ArticleThe Journal of biological chemistry2014
Phospholipid flippase activities and substrate specificities of human type IV P-type ATPases localized to the plasma membrane.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 74 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
74 citing papers in PubMed, 132 citations in OpenAlex.
- Clinical variability of ATP11C-related hemolytic anemia: expanding the phenotypic and diagnostic spectrum.Blood advances · 2026Article
- ATP8B1-TMEM30B Flippase Activity Maintains Stereocilia Lipid Asymmetry Required for Hearing.bioRxiv : the preprint server for biology · 2026Article
- Leaflet-specific phospholipid imaging using genetically encoded proximity sensors.Nature chemical biology · 2026Article
- Article
- Lipid flippases ATP9A and ATP9B form a complex and contribute to the exocytic pathway from the Golgi.Life science alliance · 2025Article
- ATP8A1-translocated endosomal phosphatidylserine fine-tunes the multivesicular body formation and the endo-lysosomal traffic.iScience · 2025Article
- The Surface Proteome of Bovine Unsexed and Sexed Spermatozoa.Animals : an open access journal from MDPI · 2025Article
- Substrates, regulation, cellular functions, and disease associations of P4-ATPases.Communications biology · 2025Review
- Context-specific eQTLs reveal causal genes underlying shared genetic architecture of critically ill COVID-19 and idiopathic pulmonary fibrosis.medRxiv : the preprint server for health sciences · 2024Article
- Functional and in silico analysis of ATP8A2 and other P4-ATPase variants associated with human genetic diseases.Disease models & mechanisms · 2024Article
- Flipping the script: Advances in understanding how and why P4-ATPases flip lipid across membranes.Biochimica et biophysica acta. Molecular cell research · 2024Review
- Glucosylceramide flippases contribute to cellular glucosylceramide homeostasis.Journal of lipid research · 2024Article
- Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease.Cell structure and function · 2024Article
- Article
- Downregulation of ATP8B2 to Assess Plasmalogen Distribution and Far1 Expression in Primary Trabecular Meshwork Cells.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Intestinal Atp8b1 dysfunction causes hepatic choline deficiency and steatohepatitis.Nature communications · 2023Article
- Activation and substrate specificity of the human P4-ATPase ATP8B1.Nature communications · 2023Article
- Reconstitution of ATP-dependent lipid transporters: gaining insight into molecular characteristics, regulation, and mechanisms.Bioscience reports · 2023Review
- Type IV P-Type ATPases: Recent Updates in Cancer Development, Progression, and Treatment.Cancers · 2023Review
- Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type IV P-type ATPases (P4-ATPases) are believed to translocate aminophospholipids from the exoplasmic to the cytoplasmic leaflets of cellular membranes. The yeast P4-ATPases, Drs2p and Dnf1p/Dnf2p, flip nitrobenzoxadiazole-labeled phosphatidylserine at the Golgi complex and nitrobenzoxadiazole-labeled phosphatidylcholine (PC) at the plasma membrane, respectively. However, the flippase activities and substrate specificities of mammalian P4-ATPases remain incompletely characterized. In this study, we established an assay for phospholipid flippase activities of plasma membrane-localized P4-ATPases using human cell lines stably expressing ATP8B1, ATP8B2, ATP11A, and ATP11C. We found that ATP11A and ATP11C have flippase activities toward phosphatidylserine and phosphatidylethanolamine but not PC or sphingomyelin. By contrast, ATPase-deficient mutants of ATP11A and ATP11C did not exhibit any flippase activity, indicating that these enzymes catalyze flipping in an ATPase-dependent manner. Furthermore, ATP8B1 and ATP8B2 exhibited preferential flippase activities toward PC. Some ATP8B1 mutants found in patients of progressive familial intrahepatic cholestasis type 1 (PFIC1), a severe liver disease caused by impaired bile flow, failed to translocate PC despite their delivery to the plasma membrane. Moreover, incorporation of PC mediated by ATP8B1 can be reversed by simultaneous expression of ABCB4, a PC floppase mutated in PFIC3 patients. Our findings elucidate the flippase activities and substrate specificities of plasma membrane-localized human P4-ATPases and suggest that phenotypes of some PFIC1 patients result from impairment of the PC flippase activity of ATP8B1.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.