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FLASH GENE
Symbol ATP6V0D2 contributors: mct/npt/pgu - updated : 10-03-2020
HGNC name ATPase, H+ transporting, lysosomal 38kDa, V0 subunit d2
HGNC id 18266
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
secondary structure a proteolipid hexameric ring that translocates protons when ATP is hydrolysed by the catalytic cytoplasmic sector (V1)
mono polymer hexamer
HOMOLOGY
interspecies homolog to murine Atp6v0d2
Homologene
FAMILY
  • V-ATPase V0D/AC39 subunit family
  • CATEGORY transport
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    text
  • is also highly expressed in plasma membrane of specialized cells in kidney and other tissues
  • basic FUNCTION
  • essential for acidification of diverse intracellular compartments
  • required for urine acidification, and in osteoclasts, playing an important role in bone resorption by acid secretion across the ruffled border membrane
  • regulator of osteoclast fusion and bone formation
  • in the epididymis and vas deferens, the vacuolar H(+)ATPase (V-ATPase), located in the apical pole of narrow and clear cells, is required to establish an acidic luminal pH and also participates in the acidification of intracellular organelles
  • plays an important role in osteoclast maturation and bone formation
  • important subunit of the V-ATPase proton pump, which regulates bone homeostasis
  • having a dual function as a regulator of cell fusion in osteoclast differentiation and as an essential component of the osteoclast-specific proton pump that mediates extracellular acidification in bone resorption
  • required for amino acid signaling to MTOR and functions between amino acids and the nucleotide loading of the Rag GTPases
  • plays a key role in enamel development, specifically lysosomal acidification
  • playing a pivotal role in acid-base homeostasis
  • is a key component of macrophage-specific autophagosome-lysosome fusion machinery maintaining macrophage organelle homeostasis and, in turn, limiting both inflammation and bacterial infection
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text proton transport
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with NFATC1 (NFATC1/ATP6V0D2 and dendritic cell-specific transmembrane protein signaling axis plays a key role in the osteoclast multinucleation process, which is essential for efficient bone resorption)
  • interacting with ADRM1, a new ATP6V0D2-interacting protein, playing an important role in osteoclast differentiation, and in particular the fusion of preosteoclasts
  • ATP6V0D2 interacts physically and also functionally with CACNA1E
  • ATP6V0D2 and CLCN5 are functionally coupled during endosomal acidification and/or endocytosis
  • is dispensable for lysosome acidification, but promotes the completion of autophagy via promotion of autophagosome-lysosome fusion through its interaction with STX17 and VAMP8
  • ELAVL1 stabilizes ATP6V0D2 mRNA, which is required for the TLR3-mediated innate immune responses
  • cell & other
    REGULATION
    induced by insulin and activation of ATP6V0D2 and NFATC1 is involved in regulation of osteoclast differentiation and fusion through ERK1/2
    Other transactivated by MEF2A and MITF (MEF2A and MITF function cooperatively with NFATC1 to transactivate the ATP6V0D2 promoter during RANKL-induced osteoclastogenesis)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    during osteoclast differentiation
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
    inactivation of Atp6v0d2 in mice results in markedly increased bone mass due to defective osteoclasts and enhanced bone formation