protein
V-type proton ATPase catalytic subunit A
aka V-ATPase subunit A
Gene
ATP6V1A
Organism
Homo sapiens(9606)
Length
617 aa
Mass
68,304 Da
ATP6V1A (V-type proton ATPase catalytic subunit A) is the catalytic component of vacuolar H+-ATPase (V-ATPase), a multisubunit enzyme that hydrolyzes ATP to pump protons across intracellular membranes and maintain compartment acidification (UniProt: P38606). The protein also regulates intracellular iron homeostasis and may support neurite development and synaptic connectivity. Beyond its housekeeping roles, ATP6V1A participates in viral membrane fusion events during Rabies virus infection (UniProt: P38606).
ATP6V1A is ubiquitously expressed and particularly relevant in neurons, where V-ATPase dysfunction has been linked to infantile epileptic encephalopathy (IECEE3) and cutis laxa autosomal recessive type 2D (ARCL2D), a neurodevelopmental disorder with seizures and hypotonia (UniProt: P38606).
In Alzheimer's disease, ATP6V1A is consistently down-regulated in post-mortem AD brain compared to age-matched controls (mean log2 fold-change −0.32 across two subcellular fractions), suggesting impaired lysosomal and endosomal acidification may contribute to AD pathophysiology (Chaparral AD proteomics).
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.390
P2
-0.253
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.3218 (2 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
Catalytic subunit of the V1 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:8463241). 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 is responsible for acidifying the extracellular environment (PubMed:32001091). 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 neurite development and synaptic connectivity (PubMed:29668857)
(Microbial infection) Plays an important role in virion uncoating during Rabies virus replication after membrane fusion. Specifically, participates in the dissociation of incoming viral matrix M proteins uncoating through direct interaction
Disease associations
Cutis laxa, autosomal recessive, 2DARCL2D
A form of cutis laxa, a disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, and a general connective tissue weakness. Most ARCL2D patients exhibit severe hypotonia as well as cardiovascular and neurologic involvement.
Epileptic encephalopathy, infantile or early childhood, 3IECEE3
A form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. IECEE3 is an autosomal dominant form characterized by onset of seizures in the first years of life. The severity of the phenotype is highly variable: some patients may be non-verbal and non-ambulatory with spastic quadriparesis and poor eye contact, whereas others have moderate intellectual disability.
Sources
Last updated 5/8/2026, 6:26:42 AM