Recombinant Human V-type proton ATPase subunit d 1 (ATP6V0D1)

Function

Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:28296633, PubMed:30374053, PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it promotes acidification of the extracellular environment (PubMed:30374053). The V-ATPase complex also acts as an activator for mTORC1 on lysosomal membrane by promoting the guanine nucleotide exchange factor (GEF) of the Ragulator complex, thereby enabling mTORC1 recruitment (PubMed:22053050). May play a role in coupling of proton transport and ATP hydrolysis (By similarity). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). May play a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium (By similarity)

Subcellular Location

Membrane (Peripheral membrane protein); Lysosome membrane (Peripheral membrane protein); Cytoplasmic vesicle, clathrin-coated vesicle membrane (Peripheral membrane protein)

Tissue Specificity

Ubiquitous

Subunit

V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (PubMed:33065002). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (PubMed:33065002). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (PubMed:33065002). Interacts with ATP6AP2; ATP6AP2 is a V-ATPase accessory protein and the interaction promotes v-ATPase complex assembly (PubMed:30374053). Interacts with TMEM9; TMEM9 is a v-ATPase assembly regulator and the interaction induces the interaction with ATP6AP2 (PubMed:30374053). Interacts with PIP4P1 (PubMed:29644770)

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• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
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• Burkard T.R. et al. Initial characterization of the human central proteome. — BMC Syst. Biol. (2011)
• Zoncu R. et al. mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase. — Science (2011)
• Chen Y. et al. A SNX10/V-ATPase pathway regulates ciliogenesis in vitro and in vivo. — Cell Res. (2012)