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).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:1902600 proton transmembrane transport | IBA GO_REF:0000033 | ACCEPT | 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. 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. Supporting Evidence: PMID:16769747 Proton pump-mediated intracellular pH transport was inhibited in GFP-B1M-transfected cells but not in GFP-B1WT cells. file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons |
| GO:0000221 vacuolar proton-transporting V-type ATPase, V1 domain | IBA GO_REF:0000033 | ACCEPT | 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. 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. Supporting Evidence: PMID:33065002 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 |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | KEEP AS NON CORE | 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. Reason: Correct but general; the functionally relevant compartment for B1 is the apical plasma membrane (GO:0016324), which is annotated separately with direct evidence. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment |
| GO:0016324 apical plasma membrane | IBA GO_REF:0000033 | ACCEPT | 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. Reason: Apical plasma membrane localization is directly demonstrated by immunoelectron microscopy and cell-based studies and is the physiologically relevant site of B1 function. Supporting Evidence: PMID:29993276 by immunoelectron microscopy the subunit is localized to the apical plasma membrane in the DCT PMID:16769747 GFP-B1WT and GFP-B1M are present in the apical membrane and increased with cellular acidification |
| GO:0007035 vacuolar acidification | IBA GO_REF:0000033 | ACCEPT | Summary: V-ATPase-mediated acidification of intracellular compartments. This is the ancestral/general function of B subunits conserved across eukaryotes. 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. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments |
| GO:0000221 vacuolar proton-transporting V-type ATPase, V1 domain | IEA GO_REF:0000117 | ACCEPT | Summary: V1 domain membership (ARBA machine-learning electronic annotation). Redundant with the IBA and IDA annotations of the same term, which carry stronger evidence. Reason: Correct complex membership; supported by direct structural evidence elsewhere in this review. Supporting Evidence: PMID:33065002 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 |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | 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. 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. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt BINDING 394 |
| GO:0016323 basolateral plasma membrane | IEA GO_REF:0000120 | KEEP AS NON CORE | 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. Reason: Transferred by orthology from rodent (Q91YH6); plausible in a subset of cells but not the core localization of B1, which is apical. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt Basolateral cell membrane {ECO:0000250|UniProtKB:Q91YH6} |
| GO:0016324 apical plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Apical plasma membrane (electronic orthology transfer). Redundant with the IDA/IBA apical plasma membrane annotations, which carry direct evidence. Reason: Correct core localization, corroborated by direct experimental evidence in this review. Supporting Evidence: PMID:29993276 by immunoelectron microscopy the subunit is localized to the apical plasma membrane in the DCT |
| GO:0033180 proton-transporting V-type ATPase, V1 domain | IEA GO_REF:0000002 | ACCEPT | Summary: V1 domain membership (general, non-vacuolar-specific parent of GO:0000221). InterPro-based electronic annotation; correct complex membership. Reason: Correct V1 domain membership; the more specific vacuolar V1 domain term (GO:0000221) is also annotated with direct structural support. Supporting Evidence: PMID:33065002 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 |
| GO:0046034 ATP metabolic process | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | 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. 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. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt Non-catalytic subunit of the V1 complex of vacuolar(H+)- |
| GO:0046961 proton-transporting ATPase activity, rotational mechanism | IEA GO_REF:0000002 | KEEP AS NON CORE | 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. 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. Supporting Evidence: PMID:33065002 ATP hydrolysis-driven proton pumps that acidify intracellular vesicles file:human/ATP6V1B1/ATP6V1B1-uniprot.txt Essential for the proper assembly and activity of V- |
| GO:1902600 proton transmembrane transport | IEA GO_REF:0000120 | ACCEPT | Summary: Core process (electronic orthology transfer). Redundant with the IBA and IMP proton transmembrane transport annotations, which carry direct evidence. Reason: Correct core function; corroborated by direct experimental evidence elsewhere in this review. Supporting Evidence: PMID:16769747 Proton pump-mediated intracellular pH transport was inhibited in GFP-B1M-transfected cells but not in GFP-B1WT cells. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | 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. 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. Supporting Evidence: PMID:32814053 generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but uninformative; the functionally relevant localization is the apical plasma membrane / V1 domain of the assembled pump. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytosol (electronic orthology transfer). Same rationale as the cytoplasm annotation; consistent with a soluble cytosolic V1 pool but low information. Reason: Consistent with the cytoplasmic V1 domain; redundant with the Reactome TAS cytosol annotations and not the core functional site. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005902 microvillus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Microvillus (electronic orthology transfer from rodent ortholog). Consistent with apical brush-border localization in renal epithelia but not directly demonstrated for human B1. Reason: Plausible apical/microvillar localization transferred from the mouse ortholog; a refinement of the apical plasma membrane localization rather than an independent core function. Supporting Evidence: PMID:29993276 significant signal was also observed in apical membrane domains of the distal nephron |
| GO:0015078 proton transmembrane transporter activity | IEA GO_REF:0000107 | KEEP AS NON CORE | 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. 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. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a membrane integral complex (V0) that translocates protons |
| GO:0016020 membrane | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic "membrane" localization (electronic orthology transfer). Uninformative parent of the more specific apical/basolateral plasma membrane annotations. Reason: Too general to be useful; the specific membrane localization (apical plasma membrane) is annotated with direct evidence. Supporting Evidence: PMID:29993276 by immunoelectron microscopy the subunit is localized to the apical plasma membrane in the DCT |
| GO:0016328 lateral plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Lateral plasma membrane (electronic orthology transfer from rodent ortholog). B1's dominant and functionally relevant localization is apical; lateral/basolateral localization is minor. Reason: Transferred by orthology; not the core localization of B1, which is apical. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt Basolateral cell membrane {ECO:0000250|UniProtKB:Q91YH6} |
| GO:0044877 protein-containing complex binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | 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. 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. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt Non-catalytic subunit of the V1 complex of vacuolar(H+)- |
| GO:0097401 synaptic vesicle lumen acidification | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | 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. 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. Supporting Evidence: PMID:14585495 Northern blotting detects a 2.2-kb Atp6v1b1 transcript in the kidney and testis, but not other major organs |
| GO:0098850 extrinsic component of synaptic vesicle membrane | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | 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. Reason: Inappropriate orthology transfer; B1 is not the neuronal/synaptic isoform. The relevant V1 localization for B1 is the apical plasma membrane V-ATPase. Supporting Evidence: PMID:14585495 Northern blotting detects a 2.2-kb Atp6v1b1 transcript in the kidney and testis, but not other major organs |
| GO:0016323 basolateral plasma membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Basolateral plasma membrane (ISS from mouse ortholog Q91YH6). Duplicate of the IEA basolateral annotation; B1's core localization is apical. Reason: Sequence-similarity transfer from rodent; plausible in a subset of cells but not the core apical localization of B1. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt Basolateral cell membrane {ECO:0000250|UniProtKB:Q91YH6} |
| GO:0097254 renal tubular secretion | IMP PMID:12414817 Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive... | ACCEPT | 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. Reason: Strong genetic and physiological evidence that B1 is required for distal nephron acid (proton) secretion into the tubular lumen. Supporting Evidence: PMID:12414817 subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA |
| GO:0000221 vacuolar proton-transporting V-type ATPase, V1 domain | IDA PMID:33065002 Structures of a Complete Human V-ATPase Reveal Mechanisms of... | ACCEPT | Summary: 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. Reason: Direct structural (IDA) evidence for B-subunit membership in the V1 domain; this is the strongest evidence for this localization. Supporting Evidence: PMID:33065002 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 |
| GO:0016324 apical plasma membrane | IDA PMID:16769747 Vacuolar H+ -ATPase B1 subunit mutations that cause inherite... | ACCEPT | Summary: Core localization with direct evidence. GFP-tagged B1 localizes to the apical membrane of inner medullary collecting duct cells, increasing with cellular acidification. Reason: Direct experimental demonstration of apical plasma membrane localization in renal epithelial cells. Supporting Evidence: PMID:16769747 GFP-B1WT and GFP-B1M are present in the apical membrane and increased with cellular acidification |
| GO:0016324 apical plasma membrane | IDA PMID:29993276 H(+)-ATPase B1 subunit localizes to thick ascending limb and... | ACCEPT | 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). Reason: Antibody specificity validated in Atp6v1b1-deficient mice; immuno-EM directly demonstrates apical plasma membrane localization. Supporting Evidence: PMID:29993276 by immunoelectron microscopy the subunit is localized to the apical plasma membrane in the DCT |
| GO:0045851 pH reduction | IMP PMID:16769747 Vacuolar H+ -ATPase B1 subunit mutations that cause inherite... | ACCEPT | Summary: B1 is required for V-ATPase-mediated lowering of pH (proton accumulation). Disease mutants abolish proton-pump-mediated intracellular pH transport. Reason: Direct functional evidence that wild-type but not mutant B1 supports proton-pump-mediated acidification. Supporting Evidence: PMID:16769747 Proton pump-mediated intracellular pH transport was inhibited in GFP-B1M-transfected cells but not in GFP-B1WT cells. |
| GO:0070072 vacuolar proton-transporting V-type ATPase complex assembly | IMP PMID:16769747 Vacuolar H+ -ATPase B1 subunit mutations that cause inherite... | ACCEPT | Summary: Core process. B1 is required for proper assembly of the V-ATPase; disease point mutants fail to form complexes with other subunits. Reason: Direct functional evidence that wild-type B1 assembles with other H+-ATPase subunits whereas mutants do not, demonstrating a role in complex assembly. Supporting Evidence: PMID:16769747 GFP-B1WT formed complexes with other H+ -ATPase subunits (c, H, and E), whereas GFP-B1M did not file:human/ATP6V1B1/ATP6V1B1-uniprot.txt Essential for the proper assembly and activity of V- |
| GO:1902600 proton transmembrane transport | IMP PMID:16769747 Vacuolar H+ -ATPase B1 subunit mutations that cause inherite... | ACCEPT | Summary: Core process with direct functional evidence. Wild-type B1 supports proton-pump-mediated transmembrane pH transport; disease mutants do not. Reason: Direct mutational evidence that B1 is required for V-ATPase proton transport activity. Supporting Evidence: PMID:16769747 Proton pump-mediated intracellular pH transport was inhibited in GFP-B1M-transfected cells but not in GFP-B1WT cells. |
| GO:0016241 regulation of macroautophagy | NAS PMID:22982048 Lipofuscin is formed independently of macroautophagy and lys... | MARK AS OVER ANNOTATED | 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. 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. Supporting Evidence: PMID:22982048 macroautophagy is responsible for the uptake of lipofuscin into the lysosomes |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | MARK AS OVER ANNOTATED | 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. Reason: Proteomic identification in exosomes is a bystander localization, not a functional compartment for the V-ATPase B1 subunit. Supporting Evidence: PMID:23533145 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | MARK AS OVER ANNOTATED | Summary: Detection in parotid gland exosomes by high-throughput proteomics (MudPIT). Bystander localization in secreted vesicles, not a functional compartment. Reason: Proteomic identification in exosomes does not indicate a site of B1 function. Supporting Evidence: PMID:19199708 Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT) |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | MARK AS OVER ANNOTATED | Summary: Detection in urinary exosomes by large-scale proteomics/phosphoproteomics. Bystander localization in secreted vesicles, not a functional compartment. Reason: Proteomic identification in exosomes does not indicate a site of B1 function; consistent with apical V-ATPase shedding into urinary vesicles. Supporting Evidence: PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exosomes |
| GO:0005737 cytoplasm | ISS PMID:14585495 Molecular cloning and characterization of Atp6v1b1, the muri... | KEEP AS NON CORE | Summary: Cytoplasm (ISS from mouse ortholog Q91YH6). Consistent with the cytoplasmic V1 domain but low-information; duplicate of the IEA cytoplasm annotation. Reason: Consistent with the cytoplasmic peripheral V1 domain but not the core functional site. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005902 microvillus | ISS PMID:14585495 Molecular cloning and characterization of Atp6v1b1, the muri... | KEEP AS NON CORE | Summary: Microvillus (ISS from mouse ortholog). Consistent with apical brush-border localization in renal epithelia; a refinement of the apical plasma membrane localization. Reason: Plausible apical/microvillar localization transferred from the mouse ortholog; not an independent core function. Supporting Evidence: PMID:29993276 significant signal was also observed in apical membrane domains of the distal nephron |
| GO:0016323 basolateral plasma membrane | ISS PMID:14585495 Molecular cloning and characterization of Atp6v1b1, the muri... | KEEP AS NON CORE | Summary: Basolateral plasma membrane (ISS from mouse ortholog). Duplicate of the other basolateral annotations; B1's core localization is apical. Reason: Sequence-similarity transfer; plausible minor localization but not the core apical localization of B1. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt Basolateral cell membrane {ECO:0000250|UniProtKB:Q91YH6} |
| GO:0016328 lateral plasma membrane | ISS PMID:14585495 Molecular cloning and characterization of Atp6v1b1, the muri... | KEEP AS NON CORE | Summary: Lateral plasma membrane (ISS from mouse ortholog). Duplicate of the IEA lateral annotation; not the core apical localization of B1. Reason: Sequence-similarity transfer; minor localization relative to the dominant apical pool. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt Basolateral cell membrane {ECO:0000250|UniProtKB:Q91YH6} |
| GO:0015078 proton transmembrane transporter activity | ISS PMID:14585495 Molecular cloning and characterization of Atp6v1b1, the muri... | KEEP AS NON CORE | 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. Reason: Holoenzyme-level activity assigned to a non-membrane, non-catalytic subunit; retained as a subunit contribution rather than an autonomous B1 function. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a membrane integral complex (V0) that translocates protons |
| GO:0042472 inner ear morphogenesis | IMP PMID:19639346 Inner ear abnormalities in four patients with dRTA and SNHL:... | KEEP AS NON CORE | 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. 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. Supporting Evidence: PMID:19639346 confirms the association of EVA and mutations in the ATP6V1B1 gene |
| GO:0007605 sensory perception of sound | IMP PMID:20622307 Distal renal tubular acidosis and its relationship with hear... | KEEP AS NON CORE | 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. 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. Supporting Evidence: PMID:20622307 a significant percentage of the children with DRTA had sensorineural hearing loss and mutation in ATP6V1B1 gene PMID:9916796 implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function |
| GO:0045851 pH reduction | IMP PMID:20622307 Distal renal tubular acidosis and its relationship with hear... | ACCEPT | 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). Reason: B1-dependent V-ATPase lowers luminal/compartmental pH; the core function is well supported, though this particular reference is a clinical correlation study. Supporting Evidence: PMID:16769747 Proton pump-mediated intracellular pH transport was inhibited in GFP-B1M-transfected cells but not in GFP-B1WT cells. |
| GO:0055074 calcium ion homeostasis | IMP PMID:20622307 Distal renal tubular acidosis and its relationship with hear... | MARK AS OVER ANNOTATED | 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. 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. Supporting Evidence: PMID:20622307 a significant percentage of the children with DRTA had sensorineural hearing loss and mutation in ATP6V1B1 gene |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1222516 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5252133 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-74723 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-917841 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9639286 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9640167 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9640168 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9640175 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9640195 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645598 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9645608 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9646468 | KEEP AS NON CORE | 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. Reason: Consistent with the cytoplasmic V1 domain but not the core functional site; redundant with other cytosol/cytoplasm annotations. Supporting Evidence: file:human/ATP6V1B1/ATP6V1B1-uniprot.txt a peripheral complex (V1) that hydrolyzes ATP |
| GO:0016324 apical plasma membrane | IDA PMID:16928804 Expression of the ammonia transporter, rh C glycoprotein, in... | ACCEPT | 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. 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). Supporting Evidence: PMID:16928804 the non-A, non-B cell expresses apical H + -ATPase in conjunction with apical pendrin and apical RhCG |
| GO:0001503 ossification | IMP PMID:16433694 Molecular investigation and long-term clinical progress in G... | MARK AS OVER ANNOTATED | 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. 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. Supporting Evidence: PMID:16433694 The five patients demonstrated the whole clinical spectrum of the disease including death in infancy, failure to thrive, rickets, nephrocalcinosis, nephrolithiasis |
| GO:0006885 regulation of pH | IMP PMID:12414817 Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive... | ACCEPT | 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. Reason: Strong genetic evidence linking B1 loss of function to impaired control of pH (urinary acidification / systemic acid-base balance). Supporting Evidence: PMID:12414817 subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA |
| GO:0016471 vacuolar proton-transporting V-type ATPase complex | IMP PMID:12414817 Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive... | ACCEPT | 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). Reason: B1 is an integral subunit of the V-ATPase; well supported genetically and structurally. Supporting Evidence: PMID:12414817 subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA PMID:33065002 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 |
| GO:1902600 proton transmembrane transport | IMP PMID:12414817 Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive... | ACCEPT | Summary: Core process. B1 loss-of-function mutations impair apical proton transport in distal nephron cells, causing dRTA. Reason: Genetic evidence that B1 is required for V-ATPase proton transport in the distal nephron. Supporting Evidence: PMID:12414817 subunits of the renal alpha-intercalated cell's apical H(+)-ATPase that cause rdRTA |
| GO:0006885 regulation of pH | IMP PMID:9916796 Mutations in the gene encoding B1 subunit of H+-ATPase cause... | ACCEPT | 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. Reason: Genetic evidence that B1 is required for control of pH in the distal nephron and inner ear. Supporting Evidence: PMID:9916796 implicate ATP6B1 in endolymph pH homeostasis and in normal auditory function |
| GO:0007605 sensory perception of sound | IMP PMID:9916796 Mutations in the gene encoding B1 subunit of H+-ATPase cause... | KEEP AS NON CORE | 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. Reason: Genuine physiological role in hearing via endolymph pH homeostasis, but downstream of the core proton-transport activity rather than a distinct molecular function. Supporting Evidence: PMID:9916796 we demonstrate expression of ATP6B1 in cochlea and endolymphatic sac |
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Download this section (compressed HTML)Q: 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?
Q: Does the C-terminal PDZ-binding motif (NHERF1/SLC4A7 interaction) regulate apical membrane targeting or stability of the B1-containing V-ATPase in vivo?
Q: Are the salt-losing and hypokalemic features of B1-related dRTA explained by B1 expression outside type A intercalated cells?
Experiment: Cell-type-specific (intercalated vs TAL/DCT) conditional Atp6v1b1 knockout in mouse to dissect the contribution of each segment to urinary acidification.
Experiment: 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.
Experiment: 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.
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