Affinage

ATP6AP1

V-type proton ATPase subunit S1 · UniProt Q15904

Round 2 corrected
Length
470 aa
Mass
52.0 kDa
Annotated
2026-04-28
130 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP6AP1 (Ac45) is an accessory subunit of the V0 sector of the vacuolar H⁺-ATPase that functions as a V-ATPase assembly factor, trafficking guide, and signaling integrator at endomembranes. Synthesized as an N-glycosylated precursor, it undergoes furin-mediated proteolytic cleavage in the secretory pathway; the processed C-terminal form directs V-ATPase through the secretory pathway to regulate organellar and extracellular acidification, Ca²⁺-dependent exocytosis in neuroendocrine cells, and lysosomal trafficking via Rab7 interaction in osteoclasts (PMID:18713856, PMID:20702583, PMID:22736765, PMID:22467241). ATP6AP1 additionally acts as an unconventional guanine nucleotide exchange factor for Rheb, coupling V-ATPase-associated lysosomal signaling to mTORC1 activation through a conserved tri-aspartate motif in its cytoplasmic tail (PMID:38448650). Hemizygous missense mutations in ATP6AP1 cause an X-linked syndrome of immunodeficiency with hypogammaglobulinemia, hepatopathy, and neurocognitive abnormalities, while somatic inactivating mutations drive granular cell tumor oncogenesis (PMID:27231034, PMID:30166553).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 High

    Establishing ATP6AP1 as a V-ATPase subunit resolved the identity of chromaffin granule glycoprotein IV and placed it within the V0 membrane sector, opening the question of what regulatory role an accessory subunit plays in proton pump function.

    Evidence Biochemical purification, amino acid sequencing, and Blue Native electrophoresis of bovine chromaffin granule membranes

    PMID:8961292

    Open questions at the time
    • No functional assay for pump activity modulation
    • Cleavage site and protease not yet defined
    • Mechanism of V0 incorporation unknown
  2. 1999 High

    Demonstrating that Ac45 is synthesized as a glycosylated precursor cleaved to a mature form enriched in neuroendocrine tissues established a biosynthetic framework and suggested that proteolytic processing activates the protein for its V-ATPase regulatory role.

    Evidence Biosynthetic pulse-chase labeling, deglycosylation, and immunocytochemistry in Xenopus pituitary; complemented by pharmacological dissection in 2002

    PMID:10336633 PMID:11952786

    Open questions at the time
    • Identity of the protease responsible for cleavage unknown
    • Functional consequence of cleavage not yet tested
  3. 2002 High

    Gene targeting showed that Ac45 is essential for mouse embryonic development, establishing it as a non-redundant gene required for fundamental cellular viability rather than a dispensable accessory factor.

    Evidence Homologous recombination knockout in ES cells with blastocyst injection chimera analysis

    PMID:11989824

    Open questions at the time
    • Mechanism of embryonic lethality uncharacterized
    • Tissue-specific requirements not dissected
    • No conditional knockout to separate early vs. late functions
  4. 2008 High

    Two advances established the mechanistic basis of Ac45 function: transgenic overexpression showed Ac45 guides V-ATPase to the plasma membrane and enhances Ca²⁺-dependent exocytosis, while identification of furin as the activating protease linked cleavage to granule acidification and regulated secretion in pancreatic beta cells.

    Evidence Transgenic Xenopus melanotrope cells with EM, secretion assays; conditional furin knockout mice with ex vivo cleavage assay and siRNA knockdown in insulinoma cells

    PMID:18657579 PMID:18713856

    Open questions at the time
    • Structural basis of furin recognition site not resolved
    • Whether other proprotein convertases can substitute for furin in vivo
  5. 2010 High

    Direct measurement of granular pH established Ac45 as the first identified positive regulator of V-ATPase proton pumping, showing it controls differential prohormone processing by tuning compartmental acidity.

    Evidence Acidotrophic dye assays and bafilomycin sensitivity in transgenic Xenopus melanotrope cells with immunoblot of POMC processing intermediates

    PMID:20702583

    Open questions at the time
    • Whether Ac45 alters V-ATPase catalytic rate vs. surface density not distinguished
    • No reconstituted in vitro pump activity assay
  6. 2012 High

    Domain mapping revealed that furin cleavage liberates the processed form for efficient secretory pathway transit, and that the cytoplasmic C-tail is specifically required for V-ATPase recruitment and regulation of exocytosis, defining the minimal functional architecture of Ac45.

    Evidence Systematic deletion mutagenesis of Ac45 domains in transgenic Xenopus melanotrope cells with localization and secretion readouts

    PMID:22736765

    Open questions at the time
    • Binding partners of the C-tail not identified
    • Structural basis of C-tail–V-ATPase interaction unknown
  7. 2012 High

    Extending Ac45 function to osteoclasts showed it is required for extracellular acidification, bone resorption, and cathepsin K exocytosis via interaction with Rab7, demonstrating a lysosomal trafficking guidance role beyond neuroendocrine secretion.

    Evidence siRNA knockdown in osteoclasts with bone resorption, extracellular acidification, lysosomal trafficking, and cathepsin K exocytosis assays; co-immunoprecipitation with Rab7

    PMID:22467241

    Open questions at the time
    • Direct vs. indirect nature of Rab7 interaction not resolved
    • No structural data on Ac45–Rab7 interface
    • Rab7 GEF/GAP mechanism not tested
  8. 2015 Medium

    In vivo AAV-mediated knockdown of Ac45 in a periodontitis model validated the osteoclast findings and revealed additional anti-inflammatory effects, suggesting broader roles in immune cell regulation at sites of bone erosion.

    Evidence AAV-shRNA knockdown in mouse periodontitis model with histology, immunochemistry, cytokine profiling, and in vitro osteoclast assays

    PMID:25952706

    Open questions at the time
    • Single-lab study not independently replicated
    • Inflammatory effects may be secondary to impaired osteoclast function rather than direct immune regulation
    • Off-target AAV effects not fully excluded
  9. 2016 High

    Identification of ATP6AP1 as the human ortholog of yeast Voa1 and discovery that hemizygous missense mutations cause X-linked immunodeficiency with hepatopathy and neurocognitive disease unified the V-ATPase assembly function with human pathology and revealed tissue-specific Ac45 isoforms.

    Evidence Whole-exome sequencing of 11 male patients, yeast Voa1 complementation assay with wild-type vs. mutant Ac45, Western blot of patient tissues

    PMID:27231034

    Open questions at the time
    • Structural basis of disease-causing mutations not determined
    • Tissue-specific isoform generation mechanism unknown
    • No mouse model recapitulating the full human phenotype
  10. 2018 High

    Discovery of recurrent somatic inactivating mutations in ATP6AP1 in granular cell tumors, validated by silencing-induced impaired acidification and oncogenic phenotypes, established ATP6AP1 as a tumor suppressor whose loss drives a specific tumor type.

    Evidence Whole-exome and targeted sequencing of GCTs; siRNA knockdown with lysosomal acidification, endosomal redistribution, and proliferation/migration/invasion assays

    PMID:30166553

    Open questions at the time
    • Mechanism linking impaired acidification to oncogenic transformation not defined
    • No in vivo tumor model with Ac45 loss
    • Relationship between GCT mutations and V-ATPase assembly not tested
  11. 2022 High

    SARS-CoV-2 NSP6 was shown to directly bind ATP6AP1 and inhibit its cleavage-mediated activation, impairing lysosome acidification and triggering NLRP3-dependent pyroptosis—revealing Ac45 as a viral target for immune evasion.

    Evidence Co-immunoprecipitation, lysosomal acidification and autophagic flux assays, caspase-1 activation, live SARS-CoV-2 infection, and pharmacological rescue in lung epithelial cells

    PMID:34997207

    Open questions at the time
    • Structural interface of NSP6–ATP6AP1 interaction not resolved
    • Whether other coronaviruses exploit the same mechanism is untested
    • Relative contribution of ATP6AP1 vs. other NSP6 targets to COVID-19 pathology unclear
  12. 2024 High

    Identification of ATP6AP1 as an unconventional GEF for Rheb via its conserved C-terminal tri-aspartate motif provided a direct mechanistic link between V-ATPase-associated lysosomal signaling and mTORC1 activation, filling a long-standing gap in Rheb regulation.

    Evidence PhastID proximity labeling, co-immunoprecipitation, in vitro GEF assay, C-tail mutagenesis, cancer cell proliferation and migration assays

    PMID:38448650

    Open questions at the time
    • Structural basis of Ac45–Rheb GEF activity not resolved
    • Whether V-ATPase proton pumping is coupled to or independent of the GEF function
    • In vivo genetic validation of the GEF function in animal models pending

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of the ATP6AP1 C-tail's dual function in V-ATPase recruitment and Rheb GEF activity, the mechanism generating tissue-specific Ac45 isoforms, and whether the V-ATPase assembly and mTORC1 signaling roles are coordinated or independent.
  • No high-resolution structure of Ac45 in complex with V0 or Rheb
  • Tissue-specific isoform biogenesis mechanism unknown
  • Coupling between proton pump regulation and mTORC1 GEF function untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0005198 structural molecule activity 2 GO:0060090 molecular adaptor activity 2 GO:0060089 molecular transducer activity 1
Localization
GO:0005764 lysosome 3 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3 GO:0005783 endoplasmic reticulum 2 GO:0005794 Golgi apparatus 2
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1643685 Disease 2 R-HSA-168256 Immune System 2 R-HSA-162582 Signal Transduction 1 R-HSA-9612973 Autophagy 1
Partners
ATP6V0A1FURINRAB7ARHEB
Complex memberships
V-ATPase V0 sector

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 ATP6AP1 (Ac45) was identified as chromaffin granule membrane glycoprotein IV and confirmed to be a membrane-integral subunit of the granule V-ATPase. Amino acid sequencing showed that Ac45/glycoprotein IV is derived from a larger precursor by removal of a 246-amino acid N-terminal sequence, yielding a mature ~29 kDa polypeptide. Blue Native electrophoresis confirmed its incorporation into the membrane sector (V0) of the V-ATPase. Membrane fractionation, lectin affinity chromatography, amino acid sequencing, enzymatic deglycosylation, Blue Native electrophoresis Neuroscience letters High 8961292
1998 ATP6AP1 (Ac45) localizes to the plasma membrane and a juxtanuclear vacuolar compartment, and is rapidly retrieved from the cell surface via endocytosis. The 26-residue cytoplasmic tail of Ac45 contains an autonomous internalization signal distinct from canonical tyrosine- or di-leucine-based motifs; multiple sites in the membrane-distal region of the tail are required for internalization. Steady-state immunolabeling, antibody internalization experiments, expression of carboxy-terminally truncated Ac45 mutants, immunolocalization in transfected CV-1 fibroblasts Journal of cell science High 9739073
1999 Xenopus ATP6AP1 (Ac45) is synthesized as an N-glycosylated ~60 kDa precursor that is intracellularly cleaved to a ~40 kDa C-terminal product, with the processed form predominating in neuroendocrine tissues. Ac45 is highly expressed in biosynthetically active melanotrope cells of the intermediate pituitary, consistent with a role in acidification of neuroendocrine secretory granules. Western blot, biosynthetic labeling, deglycosylation, immunocytochemistry in Xenopus pituitary European journal of biochemistry High 10336633
2002 Targeted disruption of the Ac45 (ATP6AP1) gene in mouse embryonic stem cells produced Ac45 null mutant (−/Y) ES cells. Injection into blastocysts led to severely impaired development, with only one low-chimeric female born that died at 6 weeks; no late abortions were detected. Results indicate that Ac45 null ES cells disrupt normal blastocyst development, consistent with an essential role for V-ATPase in early embryogenesis. Gene targeting by homologous recombination in ES cells, blastocyst injection, chimera analysis Molecular membrane biology High 11989824
2002 Newly synthesized ATP6AP1 (Ac45) is N-glycosylated to ~62 kDa and ~64 kDa forms; glycan trimming produces ~61 and ~63 kDa forms that are cleaved to a C-terminal ~42–44 kDa fragment and a previously undetected ~22 kDa N-terminal fragment. Cleavage occurs early in the secretory pathway (brefeldin A- and monensin-insensitive), has a half-life of 4–6 h, and requires proper N-glycosylation-dependent folding. The N-terminal fragment is rapidly degraded in a non-lysosomal, brefeldin A-sensitive compartment. Biosynthetic pulse-chase labeling, pharmacological inhibitors (brefeldin A, monensin, tunicamycin), endoglycosidase H resistance assay in neuroendocrine cells European journal of biochemistry High 11952786
2008 Transgenic overexpression of ATP6AP1 (Ac45) specifically in Xenopus melanotrope cells caused accumulation of the V-ATPase at the plasma membrane, increased abundance of secretory granules, plasma membrane protrusions, and enhanced Ca2+-dependent peptide secretion. Ac45 transgene did not alter levels of prohormone POMC or V-ATPase subunits, indicating Ac45 guides the V-ATPase through the secretory pathway to regulate Ca2+-dependent exocytosis. Transgenic Xenopus melanotrope cell model, immunofluorescence, electron microscopy, Ca2+-dependent secretion assay Biochimica et biophysica acta High 18657579
2008 Furin was identified as a proprotein convertase that cleaves ATP6AP1 (Ac45) in the endocrine pancreas. Furin-deficient beta cells showed significantly decreased granule acidification. Ac45 is highly expressed in islets of Langerhans, and furin cleaves Ac45 ex vivo at a defined site. Knockdown of either furin or Ac45 in insulinoma betaTC3 cells similarly reduced regulated secretion and proinsulin II processing, establishing furin as the writer of Ac45 cleavage-mediated activation. Conditional furin knockout mice (Pdx1-Cre/loxP), DAMP acidification assay, ex vivo cleavage assay, siRNA knockdown in insulinoma cells, secretion and processing assays Proceedings of the National Academy of Sciences of the United States of America High 18713856
2010 Transgenic manipulation of ATP6AP1 (Ac45) levels in Xenopus melanotrope cells demonstrated that Ac45 directly regulates V-ATPase-mediated granular acidification. Elevated Ac45 significantly increased granular acidification, reduced sensitivity to the V-ATPase inhibitor bafilomycin A1, enhanced early prohormone convertase PC1-mediated POMC processing, and suppressed late PC2-mediated POMC processing by impairing neutral pH-dependent 7B2-proPC2 maturation. Ac45 was established as the first identified regulator of the V-ATPase proton pump. Transgenic Xenopus melanotrope cell model, acidotrophic dye assays, bafilomycin sensitivity, immunoblot analysis of POMC processing intermediates Molecular biology of the cell High 20702583
2012 ATP6AP1 (Ac45) is essential for osteoclast-mediated extracellular acidification, bone resorption, lysosomal trafficking to the ruffled border, and cathepsin K exocytosis. Ac45 knockdown osteoclasts formed normal actin rings but failed to acidify extracellular space and exhibited absent lysosomal trafficking and cathepsin K exocytosis. The impaired exocytosis was specific to Ac45 deficiency, not a general V-ATPase defect. Ac45 was shown to interact with the small GTPase Rab7, suggesting a mechanism for lysosomal trafficking guidance. Ac45 knockdown also reduced osteoclast precursor proliferation and fusion via downregulation of ERK phosphorylation, c-fos, NFATc1, and Tm7sf4. siRNA knockdown in osteoclasts, bone resorption assay, extracellular acidification assay, lysosomal trafficking assay, cathepsin K exocytosis assay, co-immunoprecipitation with Rab7, RANKL-induced differentiation Journal of bone and mineral research High 22467241
2012 Domain mapping in Xenopus melanotrope cells identified that the N-terminal domain of intact Ac45 causes ER retention and poor processing, while proteolytic cleavage (generating cleaved-Ac45) enables efficient transport through the secretory pathway and V-ATPase accumulation at the plasma membrane. Removal of the C-tail from cleaved-Ac45 still permitted plasma membrane transport but abolished V-ATPase recruitment into the secretory pathway and abrogated dopaminergic inhibition of Ca2+-dependent peptide secretion. The C-tail of cleaved-Ac45 is thus specifically required for V-ATPase recruitment and regulation of Ca2+-dependent exocytosis. Transgenic Xenopus melanotrope cells expressing deletion mutants of Ac45, immunofluorescence, electron microscopy, secretion assays The Journal of biological chemistry High 22736765
2016 ATP6AP1 (Ac45) was identified as the functional human ortholog of yeast V-ATPase assembly factor Voa1. Eleven male patients with hemizygous missense mutations in ATP6AP1 displayed immunodeficiency with hypogammaglobulinemia, hepatopathy, and neurocognitive abnormalities. Processed wild-type Ac45, but not disease mutants, restored V-ATPase-dependent growth in Voa1 mutant yeast. Tissue-specific isoforms were identified: ~40 kDa processed form in brain, ~62 kDa intact form in liver, and ~50 kDa isoform in B cells, linking tissue-specific V-ATPase assembly to immunoglobulin production and cognitive function. Whole-exome sequencing, yeast complementation assay (Voa1 mutant rescue), Western blot of patient tissues, glycosylation analysis, homology detection via sequence profile comparison Nature communications High 27231034
2018 Whole-exome sequencing revealed mutually exclusive, clonal, inactivating somatic mutations in ATP6AP1 or ATP6AP2 in 72% of granular cell tumors (GCTs). In vitro silencing of ATP6AP1 resulted in impaired vesicle acidification, redistribution of endosomal compartments, accumulation of intracytoplasmic granules (recapitulating GCT histology), and acquisition of oncogenic properties, demonstrating that ATP6AP1 loss-of-function drives GCT tumorigenesis. Whole-exome sequencing, targeted sequencing, siRNA knockdown, lysosomal acidification assay (LysoSensor), endosomal compartment immunofluorescence, proliferation/migration/invasion assays Nature communications High 30166553
2022 SARS-CoV-2 NSP6 directly interacts with ATP6AP1, a V-ATPase proton pump component, and inhibits its cleavage-mediated activation, thereby impairing lysosome acidification and blocking autophagic flux, which triggers NLRP3/ASC-dependent caspase-1 activation, IL-1β/18 maturation, and pyroptosis in lung epithelial cells. The L37F NSP6 variant (associated with asymptomatic COVID-19) showed reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification. Restoration of autophagic flux by 1α,25-dihydroxyvitamin D3, metformin, or polydatin abrogated NSP6-induced pyroptosis. Co-immunoprecipitation, overexpression/knockdown studies, lysosomal acidification assay, autophagic flux assay, caspase-1 activation assay, cytokine maturation assay, live SARS-CoV-2 infection, transcriptome analysis, pharmacological rescue Cell death and differentiation High 34997207
2024 ATP6AP1 was identified as an unconventional guanine nucleotide exchange factor (GEF) for the small G protein Rheb, which directly activates mTORC1. Using proximity labeling (PhastID), ATP6AP1 was found to dynamically interact with Rheb in an insulin-stimulated manner. ATP6AP1 binds Rheb through its last 12 amino acids and utilizes a tri-aspartate motif in its highly conserved C-tail to enhance Rheb GTP loading. Targeting the ATP6AP1 C-tail blocked Rheb activation and inhibited cancer cell proliferation and migration, filling the missing link in the Rheb/mTORC1 activation pathway. PhastID proximity labeling, co-immunoprecipitation, in vitro GEF activity assay (GTP loading), deletion/mutagenesis analysis of C-tail, cancer cell proliferation and migration assays Cell research High 38448650
2015 Local AAV-mediated knockdown of ATP6AP1 (Ac45) in a periodontitis mouse model protected mice from bone erosion by >85%, reduced osteoclast-mediated extracellular acidification and bone resorption in vitro and in vivo, and attenuated gingival inflammation including decreased infiltration of T cells, dendritic cells, and macrophages, and reduced pro-inflammatory cytokine expression. AAV-mediated shRNA knockdown in mouse periodontitis model (P. gingivalis W50), histology, immunochemistry, ELISA, qRT-PCR, in vitro osteoclast acidification assay Journal of clinical periodontology Medium 25952706

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
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2014 Detection of genetic variations in Orf virus isolates epidemic in Xinjiang China. Journal of basic microbiology 20 24633847
2023 Recent advances in diagnostic approaches for orf virus. Applied microbiology and biotechnology 19 36723701
2021 Orf virus ORFV112, ORFV117 and ORFV127 contribute to ORFV IA82 virulence in sheep. Veterinary microbiology 19 33866062
2016 Molecular characterization of Orf virus in goats in Gabon, Central Africa. Virology journal 18 27178401
2016 Functional characterization of recombinant major envelope protein (rB2L) of orf virus. Archives of virology 18 27995337
2015 Functional analysis of the short isoform of orf virus protein OV20.0. Journal of virology 18 25694596
2015 Identification and molecular characterization of Orf virus in Argentina. Virus genes 18 25796398
2007 Isolation and characterization of an Indian ORF virus from goats. Zoonoses and public health 18 17542963
2007 Genetic and physiological characterization of the Borrelia burgdorferi ORF BB0374-pfs-metK-luxS operon. Microbiology (Reading, England) 18 17600074
2021 Orf Virus ORF120 Protein Positively Regulates the NF-κB Pathway by Interacting with G3BP1. Journal of virology 17 34287041
2019 Adenosine Deaminase Acting on RNA 1 Associates with Orf Virus OV20.0 and Enhances Viral Replication. Journal of virology 17 30651363
2016 Attenuation and protection efficacy of ORF C gene-deleted recombinant of infectious laryngotracheitis virus. The Journal of general virology 17 27283114
2004 Heparin binding activity of orf virus F1L protein. Virus research 17 15351483
1997 Roles for lambda Orf and Escherichia coli RecO, RecR and RecF in lambda recombination. Genetics 17 9335578
2024 An Inner Mitochondrial Membrane Microprotein from the SLC35A4 Upstream ORF Regulates Cellular Metabolism. Journal of molecular biology 16 38580077
2023 iPSC-derived natural killer cells expressing the FcγR fusion CD64/16A can be armed with antibodies for multitumor antigen targeting. Journal for immunotherapy of cancer 16 38056893
2024 The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb. Cell research 15 38448650
2022 Natural Compound Allicin Containing Thiosulfinate Moieties as Transmembrane Protein 16A (TMEM16A) Ion Channel Inhibitor for Food Adjuvant Therapy of Lung Cancer. Journal of agricultural and food chemistry 15 36574498
2015 Ac45 silencing mediated by AAV-sh-Ac45-RNAi prevents both bone loss and inflammation caused by periodontitis. Journal of clinical periodontology 15 25952706
2015 Isolation and phylogenetic analysis of caprine Orf virus in Malaysia. Virusdisease 15 26645035
2010 V-ATPase-mediated granular acidification is regulated by the V-ATPase accessory subunit Ac45 in POMC-producing cells. Molecular biology of the cell 15 20702583
2016 Ankyrin Repeat Proteins of Orf Virus Influence the Cellular Hypoxia Response Pathway. Journal of virology 14 27795413
2014 Functional evaluation of the role of C-type lectin domain family 16A at the chromosome 16p13 locus. Clinical and experimental immunology 14 24237155
2002 RAPD isolation of a Y chromosome specific ORF in a dioecious plant, Silene latifolia. Genome 14 11962638
2021 Biochemical and molecular study on serum miRNA-16a and miRNA- 451 as neonatal sepsis biomarkers. Biochemistry and biophysics reports 13 33506118
2019 iNK-CD64/16A cells: a promising approach for ADCC? Expert opinion on biological therapy 13 31510805
2014 Major cleavage-dependent epitopes for linear IgA bullous dermatosis are formed at the boundary between the non-collagenous 16A and collagenous 15 domains of BP180. Journal of dermatological science 13 25176590
2012 Identification of domains within the V-ATPase accessory subunit Ac45 involved in V-ATPase transport and Ca2+-dependent exocytosis. The Journal of biological chemistry 13 22736765
2002 The fate of newly synthesized V-ATPase accessory subunit Ac45 in the secretory pathway. European journal of biochemistry 13 11952786