ATP6V1A

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of two V1 domain A subunit isoforms and is found in all tissues. Transcript variants derived from alternative polyadenylation exist. [provided by RefSeq]

ATPase, H+ transporting, lysosomal 70kDa, V1 subunit A

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 (By similarity).
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 Fe2+ 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.

Cellular iron ion homeostasis Source: UniProtKB
Cellular response to amino acid starvation Source: Reactome
Cellular response to increased oxygen levels Source: UniProtKB
Insulin receptor signaling pathway Source: Reactome
Ion transmembrane transport Source: Reactome
Phagosome acidification Source: Reactome
Proton transmembrane transport Source: GO_Central
Regulation of macroautophagy Source: ParkinsonsUK-UCL
Transferrin transport Source: Reactome

Cytoplasm; Secretory vesicle. Co-localizes with WFS1 in the secretory granules in neuroblastoma cell lines.

Cutis laxa, autosomal recessive, 2D (ARCL2D): 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, 3 (IECEE3): 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.

Phosphorylation at Ser-384 by AMPK downregulates its enzyme activity.