protein
Phospholipid-transporting ATPase IB
Gene
ATP8A2
Organism
Homo sapiens(9606)
Length
1188 aa
Mass
133,599 Da
ATP8A2 is a phospholipid-transporting ATPase that functions as the catalytic component of a P4-ATPase flippase complex (UniProt: Q9NTI2). It catalyzes ATP-dependent translocation of aminophospholipids, particularly phosphatidylserine and phosphatidylethanolamine, from the outer to inner membrane leaflets. The protein is proposed to regulate phospholipid asymmetry in photoreceptor disk and neuronal axon membranes, support vesicle trafficking in neurons, and maintain visual and auditory function through effects on photoreceptor and spiral ganglion cell survival (UniProt: Q9NTI2).
ATP8A2 is primarily relevant to neuronal function and membrane homeostasis. Mutations in ATP8A2 cause cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 4 (CAMRQ4), an autosomal recessive congenital disorder (UniProt: Q9NTI2, MIM 615268).
In Alzheimer's disease, ATP8A2 is significantly down-regulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: −0.36; Chaparral AD proteomics). This reduction was observed across subcellular fractions in TMT-labeled proteomics analysis, suggesting compromised phospholipid homeostasis and membrane trafficking capacity in AD pathology.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.358
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.3585 (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
Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids (By similarity). Able to translocate phosphatidylserine, but not phosphatidylcholine (PubMed:34403372). Phospholipid translocation also seems to be implicated in vesicle formation and in uptake of lipid signaling molecules (By similarity). Reconstituted to liposomes, the ATP8A2:TMEM30A flippase complex predominantly transports phosphatidylserine (PS) and to a lesser extent phosphatidylethanolamine (PE) (By similarity). Phospholipid translocation is not associated with a countertransport of an inorganic ion or other charged substrate from the cytoplasmic side toward the exoplasm in connection with the phosphorylation from ATP (By similarity). ATP8A2:TMEM30A may be involved in regulation of neurite outgrowth (By similarity). Proposed to function in the generation and maintenance of phospholipid asymmetry in photoreceptor disk membranes and neuronal axon membranes (By similarity). May be involved in vesicle trafficking in neuronal cells (By similarity). Required for normal visual and auditory function; involved in photoreceptor and inner ear spiral ganglion cell survival (By similarity)
Disease associations
Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome 4CAMRQ4
An autosomal recessive, congenital cerebellar ataxia associated with dysarthia, quadrupedal gait and intellectual disability.
Sources
Last updated 5/8/2026, 6:26:27 AM
