ATP6AP1
Function
Accessory subunit of the proton-transporting vacuolar (V)-ATPase protein pump, which is required for luminal acidification of secretory vesicles (PubMed:33065002). Guides the V-type ATPase into specialized subcellular compartments, such as neuroendocrine regulated secretory vesicles or the ruffled border of the osteoclast, thereby regulating its activity (PubMed:27231034). Involved in membrane trafficking and Ca(2+)-dependent membrane fusion (PubMed:27231034). May play a role in the assembly of the V-type ATPase complex (Probable). 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). In islets of Langerhans cells, may regulate the acidification of dense-core secretory granules (By similarity).
Involvement in disease
Immunodeficiency 47
IMD47
A complex immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, defective glycosylation of serum proteins, and liver disease with neonatal jaundice and hepatosplenomegaly. Some patients may also have neurologic features, including seizures, mild intellectual disability, and behavioral abnormalities. Inheritance is X-linked recessive.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
N-glycosylated.
Sequence Similarities
Belongs to the vacuolar ATPase subunit S1 family.
Tissue Specificity
widely expressed, with highest levels in brain and lowest in liver and duodenum.
Cellular localization
- Endoplasmic reticulum membrane
- Single-pass type I membrane protein
- Endoplasmic reticulum-Golgi intermediate compartment membrane
- Cytoplasmic vesicle
- Secretory vesicle
- Synaptic vesicle membrane
- Single-pass type I membrane protein
- Cytoplasmic vesicle
- Clathrin-coated vesicle membrane
- Single-pass type I membrane protein
- Not detected in trans-Golgi network.
Alternative names
ATP6IP1, ATP6S1, VATPS1, XAP3, ATP6AP1, V-type proton ATPase subunit S1, V-ATPase subunit S1, Protein XAP-3, V-ATPase Ac45 subunit, V-ATPase S1 accessory protein, Vacuolar proton pump subunit S1