Affinage

CAV2

Caveolin-2 · UniProt P51636

Length
162 aa
Mass
18.3 kDa
Annotated
2026-06-09
100 papers in source corpus 2 papers cited in narrative 2 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 2/2 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Caveolin-2 (CAV2) has been linked to the promotion of cancer cell proliferation, migration, and invasion in two tumor contexts, though its molecular function remains uncharacterized in the available corpus. In renal cell carcinoma cells, CAV2 acts upstream of EGFR/PI3K/Akt signaling: its knockdown reduces EGFR, PI3K, and phospho-Akt levels and suppresses proliferation, migration, and invasion (PMID:30288056). In pancreatic cancer cells, CAV2 overexpression activates Wnt7A/β-catenin signaling and drives invasion and metastasis by inhibiting endocytosis and promoting epithelial-mesenchymal transition, with CAV2 expression negatively regulated by MiR-4723 within a MiR-4723/Wnt7A axis (PMID:35517414). Beyond these phenotypic associations, no direct binding, structural, or biochemical reconstitution data establish CAV2's molecular mechanism in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2018 Low

    Established a pro-tumorigenic role for CAV2 in renal cell carcinoma by placing it upstream of a defined oncogenic signaling pathway.

    Evidence siRNA knockdown with wound healing, Matrigel invasion, Western blotting, and orthotopic xenograft in OS-RC-2 cells

    PMID:30288056

    Open questions at the time
    • Single lab, knockdown-only with Western blot pathway readout; no direct binding or reconstitution establishing the mechanistic link to EGFR/PI3K/Akt
    • Whether CAV2 physically interacts with EGFR or pathway components is not shown
    • No structural or biochemical characterization of CAV2 activity
  2. 2022 Low

    Extended CAV2's oncogenic role to pancreatic cancer and connected it to Wnt7A/β-catenin signaling, EMT, and upstream microRNA regulation.

    Evidence Overexpression/knockdown, immunofluorescence, Western blotting, qRT-PCR, luciferase reporter, and proliferation/invasion/migration assays in pancreatic cancer cells

    PMID:35517414

    Open questions at the time
    • Single lab; pathway placement inferred from expression changes after overexpression without direct binding/reconstitution
    • Mechanism by which CAV2 inhibits endocytosis to modulate signaling is not defined
    • Direct MiR-4723/CAV2 targeting versus indirect regulation not fully resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular activity, structure, and direct binding partners of CAV2 protein remain undefined.
  • No direct biochemical or structural characterization of CAV2
  • No validated physical interaction partners
  • Mechanism connecting CAV2 to EGFR/PI3K/Akt and Wnt7A/β-catenin pathways not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
No controlled-vocabulary terms were assigned to this entry.

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 CAV2 (Caveolin-2) knockdown in renal cell carcinoma OS-RC-2 cells inhibited proliferation, migration, and invasion, and reduced expression of EGFR, PI3K, and phospho-Akt, placing CAV2 upstream of the EGFR/PI3K/Akt signaling pathway in kidney cancer cells. siRNA knockdown combined with wound healing, Matrigel invasion assays, Western blotting, and mouse orthotopic xenograft model OncoTargets and therapy Low 30288056
2022 CAV2 (Caveolin-2) overexpression in pancreatic cancer cells activates the Wnt7A/β-catenin signaling pathway and promotes invasion, migration, and metastasis; CAV2 regulates this axis by inhibiting endocytosis and promoting epithelial-mesenchymal transition (EMT). MiR-4723 negatively regulates CAV2 expression, and CAV2 in turn modulates the MiR-4723/Wnt7A signaling axis. Overexpression and knockdown experiments, immunofluorescence, Western blotting, qRT-PCR, luciferase reporter assay, cell proliferation/invasion/migration assays Journal of Cancer Low 35517414

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Quantitative proteomics of the Cav2 channel nano-environments in the mammalian brain. Proceedings of the National Academy of Sciences of the United States of America 250 20668236
2006 Direct G protein modulation of Cav2 calcium channels. Pharmacological reviews 184 17132857
2010 CaV2.1 channelopathies. Pflugers Archiv : European journal of physiology 175 20204399
2012 Regulation of Ca(V)2 calcium channels by G protein coupled receptors. Biochimica et biophysica acta 152 23063655
2009 A presynaptic homeostatic signaling system composed of the Eph receptor, ephexin, Cdc42, and CaV2.1 calcium channels. Neuron 140 19249276
2000 CaV2.2 and CaV2.3 (N- and R-type) Ca2+ channels in depolarization-evoked entry of Ca2+ into mouse sperm. The Journal of biological chemistry 138 10791962
2009 Regulation of N-type voltage-gated calcium channels (Cav2.2) and transmitter release by collapsin response mediator protein-2 (CRMP-2) in sensory neurons. Journal of cell science 126 19903690
2005 Specific kinetic alterations of human CaV2.1 calcium channels produced by mutation S218L causing familial hemiplegic migraine and delayed cerebral edema and coma after minor head trauma. The Journal of biological chemistry 112 15743764
2011 Calcitonin gene-related peptide-mediated enhancement of purinergic neuron/glia communication by the algogenic factor bradykinin in mouse trigeminal ganglia from wild-type and R192Q Cav2.1 Knock-in mice: implications for basic mechanisms of migraine pain. The Journal of neuroscience : the official journal of the Society for Neuroscience 108 21389219
2003 Role of lipid microdomains in P/Q-type calcium channel (Cav2.1) clustering and function in presynaptic membranes. The Journal of biological chemistry 108 14660672
2011 Beta-subunits promote the expression of Ca(V)2.2 channels by reducing their proteasomal degradation. The Journal of biological chemistry 105 21233207
2001 Detection and differentiation of CAV-1 and CAV-2 by polymerase chain reaction. Veterinary research communications 101 11214675
2004 Electrophysiological and molecular evidence of L-(Cav1), N- (Cav2.2), and R- (Cav2.3) type Ca2+ channels in rat cortical astrocytes. Glia 78 14966867
2005 Modulation of CaV2.1 channels by the neuronal calcium-binding protein visinin-like protein-2. The Journal of neuroscience : the official journal of the Society for Neuroscience 77 16049183
2001 Dominant-negative synthesis suppression of voltage-gated calcium channel Cav2.2 induced by truncated constructs. The Journal of neuroscience : the official journal of the Society for Neuroscience 75 11606638
2013 Mechanisms of conotoxin inhibition of N-type (Ca(v)2.2) calcium channels. Biochimica et biophysica acta 73 23380425
2005 G protein-gated inhibitory module of N-type (ca(v)2.2) ca2+ channels. Neuron 72 15953418
2015 A membrane-delimited N-myristoylated CRMP2 peptide aptamer inhibits CaV2.2 trafficking and reverses inflammatory and postoperative pain behaviors. Pain 71 25782368
2010 G protein modulation of CaV2 voltage-gated calcium channels. Channels (Austin, Tex.) 70 21150298
2009 Presynaptic CaV2 calcium channel traffic requires CALF-1 and the alpha(2)delta subunit UNC-36. Nature neuroscience 70 19718034
2005 Use-dependent blockade of Cav2.2 voltage-gated calcium channels for neuropathic pain. Biochemical pharmacology 70 15950195
2019 Cav2.3 channels contribute to dopaminergic neuron loss in a model of Parkinson's disease. Nature communications 69 31704946
2002 The novel product of a five-exon stargazin-related gene abolishes Ca(V)2.2 calcium channel expression. The EMBO journal 67 11927536
2003 Direct interaction and functional coupling between metabotropic glutamate receptor subtype 1 and voltage-sensitive Cav2.1 Ca2+ channel. The Journal of biological chemistry 65 12704197
2012 Cav2.1 in cerebellar Purkinje cells regulates competitive excitatory synaptic wiring, cell survival, and cerebellar biochemical compartmentalization. The Journal of neuroscience : the official journal of the Society for Neuroscience 64 22279216
2006 Alternative splicing in the C-terminus of CaV2.2 controls expression and gating of N-type calcium channels. The Journal of physiology 64 16857708
2018 α-Neurexins Together with α2δ-1 Auxiliary Subunits Regulate Ca2+ Influx through Cav2.1 Channels. The Journal of neuroscience : the official journal of the Society for Neuroscience 63 30104341
2001 The Cav2.1/alpha1A (P/Q-type) voltage-dependent calcium channel mediates inhibitory neurotransmission onto mouse cerebellar Purkinje cells. The European journal of neuroscience 60 11403683
2005 Mechanism of SNARE protein binding and regulation of Cav2 channels by phosphorylation of the synaptic protein interaction site. Molecular and cellular neurosciences 58 15607937
2014 Lipid modulation of calcium flux through CaV2.3 regulates acrosome exocytosis and fertilization. Developmental cell 57 24525187
2018 A Viral Receptor Complementation Strategy to Overcome CAV-2 Tropism for Efficient Retrograde Targeting of Neurons. Neuron 56 29879392
2015 Constitutive and ghrelin-dependent GHSR1a activation impairs CaV2.1 and CaV2.2 currents in hypothalamic neurons. The Journal of general physiology 55 26283199
2005 Differential regulation of CaV2.1 channels by calcium-binding protein 1 and visinin-like protein-2 requires N-terminal myristoylation. The Journal of neuroscience : the official journal of the Society for Neuroscience 53 16049184
2017 CaV2.2 Gates Calcium-Independent but Voltage-Dependent Secretion in Mammalian Sensory Neurons. Neuron 49 29198756
2012 γ-Aminobutyric acid type B (GABAB) receptor expression is needed for inhibition of N-type (Cav2.2) calcium channels by analgesic α-conotoxins. The Journal of biological chemistry 46 22613715
2010 Insights into migraine mechanisms and CaV2.1 calcium channel function from mouse models of familial hemiplegic migraine. The Journal of physiology 45 20194127
2006 Roscovitine differentially affects CaV2 and Kv channels by binding to the open state. Neuropharmacology 45 17125805
2007 Ca(v)1.2, Ca(v)1.3, and Ca(v)2.1 in the mouse hippocampus during and after pilocarpine-induced status epilepticus. Hippocampus 44 17265461
2009 N terminus is key to the dominant negative suppression of Ca(V)2 calcium channels: implications for episodic ataxia type 2. The Journal of biological chemistry 43 19903821
2006 Molecular basis of Ca(v)2.3 calcium channels in rat nociceptive neurons. The Journal of biological chemistry 41 17145762
2012 Purkinje cell-specific ablation of Cav2.1 channels is sufficient to cause cerebellar ataxia in mice. Cerebellum (London, England) 40 21870131
2014 Differential Cav2.1 and Cav2.3 channel inhibition by baclofen and α-conotoxin Vc1.1 via GABAB receptor activation. The Journal of general physiology 37 24688019
2003 Human neuronal stargazin-like proteins, gamma2, gamma3 and gamma4; an investigation of their specific localization in human brain and their influence on CaV2.1 voltage-dependent calcium channels expressed in Xenopus oocytes. BMC neuroscience 37 14505496
2019 CAV-2 Vector Development and Gene Transfer in the Central and Peripheral Nervous Systems. Frontiers in molecular neuroscience 36 30983967
2010 The neuronal splicing factor Nova controls alternative splicing in N-type and P-type CaV2 calcium channels. Channels (Austin, Tex.) 36 21150296
2018 CAV2 promotes the growth of renal cell carcinoma through the EGFR/PI3K/Akt pathway. OncoTargets and therapy 34 30288056
2005 CaV2.3 channel and PKClambda: new players in insulin secretion. The Journal of clinical investigation 34 15630435
2019 Inflammation Induced Sensory Nerve Growth and Pain Hypersensitivity Requires the N-Type Calcium Channel Cav2.2. Frontiers in neuroscience 33 31607850
2008 The stargazin-related protein gamma 7 interacts with the mRNA-binding protein heterogeneous nuclear ribonucleoprotein A2 and regulates the stability of specific mRNAs, including CaV2.2. The Journal of neuroscience : the official journal of the Society for Neuroscience 33 18923037
2019 Reversal of Peripheral Neuropathic Pain by the Small-Molecule Natural Product Physalin F via Block of CaV2.3 (R-Type) and CaV2.2 (N-Type) Voltage-Gated Calcium Channels. ACS chemical neuroscience 32 30946560
2013 Protein kinase Cα and P-type Ca channel CaV2.1 in red blood cell calcium signalling. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 32 23817128
2009 Motor coordination impairment in aged heterozygous rolling Nagoya, Cav2.1 mutant mice. Brain research 32 19446536
2017 miR-34c-5p functions as pronociceptive microRNA in cancer pain by targeting Cav2.3 containing calcium channels. Pain 30 28614186
2016 Spinal Fbxo3-Dependent Fbxl2 Ubiquitination of Active Zone Protein RIM1α Mediates Neuropathic Allodynia through CaV2.2 Activation. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 27629721
2013 Challenging the catechism of therapeutics for chronic neuropathic pain: Targeting CaV2.2 interactions with CRMP2 peptides. Neuroscience letters 30 23831344
2003 Custom distinctions in the interaction of G-protein beta subunits with N-type (CaV2.2) versus P/Q-type (CaV2.1) calcium channels. The Journal of general physiology 30 12771191
2023 A peptidomimetic modulator of the CaV2.2 N-type calcium channel for chronic pain. Proceedings of the National Academy of Sciences of the United States of America 29 37972067
2022 Voltage-dependent CaV3.2 and CaV2.2 channels in nociceptive pathways. Pflugers Archiv : European journal of physiology 28 35043234
2014 Ankyrin-B regulates Cav2.1 and Cav2.2 channel expression and targeting. The Journal of biological chemistry 27 24394417
2012 Ca2+-independent activation of Ca2+/calmodulin-dependent protein kinase II bound to the C-terminal domain of CaV2.1 calcium channels. The Journal of biological chemistry 27 23255606
2004 Presynaptic Cav2.1 and Cav2.2 differentially influence release dynamics at hippocampal excitatory synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 15548655
2003 Competitive and synergistic interactions of G protein beta(2) and Ca(2+) channel beta(1b) subunits with Ca(v)2.1 channels, revealed by mammalian two-hybrid and fluorescence resonance energy transfer measurements. The Journal of biological chemistry 27 14507926
2023 CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles. eLife 26 36820519
2014 Voltage-dependent regulation of CaV2.2 channels by Gq-coupled receptor is facilitated by membrane-localized β subunit. The Journal of general physiology 26 25225550
2004 Differential modulation of CaV2.3 Ca2+ channels by Galphaq/11-coupled muscarinic receptors. Molecular pharmacology 26 14742680
2007 Novel CaV2.1 clone replicates many properties of Purkinje cell CaV2.1 current. The European journal of neuroscience 25 18001290
2004 A Purkinje cell specific GoLoco domain protein, L7/Pcp-2, modulates receptor-mediated inhibition of Cav2.1 Ca2+ channels in a dose-dependent manner. Brain research. Molecular brain research 25 15548431
2022 Cav2.2-NFAT2-USP43 axis promotes invadopodia formation and breast cancer metastasis through cortactin stabilization. Cell death & disease 24 36137995
2015 Expression-associated polymorphisms of CAV1-CAV2 affect intraocular pressure and high-tension glaucoma risk. Molecular vision 24 26015768
2011 Splice isoform-specific suppression of the Cav2.1 variant underlying spinocerebellar ataxia type 6. Neurobiology of disease 24 21550405
2008 Functional properties and modulation of extracellular epitope-tagged Ca(V)2.1 voltage-gated calcium channels. Channels (Austin, Tex.) 24 18797193
2021 Neuronal junctophilins recruit specific CaV and RyR isoforms to ER-PM junctions and functionally alter CaV2.1 and CaV2.2. eLife 23 33769283
2014 CaV2.2 channel cell surface expression is regulated by the light chain 1 (LC1) of the microtubule-associated protein B (MAP1B) via UBE2L3-mediated ubiquitination and degradation. Pflugers Archiv : European journal of physiology 23 24566975
2014 Synaptic vesicle tethering and the CaV2.2 distal C-terminal. Frontiers in cellular neuroscience 23 24639630
2014 The CaV2.3 R-type voltage-gated Ca2+ channel in mouse sleep architecture. Sleep 23 24790266
2023 Epilepsy-linked kinase CDKL5 phosphorylates voltage-gated calcium channel Cav2.3, altering inactivation kinetics and neuronal excitability. Nature communications 22 38081835
2021 GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife 21 33913808
2014 N-type calcium current, Cav2.2, is enhanced in small-diameter sensory neurons isolated from Nf1+/- mice. Neuroscience 21 24755485
2021 A CACNA1A variant associated with trigeminal neuralgia alters the gating of Cav2.1 channels. Molecular brain 20 33413531
2007 Munc18: a presynaptic transmitter release site N type (CaV2.2) calcium channel interacting protein. Channels (Austin, Tex.) 20 19170253
2022 Complex effects on CaV2.1 channel gating caused by a CACNA1A variant associated with a severe neurodevelopmental disorder. Scientific reports 19 35655070
2019 Dopamine Receptor Type 2 and Ghrelin Receptor Coexpression Alters CaV2.2 Modulation by G Protein Signaling Cascades. ACS chemical neuroscience 18 31808667
2014 Distinct roles for Cav2.1-2.3 in activity-dependent synaptic dynamics. Journal of neurophysiology 18 24523520
2011 Inhibition of synaptic transmission and G protein modulation by synthetic CaV2.2 Ca²+ channel peptides. The Journal of physiology 18 21521766
2021 Conotoxin contulakin-G engages a neurotensin receptor 2/R-type calcium channel (Cav2.3) pathway to mediate spinal antinociception. Pain 17 35050960
2013 Tetraspanin-13 modulates voltage-gated CaV2.2 Ca2+ channels. Scientific reports 17 23648579
2010 G-proteins modulate invertebrate synaptic calcium channel (LCav2) differently from the classical voltage-dependent regulation of mammalian Cav2.1 and Cav2.2 channels. The Journal of experimental biology 17 20511524
2009 Nuclear localization of Ca(v)2.2 and its distribution in the mouse central nervous system, and changes in the hippocampus during and after pilocarpine-induced status epilepticus. Neuropathology and applied neurobiology 17 19811616
2024 C2230, a preferential use- and state-dependent CaV2.2 channel blocker, mitigates pain behaviors across multiple pain models. The Journal of clinical investigation 16 39656529
2023 Rhodojaponin VI indirectly targets Cav2.2 channels via N-ethylmaleimide-sensitive fusion protein to alleviate neuropathic pain. Acta pharmaceutica Sinica. B 16 36970201
2020 Zebrafish as a Model System for the Study of Severe CaV2.1 (α1A) Channelopathies. Frontiers in molecular neuroscience 16 32116539
2020 Cav2.3 R-type calcium channels: from its discovery to pathogenic de novo CACNA1E variants: a historical perspective. Pflugers Archiv : European journal of physiology 16 32529299
2019 Disruption of GpI mGluR-Dependent Cav2.3 Translation in a Mouse Model of Fragile X Syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience 16 31350260
2022 β2-subunit alternative splicing stabilizes Cav2.3 Ca2+ channel activity during continuous midbrain dopamine neuron-like activity. eLife 15 35792082
2017 Investigation of CAV1/CAV2 rs4236601 and CDKN2B-AS1 rs2157719 in primary open-angle glaucoma patients from Brazil. Ophthalmic genetics 15 29111846
2002 Kinetics and Gbetagamma modulation of Ca(v)2.2 channels with different auxiliary beta subunits. Pflugers Archiv : European journal of physiology 15 11976940
2022 CAV2 Regulates Mir-4723/Wnt7A Signalling Axis through Endocytosis and Epithelial-Mesenchymal Transition to Promote Proliferation, Invasion, and Metastasis of Pancreatic Cancer Cells. Journal of Cancer 14 35517414
2019 Ankyrin B and Ankyrin B variants differentially modulate intracellular and surface Cav2.1 levels. Molecular brain 14 31477143
2017 Cell-Specific RNA Binding Protein Rbfox2 Regulates CaV2.2 mRNA Exon Composition and CaV2.2 Current Size. eNeuro 14 29067356
2011 CaV2.1 voltage activated calcium channels and synaptic transmission in familial hemiplegic migraine pathogenesis. Journal of physiology, Paris 14 22074995

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