Affinage

ATP6V0D1

V-type proton ATPase subunit d 1 · UniProt P61421

Round 2 corrected
Length
351 aa
Mass
40.3 kDa
Annotated
2026-04-28
130 papers in source corpus 11 papers cited in narrative 11 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ATP6V0D1 is a non-integral membrane subunit of the V0 sector of the vacuolar H⁺-ATPase (V-ATPase) that is essential for V-ATPase complex assembly, lysosomal acidification, and pH-dependent cellular signaling. Loss of its yeast ortholog Vma6p destabilizes V0 integral membrane components and abolishes vacuolar ATPase activity (PMID:8509410), while in mammalian cells V-ATPase activity involving ATP6V0D1 is required for amino acid-dependent mTORC1 activation via Ragulator interactions (PMID:22053050) and for Wnt/β-catenin signal transduction (PMID:20093472). ATP6V0D1 functions as a druggable node: small molecules JTC801 and schisandrol A bind ATP6V0D1 (the latter at Cys335) to modulate V-ATPase-dependent lysosomal pH, with JTC801-stabilized ATP6V0D1 engaging STAT3 to sustain pH homeostasis and drive alkaliptosis in pancreatic cancer cells (PMID:36640329, PMID:36213534). ATP6V0D1-dependent lysosomal pH regulation also controls ABCB1-mediated multidrug resistance and lysosomal sequestration-based chemoresistance in cancer cells (PMID:38751020, PMID:40552114).

Mechanistic history

Synthesis pass · year-by-year structured walk · 8 steps
  1. 1993 High

    Establishing that the V0-sector 36-kDa subunit (Vma6p/ATP6V0D1 ortholog) is a non-integral membrane protein indispensable for V-ATPase assembly and vacuolar acidification resolved the foundational question of how V0 and V1 sectors are coupled during holoenzyme biogenesis.

    Evidence Null mutant construction in yeast, subcellular fractionation, chaotropic stripping, and vacuolar acidification/ATPase activity assays

    PMID:8509410

    Open questions at the time
    • Precise binding interfaces between Vma6p/ATP6V0D1 and other V0 subunits not mapped
    • Mechanism by which Vma6p loss destabilizes V0 integral subunits undefined
  2. 2000 Medium

    Cloning and characterization of the human VPATPD (ATP6V0D1) gene established its genomic structure and showed that despite shared tissue expression with HSD11B2, it is independently regulated, ruling out co-regulation models.

    Evidence Genomic cloning, sequencing, forskolin treatment in JEG3 cells

    PMID:11118322

    Open questions at the time
    • Transcriptional regulators of ATP6V0D1 not identified
    • Expression across broader human tissue panel not characterized
  3. 2010 High

    Demonstration that V-ATPase activity is required for Wnt/β-catenin signaling — with the prorenin receptor bridging Frizzled/LRP6 to the V-ATPase — placed the complex in a signaling pathway beyond its canonical acidification role.

    Evidence Reciprocal co-IP, RNAi knockdown, Xenopus epistasis experiments, luciferase reporter assays, V-ATPase pharmacological inhibition

    PMID:20093472

    Open questions at the time
    • Specific contribution of ATP6V0D1 subunit versus other V-ATPase subunits to Wnt signaling not dissected
    • Whether acidification or physical scaffold function mediates the effect not resolved
  4. 2011 High

    Cell-free reconstitution showing that V-ATPase ATP hydrolysis is necessary for amino acid-sensitive interactions with Ragulator and subsequent mTORC1 activation established the V-ATPase as an upstream amino acid sensor at lysosomes.

    Evidence Cell-free reconstitution, RNAi knockdown of V-ATPase subunits, co-IP with Ragulator, mTORC1 translocation assays

    PMID:22053050

    Open questions at the time
    • Direct role of ATP6V0D1 versus other subunits in Ragulator binding not isolated
    • Amino acid sensing mechanism within V-ATPase not molecularly defined
  5. 2020 Medium

    Identification of ATP6V0D1 as a direct interactor of PHF1-phosphorylated tau in human AD neurofibrillary tangles placed it within the pathological tau interactome and implicated phagosome maturation in tangle biology.

    Evidence Affinity purification–mass spectrometry with PHF1 antibody from human AD brain tissue

    PMID:32812023

    Open questions at the time
    • Functional consequence of ATP6V0D1–phospho-tau interaction on V-ATPase activity not tested
    • Whether interaction is cause or consequence of tangle formation unknown
  6. 2022 High

    Drug target identification revealed ATP6V0D1 as the direct binding target of JTC801 and schisandrol A — with schisandrol A acting allosterically at Cys335 — establishing ATP6V0D1 as a druggable node that controls lysosomal pH through distinct downstream effectors (STAT3 for alkaliptosis; BIM degradation for neuroprotection).

    Evidence CETSA, mass spectrometry-based thermal shift, Cys335 site-directed mutagenesis, co-IP of ATP6V0D1–STAT3, lysosomal pH measurements, in vivo mouse models

    PMID:36213534 PMID:36640329

    Open questions at the time
    • Structural basis of JTC801 and SolA binding to ATP6V0D1 not resolved at atomic level
    • Whether STAT3 interaction is direct or through a complex remains ambiguous
    • Specificity of Cys335 engagement across cell types not tested
  7. 2024 Medium

    Connecting ATP6V0D1-dependent lysosomal alkalinization to suppression of ABCB1 expression demonstrated a pH-dependent mechanism by which ATP6V0D1 modulates multidrug resistance in cancer.

    Evidence Gene transfection overexpression, JTC801 pharmacological stabilization, intracellular pH manipulation, ABCB1 expression analysis in drug-resistant ovarian cancer cells

    PMID:38751020

    Open questions at the time
    • Transcriptional versus post-translational mechanism for pH-dependent ABCB1 regulation not distinguished
    • In vivo validation of this resistance mechanism not performed
  8. 2025 Medium

    ATP6V0D1 was positioned downstream of Tmem9 in microglia-mediated complement activation (C1q) and synaptic pruning in AD, and separately shown to specifically mediate lysosomal sequestration-based chemoresistance distinct from other V-ATPase subunits.

    Evidence Tmem9 overexpression/knockdown in 5xFAD mice and BV2 cells; siRNA knockdown of ATP6V0D1 vs. ATP6V1H with subunit-specificity controls in neuroblastoma cells

    PMID:39871402 PMID:40552114

    Open questions at the time
    • Direct manipulation of ATP6V0D1 in the complement pathway not performed — inferred through Tmem9
    • Structural basis for subunit-specific roles in chemoresistance unknown
    • In vivo relevance of ATP6V0D1-specific chemoresistance role untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution structural model of mammalian ATP6V0D1 bound to its V0-sector partners or small-molecule ligands exists, and the mechanism by which conformational changes at Cys335 propagate to alter holoenzyme proton pumping remains unresolved.
  • Atomic-resolution structure of ATP6V0D1 in V-ATPase holoenzyme context needed
  • Allosteric mechanism coupling Cys335 engagement to proton translocation undefined
  • Tissue-specific and isoform-specific (ATP6V0D1 vs. ATP6V0D2) functional distinctions incompletely characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140657 ATP-dependent activity 2 GO:0005198 structural molecule activity 1
Localization
GO:0005764 lysosome 3 GO:0005773 vacuole 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-162582 Signal Transduction 2 R-HSA-382551 Transport of small molecules 2 R-HSA-9612973 Autophagy 1
Partners
ATP6V0A1LAMTOR1STAT3TMEM9
Complex memberships
V-ATPase (V0 sector)

Evidence

Reading pass · 11 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 The yeast VMA6 gene encodes the 36-kDa subunit of the V-ATPase membrane sector (ortholog of human ATP6V0D1/subunit d). Vma6p is a non-integral membrane component of the V0 domain required for V-ATPase complex assembly: it is removed by chaotropic agents (Na2CO3, urea) but not by detergents, and in its absence, V0 integral membrane components are destabilized and V1 peripheral subunits fail to assemble onto vacuolar membranes. Vacuolar acidification and V-ATPase activity are completely abolished in vma6 null mutants. Reverse genetics (null mutant construction), subcellular fractionation, biochemical stripping with chaotropic agents, vacuolar acidification assays, ATPase activity assays The Journal of biological chemistry High 8509410
2000 The human VPATPD gene encodes subunit D of the vacuolar proton ATPase (ATP6V0D1), located on chromosome 16q22. The encoded protein is 99.5% identical to mouse subunit D at the amino acid level. The gene spans 19 kb and consists of 8 exons. Although VPATPD and HSD11B2 are both expressed in kidney and placenta, they are regulated differently (forskolin upregulates HSD11B2 but not VPATPD), indicating independent transcriptional regulation. Genomic cloning, sequencing, gene structure determination, expression analysis in JEG3 cells with forskolin treatment Biochemical and biophysical research communications Medium 11118322
2011 The vacuolar H+-ATPase (V-ATPase), of which ATP6V0D1 is a subunit, is necessary for amino acid-stimulated mTORC1 activation. The v-ATPase engages in extensive amino acid-sensitive interactions with the Ragulator complex on the lysosomal surface. In a cell-free system, ATP hydrolysis by the v-ATPase was necessary for amino acids to regulate the v-ATPase–Ragulator interaction and promote mTORC1 translocation, placing the V-ATPase as an amino acid sensor upstream of Rag GTPases. Cell-free reconstitution, RNAi knockdown of V-ATPase subunits, co-immunoprecipitation of v-ATPase with Ragulator, mTORC1 translocation assays, pharmacological inhibition (bafilomycin) Science (New York, N.Y.) High 22053050
2010 V-ATPase activity and acidification are required for Wnt/β-catenin signaling. The prorenin receptor (PRR) acts as an adaptor between Wnt receptors (Frizzled/LRP6) and the V-ATPase complex. V-ATPase-mediated acidification is necessary for Wnt signal transduction during antero-posterior patterning, placing the V-ATPase (including its subunits such as ATP6V0D1) as a component of the Wnt receptor signaling complex. Co-immunoprecipitation, RNAi knockdown, Xenopus embryo epistasis experiments, luciferase reporter assays, pharmacological inhibition of V-ATPase Science (New York, N.Y.) High 20093472
2022 ATP6V0D1 is a direct molecular target of the opioid analgesic JTC801 that drives alkaliptosis in pancreatic ductal adenocarcinoma (PDAC) cells. Drug target identification using mass-spectrometry-based thermal shift assay and point mutation analysis showed JTC801 binds ATP6V0D1 and increases its protein stability. Stabilized ATP6V0D1 enhances interaction with STAT3, increasing STAT3 expression and activity to sustain lysosomal pH homeostasis. Pharmacological or genetic inhibition of STAT3 restores alkaliptosis sensitivity in ATP6V0D1-deficient cells, placing ATP6V0D1 upstream of STAT3 in lysosomal pH regulation. Mass-spectrometry-based drug target identification, cellular thermal shift assay (CETSA), point mutation analysis, co-immunoprecipitation (ATP6V0D1–STAT3 interaction), genetic knockdown/overexpression, pharmacological inhibition in vitro and in mouse models Cell reports High 36640329
2022 ATP6V0D1 is the direct cellular target of the natural compound schisandrol A (SolA), identified as a V-ATPase subunit in lysosomes. SolA allosterically mediates ATP6V0D1 conformation by targeting a unique cysteine 335 residue, thereby activating V-ATPase-dependent lysosomal acidification. This SolA-induced lysosomal pH downregulation creates a mitochondrial-lysosomal crosstalk by selectively promoting degradation of the mitochondrial BH3-only protein BIM, preserving mitochondrial homeostasis and neuronal cell survival against AGEs-induced apoptosis. Drug target identification (biochemical), site-directed mutagenesis (Cys335), lysosomal pH measurement, mitochondrial membrane potential assays, BIM protein level analysis, neuronal cell survival assays Acta pharmaceutica Sinica. B High 36213534
2024 ATP6V0D1 mediates downregulation of ABCB1 (MDR1/P-glycoprotein), a multidrug resistance protein, in paclitaxel-resistant ovarian cancer cells. Both overexpression of ATP6V0D1 by gene transfection and pharmacological stabilization of ATP6V0D1 protein by JTC801 inhibit ABCB1 upregulation and suppress growth of drug-resistant cells. Increasing intracellular pH to alkaline conditions (pH 8.5) suppresses ABCB1 expression, whereas acidic conditions (pH 6.5) amplify ABCB1 expression, linking ATP6V0D1-dependent lysosomal alkalinization to ABCB1 suppression as the mechanism of overcoming drug resistance. Gene transfection (overexpression), pharmacological stabilization (JTC801), pH manipulation with NaOH/HCl, ABCB1 expression analysis, cell growth/viability assays in drug-resistant cell lines Molecular carcinogenesis Medium 38751020
2025 Microglial Tmem9 promotes complement activation (C1q) and synaptic loss in Alzheimer's disease by regulating ATP6V0D1, a V-ATPase subunit that controls V-ATPase assembly. Physical exercise down-regulates Tmem9, which in turn inhibits ATP6V0D1-dependent V-ATPase function, decreasing C1q-mediated complement activation and microglial synapse engulfment in 5xFAD mice. Overexpression of Tmem9 abolishes exercise-associated neuroprotection, placing the Tmem9–ATP6V0D1 axis in a complement activation pathway. In vivo mouse model (5xFAD), genetic overexpression/knockdown of Tmem9, oAβ-stimulated BV2 cells in vitro, complement activity assays, synaptic engulfment quantification, cognitive behavioral testing Aging cell Medium 39871402
2022 A novel truncating somatic mutation in ATP6V0D1 was identified in a proinsulinoma tumor by whole exome sequencing. ATP6V0D1 is proposed to function in acidifying the β-cell compartments where prohormone convertases (PCSKs) act, and its loss-of-function mutation likely impairs proinsulin processing by reducing lysosomal/secretory granule acidification required for PC1/3 activity. Whole exome sequencing of tumor tissue, clinical correlation with suppressed insulin/C-peptide and elevated proinsulin levels Journal of the Endocrine Society Low 36694809
2020 ATP6V0D1 (vacuolar-ATPase subunit) was identified as a protein that directly interacts with PHF1-immunoreactive phosphorylated tau in neurofibrillary tangles from human Alzheimer's disease brain, detected by affinity purification-mass spectrometry. This places ATP6V0D1 in the phosphorylated tau interactome and implicates it in phagosome maturation pathways enriched in the tau interactome. Affinity purification-mass spectrometry (AP-MS) with PHF1 antibody against phosphorylated tau from human AD brain, quantitative proteomics of microdissected neurofibrillary tangles Brain : a journal of neurology Medium 32812023
2025 Knockdown of ATP6V0D1 (but not ATP6V1H) in neuroblastoma cells enhanced sensitivity to ellipticine, suppressed proliferation and migration, decreased lysosomal drug uptake, induced G2/M arrest, and suppressed ellipticine-induced endoplasmic reticulum vacuolation. These effects demonstrate a specific role for ATP6V0D1 in lysosomal sequestration-based chemoresistance that is not shared by other V-ATPase subunits. siRNA knockdown of ATP6V0D1 vs. ATP6V1H, cell viability assays, lysosomal uptake measurement, cell cycle analysis, migration assays, vacuolation quantification Molecular & cellular oncology Medium 40552114

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2011 Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular cell 1334 21906983
2011 mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. Science (New York, N.Y.) 1323 22053050
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2002 The vacuolar (H+)-ATPases--nature's most versatile proton pumps. Nature reviews. Molecular cell biology 961 11836511
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2011 A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Molecular & cellular proteomics : MCP 749 21890473
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1988 Fos-associated protein p39 is the product of the jun proto-oncogene. Science (New York, N.Y.) 700 3130660
2012 A census of human soluble protein complexes. Cell 689 22939629
2015 Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science (New York, N.Y.) 678 25567906
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2015 SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature 548 25561175
1988 fos-associated cellular p39 is related to nuclear transcription factor AP-1. Cell 523 3135941
1997 Structure, function and regulation of the vacuolar (H+)-ATPase. Annual review of cell and developmental biology 488 9442887
2010 Requirement of prorenin receptor and vacuolar H+-ATPase-mediated acidification for Wnt signaling. Science (New York, N.Y.) 471 20093472
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2011 Global identification of modular cullin-RING ligase substrates. Cell 354 21963094
1999 Vacuolar and plasma membrane proton-adenosinetriphosphatases. Physiological reviews 348 10221984
2007 Coupling of rotation and catalysis in F(1)-ATPase revealed by single-molecule imaging and manipulation. Cell 307 17662945
2016 Identification of Zika Virus and Dengue Virus Dependency Factors using Functional Genomics. Cell reports 306 27342126
2001 p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment. The Journal of neuroscience : the official journal of the Society for Neuroscience 306 11517264
2020 Phosphorylated tau interactome in the human Alzheimer's disease brain. Brain : a journal of neurology 290 32812023
2010 Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level. Molecular & cellular proteomics : MCP 262 21139048
2022 Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell 256 35063084
2000 p39 activates cdk5 in neurons, and is associated with the actin cytoskeleton. Journal of cell science 156 10683146
1996 Outer surface protein C (OspC), but not P39, is a protective immunogen against a tick-transmitted Borrelia burgdorferi challenge: evidence for a conformational protective epitope in OspC. Infection and immunity 129 8675332
1998 Region-specific expression of cyclin-dependent kinase 5 (cdk5) and its activators, p35 and p39, in the developing and adult rat central nervous system. Journal of neurobiology 124 9581970
2002 Calpain-mediated cleavage of the cyclin-dependent kinase-5 activator p39 to p29. The Journal of biological chemistry 115 11784720
1993 The Saccharomyces cerevisiae VMA6 gene encodes the 36-kDa subunit of the vacuolar H(+)-ATPase membrane sector. The Journal of biological chemistry 110 8509410
2001 Protection of BALB/c mice against Brucella abortus 544 challenge by vaccination with bacterioferritin or P39 recombinant proteins with CpG oligodeoxynucleotides as adjuvant. Infection and immunity 108 11447155
2001 Caspase-3 activation by lysosomal enzymes in cytochrome c-independent apoptosis in myelodysplastic syndrome-derived cell line P39. Cancer research 104 11306462
1988 Minute virus of mice non-structural protein NS-1 is necessary and sufficient for trans-activation of the viral P39 promoter. The Journal of general virology 102 3171551
2002 The cyclin-dependent kinase 5 activators p35 and p39 interact with the alpha-subunit of Ca2+/calmodulin-dependent protein kinase II and alpha-actinin-1 in a calcium-dependent manner. The Journal of neuroscience : the official journal of the Society for Neuroscience 99 12223541
2008 Myristoylation of p39 and p35 is a determinant of cytoplasmic or nuclear localization of active cyclin-dependent kinase 5 complexes. Journal of neurochemistry 94 18507738
2003 The regulation of cyclin-dependent kinase 5 activity through the metabolism of p35 or p39 Cdk5 activator. Neuro-Signals 80 14673209
1991 Antibody to a 39-kilodalton Borrelia burgdorferi antigen (P39) as a marker for infection in experimentally and naturally inoculated animals. Journal of clinical microbiology 75 2007630
1989 Nucleotide sequence, transcriptional mapping, and temporal expression of the gene encoding p39, a major structural protein of the multicapsid nuclear polyhedrosis virus of Orgyia pseudotsugata. Virology 75 2644736
2003 Tau phosphorylation by cyclin-dependent kinase 5/p39 during brain development reduces its affinity for microtubules. The Journal of biological chemistry 68 12536148
1988 p39, a major baculovirus structural protein: immunocytochemical characterization and genetic location. Virology 64 3059676
2004 Cyclin-dependent kinase 5 associated with p39 promotes Munc18-1 phosphorylation and Ca(2+)-dependent exocytosis. The Journal of biological chemistry 63 15123626
1995 Antibodies against whole sonicated Borrelia burgdorferi spirochetes, 41-kilodalton flagellin, and P39 protein in patients with PCR- or culture-proven late Lyme borreliosis. Journal of clinical microbiology 57 7494012
2022 ATP6V0D1 promotes alkaliptosis by blocking STAT3-mediated lysosomal pH homeostasis. Cell reports 56 36640329
2000 The expression of Cdk5, p35, p39, and Cdk5 kinase activity in developing, adult, and aged rat brains. Neurochemical research 54 10959488
1996 A vaccinia virus core protein, p39, is membrane associated. Journal of virology 53 8794334
2002 Yersinia enterocolitica as a vehicle for a naked DNA vaccine encoding Brucella abortus bacterioferritin or P39 antigen. Infection and immunity 52 11895955
2001 Induction of immune response in BALB/c mice with a DNA vaccine encoding bacterioferritin or P39 of Brucella spp. Infection and immunity 51 11553569
2000 Synaptic localization of p39, a neuronal activator of cdk5. Neuroreport 51 10923673
1994 Nucleotide sequence and analysis of the gene in Borrelia burgdorferi encoding the immunogenic P39 antigen. FEMS microbiology letters 48 8050720
1986 The minute virus of mice P39 transcription unit can encode both capsid proteins. Journal of virology 48 3951017
1987 Different types of modification in c-fos and its associated protein p39: modulation of DNA binding by phosphorylation. Oncogene research 45 3146046
2010 Membrane association facilitates degradation and cleavage of the cyclin-dependent kinase 5 activators p35 and p39. Biochemistry 42 20518484
1997 Heterogeneity of BmpA (P39) among European isolates of Borrelia burgdorferi sensu lato and influence of interspecies variability on serodiagnosis. Journal of clinical microbiology 40 9350727
1994 Marked apoptosis of human myelomonocytic leukemia cell line P39: significance of cellular differentiation. Leukemia 39 8127149
1984 Association of cytokeratin p39 with DNA in intact Novikoff hepatoma cells. Proceedings of the National Academy of Sciences of the United States of America 39 6198648
2022 Schisandrol A protects AGEs-induced neuronal cells death by allosterically targeting ATP6V0d1 subunit of V-ATPase. Acta pharmaceutica Sinica. B 37 36213534
2012 Phosphorylation of p35 and p39 by Cdk5 determines the subcellular location of the holokinase in a phosphorylation-site-specific manner. Journal of cell science 37 22467861
1994 Tick transmission of Borrelia burgdorferi to inbred strains of mice induces an antibody response to P39 but not to outer surface protein A. Infection and immunity 37 8188388
2005 Phosphorylation of FTDP-17 mutant tau by cyclin-dependent kinase 5 complexed with p35, p25, or p39. The Journal of biological chemistry 34 15994305
2001 The pharmacodynamic effect of busulfan in the P39 myeloid cell line in vitro. Leukemia 33 11480566
2005 A specific interaction between muskelin and the cyclin-dependent kinase 5 activator p39 promotes peripheral localization of muskelin. The Journal of biological chemistry 32 15797862
2016 p39 Is Responsible for Increasing Cdk5 Activity during Postnatal Neuron Differentiation and Governs Neuronal Network Formation and Epileptic Responses. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 27807169
2009 Feline calicivirus p32, p39 and p30 proteins localize to the endoplasmic reticulum to initiate replication complex formation. The Journal of general virology 31 19906938
1981 Tissue specificity and cellular distribution of Novikoff hepatoma antigenic proteins p39, p49, and p56. The Journal of biological chemistry 30 7263643
1999 Specific association of c-Jun-like immunoreactivity but not c-Jun p39 with normal and induced programmed cell death in the chick embryo. Journal of neurobiology 28 10022565
2007 Cdk5--p39 is a labile complex with the similar substrate specificity to Cdk5--p35. Journal of neurochemistry 27 17394551
2004 Association of cyclin-dependent kinase 5 and neuronal activators p35 and p39 complex in early-onset Alzheimer's disease. Neurobiology of aging 27 15917097
2002 Regulation of the 14-3-3-binding protein p39 by growth factors and nutrients in rat PC12 pheochromocytoma cells. The Biochemical journal 27 12217078
1995 Identification on melanoma cells of p39, a cysteine proteinase that cleaves C3, the third component of complement: amino-acid-sequence identities with procathepsin L. The Biochemical journal 27 8554545
2009 Protection of BALB/c mice against Brucella melitensis 16 M infection induced by vaccination with live Escherchia coli expression Brucella P39 protein. Vaccine 25 20036752
1999 Two pathways of apoptosis induced with all-trans retinoic acid and etoposide in the myeloid cell line P39. Experimental hematology 24 10428509
1984 A novel human myelomonocytoid cell line, P39/Tsugane, derived from overt leukemia following myelodysplastic syndrome. Gan 24 6597119
2016 The Activators of Cyclin-Dependent Kinase 5 p35 and p39 Are Essential for Oligodendrocyte Maturation, Process Formation, and Myelination. The Journal of neuroscience : the official journal of the Society for Neuroscience 23 26961956
2005 Borrelia burgdorferi BmpA, BmpB, and BmpD proteins are expressed in human infection and contribute to P39 immunoblot reactivity in patients with Lyme disease. Clinical and diagnostic laboratory immunology 22 16085911
2008 Molecular cloning, overproduction, purification and biochemical characterization of the p39 nsp2 protease domains encoded by three alphaviruses. Protein expression and purification 21 19013248
2018 Roles of VPH2 and VMA6 in localization of V-ATPase subunits, cell wall functions and filamentous development in Candida albicans. Fungal genetics and biology : FG & B 20 29522815
2003 The cyclin-dependent kinase 5 activator, p39, is expressed in stripes in the mouse cerebellum. Neuroscience 20 12699769
1999 Immunohistochemical localization of CDK5 activator p39 in the rat brain. Neuroreport 20 10599848
1996 The v-Jun oncoprotein replaces p39 c-Jun as the predominant AP-1 constituent in ASV17-transformed fibroblasts: implications for SAPK/JNK-mediated signal transduction. Oncogene 20 8649782
1983 The genome-linked protein of picornaviruses. VIII. Complete amino acid sequence of poliovirus VPg and carboxy-terminal analysis of its precursor, P3-9. The Journal of general virology 20 6300288
1982 Distribution of Novikoff ascites hepatoma antigens p39 and p49 in various tumorigenic cell lines. Cancer research 20 7060017
2006 A pharmacodynamic study of 5-azacytidine in the P39 cell line. Experimental hematology 19 16413389
1999 Activation of Xenopus eggs by the kinase inhibitor 6-DMAP suggests a differential regulation of cyclin B and p39(mos) proteolysis. Experimental cell research 19 10585264
1984 Characterization of monoclonal antibodies to novikoff hepatoma cytokeratin antigen p39. Cancer research 18 6209005
2011 Cyclin-Dependent Kinase 5/p35/p39: A Novel and Imminent Therapeutic Target for Diabetes Mellitus. International journal of endocrinology 17 22028710
1998 Effect of P39 gene deletion in live Brucella vaccine strains on residual virulence and protective activity in mice. Infection and immunity 16 9784574
1993 Detection of antibodies to the recombinant P39 protein of Borrelia burgdorferi using enzyme immunoassay and immunoblotting. The Journal of rheumatology 16 8496875
1992 Polymorphism and deficiency of human factor H-related proteins p39 and p37. Immunogenetics 16 1535336
2013 p39, the primary activator for cyclin-dependent kinase 5 (Cdk5) in oligodendroglia, is essential for oligodendroglia differentiation and myelin repair. The Journal of biological chemistry 15 23645679
2005 Cyclin-dependent kinase 5 activators p35 and p39 facilitate formation of functional synapses. Brain research. Molecular brain research 15 15908038
2020 p39-associated Cdk5 activity regulates dendritic morphogenesis. Scientific reports 14 33127972
2014 The Cdk5 activator P39 specifically links muskelin to myosin II and regulates stress fiber formation and actin organization in lens. Experimental cell research 14 25128817
2009 Sp1 and Sp3 regulate transcription of the cyclin-dependent kinase 5 regulatory subunit 2 (p39) promoter in neuronal cells. Biochimica et biophysica acta 14 19437621
2001 P39 immunoreactivity in glial cytoplasmic inclusions in brains with multiple system atrophy. Acta neuropathologica 14 11307616
2012 Efficacy evaluation of live Escherichia coli expression Brucella P39 protein combined with CpG oligodeoxynucleotides vaccine against Brucella melitensis 16M, in BALB/c mice. Biologicals : journal of the International Association of Biological Standardization 13 22296786
1992 Nucleotide sequence of the p39-capsid gene region of the Lymantria dispar nuclear polyhedrosis virus. The Journal of general virology 13 1607869
1985 Cell specificity of rat cytokeratin p39 during azo dye-induced hepatocarcinogenesis. Carcinogenesis 13 2410160
2016 Nonstructural protein p39 of feline calicivirus suppresses host innate immune response by preventing IRF-3 activation. Veterinary microbiology 12 26931393
1996 The genes encoding the P39 and CG30 proteins of Bombyx mori nuclear polyhedrosis virus. The Journal of general virology 12 9000108
1993 Homologous C3 deposition and homotypic cell adhesion in a human myeloid cell line, P39. European journal of immunology 12 8103747
2013 Structural basis for the different stability and activity between the Cdk5 complexes with p35 and p39 activators. The Journal of biological chemistry 11 24085300
1994 Monoclonal antibody to native P39 protein from Borrelia burgdorferi. Journal of clinical microbiology 11 8150952
2024 Alkaliptosis induction counteracts paclitaxel-resistant ovarian cancer cells via ATP6V0D1-mediated ABCB1 inhibition. Molecular carcinogenesis 10 38751020
2018 Hyper-phosphorylation of Rb S249 together with CDK5R2/p39 overexpression are associated with impaired cell adhesion and epithelial-to-mesenchymal transition: Implications as a potential lung cancer grading and staging biomarker. PloS one 10 30452490
1996 Isolation of the vma-6 gene encoding a 41 kDa subunit of the Neurospora crassa vacuolar ATPase, and an adjoining gene encoding a ribosome-associated protein. Biochimica et biophysica acta 10 8611592
2023 Feline Calicivirus P39 Inhibits Innate Immune Responses by Autophagic Degradation of Retinoic Acid Inducible Gene I. International journal of molecular sciences 9 36982330
1999 Structure and function prediction of the Brucella abortus P39 protein by comparative modeling with marginal sequence similarities. Protein engineering 9 10235622
2025 Physical Exercise Decreases Complement-Mediated Synaptic Loss and Protects Against Cognitive Impairment by Inhibiting Microglial Tmem9-ATP6V0D1 in Alzheimer's Disease. Aging cell 8 39871402
2017 Chloroplast outer envelope protein P39 in Arabidopsis thaliana belongs to the Omp85 protein family. Proteins 8 25401771
2000 Chimeras between the human immunodeficiency virus (HIV-1) Env and vaccinia virus immunogenic proteins p14 and p39 generate in mice broadly reactive antibodies and specific activation of CD8+ T cell responses to Env. Vaccine 8 10856792
2018 Immunogenicity of adenovirus and DNA vaccines co-expressing P39 and lumazine synthase proteins of Brucella abortus in BALB/c mice. Tropical animal health and production 7 29492808
2014 Preferential targeting of p39-activated Cdk5 to Rac1-induced lamellipodia. Molecular and cellular neurosciences 7 24877974
2017 Peripheral and orofacial pain sensation is unaffected by the loss of p39. Molecular pain 6 28969475
2008 P39, a novel soybean protein allergen, belongs to a plant-specific protein family and is present in protein storage vacuoles. Journal of agricultural and food chemistry 6 18284203
2007 The CDK5 activator, p39, binds specifically to myosin essential light chain. Biochemical and biophysical research communications 6 17276406
2000 Structure of the VPATPD gene encoding subunit D of the human vacuolar proton ATPase. Biochemical and biophysical research communications 6 11118322
2024 S-Nitrosylation of p39 promotes its degradation and contributes to synaptic dysfunction induced by β-amyloid peptide. Communications biology 5 39256547
2022 Valproic Acid-Induced Anxiety and Depression Behaviors are Ameliorated in p39 Cdk5 Activator-Deficient Mice. Neurochemical research 5 35674931
2018 Kinetic modeling, recovery, and molecular characterization of poly-beta-hydroxybutyrate polymer in Acinetobacter baumannii isolate P39. Bioprocess and biosystems engineering 5 30194493
2022 A Novel Somatic Mutation Implicates ATP6V0D1 in Proinsulin Processing. Journal of the Endocrine Society 3 36694809
2018 The outer membrane Omp85-like protein P39 influences metabolic homeostasis in mature Arabidopsis thaliana. Plant biology (Stuttgart, Germany) 3 29758131
2025 The Role of V-ATPase ATP6V0D1 Subunit in Chemoresistance and Ellipticine-Induced Cytoplasmic Vacuolation in Neuroblastoma Cells. Molecular & cellular oncology 1 40552114