Affinage

ATP6AP1

V-type proton ATPase subunit S1 · UniProt Q15904

Length
470 aa
Mass
52.0 kDa
Annotated
2026-06-09
100 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP6AP1 (Ac45) is a type I transmembrane accessory subunit of the vacuolar H+-ATPase (V-ATPase) that functions as a V-ATPase assembly factor and regulator of organellar acidification across the secretory and endolysosomal pathways (PMID:27231034, PMID:22044156). It is the functional human ortholog of the yeast V-ATPase assembly factor Voa1: processed wild-type Ac45, but not disease-associated missense mutants, restores V-ATPase-dependent growth in Voa1-deficient yeast (PMID:27231034). The newly synthesized protein is N-glycosylated and then proteolytically cleaved in the early secretory pathway — cleavage by furin separates an N-terminal fragment from a C-terminal fragment, and glycosylation is required for proper folding and cleavage (PMID:11952786, PMID:18713856); the intact N-terminal domain confers ER retention, while the cleaved C-tail is required to recruit V-ATPase into the secretory pathway and to support Ca2+-dependent regulated exocytosis, and the cytoplasmic tail also carries autonomous signals for retrieval from the cell surface to vacuolar compartments (PMID:22736765, PMID:9739073). Through these activities Ac45 controls intragranular pH and prohormone processing in neuroendocrine cells (PMID:20702583, PMID:18657579) and drives RANKL-induced osteoclast differentiation, extracellular acidification, lysosomal trafficking to the ruffled border, and cathepsin K exocytosis required for bone resorption (PMID:22467241, PMID:25952706). Loss-of-function mutations impair vesicle acidification, cause endosomal redistribution and intracytoplasmic granule accumulation, and confer oncogenic properties (PMID:30166553). Independent of its V-ATPase role, the conserved C-tail binds Rheb through its last 12 amino acids and uses a tri-aspartate motif to enhance Rheb GTP loading, acting as an unconventional GEF that promotes cancer cell proliferation and migration (PMID:38448650). ATP6AP1 is a target of viral subversion: SARS-CoV-2 NSP6 binds ATP6AP1 and blocks its cleavage-mediated activation, impairing lysosomal acidification and autophagic flux to trigger NLRP3/ASC-dependent caspase-1 activation and pyroptosis (PMID:34997207).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    Established that ATP6AP1/Ac45 is a neuroendocrine-enriched V-ATPase-associated protein synthesized as a glycosylated precursor that is intracellularly cleaved, defining its basic biosynthetic identity.

    Evidence cDNA cloning, biosynthetic pulse labeling, deglycosylation, and immunocytochemistry in Xenopus pituitary

    PMID:10336633

    Open questions at the time
    • Cleaving protease not identified
    • Functional consequence of cleavage unresolved
  2. 2002 High

    Defined the post-translational processing pathway, showing N-glycosylation precedes slow proteolytic cleavage in the early secretory pathway and is required for folding and cleavage.

    Evidence Pulse-chase radiolabeling with endoglycosidase H, tunicamycin, brefeldin A, and monensin treatments

    PMID:11952786

    Open questions at the time
    • Protease responsible not yet identified
    • Fate/function of cleavage fragments not assigned
  3. 2002 High

    Mapped autonomous endocytic sorting determinants in the cytoplasmic tail, explaining how Ac45 is retrieved from the cell surface to vacuolar compartments.

    Evidence Chimeric Tac-tail constructs and truncation mutants with antibody internalization assays in CV-1 fibroblasts

    PMID:9739073

    Open questions at the time
    • Trafficking adaptors mediating retrieval unknown
    • Distinct from canonical tyrosine/di-leucine motifs but motif identity undefined
  4. 2002 Medium

    Tested organismal requirement by gene disruption, indicating an essential role in early development consistent with V-ATPase biology.

    Evidence Homologous recombination in mouse ES cells and blastocyst injection with developmental assessment

    PMID:11989824

    Open questions at the time
    • Developmental lethality prevents mechanistic dissection
    • Tissue-specific roles not addressed
  5. 2008 High

    Identified furin as the protease cleaving Ac45 and placed the furin–Ac45–V-ATPase axis in control of granule acidification and regulated secretion.

    Evidence Pdx1-Cre furin knockout mice, ex vivo cleavage-site mapping, DAMP acidification, and siRNA in betaTC3 cells

    PMID:18713856

    Open questions at the time
    • Whether furin is the sole protease in all tissues unclear
    • Structural basis of cleavage-dependent activation unresolved
  6. 2008 High

    Demonstrated through gain-of-function that Ac45 guides V-ATPase trafficking and enhances Ca2+-dependent secretion, linking acidification machinery to exocytosis.

    Evidence Transgenic Xenopus melanotrope overexpression with immunofluorescence, electron microscopy, and secretion assays

    PMID:18657579

    Open questions at the time
    • Direct molecular partners in exocytosis not identified
    • Mechanism coupling V-ATPase to fusion machinery unknown
  7. 2010 High

    Showed Ac45 regulates granular acidification required for prohormone processing, establishing it as the first identified regulator of V-ATPase-mediated granular pH.

    Evidence Transgenic Xenopus melanotrope model with granular acidification, inhibitor sensitivity, and POMC processing assays

    PMID:20702583

    Open questions at the time
    • Differential effect on PC1 vs PC2 maturation mechanistically unexplained
  8. 2012 High

    Resolved the domain logic of Ac45 trafficking, showing intact N-terminal domain confers ER retention while the cleaved C-tail recruits V-ATPase into the secretory pathway for regulated exocytosis.

    Evidence Deletion-mutant structure-function analysis in transgenic Xenopus melanotrope cells with imaging and secretion readouts

    PMID:22736765

    Open questions at the time
    • Receptor/adaptor reading the C-tail signal unidentified
    • C-tail interaction partners not defined
  9. 2012 High

    Demonstrated a cell-type-specific requirement for Ac45 in osteoclast differentiation, acidification, lysosomal trafficking, and cathepsin K exocytosis beyond generic V-ATPase function.

    Evidence siRNA knockdown with bone resorption, acidification, trafficking, exocytosis, and signaling Western blots

    PMID:22467241

    Open questions at the time
    • Proposed Rab7 interaction not biochemically confirmed
    • Link from acidification to ERK/c-fos/NFATc1 signaling indirect
  10. 2012 Medium

    Consolidated the V0-association model, framing Ac45 as a V0-sector partner governing intragranular pH and exocytotic membrane fusion.

    Evidence Review synthesis of biochemical co-purification and neuroendocrine cell studies

    PMID:22044156

    Open questions at the time
    • Review-level synthesis, not new primary data
    • Stoichiometry and structural arrangement within V0 not defined
  11. 2015 Medium

    Validated the osteoclast role in vivo, showing Ac45 knockdown protects against bone erosion and attenuates inflammation in periodontitis.

    Evidence AAV-shRNA knockdown in a mouse periodontitis model with histology, ELISA, and qRT-PCR

    PMID:25952706

    Open questions at the time
    • Single lab in vivo knockdown
    • Mechanism of anti-inflammatory effect not dissected
  12. 2016 High

    Established ATP6AP1 as the human functional ortholog of yeast V-ATPase assembly factor Voa1 and tied disease mutations to failed assembly.

    Evidence Yeast complementation with wild-type vs patient missense mutants, homology detection, and tissue isoform Western blots

    PMID:27231034

    Open questions at the time
    • Molecular step of assembly that Ac45 chaperones not defined
    • Basis of tissue-specific isoform pattern unknown
  13. 2018 High

    Linked ATP6AP1 loss-of-function to vesicle de-acidification, endosomal disruption, granule accumulation, and oncogenic transformation in granular cell tumors.

    Evidence Tumor exome/targeted sequencing plus in vitro siRNA recapitulation with acidification and oncogenic assays

    PMID:30166553

    Open questions at the time
    • Mechanism converting acidification loss to oncogenic properties unresolved
  14. 2020 Medium

    Extended the phenotypic spectrum of ATP6AP1 deficiency to peroxisomal dysfunction and disrupted copper homeostasis via a new hemizygous mutation.

    Evidence Patient fibroblast ROS assay, hepatic copper quantification, and tissue-specific Western blot in two siblings

    PMID:32216104

    Open questions at the time
    • Single family case report
    • Mechanistic link between V-ATPase defect and copper accumulation unestablished
  15. 2022 High

    Identified ATP6AP1 as a target of SARS-CoV-2 NSP6, defining a viral mechanism that blocks Ac45 activation to impair lysosomal acidification and trigger pyroptosis.

    Evidence Reciprocal co-IP, lysosomal acidification and autophagic flux assays, inflammasome/caspase-1 readouts, and an NSP6 L37F binding-deficient variant

    PMID:34997207

    Open questions at the time
    • Structural interface of NSP6–ATP6AP1 binding not resolved
    • Step of cleavage-activation blocked by NSP6 undefined
  16. 2024 High

    Uncovered a non-canonical, V-ATPase-independent function of the ATP6AP1 C-tail as an unconventional GEF for Rheb that activates mTORC1 signaling and drives cancer phenotypes.

    Evidence Proximity labeling, co-IP, in vitro GTP loading, tri-aspartate motif mutagenesis, and proliferation/migration assays

    PMID:38448650

    Open questions at the time
    • Whether GEF and V-ATPase functions are spatially/temporally separated unclear
    • In vivo contribution to mTORC1 regulation not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ATP6AP1 partitions between its V-ATPase assembly/acidification role and its Rheb-GEF/mTORC1 role, and how cleavage state governs that switch, remains unresolved.
  • No structural model of full-length or cleaved Ac45 within V0
  • Determinants directing the C-tail to V-ATPase versus Rheb unknown
  • Tissue-specific consequences of dual function not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005764 lysosome 2 GO:0005768 endosome 2 GO:0005783 endoplasmic reticulum 2 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-382551 Transport of small molecules 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-162582 Signal Transduction 1 R-HSA-9612973 Autophagy 1
Partners
FURINNSP6 (SARS-COV-2)RHEB
Complex memberships
V-ATPase (V0 sector)

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2024 ATP6AP1 directly 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, functioning as an unconventional guanine nucleotide exchange factor (GEF) for Rheb; targeting the ATP6AP1 C-tail blocks Rheb activation and inhibits cancer cell proliferation and migration. Proximity labeling (PhastID), co-immunoprecipitation, in vitro GTP loading assay, domain deletion/mutagenesis, functional cell proliferation and migration assays Cell research High 38448650
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 autophagic flux, which triggers NLRP3/ASC-dependent caspase-1 activation and pyroptosis in lung epithelial cells. Co-immunoprecipitation, overexpression, lysosomal acidification assays, autophagic flux assays, inflammasome/caspase-1 activation assays, pharmacological rescue experiments Cell death and differentiation High 34997207
2016 ATP6AP1 (Ac45) is the functional human ortholog of yeast V-ATPase assembly factor Voa1; processed wild-type Ac45, but not disease-associated missense mutants, restores V-ATPase-dependent growth in Voa1 mutant yeast, establishing its role in V-ATPase assembly. Tissue-specific isoforms (40-kDa in brain, 62-kDa in liver, 50-kDa in B-cells) are present, linking V-ATPase assembly to immunoglobulin production and cognitive function. Yeast complementation assay, sequence profile homology detection, patient mutation analysis, Western blot of tissue-specific isoforms Nature communications High 27231034
2012 ATP6AP1 (Ac45) is required for RANKL-induced osteoclast differentiation, extracellular acidification, lysosomal trafficking to the ruffled border, and cathepsin K exocytosis; Ac45 knockdown severely impairs bone resorption and reduces osteoclast precursor proliferation and fusion, partially via downregulation of ERK phosphorylation and c-fos/NFATc1/Tm7sf4 expression. The effect on exocytosis is specific to Ac45 deficiency, distinct from general V-ATPase defects, and may involve interaction with the small GTPase Rab7. siRNA knockdown, bone resorption assays, extracellular acidification assay, lysosomal trafficking immunofluorescence, cathepsin K exocytosis assay, Western blot for signaling molecules Journal of bone and mineral research High 22467241
2010 Transgenic overexpression of Ac45 (ATP6AP1) specifically in Xenopus melanotrope cells increases granular acidification, reduces sensitivity to V-ATPase inhibitor, enhances early POMC processing by PC1, but reduces PC2 maturation; establishing Ac45 as the first identified regulator of V-ATPase-mediated granular acidification required for prohormone processing. Transgenic Xenopus melanotrope cell model, granular acidification assay, V-ATPase inhibitor sensitivity assay, prohormone processing Western blot analysis Molecular biology of the cell High 20702583
2008 Transgenic expression of Ac45 (ATP6AP1) in Xenopus melanotrope cells causes accumulation of V-ATPase at the plasma membrane, increased abundance of secretory granules, plasma membrane protrusions, and increased Ca2+-dependent secretion efficiency, demonstrating that Ac45 guides V-ATPase through the secretory pathway and regulates Ca2+-dependent peptide secretion. Transgenic Xenopus melanotrope cell model, immunofluorescence, electron microscopy, Ca2+-dependent secretion assay Biochimica et biophysica acta High 18657579
2008 Furin cleaves Ac45 (ATP6AP1) at a defined site in pancreatic beta cells; furin knockout reduces granule acidification, and Ac45 knockdown similarly reduces regulated secretion and proinsulin II processing, establishing a furin–Ac45–V-ATPase axis controlling intragranular acidification in the regulated secretory pathway. Pdx1-Cre/loxP furin knockout mice, DAMP acidification assay, ex vivo cleavage assay to determine cleavage site, siRNA knockdown of furin and Ac45 in betaTC3 cells, insulin/proinsulin processing assays Proceedings of the National Academy of Sciences of the United States of America High 18713856
2012 Ac45 (ATP6AP1) interacts with the V0 sector of the V-ATPase complex in neuroendocrine cells, regulating intragranular pH and Ca2+-dependent exocytotic membrane fusion. Biochemical co-purification/interaction studies, neuroendocrine cell models (review/synthesis of prior experimental work cited therein) Current protein & peptide science Medium 22044156
2012 The N-terminal domain of Ac45 (ATP6AP1) controls its retention in the endoplasmic reticulum when intact; proteolytic cleavage releasing the N-terminal domain enables transport through the secretory pathway. The C-tail of cleaved Ac45 is required for V-ATPase recruitment into the secretory pathway and for Ca2+-dependent regulated exocytosis, but not for plasma membrane targeting. Deletion mutant analysis in transgenic Xenopus melanotrope cells, immunofluorescence, electron microscopy, secretion assays The Journal of biological chemistry High 22736765
2002 The cytoplasmic tail of Ac45 (ATP6AP1) contains autonomous internalization signal(s) in its membrane-distal region that mediate rapid retrieval from the cell surface and targeting to vacuolar compartments; multiple sites rather than a single short linear motif are responsible, and this routing is distinct from known tyrosine- or di-leucine-based sorting motifs. Transfection in CV-1 fibroblasts, antibody internalization experiments, chimeric protein (Ac45 tail fused to Tac), C-terminally truncated mutant expression, immunolocalization Journal of cell science High 9739073
2002 Newly synthesized Ac45 (ATP6AP1) undergoes N-linked glycosylation (to ~62 kDa from ~46 kDa unglycosylated form), followed by slow proteolytic cleavage (half-life ~4–6 h) in the early secretory pathway producing an N-terminal (~22 kDa) and C-terminal (~42–44 kDa) fragment; N-linked glycosylation is required for proper folding and cleavage. The N-terminal fragment is rapidly degraded in a non-lysosomal, brefeldin A-sensitive manner. Pulse-chase radiolabeling, endoglycosidase H resistance assay, tunicamycin treatment, brefeldin A treatment, monensin treatment, deglycosylation, Western blot European journal of biochemistry High 11952786
1999 Xenopus Ac45 (ATP6AP1 ortholog) is synthesized as an N-glycosylated ~60 kDa precursor that is intracellularly cleaved to an ~40 kDa product; expression is predominantly in neuroendocrine tissues. The protein is associated with V-ATPase and localizes to biosynthetically active melanotrope cells in pituitary. cDNA cloning, Western blot, deglycosylation assay, biosynthetic pulse labeling, immunocytochemistry in Xenopus pituitary European journal of biochemistry High 10336633
2018 Loss-of-function mutations in ATP6AP1 impair vesicle acidification, cause redistribution of endosomal compartments, and lead to accumulation of intracytoplasmic granules in granular cell tumors; ATP6AP1 depletion in vitro recapitulates these phenotypes and results in acquisition of oncogenic properties. Whole-exome and targeted sequencing of patient tumors, in vitro siRNA silencing, vesicle acidification assay, endosomal compartment imaging, granule accumulation assay, oncogenic property assays Nature communications High 30166553
2015 AAV-mediated Ac45 (ATP6AP1) knockdown in a mouse periodontitis model impairs osteoclast-mediated extracellular acidification and bone resorption in vivo, protects against bone erosion by >85%, and attenuates periodontal inflammation including reduced pro-inflammatory cytokine expression and immune cell infiltration. AAV-shRNA knockdown in vivo (mouse periodontitis model), histology, immunochemistry, ELISA, qRT-PCR Journal of clinical periodontology Medium 25952706
2002 Targeted disruption of the Ac45 (ATP6AP1) gene in mouse embryonic stem cells generates null mutant (−/Y) ES cells; injection into blastocysts produced chimeric mice with severely compromised development, suggesting an essential role in early embryonic development consistent with other V-ATPase subunit knockouts. Gene targeting/homologous recombination in mouse ES cells, blastocyst injection, developmental phenotype assessment Molecular membrane biology Medium 11989824
2020 A novel hemizygous ATP6AP1 mutation (c.221T>C, p.L74P) causes increased reactive oxygen species in patient fibroblasts and striking hepatic copper accumulation, with tissue-specific differences in ATP6AP1 protein levels and post-translational modification pattern, demonstrating that ATP6AP1 deficiency leads to peroxisomal dysfunction and disrupted copper homeostasis. Patient fibroblast analysis, ROS assay, hepatic copper quantification, Western blot of tissue-specific protein pattern Journal of inherited metabolic disease Medium 32216104

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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1987 HIV F/3' orf encodes a phosphorylated GTP-binding protein resembling an oncogene product. Nature 521 3118220
2002 ORF-FINDER: a vector for high-throughput gene identification. Gene 315 11814675
2004 Genomes of the parapoxviruses ORF virus and bovine papular stomatitis virus. Journal of virology 233 14671098
2013 The structural and accessory proteins M, ORF 4a, ORF 4b, and ORF 5 of Middle East respiratory syndrome coronavirus (MERS-CoV) are potent interferon antagonists. Protein & cell 223 24318862
1998 Ovine diseases. Orf. Veterinary research 188 9689744
2022 SARS-CoV-2 non-structural protein 6 triggers NLRP3-dependent pyroptosis by targeting ATP6AP1. Cell death and differentiation 156 34997207
2016 ATP6AP1 deficiency causes an immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation. Nature communications 121 27231034
2015 Molecular genetic analysis of orf virus: a poxvirus that has adapted to skin. Viruses 121 25807056
2002 Immunity and counter-immunity during infection with the parapoxvirus orf virus. Virus research 111 12297324
2018 Loss-of-function mutations in ATP6AP1 and ATP6AP2 in granular cell tumors. Nature communications 105 30166553
2005 Genome annotation past, present, and future: how to define an ORF at each locus. Genome research 90 16339376
1994 Phosphorylation of varicella-zoster virus open reading frame (ORF) 62 regulatory product by viral ORF 47-associated protein kinase. Journal of virology 83 8107200
1993 Phylogenetic and structural analyses of MMTV LTR ORF sequences of exogenous and endogenous origins. Virology 83 8382394
1999 The human herpesvirus-8 ORF 57 gene and its properties. The Journal of general virology 69 10567653
2012 The transmembrane protein 16A Ca(2+)-activated Cl- channel in airway smooth muscle contributes to airway hyperresponsiveness. American journal of respiratory and critical care medicine 68 23239156
2008 Role of furin in granular acidification in the endocrine pancreas: identification of the V-ATPase subunit Ac45 as a candidate substrate. Proceedings of the National Academy of Sciences of the United States of America 68 18713856
2014 Transmembrane protein with unknown function 16A overexpression promotes glioma formation through the nuclear factor-κB signaling pathway. Molecular medicine reports 66 24401903
1987 The structure and cloning of orf virus DNA. Virology 65 3029950
2006 Orf virus infection and host immunity. Current opinion in infectious diseases 57 16514336
2012 V-ATPase subunit ATP6AP1 (Ac45) regulates osteoclast differentiation, extracellular acidification, lysosomal trafficking, and protease exocytosis in osteoclast-mediated bone resorption. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 55 22467241
1992 Serine protein kinase associated with varicella-zoster virus ORF 47. Virology 53 1329339
2000 Sequence and functional analysis of a homolog of interleukin-10 encoded by the parapoxvirus orf virus. Virus genes 52 11022792
2007 Identification and phylogenetic analysis of orf virus from goats in Taiwan. Virus genes 51 17682935
1993 Conservation of gene structure and arrangement between vaccinia virus and orf virus. Virology 50 8317094
2019 Magnesium-sensitive upstream ORF controls PRL phosphatase expression to mediate energy metabolism. Proceedings of the National Academy of Sciences of the United States of America 49 30718434
2018 Bile acids stimulate cholangiocyte fluid secretion by activation of transmembrane member 16A Cl- channels. Hepatology (Baltimore, Md.) 48 29360145
2017 Inhibition of transmembrane member 16A calcium-activated chloride channels by natural flavonoids contributes to flavonoid anticancer effects. British journal of pharmacology 47 28452066
1997 The immune and inflammatory response to orf virus. Comparative immunology, microbiology and infectious diseases 46 9280386
2021 A short ORF-encoded transcriptional regulator. Proceedings of the National Academy of Sciences of the United States of America 43 33468658
2024 Widespread stable noncanonical peptides identified by integrated analyses of ribosome profiling and ORF features. Nature communications 42 38431639
2011 Orf-I and orf-II-encoded proteins in HTLV-1 infection and persistence. Viruses 42 21994758
2007 A duplex PCR assay for simultaneous detection and differentiation of Capripoxvirus and Orf virus. Molecular and cellular probes 42 17350223
2018 Orf virus: A promising new therapeutic agent. Reviews in medical virology 40 30370570
2020 Developmental regulation of canonical and small ORF translation from mRNAs. Genome biology 39 32471506
2019 MiR-16a Regulates Milk Fat Metabolism by Targeting Large Tumor Suppressor Kinase 1 (LATS1) in Bovine Mammary Epithelial Cells. Journal of agricultural and food chemistry 39 31542928
1994 Expression of the rubella virus nonstructural protein ORF and demonstration of proteolytic processing. Virology 39 8291241
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2014 Expression and detection of LINE-1 ORF-encoded proteins. Mobile genetic elements 35 25054082
2022 Analysis of inhibitors of the anoctamin-1 chloride channel (transmembrane member 16A, TMEM16A) reveals indirect mechanisms involving alterations in calcium signalling. British journal of pharmacology 34 36444690
2011 Orf virus DNA vaccines expressing ORFV 011 and ORFV 059 chimeric protein enhances immunogenicity. Virology journal 34 22204310
2002 Targeted disruption of the mouse gene encoding the V-ATPase accessory subunit Ac45. Molecular membrane biology 34 11989824
2002 Orf virus immuno-modulation and the host immune response. Veterinary immunology and immunopathology 34 12072264
1999 Immunomodulation by virulence proteins of the parapoxvirus orf virus. Veterinary immunology and immunopathology 34 10614496
2019 Human Infection with Orf Virus and Description of Its Whole Genome, France, 2017. Emerging infectious diseases 33 31742503
2013 Common variant of leucine-rich repeat-containing 16A (LRRC16A) gene is associated with gout susceptibility. Human cell 33 24318514
1998 The pnk/pnl gene (ORF 86) of Autographa californica nucleopolyhedrovirus is a non-essential, immediate early gene. The Journal of general virology 33 9519844
1999 Biosynthesis of the vacuolar H+-ATPase accessory subunit Ac45 in Xenopus pituitary. European journal of biochemistry 32 10336633
2012 Novel insights into V-ATPase functioning: distinct roles for its accessory subunits ATP6AP1/Ac45 and ATP6AP2/(pro) renin receptor. Current protein & peptide science 31 22044156
2020 N6-methyladenosine modifications enhance enterovirus 71 ORF translation through METTL3 cytoplasmic distribution. Biochemical and biophysical research communications 30 32446384
2022 ORF-Interrupting Mutations in Monkeypox Virus Genomes from Washington and Ohio, 2022. Viruses 26 36366490
2008 Accessory subunit Ac45 controls the V-ATPase in the regulated secretory pathway. Biochimica et biophysica acta 26 18657579
1995 Identification and characterization of the orf virus type I topoisomerase. Virology 26 7831775
1998 Intracellular trafficking of the vacuolar H+-ATPase accessory subunit Ac45. Journal of cell science 25 9739073
1996 Cytokines and their inhibitors in orf virus infection. Veterinary immunology and immunopathology 25 8988872
2022 DAP5 enables main ORF translation on mRNAs with structured and uORF-containing 5' leaders. Nature communications 24 36473845
2018 Muscle-Specific Histone H3K36 Dimethyltransferase SET-18 Shortens Lifespan of Caenorhabditis elegans by Repressing daf-16a Expression. Cell reports 24 29514099
2021 Understanding small ORF diversity through a comprehensive transcription feature classification. DNA research : an international journal for rapid publication of reports on genes and genomes 23 34240112
2018 Transmembrane member 16A participates in hydrogen peroxide-induced apoptosis by facilitating mitochondria-dependent pathway in vascular smooth muscle cells. British journal of pharmacology 22 29968377
2017 An Overwiev of ORF Virus Infection in Humans and Animals. Recent patents on anti-infective drug discovery 22 28571550
2012 Partial sequence analysis of B2L gene of Brazilian orf viruses from sheep and goats. Veterinary microbiology 22 23200438
2020 Severe phenotype of ATP6AP1-CDG in two siblings with a novel mutation leading to a differential tissue-specific ATP6AP1 protein pattern, cellular oxidative stress and hepatic copper accumulation. Journal of inherited metabolic disease 21 32216104
2013 Isolation and characterization of orf viruses from Korean black goats. Journal of veterinary science 21 23814477
2022 Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c). Diabetes & metabolism journal 20 35656563
2019 Recombinant B2L and Kisspeptin-54 DNA Vaccine Induces Immunity Against Orf Virus and Inhibits Spermatogenesis In Rats. Scientific reports 20 31700161
2019 Role of HTLV-1 orf-I encoded proteins in viral transmission and persistence. Retrovirology 20 31852543
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 Functional characterization of recombinant major envelope protein (rB2L) of orf virus. Archives of virology 19 27995337
1987 3'-orf and sor genes of human immunodeficiency virus: in vitro transcription-translation and immunoreactive domains. Proceedings of the National Academy of Sciences of the United States of America 19 3496604
2024 The rapid proximity labeling system PhastID identifies ATP6AP1 as an unconventional GEF for Rheb. Cell research 18 38448650
2024 An Inner Mitochondrial Membrane Microprotein from the SLC35A4 Upstream ORF Regulates Cellular Metabolism. Journal of molecular biology 18 38580077
2021 Orf Virus ORF120 Protein Positively Regulates the NF-κB Pathway by Interacting with G3BP1. Journal of virology 18 34287041
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
2015 Regulation of PACT-Mediated Protein Kinase Activation by the OV20.0 Protein of Orf Virus. Journal of virology 18 26355092
2007 Genetic and physiological characterization of the Borrelia burgdorferi ORF BB0374-pfs-metK-luxS operon. Microbiology (Reading, England) 18 17600074
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 17 38056893
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
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
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
2018 Orf Virus Encoded Protein ORFV119 Induces Cell Apoptosis Through the Extrinsic and Intrinsic Pathways. Frontiers in microbiology 13 29896166
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
1998 Repetitive DNA insertion in a protein kinase ORF of a latent FSV (Feldmannia sp. virus) genome. Virology 13 9705253
2023 Host range, severity and trans boundary transmission of Orf virus (ORFV). Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 12 37217030
2020 Prenatal and postnatal phenotype of a pathologic variant in the ATP6AP1 gene. European journal of medical genetics 12 32058063
2017 Human orf complicated by epidermolysis bullosa acquisita. The British journal of dermatology 12 28338219
1996 Gene homology between orf virus and smallpox variola virus. Virus genes 12 8972571
2001 Expression and functional properties of proteins encoded in the x-II ORF of HTLV-I. Virus research 11 11520578

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