id: P15313 gene_symbol: ATP6V1B1 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9606 label: Homo sapiens description: ATP6V1B1 encodes the B1 isoform of the non-catalytic B subunit of the V1 peripheral domain of the vacuolar H+-ATPase (V-ATPase). Three copies of the B subunit alternate with three catalytic A subunits to form the (AB)3 heterohexameric head of the cytoplasmic V1 complex, which hydrolyzes ATP to drive proton translocation through the membrane-embedded V0 domain. The B subunit binds ATP at non-catalytic nucleotide sites and is essential for proper assembly and activity of the holoenzyme. ATP6V1B1 is the tissue-restricted (kidney, inner ear, epididymis, salivary gland) paralog of the ubiquitously expressed B2 subunit. In the kidney it localizes to the apical plasma membrane of intercalated cells (and other early distal nephron segments), where the plasma-membrane V-ATPase secretes protons into the urine to mediate distal urinary acidification; it is also expressed in the cochlea and endolymphatic sac, where V-ATPase activity maintains endolymph pH. A C-terminal PDZ-binding motif mediates interactions (e.g. with NHERF1 and the bicarbonate transporter SLC4A7) implicated in apical membrane targeting and scaffolding. Loss-of-function mutations cause autosomal recessive distal renal tubular acidosis with progressive sensorineural hearing loss (DRTA2). existing_annotations: - term: id: GO:1902600 label: proton transmembrane transport evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: Core biological process. As the non-catalytic B subunit of the V1 head, ATP6V1B1 is part of the V-ATPase that couples ATP hydrolysis to transmembrane proton transport. Directly supported by functional studies of B1 mutants. action: ACCEPT reason: Proton transmembrane transport is the defining function of the V-ATPase, and B1 is required for the assembly and activity of the pump. Phylogenetic (IBA) transfer is corroborated by direct experimental evidence in B1-expressing cells. supported_by: - reference_id: PMID:16769747 supporting_text: Proton pump-mediated intracellular pH transport was inhibited in GFP-B1M-transfected cells but not in GFP-B1WT cells. reference_section_type: ABSTRACT - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons reference_section_type: DATABASE_ENTRY - term: id: GO:0000221 label: vacuolar proton-transporting V-type ATPase, V1 domain evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: part_of review: summary: Core localization/complex membership. ATP6V1B1 is one of the three B subunits of the (AB)3 hexamer that forms the ATP-hydrolytic V1 domain of the V-ATPase. action: ACCEPT reason: Membership of the B subunit in the V1 domain is established by the cryo-EM structure of the complete human V-ATPase and is consistent across orthologs. supported_by: - reference_id: PMID:33065002 supporting_text: The V 1 ATPase is composed of three copies of subunits A, B, E, and G, and one copy of subunit C, D, F, and H reference_section_type: RESULTS - term: id: GO:0005886 label: plasma membrane evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: Plasma membrane localization. In specialized cells (notably renal intercalated cells), the V-ATPase containing B1 is targeted to the plasma membrane where it acidifies the extracellular space. More specifically captured by the apical plasma membrane annotation below. action: KEEP_AS_NON_CORE reason: Correct but general; the functionally relevant compartment for B1 is the apical plasma membrane (GO:0016324), which is annotated separately with direct evidence. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment reference_section_type: DATABASE_ENTRY - term: id: GO:0016324 label: apical plasma membrane evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: Core localization. The plasma-membrane V-ATPase containing B1 is active at the apical membrane of renal intercalated cells and other distal nephron epithelia, where it secretes protons into the urine. action: ACCEPT reason: Apical plasma membrane localization is directly demonstrated by immunoelectron microscopy and cell-based studies and is the physiologically relevant site of B1 function. supported_by: - reference_id: PMID:29993276 supporting_text: by immunoelectron microscopy the subunit is localized to the apical plasma membrane in the DCT reference_section_type: DISCUSSION - reference_id: PMID:16769747 supporting_text: GFP-B1WT and GFP-B1M are present in the apical membrane and increased with cellular acidification reference_section_type: ABSTRACT - term: id: GO:0007035 label: vacuolar acidification evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: V-ATPase-mediated acidification of intracellular compartments. This is the ancestral/general function of B subunits conserved across eukaryotes. action: ACCEPT reason: Acidification of intracellular compartments is the canonical V-ATPase function; the phylogenetic transfer is appropriate for a B subunit, supported by the UniProt FUNCTION statement. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments reference_section_type: DATABASE_ENTRY - term: id: GO:0000221 label: vacuolar proton-transporting V-type ATPase, V1 domain evidence_type: IEA original_reference_id: GO_REF:0000117 qualifier: part_of review: summary: V1 domain membership (ARBA machine-learning electronic annotation). Redundant with the IBA and IDA annotations of the same term, which carry stronger evidence. action: ACCEPT reason: Correct complex membership; supported by direct structural evidence elsewhere in this review. supported_by: - reference_id: PMID:33065002 supporting_text: The V 1 ATPase is composed of three copies of subunits A, B, E, and G, and one copy of subunit C, D, F, and H reference_section_type: RESULTS - term: id: GO:0005524 label: ATP binding evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: Core molecular function. The B subunit binds ATP at non-catalytic nucleotide sites of the (AB)3 hexamer; UniProt annotates an ATP-binding residue at position 394. action: ACCEPT reason: ATP binding at the non-catalytic site is a conserved property of V-ATPase B subunits and is consistent with the InterPro nucleotide-binding domain assignment and the UniProt ATP-binding feature. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: BINDING 394 reference_section_type: DATABASE_ENTRY - term: id: GO:0016323 label: basolateral plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Basolateral plasma membrane (electronic orthology transfer from mouse/rat orthologs). B1 localization is predominantly apical; basolateral V-ATPase is seen in some intercalated cell subtypes (type B), but for B1 the dominant and functionally relevant localization is apical. action: KEEP_AS_NON_CORE reason: Transferred by orthology from rodent (Q91YH6); plausible in a subset of cells but not the core localization of B1, which is apical. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: Basolateral cell membrane {ECO:0000250|UniProtKB:Q91YH6} reference_section_type: DATABASE_ENTRY - term: id: GO:0016324 label: apical plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: located_in review: summary: Apical plasma membrane (electronic orthology transfer). Redundant with the IDA/IBA apical plasma membrane annotations, which carry direct evidence. action: ACCEPT reason: Correct core localization, corroborated by direct experimental evidence in this review. supported_by: - reference_id: PMID:29993276 supporting_text: by immunoelectron microscopy the subunit is localized to the apical plasma membrane in the DCT reference_section_type: DISCUSSION - term: id: GO:0033180 label: proton-transporting V-type ATPase, V1 domain evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: part_of review: summary: V1 domain membership (general, non-vacuolar-specific parent of GO:0000221). InterPro-based electronic annotation; correct complex membership. action: ACCEPT reason: Correct V1 domain membership; the more specific vacuolar V1 domain term (GO:0000221) is also annotated with direct structural support. supported_by: - reference_id: PMID:33065002 supporting_text: The V 1 ATPase is composed of three copies of subunits A, B, E, and G, and one copy of subunit C, D, F, and H reference_section_type: RESULTS - term: id: GO:0046034 label: ATP metabolic process evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in review: summary: ATP metabolic process (InterPro electronic transfer). The V-ATPase hydrolyzes ATP, but B1 is the non-catalytic subunit; this broad term is a generic property of the holoenzyme rather than an informative B1-specific process. action: MARK_AS_OVER_ANNOTATED reason: Overly broad and derived from the catalytic A-subunit-like domain signature. ATP hydrolysis is performed by the catalytic A subunits; B1 binds but does not hydrolyze ATP. Proton transmembrane transport better captures the relevant process. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: Non-catalytic subunit of the V1 complex of vacuolar(H+)- reference_section_type: DATABASE_ENTRY - term: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables review: summary: Rotational proton-transporting ATPase activity. This is the molecular function of the assembled V-ATPase holoenzyme. As a non-catalytic structural subunit of the ATP-hydrolytic head, B1 contributes to but does not by itself enable this activity; GO commonly annotates obligate subunits with the holoenzyme activity. action: KEEP_AS_NON_CORE reason: The rotational ATPase activity is a property of the holoenzyme; B1 is an essential non-catalytic subunit. Accepting the term as a subunit contribution is reasonable but it is not an autonomous B1 function, so it is retained as non-core. supported_by: - reference_id: PMID:33065002 supporting_text: ATP hydrolysis-driven proton pumps that acidify intracellular vesicles reference_section_type: INTRODUCTION - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: Essential for the proper assembly and activity of V- reference_section_type: DATABASE_ENTRY - term: id: GO:1902600 label: proton transmembrane transport evidence_type: IEA original_reference_id: GO_REF:0000120 qualifier: involved_in review: summary: Core process (electronic orthology transfer). Redundant with the IBA and IMP proton transmembrane transport annotations, which carry direct evidence. action: ACCEPT reason: Correct core function; corroborated by direct experimental evidence elsewhere in this review. supported_by: - reference_id: PMID:16769747 supporting_text: Proton pump-mediated intracellular pH transport was inhibited in GFP-B1M-transfected cells but not in GFP-B1WT cells. reference_section_type: ABSTRACT - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:32814053 qualifier: enables review: summary: Bare "protein binding" from a large-scale neurodegeneration yeast-two-hybrid interactome (partners include ATXN1, TARDBP, WFS1, HSPB1, DNAJB6). Uninformative as a molecular function and not specific to ATP6V1B1 biology. action: MARK_AS_OVER_ANNOTATED reason: "Bare protein binding conveys no specific molecular function. The hits are\ \ high-throughput Y2H interactions; biologically meaningful binding (PDZ→\ NHERF1/SLC4A7 and the AB hexamer assembly) is captured by complex-membership and\ \ domain annotations rather than this generic term." supported_by: - reference_id: PMID:32814053 supporting_text: generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins reference_section_type: ABSTRACT - term: id: GO:0005737 label: cytoplasm evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Cytoplasm (electronic orthology transfer). The V1 domain is cytoplasmic and peripheral, so a cytoplasmic pool of the soluble V1 subassembly is expected, but this is a low-information localization. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but uninformative; the functionally relevant localization is the apical plasma membrane / V1 domain of the assembled pump. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Cytosol (electronic orthology transfer). Same rationale as the cytoplasm annotation; consistent with a soluble cytosolic V1 pool but low information. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain; redundant with the Reactome TAS cytosol annotations and not the core functional site. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005902 label: microvillus evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Microvillus (electronic orthology transfer from rodent ortholog). Consistent with apical brush-border localization in renal epithelia but not directly demonstrated for human B1. action: KEEP_AS_NON_CORE reason: Plausible apical/microvillar localization transferred from the mouse ortholog; a refinement of the apical plasma membrane localization rather than an independent core function. supported_by: - reference_id: PMID:29993276 supporting_text: significant signal was also observed in apical membrane domains of the distal nephron reference_section_type: ABSTRACT - term: id: GO:0015078 label: proton transmembrane transporter activity evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: Proton transmembrane transporter activity (electronic orthology transfer). This activity is mediated by the membrane-embedded V0 proton-conducting subunits; the cytoplasmic B1 subunit does not itself conduct protons. action: KEEP_AS_NON_CORE reason: B1 is a non-membrane, non-catalytic subunit; the transporter activity is a holoenzyme property residing in V0. Retained as a subunit-level contribution rather than an autonomous B1 function. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a membrane integral complex (V0) that translocates protons reference_section_type: DATABASE_ENTRY - term: id: GO:0016020 label: membrane evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Generic "membrane" localization (electronic orthology transfer). Uninformative parent of the more specific apical/basolateral plasma membrane annotations. action: MARK_AS_OVER_ANNOTATED reason: Too general to be useful; the specific membrane localization (apical plasma membrane) is annotated with direct evidence. supported_by: - reference_id: PMID:29993276 supporting_text: by immunoelectron microscopy the subunit is localized to the apical plasma membrane in the DCT reference_section_type: DISCUSSION - term: id: GO:0016328 label: lateral plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: located_in review: summary: Lateral plasma membrane (electronic orthology transfer from rodent ortholog). B1's dominant and functionally relevant localization is apical; lateral/basolateral localization is minor. action: KEEP_AS_NON_CORE reason: Transferred by orthology; not the core localization of B1, which is apical. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: Basolateral cell membrane {ECO:0000250|UniProtKB:Q91YH6} reference_section_type: DATABASE_ENTRY - term: id: GO:0044877 label: protein-containing complex binding evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: enables review: summary: Protein-containing complex binding (electronic orthology transfer). Generic binding term; B1 is an integral constituent of the V-ATPase rather than a binder of an external complex. action: MARK_AS_OVER_ANNOTATED reason: Low-information binding term transferred by orthology; B1's relationship to the V-ATPase is captured by complex-membership (part_of) annotations, which are more informative than a generic complex-binding molecular function. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: Non-catalytic subunit of the V1 complex of vacuolar(H+)- reference_section_type: DATABASE_ENTRY - term: id: GO:0097401 label: synaptic vesicle lumen acidification evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: involved_in review: summary: Synaptic vesicle lumen acidification (electronic orthology transfer). This is a neuronal V-ATPase function attributable to the ubiquitous/brain B2 isoform (ATP6V1B2), not the kidney/inner-ear-restricted B1 isoform. action: MARK_AS_OVER_ANNOTATED reason: B1 is tissue-restricted (kidney, inner ear, epididymis, salivary gland) and is not the neuronal/synaptic isoform; this annotation is an inappropriate orthology transfer better assigned to ATP6V1B2. supported_by: - reference_id: PMID:14585495 supporting_text: Northern blotting detects a 2.2-kb Atp6v1b1 transcript in the kidney and testis, but not other major organs reference_section_type: ABSTRACT - term: id: GO:0098850 label: extrinsic component of synaptic vesicle membrane evidence_type: IEA original_reference_id: GO_REF:0000107 qualifier: is_active_in review: summary: Extrinsic component of synaptic vesicle membrane (electronic orthology transfer). A neuronal localization attributable to the brain B2 isoform, not the kidney/inner-ear B1 isoform. action: MARK_AS_OVER_ANNOTATED reason: Inappropriate orthology transfer; B1 is not the neuronal/synaptic isoform. The relevant V1 localization for B1 is the apical plasma membrane V-ATPase. supported_by: - reference_id: PMID:14585495 supporting_text: Northern blotting detects a 2.2-kb Atp6v1b1 transcript in the kidney and testis, but not other major organs reference_section_type: ABSTRACT - term: id: GO:0016323 label: basolateral plasma membrane evidence_type: ISS original_reference_id: GO_REF:0000024 qualifier: located_in review: summary: Basolateral plasma membrane (ISS from mouse ortholog Q91YH6). Duplicate of the IEA basolateral annotation; B1's core localization is apical. action: KEEP_AS_NON_CORE reason: Sequence-similarity transfer from rodent; plausible in a subset of cells but not the core apical localization of B1. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: Basolateral cell membrane {ECO:0000250|UniProtKB:Q91YH6} reference_section_type: DATABASE_ENTRY - term: id: GO:0097254 label: renal tubular secretion evidence_type: IMP original_reference_id: PMID:12414817 qualifier: involved_in review: summary: Renal tubular secretion of protons. B1-containing apical V-ATPase secretes H+ into the urine in distal nephron cells; loss-of-function mutations impair this and cause distal renal tubular acidosis. action: ACCEPT reason: Strong genetic and physiological evidence that B1 is required for distal nephron acid (proton) secretion into the tubular lumen. supported_by: - reference_id: PMID:12414817 supporting_text: subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA reference_section_type: ABSTRACT - term: id: GO:0000221 label: vacuolar proton-transporting V-type ATPase, V1 domain evidence_type: IDA original_reference_id: PMID:33065002 qualifier: part_of review: summary: Core complex membership with direct structural evidence. Cryo-EM of the complete human V-ATPase places the B subunit in the (AB)3 hexamer of the V1 ATP-hydrolytic head. action: ACCEPT reason: Direct structural (IDA) evidence for B-subunit membership in the V1 domain; this is the strongest evidence for this localization. supported_by: - reference_id: PMID:33065002 supporting_text: The V 1 ATPase is composed of three copies of subunits A, B, E, and G, and one copy of subunit C, D, F, and H reference_section_type: RESULTS - term: id: GO:0016324 label: apical plasma membrane evidence_type: IDA original_reference_id: PMID:16769747 qualifier: located_in review: summary: Core localization with direct evidence. GFP-tagged B1 localizes to the apical membrane of inner medullary collecting duct cells, increasing with cellular acidification. action: ACCEPT reason: Direct experimental demonstration of apical plasma membrane localization in renal epithelial cells. supported_by: - reference_id: PMID:16769747 supporting_text: GFP-B1WT and GFP-B1M are present in the apical membrane and increased with cellular acidification reference_section_type: ABSTRACT - term: id: GO:0016324 label: apical plasma membrane evidence_type: IDA original_reference_id: PMID:29993276 qualifier: located_in review: summary: Core localization with direct evidence. Immunoelectron microscopy in human and rodent kidney localizes the B1 subunit to the apical plasma membrane of intercalated cells and the early distal nephron (TAL, DCT). action: ACCEPT reason: Antibody specificity validated in Atp6v1b1-deficient mice; immuno-EM directly demonstrates apical plasma membrane localization. supported_by: - reference_id: PMID:29993276 supporting_text: by immunoelectron microscopy the subunit is localized to the apical plasma membrane in the DCT reference_section_type: DISCUSSION - term: id: GO:0045851 label: pH reduction evidence_type: IMP original_reference_id: PMID:16769747 qualifier: involved_in review: summary: B1 is required for V-ATPase-mediated lowering of pH (proton accumulation). Disease mutants abolish proton-pump-mediated intracellular pH transport. action: ACCEPT reason: Direct functional evidence that wild-type but not mutant B1 supports proton-pump-mediated acidification. supported_by: - reference_id: PMID:16769747 supporting_text: Proton pump-mediated intracellular pH transport was inhibited in GFP-B1M-transfected cells but not in GFP-B1WT cells. reference_section_type: ABSTRACT - term: id: GO:0070072 label: vacuolar proton-transporting V-type ATPase complex assembly evidence_type: IMP original_reference_id: PMID:16769747 qualifier: involved_in review: summary: Core process. B1 is required for proper assembly of the V-ATPase; disease point mutants fail to form complexes with other subunits. action: ACCEPT reason: Direct functional evidence that wild-type B1 assembles with other H+-ATPase subunits whereas mutants do not, demonstrating a role in complex assembly. supported_by: - reference_id: PMID:16769747 supporting_text: GFP-B1WT formed complexes with other H+ -ATPase subunits (c, H, and E), whereas GFP-B1M did not reference_section_type: ABSTRACT - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: Essential for the proper assembly and activity of V- reference_section_type: DATABASE_ENTRY - term: id: GO:1902600 label: proton transmembrane transport evidence_type: IMP original_reference_id: PMID:16769747 qualifier: involved_in review: summary: Core process with direct functional evidence. Wild-type B1 supports proton-pump-mediated transmembrane pH transport; disease mutants do not. action: ACCEPT reason: Direct mutational evidence that B1 is required for V-ATPase proton transport activity. supported_by: - reference_id: PMID:16769747 supporting_text: Proton pump-mediated intracellular pH transport was inhibited in GFP-B1M-transfected cells but not in GFP-B1WT cells. reference_section_type: ABSTRACT - term: id: GO:0016241 label: regulation of macroautophagy evidence_type: NAS original_reference_id: PMID:22982048 qualifier: involved_in review: summary: NAS annotation from a lipofuscin/senescence study that concerns lysosomal and autophagic activity generally, not ATP6V1B1 specifically. V-ATPase-driven lysosomal acidification supports autophagic flux, but this is a generic V-ATPase property and B1 is the tissue-restricted kidney/inner-ear isoform. action: MARK_AS_OVER_ANNOTATED reason: Weak NAS link; the cited paper does not provide direct evidence that the B1 subunit regulates macroautophagy. Any contribution is an indirect, generic consequence of lysosomal acidification mediated by V-ATPase as a whole. supported_by: - reference_id: PMID:22982048 supporting_text: macroautophagy is responsible for the uptake of lipofuscin into the lysosomes reference_section_type: ABSTRACT - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:23533145 qualifier: located_in review: summary: Detection in prostatic-secretion/urinary exosomes by high-throughput mass-spectrometry proteomics. Reflects presence in secreted vesicles (consistent with apical plasma-membrane V-ATPase shedding) rather than a site of function. action: MARK_AS_OVER_ANNOTATED reason: Proteomic identification in exosomes is a bystander localization, not a functional compartment for the V-ATPase B1 subunit. supported_by: - reference_id: PMID:23533145 supporting_text: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine reference_section_type: TITLE - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19199708 qualifier: located_in review: summary: Detection in parotid gland exosomes by high-throughput proteomics (MudPIT). Bystander localization in secreted vesicles, not a functional compartment. action: MARK_AS_OVER_ANNOTATED reason: Proteomic identification in exosomes does not indicate a site of B1 function. supported_by: - reference_id: PMID:19199708 supporting_text: Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT) reference_section_type: TITLE - term: id: GO:0070062 label: extracellular exosome evidence_type: HDA original_reference_id: PMID:19056867 qualifier: located_in review: summary: Detection in urinary exosomes by large-scale proteomics/phosphoproteomics. Bystander localization in secreted vesicles, not a functional compartment. action: MARK_AS_OVER_ANNOTATED reason: Proteomic identification in exosomes does not indicate a site of B1 function; consistent with apical V-ATPase shedding into urinary vesicles. supported_by: - reference_id: PMID:19056867 supporting_text: Large-scale proteomics and phosphoproteomics of urinary exosomes reference_section_type: TITLE - term: id: GO:0005737 label: cytoplasm evidence_type: ISS original_reference_id: PMID:14585495 qualifier: located_in review: summary: Cytoplasm (ISS from mouse ortholog Q91YH6). Consistent with the cytoplasmic V1 domain but low-information; duplicate of the IEA cytoplasm annotation. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic peripheral V1 domain but not the core functional site. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005902 label: microvillus evidence_type: ISS original_reference_id: PMID:14585495 qualifier: located_in review: summary: Microvillus (ISS from mouse ortholog). Consistent with apical brush-border localization in renal epithelia; a refinement of the apical plasma membrane localization. action: KEEP_AS_NON_CORE reason: Plausible apical/microvillar localization transferred from the mouse ortholog; not an independent core function. supported_by: - reference_id: PMID:29993276 supporting_text: significant signal was also observed in apical membrane domains of the distal nephron reference_section_type: ABSTRACT - term: id: GO:0016323 label: basolateral plasma membrane evidence_type: ISS original_reference_id: PMID:14585495 qualifier: located_in review: summary: Basolateral plasma membrane (ISS from mouse ortholog). Duplicate of the other basolateral annotations; B1's core localization is apical. action: KEEP_AS_NON_CORE reason: Sequence-similarity transfer; plausible minor localization but not the core apical localization of B1. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: Basolateral cell membrane {ECO:0000250|UniProtKB:Q91YH6} reference_section_type: DATABASE_ENTRY - term: id: GO:0016328 label: lateral plasma membrane evidence_type: ISS original_reference_id: PMID:14585495 qualifier: located_in review: summary: Lateral plasma membrane (ISS from mouse ortholog). Duplicate of the IEA lateral annotation; not the core apical localization of B1. action: KEEP_AS_NON_CORE reason: Sequence-similarity transfer; minor localization relative to the dominant apical pool. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: Basolateral cell membrane {ECO:0000250|UniProtKB:Q91YH6} reference_section_type: DATABASE_ENTRY - term: id: GO:0015078 label: proton transmembrane transporter activity evidence_type: ISS original_reference_id: PMID:14585495 qualifier: enables review: summary: Proton transmembrane transporter activity (ISS from mouse ortholog). The proton-conducting activity resides in the membrane-embedded V0 subunits; the cytoplasmic B1 subunit contributes to the holoenzyme but does not itself conduct protons. action: KEEP_AS_NON_CORE reason: Holoenzyme-level activity assigned to a non-membrane, non-catalytic subunit; retained as a subunit contribution rather than an autonomous B1 function. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a membrane integral complex (V0) that translocates protons reference_section_type: DATABASE_ENTRY - term: id: GO:0042472 label: inner ear morphogenesis evidence_type: IMP original_reference_id: PMID:19639346 qualifier: involved_in review: summary: ATP6V1B1 mutations are associated with inner-ear structural abnormalities, notably enlarged vestibular aqueduct (EVA), in patients with dRTA and sensorineural hearing loss. This is a downstream developmental/physiological consequence of impaired endolymph pH homeostasis rather than a direct morphogenetic function. action: KEEP_AS_NON_CORE reason: Disease-phenotype association (EVA) is a downstream consequence of defective V-ATPase-mediated endolymph acidification, not a primary morphogenetic role of the B1 subunit. Retained as a non-core process. supported_by: - reference_id: PMID:19639346 supporting_text: confirms the association of EVA and mutations in the ATP6V1B1 gene reference_section_type: ABSTRACT - term: id: GO:0007605 label: sensory perception of sound evidence_type: IMP original_reference_id: PMID:20622307 qualifier: involved_in review: summary: ATP6V1B1 mutations cause sensorineural hearing loss; the gene is expressed in cochlea and endolymphatic sac, where V-ATPase activity maintains endolymph pH required for normal hearing. action: KEEP_AS_NON_CORE reason: A genuine physiological role (via endolymph pH homeostasis), but it is a tissue-specific downstream consequence of the core proton-transport function rather than a distinct molecular activity. Retained as a non-core process. supported_by: - reference_id: PMID:20622307 supporting_text: a significant percentage of the children with DRTA had sensorineural hearing loss and mutation in ATP6V1B1 gene reference_section_type: ABSTRACT - reference_id: PMID:9916796 supporting_text: implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function reference_section_type: ABSTRACT - term: id: GO:0045851 label: pH reduction evidence_type: IMP original_reference_id: PMID:20622307 qualifier: involved_in review: summary: pH reduction (proton accumulation) via V-ATPase. This clinical-genetics hearing-loss study supports the disease association; pH reduction is the core consequence of B1-dependent proton pumping (also directly demonstrated in PMID:16769747). action: ACCEPT reason: B1-dependent V-ATPase lowers luminal/compartmental pH; the core function is well supported, though this particular reference is a clinical correlation study. supported_by: - reference_id: PMID:16769747 supporting_text: Proton pump-mediated intracellular pH transport was inhibited in GFP-B1M-transfected cells but not in GFP-B1WT cells. reference_section_type: ABSTRACT - term: id: GO:0055074 label: calcium ion homeostasis evidence_type: IMP original_reference_id: PMID:20622307 qualifier: involved_in review: summary: Calcium ion homeostasis. The cited paper is a clinical correlation report on hearing loss in dRTA and provides no direct calcium-homeostasis experiment. Disturbed calcium handling (nephrocalcinosis, decreased urinary calcium solubility) is a downstream consequence of distal renal tubular acidosis, not a direct B1 function. action: MARK_AS_OVER_ANNOTATED reason: Indirect downstream physiological consequence of impaired urinary acidification; not a direct molecular role of the B1 subunit, and the cited reference does not test calcium homeostasis. supported_by: - reference_id: PMID:20622307 supporting_text: a significant percentage of the children with DRTA had sensorineural hearing loss and mutation in ATP6V1B1 gene reference_section_type: ABSTRACT - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-1222516 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-5252133 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-74723 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-917841 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9639286 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640167 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640168 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640175 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9640195 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9645598 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9645608 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0005829 label: cytosol evidence_type: TAS original_reference_id: Reactome:R-HSA-9646468 qualifier: located_in review: summary: Cytosol localization (Reactome TAS). The peripheral V1 domain is cytoplasmic, so cytosol is acceptable but low-information and redundant across many Reactome pathway records. action: KEEP_AS_NON_CORE reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. supported_by: - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: a peripheral complex (V1) that hydrolyzes ATP reference_section_type: DATABASE_ENTRY - term: id: GO:0016324 label: apical plasma membrane evidence_type: IDA original_reference_id: PMID:16928804 qualifier: located_in review: summary: Apical plasma membrane localization. In this study the apical H+-ATPase is used as a marker for co-localization with the RhCG ammonia transporter in A-type intercalated cells; it documents apical H+-ATPase localization but is not a dedicated functional study of B1. action: ACCEPT reason: Consistent with the well-supported apical plasma membrane localization of the renal H+-ATPase; corroborated by the stronger IDA evidence (PMID:16769747, PMID:29993276). supported_by: - reference_id: PMID:16928804 supporting_text: the non-A, non-B cell expresses apical H + -ATPase in conjunction with apical pendrin and apical RhCG reference_section_type: DISCUSSION - term: id: GO:0001503 label: ossification evidence_type: IMP original_reference_id: PMID:16433694 qualifier: involved_in review: summary: The cited paper is a clinical genetics study of dRTA/deafness families that notes rickets/impaired bone among the clinical spectrum. Bone phenotype is a downstream consequence of chronic metabolic acidosis, not a direct role of B1 in ossification. action: MARK_AS_OVER_ANNOTATED reason: Indirect, disease-phenotype-derived annotation; the bone manifestations (rickets) result from systemic acidosis secondary to impaired renal acid secretion, not from a direct molecular function of B1 in bone formation. supported_by: - reference_id: PMID:16433694 supporting_text: The five patients demonstrated the whole clinical spectrum of the disease including death in infancy, failure to thrive, rickets, nephrocalcinosis, nephrolithiasis reference_section_type: ABSTRACT - term: id: GO:0006885 label: regulation of pH evidence_type: IMP original_reference_id: PMID:12414817 qualifier: involved_in review: summary: B1 contributes to regulation of pH through V-ATPase-mediated apical proton secretion; loss-of-function mutations impair urinary acidification and cause distal renal tubular acidosis. action: ACCEPT reason: Strong genetic evidence linking B1 loss of function to impaired control of pH (urinary acidification / systemic acid-base balance). supported_by: - reference_id: PMID:12414817 supporting_text: subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA reference_section_type: ABSTRACT - term: id: GO:0016471 label: vacuolar proton-transporting V-type ATPase complex evidence_type: IMP original_reference_id: PMID:12414817 qualifier: part_of review: summary: Core complex membership. ATP6V1B1 is a subunit of the vacuolar H+-ATPase complex; this is the whole-complex term (parent of the V1 domain term). action: ACCEPT reason: B1 is an integral subunit of the V-ATPase; well supported genetically and structurally. supported_by: - reference_id: PMID:12414817 supporting_text: subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA reference_section_type: ABSTRACT - reference_id: PMID:33065002 supporting_text: The V 1 ATPase is composed of three copies of subunits A, B, E, and G, and one copy of subunit C, D, F, and H reference_section_type: RESULTS - term: id: GO:1902600 label: proton transmembrane transport evidence_type: IMP original_reference_id: PMID:12414817 qualifier: involved_in review: summary: Core process. B1 loss-of-function mutations impair apical proton transport in distal nephron cells, causing dRTA. action: ACCEPT reason: Genetic evidence that B1 is required for V-ATPase proton transport in the distal nephron. supported_by: - reference_id: PMID:12414817 supporting_text: subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA reference_section_type: ABSTRACT - term: id: GO:0006885 label: regulation of pH evidence_type: IMP original_reference_id: PMID:9916796 qualifier: acts_upstream_of_or_within review: summary: Regulation of pH via apical proton secretion. The founding dRTA paper showed ATP6B1 mutations impair distal nephron acid secretion and implicated the gene in endolymph pH homeostasis. action: ACCEPT reason: Genetic evidence that B1 is required for control of pH in the distal nephron and inner ear. supported_by: - reference_id: PMID:9916796 supporting_text: implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function reference_section_type: ABSTRACT - term: id: GO:0007605 label: sensory perception of sound evidence_type: IMP original_reference_id: PMID:9916796 qualifier: acts_upstream_of_or_within review: summary: ATP6B1 mutations cause sensorineural hearing loss; the gene is expressed in cochlea and endolymphatic sac, where V-ATPase maintains endolymph pH required for hearing. A tissue-specific downstream consequence of the core proton-transport function. action: KEEP_AS_NON_CORE reason: Genuine physiological role in hearing via endolymph pH homeostasis, but downstream of the core proton-transport activity rather than a distinct molecular function. supported_by: - reference_id: PMID:9916796 supporting_text: we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac reference_section_type: ABSTRACT core_functions: - description: As the non-catalytic B1 subunit of the V1 domain of the vacuolar H+-ATPase, binds ATP at non-catalytic nucleotide sites and is an essential structural component of the (AB)3 hexameric catalytic head, enabling ATP-hydrolysis-coupled proton transport by the holoenzyme. molecular_function: id: GO:0005524 label: ATP binding supported_by: - reference_id: PMID:33065002 supporting_text: The V 1 ATPase is composed of three copies of subunits A, B, E, and G, and one copy of subunit C, D, F, and H reference_section_type: RESULTS - reference_id: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt supporting_text: Essential for the proper assembly and activity of V- reference_section_type: DATABASE_ENTRY - description: Required for assembly and activity of the vacuolar H+-ATPase, which secretes protons across the apical plasma membrane of renal intercalated cells (and other distal nephron segments) to acidify the urine and maintain systemic acid-base balance. molecular_function: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism locations: - id: GO:0016324 label: apical plasma membrane supported_by: - reference_id: PMID:16769747 supporting_text: Proton pump-mediated intracellular pH transport was inhibited in GFP-B1M-transfected cells but not in GFP-B1WT cells. reference_section_type: ABSTRACT - reference_id: PMID:12414817 supporting_text: subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA reference_section_type: ABSTRACT - description: Maintains endolymph pH in the cochlea and endolymphatic sac, which is required for normal auditory function; loss of function causes sensorineural hearing loss. molecular_function: id: GO:0046961 label: proton-transporting ATPase activity, rotational mechanism supported_by: - reference_id: PMID:9916796 supporting_text: implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function reference_section_type: ABSTRACT proposed_new_terms: [] suggested_questions: - question: Beyond intercalated cells, what is the functional contribution of the apical B1-containing V-ATPase in the thick ascending limb and distal convoluted tubule to acid-base handling? - question: Does the C-terminal PDZ-binding motif (NHERF1/SLC4A7 interaction) regulate apical membrane targeting or stability of the B1-containing V-ATPase in vivo? - question: Are the salt-losing and hypokalemic features of B1-related dRTA explained by B1 expression outside type A intercalated cells? suggested_experiments: - description: Cell-type-specific (intercalated vs TAL/DCT) conditional Atp6v1b1 knockout in mouse to dissect the contribution of each segment to urinary acidification. - description: Cryo-EM or biochemical reconstitution of a B1-containing human V-ATPase to confirm the B1 paralog occupies the canonical B-subunit position and characterize its non-catalytic nucleotide site. - description: Structure-function analysis of the PDZ-binding motif (e.g. L513G knock-in) to test its role in apical targeting and in the renal/auditory phenotypes. 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:0000107 title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara findings: [] - id: GO_REF:0000117 title: Electronic Gene Ontology annotations created by ARBA machine learning models findings: [] - id: GO_REF:0000120 title: Combined Automated Annotation using Multiple IEA Methods findings: [] - id: PMID:12414817 title: Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss. findings: [] - id: PMID:14585495 title: Molecular cloning and characterization of Atp6v1b1, the murine vacuolar H+ -ATPase B1-subunit. findings: [] - id: PMID:16433694 title: Molecular investigation and long-term clinical progress in Greek Cypriot families with recessive distal renal tubular acidosis and sensorineural deafness due to mutations in the ATP6V1B1 gene. findings: [] - id: PMID:16769747 title: Vacuolar H+ -ATPase B1 subunit mutations that cause inherited distal renal tubular acidosis affect proton pump assembly and trafficking in inner medullary collecting duct cells. findings: [] - id: PMID:16928804 title: Expression of the ammonia transporter, rh C glycoprotein, in normal and neoplastic human kidney. findings: [] - id: PMID:19056867 title: Large-scale proteomics and phosphoproteomics of urinary exosomes. findings: [] - id: PMID:19199708 title: Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). findings: [] - id: PMID:19639346 title: 'Inner ear abnormalities in four patients with dRTA and SNHL: clinical and genetic heterogeneity.' findings: [] - id: PMID:20622307 title: 'Distal renal tubular acidosis and its relationship with hearing loss in children: preliminary report.' findings: [] - id: PMID:22982048 title: Lipofuscin is formed independently of macroautophagy and lysosomal activity in stress-induced prematurely senescent human fibroblasts. findings: [] - id: PMID:23533145 title: In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. findings: [] - id: PMID:29993276 title: H(+)-ATPase B1 subunit localizes to thick ascending limb and distal convoluted tubule of rodent and human kidney. findings: [] - id: PMID:32814053 title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains. findings: [] - id: PMID:33065002 title: Structures of a Complete Human V-ATPase Reveal Mechanisms of Its Assembly. findings: [] - id: PMID:9916796 title: Mutations in the gene encoding B1 subunit of H+-ATPase cause renal tubular acidosis with sensorineural deafness. findings: [] - id: Reactome:R-HSA-1222516 title: Intraphagosomal pH is lowered to 5 by V-ATPase findings: [] - id: Reactome:R-HSA-5252133 title: ATP6AP1 binds V-ATPase findings: [] - id: Reactome:R-HSA-74723 title: Endosome acidification findings: [] - 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: [] - id: Reactome:R-HSA-9646468 title: mTORC1 binds RHEB:GTP findings: []