Affinage

CADPS

Calcium-dependent secretion activator 1 · UniProt Q9ULU8

Round 2 corrected
Length
1353 aa
Mass
152.8 kDa
Annotated
2026-04-28
130 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CADPS (CAPS1) is a calcium-dependent activator of dense-core vesicle (DCV) exocytosis that functions as a vesicle-resident priming factor in neural and endocrine cells (PMID:1516133, PMID:9697858, PMID:12438120). It drives trans-SNARE complex assembly by directly binding syntaxin-1, SNAP-25, and VAMP-2 through its Munc13-homology domain 1 (MHD1) in a PI(4,5)P2-dependent manner, thereby promoting vesicle docking and fusion competence (PMID:19805029, PMID:20826818, PMID:21803295, PMID:26700319). CADPS also facilitates DCV biogenesis and trafficking from the trans-Golgi network through PH domain–mediated interaction with ARF4/ARF5 GTPases, and its activity is modulated by PKC phosphorylation, A-to-I RNA editing that alters syntaxin-1A binding preference, and interaction with D2 dopamine receptors (PMID:20921225, PMID:1429734, PMID:27851964, PMID:15857609). Loss of CAPS proteins in pancreatic β-cells impairs insulin granule priming and glucose-stimulated insulin secretion, and CAPS orthologs are essential for neurosecretion-dependent behaviors in C. elegans and Drosophila (PMID:18177725, PMID:8325482, PMID:11516399).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1992 High

    The identity of the cytosolic factor required for Ca²⁺-activated DCV exocytosis was unknown; purification of a 145-kDa brain protein (p145/CAPS) that reconstitutes secretion in permeable PC12 cells and whose antibody blocks release established CAPS as an essential exocytosis factor.

    Evidence Biochemical reconstitution and antibody inhibition in permeabilized PC12 cells

    PMID:1516133

    Open questions at the time
    • Molecular identity (cDNA) not yet known
    • Mechanism of action on fusion machinery undefined
    • In vivo relevance undemonstrated
  2. 1993 Medium

    Whether CAPS function was conserved in vivo was untested; identification of C. elegans unc-31 as a CAPS ortholog whose loss causes pleiotropic neurosecretory defects established a conserved genetic requirement for CAPS in regulated secretion.

    Evidence Forward genetic screen and behavioral phenotyping in C. elegans unc-31 loss-of-function mutants

    PMID:8325482

    Open questions at the time
    • Molecular mechanism linking UNC-31 to exocytosis unknown
    • Vertebrate in vivo function not yet tested
  3. 1997 High

    Cloning of rat CAPS cDNA and demonstration that recombinant protein reconstitutes Ca²⁺-triggered (but not ATP-dependent priming) exocytosis placed CAPS at the Ca²⁺-dependent triggering step and revealed moderate-affinity Ca²⁺ binding.

    Evidence cDNA cloning; recombinant protein reconstitution in permeable PC12 cells; Ca²⁺-binding assay

    PMID:9289490

    Open questions at the time
    • Subcellular localization unresolved
    • Lipid-binding specificity untested
    • SNARE interaction not yet demonstrated
  4. 1998 High

    Two key questions—where CAPS acts and what lipid signals govern it—were resolved: CAPS localizes to DCVs and plasma membrane (not synaptic vesicles) and specifically binds PI(4,5)P2, which induces a conformational change, establishing CAPS as a PI(4,5)P2-effector on DCVs.

    Evidence Subcellular fractionation; liposome binding with phosphoinositide specificity controls; limited proteolysis and photoaffinity labeling

    PMID:9525942 PMID:9697858

    Open questions at the time
    • Direct SNARE interaction not demonstrated
    • Role in vesicle docking vs. fusion not distinguished
  5. 2000 High

    Whether CAPS participates in all or a subset of DCV fusion events was unclear; electrophysiological dissection in melanotrophs showed CAPS is required specifically for the rapid, high-Ca²⁺-sensitivity component of DCV exocytosis, defining a CAPS-dependent and a CAPS-independent DCV release pathway.

    Evidence Patch-clamp capacitance with flash photolysis of caged Ca²⁺; antibody injection; botulinum neurotoxin controls in rat melanotrophs

    PMID:10792045

    Open questions at the time
    • Identity of CAPS-independent pathway unknown
    • Mechanism by which CAPS confers rapid kinetics unresolved
  6. 2001 High

    Drosophila null mutants established that CAPS is essential for DCV release and contributes to synaptic vesicle fusion, with DCV accumulation in terminals confirming a role upstream of fusion.

    Evidence Genetic nulls with electrophysiology, electron microscopy, and transgenic rescue at Drosophila NMJ

    PMID:11516399

    Open questions at the time
    • Mechanism of effect on synaptic vesicle fusion unclear (cell-nonautonomous)
    • Vertebrate knockout not yet available
  7. 2007 High

    Single-vesicle imaging in C. elegans neurons revealed UNC-31/CAPS is required for DCV docking at the plasma membrane—a step upstream of fusion—and that this docking defect is bypassed by PKA activation, linking CAPS to PKA-dependent priming.

    Evidence TIRF microscopy of single DCV events; amperometry and capacitance in cultured C. elegans neurons; epistasis with unc-13

    PMID:18031683

    Open questions at the time
    • Direct biochemical mechanism of docking promotion unknown
    • PKA phosphorylation site on CAPS not mapped
  8. 2008 High

    Vertebrate in vivo relevance was confirmed: CAPS2 knockout and CAPS1/2 compound mutant mice show glucose intolerance due to impaired insulin granule priming and exocytosis, establishing CAPS as essential for pancreatic β-cell function.

    Evidence Knockout mice; glucose tolerance tests; patch-clamp capacitance; electron microscopy; lysosomal enzyme assay in β-cells

    PMID:18177725

    Open questions at the time
    • Relative contributions of CAPS1 vs. CAPS2 in β-cells not fully resolved
    • CAPS1 single-KO β-cell phenotype not reported
  9. 2009 High

    The central mechanistic question—how CAPS promotes fusion—was answered by reconstituted liposome assays showing CAPS drives trans-SNARE complex assembly in a PI(4,5)P2-dependent, syntaxin-1-binding-dependent manner, establishing it as a bona fide priming factor.

    Evidence Reconstituted SNARE-dependent liposome fusion assay with truncation analysis and PI(4,5)P2 requirement

    PMID:19805029

    Open questions at the time
    • Structural basis of CAPS–syntaxin interaction unresolved
    • Relationship to Munc13-mediated priming not fully delineated
  10. 2010 High

    CAPS was shown to bind all three neuronal SNAREs (syntaxin-1, SNAP-25, VAMP-2) with isoform specificity and at a syntaxin-1 site distinct from Munc18-1, and separately to interact with ARF4/ARF5 via its PH domain to mediate TGN-to-DCV trafficking, revealing a dual function in vesicle biogenesis and priming.

    Evidence Liposome co-sedimentation for SNARE binding; Co-IP and pulldown for ARF4/ARF5; siRNA knockdown with chromogranin secretion assay

    PMID:20826818 PMID:20921225

    Open questions at the time
    • Structural model of CAPS–SNARE complex lacking
    • How ARF-binding and SNARE-binding functions are coordinated in vivo is unclear
  11. 2011 High

    The MHD1 domain was identified as the core SNARE-binding unit; a single-helix deletion abolishes both SNARE binding and exocytosis, pinpointing the minimal functional domain.

    Evidence Domain deletion/mutation analysis with SNARE binding and Ca²⁺-triggered exocytosis assays in PC12 cells

    PMID:21803295

    Open questions at the time
    • Atomic-resolution structure of MHD1–SNARE interface not determined
    • Whether MHD1 opens closed syntaxin directly is unresolved
  12. 2015 High

    Live single-vesicle imaging established that CAPS is a resident DCV protein present at all exocytic events, and that vesicle-localized CAPS (~9-molecule clusters) is essential for VAMP-2-dependent docking and fusion, resolving the question of whether CAPS acts from the vesicle or plasma membrane.

    Evidence TIRF microscopy of single DCV events in PC12 cells; shRNA knockdown; CAPS ΔC135 vesicle-targeting mutant rescue

    PMID:26700319

    Open questions at the time
    • Mechanism of CAPS recruitment to DCV membrane not defined
    • Whether stoichiometry of ~9 molecules is functionally required is untested
  13. 2016 High

    A-to-I RNA editing of CAPS1 was shown to enhance DCV exocytosis by shifting CAPS1 binding preference toward open syntaxin-1A, revealing a post-transcriptional regulatory mechanism that tunes secretory output.

    Evidence RNA editing knock-in mice; chromaffin cell electrophysiology; Co-IP with syntaxin-1A conformational mutants

    PMID:27851964

    Open questions at the time
    • Physiological contexts controlling editing levels are unknown
    • Whether editing affects CAPS2 is untested
  14. 2017 High

    Systematic domain mutagenesis in CAPS-null hippocampal neurons confirmed that C2, PH, MHD1, and DCV-binding domains are each required for DCV exocytosis, and quantified a 96% inhibition of DCV exocytosis vs. 39% for SV exocytosis in the absence of CAPS.

    Evidence CAPS1/2 double-KO hippocampal neurons; domain mutation rescue; DCV exocytosis imaging and SV electrophysiology

    PMID:28883501

    Open questions at the time
    • Mechanism of partial SV exocytosis impairment not characterized
    • Interdomain cooperativity not structurally resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of CAPS (full-length or MHD1–SNARE complex) is lacking, the mechanism by which CAPS cooperates with or is distinguished from Munc13 in priming remains incompletely defined, and how somatic TGN-trafficking and synaptic priming functions are spatiotemporally coordinated is unresolved.
  • No crystal or cryo-EM structure available
  • Functional overlap with Munc13 not delineated at molecular level
  • In vivo regulation of CAPS by PKA phosphorylation site not mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0008289 lipid binding 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005886 plasma membrane 3 GO:0005794 Golgi apparatus 2 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 6 R-HSA-112316 Neuronal System 5 R-HSA-162582 Signal Transduction 3
Partners
ARF4ARF5DRD2SNAP25STX1ASTXBP5VAMP2

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1992 A novel 145 kDa brain cytosolic protein (p145, later named CAPS) was identified as the cytosolic factor that reconstitutes Ca2+-activated dense-core vesicle (DCV) exocytosis in permeable neuroendocrine (PC12) cells. The protein forms dimers, exhibits Ca2+-dependent interaction with hydrophobic matrices, and binds phospholipid vesicles, indicating a membrane-associated function. A p145-specific antibody inhibits Ca2+-activated secretion, demonstrating an essential role. Biochemical reconstitution of Ca2+-dependent secretion in permeabilized PC12 cells; antibody inhibition; phospholipid binding assay Cell High 1516133
1992 PKC stimulation of Ca2+-dependent norepinephrine secretion from semi-intact PC12 cells requires the presence of p145 (CAPS). PKC phosphorylates p145 under conditions of fully reconstituted Ca2+-activated secretion, suggesting that PKC's stimulatory effect on exocytosis is mediated largely through p145/CAPS phosphorylation. PKC-deficient semi-intact PC12 cell reconstitution assay; phosphorylation analysis of p145 with purified PKC The Journal of biological chemistry Medium 1429734
1993 The C. elegans gene unc-31 (ortholog of CADPS/CAPS) affects multiple nervous system-controlled functions including locomotion, feeding, egg-laying, and dauer larvae recovery, establishing an early genetic requirement for UNC-31 in neurosecretion in vivo. Forward genetic screen; behavioral phenotyping of loss-of-function mutants in C. elegans Genetics Medium 8325482
1997 Rat CAPS cDNA was cloned and the protein was identified as the vertebrate homologue of C. elegans UNC-31. Recombinant CAPS reconstitutes the Ca2+-dependent triggering step (but not the ATP-dependent priming step) in permeable PC12 cells. CAPS binds Ca2+ with moderate affinity (Kd ~270 µM, 2 mol Ca2+/mol dimer), consistent with a role at a Ca2+-regulated step in exocytosis. cDNA cloning; recombinant protein reconstitution of Ca2+-triggered exocytosis in permeable PC12 cells; Ca2+-binding assay The Journal of biological chemistry High 9289490
1998 CAPS localizes as a peripherally membrane-associated protein to the plasma membrane and to dense-core vesicles (DCVs) but not to small clear synaptic vesicles (SVs) in brain homogenates. CAPS exhibits high-affinity, saturable binding to DCVs via bilayer phospholipids. CAPS antibodies inhibit Ca2+-activated norepinephrine release from lysed synaptosomes, indicating membrane-bound CAPS is essential for neural DCV exocytosis. Subcellular fractionation; DCV binding assay; antibody inhibition of norepinephrine release from synaptosomes Neuron High 9697858
1998 CAPS specifically binds phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] but not other phosphoinositides (including PI(3,4)P2 and PI(3,4,5)P3). PI(4,5)P2 binding promotes a conformational change in CAPS (altered protease susceptibility) and involves a hydrophobic interaction demonstrated by photoaffinity labeling. CAPS is proposed to function as a PI(4,5)P2 effector in regulated exocytosis. Liposome binding assay; limited proteolysis; photoaffinity labeling with PI(4,5)P2 analog The Journal of biological chemistry High 9525942
2000 CAPS is required specifically for the rapid, high-Ca2+-sensitivity component of dense-core vesicle exocytosis in rat melanotrophs. Anti-CAPS antibody abolishes the rapid (but not the slow) capacitance component evoked by flash photolysis of caged Ca2+. Both components require SNARE-dependent fusion (blocked by BoNT/B and BoNT/E). Immunocytochemistry shows CAPS is present on only a subset of DCVs, defining two parallel DCV exocytosis pathways. Patch-clamp membrane capacitance measurement; flash photolysis of caged Ca2+; CAPS antibody injection; botulinum neurotoxin treatment; immunocytochemistry in rat melanotrophs Proceedings of the National Academy of Sciences of the United States of America High 10792045
2001 Drosophila CAPS (dCAPS) is essential for dense-core vesicle (DCV) release and modulates synaptic vesicle fusion. Null dCAPS mutants show embryonic lethality, 50% reduction in evoked glutamatergic transmission, accumulation of synaptic vesicles at active zones, and a 3-fold accumulation of DCVs in synaptic terminals. Cell-autonomous transgenic rescue in motoneurons fails to restore neurotransmission, revealing a cell-nonautonomous role in synaptic vesicle fusion. Genetic null mutants; electrophysiology at NMJ; electron microscopy of synaptic terminals; targeted transgenic rescue Neuron High 11516399
2002 CAPS1 protein localizes exclusively to neural and endocrine tissues including adrenal medulla, pancreatic islets, anterior pituitary, thyroid parafollicular C cells, GI G cells, renal juxtaglomerular cells, and CNS gray matter, consistent with a widespread role in regulated DCV exocytosis in the nervous and endocrine systems. Immunohistochemistry of multiple tissue types Annals of the New York Academy of Sciences Medium 12438120
2003 Human CADPS and CADPS2 were cloned and characterized as homologs of mouse Cadps. Both proteins contain a C2 domain implicated in calcium and phospholipid interactions. CADPS expression is restricted to neural and endocrine tissues, while CADPS2 is expressed ubiquitously, suggesting CADPS functions as a calcium sensor in regulated exocytosis and CADPS2 in constitutive vesicle trafficking. Full-length cDNA cloning; domain analysis (C2 domain identification); Northern/RT-PCR expression profiling; mutation screening Genomics Medium 12659812
2003 CAPS2 (the second mammalian CAPS isoform) was cloned and found to functionally rescue LDCV exocytosis from PC12 cells similarly to CAPS1. Both isoforms localize to synaptic cytosol fractions and vesicular fractions in brain. CAPS1 is enriched specifically in glutamatergic nerve terminals by ultrastructural analysis. CAPS2 is expressed in lung, liver, and testis in addition to brain, unlike the brain/neuroendocrine-restricted CAPS1. cDNA cloning; PC12 cell exocytosis reconstitution; subcellular fractionation of brain; immunoelectron microscopy The Journal of biological chemistry High 14530279
2005 CAPS1 was identified as a D2 dopamine receptor interacting protein (DRIP) in a yeast two-hybrid screen. The interaction was confirmed by pulldown and co-immunoprecipitation. The D2 receptor binding site was mapped to the C-terminal region of CAPS1. In PC12 cells, CAPS1 and D2 receptors colocalize in cytosolic and plasma membrane compartments. Overexpression of a truncated D2 receptor fragment specifically reduces K+-evoked dopamine (but not norepinephrine or BDNF) release, suggesting D2 receptors modulate dopamine vesicle release via direct interaction with CAPS. Yeast two-hybrid screen; pulldown; co-immunoprecipitation; deletion mapping; immunofluorescence colocalization; dopamine release assay in PC12 cells Biochemical pharmacology Medium 15857609
2006 CAPS1 and CAPS2 show complementary expression in the embryonic nervous system and distinct distributions in the postnatal brain. CAPS2 distribution patterns coincide with BDNF in multiple brain regions, and CAPS2 immunolabels colocalize with exocytosis-related proteins (VAMP, SNAP-25) and endocytosis-related dynamin I in cell soma and processes, suggesting CAPS2 is involved in BDNF secretion in many brain areas. Immunohistochemistry; double-label immunofluorescence colocalization in mouse brain sections The Journal of comparative neurology Medium 16506193
2007 UNC-31 (C. elegans CAPS ortholog) is required for docking of dense-core vesicles (DCVs) at the plasma membrane, as demonstrated by TIRF microscopy of single DCV fusion events. The DCV docking defect in unc-31 mutants is fully rescued by PKA activation. UNC-31 is also required for UNC-13-mediated augmentation of DCV exocytosis. Membrane capacitance measurement; amperometry; TIRF microscopy of single DCV docking/fusion in cultured C. elegans neurons; mutant epistasis analysis Neuron High 18031683
2007 Tomosyn (TOM-1) negatively regulates UNC-31 (CAPS)-dependent dense-core vesicle exocytosis in C. elegans. Loss of TOM-1 suppresses the DCV accumulation, electrophysiological defects, and behavioral phenotypes of unc-31 mutants. Double mutant analysis distinguishes direct effects on DCV release from secondary effects via altered synaptic vesicle release. Genetic epistasis (tom-1;unc-31 double mutants); electron microscopy; electrophysiology; behavioral assays in C. elegans The Journal of neuroscience High 17881523
2008 CAPS2-/- and CAPS1+/-;CAPS2-/- mice are glucose intolerant due to reduced glucose-induced insulin secretion, correlating with diminished Ca2+-dependent exocytosis, reduced morphologically docked vesicle pool, decreased readily releasable pool, slowed granule priming, and suppressed second-phase insulin secretion. CAPS1+/-;CAPS2-/- beta cells show reduced insulin content and granule numbers with increased lysosome activity, indicating CAPS proteins regulate insulin granule priming, exocytosis, and stability. Knockout mouse phenotyping; glucose tolerance test; patch-clamp capacitance measurement; electron microscopy; lysosomal enzyme activity assay Cell metabolism High 18177725
2009 CAPS drives trans-SNARE complex formation and membrane fusion in a reconstituted SNARE-dependent liposome fusion assay. CAPS stimulation requires PI(4,5)P2 in acceptor liposomes and is independent of Ca2+ alone, but Ca2+ dependence is restored by synaptotagmin. CAPS binds syntaxin-1, and truncations that competitively inhibit syntaxin-1 binding also inhibit CAPS-dependent fusion, establishing CAPS as a priming protein that accelerates fusion by promoting trans-SNARE complex assembly. Reconstituted SNARE-dependent liposome fusion assay; CAPS truncation analysis; syntaxin-1 binding assay; PI(4,5)P2 requirement assay Proceedings of the National Academy of Sciences of the United States of America High 19805029
2010 CAPS exhibits high-affinity binding to syntaxin-1 and SNAP-25 and moderate affinity binding to VAMP-2. CAPS binding is specific for exocytic SNARE isoforms and requires membrane integration of SNARE proteins. CAPS binding to syntaxin-1 is mediated by SNARE motifs and occurs at a C-terminal site that does not overlap the Munc18-1 binding site, allowing CAPS and Munc18-1 to co-reside on membrane-integrated syntaxin-1. Liposome co-sedimentation; binding affinity measurements; SNARE isoform specificity assays; CAPS-stimulated liposome fusion with syntaxin-1 truncation mutants The Journal of biological chemistry High 20826818
2010 CAPS1 interacts specifically with class II ARF GTPases (ARF4 and ARF5) but not other ARF classes, via its pleckstrin homology (PH) domain in a GDP-bound form-specific manner. The PH domain recruits ARF4/ARF5 to the Golgi complex. Knockdown of CAPS1 or ARF4/ARF5 causes accumulation of chromogranin (DCV marker) in the Golgi and reduces DCV secretion. CAPS1-binding-deficient ARF5 mutants phenocopy this DCV trafficking defect, establishing a role for somal CAPS1 in TGN-to-DCV trafficking. Co-immunoprecipitation; GST pulldown; yeast two-hybrid; siRNA knockdown; Golgi localization by immunofluorescence; chromogranin secretion assay The Journal of biological chemistry High 20921225
2011 The Munc13 homology domain-1 (MHD1) of CAPS was identified as the core SNARE-binding domain. CAPS lacking a single helix in MHD1 fails to bind SNARE proteins and cannot support Ca2+-triggered exocytosis of either docked or newly arrived dense-core vesicles in PC12 cells, demonstrating that SNARE protein binding via MHD1 is essential for CAPS function in DCV exocytosis. Domain deletion/mutation analysis; SNARE binding assay; Ca2+-triggered DCV exocytosis assay in PC12 cells Cell metabolism High 21803295
2013 Conditional knockout of CAPS1 in forebrain causes reduced DCV marker (secretogranin II) immunoreactivity, reduced presynaptic DCV numbers, dilated trans-Golgi cisternae, and reduced TGN marker syntaxin-6, establishing CAPS1's role in TGN-to-DCV trafficking. Cerebellar-specific CAPS1 cKO reduces BDNF along climbing fibers and decreases DCV numbers at climbing fiber synapses, impairing synaptic transmission by reducing presynaptic release probability. Conditional knockout mice; immunohistochemistry; electron microscopy; electrophysiology (EPSC amplitude and paired-pulse depression) at climbing fiber–Purkinje cell synapses The Journal of neuroscience High 24174665
2015 CAPS resides on dense-core vesicles (DCVs) as a resident protein and is present in clusters (~9 molecules) near the plasma membrane at sites of vesicle docking. CAPS accompanies vesicles to the plasma membrane and is present at all exocytic events imaged by TIRF microscopy. shRNA knockdown of CAPS eliminates VAMP-2-dependent vesicle docking and evoked exocytosis. A CAPS mutant that does not localize to vesicles (CAPS ΔC135) fails to rescue docking or exocytosis, establishing that CAPS residence on vesicles is essential for docking and fusion competence. TIRF microscopy of single-vesicle fusion events in live PC12 cells; shRNA knockdown; CAPS truncation mutant rescue experiments Molecular biology of the cell High 26700319
2016 CAPS1 pre-mRNA undergoes adenosine-to-inosine RNA editing resulting in a glutamate-to-glycine conversion in its C-terminal region. Mice expressing only edited CAPS1 show increased DCV exocytosis in chromaffin cells and neurons, and edited CAPS1 preferentially binds the activated (open) conformation of syntaxin-1A. This demonstrates that A-to-I RNA editing of CAPS1 modulates DCV exocytosis by altering its interaction with the exocytotic SNARE machinery. RNA editing knock-in mice; electrophysiological DCV exocytosis assay in chromaffin cells; co-immunoprecipitation of CAPS1 with syntaxin-1A conformational mutants Cell reports High 27851964
2017 CAPS-1 requires its C2, pleckstrin homology (PH), MHD1, and DCV-binding domains for DCV exocytosis in mammalian hippocampal neurons. Mutations in C2 (K428E or G476E) or PH (R558D/K560E/K561E) domains do not affect synaptic enrichment of CAPS-1, but all mutants rescue DCV exocytosis to only ~20% of wild-type capacity. Truncation of the C-terminus impairs synaptic enrichment. CAPS deficiency impairs DCV exocytosis more severely (96% inhibition) than SV exocytosis (39% inhibition). CAPS-1/-2 double knockout mouse hippocampal neurons; domain mutation rescue assay; DCV exocytosis imaging; SV exocytosis electrophysiology Scientific reports High 28883501
2019 CAPS1 is upregulated in colorectal cancer and promotes cancer cell migration, invasion, and liver metastasis in vivo without affecting proliferation. CAPS1 induces epithelial-mesenchymal transition (EMT) by decreasing E-cadherin/ZO-1 and increasing N-cadherin/Snail. Snail knockdown reverses CAPS1-induced EMT. CAPS1 binds Septin2 and p85 (PI3K subunit), and PI3K/Akt inhibitors abolish CAPS1-induced Akt/GSK3β activity and Snail upregulation, placing CAPS1 in a PI3K/Akt/GSK3β/Snail signaling axis for metastasis. Overexpression and knockdown in CRC cell lines; in vivo liver metastasis model; co-immunoprecipitation of CAPS1 with Septin2 and p85; PI3K inhibitor treatment; EMT marker immunoblotting Oncogene Medium 30742066

Source papers

Stage 0 corpus · 130 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
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
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
2019 Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium. Gut 469 31672839
1991 Microtubule dynamics and microtubule caps: a time-resolved cryo-electron microscopy study. The Journal of cell biology 439 1874792
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
2005 Dynamic sorting of nuclear components into distinct nucleolar caps during transcriptional inhibition. Molecular biology of the cell 318 15758027
2013 Loci associated with N-glycosylation of human immunoglobulin G show pleiotropy with autoimmune diseases and haematological cancers. PLoS genetics 292 23382691
2006 Control of mammalian translation by mRNA structure near caps. RNA (New York, N.Y.) 265 16540693
2022 Tau interactome maps synaptic and mitochondrial processes associated with neurodegeneration. Cell 256 35063084
1992 A novel 145 kd brain cytosolic protein reconstitutes Ca(2+)-regulated secretion in permeable neuroendocrine cells. Cell 249 1516133
2016 NLRP3 inflammasome inhibition is disrupted in a group of auto-inflammatory disease CAPS mutations. Nature immunology 222 27548431
2002 The cell surface receptor DC-SIGN discriminates between Mycobacterium species through selective recognition of the mannose caps on lipoarabinomannan. The Journal of biological chemistry 197 12496255
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
2016 Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS). Annals of the rheumatic diseases 153 27707729
1986 Purification and initial characterization of a protein from skeletal muscle that caps the barbed ends of actin filaments. The Journal of biological chemistry 152 3733738
2006 Mesoderm induction: from caps to chips. Nature reviews. Genetics 150 16619051
1997 Novel Ca2+-binding protein (CAPS) related to UNC-31 required for Ca2+-activated exocytosis. The Journal of biological chemistry 150 9289490
1979 Isolation of concanavalin A caps during various stages of formation and their association with actin and myosin. The Journal of cell biology 150 457767
1997 Chromosome ends: all the same under their caps. Current opinion in genetics & development 140 9468793
2011 Augmented expression and activity of extracellular matrix-degrading enzymes in regions of low endothelial shear stress colocalize with coronary atheromata with thin fibrous caps in pigs. Circulation 125 21282495
2008 Dynamic movement of the calcium sensor STIM1 and the calcium channel Orai1 in activated T-cells: puncta and distal caps. Molecular biology of the cell 124 18448669
2001 Drosophila CAPS is an essential gene that regulates dense-core vesicle release and synaptic vesicle fusion. Neuron 124 11516399
1998 CAPS (mammalian UNC-31) protein localizes to membranes involved in dense-core vesicle exocytosis. Neuron 123 9697858
2012 The genetic architecture of economic and political preferences. Proceedings of the National Academy of Sciences of the United States of America 121 22566634
2019 Systematic bromodomain protein screens identify homologous recombination and R-loop suppression pathways involved in genome integrity. Genes & development 110 31753913
1993 The Caenorhabditis elegans unc-31 gene affects multiple nervous system-controlled functions. Genetics 110 8325482
2010 Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Molecular medicine (Cambridge, Mass.) 108 20379614
2008 Storage of cellular 5' mRNA caps in P bodies for viral cap-snatching. Proceedings of the National Academy of Sciences of the United States of America 107 19047634
2000 Activated mutants of SHP-2 preferentially induce elongation of Xenopus animal caps. Molecular and cellular biology 104 10594032
1998 Specific binding of phosphatidylinositol 4,5-bisphosphate to calcium-dependent activator protein for secretion (CAPS), a potential phosphoinositide effector protein for regulated exocytosis. The Journal of biological chemistry 102 9525942
2015 CAPS--pathogenesis, presentation and treatment of an autoinflammatory disease. Seminars in immunopathology 100 25963520
2003 A family of Ca2+-dependent activator proteins for secretion: comparative analysis of structure, expression, localization, and function. The Journal of biological chemistry 91 14530279
2000 Op18/stathmin caps a kinked protofilament-like tubulin tetramer. The EMBO journal 89 10675326
2004 SCAR and CAPS mapping of CRb, a gene conferring resistance to Plasmodiophora brassicae in Chinese cabbage ( Brassica rapa ssp. pekinensis). TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik 88 14997298
2002 Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs. Genome research 82 12421765
1990 trans-spliced Caenorhabditis elegans mRNAs retain trimethylguanosine caps. Molecular and cellular biology 76 2157142
2000 Rapid regulated dense-core vesicle exocytosis requires the CAPS protein. Proceedings of the National Academy of Sciences of the United States of America 75 10792045
2004 Guide RNAs with 5' caps and novel box C/D snoRNA-like domains for modification of snRNAs in metazoa. Current biology : CB 74 15556860
1996 The Agaricus bisporus hypA gene encodes a hydrophobin and specifically accumulates in peel tissue of mushroom caps during fruit body development. Journal of molecular biology 73 8632464
2012 Effect of arabinogalactan proteins from the root caps of pea and Brassica napus on Aphanomyces euteiches zoospore chemotaxis and germination. Plant physiology 72 22645070
2018 Local Delivery of miR-21 Stabilizes Fibrous Caps in Vulnerable Atherosclerotic Lesions. Molecular therapy : the journal of the American Society of Gene Therapy 70 29503197
2021 Diagnosis and Management of the Cryopyrin-Associated Periodic Syndromes (CAPS): What Do We Know Today? Journal of clinical medicine 68 33401496
2021 Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy. Acta pharmaceutica Sinica. B 66 35256949
2014 Anakinra use during pregnancy in patients with cryopyrin-associated periodic syndromes (CAPS). Arthritis & rheumatology (Hoboken, N.J.) 66 25223501
2008 Tweaking the hinge and caps: testing a model of the organization of jaws. Journal of experimental zoology. Part B, Molecular and developmental evolution 66 18027841
2003 Cloning and characterization of human CADPS and CADPS2, new members of the Ca2+-dependent activator for secretion protein family. Genomics 66 12659812
2009 CAPS drives trans-SNARE complex formation and membrane fusion through syntaxin interactions. Proceedings of the National Academy of Sciences of the United States of America 65 19805029
2012 Genetic variants associated with breast size also influence breast cancer risk. BMC medical genetics 64 22747683
2007 PKA activation bypasses the requirement for UNC-31 in the docking of dense core vesicles from C. elegans neurons. Neuron 64 18031683
2001 Microtubules don and doff their caps: dynamic attachments at plus and minus ends. Current opinion in cell biology 63 11163139
2015 Microbial diversity on Icelandic glaciers and ice caps. Frontiers in microbiology 62 25941518
2000 Toxofilin, a novel actin-binding protein from Toxoplasma gondii, sequesters actin monomers and caps actin filaments. Molecular biology of the cell 61 10637313
2015 Influenza A virus preferentially snatches noncoding RNA caps. RNA (New York, N.Y.) 59 26428694
2008 CAPS1 and CAPS2 regulate stability and recruitment of insulin granules in mouse pancreatic beta cells. Cell metabolism 57 18177725
2011 Genome-wide molecular characterization of central nervous system primitive neuroectodermal tumor and pineoblastoma. Neuro-oncology 56 21798848
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2020 Mammalian Nudix proteins cleave nucleotide metabolite caps on RNAs. Nucleic acids research 50 32432673
2020 Dinucleoside polyphosphates act as 5'-RNA caps in bacteria. Nature communications 48 32103016
2007 Tomosyn negatively regulates CAPS-dependent peptide release at Caenorhabditis elegans synapses. The Journal of neuroscience : the official journal of the Society for Neuroscience 47 17881523
2010 Novel interactions of CAPS (Ca2+-dependent activator protein for secretion) with the three neuronal SNARE proteins required for vesicle fusion. The Journal of biological chemistry 45 20826818
2002 Nephron induction revisited: from caps to condensates. Current opinion in nephrology and hypertension 45 11753082
1990 The lymphocyte-specific protein LSP1 is associated with the cytoskeleton and co-caps with membrane IgM. Journal of immunology (Baltimore, Md. : 1950) 45 2212669
1963 CHEMICAL AND PHYSICAL CHARACTERIZATION OF "NUCLEAR CAPS" ISOLATED FROM BLASTOCLADIELLA ZOOSPORES. Journal of bacteriology 45 14047213
2013 Genome-wide association study of a heart failure related metabolomic profile among African Americans in the Atherosclerosis Risk in Communities (ARIC) study. Genetic epidemiology 42 23934736
2020 Consensus protocols for the diagnosis and management of the hereditary autoinflammatory syndromes CAPS, TRAPS and MKD/HIDS: a German PRO-KIND initiative. Pediatric rheumatology online journal 41 32066461
2017 Applications of Phosphate Modification and Labeling to Study (m)RNA Caps. Topics in current chemistry (Cham) 41 28116583
2011 Munc13 homology domain-1 in CAPS/UNC31 mediates SNARE binding required for priming vesicle exocytosis. Cell metabolism 41 21803295
2005 Regulation of dense core vesicle release from PC12 cells by interaction between the D2 dopamine receptor and calcium-dependent activator protein for secretion (CAPS). Biochemical pharmacology 38 15857609
1999 Characterization of cDNA clones selected by the GeneMark analysis from size-fractionated cDNA libraries from human brain. DNA research : an international journal for rapid publication of reports on genes and genomes 38 10574461
2018 Mosaicism in autoinflammatory diseases: Cryopyrin-associated periodic syndromes (CAPS) and beyond. A systematic review. Critical reviews in clinical laboratory sciences 37 30035647
2010 Rilonacept in the management of cryopyrin-associated periodic syndromes (CAPS). Journal of inflammation research 37 22096352
2015 Resident CAPS on dense-core vesicles docks and primes vesicles for fusion. Molecular biology of the cell 36 26700319
2020 Np4A alarmones function in bacteria as precursors to RNA caps. Proceedings of the National Academy of Sciences of the United States of America 35 32019889
2020 DXO/Rai1 enzymes remove 5'-end FAD and dephospho-CoA caps on RNAs. Nucleic acids research 35 32374864
2003 Antiatherogenic effect of Caps HT2, a herbal Ayurvedic medicine formulation. Phytomedicine : international journal of phytotherapy and phytopharmacology 34 13678230
2019 CAPS1 promotes colorectal cancer metastasis via Snail mediated epithelial mesenchymal transformation. Oncogene 33 30742066
2010 Interaction of calcium-dependent activator protein for secretion 1 (CAPS1) with the class II ADP-ribosylation factor small GTPases is required for dense-core vesicle trafficking in the trans-Golgi network. The Journal of biological chemistry 33 20921225
2005 The structural basis of recognition and removal of cellular mRNA 7-methyl G 'caps' by a viral capsid protein: a unique viral response to host defense. Journal of molecular recognition : JMR 33 15597333
1997 Cloning of genes whose expression is correlated with mitosis and localized in dividing cells in root caps of Pisum sativum L. Plant molecular biology 33 9426627
2022 Therapeutic effect of NLRP3 inhibition on hearing loss induced by systemic inflammation in a CAPS-associated mouse model. EBioMedicine 32 35870427
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2011 Translation, stability, and resistance to decapping of mRNAs containing caps substituted in the triphosphate chain with BH3, Se, and NH. RNA (New York, N.Y.) 31 21447710
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2012 Structure and dynamics of photogenerated triplet radical ion pairs in DNA hairpin conjugates with anthraquinone end caps. Journal of the American Chemical Society 30 22676136
2011 Composition of yeast snRNPs and snoRNPs in the absence of trimethylguanosine caps reveals nuclear cap binding protein as a gained U1 component implicated in the cold-sensitivity of tgs1Δ cells. Nucleic acids research 30 21558325
2009 Formation of STIM and Orai complexes: puncta and distal caps. Immunological reviews 30 19754895
1998 Structural differences between two types of basidiomycete septal pore caps. Microbiology (Reading, England) 30 9695906
2018 Collision of Expanding Actin Caps with Actomyosin Borders for Cortical Bending and Mitotic Rounding in a Syncytium. Developmental cell 29 29804877
2020 Extensive 5'-surveillance guards against non-canonical NAD-caps of nuclear mRNAs in yeast. Nature communications 28 33139726
2021 Isolation and identification of pigments from oyster mushrooms with black, yellow and pink caps. Food chemistry 26 34601416
2017 Design, synthesis and anti-tumor activity study of novel histone deacetylase inhibitors containing isatin-based caps and o-phenylenediamine-based zinc binding groups. Bioorganic & medicinal chemistry 26 28511906
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1998 Gelsolin, a protein that caps the barbed ends and severs actin filaments, enhances the actin-based motility of Listeria monocytogenes in host cells. Infection and immunity 26 9673261
2016 Replication and hematological characterization of human platelet reactivity genetic associations in men from the Caerphilly Prospective Study (CaPS). Journal of thrombosis and thrombolysis 25 26519038
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2013 CAPS1 deficiency perturbs dense-core vesicle trafficking and Golgi structure and reduces presynaptic release probability in the mouse brain. The Journal of neuroscience : the official journal of the Society for Neuroscience 23 24174665
2020 Slc6a3-dependent expression of a CAPS-associated Nlrp3 allele results in progressive behavioral abnormalities and neuroinflammation in aging mice. Journal of neuroinflammation 22 32680528
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2013 Comparative studies on chemical parameters and antioxidant properties of stipes and caps of shiitake mushroom as affected by different drying methods. Journal of the science of food and agriculture 21 23553427
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2008 Construction of an integrated pepper map using RFLP, SSR, CAPS, AFLP, WRKY, rRAMP, and BAC end sequences. Molecules and cells 20 19214431
2017 Terminating DNA Tile Assembly with Nanostructured Caps. ACS nano 18 28901745
2012 Nucleobindin 1 caps human islet amyloid polypeptide protofibrils to prevent amyloid fibril formation. Journal of molecular biology 18 22542527
1989 A fragmin-like protein from plasmodium of Physarum polycephalum that severs F-actin and caps the barbed end of F-actin in a Ca2+-sensitive way. Journal of biochemistry 18 2553683
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2019 Par-1 controls the composition and growth of cortical actin caps during Drosophila embryo cleavage. The Journal of cell biology 17 31641019
2018 Development and effect of antibodies to anakinra during treatment of severe CAPS: sub-analysis of a long-term safety and efficacy study. Clinical rheumatology 17 29982913
2016 Development of cleaved amplified polymorphic sequence markers and a CAPS-based genetic linkage map in watermelon (Citrullus lanatus [Thunb.] Matsum. and Nakai) constructed using whole-genome re-sequencing data. Breeding science 17 27162496
2022 Predicting Collagen Triple Helix Stability through Additive Effects of Terminal Residues and Caps. Angewandte Chemie (International ed. in English) 16 36409045
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2010 When the caps fall off: responses to telomere uncapping in yeast. FEBS letters 16 20600003
2004 Kinetic role of helix caps in protein folding is context-dependent. Biochemistry 16 15049688
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2015 Direct NMR detection of bifurcated hydrogen bonding in the α-helix N-caps of ankyrin repeat proteins. Journal of the American Chemical Society 15 25578373