Affinage

PIK3C2A

Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha · UniProt O00443

Length
1686 aa
Mass
190.7 kDa
Annotated
2026-06-10
33 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PIK3C2A (PI3K-C2α) is a class II phosphoinositide 3-kinase that generates spatially restricted pools of PI(3)P and PI(3,4)P2 to couple membrane trafficking with receptor signaling, ciliogenesis, and mitotic fidelity (PMID:10766823, PMID:20061534, PMID:22983395). It is constitutively membrane-associated and concentrated on clathrin-coated vesicles and the trans-Golgi network in an ARF-dependent manner (PMID:10766823), and together with PI3K-C2β it is required for clathrin-mediated pinocytosis up to delivery to early endosomes (PMID:30374841). Through this endocytic activity it controls internalization and downstream signaling of multiple receptors: it produces PI(3,4)P2 at plasma membrane microdomains to drive insulin receptor isoform B-dependent PKBα/Akt1 activation in pancreatic β-cells (PMID:20061534, PMID:26387957), and it directs TGFβ receptor uptake into SARA-containing early endosomes—via an ordered phosphoinositide conversion engaging synaptojanin1 and INPP4B—to enable Smad2/3 activation (PMID:25614622, PMID:31913757). In endothelial cells PI3K-C2α generates PI(3)P-enriched endosomes required for VEGF receptor internalization, endosomal RhoA activation, VE-cadherin delivery, and junction assembly, and its loss causes embryonic lethality with defective angiogenesis and vascular barrier function (PMID:22983395). Independent of its catalytic activity, PI3K-C2α acts as a scaffold that organizes clathrin and TACC3 into inter-microtubule bridges crosslinking kinetochore fibers, ensuring proper spindle function and genomic stability (PMID:29017056). It also generates PI(3)P at the primary cilium to initiate a shear-stress-induced, ULK1/BECN1-independent form of autophagy (PMID:32102612), and connects endocytic and autophagic trafficking through interaction with ATG9 (PMID:28910396). Homozygous loss-of-function mutations in PIK3C2A cause a Mendelian disorder of short stature, cataracts, skeletal abnormalities, and neurological manifestations, with patient fibroblasts showing impaired ciliogenesis and proliferation (PMID:31034465).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1998 Medium

    Established that PI3K-C2α is an agonist-responsive lipid kinase distinct from class IA PI3K, answering whether the enzyme is regulated by physiological stimuli.

    Evidence MCP-1-stimulated IP lipid kinase assay with wortmannin/pertussis toxin dissection

    PMID:9748276

    Open questions at the time
    • Direct lipid product specificity in vivo not resolved
    • Receptor coupling mechanism to the kinase undefined
  2. 2000 High

    Defined where PI3K-C2α operates by localizing it to clathrin-coated vesicles and the ARF-dependent trans-Golgi network, linking the enzyme to membrane trafficking compartments.

    Evidence Subcellular fractionation, dual-label immunofluorescence, brefeldin A, and deletion mutants

    PMID:10766823

    Open questions at the time
    • Which trafficking step the lipid product controls not shown
    • Functional consequence of TGN localization untested
  3. 2008 Medium

    Provided structural basis for phosphoinositide recognition by resolving PX-domain conformations associated with ligand binding.

    Evidence X-ray crystallography of the PX domain at 2.1 and 2.5 Å

    PMID:18312637

    Open questions at the time
    • No functional mutagenesis validating the binding model
    • Full-length enzyme architecture not determined
  4. 2010 High

    Identified the lipid product (PI(3,4)P2) and signaling output (PKBα/Akt1) of insulin-stimulated PI3K-C2α, establishing its role in metabolic signaling and insulin secretion.

    Evidence siRNA knockdown, PI-lipid profiling, TIRF/confocal imaging, and insulin secretion assays in β-cells

    PMID:20061534

    Open questions at the time
    • Mechanism linking PI(3,4)P2 to glucokinase and AS160 not detailed
    • Receptor microdomain organization mechanism unknown
  5. 2012 High

    Demonstrated an essential endosomal trafficking role in endothelial cells, linking PI3K-C2α-derived PI(3)P to VEGFR internalization, RhoA signaling, junction assembly, and angiogenesis in vivo.

    Evidence siRNA, conditional and global knockout mice, in vivo angiogenesis and barrier assays

    PMID:22983395

    Open questions at the time
    • Direct effector reading the endosomal PI(3)P pool not identified
    • Distinction between trafficking defect and signaling defect not fully separated
  6. 2015 High

    Placed PI3K-C2α upstream of TGFβ receptor endocytosis and Smad2/3 signaling, defining its requirement for clathrin/dynamin-dependent uptake into SARA-positive endosomes.

    Evidence siRNA, phosphoinositide measurements, dynamin inhibitor, EC-specific knockout mice, Matrigel assay

    PMID:25614622

    Open questions at the time
    • Order of phosphoinositide conversions not yet resolved at this stage
    • Direct partners coordinating SARA recruitment unclear
  7. 2015 High

    Distinguished the requirement for kinase activity by showing kinase-dead PI3K-C2α causes platelet morphology, granule, and cytoskeletal defects affecting thrombus formation.

    Evidence Heterozygous kinase-dead knock-in mice, EM, PI(3)P quantification, thrombosis assays

    PMID:26109204

    Open questions at the time
    • Identity of mislocalized membrane skeleton proteins not mechanistically mapped
    • Link between basal PI(3)P pool and cytoskeleton coupling undefined
  8. 2015 High

    Showed kinase-dependent PI(3)P production at protrusion membranes is required for Shigella cell-to-cell spread, extending the enzyme's role to pathogen dissemination.

    Evidence siRNA, RNAi-resistant WT vs kinase-dead rescue, PI(3)P reporter, time-lapse imaging

    PMID:25667265

    Open questions at the time
    • Host effector downstream of PI(3)P at protrusions unknown
    • Interplay with bacterial T3SS effectors not detailed
  9. 2015 Medium

    Connected endocytic and autophagic trafficking by demonstrating kinase-dependent regulation of autophagy and physical interaction with ATG9.

    Evidence siRNA, kinase-dead rescue, transferrin labeling, co-IP with ATG9, double knockdown

    PMID:28910396

    Open questions at the time
    • Reciprocal validation of ATG9 interaction limited
    • Site of PI(3)P production driving autophagy not localized
  10. 2015 Medium

    Revealed cascade-selective insulin signaling, where loss of PI3K-C2α reroutes IR-B from the metabolic Akt axis to mitogenic Shc/ERK signaling within a single cell type.

    Evidence siRNA, IP, Western blot, live imaging, glucose-stimulated insulin secretion in β-cells

    PMID:26387957

    Open questions at the time
    • Molecular switch directing receptor adaptor choice unknown
    • Not independently replicated
  11. 2016 Medium

    Extended metabolic function in vivo by showing kinase-dead PI3K-C2α causes hypothalamic leptin resistance and sex-specific obesity, distinct from peripheral insulin signaling.

    Evidence Heterozygous kinase-dead knock-in mice, metabolic phenotyping, hypothalamic leptin assays

    PMID:27138914

    Open questions at the time
    • Basis of male-specific phenotype unexplained
    • Direct role in leptin receptor trafficking not shown
  12. 2017 High

    Defined a kinase-independent scaffold function organizing clathrin-TACC3 bridges at kinetochore fibers to maintain genomic stability, separating structural from catalytic roles.

    Evidence siRNA, live imaging, co-IP, WT vs kinase-dead rescue, breast cancer xenografts

    PMID:29017056

    Open questions at the time
    • How the scaffold is targeted to K-fibers not resolved
    • Relationship between scaffold and lipid kinase pools unclear
  13. 2018 Medium

    Distinguished isoform-specific roles, showing PI3K-C2α and C2β both support clathrin-mediated pinocytosis but only C2β couples to actin-associated clathrin structures.

    Evidence siRNA of each isoform, FITC-dextran uptake, transferrin labeling, co-localization

    PMID:30374841

    Open questions at the time
    • No rescue confirming specificity
    • Mechanistic basis for differential actin coupling unknown
  14. 2018 Medium

    Identified a viral cofactor role, where KSHV pK15 recruits PI3K-C2α to drive PLCγ1/Erk signaling and lytic viral gene expression.

    Evidence Co-IP/MS, immunofluorescence, siRNA, signaling and viral gene assays

    PMID:29950425

    Open questions at the time
    • Whether kinase activity is required for pK15 signaling untested
    • Direct vs indirect interaction not resolved
  15. 2019 Medium

    Established PIK3C2A as the cause of a human Mendelian disorder, linking loss of function to defective ciliogenesis and proliferation.

    Evidence Exome sequencing of consanguineous families, patient fibroblast cilia and proliferation assays

    PMID:31034465

    Open questions at the time
    • Tissue-specific mechanisms behind skeletal/neurological phenotypes not dissected
    • Lipid product driving ciliogenesis not mapped in patient cells
  16. 2020 Medium

    Defined a distinct autophagy pathway in which ciliary PI(3)P from PI3K-C2α initiates shear-stress autophagy independent of ULK1/BECN1 and VPS34.

    Evidence Parallel PIK3C2A vs PIK3C3 knockdown, PI(3)P reporters, shear-stress autophagy assays

    PMID:32102612

    Open questions at the time
    • Downstream autophagy machinery reading ciliary PI(3)P unknown
    • How shear stress activates the enzyme not defined
  17. 2020 High

    Resolved the ordered phosphoinositide conversion for TGFβ receptor endocytosis, placing PI3K-C2α at the head of a synaptojanin1/INPP4B cascade required for Smad2/3 activation.

    Evidence Isoform/phosphatase-specific siRNA panel, PI biosensors, co-localization, Smad2/3 phosphorylation

    PMID:31913757

    Open questions at the time
    • Spatial recruitment hierarchy of the enzymes not fully mapped
    • Generality to other receptors untested
  18. 2022 Medium

    Identified upstream transcriptional control by C/EBPα and a role in vascular smooth muscle autophagy and phenotypic switching during aortic dissection.

    Evidence ChIP, gain/loss-of-function, aortic ring stretch model, in vivo shRNA

    PMID:36132983

    Open questions at the time
    • Whether kinase activity mediates the VSMC phenotype untested
    • Single lab, mechanism downstream of PIK3C2A in VSMC unclear
  19. 2025 High

    Placed endothelial PI3K-C2α upstream of extrinsic cell death, showing its inactivation sensitizes to endotoxic shock via caspase-8/RIPK3-dependent death.

    Evidence Inducible and EC-specific knockout mice, LPS challenge, caspase-8/RIPK3 double-KO epistasis rescue

    PMID:40674428

    Open questions at the time
    • Molecular link from lipid signaling to death pathway suppression unknown
    • Whether kinase or scaffold function is required not resolved
  20. 2025 Medium

    Defined TTC7A as a chaperone delivering PIK3C2A to the apical membrane to generate PI(3,4)P2 specifying apical identity during lumen formation.

    Evidence Patient organoids, trafficking and Rab11a co-localization, PI(3,4)P2 reporter, lipid/pharmacological rescue (preprint)

    PMID:bio_10.1101_2025.03.22.644724

    Open questions at the time
    • Not peer-reviewed
    • Direct biochemical TTC7A-PIK3C2A binding details limited

Open questions

Synthesis pass · forward-looking unresolved questions
  • How PI3K-C2α's distinct PI(3)P and PI(3,4)P2 pools, its kinase-independent scaffold function, and its compartment-specific recruitment are coordinated to produce its diverse physiological roles remains unresolved.
  • No unifying model linking lipid products to specific effectors across compartments
  • Mechanism of stimulus-specific enzyme activation undefined
  • Structural basis of full-length enzyme regulation unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 4 GO:0008289 lipid binding 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005768 endosome 3 GO:0005886 plasma membrane 3 GO:0005929 cilium 2 GO:0031410 cytoplasmic vesicle 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1266738 Developmental Biology 2 R-HSA-9612973 Autophagy 2 R-HSA-1640170 Cell Cycle 1 R-HSA-5357801 Programmed Cell Death 1
Partners
ATG9ACLTCINPP4BSARASYNJ1TACC3TTC7A
Complex memberships
clathrin–TACC3 inter-microtubule bridge

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 PI3K-C2α is constitutively associated with phospholipid membranes and co-purifies with clathrin-coated vesicles (CCVs). Its perinuclear localization co-distributes with γ-adaptin (AP-1) and TGN-46, placing it at the trans-Golgi network. Brefeldin A treatment disrupted this localization, demonstrating dependence on ARF GTPase activity. Neither the PX nor C2 C-terminal domains were required for membrane association or TGN localization. Differential centrifugation, Western blot, immunofluorescence dual-label, brefeldin A treatment, deletion mutant expression The Journal of biological chemistry High 10766823
1998 MCP-1 stimulates lipid kinase activity in PI3K-C2α immunoprecipitates with kinetics paralleling intracellular PI(3,4,5)P3 accumulation. This activation is inhibited by pertussis toxin but not by wortmannin, distinguishing PI3K-C2α activation from the class IA p85/p110 isoform and identifying PI3K-C2α as the likely source of MCP-1-induced D-3 phosphoinositide production in vivo. Immunoprecipitation lipid kinase assay, pharmacological inhibition (wortmannin, pertussis toxin), PI lipid profiling The Journal of biological chemistry Medium 9748276
2010 In response to insulin, PI3K-C2α generates PI(3,4)P2 (not PI(3)P), which selectively activates PKBα/Akt1. PI3K-C2α and PKBα/Akt1 co-distribute with insulin receptor isoform B in the same plasma membrane microdomains. Knockdown of PI3K-C2α impaired glucose-stimulated insulin secretion in pancreatic β-cells, at least partly through reduced glucokinase expression and increased AS160 activity. siRNA knockdown, pharmacological inhibitors, PI-lipid profiling, live-cell confocal and TIRF microscopy, transient overexpression FASEB journal High 20061534
2012 PI3K-C2α knockdown in endothelial cells decreased PI(3)P-enriched endosomes, impaired endosomal trafficking, blocked VE-cadherin delivery to cell junctions, and prevented junction assembly. It also impaired VEGF receptor internalization and endosomal RhoA activation. Global or endothelial-specific PI3K-C2α knockout caused embryonic lethality with defects in sprouting angiogenesis and vascular maturation. In vivo, endothelial PI3K-C2α deficiency suppressed postischemic and tumor angiogenesis and diminished vascular barrier function. siRNA knockdown, conditional and global knockout mice, immunofluorescence, in vivo angiogenesis assays, barrier function assays Nature medicine High 22983395
2015 PI3K-C2α knockdown in endothelial cells abolished TGFβ1-induced phosphorylation and nuclear translocation of Smad2/3. PI3K-C2α was required for TGFβ-induced PI(3,4)P2 increases at the plasma membrane and for TGFβ receptor internalization into SARA-containing early endosomes, and for SARA–Smad2/3 complex formation. Dynamin inhibition phenocopied PI3K-C2α knockdown, indicating clathrin-dependent endocytosis is required. EC-specific PI3K-C2α deletion in mice attenuated TGFβ1-induced microvessel formation. siRNA knockdown, phosphoinositide measurements, immunofluorescence, dynamin inhibitor, EC-specific knockout mice, Matrigel plug assay The Journal of biological chemistry High 25614622
2015 PI3K-C2α heterozygous kinase-dead knock-in in mice caused aberrant platelet morphology (excess barbell-shaped proplatelets), defects in α-granules and membrane structure, increased platelet rigidity, inability to form filopodia, and reduced basal PI(3)P pool. Mislocalization of membrane skeleton proteins controlling plasma membrane–cytoskeleton interactions was observed in affected platelets. These defects led to delayed arterial occlusion and impaired thrombus formation. Constitutive kinase-dead knock-in mouse, flow cytometry, electron microscopy, PI3P quantification, ex vivo thrombosis assay, in vivo arterial occlusion model Blood High 26109204
2015 PI3K-C2α knockdown impaired Shigella flexneri dissemination by blocking resolution of protrusions into vacuoles via an intermediate vacuole-like protrusion (VLP). Genetic rescue with RNAi-resistant cDNA (but not kinase-dead PI3K-C2α) restored VLP formation, requiring kinase activity in primary infected cells. PI3K-C2α produced PI(3)P at the protrusion plasma membrane, regulated by host tyrosine kinase signaling and the bacterial T3SS. siRNA knockdown, time-lapse microscopy, RNAi-resistant rescue constructs, PI(3)P reporter, kinase-dead mutant Infection and immunity High 25667265
2015 PI3K-C2α knockdown decreased autophagy and caused accumulation of endocytic vesicles at recycling endosomes. Kinase-dead PI3K-C2α failed to rescue autophagy, establishing a requirement for catalytic activity. PI3K-C2α co-localizes with endocytic markers and interacts with ATG9. Double knockdown of PIK3C2A and ATG9A/B phenocopied each other, suggesting a shared pathway connecting endocytic and autophagic trafficking. siRNA knockdown, confocal microscopy, transferrin labeling, membrane fractionation, co-immunoprecipitation, kinase-dead rescue PloS one Medium 28910396
2015 PI3K-C2α knockdown in pancreatic β-cells rerouted insulin signaling from the IR-B/PI3K-C2α/PKBα metabolic axis to IR-B/Shc/ERK mitogenic signaling, causing a switch from a glucose-responsive differentiated state to a proliferative state, demonstrating cascade-selective insulin resistance within a single cell type. siRNA knockdown, immunoprecipitation, Western blot, live-cell imaging, glucose-stimulated insulin secretion assays Cell reports Medium 26387957
2016 Heterozygous kinase-dead PI3K-C2α knock-in male mice developed early-onset leptin resistance with a defect in leptin signaling in the hypothalamus, correlating with age-dependent obesity, insulin resistance, and glucose intolerance. No metabolic phenotypes were detected in female mice. Importantly, insulin signaling in peripheral insulin target tissues was unaffected in these mice. Constitutive heterozygous kinase-dead knock-in mice, metabolic phenotyping, glucose tolerance tests, hypothalamic leptin signaling assays Diabetologia Medium 27138914
2017 PI3K-C2α acts as a kinase-independent scaffold organizing clathrin and TACC3 into inter-microtubule bridge complexes that crosslink kinetochore fibers (K-fibers) during mitosis. Downregulation of PI3K-C2α caused spindle alterations, delayed anaphase onset, and aneuploidy. Reduced PI3K-C2α expression in breast cancer initially impaired tumor growth but led to evolution of fast-growing clones with mitotic checkpoint defects and increased taxane sensitivity. siRNA knockdown, live-cell imaging, co-immunoprecipitation (clathrin/TACC3 complex), rescue with kinase-dead vs. WT construct, breast cancer xenograft models Cancer cell High 29017056
2018 PI3K-C2α and PI3K-C2β both localize to clathrin-coated pits and are required for clathrin-mediated (but not clathrin-independent) pinocytosis up to the step of delivery to early endosomes. PI3K-C2β, but not PI3K-C2α, co-localizes with actin filament-associated clathrin-coated structures and is required for actin filament formation at those structures, distinguishing their specific roles. siRNA knockdown, FITC-dextran uptake assay, transferrin labeling, confocal co-localization, clathrin heavy chain knockdown The journal of physiological sciences Medium 30374841
2018 KSHV nonstructural membrane protein pK15 interacts and co-localizes with PI3K-C2α in perinuclear vesicular structures. PI3K-C2α contributes to pK15-dependent phosphorylation of PLCγ1 and Erk1/2. Depletion of PI3K-C2α in KSHV-infected endothelial cells reduced expression of viral lytic genes K-bZIP and ORF45 and decreased release of infectious virus. Co-immunoprecipitation with mass spectrometry, immunofluorescence co-localization, siRNA knockdown, Western blot for signaling targets, viral gene expression assays Journal of virology Medium 29950425
2019 Homozygous loss-of-function mutations in PIK3C2A cause a Mendelian disorder with short stature, cataracts, skeletal abnormalities, and neurological manifestations. Patient-derived fibroblasts lacking PIK3C2A protein showed impaired cilia formation and function and reduced proliferative capacity, establishing PIK3C2A as essential for ciliogenesis and cell proliferation. Exome sequencing of consanguineous families, patient-derived fibroblast analysis, cilia formation assay, proliferation assay, Western blot PLoS genetics Medium 31034465
2020 PI3K-C2α generates PI(3)P at the primary cilium in response to shear stress (urinary flow) to initiate cilium-dependent autophagy in kidney proximal tubule epithelial cells. This pathway is independent of ULK1 and BECN1, distinguishing it from starvation-induced autophagy driven by PIK3C3/VPS34. siRNA knockdown of PIK3C2A vs. PIK3C3, PI(3)P reporters, shear stress assay, autophagy markers, confocal microscopy Autophagy Medium 32102612
2020 PI3K-C2α is required for TGFβ receptor endocytosis through sequential phosphoinositide conversions: PI3K-C2α KD abolished TGFβ-induced PI(3,4)P2 increases and also prevented synaptojanin1 recruitment to the plasma membrane, PI(4,5)P2 decreases, and PI(4)P increases. Synaptojanin1 and INPP4B (but not PI3K-C2β, Synj2, or INPP4A) work sequentially with PI3K-C2α. These phosphoinositide conversions are necessary for Smad2/3 activation. siRNA knockdown of individual PI3K and phosphatase isoforms, phosphoinositide biosensors/quantification, co-localization imaging, Smad2/3 phosphorylation assay Molecular biology of the cell High 31913757
2008 Crystal structures of the PI3K-C2α PX domain at 2.1 Å and 2.5 Å revealed two conformations of the phosphoinositide-binding loops, with one structure containing a putative ligand in the binding site. This demonstrated that the PX domain undergoes a conformational change associated with ligand binding and clarified the molecular basis for PI specificity. X-ray crystallography (2.1 Å and 2.5 Å structures of PX domain) BMC structural biology Medium 18312637
2022 C/EBPα transcriptionally activates PIK3C2A by binding to a site in its promoter (established by ChIP assay). C/EBPα and PIK3C2A promote autophagy and phenotypic switching (synthetic to contractile) in vascular smooth muscle cells under aortic dissection conditions. PIK3C2A knockdown reversed C/EBPα-driven autophagy activation, MMP upregulation, and VSMC phenotype switching. ChIP assay, siRNA/plasmid-based gain/loss-of-function, Western blot, aortic ring stretch-stress model, in vivo tail-vein shRNA injection Journal of immunology research Medium 36132983
2025 Inducible genetic inactivation of PI3K-C2α in adult mice sensitized them to LPS-induced endotoxic shock. Vascular endothelial-specific deletion recapitulated this phenotype. Sensitization was fully rescued by combined deficiency of caspase-8 and RIPK3, placing PI3K-C2α upstream of extrinsic cell death pathway activation in endothelial cells. Inducible conditional knockout mice, vascular endothelial-specific deletion, LPS challenge model, genetic epistasis (caspase-8/RIPK3 double knockout rescue) Proceedings of the National Academy of Sciences of the United States of America High 40674428
2025 TTC7A functions as a molecular chaperone for PIK3C2A and is required for its trafficking to the plasma membrane via Rab11a-positive vesicles. PIK3C2A generates PI(3,4)P2 at the apical membrane to specify apical identity during intestinal lumen formation. Defective lumen formation in TTC7A loss-of-function was rescued by exogenous PI(3,4)P2 or small molecules modulating phosphoinositide homeostasis. Patient-derived organoids, protein trafficking assays, Rab11a co-localization, PI(3,4)P2 reporter, exogenous lipid rescue, pharmacological rescue bioRxivpreprint Medium bio_10.1101_2025.03.22.644724

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Endothelial PI3K-C2α, a class II PI3K, has an essential role in angiogenesis and vascular barrier function. Nature medicine 185 22983395
1998 The CC chemokine monocyte chemotactic peptide-1 activates both the class I p85/p110 phosphatidylinositol 3-kinase and the class II PI3K-C2alpha. The Journal of biological chemistry 150 9748276
2000 The class II phosphoinositide 3-kinase PI3K-C2alpha is concentrated in the trans-Golgi network and present in clathrin-coated vesicles. The Journal of biological chemistry 123 10766823
2010 Insulin-feedback via PI3K-C2alpha activated PKBalpha/Akt1 is required for glucose-stimulated insulin secretion. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 97 20061534
2017 Mitotic Spindle Assembly and Genomic Stability in Breast Cancer Require PI3K-C2α Scaffolding Function. Cancer cell 82 29017056
2015 Essential role of class II PI3K-C2α in platelet membrane morphology. Blood 55 26109204
2019 Mutations in PIK3C2A cause syndromic short stature, skeletal abnormalities, and cataracts associated with ciliary dysfunction. PLoS genetics 54 31034465
2015 Phosphatidylinositol 3-kinase class II α-isoform PI3K-C2α is required for transforming growth factor β-induced Smad signaling in endothelial cells. The Journal of biological chemistry 43 25614622
2015 PI3K-C2α: One enzyme for two products coupling vesicle trafficking and signal transduction. FEBS letters 34 25979177
2016 PIK3C2A is a gene-specific target of microRNA-518a-5p in imatinib mesylate-resistant gastrointestinal stromal tumor. Laboratory investigation; a journal of technical methods and pathology 32 26950487
2015 PI3K-C2α Knockdown Results in Rerouting of Insulin Signaling and Pancreatic Beta Cell Proliferation. Cell reports 30 26387957
2015 The class II phosphatidylinositol 3-phosphate kinase PIK3C2A promotes Shigella flexneri dissemination through formation of vacuole-like protrusions. Infection and immunity 29 25667265
2016 Inactivation of class II PI3K-C2α induces leptin resistance, age-dependent insulin resistance and obesity in male mice. Diabetologia 28 27138914
2018 The class II phosphoinositide 3-kinases PI3K-C2α and PI3K-C2β differentially regulate clathrin-dependent pinocytosis in human vascular endothelial cells. The journal of physiological sciences : JPS 27 30374841
2017 PI3K-C2α knockdown decreases autophagy and maturation of endocytic vesicles. PloS one 26 28910396
2020 TGFβ receptor endocytosis and Smad signaling require synaptojanin1, PI3K-C2α-, and INPP4B-mediated phosphoinositide conversions. Molecular biology of the cell 24 31913757
2014 Inhibition of cell proliferation and migration by miR-509-3p that targets CDK2, Rac1, and PIK3C2A. Molecules and cells 24 24802056
2018 Kaposi's Sarcoma-Associated Herpesvirus Nonstructural Membrane Protein pK15 Recruits the Class II Phosphatidylinositol 3-Kinase PI3K-C2α To Activate Productive Viral Replication. Journal of virology 23 29950425
2016 PIK3C2A mRNA functions as a miR-124 sponge to facilitate CD151 expression and enhance malignancy of hepatocellular carcinoma cells. Oncotarget 17 27270320
2019 Low expression of PIK3C2A gene: A potential biomarker to predict the risk of acute myocardial infarction. Medicine 14 30946353
2021 LncRNA KCNQ1OT1 attenuates osteoarthritic chondrocyte dysfunction via the miR-218-5p/PIK3C2A axis. Cell and tissue research 13 33783609
2018 MicroRNA-31 inhibits osteosarcoma cell proliferation, migration and invasion by targeting PIK3C2A. European review for medical and pharmacological sciences 13 30468462
2021 Anti-apoptotic Effect of MiR-223-3p Suppressing PIK3C2A in Cardiomyocytes from Myocardial Infarction Rat Through Regulating PI3K/Akt Signaling Pathway. Cardiovascular toxicology 10 33999393
2020 Primary cilium-dependent autophagy drafts PIK3C2A to generate PtdIns3P in response to shear stress. Autophagy 10 32102612
2008 Crystal structures of PI3K-C2alpha PX domain indicate conformational change associated with ligand binding. BMC structural biology 9 18312637
2022 C/EBPα-Mediated Transcriptional Activation of PIK3C2A Regulates Autophagy, Matrix Metalloproteinase Expression, and Phenotypic of Vascular Smooth Muscle Cells in Aortic Dissection. Journal of immunology research 7 36132983
2017 Gene delivery to Nile tilapia cells for transgenesis and the role of PI3K-c2α in angiogenesis. Scientific reports 7 28317860
2023 Cezanne promoted autophagy through PIK3C3 stabilization and PIK3C2A transcription in lung adenocarcinoma. Cell death discovery 5 37596251
2022 Expanding the phenotype of PIK3C2A related syndrome: Report of two siblings with novel features and genotype. American journal of medical genetics. Part A 5 35770347
2025 PIK3C2A-Related Clinical Phenotype and Cellular Charaterization Linked to Functional SHH Primary Cilia Defect. Clinical genetics 3 40542664
2023 Various Expressions of PIK3C2A and TXNIP Genes and Their Potential Role as Independent Risk Factors for Chronic Stable Angina and Acute Coronary Syndrome. Biomolecules 3 36830671
2025 CRISPR Screens Identify PIK3C2A as a Novel Mediator of EGFR Inhibitor Resistance in Head and Neck Squamous Cell Carcinoma. Head & neck 2 40985049
2025 Inactivation of PI3K-C2α deregulates cell death pathways and sensitizes to endotoxic shock. Proceedings of the National Academy of Sciences of the United States of America 1 40674428

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