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protein

Phospholipid-transporting ATPase IB

ATP8A2
protein:Q9NTI2disease:adad:direction:down

Gene

ATP8A2

Organism

Homo sapiens(9606)

Length

1188 aa

Mass

133,599 Da

AI summarysource-grounded · cited inline
claude-haiku-4-5-20251001

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 AD

P3

-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.

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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