Affinage

ANXA6

Annexin A6 · UniProt P08133

Round 2 corrected
Length
673 aa
Mass
75.9 kDa
Annotated
2026-04-28
61 papers in source corpus 20 papers cited in narrative 22 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ANXA6 is a Ca²⁺-dependent phospholipid-binding scaffold protein that organizes membrane-associated signaling platforms, regulates vesicular trafficking and autophagy, and modulates metabolic and innate immune pathways. Its eight-repeat annexin fold binds phosphatidylserine, phosphatidic acid, phosphatidylinositol, and phosphatidylethanolamine in a Ca²⁺-dependent manner and inhibits phospholipid vesicle fusion (PMID:2138016); Ca²⁺ also drives its partitioning into cholesterol/sphingomyelin-enriched membrane microdomains (PMID:23360953). ANXA6 suppresses EGFR–ERK1/2 signaling by facilitating PKCα–EGFR complex formation, an activity enhanced by SUMO1 modification at K299, and loss of this SUMOylation confers gefitinib resistance (PMID:37528485, PMID:39528080). ANXA6 additionally promotes autophagy through dual inhibition of PI3K/AKT/mTOR signaling and facilitation of ATG9A vesicle trafficking via RAB GTPases/F-actin (PMID:32373608, PMID:33135350), functions as a host restriction factor for influenza A virus (PMID:34673207), is required for hepatic alanine-dependent gluconeogenesis (PMID:40802799), and inhibits the cGAS–STING pathway by promoting K63-linked ubiquitination of cGAS (PMID:41219880).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 1988 High

    Determining the primary structure of ANXA6 established it as a Ca²⁺-binding annexin family member with an unusual eight-repeat architecture, providing the molecular framework for all subsequent functional studies.

    Evidence cDNA cloning and sequence analysis of human p68/ANXA6

    PMID:3258820

    Open questions at the time
    • No three-dimensional structure resolved at this stage
    • Biological function and lipid-binding specificity not yet characterized
  2. 1990 High

    Reconstitution with defined lipid vesicles revealed that ANXA6 uniquely inhibits membrane fusion at threshold Ca²⁺ and binds selectively to anionic phospholipids, distinguishing its biophysical activity from other annexins.

    Evidence In vitro phospholipid vesicle aggregation and fusion assays with purified ANXA6

    PMID:2138016

    Open questions at the time
    • Cellular consequences of fusion inhibition not demonstrated
    • Whether ANXA6 inhibits fusion in vivo remains untested
  3. 2013 Medium

    Showing that Ca²⁺ drives ANXA6 into cholesterol/sphingomyelin-enriched microdomains connected its lipid-binding activity to raft-dependent signaling and linked it mechanistically to Niemann-Pick type C pathology.

    Evidence Detergent-resistant membrane fractionation and Langmuir monolayer assays in NPC cells

    PMID:23360953

    Open questions at the time
    • Whether ANXA6 raft partitioning is causative versus correlative in NPC disease
    • Structural basis for cholesterol/sphingomyelin selectivity not resolved
  4. 2016 High

    Identification of a stable ANXA6/LRP1/TSP1 complex in cancer-associated fibroblast-derived extracellular vesicles established ANXA6 as a scaffolding component of pro-tumorigenic paracrine signaling in pancreatic cancer.

    Evidence Reciprocal co-immunoprecipitation, EV uptake, ANXA6 depletion in CAFs, in vivo xenograft and metastasis assays

    PMID:27701147

    Open questions at the time
    • Mechanism by which ANXA6 recruits LRP1 and TSP1 into EVs is unknown
    • Direct stoichiometry and structure of the ternary complex not determined
  5. 2018 High

    Anxa6-knockout mice revealed an unexpected metabolic role: despite intact insulin–Akt signaling, ANXA6 loss uncouples insulin action from suppression of hepatic gluconeogenesis, positioning ANXA6 as a fine-tuning scaffold for hepatic glucose metabolism.

    Evidence Anxa6-KO mouse model with high-fat diet, glucose/insulin tolerance tests, Akt/S6K phosphorylation, glucose production assay in AnxA6-depleted hepatocytes

    PMID:30110341

    Open questions at the time
    • Direct protein target through which ANXA6 controls gluconeogenesis downstream of Akt not identified
    • Whether phenotype is liver-autonomous versus systemic not fully resolved
  6. 2020 Medium

    Two independent studies converged to show ANXA6 promotes autophagy through dual mechanisms—inhibition of PI3K/AKT/mTOR signaling and facilitation of ATG9A vesicle trafficking via RAB GTPases and F-actin—resolving how ANXA6 connects membrane dynamics to autophagosome biogenesis.

    Evidence ANXA6 knockdown/rescue with LC3 and ATG9A trafficking readouts, epistasis with PI3K inhibitor CAL101, mTOR/ERK pathway analysis

    PMID:32373608 PMID:33135350

    Open questions at the time
    • Which RAB GTPases directly interact with ANXA6 for ATG9A sorting not defined
    • Structural basis for ANXA6 engagement with autophagic machinery unknown
    • Whether the PI3K/AKT arm and the ATG9A trafficking arm are independent or coupled is unclear
  7. 2021 Medium

    CRISPR knockout demonstrated that endogenous ANXA6 restricts influenza A virus replication, expanding its functional repertoire to innate antiviral defense.

    Evidence CRISPR-Cas9 ANXA6 KO in HEK293FT cells, TCID50 viral titer and growth curve assays

    PMID:34673207

    Open questions at the time
    • Mechanism of viral restriction (virion packaging, entry, or egress) not delineated
    • Relevance in primary airway epithelial cells not tested
    • Whether ANXA6 restricts other viruses is unknown
  8. 2023 High

    Identification of K299 as a SUMO1 modification site explained how ANXA6 suppresses EGFR–ERK1/2 signaling: SUMOylated ANXA6 bridges EGFR and PKCα, and loss of this modification confers resistance to EGFR-targeted therapy, unifying the tumor-suppressive and drug-sensitizing activities of ANXA6.

    Evidence LC-MS/MS SUMOylation site mapping, K299R mutagenesis, co-IP for EGFR–PKCα complex, in vitro and xenograft assays

    PMID:37528485

    Open questions at the time
    • E3 SUMO ligase responsible for K299 modification not identified
    • Whether SUMOylation modulates ANXA6 lipid-binding or raft partitioning is untested
  9. 2025 Medium

    Anxa6-KO mice challenged with alanine revealed a specific requirement for ANXA6 in the glucose–alanine cycle, pinpointing the metabolic defect to alanine-dependent hepatic gluconeogenesis and linking ANXA6 to SNAT4/Gpt2 expression.

    Evidence Anxa6-KO mouse model, alanine challenge, indirect calorimetry, transporter and enzyme expression analysis

    PMID:40802799

    Open questions at the time
    • Whether ANXA6 directly regulates SNAT4 trafficking or Gpt2 transcription is unknown
    • Tissue-specific rescue experiments not reported
  10. 2025 Medium

    Demonstration that ANXA6 promotes K63-linked ubiquitination of cGAS to suppress the cGAS–STING–IFN axis established a new role for ANXA6 in tuning innate immune DNA sensing, with consequences for ferroptosis induction when ANXA6 is lost.

    Evidence Co-IP for ANXA6–cGAS, K63-ubiquitination assay, ANXA6 knockdown with STING pathway and ferroptosis readouts in cervical cancer cells

    PMID:41219880

    Open questions at the time
    • E3 ubiquitin ligase recruited by ANXA6 to ubiquitinate cGAS not identified
    • Whether ANXA6 directly binds cGAS or acts via an intermediate is unresolved
    • In vivo validation of the cGAS–STING suppressive role is lacking

Open questions

Synthesis pass · forward-looking unresolved questions
  • The upstream signals that coordinate ANXA6's scaffolding functions across its diverse pathways—EGFR suppression, autophagy, gluconeogenesis, cGAS regulation, and membrane repair—remain mechanistically unintegrated; a unifying structural or regulatory model is absent.
  • No full-length ANXA6 structure in complex with any signaling partner exists
  • How SUMOylation, Ca²⁺ binding, and lipid raft partitioning are coordinately regulated is unknown
  • Tissue-specific isoform functions arising from alternative splicing remain largely unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0060090 molecular adaptor activity 3 GO:0008289 lipid binding 2
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 3 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-9612973 Autophagy 4 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-1430728 Metabolism 2 R-HSA-168256 Immune System 2
Partners
ATG9ACGASEGFRLRP1PRKCASNAP23THBS1TRIM72
Complex memberships
ANXA6/LRP1/TSP1 (CAF-derived EV complex)EGFR/PKCα/ANXA6 complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1988 The primary amino acid sequence of human p68 (later named ANXA6) was determined from cDNA clones, revealing it is a membrane-associated Ca2+-binding protein with an internally repetitive structure comprising eight repeats, each containing a conserved sequence motif. It was identified as a member of the annexin family, related to p36, lipocortin I, and protein II, and the cDNA data suggested alternatively spliced mRNAs could encode different p68 protein species. cDNA cloning, sequencing, and sequence analysis The EMBO journal High 3258820
1990 ANXA6 (referred to as p68) was shown to inhibit phospholipid vesicle membrane fusion at threshold Ca2+ concentrations, distinguishing it functionally from other annexins. It binds Ca2+-dependently to phosphatidic acid, phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine vesicles, but not phosphatidylcholine vesicles. These quantitative and qualitative differences among annexins suggest distinct intracellular functions. In vitro phospholipid vesicle binding assay, vesicle aggregation and fusion assays with defined lipid compositions and Ca2+ concentrations The Biochemical journal High 2138016
2013 In Niemann-Pick type C (NPC) disease cells, AnxA6 translocates to lipid microdomains (detergent-resistant membranes, DRMs) enriched in cholesterol and sphingomyelin upon a rise in Ca2+ concentration. In vitro Langmuir monolayer experiments showed that Ca2+ is the primary factor regulating AnxA6 interaction with neutral lipid monolayers (DPPC and sphingomyelin), indicating Ca2+-driven partitioning of AnxA6 into cholesterol/sphingomyelin-enriched microdomains contributes to NPC pathology. Lipid microdomain (DRM) isolation and fractionation, Langmuir monolayer in vitro lipid-protein interaction assays, calcium titration Molecular bioSystems Medium 23360953
2016 Cancer-associated fibroblasts (CAFs) secrete ANXA6-containing extracellular vesicles (EVs) that carry an ANXA6/LRP1/TSP1 complex. Formation of this complex is restricted to CAFs under physiopathologic conditions. Tumor cell uptake of CAF-derived ANXA6+ EVs promotes pancreatic ductal adenocarcinoma (PDA) cell survival and migration. Depletion of ANXA6 in CAFs impaired complex formation and reduced PDA aggressiveness and metastasis in vivo, while injection of ANXA6+ EVs enhanced tumorigenesis. Proteomic stromal signature analysis, co-immunoprecipitation to identify the ANXA6/LRP1/TSP1 complex, ANXA6 depletion in CAFs, in vivo xenograft and metastasis assays, EV uptake experiments The Journal of clinical investigation High 27701147
2017 AnxA6 was identified as the target antigen of the inhibitory monoclonal antibody MAb 9E1 using immunoprecipitation/LC-MS/MS. Silencing of AnxA6 markedly reduced the invasive capacity of pancreatic and lung squamous cancer cells in vitro, identifying AnxA6 as a functionally relevant pro-invasive target at the cancer cell surface. Immunoprecipitation/LC-MS/MS target identification, AnxA6 siRNA knockdown, invasion assays in vitro British journal of cancer Medium 28881357
2018 AnxA6-knockout (KO) mice fed a high-fat diet gained less weight and showed reduced adiposity compared to wild-type controls. AnxA6-KO mice displayed increased insulin-inducible phosphorylation of Akt and S6K in liver, but failed to downregulate hepatic gluconeogenesis despite normal insulin signaling. AnxA6-depleted HuH7 hepatocytes were unable to reduce glucose production upon insulin exposure, and KO animals showed increased hepatic glycogen storage, demonstrating that AnxA6 contributes to fine-tuning of hepatic glucose metabolism. AnxA6-KO mouse model, high-fat diet feeding, oral glucose tolerance tests (OGTT), insulin tolerance tests (ITT), Western blot for Akt/S6K phosphorylation, glucose production assay in AnxA6-depleted hepatocytes PloS one High 30110341
2020 ANXA6 promotes autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway in nasopharyngeal carcinoma cells, thereby contributing to radioresistance. ANXA6 siRNA suppressed autophagy through activation (de-repression) of PI3K/AKT/mTOR, and the PI3K inhibitor CAL101 reversed siANXA6-reduced autophagy. A negative feedback loop was identified in which suppression of PI3K/AKT/mTOR by CAL101 increased ANXA6 expression. ANXA6 siRNA knockdown, LC3 siRNA knockdown, PI3K/AKT/mTOR inhibitor (CAL101) treatment, autophagy assays, Western blot for pathway components Frontiers in cell and developmental biology Medium 32373608
2020 EHEC effector protein EspF physically interacts with host protein ANXA6 through its C-terminal domain, as verified by FRET and co-immunoprecipitation. Co-expression of EspF-ANXA6 activated myosin light chain kinase (MLCK), induced phosphorylation of myosin light chain (MLC) and PKCα, downregulated Calmodulin, and decreased levels and disrupted distribution of tight junction proteins ZO-1 and occludin, revealing a mechanism by which bacterial infection perturbs epithelial barrier function through ANXA6. FRET, co-immunoprecipitation, domain mapping, Western blot for MLCK/MLC/PKCα phosphorylation and tight junction proteins, confocal microscopy for ZO-1 distribution Frontiers in cell and developmental biology Medium 33425920
2020 ANXA6 enables appropriate ATG9A+ vesicle trafficking from endosomes to autophagosomes through RAB GTPases and/or F-actin, thereby facilitating autophagosome formation. ANXA6 knockdown attenuated starvation-induced autophagy, while restoration of expression enhanced it. ANXA6 also suppresses mTOR activity through inhibition of PI3K-AKT and ERK signaling pathways, providing dual control of autophagy. ANXA6 siRNA knockdown, ANXA6 rescue overexpression, GO analysis of ANXA6 interaction targets, ATG9A vesicle trafficking assays, mTOR/PI3K-AKT/ERK signaling Western blot, LC3 reporter assays Clinical and translational medicine Medium 33135350
2021 ANXA6-containing exosomes (ANXA6-exo) derived from breast cancer stem cells promote paclitaxel resistance and cancer progression in recipient cells via autophagy induction in a YAP1-dependent manner. ANXA6-exo upregulated YAP1 to dysregulate the Hippo pathway, and silencing YAP1 abrogated the resistance effects. Autophagy inhibition with 3-methyladenine blocked ANXA6-exo-mediated PTX resistance. Exosome isolation and transfer experiments, ANXA6 and YAP1 siRNA knockdown, autophagy inhibitor (3-methyladenine), paclitaxel resistance assays, stem cell enrichment assays Frontiers in cell and developmental biology Medium 34676207
2021 CRISPR-Cas9 knockout of the ANXA6 gene in HEK293FT cells significantly increased influenza A virus replication and accumulation, demonstrating that endogenous ANXA6 functions as a host restriction factor that counteracts influenza virion packaging. CRISPR-Cas9 gene knockout, TCID50 viral titer assay, flow cytometry, viral growth curve experiments in ANXA6-/- versus parental cells Gene Medium 34673207
2022 In osteoblasts, AnxA6 plays a role in matrix vesicle-mediated mineralization. Apigenin treatment disrupted intracellular distribution of AnxA6 by blocking AnxA6 aggregation and TNAP attachment to membranes, and modulated TNAP enzymatic activity, affecting mineral composition and structure. AnxA6 distribution was examined by fluorescence microscopy and TEM-gold in cells and vesicles. Fluorescence microscopy (FM), TEM-gold labeling of vesicles, ELISA for TNAP activity, AR-S/CPC mineralization assay, apigenin pharmacological treatment in hFOB1.19, Saos-2, and HCASMC cell lines International journal of molecular sciences Medium 36361965
2022 miR-24-3p directly binds the 3'UTR of ANXA6 mRNA and suppresses ANXA6 expression, thereby promoting proliferation and inhibiting adipogenic differentiation of chicken intramuscular preadipocytes. Overexpression of ANXA6 inhibited proliferation and promoted differentiation, while ANXA6 knockdown had opposite effects. Rescue with an ANXA6 overexpression vector eliminated the impact of miR-24-3p mimics, confirming ANXA6 as the functional mediator. Dual-luciferase reporter assay for miR-24-3p binding to ANXA6 3'UTR, ANXA6 overexpression and knockdown, miR-24-3p mimics/inhibitors, cell proliferation and adipogenic differentiation assays Genes Medium 35456441
2023 AnxA6 is SUMOylated by SUMO1, with K299 identified as a key SUMOylation site. SUMOylated AnxA6 preferentially binds EGFR upon EGF stimulation and facilitates EGFR-PKCα complex formation, which decreases EGF-induced phosphorylation of EGFR and ERK1/2 and reduces cyclin D1 expression. The SUMO-site mutant AnxA6K299R showed reduced suppression of EGFR-ERK1/2 phosphorylation, reduced tumor suppression, and conferred gefitinib resistance. This mechanism also operates on mutant EGFR (T790M/L858R). Co-transfection with SUMO1/UBC9 plasmids, immunoprecipitation for SUMOylated AnxA6, LC-MS/MS for SUMOylation site mapping, site-directed mutagenesis (K299R), shRNA knockdown, lentiviral overexpression, Western blot, CCK8/colony/wound healing assays, xenograft nude mouse model Cell communication and signaling High 37528485
2023 The ANXA6/TRPV2 axis promotes lymphatic metastasis in head and neck squamous cell carcinoma by inducing autophagy through inhibition of the AKT/mTOR signaling pathway. ANXA6 expression positively correlated with TRPV2 expression, and TRPV2 inhibition reversed ANXA6-induced autophagy and lymphatic metastasis, placing TRPV2 downstream of ANXA6 in this pathway. RNA sequencing of clinical specimens, ANXA6 overexpression/knockdown, in vitro proliferation and migration assays, in vivo lymphatic metastasis assays, TRPV2 inhibitor treatment, AKT/mTOR pathway Western blot Experimental hematology & oncology Medium 37138336
2024 PRRX1 was identified as a transcription factor that directly promotes ANXA6 expression in bladder cancer via ChIP-PCR and dual-luciferase assays. ANXA6 in turn promotes PKCα/EGFR complex formation (confirmed by mass spectrometry, immunofluorescence, and co-immunoprecipitation), inhibiting EGFR phosphorylation and downstream AKT and ERK1/2 signaling, thereby enhancing cisplatin sensitivity and re-sensitizing resistant cells. ChIP-PCR, dual-luciferase reporter assay for PRRX1 binding to ANXA6 promoter, mass spectrometry, immunofluorescence, co-immunoprecipitation, CCK-8, colony formation, flow cytometry (ROS, apoptosis), comet assay, xenograft model Life sciences Medium 39528080
2025 Anxa6-/- mice display rapid fasting-induced hypoglycemia due to a specific impairment in the glucose-alanine cycle: these mice cannot utilize alanine for hepatic gluconeogenesis (GNG). Fasted Anxa6-/- mice showed elevated glucagon, increased lipid oxidation, and slightly reduced expression of alanine aminotransferase 2 (Gpt2), lactate dehydrogenase (Ldha2), and the hepatic alanine transporter SNAT4, demonstrating a critical role for ANXA6 in alanine-dependent hepatic GNG. Anxa6-/- knockout mouse model, indirect calorimetry, glucose/insulin/glucagon tolerance tests, alanine challenge tests, respiratory exchange ratio measurement, biochemical enzyme expression analysis Journal of cellular physiology Medium 40802799
2025 ANXA6 overexpression in decidual macrophages promotes macrophage M1 polarization and pyroptosis through the NF-κB signaling pathway, leading to mitochondrial ROS accumulation and decreased mitochondrial membrane potential. Inhibition of NLRP3 rescued ANXA6-overexpression-induced M1 polarization and pyroptosis. ANXA6-overexpressing macrophages inhibited trophoblast function in vitro via TNF-α-mediated inhibition of the PI3K/AKT axis. ANXA6 overexpression in macrophages, ROS/mitochondrial membrane potential assays, NLRP3 inhibitor treatment, ROS inhibitor treatment, NF-κB pathway analysis, M1/M2 polarization markers, trophoblast co-culture, PI3K/AKT pathway Western blot International journal of biological sciences Medium 40959268
2025 MG53 binds AnxA6 at membrane injury sites, and AnxA6 overexpression abolishes MG53's cytoprotective effects in iPSCs under hypoxia/reoxygenation stress, placing AnxA6 as a negative regulator of MG53-mediated membrane repair. MG53 treatment enhanced iPSC survival and functional integration in myocardial tissue post-ischemia-reperfusion injury in vivo. Co-binding assay/interaction studies (MG53-AnxA6), AnxA6 overexpression rescue experiment, H/R injury model in iPSCs, in vivo MIRI model with MG53 treatment and iPSC transplantation Cellular signalling Low 41106752
2025 ANXA6 co-localizes with cGAS and acts as an inhibitor of the cGAS-STING signaling pathway by promoting K63-linked ubiquitination of cGAS, thereby reducing cGAS protein levels. ANXA6 knockdown impeded cGAS K63-ubiquitination, increased cGAS expression, activated downstream TBK1, IRF3, and type I IFN-stimulated genes (MX1, ISG15, ISG56), elevated ROS and lipid peroxides, and induced ferroptosis in cervical cancer cells. Co-localization by immunofluorescence, co-immunoprecipitation for ANXA6-cGAS interaction, ubiquitination assays (K63-linkage specificity), ANXA6 siRNA knockdown, Western blot for cGAS-STING pathway components, ROS/lipid peroxide assays, ferroptosis detection Cancer cell international Medium 41219880
2025 In DMD skeletal muscle cells, ANXA5 and ANXA6 fail to upregulate in response to mechanical membrane stress, while control cells upregulate both proteins as part of an adaptive membrane repair mechanism. This was established by live-cell imaging of GFP-tagged annexins, Western blotting, and a shear stress-based injury assay, placing ANXA6 as part of the adaptive membrane repair response in skeletal muscle. Live-cell imaging of GFP-tagged ANXA6, shear stress-based membrane injury assay, Western blot for annexin expression, immunohistochemistry of DMD patient biopsies bioRxivpreprint Low
2024 AnxA6 interacts with SNAP23 (a SNARE protein) and this interaction is required for the translocation of AnxA6 to cellular membranes and subsequent secretion of pro-inflammatory cytokines (MCP-1/CCL2, IL-8, DKK1, TSP-1, osteopontin) and small extracellular vesicles (EVs) in triple-negative breast cancer cells. AnxA6 downregulation strongly reduced EV secretion and cytokine levels; upregulation promoted EV-associated Rab7, cholesterol, and MCP-1. AnxA6 neutralizing antibodies reduced survival of AnxA6-low TNBC cells. Co-immunoprecipitation (AnxA6-SNAP23), cytokine arrays on conditioned media, EV isolation and characterization, AnxA6 siRNA knockdown and overexpression, cholesterol measurement in EVs, membrane translocation assays bioRxivpreprint Medium

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2016 ATPase-Modulated Stress Granules Contain a Diverse Proteome and Substructure. Cell 1233 26777405
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2021 Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV. Nature 532 33845483
2011 Analysis of the myosin-II-responsive focal adhesion proteome reveals a role for β-Pix in negative regulation of focal adhesion maturation. Nature cell biology 490 21423176
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2016 Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing. Cell 423 26871637
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2010 Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics. Cell 318 21145461
2017 Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proceedings of the National Academy of Sciences of the United States of America 282 28611215
1990 Characterization of Ca2(+)-dependent phospholipid binding, vesicle aggregation and membrane fusion by annexins. The Biochemical journal 276 2138016
2012 A high-throughput approach for measuring temporal changes in the interactome. Nature methods 273 22863883
2022 Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell 256 35063084
2010 MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunology and cell biology 221 20458337
2014 Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver. BMC cancer 203 25037231
2020 Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions. Nature cell biology 194 32203420
2017 Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics. Journal of proteome research 185 28675934
2016 Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness. The Journal of clinical investigation 182 27701147
1988 Primary structure of the human, membrane-associated Ca2+-binding protein p68 a novel member of a protein family. The EMBO journal 161 3258820
2019 A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape. Nature immunology 159 30833792
2006 Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes. Journal of proteome research 150 17081065
2020 ANXA6 Contributes to Radioresistance by Promoting Autophagy via Inhibiting the PI3K/AKT/mTOR Signaling Pathway in Nasopharyngeal Carcinoma. Frontiers in cell and developmental biology 41 32373608
2020 ANXA6 suppresses the tumorigenesis of cervical cancer through autophagy induction. Clinical and translational medicine 34 33135350
2021 Breast Cancer Stem Cell-Derived ANXA6-Containing Exosomes Sustain Paclitaxel Resistance and Cancer Aggressiveness in Breast Cancer. Frontiers in cell and developmental biology 27 34676207
2022 miR-24-3p Dominates the Proliferation and Differentiation of Chicken Intramuscular Preadipocytes by Blocking ANXA6 Expression. Genes 26 35456441
2013 TNIP1/ANXA6 and CSMD1 variants interacting with cigarette smoking, alcohol intake affect risk of psoriasis. Journal of dermatological science 25 23541940
2018 Altered hepatic glucose homeostasis in AnxA6-KO mice fed a high-fat diet. PloS one 21 30110341
2017 A novel inhibitory anti-invasive MAb isolated using phenotypic screening highlights AnxA6 as a functionally relevant target protein in pancreatic cancer. British journal of cancer 21 28881357
2023 ANXA6: a key molecular player in cancer progression and drug resistance. Discover oncology 20 37129645
2022 MANF/EWSR1/ANXA6 pathway might as the bridge between hypolipidemia and major depressive disorder. Translational psychiatry 19 36585419
2015 Gene-based meta-analysis of genome-wide association study data identifies independent single-nucleotide polymorphisms in ANXA6 as being associated with systemic lupus erythematosus in Asian populations. Arthritis & rheumatology (Hoboken, N.J.) 15 26202167
2023 ANXA6/TRPV2 axis promotes lymphatic metastasis in head and neck squamous cell carcinoma by inducing autophagy. Experimental hematology & oncology 14 37138336
2022 The mouse Anxa6/miR-9-5p/Anxa2 axis modulates TGF-β1-induced mouse hepatic stellate cell (mHSC) activation and CCl4-caused liver fibrosis. Toxicology letters 14 35483553
2023 SUMOylation of AnxA6 facilitates EGFR-PKCα complex formation to suppress epithelial cancer growth. Cell communication and signaling : CCS 13 37528485
2020 Enterohemorrhagic Escherichia coli Effector Protein EspF Interacts With Host Protein ANXA6 and Triggers Myosin Light Chain Kinase (MLCK)-Dependent Tight Junction Dysregulation. Frontiers in cell and developmental biology 12 33425920
2022 Apigenin Modulates AnxA6- and TNAP-Mediated Osteoblast Mineralization. International journal of molecular sciences 10 36361965
2021 The Impact of ANxA6 Gene Polymorphism on the Efficacy of Methotrexate Treatment in Psoriasis Patients. Dermatology (Basel, Switzerland) 10 33582672
2022 EZH2 Regulates ANXA6 Expression via H3K27me3 and Is Involved in Angiotensin II-Induced Vascular Smooth Muscle Cell Senescence. Oxidative medicine and cellular longevity 9 36160712
2021 CRISPR-Cas9 mediated knockout of AnxA6 gene enhances influenza A virus replication in low-permissive HEK293FT cell line. Gene 8 34673207
2013 Interaction of AnxA6 with isolated and artificial lipid microdomains; importance of lipid composition and calcium content. Molecular bioSystems 6 23360953
2024 ANXA6 expression as a potential indicator of tumor diagnosis, metastasis and immunity in nasopharyngeal carcinoma. International journal of biological macromolecules 5 39577524
2024 Transcription factor PRRX1-activated ANXA6 facilitates EGFR-PKCα complex formation and enhances cisplatin sensitivity in bladder cancer. Life sciences 3 39528080
2023 Comprehensive analysis the diagnosis, malignant progression and immune infiltrate of ANXA6 in prostate cancer. Genes & genomics 3 37311953
2026 Multi-omics integration reveals ANXA6-high γδ T cell-endothelial communication as a potential link between periodontitis and MASLD. NPJ systems biology and applications 0 41876560
2025 [Ursolic acid down-regulates ANXA6 and inhibits breast cancer cell growth and metastasis]. Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] 0 40374359
2025 Fasting-Induced Hepatic Gluconeogenesis Is Compromised In Anxa6-/- Mice. Journal of cellular physiology 0 40802799
2025 ANXA6 Overexpression Causes Abnormal Decidual Macrophage-Trophoblast Crosstalk in Recurrent Spontaneous Abortion. International journal of biological sciences 0 40959268
2025 Identification of Core SASP-Related Genes TGFBI and ANXA6 for Diagnosing Ulcerative Colitis-Related Colorectal Cancer Through Machine Learning. Journal of inflammation research 0 40989757
2025 Mitsugumin 53 improves myocardial ischemia-reperfusion injury by promoting iPSCs survival through regulating AnxA6 axis. Cellular signalling 0 41106752
2025 Mechanism of interaction between ANXA6 and cGAS to regulate STING signaling pathway and promote ferroptosis in cervical cancer. Cancer cell international 0 41219880
2023 The polymorphisms of ANXA6 influence head and neck cancer susceptibility in the Chinese Han population. Frontiers in oncology 0 36998449
2023 Retracted: EZH2 Regulates ANXA6 Expression via H3K27me3 and Is Involved in Angiotensin II-Induced Vascular Smooth Muscle Cell Senescence. Oxidative medicine and cellular longevity 0 38188996