id: Q99437 gene_symbol: ATP6V0B product_type: PROTEIN taxon: id: NCBITaxon:9606 label: Homo sapiens description: '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.' existing_annotations: - term: id: GO:0016020 label: membrane evidence_type: IBA original_reference_id: GO_REF:0000033 review: summary: Accept membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0006811 label: monoatomic ion transport evidence_type: IEA original_reference_id: GO_REF:0000043 review: summary: The annotation is directionally correct but too broad for ATP6V0B. action: MODIFY 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_replacement_terms: - id: GO:1902600 label: proton transmembrane transport supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0015078 label: proton transmembrane transporter activity evidence_type: IEA original_reference_id: GO_REF:0000120 review: summary: The proton-transporter concept is correct, but the more precise complex activity is V-type ATPase rotational proton pumping. action: MODIFY 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_replacement_terms: - id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: 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. - term: id: GO:0030665 label: clathrin-coated vesicle membrane evidence_type: IEA original_reference_id: GO_REF:0000044 review: summary: Accept clathrin-coated vesicle membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0031410 label: cytoplasmic vesicle evidence_type: IEA original_reference_id: GO_REF:0000043 review: summary: Keep this localization as a valid but non-core or context-specific site for V-ATPase complexes. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: Reactome:R-HSA-1222516 supporting_text: When pumping, ATP hydrolysis drives a 120 degree rotation of the rotor which leads to movement of three protons into the phagosome - term: id: GO:0033177 label: proton-transporting two-sector ATPase complex, proton-transporting domain evidence_type: IEA original_reference_id: GO_REF:0000002 review: summary: This component annotation is consistent with ATP6V0B being the c'' proteolipid subunit of the V0 proton-translocating sector of V-ATPase. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: 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. - term: id: GO:0033179 label: proton-transporting V-type ATPase, V0 domain evidence_type: IEA original_reference_id: GO_REF:0000002 review: summary: This component annotation is consistent with ATP6V0B being the c'' proteolipid subunit of the V0 proton-translocating sector of V-ATPase. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: 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. - term: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism evidence_type: IEA original_reference_id: GO_REF:0000002 review: summary: Accept the V-type ATPase rotational proton-pump activity as the complex activity to which ATP6V0B contributes. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: 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. - term: id: GO:1902600 label: proton transmembrane transport evidence_type: IEA original_reference_id: GO_REF:0000120 review: summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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 - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:23864651 review: summary: Remove the generic protein binding annotation from the GLP-1R interaction screen. action: REMOVE 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. supported_by: - reference_id: PMID:23864651 supporting_text: 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. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32296183 review: summary: Remove the generic protein binding annotation from the high-throughput binary interactome map. action: REMOVE 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. supported_by: - reference_id: PMID:32296183 supporting_text: 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 - term: id: GO:0005768 label: endosome evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: Accept endosome as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0016020 label: membrane evidence_type: IEA original_reference_id: GO_REF:0000120 review: summary: Accept membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0033176 label: proton-transporting V-type ATPase complex evidence_type: IEA original_reference_id: GO_REF:0000107 review: summary: This component annotation is consistent with ATP6V0B being the c'' proteolipid subunit of the V0 proton-translocating sector of V-ATPase. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: 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. - term: id: GO:0000139 label: Golgi membrane evidence_type: NAS original_reference_id: PMID:32001091 review: summary: Accept Golgi membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0005765 label: lysosomal membrane evidence_type: NAS original_reference_id: PMID:32001091 review: summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0005886 label: plasma membrane evidence_type: NAS original_reference_id: PMID:32001091 review: summary: Keep this localization as a valid but non-core or context-specific site for V-ATPase complexes. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: Reactome:R-HSA-1222516 supporting_text: When pumping, ATP hydrolysis drives a 120 degree rotation of the rotor which leads to movement of three protons into the phagosome - term: id: GO:0007035 label: vacuolar acidification evidence_type: NAS original_reference_id: PMID:32001091 review: summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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 - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0007042 label: lysosomal lumen acidification evidence_type: NAS original_reference_id: PMID:32001091 review: summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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 - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0007042 label: lysosomal lumen acidification evidence_type: NAS original_reference_id: PMID:33065002 review: summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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 - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0010008 label: endosome membrane evidence_type: NAS original_reference_id: PMID:32001091 review: summary: Accept endosome membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0016020 label: membrane evidence_type: IDA original_reference_id: PMID:33065002 review: summary: Accept membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0033176 label: proton-transporting V-type ATPase complex evidence_type: NAS original_reference_id: PMID:33065002 review: summary: This component annotation is consistent with ATP6V0B being the c'' proteolipid subunit of the V0 proton-translocating sector of V-ATPase. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: 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. - term: id: GO:0048388 label: endosomal lumen acidification evidence_type: NAS original_reference_id: PMID:32001091 review: summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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 - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0051452 label: intracellular pH reduction evidence_type: NAS original_reference_id: PMID:32001091 review: summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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 - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0061795 label: Golgi lumen acidification evidence_type: NAS original_reference_id: PMID:32001091 review: summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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 - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:1902600 label: proton transmembrane transport evidence_type: NAS original_reference_id: PMID:33065002 review: summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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 - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism evidence_type: TAS original_reference_id: PMID:9653649 review: summary: Accept the V-type ATPase rotational proton-pump activity as the complex activity to which ATP6V0B contributes. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: 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. - term: id: GO:0000220 label: vacuolar proton-transporting V-type ATPase, V0 domain evidence_type: ISS original_reference_id: GO_REF:0000024 review: summary: This component annotation is consistent with ATP6V0B being the c'' proteolipid subunit of the V0 proton-translocating sector of V-ATPase. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: 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. - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9639286 review: summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9640167 review: summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9640168 review: summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9640175 review: summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9640195 review: summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9645598 review: summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9645608 review: summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - reference_id: Reactome:R-HSA-9645608 supporting_text: Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9646468 review: summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0005765 label: lysosomal membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-9858940 review: summary: Accept lysosomal membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - reference_id: Reactome:R-HSA-9858940 supporting_text: MITF has been implicated in the regulation of expression of many components of the v-ATPase, including the transmembrane component ATP6V0B - term: id: GO:0016241 label: regulation of macroautophagy evidence_type: NAS original_reference_id: PMID:22982048 review: summary: Macroautophagy regulation is an over-annotation for ATP6V0B as an individual V-ATPase subunit. action: MARK_AS_OVER_ANNOTATED 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. supported_by: - reference_id: PMID:22982048 supporting_text: macroautophagy is responsible for the uptake of lipofuscin into the lysosomes - reference_id: PMID:33065002 supporting_text: 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 - term: id: GO:0030670 label: phagocytic vesicle membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-1222516 review: summary: Keep this localization as a valid but non-core or context-specific site for V-ATPase complexes. action: KEEP_AS_NON_CORE 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: Reactome:R-HSA-1222516 supporting_text: When pumping, ATP hydrolysis drives a 120 degree rotation of the rotor which leads to movement of three protons into the phagosome - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-5252133 review: summary: Accept endosome membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-74723 review: summary: Accept endosome membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - reference_id: Reactome:R-HSA-74723 supporting_text: The effect of the proton pump is to allow entry of [H+] ions into the lumen of the endosome. - term: id: GO:0010008 label: endosome membrane evidence_type: TAS original_reference_id: Reactome:R-HSA-917841 review: summary: Accept endosome membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0016020 label: membrane evidence_type: TAS original_reference_id: PMID:9653649 review: summary: Accept membrane as a supported V-ATPase membrane localization. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:1902600 label: proton transmembrane transport evidence_type: TAS original_reference_id: PMID:9653649 review: summary: Accept this acidification/proton-transport process annotation for the ATP6V0B-containing V-ATPase complex. action: ACCEPT 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. supported_by: - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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 - reference_id: PMID:9653649 supporting_text: The proteolipid domain of vacuolar H(+)-ATPase (V-ATPase) plays a major role in H+ transport in microvesicles and other acidic organelles. - term: id: GO:0046610 label: lysosomal proton-transporting V-type ATPase, V0 domain evidence_type: RCA original_reference_id: 'file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv' review: summary: Add the conservative PN-projected lysosomal V0-domain component annotation. action: NEW 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. supported_by: - reference_id: 'file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv' supporting_text: "ATP6V0B\t\tAutophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, upstream|Nutrient sensing|V0 lysosomal v-ATPase proton pump component" - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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 - reference_id: file:human/ATP6V0B/ATP6V0B-deep-research-falcon.md supporting_text: 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. references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms. findings: [] - id: GO_REF:0000024 title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity. findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees findings: [] - id: GO_REF:0000043 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt. findings: [] - id: GO_REF:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara. findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods. findings: [] - id: PMID:22982048 title: Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts. findings: - statement: This paper supports a macroautophagy/lysosome context, but not a specific ATP6V0B regulatory function. supporting_text: macroautophagy is responsible for the uptake of lipofuscin into the lysosomes reference_section_type: ABSTRACT - id: PMID:23864651 title: The identification of novel proteins that interact with the GLP-1 receptor and restrain its activity. findings: - statement: The GLP-1R interaction study used a membrane yeast two-hybrid screen and does not define ATP6V0B core molecular function. supporting_text: 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. reference_section_type: ABSTRACT - id: PMID:32001091 title: Structure and Roles of V-type ATPases. findings: - statement: V-ATPases are membrane-embedded ATP-driven proton pumps and are the primary source of organellar acidification in eukaryotes. supporting_text: V-ATPases are membrane-embedded protein complexes that function as ATP hydrolysis-driven proton pumps. reference_section_type: ABSTRACT - id: PMID:32296183 title: A reference map of the human binary protein interactome. findings: - statement: The HuRI study is a large-scale binary interactome resource, not ATP6V0B-specific functional evidence. supporting_text: 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 reference_section_type: RESULTS - id: PMID:33065002 title: Structures of a Complete Human V-ATPase Reveal Mechanisms of Its Assembly. findings: - statement: Human V-ATPase is an ATP-driven proton pump with a cytoplasmic V1 ATP-hydrolysis sector and a membrane-embedded Vo proton-transfer sector. supporting_text: 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. reference_section_type: ABSTRACT - statement: Organellar V-ATPases maintain endosome and lysosome pH homeostasis and support trafficking and protein degradation. supporting_text: 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 reference_section_type: INTRODUCTION - id: PMID:9653649 title: Identification and characterization of the gene encoding a second proteolipid subunit of human vacuolar H(+)-ATPase (ATP6F). findings: - statement: ATP6V0B/ATP6F is the human second V-ATPase proteolipid, a five-transmembrane c subunit with conserved Glu98 required for H+ transport. supporting_text: 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. reference_section_type: ABSTRACT - id: Reactome:R-HSA-1222516 title: Intraphagosomal pH is lowered to 5 by V-ATPase findings: - statement: Reactome describes V-ATPase rotary pumping into the phagosome. supporting_text: When pumping, ATP hydrolysis drives a 120 degree rotation of the rotor which leads to movement of three protons into the phagosome - id: Reactome:R-HSA-5252133 title: ATP6AP1 binds V-ATPase findings: [] - id: Reactome:R-HSA-74723 title: Endosome acidification findings: - statement: Reactome describes endosomal acidification as proton-pump driven entry of H+ into the endosome lumen. supporting_text: The effect of the proton pump is to allow entry of [H+] ions into the lumen of the endosome. - id: Reactome:R-HSA-917841 title: Acidification of Tf:TfR1 containing endosome findings: [] - id: Reactome:R-HSA-9639286 title: RRAGC,D exchanges GTP for GDP findings: [] - id: Reactome:R-HSA-9640167 title: RRAGA,B exchanges GDP for GTP findings: [] - id: Reactome:R-HSA-9640168 title: v-ATPase:Ragulator:RRAGA,B:GTP:RRAGC,D:GDP:SLC38A9:Arginine dissociates yielding v-ATPase:Ragulator:RRAGA,B:GTP:RRAGC,D:GDP and SLC38A9:Arginine findings: [] - id: Reactome:R-HSA-9640175 title: v-ATPase:Ragulator:RagA,B:GDP:RagC,D:GDP binds SLC38A9:Arginine findings: [] - id: Reactome:R-HSA-9640195 title: RRAGA,B hydrolyzes GTP findings: [] - id: Reactome:R-HSA-9645598 title: RRAGC,D hydrolyzes GTP findings: [] - id: Reactome:R-HSA-9645608 title: v-ATPase:Ragulator:RRAGA,B:GTP:RRAGC,D:GDP binds mTORC1 findings: - statement: Reactome places V-ATPase activity upstream of lysosomal mTORC1 recruitment. supporting_text: Hydrolysis of ATP by the v-ATPase complex is also required for recruitment of mTORC1 - id: Reactome:R-HSA-9646468 title: mTORC1 binds RHEB:GTP findings: [] - id: Reactome:R-HSA-9858940 title: MITF-M-dependent ATP6V0B gene expression findings: - statement: Reactome records MITF-dependent expression of ATP6V0B and the lysosome/endosome acidification role of V-ATPase. supporting_text: MITF has been implicated in the regulation of expression of many components of the v-ATPase, including the transmembrane component ATP6V0B - id: file:human/ATP6V0B/ATP6V0B-deep-research-falcon.md title: Falcon deep research report on ATP6V0B findings: - statement: Falcon deep research supports ATP6V0B as the human V-ATPase V0 c'' proteolipid subunit and highlights the PN-relevant lysosomal acidification role. supporting_text: ATP6V0B-containing V-ATPases acidify lysosomes, endosomes, Golgi, and secretory/synaptic vesicles and can localize to plasma membranes in specialized cells. - id: file:human/ATP6V0B/ATP6V0B-deep-research-cyberian.md title: Cyberian deep research on ATP6V0B function findings: [] - id: file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv title: Proteostasis PN projected annotations for ATP6V0B findings: - statement: PN projection maps ATP6V0B in the V0 lysosomal V-ATPase proton pump component leaf to GO:0046610. supporting_text: "ATP6V0B\t\tAutophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, upstream|Nutrient sensing|V0 lysosomal v-ATPase proton pump component" status: COMPLETE core_functions: - contributes_to_molecular_function: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism directly_involved_in: - id: GO:1902600 label: proton transmembrane transport - id: GO:0007042 label: lysosomal lumen acidification - id: GO:0048388 label: endosomal lumen acidification - id: GO:0061795 label: Golgi lumen acidification locations: - id: GO:0005765 label: lysosomal membrane - id: GO:0010008 label: endosome membrane - id: GO:0000139 label: Golgi membrane in_complex: id: GO:0046610 label: lysosomal proton-transporting V-type ATPase, V0 domain description: ATP6V0B is the V0 c'' proteolipid subunit of the V-ATPase proton pump. It contributes to the complex-level rotary proton-transporting ATPase activity by forming part of the membrane c-ring/proton-transfer sector, rather than independently hydrolyzing ATP. This activity acidifies lysosomal, endosomal and Golgi lumens, supporting endolysosomal protein degradation, trafficking and nutrient-signaling contexts. The PN projection to GO:0046610 is a conservative component-level refinement of existing V0 domain and lysosomal acidification annotations. supported_by: - reference_id: PMID:9653649 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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. - reference_id: PMID:33065002 supporting_text: 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 - reference_id: 'file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_annotations.tsv' supporting_text: "ATP6V0B\t\tAutophagy-Lysosome Pathway|Pre-initiation autophagy signaling|mTORC1 pathway, upstream|Nutrient sensing|V0 lysosomal v-ATPase proton pump component" proposed_new_terms: [] suggested_questions: - question: 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? experts: - V-ATPase biology curators - GO cellular component annotation experts suggested_experiments: - experiment_type: ATP6V0B-specific knockout/rescue in human lysosome pH assays 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. description: 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.