Affinage

ANO6

Anoctamin-6 · UniProt Q4KMQ2

Length
910 aa
Mass
106.2 kDa
Annotated
2026-04-28
99 papers in source corpus 45 papers cited in narrative 45 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANO6 (TMEM16F) is a Ca²⁺-activated plasma membrane protein that functions as both a phospholipid scramblase and a non-selective ion channel, serving as the principal mediator of Ca²⁺-dependent phosphatidylserine externalization across diverse cell types. Ca²⁺ binds directly to conserved acidic residues in the transmembrane domain, inducing conformational rearrangements—including formation of an X-shaped groove—that open physically distinct but structurally coupled pathways for bidirectional lipid translocation (~4.5×10⁴ lipids/s, preferring PS and PC) and ion permeation, with activity further modulated by PIP₂, intracellular pH, and the actin cytoskeleton (PMID:21107324, PMID:29507235, PMID:37573365, PMID:41998358, PMID:33346788). Upstream Ca²⁺ sources including PIEZO1 and TRPV4 feed into TMEM16F activation in cell-type-specific contexts (PMID:38033286, PMID:35670667). TMEM16F-driven PS exposure is essential for platelet procoagulant activity, trophoblast syncytialization, osteoblast mineralization, plasma membrane repair, microglial phagocytosis, ectosome/extracellular vesicle biogenesis, TCR signal modulation, and endothelial angiogenesis (PMID:23021219, PMID:32494719, PMID:22936354, PMID:31995754, PMID:27332874, PMID:41604453, PMID:33758060, PMID:38940198). Loss-of-function mutations in ANO6 cause Scott syndrome, a bleeding disorder characterized by defective platelet phospholipid scrambling (PMID:21107324, PMID:23303820).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2010 High

    The identity of the long-sought Ca²⁺-dependent phospholipid scramblase was unknown; expression cloning identified TMEM16F as the essential component, and a Scott syndrome patient mutation provided human genetic validation, establishing TMEM16F as the Ca²⁺-dependent scramblase.

    Evidence Expression cloning in Ba/F3 cells with FACS-based PS assay, patient mutation sequencing

    PMID:21107324

    Open questions at the time
    • Mechanism of scrambling (channel vs. transporter) unresolved
    • Whether TMEM16F also conducts ions was unknown
    • Structure of the protein undetermined
  2. 2012 High

    Whether TMEM16F conducted ions and what its in vivo physiological role was remained open; electrophysiology revealed TMEM16F generates Ca²⁺-activated nonselective cation currents, and knockout mice demonstrated essential roles in platelet procoagulant activity and hemostasis.

    Evidence TMEM16F KO mouse, patch-clamp in megakaryocytes, pore-region mutagenesis

    PMID:23021219

    Open questions at the time
    • Whether ion conduction and scrambling are mechanistically separable was unresolved
    • Structural basis of ion selectivity unknown
  3. 2013 High

    The relationship between TMEM16F's channel and scramblase activities, ion selectivity properties, and physiological roles beyond platelets needed clarification; multiple studies established that scrambling can occur independently of ion currents, identified the functional pore region (TM5-TM6), demonstrated roles in osteoblast mineralization, and dissected pathway-specific PS exposure in Scott syndrome platelets.

    Evidence Patch-clamp with pharmacological dissection and Scott patient cells; pore-region mutagenesis in HEK293; Ano6 KO mouse osteoblast mineralization assays; flow cytometry of Scott patient platelets

    PMID:22936354 PMID:23303820 PMID:23426967 PMID:23618909 PMID:23630341

    Open questions at the time
    • Structural basis for dual function undetermined
    • How Ca²⁺ binds and gates the protein unknown
    • Molecular determinants distinguishing scramblase from channel activity not identified
  4. 2015 High

    What structural domain confers scramblase activity, and whether TMEM16F functions as a monomer or oligomer, was unknown; chimera studies identified a specific scramblase domain transferable to the channel-only paralog TMEM16A, cross-linking revealed homodimers, and isoform analysis with gain-of-function mutations confirmed both activities reside in one protein.

    Evidence ANO1-ANO6 chimeras with PS and electrophysiology readouts; chemical cross-linking; splice-variant characterization; D409G activating mutation; platelet-specific conditional KO

    PMID:24478309 PMID:26057829 PMID:26108457 PMID:26417084

    Open questions at the time
    • Atomic structure not yet available
    • Ca²⁺-binding site residues in TMEM16F not directly identified
    • Whether ion and lipid pathways are physically the same groove remained debated
  5. 2016 High

    TMEM16F's roles beyond hemostasis and bone were largely unexplored; conditional KO studies revealed TMEM16F in late endosomes controls TCR degradation and T cell signal termination, and in microglia it is essential for phagocytosis and neuropathic pain responses, while biochemical studies identified specific Ca²⁺-binding residues.

    Evidence Conditional KO mice in T cells and microglia; late-endosome localization; TCR degradation and viral infection models; blue-native PAGE and comprehensive mutagenesis of Ca²⁺-coordinating acidic residues

    PMID:27227820 PMID:27332874 PMID:27810927

    Open questions at the time
    • Structural mechanism of Ca²⁺-dependent gating unknown
    • How TMEM16F reaches late endosomes was unexplained
    • Whether late-endosomal and plasma membrane functions are mechanistically identical was unclear
  6. 2018 High

    Regulatory mechanisms controlling TMEM16F activity in situ were poorly understood; studies identified PIP₂ as a positive modulator acting via N-terminal cationic residues, the actin cytoskeleton as a negative kinetic regulator, and purified single-molecule reconstitution quantified scrambling rates consistent with a facilitated-diffusion mechanism.

    Evidence Excised patch with PIP₂ application and N-terminal mutagenesis; cytoskeleton-modulating agents with patch-clamp; purified TMEM16F dimer reconstituted in lipid bilayer microarray for single-molecule scrambling

    PMID:29382763 PMID:29507235 PMID:29964013

    Open questions at the time
    • Structural basis of PIP₂ regulation not visualized
    • How actin physically interacts with TMEM16F unknown
    • Contributions of additional regulators (e.g., pH) not yet explored
  7. 2019 High

    The structural basis for TMEM16F's dual activity and whether ion and lipid pathways are the same remained debated; cryo-EM structures revealed Ca²⁺-bound and Ca²⁺-free conformations, mutagenesis identified a hydrophobic inner activation gate (F518/Y563/I612), dynamic ion selectivity shifting with Ca²⁺ was demonstrated, and roles in membrane expansion/ectosome shedding and ferroptosis were established.

    Evidence Cryo-EM of apo and Ca²⁺-bound TMEM16F; constitutively active gate mutants; ion substitution with varying Ca²⁺; live-cell microscopy with KO Jurkat cells; tissue-specific KO with ferroptosis inducers

    PMID:30679690 PMID:30785399 PMID:31015464 PMID:31060306 PMID:31291589 PMID:31318330

    Open questions at the time
    • Cryo-EM captured only intermediate states, not the fully open active conformation
    • Whether the gate mutant phenotype reflects the physiological open state was uncertain
    • Mechanism of membrane expansion coupling to scrambling was unclear
  8. 2020 High

    Whether TMEM16F contributes to membrane repair and trophoblast fusion in vivo was untested; KO studies showed TMEM16F-mediated blebbing and EV release are essential for plasma membrane repair after pore-forming toxin injury, and TMEM16F drives PS-dependent trophoblast syncytialization required for placental development.

    Evidence TMEM16F-deficient cells/mice with pore-forming toxin and Listeria infection; TMEM16F KO mouse placental histology and trophoblast fusion assays

    PMID:31995754 PMID:32494719

    Open questions at the time
    • Whether TMEM16F directly interacts with fusion machinery was unknown
    • Role of specific upstream Ca²⁺ channels in trophoblast context not identified
  9. 2021 High

    How TMEM16F scrambling translates into membrane expansion and TCR signaling modulation was mechanistically unclear; studies revealed TMEM16F lipid scrambling relaxes dynamin-held membrane invaginations to expand the cell surface, and at the immunological synapse PS redistribution reduces electrostatic potential to release bystander TCR-CD3 tails, amplifying signaling.

    Evidence TMEM16F/dynamin double-KO with live imaging; T cell activation assays with membrane electrostatic probes and TCR-CD3 association measurements

    PMID:33758060 PMID:34404808

    Open questions at the time
    • Whether dynamin directly binds TMEM16F or acts indirectly via lipid sensing was unresolved
    • Quantitative contribution of electrostatic mechanism vs. other signaling effects unknown
  10. 2022 High

    The structural basis for physically separating ion and lipid permeation paths, upstream Ca²⁺ sources in trophoblasts, and viral exploitation of TMEM16F were open questions; cryo-EM of activating mutants revealed hydrophilic patch exposure and concomitant pore opening, TRPV4 was identified as the upstream Ca²⁺ channel coupling to TMEM16F in trophoblasts, PIEZO1 was shown to couple to TMEM16F in RBCs, and Spike-mediated SARS-CoV-2 entry was found to require TMEM16F-dependent PS scrambling.

    Evidence Cryo-EM of activating mutants; TRPV4 agonist/antagonist with trophoblast patch-clamp; PIEZO1-TMEM16F coupling in hereditary xerocytosis RBCs; SARS-CoV-2 pseudovirus and authentic infection with ANO6 inhibitor

    PMID:35670667 PMID:35839776 PMID:36335104 PMID:38033286

    Open questions at the time
    • Full open-state structure in lipid environment not yet captured
    • Whether PIEZO1-TMEM16F coupling involves direct interaction or only Ca²⁺ microdomain proximity was unclear
  11. 2023 High

    Whether ion and lipid pathways are truly physically distinct at atomic resolution was debated; drug-bound cryo-EM structures revealed a lipid scrambling groove outside the ion pore with a druggable pocket, and mutagenesis selectively affected scrambling without impairing ion conduction, providing the clearest structural evidence for separate pathways.

    Evidence Cryo-EM with bound niclosamide/1PBC, structure-guided mutagenesis with parallel scramblase and channel assays

    PMID:37573365

    Open questions at the time
    • Whether the drug-binding pocket represents a physiological regulatory site unknown
    • Resolution of lipid headgroup interactions within the groove not achieved
  12. 2024 High

    TMEM16F's roles in neurodegeneration and vascular biology were emerging; neuron-specific KO reduced tau pathology and α-synuclein spread, endothelial KO impaired retinal angiogenesis via Src/VE-cadherin signaling, and AFM revealed structurally diverse TMEM16F assemblies with Ca²⁺-induced stepwise mechanical changes.

    Evidence Cell-type-specific KO in PS19 tauopathy and PD models; endothelial KO retinal angiogenesis with Src phosphorylation analysis; AFM under physiological conditions

    PMID:38167485 PMID:38940198 PMID:38941274 PMID:39487963

    Open questions at the time
    • Whether PS exposure directly mediates tau/α-syn pathology or acts indirectly through phagocytic signals unclear
    • Direct physical basis for Src membrane retention change not structurally resolved
    • Physiological significance of TMEM16F structural heterogeneity unknown
  13. 2025 High

    The fully active conformation of TMEM16F in a lipid environment had never been captured; cryo-EM in liposomes revealed an X-shaped groove formed by cytosolic domain rotation that simultaneously enables ion flux through a central pore and lipid scrambling along the groove periphery, while cell-based assays showed unexpected PS/PC preference over PE.

    Evidence Cryo-EM in liposomes with MD simulations and mutagenesis; live-cell fluorescence polarization scrambling assay with multiple lipid species

    PMID:41166415 PMID:41998358

    Open questions at the time
    • Whether the X-shaped groove is the sole active conformation or one of multiple substates is uncertain
    • Molecular determinants of headgroup selectivity not identified
    • How lipid preference relates to physiological PS exposure vs. other lipid movements unknown
  14. 2026 High

    Whether lipid scrambling alone suffices for extracellular vesicle biogenesis without cytoskeletal or Ca²⁺ signaling changes was untested; inducible constitutively active TMEM16F demonstrated that scrambling alone drives lipid domain segregation, cholesterol redistribution, GPI-anchor clustering, PE-mediated concave curvature, and vesicle scission.

    Evidence Inducible constitutively active TMEM16F with live-cell lipid domain and EV analysis

    PMID:41604453

    Open questions at the time
    • Whether this mechanism operates in physiological (non-overexpressed) contexts uncertain
    • Identity of scission machinery (if any) beyond lipid curvature not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the complete conformational trajectory from resting to fully active states in native membranes, the molecular basis of phospholipid headgroup selectivity, whether TMEM16F directly interacts with upstream Ca²⁺ channels or acts solely through Ca²⁺ microdomains, and how TMEM16F's scramblase activity is differentially harnessed across its many physiological contexts (hemostasis, fusion, neurodegeneration, immunity).
  • Complete gating cycle at atomic resolution in native membranes not captured
  • Molecular basis for headgroup selectivity unidentified
  • Direct vs. microdomain-mediated coupling to upstream channels unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 6 GO:0005215 transporter activity 5 GO:0140104 molecular carrier activity 5
Localization
GO:0005886 plasma membrane 6 GO:0005768 endosome 1
Partners
DNM2PIEZO1TRPV4

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 TMEM16F (ANO6) is an essential component for Ca2+-dependent exposure of phosphatidylserine on the cell surface; wild-type TMEM16F localizes to the plasma membrane and confers Ca2+-dependent bidirectional phospholipid scrambling activity. A patient with Scott syndrome carries a splice-acceptor site mutation causing premature termination of TMEM16F, linking loss-of-function to defective phospholipid scrambling. Expression cloning in Ba/F3 cells, FACS-based PtdSer exposure assay, plasma membrane localization by fluorescence, patient mutation sequencing Nature High 21107324
2012 TMEM16F generates a small-conductance Ca2+-activated nonselective cation (SCAN) current permeable to both monovalent and divalent cations including Ca2+, with synergistic gating by Ca2+ and voltage. TMEM16F knockout mice lack Ca2+-dependent phosphatidylserine exposure and procoagulant activity in megakaryocytes, and exhibit bleeding defects and protection from arterial thrombosis. A pore-region residue determines cation vs. anion selectivity. TMEM16F knockout mouse generation, patch-clamp electrophysiology in megakaryocytes, heterologous expression, site-directed mutagenesis of pore region Cell High 23021219
2013 TMEM16F (ANO6) functions as a component of a Ca2+-activated Cl- channel with high Ca2+ threshold (~9.6 µM), anion selectivity sequence I->Br->Cl->F->aspartate-, and outward rectification. It is not related to volume-sensitive outwardly rectifying Cl- channel (VSOR) activity. Whole-cell patch-clamp in TMEM16F-transfected HEK293T cells, ion substitution experiments, siRNA knockdown American Journal of Physiology - Cell Physiology High 23426967
2013 ANO6-mediated Ca2+-dependent phospholipid scrambling can occur independently of its ion currents. Ca2+-independent phospholipid scrambling during apoptosis (intrinsic or extrinsic) does not require ANO6. ANO6 Cl- currents can be activated Ca2+-independently via Fas receptor stimulation. Patch-clamp electrophysiology, PS exposure assay (annexin V), Cl- channel blockers, siRNA knockdown, Scott syndrome patient B-lymphocytes Cell Death & Disease High 23618909
2013 ANO6 (TMEM16F) mediates Ca2+-dependent phospholipid scrambling in osteoblasts; deletion in mice results in impaired PS scrambling in osteoblasts and delayed mineralization, with increased areas of uncalcified osteoid postnatally. This establishes a cell-autonomous role for ANO6 in bone mineralization via PS exposure. Ano6 knockout mouse generation, primary osteoblast culture, mineralization assays, Ca2+-dependent PS scrambling assay in osteoblasts Journal of Bone and Mineral Research High 22936354
2013 In Scott syndrome patients, TMEM16F-dependent high-PS-exposing platelet fraction is absent upon convulxin/thrombin stimulation. TMEM16F is required for Ca2+-mobilizing agonist-induced PS exposure that depends on mitochondrial depolarization, but is not required for caspase-dependent basal PS exposure. Flow cytometry with annexin V, caspase inhibitors, Ca2+ chelation, Scott syndrome patient platelets vs. controls Blood High 23303820
2013 Mouse TMEM16F expressed in HEK293 cells produces a Ca2+-activated anion channel current (EC50 ~100 µM Ca2+) with delayed activation, Eisenman type 1 anion selectivity, and outward rectification. Pore-region mutations (R592E, K616E, R636E) alter or abolish currents, identifying the pore region between TM5 and TM6 as functional. Heterologous expression in HEK293, whole-cell patch-clamp, site-directed mutagenesis of pore residues Journal of General Physiology High 23630341
2015 TMEM16F is the only TMEM16 family member highly expressed in mouse platelets. Platelet-specific TMEM16F knockout causes defects in activation-induced PS exposure, microparticle shedding, and thrombin generation in vitro and in vivo (laser-induced thrombus model), without affecting granule release or clot retraction. Platelet-specific TMEM16F conditional KO mice, flow cytometry, thrombin generation assay, laser-induced thrombosis imaging in vivo PNAS High 26417084
2015 A specific domain in ANO6 is necessary and sufficient for phospholipid scrambling activity. By analyzing ANO1-ANO6 chimeric proteins, a scramblase domain was identified in ANO6 that, when transferred to ANO1 (which normally does not scramble), confers scramblase activity. Homology modeling shows this domain forms a hydrophilic cleft facing the lipid bilayer. Ion currents in ANO6 are explained by ionic leak during phospholipid translocation. Patch-clamp combined with PS exposure assay, ANO1-ANO6 chimera construction, homology modeling eLife High 26057829
2015 TMEM16F forms homodimers (shown by chemical cross-linking). The pore region between TM5 and TM6 is essential for both scramblase activity of TMEM16F and Cl- channel activity of TMEM16A. N-terminal and C-terminal cytoplasmic domains control plasma membrane localization and protein stability, respectively, and are functionally interchangeable between TMEM16A and TMEM16F. Chemical cross-linking, domain-swap chimeras, deletion analysis, functional assays in 293T cells and TMEM16F-/- thymocytes Journal of Biological Chemistry High 24478309
2015 TMEM16F isoforms generated by alternative splicing (V1, V2, V5) show plasma membrane localization and Ca2+-activated ion channel and scramblase activities, while V3 isoform (unique C-terminus) is intracellularly localized and inactive. An activating mutation D409G markedly increases apparent Ca2+ sensitivity of both channel and scramblase activities, directly demonstrating TMEM16F mediates both functions. Whole-cell patch-clamp, annexin V binding assay for PS, subcellular localization, activating mutation introduction, siRNA knockdown Journal of Physiology High 26108457
2016 TMEM16F is located in late endosomes in T lymphocytes, where it facilitates generation of multivesicular bodies for TCR degradation and signal termination. TMEM16F-deficient T cells show sustained TCR signaling, augmented activation, and increased proliferation and cytokine production in chronic viral infection, ultimately leading to T cell exhaustion. Conditional TMEM16F KO mice, viral chronic infection model, late endosome localization by imaging, TCR degradation assay, T cell functional assays Journal of Experimental Medicine High 27810927
2016 TMEM16F conditional knockout in microglia prevents mechanical hypersensitivity after nerve injury; TMEM16F-deficient microglia show deficits in process motility and phagocytosis. This establishes TMEM16F as essential for microglial responses to nerve injury in neuropathic pain. Conditional TMEM16F KO in microglia, neuropathic pain behavioral testing, microglial motility and phagocytosis assays Cell Reports High 27332874
2016 Ca2+ directly binds to TMEM16F; five acidic residues conserved between TMEM16F and TMEM16K are critical for Ca2+ binding (identified by comprehensive mutagenesis of TMEM16K). Point mutations of corresponding residues in TMEM16F reduce Ca2+-dependent phospholipid scrambling. Ca2+ stabilizes TMEM16F structure and induces conformational changes. Blue-native PAGE, comprehensive acidic-residue mutagenesis, Ca2+ binding assay, scramblase activity assay Biochemistry High 27227820
2017 TMEM16F/ANO6 ion currents and phospholipid scrambling can be activated by modification of plasma membrane phospholipids via reactive oxygen species and phospholipase A2 (PLA2), independently of intracellular Ca2+. Mutations within TMEM16F similarly change both Cl- currents and phospholipid scrambling, suggesting Cl- and phospholipids use the same intramolecular pathway. Whole-cell patch-clamp, annexin V PS exposure assay, PLA2 activation/inhibition, ROS donors, chimera/mutant analysis Journal of Physiology High 29134661
2018 Single purified TMEM16F dimeric molecules transport phospholipids nonspecifically and bidirectionally between membrane bilayer leaflets in a Ca2+-dependent manner at ~4.5×10^4 lipids/second at 25°C, with activation free energy of 47 kJ/mol. This biophysical profile is consistent with a channel-like facilitated diffusion ('stepping-stone') mechanism. Purification of mouse TMEM16F from stable cell line, single-molecule scramblase assay in lipid bilayer microarray, thermodynamic analysis PNAS High 29507235
2018 TMEM16F Ca2+-activated current is desensitized by brief high Ca2+ exposure associated with PIP2 depletion from the inner membrane leaflet. Application of PIP2 restores TMEM16F channel activity. PIP2 modulation requires positively charged amino acids in the cytoplasmic N-terminal domain and acts synergistically with membrane depolarization to facilitate Ca2+-gating. Excised patch and whole-cell patch-clamp, PIP2 application/depletion, N-terminal domain mutagenesis PNAS High 29382763
2019 Cryo-EM structures of murine TMEM16F in absence and presence of Ca2+ reveal a ligand-free closed conformation and a Ca2+-bound intermediate. Both conformations resemble TMEM16A counterparts but with distinct differences in ion/lipid permeation region. Ion conduction and lipid scrambling are activated by a common Ca2+-binding mechanism but appear mediated by alternate protein conformations at equilibrium in the Ca2+-bound state. Cryo-EM structure determination, functional electrophysiology, Ca2+-dependent activity assays eLife High 30785399
2019 Cryo-EM structural analysis reveals coexistence of an intact channel pore and PIP2-dependent membrane distortion in TMEM16F. Mutagenesis of lipid-binding residues near membrane distortion sites specifically alters onset of lipid scrambling without affecting Ca2+ influx, providing structural evidence for separate pathways for lipid scrambling and ion permeation. Cryo-EM, structure-based mutagenesis, functional assays for Ca2+ influx and PS exposure Cell Reports High 31291589
2019 TMEM16F contains an inner activation gate formed by three hydrophobic residues (F518, Y563, I612) in the middle of the phospholipid permeation pathway. Lysine substitutions of F518 and Y563 generate constitutively active scramblases bypassing Ca2+-dependent activation. An analogous mutation (L543K) in TMEM16A confers CaPLSase activity to this otherwise Cl- channel. Site-directed mutagenesis, PS exposure assay, patch-clamp electrophysiology, gain-of-function and loss-of-function analysis Nature Communications High 31015464
2019 TMEM16F ion selectivity dynamically shifts from cation-selective to anion-selective in response to increasing intracellular Ca2+, reflecting alteration of electrostatic field in the permeation pathway (charge-screening mechanism). The Q559K mutant reveals this selectivity shift is independent of channel activation state. Excised inside-out patch-clamp, ion substitution experiments with varying Ca2+ concentrations, mutagenesis eLife High 31318330
2019 TMEM16F activation by Ca2+ ionophores in Jurkat T cells triggers large-scale plasma membrane expansion coinciding with phospholipid scrambling, followed by ectosome shedding. PD-1 is selectively incorporated into ectosomes in a transmembrane-sequence-dependent manner. TMEM16F-deficient cells fail to expand surface membrane and instead undergo rapid massive endocytosis with PD-1 internalization. Live-cell microscopy, patch-clamp, flow cytometry, TMEM16F-KO Jurkat cells, PD-1 trafficking assays Scientific Reports High 30679690
2020 TMEM16F is essential for plasma membrane repair after pore-forming agent injury: pore formation triggers Ca2+ influx activating TMEM16F-mediated lipid scrambling, membrane blebbing, and extracellular vesicle release that preserve membrane integrity and cell viability. TMEM16F-deficient mice show compromised control of Listeria infection due to greater neutrophil sensitivity to listeriolysin O. TMEM16F-deficient cell lines and mice, pore-forming toxin treatment, cell viability assays, EV quantification, Listeria infection model Cell Reports High 31995754
2020 TMEM16F knockout mice show deficiency in trophoblast syncytialization and placental development leading to perinatal lethality. TMEM16F CaPLSase translocates PS to the cell surface independently of apoptosis during trophoblast fusion. TMEM16F KO mouse generation, placental histology, trophoblast fusion assays, PS exposure measurement Science Advances High 32494719
2020 TMEM16F governs Ca2+-activated Cl- conductance in spinal motoneurons and is expressed in synaptic clusters facing cholinergic C-boutons. Tmem16f exon-deleted mice show decreased motor performance under high-demanding tasks and increased recruitment threshold of fast α-motoneurons. Loss of TMEM16F in ALS mouse model delays disease onset and preserves strength in male mice. Targeted exon deletion mouse, immunolocalization at C-boutons, patch-clamp in motoneurons, motor behavioral assays, ALS mouse model Cell Reports High 32101737
2021 TMEM16F mediates Ca2+-dependent plasma membrane expansion via invaginations held shut by dynamin. Upon Ca2+ activation of TMEM16F, anionic phospholipids escape from the cytoplasmic monolayer and dynamins relax, opening compartments. Deletion of TMEM16F or dynamins blocks expansion; dynamin2 GTPase-inactivated mutant can regenerate reserve compartments but lipid-binding mutant cannot. TMEM16F KO cells, dynamin KO/re-expression, live-cell microscopy, dynamin2-GFP imaging, Ca2+-permeable mechanosensitive channel activation Nature Communications High 34404808
2021 TMEM16F Ca2+-dependent activation of PS scramblase during immunological synapse formation locally redistributes PS, reducing the electrostatic potential of the plasma membrane, which increases dissociation of bystander TCR-CD3 cytoplasmic domains from the membrane and enhances TCR-dependent signaling. This establishes the molecular basis for TMEM16F-mediated bystander TCR signal amplification. T cell activation assays, PS externalization measurement, membrane electrostatic potential probes, TCR-CD3 membrane association assays Science Signaling High 33758060
2021 TMEM16F channel and scramblase activities are strongly regulated by intracellular pH (pHi): low pHi attenuates and high pHi potentiates both activities. pHi sensitivity depends on [Ca2+]i and shows a bell-shaped relationship with [Ca2+]i. A Ca2+-binding residue mutation (E667Q) shifts the peak [Ca2+]i of pHi sensitivity, establishing that protons compete with Ca2+ at primary Ca2+-binding sites in the pore to regulate TMEM16F activation. Whole-cell patch-clamp, PS exposure assay at varying pHi and Ca2+ levels, Ca2+-binding residue mutagenesis (E667Q) Journal of General Physiology High 33346788
2022 TMEM16F is activated by SARS-CoV-2 Spike protein binding (via ACE2) to mediate PS externalization critical for viral entry. ANO6-selective inhibitor A6-001 identified by high-throughput screening inhibits both Spike-induced PS scrambling and authentic SARS-CoV-2 replication in multiple cell types. SARS2 pseudotyped virus, Ca2+ imaging, annexin V flow cytometry, high-throughput drug screening, authentic SARS-CoV-2 infection assays in Vero/Calu-3/primary nasal cells Cell Reports High 35839776
2022 Cryo-EM structures of activating TMEM16F mutants reveal major rearrangements leading to exposure of hydrophilic patches to the membrane, whose distortion facilitates lipid diffusion. Concomitant opening of a pore promotes ion conduction in the same protein conformation, revealing a mechanism distinct from other TMEM16 family members. Cryo-EM structure determination of activating mutants, functional scramblase and ion channel assays Nature Communications High 36335104
2022 TRPV4 Ca2+ influx channel is functionally coupled to TMEM16F within Ca2+ microdomains in human trophoblasts. TRPV4-specific agonist activates TMEM16F in trophoblasts; pharmacological inhibition or gene silencing of TRPV4 impairs TMEM16F activation and subsequent trophoblast syncytialization. Patch-clamp electrophysiology, TRPV4 agonist/antagonist treatment, gene silencing, PS exposure assay, trophoblast fusion assay eLife High 35670667
2023 Cryo-EM structures of TMEM16F with bound niclosamide or 1PBC reveal a lipid scrambling pathway along a groove outside the ion permeation pore containing a drug-binding pocket. Mutations in this groove specifically affect lipid scrambling but not ion conduction; some mutations preferentially reduce inhibition of PS exposure vs. Ca2+ influx, providing structural evidence for separate ion permeation and lipid scrambling pathways. Cryo-EM structure determination with bound drugs, mutagenesis, patch-clamp, PS exposure assay Nature Communications High 37573365
2024 TMEM16F (the RBC Ca2+-activated phospholipid scramblase) is activated downstream of Ca2+ influx through the mechanosensitive channel PIEZO1 in red blood cells. In hereditary xerocytosis (PIEZO1 gain-of-function), enhanced PIEZO1-TMEM16F coupling increases propensity for PS exposure, contributing to anemia, splenomegaly and thrombosis. Inhibition of PIEZO1 with benzbromarone prevents force-induced PS exposure. Electrophysiology, flow cytometry, imaging in RBCs from HX patients and controls; pharmacological PIEZO1 inhibition; functional hemolysis and PS assays Blood High 38033286
2024 TMEM16F deficiency in neurons (but not microglia) reduces tau pathology and microgliosis in a PS19 tauopathy mouse model. TMEM16F mediates aberrant PS exposure in neurons with phospho-tau burden, establishing a neuronal-autonomous role for TMEM16F in tau pathology. Cell-type-specific TMEM16F KO in PS19 tau mouse model, immunohistochemistry, PS exposure assay in neurons PNAS High 38941274
2024 TMEM16F deficiency in endothelial cells impairs developmental retinal angiogenesis. Biochemically, TMEM16F absence enhances plasma membrane association of activated Src kinase (Y416 phosphorylation), increases VE-cadherin phosphorylation and downregulation, suppressing angiogenesis. This establishes an intracellular signaling role for TMEM16F in endothelial cells. Endothelial-specific TMEM16F KO mice, retinal angiogenesis assay, Src kinase phosphorylation, VE-cadherin Western blot/immunofluorescence, HUVEC siRNA knockdown Journal of Cell Science High 38940198
2024 TMEM16F regulates pathologic α-synuclein (α-synA53T) spread in neurons. Neurons from TMEM16F KO mice show reduced donor-to-recipient spread of α-synA53T. In vivo PD mouse model shows attenuated α-synA53T spread upon TMEM16F ablation. A missense SNP (Ala703Ser) in TMEM16F with enhanced scramblase activity is associated with altered α-synA53T secretion in Ashkenazi Jewish PD patients. TMEM16F KO neurons with reporter-based spread assay, in vivo PD mouse model, lipid scramblase activity assay for Ala703Ser variant Aging Cell High 39487963
2018 ANO6/TMEM16F Cl- channel activation kinetics are negatively regulated by the intact actin cytoskeleton (cytochalasin-D accelerates, phalloidin/jasplakinolide inhibit activation) and positively modulated by intracellular MgATP (prevents inactivation). Inside-out patches show immediate Ca2+-dependent activation, suggesting cytosolic factors including cytoskeleton and ATP mediate the slow whole-cell activation. Whole-cell and inside-out patch-clamp, cytoskeleton-disrupting/stabilizing agents, intracellular ATP manipulation Biochemical and Biophysical Research Communications Medium 29964013
2023 ANO6-dependent trogocytosis in cancer-associated fibroblasts (CAFs) is triggered by cytosolic Ca2+ influx via Orai channels, which activates ANO6 causing PS exposure on CAF plasma membranes, initiating membrane lipid transfer (including cholesterol) to pancreatic cancer cells. ANO6-dependent trogocytosis also supports immunosuppressive function of CAFs toward cytotoxic T cells. CRISPR KO of ANO6, Ca2+ imaging, annexin V/PS exposure assay, cholesterol transfer assay, T cell cytotoxicity assay bioRxiv (preprint)preprint Medium 37745612
2025 High-resolution cryo-EM of TMEM16F active in liposomes reveals two conformations in high-activity conditions: the canonical Ca2+-bound closed state and a novel X-shaped groove conformation where upward rotation of the cytosolic domain forms a transmembrane pore and locally thins the membrane. Mutagenesis, functional assays, and MD simulations show the X-shaped groove mediates nonselective ion flux and lipid scrambling through distinct pathways (ions within the pore, lipids skirting the groove). Cryo-EM in liposomes, site-directed mutagenesis, functional ion flux and scramblase assays, molecular dynamics simulations Nature Structural & Molecular Biology High 41998358
2025 TMEM16F preferentially scrambles phosphatidylserine and phosphatidylcholine over phosphatidylethanolamine on the plasma membrane of living cells, contrary to the prevailing view that scramblases act without headgroup preference. Cell-based fluorescence polarization scrambling assay with NBD-labeled phospholipids, kinetic monitoring on live cell plasma membranes PNAS Medium 41166415
2019 TMEM16F activation contributes to ferroptotic cell death: ferroptosis inducers (erastin, RSL3) activate TMEM16F currents in intestinal epithelium and macrophages, and cell death is largely reduced in tissue-specific TMEM16F KO mice. Inhibitors of ferroptosis (ferrostatin-1) block TMEM16F currents. Tissue-specific TMEM16F KO mice, ferroptosis induction with erastin/RSL3, cell death assays, patch-clamp recording Cancers High 31060306
2018 TMEM16F contributes to pyroptotic cell death downstream of gasdermin-D pore formation. GD-N expression induces Ca2+ elevation activating TMEM16F, which generates large whole-cell currents; knockdown or inhibition of TMEM16F suppresses these currents and reduces cell death in HEK293 and HAP1 cells. GD-N expression, TMEM16F knockdown/inhibition, whole-cell patch-clamp, cell viability assays Cell Death & Disease Medium 29463790
2021 N-terminal domain of ANO6 contains a putative Ca2+-transferring reservoir (Nt-CaRes) that regulates Ca2+ sensitivity. Chimera ANO6-1-6 (with ANO1 Nt-CaRes substituted) shows higher Ca2+ sensitivity than ANO6. Mutagenesis of acidic amino acids in Nt-CaRes reduces Ca2+ sensitivity, consistent with direct Ca2+ interactions at these residues. Chimera construction, site-directed mutagenesis of acidic residues, patch-clamp Ca2+ dose-response, molecular dynamics simulation Molecules and Cells Medium 33658434
2024 Atomic force microscopy under physiological conditions reveals structurally and mechanically diverse TMEM16F assemblies with variable inter-subunit dimerization interfaces. Ca2+-induced activation is associated with stepwise changes in the pore region affecting mechanical properties of TM3, TM4, and TM6. Direct observation of membrane remodeling links structural heterogeneity to ion and lipid permeation. Atomic force microscopy in physiological conditions, cryo-EM comparison, patch-clamp electrophysiology Nature Communications High 38167485
2026 Plasmalemmal lipid scrambling by TMEM16F (using inducible active form) is sufficient to release apoptotic-like vesicles without changes in cytosolic Ca2+ or submembrane cytoskeleton. Scrambling causes segregation of exofacial lipids, redistribution of cholesterol to inner leaflet, GPI-anchored protein clustering forming convex curvature, and PE accumulation forming concave curvature facilitating vesicle scission. Inducible constitutively active TMEM16F, live-cell imaging, lipid domain analysis, extracellular vesicle quantification Molecular Biology of the Cell High 41604453

Source papers

Stage 0 corpus · 99 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Calcium-dependent phospholipid scrambling by TMEM16F. Nature 779 21107324
2012 TMEM16F forms a Ca2+-activated cation channel required for lipid scrambling in platelets during blood coagulation. Cell 386 23021219
2015 TMEM16F is required for phosphatidylserine exposure and microparticle release in activated mouse platelets. Proceedings of the National Academy of Sciences of the United States of America 207 26417084
2015 Identification of a lipid scrambling domain in ANO6/TMEM16F. eLife 155 26057829
2019 Cryo-EM structures and functional characterization of the murine lipid scramblase TMEM16F. eLife 128 30785399
2013 TMEM16F is a component of a Ca2+-activated Cl- channel but not a volume-sensitive outwardly rectifying Cl- channel. American journal of physiology. Cell physiology 111 23426967
2013 Inactivation of anoctamin-6/Tmem16f, a regulator of phosphatidylserine scrambling in osteoblasts, leads to decreased mineral deposition in skeletal tissues. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 106 22936354
2013 Both TMEM16F-dependent and TMEM16F-independent pathways contribute to phosphatidylserine exposure in platelet apoptosis and platelet activation. Blood 104 23303820
2013 TMEM16F (Anoctamin 6), an anion channel of delayed Ca(2+) activation. The Journal of general physiology 99 23630341
2013 Molecular functions of anoctamin 6 (TMEM16F): a chloride channel, cation channel, or phospholipid scramblase? Pflugers Archiv : European journal of physiology 89 23748496
2020 TMEM16F phospholipid scramblase mediates trophoblast fusion and placental development. Science advances 88 32494719
2020 Critical Role of Lipid Scramblase TMEM16F in Phosphatidylserine Exposure and Repair of Plasma Membrane after Pore Formation. Cell reports 87 31995754
2019 Cryo-EM Studies of TMEM16F Calcium-Activated Ion Channel Suggest Features Important for Lipid Scrambling. Cell reports 84 31291589
2015 Ion channel and lipid scramblase activity associated with expression of TMEM16F/ANO6 isoforms. The Journal of physiology 78 26108457
2018 Single-molecule analysis of phospholipid scrambling by TMEM16F. Proceedings of the National Academy of Sciences of the United States of America 77 29507235
2019 An inner activation gate controls TMEM16F phospholipid scrambling. Nature communications 74 31015464
2017 Regulation of TMEM16A/ANO1 and TMEM16F/ANO6 ion currents and phospholipid scrambling by Ca2+ and plasma membrane lipid. The Journal of physiology 63 29134661
2013 Calcium-activated and apoptotic phospholipid scrambling induced by Ano6 can occur independently of Ano6 ion currents. Cell death & disease 61 23618909
2018 Phosphatidylinositol-(4, 5)-bisphosphate regulates calcium gating of small-conductance cation channel TMEM16F. Proceedings of the National Academy of Sciences of the United States of America 60 29382763
2013 The role of TMEM16A (ANO1) and TMEM16F (ANO6) in cell migration. Pflugers Archiv : European journal of physiology 55 23832500
2016 TMEM16F Regulates Spinal Microglial Function in Neuropathic Pain States. Cell reports 52 27332874
2019 TMEM16F activation by Ca2+ triggers plasma membrane expansion and directs PD-1 trafficking. Scientific reports 51 30679690
2022 Structural basis for the activation of the lipid scramblase TMEM16F. Nature communications 45 36335104
2019 TMEM16F/Anoctamin 6 in Ferroptotic Cell Death. Cancers 45 31060306
2018 Contribution of TMEM16F to pyroptotic cell death. Cell death & disease 45 29463790
2012 Expression and functional significance of the Ca(2+)-activated Cl(-) channel ANO6 in dendritic cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 45 23159814
2020 TMEM16F Aggravates Neuronal Loss by Mediating Microglial Phagocytosis of Neurons in a Rat Experimental Cerebral Ischemia and Reperfusion Model. Frontiers in immunology 43 32733436
2016 Ca2+ signals, cell membrane disintegration, and activation of TMEM16F during necroptosis. Cellular and molecular life sciences : CMLS 42 27535660
2004 Identification and characterization of TMEM16E and TMEM16F genes in silico. International journal of oncology 42 15067359
2016 Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion. The Journal of experimental medicine 36 27810927
2017 CFTR supports cell death through ROS-dependent activation of TMEM16F (anoctamin 6). Pflugers Archiv : European journal of physiology 34 28875346
2022 Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion. eLife 33 35670667
2022 Amelioration of SARS-CoV-2 infection by ANO6 phospholipid scramblase inhibition. Cell reports 33 35839776
2017 Activation of the phospholipid scramblase TMEM16F by nanosecond pulsed electric fields (nsPEF) facilitates its diverse cytophysiological effects. The Journal of biological chemistry 33 28982976
2023 Identification of a drug binding pocket in TMEM16F calcium-activated ion channel and lipid scramblase. Nature communications 30 37573365
2015 A TMEM16F point mutation causes an absence of canine platelet TMEM16F and ineffective activation and death-induced phospholipid scrambling. Journal of thrombosis and haemostasis : JTH 28 26414452
2024 Deciphering and disrupting PIEZO1-TMEM16F interplay in hereditary xerocytosis. Blood 27 38033286
2020 Spinal Motoneuron TMEM16F Acts at C-boutons to Modulate Motor Resistance and Contributes to ALS Pathogenesis. Cell reports 24 32101737
2019 Dynamic change of electrostatic field in TMEM16F permeation pathway shifts its ion selectivity. eLife 24 31318330
2014 Functional swapping between transmembrane proteins TMEM16A and TMEM16F. The Journal of biological chemistry 24 24478309
2023 TMEM16F may be a new therapeutic target for Alzheimer's disease. Neural regeneration research 23 36018189
2015 Involvement of Ca2+ Activated Cl- Channel Ano6 in Platelet Activation and Apoptosis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 23 26584292
2021 Hyperuricemia enhances procoagulant activity of vascular endothelial cells through TMEM16F regulated phosphatidylserine exposure and microparticle release. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 22 34390515
2019 ANO6 promotes cell proliferation and invasion in glioma through regulating the ERK signaling pathway. OncoTargets and therapy 22 31692479
2021 TMEM16F mediates bystander TCR-CD3 membrane dissociation at the immunological synapse and potentiates T cell activation. Science signaling 21 33758060
2021 TMEM16F and dynamins control expansive plasma membrane reservoirs. Nature communications 21 34404808
2018 TMEM16F/ANO6, a Ca2+-activated anion channel, is negatively regulated by the actin cytoskeleton and intracellular MgATP. Biochemical and biophysical research communications 21 29964013
2021 Molecular underpinning of intracellular pH regulation on TMEM16F. The Journal of general physiology 20 33346788
2016 Role of Ca(2+) in the Stability and Function of TMEM16F and 16K. Biochemistry 20 27227820
2022 The allosteric mechanism leading to an open-groove lipid conductive state of the TMEM16F scramblase. Communications biology 17 36123525
2015 Selective serotonin reuptake inhibitors facilitate ANO6 (TMEM16F) current activation and phosphatidylserine exposure. Pflugers Archiv : European journal of physiology 16 25630304
2021 Anion and Cation Permeability of the Mouse TMEM16F Calcium-Activated Channel. International journal of molecular sciences 15 34445284
2023 Trogocytosis of cancer-associated fibroblasts promotes pancreatic cancer growth and immune suppression via phospholipid scramblase anoctamin 6 (ANO6). bioRxiv : the preprint server for biology 14 37745612
2022 TMEM16F mediated phosphatidylserine exposure and microparticle release on erythrocyte contribute to hypercoagulable state in hyperuricemia. Blood cells, molecules & diseases 14 35567997
2019 TMEM16F inhibition limits pain-associated behavior and improves motor function by promoting microglia M2 polarization in mice. Biochemical and biophysical research communications 13 31409484
2024 TMEM16F scramblase regulates angiogenesis via endothelial intracellular signaling. Journal of cell science 12 38940198
2023 SARS-CoV-2 Spike protein activates TMEM16F-mediated platelet procoagulant activity. Frontiers in cardiovascular medicine 12 36684586
2018 CCR7 regulates ANO6 to promote migration of pancreatic ductal adenocarcinoma cells via the ERK signaling pathway. Oncology letters 12 30013654
2022 Supporting Cells of the Human Olfactory Epithelium Co-Express the Lipid Scramblase TMEM16F and ACE2 and May Cause Smell Loss by SARS-CoV-2 Spike-Induced Syncytia. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 11 35670331
2019 Temperature-dependent increase in the calcium sensitivity and acceleration of activation of ANO6 chloride channel variants. Scientific reports 11 31040335
2015 Haploinsufficiency of ANO6, NELL2 and DBX2 in a boy with intellectual disability and growth delay. American journal of medical genetics. Part A 11 25846056
2022 Activation of TMEM16F by inner gate charged mutations and possible lipid/ion permeation mechanisms. Biophysical journal 10 35978550
2020 Lysophosphatidic acid-induced pro-thrombotic phosphatidylserine exposure and ionophore-induced microvesiculation is mediated by the scramblase TMEM16F in erythrocytes. Blood cells, molecules & diseases 10 32222693
2020 Evidence that polyphenols do not inhibit the phospholipid scramblase TMEM16F. The Journal of biological chemistry 10 32709749
2024 TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 39136057
2016 TMEM16F Regulates Baseline Phosphatidylserine Exposure and Cell Viability in Human Embryonic Kidney Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 9 27287741
2024 Structural heterogeneity of the ion and lipid channel TMEM16F. Nature communications 8 38167485
2024 ANO6 (TMEM16F) inhibits gastrointestinal stromal tumor growth and induces ferroptosis. Open medicine (Warsaw, Poland) 8 38756246
2022 Paneth Cell Secretion in vivo Requires Expression of Tmem16a and Tmem16f. Gastro hep advances 7 39131261
2019 A major interspecies difference in the ionic selectivity of megakaryocyte Ca2+-activated channels sensitive to the TMEM16F inhibitor CaCCinh-A01. Platelets 7 31008669
2018 Regulation and Function of TMEM16F in Renal Podocytes. International journal of molecular sciences 6 29912162
2021 Ca2+ Sensitivity of Anoctamin 6/TMEM16F Is Regulated by the Putative Ca2+-Binding Reservoir at the N-Terminal Domain. Molecules and cells 4 33658434
2024 OxLDL enhances procoagulant activity of endothelial cells by TMEM16F-mediated phosphatidylserine exposure. Cell biology international 3 38444077
2024 TMEM16F exacerbates tau pathology and mediates phosphatidylserine exposure in phospho-tau-burdened neurons. Proceedings of the National Academy of Sciences of the United States of America 3 38941274
2024 TMEM16F regulates pathologic α-synuclein secretion and spread in cellular and mouse models of Parkinson's disease. Aging cell 3 39487963
2020 Ano6 disruption impairs acinar cell regulatory volume decrease and protein secretion in murine submandibular salivary glands. Journal of cellular physiology 3 32329061
2025 ANO6 Targets TMEM30A to Regulate Endoplasmic Reticulum Stress-Induced Lipid Peroxidation and Ferroptosis in Alzheimer's Cells. Cell biochemistry and biophysics 2 40221538
2024 Comprehensive functional characterization of a novel ANO6 variant in a new patient with Scott syndrome. Journal of thrombosis and haemostasis : JTH 2 38492852
2025 ENDOTHELIAL-SPECIFIC KNOCKOUT OF THE SCRAMBLASE TMEM16F IMPAIRS IN VIVO CLOT FORMATION. Shock (Augusta, Ga.) 1 39874534
2025 Pan-Cancer Analysis of ANO6 and Experimental Validation in Metastatic Melanoma. Biochemical genetics 1 40042755
2025 Ion Channel Function of Human TMEM16F Is Associated with Phospholipid Transport through Its Subunit Cavity. Biological & pharmaceutical bulletin 1 40350307
2025 Phospholipid Scramblases TMEM16F and Xkr8 mediate distinct features of Phosphatidylserine (PS) externalization and immune suppression to promote tumor growth. bioRxiv : the preprint server for biology 1 40391322
2025 Targeting PIEZO1-TMEM16F Coupling to Mitigate Sickle Cell Disease Complications. bioRxiv : the preprint server for biology 1 40501573
2025 Multiple roles of ANO6 in tumors, molecular mechanism and its potential therapeutic value. Biochemistry and biophysics reports 1 41080742
2025 TMEM16F phospholipid scramblase regulates tumorigenesis by modulating the tumor immune microenvironment. Proceedings of the National Academy of Sciences of the United States of America 1 41100671
2025 A cell-based scrambling assay reveals the phospholipid headgroup preference of TMEM16F on the plasma membrane. Proceedings of the National Academy of Sciences of the United States of America 1 41166415
2024 Generation of human TMEM16F-specific affibodies using purified TMEM16F. Frontiers in molecular biosciences 1 38274091
2024 The Effect of Calcium Ions on the Electrophysiological Properties of Single ANO6 Channels. Acta naturae 1 38698960
2023 Endothelial TMEM16F lipid scramblase regulates angiogenesis. bioRxiv : the preprint server for biology 1 37645870
2026 Lipid scrambling via TMEM16F mediates the formation and release of extracellular vesicles. Molecular biology of the cell 0 41604453
2026 ANO6 Confers Paclitaxel Resistance by Targeting Ferroptosis in Cervical Cancer. BioFactors (Oxford, England) 0 41782241
2026 Calcium dependent activation of the TMEM16F scramblase and ion channel. Nature structural & molecular biology 0 41998358
2025 Benzbromarone improves blood hypercoagulability after TBI by reducing phosphatidylserine externalization through inhibition of TMEM16F expression. Life sciences 0 39983827
2025 A cell-based scrambling assay reveals phospholipid headgroup preference of TMEM16F on the plasma membrane. bioRxiv : the preprint server for biology 0 40667283
2025 Characterization of TMEM16F-Specific Affibodies and Their Cellular Effects. Membranes 0 41002890
2025 Targeting PIEZO1-TMEM16F Coupling to Mitigate Sickle Cell Disease Complications. American journal of hematology 0 41059931
2025 Phospholipid scramblases TMEM16F and Xkr8 mediate distinct features of phosphatidylserine (PS) externalization and immune suppression to promote tumor growth. Cell death discovery 0 41198619
2025 NRF2/miR-17-5p/TMEM16F axis regulates the crosstalk of inflammation and thrombosis in sepsis. Journal of thrombosis and haemostasis : JTH 0 41448544
2024 Analysis of ANO6, HAPLN1, and EDIL3 Polymorphisms in Patients with Ankylosing Spondylitis in a Chinese Han Population: A Case-Control Study. Genetic testing and molecular biomarkers 0 39358671