V-type ATPases. | ACCEPT | Summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. Reason: The ATP6V0B-containing V0 sector contributes to proton transfer by V-ATPase. Human V-ATPases maintain acidic endosomes and lysosomes and support membrane trafficking and protein degradation, so proton transport and organelle lumen acidification annotations reflect the core biological consequence of this subunit's role in the pump. 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. PMID:33065002 Vesicular and organellar V-ATPases are essential in establishing and maintaining the pH homeostasis of endosomes and lysosomes and in supporting intracellular membrane trafficking and protein degradation PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0051452 intracellular pH reduction | NAS PMID:32001091 Structure and Roles of V-type ATPases. | ACCEPT | Summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. Reason: The ATP6V0B-containing V0 sector contributes to proton transfer by V-ATPase. Human V-ATPases maintain acidic endosomes and lysosomes and support membrane trafficking and protein degradation, so proton transport and organelle lumen acidification annotations reflect the core biological consequence of this subunit's role in the pump. 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. PMID:33065002 Vesicular and organellar V-ATPases are essential in establishing and maintaining the pH homeostasis of endosomes and lysosomes and in supporting intracellular membrane trafficking and protein degradation PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0061795 Golgi lumen acidification | NAS PMID:32001091 Structure and Roles of V-type ATPases. | ACCEPT | Summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. Reason: The ATP6V0B-containing V0 sector contributes to proton transfer by V-ATPase. Human V-ATPases maintain acidic endosomes and lysosomes and support membrane trafficking and protein degradation, so proton transport and organelle lumen acidification annotations reflect the core biological consequence of this subunit's role in the pump. 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. PMID:33065002 Vesicular and organellar V-ATPases are essential in establishing and maintaining the pH homeostasis of endosomes and lysosomes and in supporting intracellular membrane trafficking and protein degradation PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:1902600 proton transmembrane transport | NAS PMID:33065002 Structures of a Complete Human V-ATPase Reveal Mechanisms of... | ACCEPT | Summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. Reason: The ATP6V0B-containing V0 sector contributes to proton transfer by V-ATPase. Human V-ATPases maintain acidic endosomes and lysosomes and support membrane trafficking and protein degradation, so proton transport and organelle lumen acidification annotations reflect the core biological consequence of this subunit's role in the pump. 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. PMID:33065002 Vesicular and organellar V-ATPases are essential in establishing and maintaining the pH homeostasis of endosomes and lysosomes and in supporting intracellular membrane trafficking and protein degradation PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0046961 proton-transporting ATPase activity, rotational mechanism | TAS PMID:9653649 Identification and characterization of the gene encoding a s... | ACCEPT | Summary: Accept the V-type ATPase rotational proton-pump activity as the complex activity to which ATP6V0B contributes. Reason: ATP6V0B is not the ATP-hydrolytic catalytic subunit, but it is an essential V0 c-ring proteolipid required for proton translocation by the rotary V-ATPase. This is the correct complex-level molecular function for the ATP6V0B-containing V-ATPase machinery. 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. PMID:9653649 hATP6F is a hydrophobic protein with five putative transmembrane segments, having 61% amino acid identity and 83% similarity to the yeast protein, except in the N-terminus, and contains a conserved glutamic acid residue (Glu98) that is essential for H(+)-transporting activity. |
| GO:0000220 vacuolar proton-transporting V-type ATPase, V0 domain | ISS GO_REF:0000024 | ACCEPT | Summary: This component annotation is consistent with ATP6V0B being the c'' proteolipid subunit of the V0 proton-translocating sector of V-ATPase. Reason: ATP6V0B is experimentally identified as a five-transmembrane human V-ATPase proteolipid with conserved Glu98 required for H+ transport, and human V-ATPase structures place V0 subunits in the membrane-embedded proton-transfer module. The component annotation is therefore part of the core molecular role of ATP6V0B. 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. PMID:9653649 hATP6F is a hydrophobic protein with five putative transmembrane segments, having 61% amino acid identity and 83% similarity to the yeast protein, except in the N-terminus, and contains a conserved glutamic acid residue (Glu98) that is essential for H(+)-transporting activity. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9639286 | ACCEPT | Summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9640167 | ACCEPT | Summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9640168 | ACCEPT | Summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9640175 | ACCEPT | Summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9640195 | ACCEPT | Summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9645598 | ACCEPT | Summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9645608 | ACCEPT | Summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. Reactome:R-HSA-9645608 Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9646468 | ACCEPT | Summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0005765 lysosomal membrane | TAS Reactome:R-HSA-9858940 | ACCEPT | Summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. Reactome:R-HSA-9858940 MITF has been implicated in the regulation of expression of many components of the v-ATPase, including the transmembrane component ATP6V0B |
| GO:0016241 regulation of macroautophagy | NAS PMID:22982048 Lipofuscin is formed independently of macroautophagy and lys... | MARK AS OVER ANNOTATED | Summary: Macroautophagy regulation is an over-annotation for ATP6V0B as an individual V-ATPase subunit. Reason: ATP6V0B-containing V-ATPase complexes support autophagic flux indirectly by acidifying lysosomes, but the cited study concerns lipofuscin handling and macroautophagy/lysosomal activity rather than a specific regulatory role for ATP6V0B. The safer annotation is lysosomal lumen acidification, not regulation of macroautophagy. Supporting Evidence: PMID:22982048 macroautophagy is responsible for the uptake of lipofuscin into the lysosomes PMID:33065002 Vesicular and organellar V-ATPases are essential in establishing and maintaining the pH homeostasis of endosomes and lysosomes and in supporting intracellular membrane trafficking and protein degradation |
| GO:0030670 phagocytic vesicle membrane | TAS Reactome:R-HSA-1222516 | KEEP AS NON CORE | Summary: Keep this localization as a valid but non-core or context-specific site for V-ATPase complexes. Reason: ATP6V0B is a membrane V-ATPase subunit and V-ATPases can act in vesicular or specialized plasma/phagosomal compartments. For ATP6V0B's core annotation, however, lysosomal/endosomal/Golgi V0-domain component and acidification terms are more informative than this broad or context-specific location. 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. 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-5252133 | ACCEPT | Summary: Accept endosome membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-74723 | ACCEPT | Summary: Accept endosome membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. 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-917841 | ACCEPT | Summary: Accept endosome membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0016020 membrane | TAS PMID:9653649 Identification and characterization of the gene encoding a s... | ACCEPT | Summary: Accept membrane as a supported V-ATPase membrane localization. Reason: ATP6V0B is an integral membrane subunit of V-ATPase. Human V-ATPase structures and reviews support its role in organellar and vesicular proton-pump complexes; the broad membrane/localization annotation is correct, although more specific endolysosomal V-ATPase component terms are more informative. 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. PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:1902600 proton transmembrane transport | TAS PMID:9653649 Identification and characterization of the gene encoding a s... | ACCEPT | Summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. Reason: The ATP6V0B-containing V0 sector contributes to proton transfer by V-ATPase. Human V-ATPases maintain acidic endosomes and lysosomes and support membrane trafficking and protein degradation, so proton transport and organelle lumen acidification annotations reflect the core biological consequence of this subunit's role in the pump. 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. PMID:33065002 Vesicular and organellar V-ATPases are essential in establishing and maintaining the pH homeostasis of endosomes and lysosomes and in supporting intracellular membrane trafficking and protein degradation PMID:9653649 The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. |
| GO:0046610 lysosomal proton-transporting V-type ATPase, V0 domain | RCA file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv | NEW | Summary: Add the conservative PN-projected lysosomal V0-domain component annotation. Reason: The PN projection places ATP6V0B in the V0 lysosomal V-ATPase proton pump component leaf and maps that leaf to GO:0046610. This is more specific than ATP6V0B's current GOA component annotations, but it is supported by the established human V-ATPase structure, lysosomal V-ATPase biology, and existing GOA annotations to lysosomal membrane, lysosomal lumen acidification, and the broader V-type ATPase V0 domain. This adds component specificity rather than a new biological process claim. Supporting Evidence: file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv ATP6V0B Autophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, upstream|Nutrient sensing|V0 lysosomal v-ATPase proton pump component 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. PMID:33065002 Vesicular and organellar V-ATPases are essential in establishing and maintaining the pH homeostasis of endosomes and lysosomes and in supporting intracellular membrane trafficking and protein degradation file:human/ATP6V0B/ATP6V0B-deep-research-falcon.md The target is human ATP6V0B (UniProt Q99437), encoding the V-ATPase V0 21 kDa proteolipid subunit c'' (also called c-double-prime), a member of the V-ATPase proteolipid subunit family. |
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Download this section (compressed HTML)Q: Is ATP6V0B ever functionally limiting for plasma-membrane V-ATPase activity in specialized human cells, or should plasma membrane annotations remain non-core generic V-ATPase complex localizations?
Suggested experts: V-ATPase biology curators, GO cellular component annotation experts
Experiment: Generate ATP6V0B knockout human cells, rescue with wild-type ATP6V0B and a Glu98-neutralized mutant, and quantify LysoSensor/LysoTracker pH, cathepsin maturation, V1-V0 assembly and autophagic flux. This would directly test the PN-projected lysosomal V0-domain role at the gene-product level.
Hypothesis: Loss of ATP6V0B specifically disrupts assembly or activity of the lysosomal V0 domain, reducing lysosomal acidification without implying a standalone ATPase activity for the subunit.
Type: ATP6V0B-specific knockout/rescue in human lysosome pH assays
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