protein
V-type proton ATPase subunit S1
aka V-ATPase subunit S1
Gene
ATP6AP1
Organism
Homo sapiens(9606)
Length
470 aa
Mass
52,026 Da
ATP6AP1 encodes V-type proton ATPase subunit S1, an accessory component of the vacuolar H+-ATPase complex (UniProt: Q15904). This protein guides V-ATPase into specialized subcellular compartments including secretory vesicles and osteoclast ruffled borders, regulating luminal acidification and membrane trafficking. It also participates in intracellular iron homeostasis by modulating HIF1A hydroxylation in aerobic conditions.
ATP6AP1 is implicated in Immunodeficiency 47 (IMD47), an X-linked recessive disorder characterized by hypogammaglobulinemia, recurrent infections, and abnormal protein glycosylation, with neurologic manifestations including seizures and behavioral abnormalities in some patients (UniProt: Q15904).
In Alzheimer's Disease, ATP6AP1 is significantly downregulated in post-mortem AD brain relative to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.76 across subcellular fractions. This reduction may reflect impaired vesicular acidification and membrane dynamics pathways relevant to amyloid and tau metabolism in AD neurodegeneration.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.761
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.7612 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
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)
Disease associations
Immunodeficiency 47IMD47
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.
Sources
Last updated 5/8/2026, 6:27:08 AM