protein
Sodium/potassium-transporting ATPase subunit alpha-3
aka Na(+)/K(+) ATPase alpha-3 subunit
Gene
ATP1A3
Organism
Homo sapiens(9606)
Length
1013 aa
Mass
111,749 Da
ATP1A3 encodes the catalytic alpha-3 subunit of the Na+/K+-ATPase, which catalyzes ATP-dependent exchange of sodium and potassium ions across the plasma membrane to establish the electrochemical gradients essential for neuronal excitability and active nutrient transport (UniProt: P13637). The protein is widely expressed and particularly critical in the nervous system for maintaining neuronal ion homeostasis.
ATP1A3 mutations cause several neurodevelopmental and neurological disorders including Dystonia 12, Alternating Hemiplegia of Childhood 2, cerebellar ataxia syndromes, and Developmental and Epileptic Encephalopathy 99 (UniProt: P13637), reflecting its essential role in neuronal function. These genetic associations underscore the protein's importance in maintaining proper neurological homeostasis.
In Alzheimer's disease, ATP1A3 is upregulated in post-mortem AD brain relative to age-matched controls (mean log2FC = 0.648, Chaparral AD proteomics). This elevation may reflect compensatory responses to neuronal stress or altered ion homeostasis in AD pathology, potentially linking metabolic dysregulation to AD neurodegeneration.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
+0.648
S3
not detected
Mean log₂FC across detected fractions: +0.648 (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
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients
Disease associations
Dystonia 12DYT12
An autosomal dominant dystonia-parkinsonism disorder. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DYT12 patients develop dystonia and parkinsonism between 15 and 45 years of age. The disease is characterized by an unusually rapid evolution of signs and symptoms. The sudden onset of symptoms over hours to a few weeks, often associated with physical or emotional stress, suggests a trigger initiating a nervous system insult resulting in permanent neurologic disability.
Alternating hemiplegia of childhood 2AHC2
A rare syndrome of episodic hemi- or quadriplegia lasting minutes to days. Most cases are accompanied by dystonic posturing, choreoathetoid movements, nystagmus, other ocular motor abnormalities, autonomic disturbances, and progressive cognitive impairment. It is typically distinguished from familial hemiplegic migraine by infantile onset and high prevalence of associated neurological deficits that become increasingly obvious with age.
Cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing lossCAPOS
An autosomal dominant neurologic disorder characterized by relapsing and partially remitting, early-onset cerebellar ataxia following a febrile illness. Other features include progressive optic atrophy and sensorineural hearing loss, generalized hypotonia, areflexia and pes cavus without evidence of a peripheral neuropathy on neurophysiological studies.
Developmental and epileptic encephalopathy 99DEE99
A form of epileptic encephalopathy, a heterogeneous group of early-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. DEE99 is an autosomal dominant form characterized by onset of seizures in early childhood.
Sources
Last updated 5/8/2026, 6:28:07 AM