Affinage

CAPZA2

F-actin-capping protein subunit alpha-2 · UniProt P47755

Length
286 aa
Mass
32.9 kDa
Annotated
2026-06-09
52 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CAPZA2 encodes the α2 subunit of the heterodimeric actin-capping protein CapZ, which binds the barbed ends of actin filaments with sub-nanomolar affinity to block both polymerization and depolymerization, while also nucleating new filaments (PMID:2557904). The crystal structure resolves CapZ as a pseudo-twofold symmetric α/β heterodimer bearing two mobile C-terminal extensions ("tentacles"); the β-tentacle's C-terminal region mediates actin binding, and the α-subunit tentacle serves as a protein-targeting interface (PMID:1370838, PMID:12660160). Capping activity is regulated by competing inputs at these surfaces: PIP2 binds CapZ and abolishes capping (PMID:1653607), the α-subunit C-terminus (TRTK-12 epitope) engages S100B and S100A1 in a Ca2+-dependent manner that competes with polyphosphoinositides for the same site (PMID:7540176, PMID:8660341), and stress-activated phosphorylation of the partner protein CapZIP by MAPKAP-K2/K3 triggers its dissociation from CapZ (PMID:15850461). In striated muscle, CapZ localizes to nascent Z-discs and is required for ordered sarcomere assembly, where it is positioned and stabilized through interactions with α-actinin, nebulin, and the BAG3–Hsc70 chaperone axis (PMID:8402953, PMID:7822423, PMID:10412090, PMID:18272787, PMID:20884878). At the cardiac Z-disc CapZ further acts as a scaffold anchoring PKC-βII and PP1α to tune myofilament Ca2+ sensitivity, and its actin-binding dynamics are tuned by integrated PIP2/PKC signaling and acetylation in response to mechanical and hypertrophic stimuli (PMID:16870209, PMID:18364747, PMID:27185186, PMID:30808692, PMID:40832763). Beyond the sarcomere, CapZ shapes membranes and traffic: it binds PtdIns(3)P to drive actin polymerization during autophagosomal membrane shaping (PMID:26237647), transiently associates with early endosomes to permit early-to-late endosome maturation and viral genome escape (PMID:38273307), and promotes EPAC1-dependent CFTR plasma-membrane trafficking (PMID:32573649). CapZ also localizes to dendritic spines in an activity-dependent manner (PMID:20545768), and human CAPZA2 loss-of-function variants cause a neurodevelopmental disorder, with mouse models showing altered dendritic spine density, synaptic protein levels, and transcriptional dysregulation (PMID:32338762, PMID:40659881).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1989 High

    Established the core biochemical activity: how CapZ controls actin filament ends, answering whether it caps, severs, or nucleates.

    Evidence In vitro pyrene-actin polymerization, depolymerization, and critical-concentration assays with purified CapZ

    PMID:2557904

    Open questions at the time
    • Did not localize the actin-binding determinants within the heterodimer
    • In vitro reconstitution did not address cellular regulation
  2. 1991 High

    Identified PIP2 as a direct inhibitory regulator, providing the first lipid-based off-switch for capping.

    Evidence In vitro actin polymerization assays with phospholipid vesicles/micelles

    PMID:1653607

    Open questions at the time
    • Did not map the lipid-binding site on the heterodimer
    • In vivo relevance of PIP2 regulation not yet demonstrated
  3. 1992 High

    Localized the actin-binding determinant to the C-terminal region of the β-subunit, defining the structural basis of capping.

    Evidence Deletion mutagenesis, monoclonal antibody inhibition, and peptide-actin binding assays

    PMID:1370838

    Open questions at the time
    • Role of the α-subunit C-terminus left undefined
    • Did not address regulation of this site
  4. 1995 High

    Demonstrated CapZ is required in cells for ordered sarcomere assembly, linking the in vitro capping activity to myofibrillogenesis.

    Evidence Inhibitory antibody microinjection and dominant-negative actin-binding mutant expression in cultured myotubes, plus immunofluorescence of nascent Z-discs

    PMID:7822423 PMID:8402953

    Open questions at the time
    • Did not identify the Z-disc targeting partners that recruit CapZ
    • Mechanism of barbed-end alignment unresolved
  5. 1996 High

    Defined the α-subunit C-terminus as a Ca2+-dependent protein-targeting interface engaged by S100 proteins that competes with phosphoinositides.

    Evidence Phage display, fluorescence spectrophotometry, cross-linking, and TRTK-12 competition with S100B and S100A1

    PMID:7540176 PMID:8660341

    Open questions at the time
    • Functional consequence of S100 binding on capping in cells not established
    • Did not resolve the structural basis of the interaction
  6. 2003 High

    Provided the atomic architecture, revealing the pseudo-symmetric heterodimer and the two mobile tentacles that separate actin-binding from protein-targeting roles.

    Evidence X-ray crystallography of chicken sarcomeric CapZ at 2.1 Å

    PMID:12660160

    Open questions at the time
    • Did not capture CapZ bound to actin
    • Conformational dynamics of the tentacles in regulation not directly visualized
  7. 2005 High

    Identified stress-kinase control of capping via the partner protein CapZIP, establishing a signal-triggered dissociation mechanism.

    Evidence Co-IP, in vitro MAPKAP-K2/K3 kinase assays, MS phosphosite mapping, and stress treatment in Jurkat cells

    PMID:15850461

    Open questions at the time
    • How CapZIP dissociation alters actin dynamics in situ not quantified
    • Tissue-specificity of CapZIP regulation unclear
  8. 2008 High

    Resolved Z-disc targeting partners, showing nebulin recruits CapZ via a non-actin-binding region to align barbed ends.

    Evidence Blot overlay, solid-phase binding, fluorescence, and nebulin siRNA knockdown in chick myotubes

    PMID:10412090 PMID:18272787

    Open questions at the time
    • Relative contributions of nebulin versus α-actinin not dissected
    • Does not address non-muscle targeting
  9. 2009 Medium

    Established that physiological agonists tune CapZ dynamics through PIP2- and PKC-dependent pathways acting on the β-tentacle.

    Evidence Live-cell FRAP of GFP-CapZβ1 in cardiomyocytes with PIP2 and PKC pharmacological dissection

    PMID:19295171

    Open questions at the time
    • Phosphosite not yet mapped at this stage
    • Direct biophysical link between dynamics and contractile output not measured
  10. 2010 High

    Defined the chaperone- and scaffold-dependent stabilization and signaling roles of CapZ at the cardiac myofilament, and its activity-dependent presence in dendritic spines.

    Evidence BAG3/Hsc70 co-IP and rescue in cardiomyocytes; PKC-βII/PP1α anchoring via CapZ extraction; structural NMR/crystallography of S100–TRTK-12; activity-dependent spine imaging

    PMID:16870209 PMID:18364747 PMID:19452629 PMID:20053360 PMID:20545768 PMID:20884878

    Open questions at the time
    • Mechanism linking spine CapZ to synaptic remodeling unresolved
    • Whether scaffolding roles are separable from capping activity unclear
  11. 2016 High

    Showed that mechanical and hypertrophic stimuli converge on post-translational modification of the β-subunit (Ser/Thr phosphorylation, Lys acetylation) to control capping dynamics.

    Evidence MS PTM identification, FRAP, dominant-negative PKCε, and HDAC3-myofibril association assays

    PMID:23493359 PMID:27185186

    Open questions at the time
    • Quantitative impact of each PTM on barbed-end affinity not resolved
    • Crosstalk between acetylation and phosphorylation not dissected
  12. 2019 High

    Integrated PIP2 and PKC inputs into a unified model where β-tentacle phosphorylation at T267 modulates lipid interaction to set capping kinetics.

    Evidence FRAP across substrate stiffness, FRET for PIP2–CapZ, molecular dynamics simulation, and β-tentacle deletion in cardiomyocytes

    PMID:30808692

    Open questions at the time
    • Simulation predictions not validated by direct structural data on the modified state
    • Generality beyond cardiac myocytes untested
  13. 2026 High

    Expanded CapZ function beyond the sarcomere into membrane shaping, endosomal maturation, channel trafficking, and neurodevelopment, defining its disease relevance.

    Evidence PtdIns(3)P-driven autophagosome shaping (siRNA), endosome tethering/KO and viral infection assays, CFTR trafficking assays, Drosophila rescue of patient variants, and CAPZA2 mouse models

    PMID:26237647 PMID:32338762 PMID:32573649 PMID:38273307 PMID:40659881

    Open questions at the time
    • Whether a single capping mechanism underlies all membrane/traffic roles is unresolved
    • Molecular link from CAPZA2 deficiency to specific neurodevelopmental phenotypes incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CapZ's many context-specific partner interactions and lipid/PTM regulatory inputs are coordinated to produce distinct outcomes in muscle, membranes, and neurons remains unresolved.
  • No unified model linking partner selection to functional output
  • Tissue-specific regulation of the α2 (CAPZA2) subunit versus other α isoforms not dissected
  • Structural basis of CapZ engagement with membrane lipids in vivo unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 5 GO:0060090 molecular adaptor activity 4 GO:0008289 lipid binding 2
Localization
GO:0005856 cytoskeleton 3 GO:0005768 endosome 1 GO:0005829 cytosol 1
Pathway
R-HSA-397014 Muscle contraction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-5653656 Vesicle-mediated transport 2 R-HSA-9612973 Autophagy 1
Partners
ACTN2BAG3CAPZBCAPZIP (RCSD1)CFTRNEBS100A1S100B
Complex memberships
CapZ (F-actin capping protein heterodimer)Z-disc/sarcomere

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 CapZ caps barbed ends of actin filaments with Kd ~0.5–1 nM, blocking polymerization and depolymerization at the barbed end with no effect at the pointed end, no severing activity, and nucleates actin polymerization in a concentration-dependent manner. In vitro actin polymerization assays (pyrene-actin elongation, depolymerization, critical concentration), equilibrium ultracentrifugation, fluorescence photobleaching recovery Biochemistry High 2557904
1991 PIP2 micelles bind CapZ and completely inhibit its actin-capping activity; other anionic phospholipids at higher concentrations also inhibit CapZ; neutral phospholipids have no effect. In vitro actin polymerization assays with phospholipid vesicles/micelles Biochemistry High 1653607
1992 The C-terminal region of the CapZ β-subunit is an actin-binding site: deletion of the β C-terminus abolishes barbed-end capping and actin nucleation; a peptide from this region binds actin monomers; a monoclonal antibody (1E5) targeting this region blocks CapZ–actin interaction. Monoclonal antibody inhibition, deletion mutagenesis, fusion protein actin-binding assay, in vitro actin polymerization assay The Journal of cell biology High 1370838
1993 CapZ localizes to nascent Z-discs before actin achieves a striated pattern during myofibrillogenesis in cultured chicken skeletal muscle, consistent with CapZ directing actin filament organization during sarcomere assembly. Double immunofluorescence microscopy of developing myotubes in culture Cell motility and the cytoskeleton Medium 8402953
1995 Inhibiting CapZ–actin interaction by injection of a blocking monoclonal antibody disrupts non-striated actin bundles in early myofibrillogenesis; expression of an actin-binding-deficient CapZ mutant delays appearance of striated actin and alpha-actinin in sarcomeres. Microinjection of inhibitory monoclonal antibody, expression of actin-binding mutant CapZ in cultured myotubes, immunofluorescence The Journal of cell biology High 7822423
1995 S100B binds to the C-terminal region of the CapZ α-subunit (peptide TRTK-12, residues 265–276) in a Ca2+-dependent manner; this interaction is blocked by excess TRTK-12 peptide. Phage peptide display library screening, fluorescence spectrophotometry, gel overlay, chemical cross-linking The Journal of biological chemistry High 7540176
1996 S100A0 (S100A1) interacts with CapZ in a Ca2+-dependent manner via the COOH-terminal region of the CapZ α-subunit (TRTK-12 epitope), which also binds phosphatidylinositol 4-monophosphate, suggesting S100A0 and polyphosphoinositides compete for the same site on CapZα. Chemical cross-linking, fluorescence spectrophotometry, competitive inhibition with TRTK-12 peptide Biochemical and biophysical research communications Medium 8660341
1997 NMR chemical shift mapping identified the binding site for the CapZ α TRTK-12 peptide on S100B as a patch near the C-terminal helix and residues Val-8 to Asp-12 of the N-terminal helix of S100B, involving the dimer interface. 15N-HSQC NMR chemical shift perturbation mapping of 15N-labeled S100B with TRTK-12 peptide Protein science High 9416599
1997 Erythrocyte CapZ (α1β2 isoform) is functional in vitro (caps barbed ends with Kcap ~1–5 nM, nucleates polymerization) but is located exclusively in the cytosol and does not bind to erythrocyte membrane actin filaments; instead, adducin caps the barbed ends of erythrocyte actin filaments. Protein purification, 2D gel electrophoresis, actin elongation/depolymerization assays, cosedimentation with membranes Biochemistry High 9354614
1998 CapZ was identified (cofilin, coronin, Rac, and capZ) as a component of Listeria actin tails and localizes to Listeria actin tail structures in infected cells. Listeria affinity pulldown from bovine brain extracts, peptide sequencing, immunofluorescence in infected cells Journal of cell science Medium 9730980
1999 CapZ interacts directly with alpha-actinin in the Z-line; affinity is in the micromolar range, the interaction is independent of actin, and is weakened by phosphoinositides; binding contacts on alpha-actinin lie in the 55 kDa repetitive domain. Fluorescence binding assay, immunochemical assay, affinity purification with purified proteins Journal of muscle research and cell motility Medium 10412090
1999 CapZ shortens actin filament length at cellular concentrations (1:500 CapZ:actin molar ratio), producing uniformly short filaments; networks of such short actin filaments are more fluid and less elastic than networks of longer filaments. Fluorescence microscopy of rhodamine-phalloidin-labeled actin filaments, viscoelasticity measurements Cell motility and the cytoskeleton Medium 9915586
2003 Crystal structure of chicken sarcomeric CapZ at 2.1 Å resolution revealed a pseudo 2-fold symmetric heterodimer with striking structural similarity between α and β subunits; the molecule has a pair of mobile C-terminal extensions (tentacles) for actin binding, one of which also binds another protein for filament targeting. X-ray crystallography at 2.1 Å resolution The EMBO journal High 12660160
2003 CAPZ (CapZ) is linked to the T cell surface protein CD2 via a molecular chain: CD2 proline-rich tail → CMS (CD2AP) or CIN85 SH3 domains → CapZ bound to the C-terminal half of CMS/CIN85, providing a physical bridge to the actin cytoskeleton. Peptide affinity pulldown from T cell lysates, BIAcore binding analyses, co-immunoprecipitation The Journal of biological chemistry Medium 12690097
2005 CapZIP (CapZ-interacting protein) binds CapZ in splenocytes; MAPKAP-K2/K3 phosphorylate CapZIP at Ser-179 and Ser-244 in vitro; osmotic shock or anisomycin treatment induces phosphorylation of CapZIP and triggers its dissociation from CapZ in Jurkat cells. Co-immunoprecipitation, in vitro kinase assay, mass spectrometry phosphosite identification, stress kinase inhibitors in cells The Biochemical journal High 15850461
2005 V-1 (an ankyrin repeat protein) physically associates with CapZ-β in PC12D cells; this association is reduced by cAMP elevation (forskolin treatment) and recovers after 12 h, indicating cAMP-dependent signaling regulates V-1–CapZ complex assembly. Co-immunoprecipitation, Western blot, immunohistochemistry in rat cerebellum, forskolin treatment Biochemical and biophysical research communications Medium 15845376
2006 CapZ anchors PKC-βII at cardiac myofilaments; CapZ-deficient transgenic myofilaments lack myofilament-associated PKC-βII and show attenuated PKC-βII-dependent reduction of myofilament Ca2+ sensitivity; CapZ extraction from wild-type myofilaments also reduces myofilament-associated PKC-βII. Transgenic mouse model (reduced CapZ), PIP2-mediated CapZ extraction, immunoblotting, actomyosin MgATPase assay, single myocyte mechanics Journal of molecular and cellular cardiology High 16870209
2008 CapZ specifically interacts with the C-terminus of nebulin (modules 160–164) via a region of CapZ distinct from its two C-terminal actin-binding regions; nebulin knockdown reduces assembled CapZ and disrupts uniform barbed-end alignment at the Z-disc. Blot overlay, solid-phase binding assay, tryptophan fluorescence, SPOTs membrane assay, siRNA knockdown in chick skeletal myotubes, immunofluorescence Molecular biology of the cell High 18272787
2008 PP1α binds to cardiac myofilaments and its effects (increased Ca2+ sensitivity, dephosphorylation of myofilament proteins) are attenuated by CapZ extraction, demonstrating that CapZ helps anchor PP1α at the myofilament. Exogenous PP1α treatment of isolated myofilaments, CapZ extraction with PIP2, immunoblotting, actomyosin MgATPase assay Biochemistry and cell biology Medium 18364747
2009 Endothelin-1 and phenylephrine increase CapZ dynamics (faster FRAP exchange) in cardiac myocytes through PIP2- and PKC-dependent pathways; PIP2 sequestration by neomycin or PKC inhibition by chelerythrine blocked the agonist-induced increase in CapZ exchange. FRAP of GFP-CapZβ1 in neonatal rat ventricular myocytes, pharmacological inhibitors American journal of physiology. Cell physiology Medium 19295171
2009 NAP-22, a neuronal presynaptic membrane protein, directly binds CapZ (identified by pulldown and mass spectrometry); the N-terminal myristoyl moiety of NAP-22 is not required for binding; NAP-22 binding does not affect CapZ actin-nucleation activity. NAP-22-Sepharose pulldown from brain extract, mass spectrometry, Western blot, E. coli expression of recombinant CapZ, actin nucleation assay Journal of neuroscience research Medium 19267422
2009 NMR structure of Ca2+-S100A1 bound to TRTK-12 (CapZ α-derived peptide) shows TRTK-12 forms an amphipathic helix interacting with a hydrophobic binding pocket in Ca2+-S100A1 formed by helices 2 and 3 and loop 2; Ca2+-binding affinity of S100A1 is increased >3-fold when TRTK-12 is bound. Solution NMR structure determination, ITC, fluorescence binding assays Journal of molecular biology High 19452629
2010 Crystal structure of Ca2+-S100B–TRTK-12 complex at 2.0 Å shows the interaction is dominated by Trp7 of TRTK-12 and a hydrophobic pocket on Ca2+-S100B (helices 2 and 3, loop 2); TRTK-12 binding eliminates dynamic properties of EF2 in Ca2+-S100B and increases Ca2+-binding affinity without changing Ca2+ coordination geometry. X-ray crystallography (1.5 Å Ca2+-S100B; 2.0 Å complex), NMR 15N relaxation studies Journal of molecular biology High 20053360
2010 BAG3 promotes association of Hsc70 with CapZβ1 and regulates CapZβ1 distribution to correct sarcomeric locations; loss of BAG3 leads to ubiquitin-proteasome-mediated degradation of CapZ and myofibrillar degeneration under mechanical stress. Overexpression of CapZβ1 rescues myofibrillar disruption in bag3 knockdown cardiomyocytes. shRNA knockdown of bag3, in vitro mechanical stretch assay in neonatal cardiomyocytes, co-immunoprecipitation, immunofluorescence, bag3-/- mouse heart function assay Circulation research High 20884878
2010 CapZ localizes in dendritic spines of hippocampal neurons in an activity-dependent manner; neuronal firing suppression by tetrodotoxin decreases CapZ spine content rapidly; high-frequency stimulation increases CapZ immunoreactivity specifically in stimulated synaptic layers. Immunostaining of brain sections and cultured hippocampal neurons, tetrodotoxin treatment, high-frequency electrical stimulation in awake rats Genes to cells Medium 20545768
2013 Mechanical cyclic strain increases CapZ dynamics in cardiac myocytes (increased FRAP Kfrap) that abate 2–3 h after strain ends; expression of CapZβ1 with C-terminal deletion (CapZβ1ΔC, lacking the β-tentacle) mimics strain-induced actin dynamics increase, suggesting mechanical stimulation acts through the CapZβ1 C-terminus to regulate actin capping. Cyclic mechanical strain (10%, 1 Hz) of neonatal rat ventricular myocytes, FRAP of GFP-CapZβ1 and GFP-actin, dominant-negative CapZβ1ΔC expression Journal of applied physiology Medium 23493359
2015 CapZ binds PtdIns(3)P (enriched at omegasomes) and this binding stimulates actin polymerization inside the isolation membrane (IM); CapZβ knockdown collapses IMs and omegasomes into mixed-membrane bundles, blocking autophagosomal membrane shaping. siRNA knockdown of CapZβ, PI(3)K inhibition (3-MA), Beclin-1 knockdown, live imaging, protein-lipid binding assay Nature cell biology High 26237647
2016 During cardiac hypertrophy, CapZβ1 is phosphorylated at Ser-204 by PKCε and acetylated at Lys-199 (near the actin-binding surface); PKCε dominant-negative expression blunts hypertrophy-induced CapZ dynamics and reduces both modifications; HDAC3 dissociates from myofibrils in response to hypertrophic stimulation, increasing Lys-199 acetylation and CapZ/actin dynamics. 2D gel electrophoresis, mass spectrometry, FRAP of GFP-CapZβ1, dominant-negative PKCε expression, HDAC inhibitor treatment, immunoprecipitation for HDAC3-myofibril association Cellular signalling High 27185186
2016 INF2 (inverted formin 2) interacts with CapZ α-1; disease-causing INF2 mutations (E184K, S186P, R218Q) that increase INF2–actin association also increase INF2 interaction with CapZ α-1 and profilin 2. GFP-Trap pulldown of GFP-INF2 from human podocytes coupled with mass spectrometry, confirmed by Western blot Bioscience reports Medium 26764407
2019 CapZ integrates PIP2 and PKC (phosphorylation at T267 on the β-tentacle) signaling to regulate actin-capping dynamics in cardiac myocytes: substrate stiffness or PKC activation (PMA) increases CapZ kinetic exchange (FRAP), which is blocked by PIP2 reduction; molecular simulations show PIP2 interacts closely with the β-tentacle and phosphorylation at T267 modifies this interaction; CapZ lacking the β-tentacle shows increased FRAP kinetics insensitive to PMA or PIP2. FRAP of GFP-CapZ in neonatal rat ventricular myocytes on substrates of varying stiffness, FRET for PIP2–CapZ interaction, molecular dynamics simulation, β-tentacle deletion mutant, pharmacological agents (neomycin, PMA) The Journal of general physiology High 30808692
2020 CAPZA2 variants identified in patients with intellectual disability fail to rescue Drosophila cpa loss-of-function lethality at normal efficiency and disrupt actin-dependent bristle morphogenesis, placing CAPZA2 function in a developmental actin polymerization pathway. Drosophila cpa null complementation assay (lethality rescue), bristle morphogenesis phenotyping with human reference and variant CAPZA2 transgenes Human molecular genetics Medium 32338762
2020 CAPZA2 promotes CFTR trafficking to the plasma membrane under EPAC1 activation; CAPZA2 was identified as a CFTR-interacting protein and its reduction decreases CFTR surface levels. Protein interaction profiling (affinity pulldown/co-IP with EPAC1 activation), bioinformatic analysis, siRNA knockdown, CFTR surface biotinylation assay The Biochemical journal Medium 32573649
2024 CapZ transiently associates with early endosomes (EEs) and is released upon EE maturation (facilitated by PI(3)P→PI(3,5)P2 conversion); artificially tethering CapZ to EEs blocks EE-to-late-endosome transition; CapZ knockout or tethering to EEs inhibits flavivirus (ZIKV, DENV) and coronavirus (MHV) infection by preventing viral genome escape from endocytic vesicles. Live-cell imaging of CapZ–EE association, rapamycin-induced CapZ tethering to EEs (chemogenetic), CapZ knockout cells, vacuolin-1 treatment, viral infection assays BMC biology High 38273307
2025 In cardiac myocytes during exercise, CapZ–actin binding is rapidly weakened (increased CapZIP levels, decreased phospho-CapZIP at myofilaments); CapZ-deficient transgenic mice have reduced exercise capacity, impaired actomyosin MgATPase activity, altered myofilament PKC-α and -ε translocation, and reduced telethonin/Tcap levels. Transgenic mouse model (reduced CapZ), swimming/running exhaustion protocols, myofilament isolation, actomyosin MgATPase assay, ProQ Diamond phosphoprotein staining, immunoblotting FASEB journal Medium 40832763
2025 CAPZA2 heterozygous knockout and point-mutant knock-in mice show decreased CAPZA2 expression in hippocampus and PFC, increased dendritic spine density with altered morphology, decreased dendritic complexity in PFC, altered PSD95 and glutamate receptor levels, and transcriptional dysregulation of neurodevelopmental and synaptic genes. CAPZA2+/- and CAPZA2c.G776T/+ mouse models, behavioral assays, morphological analysis, single-cell RNA-seq, immunoblotting for synaptic proteins Communications biology Medium 40659881

Source papers

Stage 0 corpus · 52 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1989 Effects of CapZ, an actin capping protein of muscle, on the polymerization of actin. Biochemistry 157 2557904
2003 Crystal structure of CapZ: structural basis for actin filament barbed end capping. The EMBO journal 136 12660160
2015 CapZ regulates autophagosomal membrane shaping by promoting actin assembly inside the isolation membrane. Nature cell biology 125 26237647
2010 BAG3 and Hsc70 interact with actin capping protein CapZ to maintain myofibrillar integrity under mechanical stress. Circulation research 122 20884878
1995 Characterization of S-100b binding epitopes. Identification of a novel target, the actin capping protein, CapZ. The Journal of biological chemistry 121 7540176
1995 Inhibition of CapZ during myofibrillogenesis alters assembly of actin filaments. The Journal of cell biology 112 7822423
1991 Regulation of CapZ, an actin capping protein of chicken muscle, by anionic phospholipids. Biochemistry 99 1653607
2003 Linking the T cell surface protein CD2 to the actin-capping protein CAPZ via CMS and CIN85. The Journal of biological chemistry 97 12690097
1999 Alpha actinin-CapZ, an anchoring complex for thin filaments in Z-line. Journal of muscle research and cell motility 75 10412090
2008 Nebulin interacts with CapZ and regulates thin filament architecture within the Z-disc. Molecular biology of the cell 74 18272787
1992 Identification and characterization of an actin-binding site of CapZ. The Journal of cell biology 69 1370838
2005 The phosphorylation of CapZ-interacting protein (CapZIP) by stress-activated protein kinases triggers its dissociation from CapZ. The Biochemical journal 59 15850461
2003 F-actin capping (CapZ) and other contractile saphenous vein smooth muscle proteins are altered by hemodynamic stress: a proteonomic approach. Molecular & cellular proteomics : MCP 59 14612593
1998 Generation of functional beta-actinin (CapZ) in an E. coli expression system. Journal of muscle research and cell motility 59 9742448
1991 Direct observation of actin filament severing by gelsolin and binding by gCap39 and CapZ. The Journal of cell biology 57 1661732
1998 Identification of cofilin, coronin, Rac and capZ in actin tails using a Listeria affinity approach. Journal of cell science 56 9730980
1993 Localization of CapZ during myofibrillogenesis in cultured chicken muscle. Cell motility and the cytoskeleton 52 8402953
1997 Purification and characterization of an alpha 1 beta 2 isoform of CapZ from human erythrocytes: cytosolic location and inability to bind to Mg2+ ghosts suggest that erythrocyte actin filaments are capped by adducin. Biochemistry 49 9354614
2010 The effects of CapZ peptide (TRTK-12) binding to S100B-Ca2+ as examined by NMR and X-ray crystallography. Journal of molecular biology 45 20053360
2013 Randomized phase III trial of gemcitabine and cisplatin vs. gemcitabine alone in patients with advanced non-small cell lung cancer and a performance status of 2: the CAPPA-2 study. Lung cancer (Amsterdam, Netherlands) 43 23643177
2009 Solution structure of S100A1 bound to the CapZ peptide (TRTK12). Journal of molecular biology 42 19452629
1999 Effect of capping protein, CapZ, on the length of actin filaments and mechanical properties of actin filament networks. Cell motility and the cytoskeleton 41 9915586
1997 Identification of the binding site on S100B protein for the actin capping protein CapZ. Protein science : a publication of the Protein Society 35 9416599
1996 Interaction of S100a0 protein with the actin capping protein, CapZ: characterization of a putative S100a0 binding site in CapZ alpha-subunit. Biochemical and biophysical research communications 34 8660341
2009 CapZ dynamics are altered by endothelin-1 and phenylephrine via PIP2- and PKC-dependent mechanisms. American journal of physiology. Cell physiology 33 19295171
2013 CapZ and actin capping dynamics increase in myocytes after a bout of exercise and abates in hours after stimulation ends. Journal of applied physiology (Bethesda, Md. : 1985) 27 23493359
2008 Cardiac myofilament regulation by protein phosphatase type 1alpha and CapZ. Biochemistry and cell biology = Biochimie et biologie cellulaire 27 18364747
1991 Variant cDNAs encoding proteins similar to the alpha subunit of chicken CapZ. Cell motility and the cytoskeleton 27 1711931
2020 Variants in CAPZA2, a member of an F-actin capping complex, cause intellectual disability and developmental delay. Human molecular genetics 26 32338762
2006 Control of cardiac myofilament activation and PKC-betaII signaling through the actin capping protein, CapZ. Journal of molecular and cellular cardiology 26 16870209
2016 Myofibril growth during cardiac hypertrophy is regulated through dual phosphorylation and acetylation of the actin capping protein CapZ. Cellular signalling 25 27185186
2011 Reduced cardiac CapZ protein protects hearts against acute ischemia-reperfusion injury and enhances preconditioning. Journal of molecular and cellular cardiology 21 22155006
1996 Purification and properties of a Ca(2+)-independent barbed-end actin filament capping protein, CapZ, from human polymorphonuclear leukocytes. Biochemistry 21 8639502
2020 Cytoskeleton regulators CAPZA2 and INF2 associate with CFTR to control its plasma membrane levels under EPAC1 activation. The Biochemical journal 19 32573649
2016 Disease causing mutations in inverted formin 2 regulate its binding to G-actin, F-actin capping protein (CapZ α-1) and profilin 2. Bioscience reports 19 26764407
2009 Biochemical interaction of an actin-capping protein, CapZ, with NAP-22. Journal of neuroscience research 18 19267422
2019 CapZ integrates several signaling pathways in response to mechanical stiffness. The Journal of general physiology 16 30808692
2012 Thermodynamic and kinetic analysis of peptides derived from CapZ, NDR, p53, HDM2, and HDM4 binding to human S100B. Biochemistry 16 22913742
2010 Activity-dependent localization in spines of the F-actin capping protein CapZ screened in a rat model of dementia. Genes to cells : devoted to molecular & cellular mechanisms 15 20545768
2005 Intracellular cAMP controls a physical association of V-1 with CapZ in cultured mammalian endocrine cells. Biochemical and biophysical research communications 13 15845376
2006 CapZ-lipid membrane interactions: a computer analysis. Theoretical biology & medical modelling 10 16914033
2000 In vitro refolding of heterodimeric CapZ expressed in E. coli as inclusion body protein. Protein expression and purification 10 10648164
2012 Actin capping proteins, CapZ (β-actinin) and tropomodulin in amphioxus striated muscle. Gene 9 22951807
2024 The temporal association of CapZ with early endosomes regulates endosomal trafficking and viral entry into host cells. BMC biology 6 38273307
1999 Use of a chaotropic anion iodide in the purification of Z-line proteins: isolation of CapZ from fish white muscle. Protein expression and purification 5 10497062
2012 Identifying a role of the actin capping protein CapZ in β-adrenergic receptor signalling. Acta physiologica (Oxford, England) 4 22882973
2017 The CapZ interacting protein Rcsd1 is required for cardiogenesis downstream of Wnt11a in Xenopus laevis. Developmental biology 3 28237811
2000 Interaction of actin with the capping protein, CapZ from sea bass (Dicentrarchus labrax) white skeletal muscle. Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology 3 11281272
2025 Deciphering the role of CAPZA2 in neurodevelopmental disorders: insights from mouse models. Communications biology 2 40659881
2024 Heterozygous CAPZA2 mutations cause global developmental delay, hypotonia with epilepsy: a case report and the literature review. Journal of human genetics 2 38374166
2007 Sequence characterization, polymorphism, and chromosomal localizations of the porcine CapZ genes. Biochemical genetics 2 17939027
2025 Cardiac CapZ Regulation During Acute Exercise in Female Mice. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 1 40832763

Missed literature

Know a paper Affinage missed for CAPZA2? Flag it for the maintainers and the community.

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