Affinage

DOC2B

Double C2-like domain-containing protein beta · UniProt Q14184

Length
412 aa
Mass
45.9 kDa
Annotated
2026-06-09
33 papers in source corpus 24 papers cited in narrative 24 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

DOC2B is a cytosolic, high-affinity Ca2+ sensor built from tandem C2 domains that couples intracellular Ca2+ rises to regulated vesicle exocytosis in both neuronal and metabolic tissues (PMID:20150444, PMID:15033971). A Ca2+ rise alone is sufficient to drive Munc13-independent translocation of DOC2B to the plasma membrane, where its C2 domains bind phospholipids in a Ca2+-dependent manner with a translocation threshold of ~200 nM; structural and domain-dissection work establishes C2B as the primary high-affinity Ca2+-sensing unit, with C2A enhancing membrane engagement (PMID:15033971, PMID:23994332, PMID:16305808). At the membrane DOC2B acts as a Ca2+ sensor for spontaneous and asynchronous release, binding SNARE complexes in competition with synaptotagmin-1, and functions as a priming factor that augments the readily releasable pool while inhibiting sustained release to favor synchronized fusion (PMID:20150444, PMID:18596155, PMID:24133251). Biophysically, its C2AB module directly bends membrane bilayers and drives Ca2+- and phosphatidylserine-dependent hemifusion of SNARE-free membranes, an activity essential for its stimulatory role in fusion (PMID:23427263, PMID:26395669). DOC2B also serves as a scaffold that bridges Munc18 isoforms and recruits Munc13-1 to the membrane in a Ca2+-dependent manner, organizing the priming machinery (PMID:24062723, PMID:25190515). In non-neuronal tissues DOC2B drives insulin-granule and GLUT4-vesicle exocytosis through Ca2+-dependent binding to syntaxin-4 and promotion of Munc18c–syntaxin-4 dissociation and SNARE assembly, and insulin/glucose stimulation triggers Src-family-kinase (YES)-mediated Y301 tyrosine phosphorylation that recruits kinesin light chain 1 and supports vesicle trafficking (PMID:19033398, PMID:22698913, PMID:30707251, PMID:35377441). Distinct from its exocytic role, DOC2B has Ca2+-dependent tumor-suppressive activity in cervical cancer, interacting with CDH1, antagonizing Wnt/β-catenin signaling, and inducing mitochondrial dysfunction and senescence (PMID:33758996, PMID:35500882, PMID:36913987).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2004 High

    Established that DOC2B is intrinsically Ca2+-responsive, answering whether its membrane recruitment requires partner proteins or follows directly from Ca2+ binding.

    Evidence Phospholipid binding with purified protein and live-cell imaging of EGFP-DOC2B translocation in neurons

    PMID:15033971

    Open questions at the time
    • Did not resolve which C2 domain provides the dominant Ca2+ sensitivity
    • Lipid specificity of the Ca2+-dependent interaction not defined
  2. 2005 Medium

    Quantified the Ca2+ threshold and kinetics of DOC2B membrane translocation, defining it as a sensor reporting local submembrane Ca2+.

    Evidence Live-cell EGFP-DOC2B imaging with simultaneous Ca2+ imaging in Aplysia neurons

    PMID:16305808

    Open questions at the time
    • Bulk vs. true submembrane Ca2+ values not directly reconciled
    • Functional consequence of translocation kinetics on release not measured here
  3. 2008 High

    Linked DOC2B membrane translocation to vesicle priming and fusion-pore control, and extended its role beyond neurons to insulin-stimulated GLUT4 exocytosis via Ca2+-dependent syntaxin-4 binding.

    Evidence Electrophysiology/TIRF in secretory cells and yeast two-hybrid, Co-IP, GST pulldown, and glucose-uptake assays in adipocytes

    PMID:18596155 PMID:19033398

    Open questions at the time
    • Whether the same priming mechanism operates in neuronal and metabolic tissues not directly compared
    • Domain basis of syntaxin-4 binding not yet mapped
  4. 2009 Medium

    Showed phase-specificity of DOC2B in insulin secretion, distinguishing its action on second-phase release and confirming syntaxin-4 (not syntaxin-1) selectivity in β-cells.

    Evidence Co-IP, fractionation, and knockdown/overexpression with insulin-secretion assays in MIN6 cells

    PMID:19410553

    Open questions at the time
    • Mechanism distinguishing first- vs second-phase contribution unresolved
    • Single-lab Co-IP for syntaxin selectivity
  5. 2010 High

    Defined DOC2B as a high-affinity Ca2+ sensor for spontaneous neurotransmitter release acting in competition with synaptotagmin-1 on SNARE complexes.

    Evidence SNARE competition binding assays, neuronal electrophysiology, and knockout mouse analysis

    PMID:20150444

    Open questions at the time
    • Structural basis of competition with synaptotagmin-1 not resolved
    • Relative contribution to spontaneous vs evoked release left open
  6. 2012 High

    Established in vivo that Doc2b positively regulates Munc18c–syntaxin-4 exocytosis, mechanistically by promoting Munc18c–syntaxin-4 dissociation and SNARE assembly across metabolic tissues.

    Evidence Doc2b knockout mice, glucose/insulin tolerance tests, islet secretion, GLUT4 translocation, and SNARE assembly assays

    PMID:22698913

    Open questions at the time
    • How Doc2b triggers Munc18c displacement biochemically not fully defined
    • Tissue-specific contributions not separated
  7. 2013 High

    Reconstitution, structural, and biophysical work resolved the molecular activities of DOC2B: SNARE-dependent fusion acceleration, membrane bending, and identification of C2B as the dominant Ca2+ sensor with C2A enhancing membrane engagement; chromaffin work added its dual role in augmenting the RRP and suppressing sustained release.

    Evidence Proteoliposome fusion and EM, X-ray crystallography of C2A/C2B with SAXS of C2AB and live-cell domain translocation, and KO/OE capacitance electrophysiology with EM

    PMID:23427263 PMID:23994332 PMID:24133251

    Open questions at the time
    • Full-length tandem-domain structure on a membrane not solved
    • Molecular basis of the inhibitory action on sustained release incompletely defined
  8. 2013 Medium

    Identified DOC2B as a recruiter of Munc13-1 to the plasma membrane, placing it upstream in priming-machinery assembly.

    Evidence Live-cell imaging of co-expressed tagged proteins and a Munc13-1 DAG-binding mutant in PC12 cells

    PMID:24062723

    Open questions at the time
    • Direct binding interface between Doc2b and Munc13-1 not mapped biochemically
    • Single-lab imaging-based evidence
  9. 2014 Medium

    Demonstrated DOC2B acts as a scaffold bridging Munc18-1 (via C2A) and Munc18c (via C2B), and that its overexpression enhances syntaxin-4 SNARE assembly and improves whole-body insulin sensitivity.

    Evidence Co-IP and GST competition/domain mapping in β-cells and tetracycline-repressible Doc2b transgenic mice with SNARE/GLUT4 assays

    PMID:24705606 PMID:25190515

    Open questions at the time
    • Stoichiometry and structure of the Doc2b-Munc18 ternary complex unknown
    • Single-lab biochemistry
  10. 2015 High

    Provided direct biophysical proof that the DOC2B C2AB module itself drives Ca2+/PS-dependent membrane hemifusion independent of SNAREs.

    Evidence Optical tweezers with SNARE-free synthetic membranes and lipid/content-mixing fluorescence assays

    PMID:26395669

    Open questions at the time
    • How hemifusion intermediate couples to SNARE-driven full fusion in vivo unresolved
    • Physiological relevance of 600 pN stalk strength not established
  11. 2017 High

    Dissected DOC2B into separable priming functions, mapping an upstream C2A-dependent step, a downstream SNARE/C2B/Munc13-2/synaptotagmin-1-dependent step, and a MID-domain inhibitory function.

    Evidence Ca2+-coordinating residue mutagenesis with epistasis to Munc13-2 and synaptotagmin-1 and electrophysiology in chromaffin cells

    PMID:29274147

    Open questions at the time
    • Molecular basis of the MID-domain inhibitory action not defined
    • Generalizability to neuronal synapses not tested
  12. 2019 High

    Identified insulin-stimulated Y301 tyrosine phosphorylation as a regulatory switch coupling DOC2B to kinesin light chain 1 for GLUT4 vesicle trafficking.

    Evidence Co-IP, mass spectrometry, Y301 mutagenesis, and GLUT4 assays in skeletal-muscle-specific transgenic mice

    PMID:30707251

    Open questions at the time
    • Kinase responsible in muscle not identified here
    • Whether phosphorylation alters Ca2+ sensing not tested
  13. 2020 Medium

    Tested the necessity of Doc2b at a defined synapse and found it dispensable for release at mature Purkinje-to-DCN synapses, bounding its physiological role.

    Evidence Doc2b knockout mice with electrophysiology in acute cerebellar slices (negative result)

    PMID:32347796

    Open questions at the time
    • Possible redundancy or developmental compensation not excluded
    • Result is synapse-specific and may not generalize
  14. 2022 High

    Resolved the upstream signaling of DOC2B Y301 phosphorylation in β-cells, identifying YES kinase as the modifier and linking phospho-DOC2B to VAMP2 surface delivery and ERM activation in secretion.

    Evidence Co-IP, Y301 mutagenesis, VAMP2 localization, and ERM knockdown in human islets and clonal β-cells

    PMID:35377441

    Open questions at the time
    • Direct ERM-DOC2B mechanistic link not fully defined
    • Whether YES phosphorylation operates identically in muscle not confirmed
  15. 2021 Medium

    Opened a non-exocytic axis for DOC2B as a Ca2+-dependent tumor suppressor in cervical cancer through CDH1 interaction, EMT inhibition, and senescence induction.

    Evidence Overexpression/knockdown, Ca2+ chelation, Co-IP with CDH1, and xenograft assays

    PMID:33758996

    Open questions at the time
    • How a vesicle-fusion Ca2+ sensor engages CDH1 mechanistically unclear
    • Single-lab evidence
  16. 2022 Medium

    Extended the tumor-suppressive mechanism to negative regulation of Wnt/β-catenin signaling via destruction-complex enhancement and DKK1 upregulation.

    Evidence Overexpression/knockdown, β-catenin and proteasome assays, and DKK1 pharmacological inhibition

    PMID:35500882

    Open questions at the time
    • Direct molecular link between DOC2B and destruction-complex components unestablished
    • GSK3β-independent degradation route undefined
  17. 2023 Medium

    Added a mitochondrial localization and Ca2+-mediated lipotoxicity function for DOC2B in cancer cells, and a protective role against palmitate-induced GLUT4 trafficking failure in muscle.

    Evidence Mitochondrial fractionation and functional/ROS/lipid-peroxidation assays, and L6 muscle overexpression with cofilin and GLUT4 readouts under palmitate stress

    PMID:36913987 PMID:38203312

    Open questions at the time
    • How a plasma-membrane Ca2+ sensor localizes to and acts at mitochondria not explained
    • Direct molecular target for cofilin regulation not identified
  18. 2025 Medium

    Implicated DOC2B in dampening β-cell inflammatory signaling through physical association with IKKβ, NF-κB p65, and STAT-1, reducing cytokine-induced CXCL10.

    Evidence Co-IP, enrichment/depletion in human islets and β-cell lines, qPCR, proteomics, and imaging

    PMID:39805534

    Open questions at the time
    • Whether DOC2B directly inhibits these kinases/transcription factors or acts indirectly unresolved
    • Single-lab Co-IP-based associations

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single Ca2+-sensing exocytic protein is repurposed for nuclear/cytoplasmic tumor suppression, mitochondrial regulation, and inflammatory signaling — and whether these reflect direct mechanisms or downstream consequences of altered Ca2+ handling — remains unresolved.
  • No structural model of full-length DOC2B engaging SNAREs or Munc18 on a membrane
  • Mechanistic basis of mitochondrial localization undefined
  • Direct vs indirect nature of Wnt and inflammatory-pathway regulation untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 3 GO:0098772 molecular function regulator activity 3 GO:0140299 molecular sensor activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-1430728 Metabolism 3 R-HSA-112316 Neuronal System 2 R-HSA-162582 Signal Transduction 2
Partners
CDH1KLC1MUNC18CSTX4STXBP1UNC13AUNC13BYES1
Complex memberships
Doc2b-Munc18-1-Munc18c scaffoldSNARE complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 DOC2B acts as a high-affinity Ca2+ sensor for spontaneous neurotransmitter release. Doc2 proteins are cytosolic but function analogously to synaptotagmin-1, binding SNARE complexes in competition with synaptotagmin-1 and triggering spontaneous vesicle fusion with higher Ca2+ sensitivity than synaptotagmin-1. Biochemical binding assays (SNARE competition), electrophysiology in neurons, knockout mouse analysis Science High 20150444
2008 The C2A domain of DOC2B interacts directly with the plasma membrane in a calcium-dependent manner. DOC2B acts as a priming factor, increasing the number of fusion-competent vesicles, must translocate to the plasma membrane to exert its effect, and interacts with plasma membrane SNAREs to affect fusion pore kinetics during catecholamine secretion. Biochemical and biophysical measurements, electrophysiology, TIRF microscopy, morphological analysis The Journal of Neuroscience High 18596155
2008 DOC2B directly associates with syntaxin-4 in an intracellular Ca2+-dependent manner and is essential for GLUT4 vesicle fusion in adipocytes. DOC2B translocates to the plasma membrane upon insulin stimulation, and Ca2+-binding domain mutants or DOC2B knockdown inhibit insulin-stimulated glucose uptake. Yeast two-hybrid screening, immunoprecipitation, GST pull-down, confocal microscopy, GLUT4 externalization assay, glucose uptake measurement, siRNA knockdown Diabetes High 19033398
2004 A rise in intracellular Ca2+ is sufficient for Munc13-independent recruitment of DOC2B to the target membrane. Purified DOC2B binds phospholipids in a Ca2+-dependent manner via its C2 domain, and Ca2+-induced translocation occurs in neurons within 5 seconds of depolarization. Phospholipid binding assay with purified protein, live-cell fluorescence imaging (EGFP-DOC2B in neurons), Ca2+-dependent translocation assays The Journal of Biological Chemistry High 15033971
2013 Doc2b binds GLUT4 exocytic SNAREs and potently accelerates SNARE-dependent fusion kinetics in a Ca2+-dependent manner. Ca2+-binding sites on both C2A and C2B domains are required. Doc2b strongly bends membrane bilayers, and this membrane-bending activity is essential for its stimulatory function in GLUT4 vesicle fusion. Reconstituted proteoliposome SNARE-dependent fusion assay, electron microscopy for membrane bending, site-directed mutagenesis of Ca2+-binding sites Molecular Biology of the Cell High 23427263
2013 Crystal structures of the isolated C2A and C2B domains of DOC2B were determined, and small-angle X-ray scattering characterized the solution structure of the tandem C2AB domain. C2B binds Ca2+ with considerably higher affinity than C2A. In cells, isolated C2B translocates to the plasma membrane with an EC50 of ~400 nM while C2A does not translocate at submicromolar Ca2+. C2A enhances the interaction of C2AB with the plasma membrane but C2B is the primary Ca2+ sensing unit. X-ray crystallography of C2A and C2B domains, SAXS of C2AB, Ca2+ binding kinetics, live-cell imaging of domain translocation Journal of Molecular Biology High 23994332
2012 Doc2b is required for both phases of glucose-stimulated insulin secretion and for insulin-stimulated GLUT4 vesicle translocation in skeletal muscle. Doc2b deficiency impairs Munc18c-syntaxin 4 dissociation and SNARE complex assembly. Doc2b acts as a positive regulator of Munc18c-syntaxin 4-mediated exocytosis in vivo. Doc2b heterozygous and homozygous knockout mice, in vivo glucose/insulin tolerance tests, ex vivo islet insulin secretion, skeletal muscle GLUT4 translocation assay, SNARE complex assembly assay Diabetes High 22698913
2015 The C2AB domain of Doc2b directly induces membrane hemifusion in a Ca2+- and phosphatidylserine-dependent manner in a cell-free system. Doc2b-coated membrane stalks between SNARE-free synthetic membranes resist forces up to 600 pN. Phospholipid but not content mixing occurs, confirming hemifusion rather than full fusion. Optical tweezers with SNARE-free synthetic membrane beads, real-time fluorescence imaging for lipid/content mixing Nature Communications High 26395669
2017 Doc2B plays distinct roles in two sequential vesicle priming steps in chromaffin cells. Mutating Ca2+-coordinating aspartates in C2A renders an upstream priming step Ca2+-independent. A downstream priming function depends on SNARE-binding, Ca2+-binding to C2B, interaction with ubMunc13-2, and the presence of synaptotagmin-1. A separate inhibitory function during sustained Ca2+ elevations depends on the MID-domain. Site-directed mutagenesis of Ca2+-coordinating residues, overexpression and knockdown in mouse adrenal chromaffin cells, electrophysiological exocytosis measurements, genetic epistasis with Munc13-2 and synaptotagmin-1 eLife High 29274147
2009 DOC2b associates with insulin vesicles and translocates to the plasma membrane upon glucose stimulation, then interacts specifically with syntaxin-4 (not syntaxin-1). DOC2b knockdown inhibits second-phase insulin secretion without affecting first-phase secretion; DOC2b overexpression enhances glucose-stimulated insulin secretion. Immunoprecipitation, subcellular fractionation/localization, siRNA knockdown, overexpression in MIN6 cells, insulin secretion assays Biochemical and Biophysical Research Communications Medium 19410553
2013 Doc2b synchronizes exocytosis in chromaffin cells by augmenting the readily releasable pool (RRP) and inhibiting the sustained release component. In the absence of Doc2b, RRP refilling is faster but incomplete, leading to premature fusion. Doc2b inhibits vesicle priming during prolonged calcium elevations to protect unprimed vesicles and favor synchronized release. Doc2b knockout mice, high temporal resolution electrophysiological capacitance measurements, electron microscopy of vesicle pools, Doc2b overexpression The Journal of Neuroscience High 24133251
2013 Munc13-1 translocates to the plasma membrane in a Doc2B- and Ca2+-dependent manner in PC12 cells. Munc13-1 co-translocation requires its interaction with Doc2B and depends on diacylglycerol for accumulation. Doc2B dislocates from the membrane faster than Munc13-1 upon Ca2+ removal. Fluorescence live-cell imaging of co-expressed fluorescent-tagged proteins in PC12 cells, Munc13-1(H567K) DAG-binding mutant analysis Frontiers in Endocrinology Medium 24062723
2014 Doc2b serves as a scaffolding platform in pancreatic β-cells that simultaneously binds Munc18-1 (via C2A) and Munc18c (via C2B) to form a macromolecular complex. Doc2b bridges the interaction between Munc18c and Munc18-1; these two proteins fail to associate in the absence of Doc2b. This scaffold function supports both phases of glucose-stimulated insulin secretion. Co-immunoprecipitation from β-cells, in vitro GST-Doc2b interaction/competition assays, domain mapping The Biochemical Journal Medium 25190515
2005 The Ca2+ concentration threshold for DOC2B translocation to the plasma membrane in cultured neurons is approximately 200 nM in the bulk cytoplasm. Translocation rate is slower than Ca2+ elevation rate, while detachment from the membrane is faster than Ca2+ removal. The extent of translocation reflects local submembrane Ca2+ concentration. Live-cell imaging of EGFP-DOC2B in Aplysia neurons with simultaneous Ca2+ imaging Cell Calcium Medium 16305808
2014 Doc2b enrichment enhances syntaxin-4-SNARE complex formation in skeletal muscle cells and increases insulin-stimulated GLUT4 vesicle accumulation at the cell surface, improving glucose tolerance and peripheral insulin sensitivity in transgenic mice overexpressing Doc2b. Tetracycline-repressible transgenic mice overexpressing Doc2b, SNARE complex assays, GLUT4 translocation assay, glucose/insulin tolerance tests Diabetologia Medium 24705606
2019 DOC2B is phosphorylated on tyrosine (Y301) upon insulin stimulation in skeletal muscle cells, enhancing its interaction with kinesin light chain 1 (KLC1). Mutation of Y301 blocks insulin-stimulated DOC2B phosphorylation, reduces DOC2B-KLC1 interaction, and impairs insulin-stimulated GLUT4 accumulation at the plasma membrane. Co-immunoprecipitation, mass spectrometry, site-directed mutagenesis of Y301, GLUT4 translocation assays, skeletal-muscle-specific transgenic mice Diabetologia High 30707251
2019 Syt1 and Doc2b exhibit distinct membrane-remodeling mechanisms. Both Syt1 C2AB and Doc2b C2AB can induce hemifusion of SNARE-free membranes and reduce the membrane-bending modulus in a Ca2+-dependent manner, but Doc2b is more effective when both membranes are loaded, whereas Syt1 is more effective with single-membrane loading. Significantly higher Syt1 concentrations are required for hemifusion than Doc2b. Optical tweezers with synthetic membranes, lipid-mixing confocal assay, AFM membrane-bending modulus measurement Biophysical Journal Medium 31952804
2022 DOC2b is tyrosine-phosphorylated at Y301 within 2 minutes of glucose stimulation in β-cells, mediated by the Src family kinase YES. Y301 phosphorylation is required for DOC2b's interaction with YES kinase, increased VAMP2 at the plasma membrane, and enhanced glucose-stimulated insulin secretion. Tyrosine-phosphorylated DOC2b also increases ERM protein activation; ERM knockdown impairs DOC2b-mediated GSIS. Biochemical analysis of human islets and clonal β-cells, co-immunoprecipitation, site-directed mutagenesis of Y301, VAMP2 plasma membrane localization assay, ERM knockdown Diabetes High 35377441
2021 DOC2B inhibits EMT and promotes cellular senescence in cervical cancer cells via a calcium-dependent process. DOC2B interacts with CDH1 in a calcium-dependent manner, and this interaction is associated with suppression of EMT and induction of senescence. DOC2B overexpression and knockdown, calcium chelation, co-immunoprecipitation of DOC2B with CDH1, in vivo xenograft model Cell Biology and Toxicology Medium 33758996
2022 DOC2B negatively regulates Wnt/β-catenin signaling by enhancing expression of components of the CTNNB1 destruction complex and promoting proteasomal degradation of CTNNB1 in a GSK3β-independent manner. DOC2B upregulates DKK1, and DKK1 inhibition reactivates Wnt/β-catenin signaling and reverses DOC2B-induced senescence and anti-tumor effects. DOC2B overexpression and knockdown, β-catenin protein assays, proteasome inhibitor studies, DKK1 pharmacological inhibition (WAY262611) Pharmacological Research Medium 35500882
2023 DOC2B is localized to mitochondria and induces Ca2+-mediated lipotoxicity in cervical cancer cells. DOC2B expression causes mitochondrial morphological changes, reduces mitochondrial DNA copy number, membrane potential, and complex-IV activity, and elevates intracellular Ca2+, ROS, and lipid peroxidation. These effects are Ca2+-dependent. DOC2B overexpression and knockdown, mitochondrial fractionation/localization assays, mitochondrial functional assays, Ca2+ chelation, lipid peroxidation assays Free Radical Biology and Medicine Medium 36913987
2025 DOC2b enrichment attenuates cytokine-induced CXCL10 expression in β-cells and human islets by reducing IKKβ activation, reducing NF-κB p65 levels, and reducing STAT-1 activation. IKKβ, NF-κB p65, and STAT-1 physically associate with DOC2b in cytokine-challenged β-cells. DOC2b also prevents ER-stress-IKKβ and STAT-1 crosstalk. Co-immunoprecipitation, DOC2b enrichment/depletion in human islets and β-cell lines, qPCR, proteomics, immunoconfocal microscopy Metabolism: Clinical and Experimental Medium 39805534
2020 Loss of Doc2b does not influence spontaneous neurotransmitter release, synaptic strength, evoked release time course, responses to sustained high-frequency stimulation, or short-term plasticity at mature Purkinje cell-to-deep cerebellar nuclei synapses under physiological conditions, despite Doc2b being the sole Doc2 isoform expressed in Purkinje cells. Doc2b knockout mice, electrophysiological recordings at PC-to-DCN synapses in acute cerebellar slices eLife Medium 32347796
2023 DOC2B enrichment in skeletal muscle cells prevents palmitate-induced cofilin phosphorylation, preserves insulin- and β2-adrenergic receptor-stimulated GLUT4 trafficking to the plasma membrane, and rescues glucose uptake under lipotoxic conditions. DOC2B overexpression in rat L6 skeletal muscle cells, GLUT4 translocation assay, cofilin phosphorylation assay, glucose uptake measurement under palmitate stress International Journal of Molecular Sciences Low 38203312

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release. Science (New York, N.Y.) 261 20150444
2013 Doc2b promotes GLUT4 exocytosis by activating the SNARE-mediated fusion reaction in a calcium- and membrane bending-dependent manner. Molecular biology of the cell 49 23427263
2008 DOC2B acts as a calcium switch and enhances vesicle fusion. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 18596155
2008 DOC2B: a novel syntaxin-4 binding protein mediating insulin-regulated GLUT4 vesicle fusion in adipocytes. Diabetes 47 19033398
2012 Doc2b is a key effector of insulin secretion and skeletal muscle insulin sensitivity. Diabetes 43 22698913
2004 Ca(2+)-induced recruitment of the secretory vesicle protein DOC2B to the target membrane. The Journal of biological chemistry 41 15033971
2014 DNA promoter methylation-dependent transcription of the double C2-like domain β (DOC2B) gene regulates tumor growth in human cervical cancer. The Journal of biological chemistry 36 24570007
2015 Direct quantitative detection of Doc2b-induced hemifusion in optically trapped membranes. Nature communications 32 26395669
2017 Doc2B acts as a calcium sensor for vesicle priming requiring synaptotagmin-1, Munc13-2 and SNAREs. eLife 28 29274147
2014 Doc2b enrichment enhances glucose homeostasis in mice via potentiation of insulin secretion and peripheral insulin sensitivity. Diabetologia 28 24705606
2010 DOC2B, C2 domains, and calcium: A tale of intricate interactions. Molecular neurobiology 27 20052564
2019 DOC2B promotes insulin sensitivity in mice via a novel KLC1-dependent mechanism in skeletal muscle. Diabetologia 22 30707251
2009 DOC2b is a SNARE regulator of glucose-stimulated delayed insulin secretion. Biochemical and biophysical research communications 22 19410553
2013 The C2B domain is the primary Ca2+ sensor in DOC2B: a structural and functional analysis. Journal of molecular biology 19 23994332
2021 Metastatic suppression by DOC2B is mediated by inhibition of epithelial-mesenchymal transition and induction of senescence. Cell biology and toxicology 18 33758996
2014 Doc2b serves as a scaffolding platform for concurrent binding of multiple Munc18 isoforms in pancreatic islet β-cells. The Biochemical journal 18 25190515
2013 Munc13-1 Translocates to the Plasma Membrane in a Doc2B- and Calcium-Dependent Manner. Frontiers in endocrinology 18 24062723
2022 DOC2B is a negative regulator of Wnt/β-catenin signaling pathway in cervical cancer. Pharmacological research 17 35500882
2018 Doc2b Protects β-Cells Against Inflammatory Damage and Enhances Function. Diabetes 17 29661782
2019 Synaptotagmin-1 and Doc2b Exhibit Distinct Membrane-Remodeling Mechanisms. Biophysical journal 16 31952804
2005 Calcium concentration threshold and translocation kinetics of EGFP-DOC2B expressed in cultured Aplysia neurons. Cell calcium 16 16305808
2018 Exocytosis Protein DOC2B as a Biomarker of Type 1 Diabetes. The Journal of clinical endocrinology and metabolism 15 29506054
2013 Doc2b synchronizes secretion from chromaffin cells by stimulating fast and inhibiting sustained release. The Journal of neuroscience : the official journal of the Society for Neuroscience 14 24133251
2000 Different spatiotemporal expression of DOC2 genes in the developing rat brain argues for an additional, nonsynaptic role of DOC2B in early development. The European journal of neuroscience 13 10651871
2023 Double C-2 like domain beta (DOC2B) induces calcium dependent oxidative stress to promote lipotoxicity and mitochondrial dysfunction for its tumor suppressive function. Free radical biology & medicine 11 36913987
2022 DOC2b Enhances β-Cell Function via a Novel Tyrosine Phosphorylation-Dependent Mechanism. Diabetes 8 35377441
2023 A Novel Role for DOC2B in Ameliorating Palmitate-Induced Glucose Uptake Dysfunction in Skeletal Muscle Cells via a Mechanism Involving β-AR Agonism and Cofilin. International journal of molecular sciences 5 38203312
2020 Loss of Doc2b does not influence transmission at Purkinje cell to deep nuclei synapses under physiological conditions. eLife 5 32347796
2025 DOC2b enrichment mitigates proinflammatory cytokine-induced CXCL10 expression by attenuating IKKβ and STAT-1 signaling in human islets. Metabolism: clinical and experimental 4 39805534
2024 DOC2b enrichment mitigates proinflammatory cytokine-induced CXCL10 expression by attenuating IKKβ and STAT-1 signaling in human islets. bioRxiv : the preprint server for biology 1 39763877
2026 Loss of Exocytosis Protein DOC2B is an Early Event in Type 1 Diabetes Development. bioRxiv : the preprint server for biology 0 41509347
2026 Revisiting the Platelet-β-Cell Axis: Insights into How Platelet-Derived Mediators, Lipid Signaling, and DOC2B Pathways Converge to Drive β-Cell Dysfunction in Type 2 Diabetes. EJIFCC 0 41659295
2025 doc2a and doc2b contribute to locomotor and social behaviors by down-regulating npas4b in zebrafish. BMC biology 0 40597089

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