Affinage

MICAL1

[F-actin]-monooxygenase MICAL1 · UniProt Q8TDZ2

Length
1067 aa
Mass
117.9 kDa
Annotated
2026-04-28
100 papers in source corpus 31 papers cited in narrative 31 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MICAL1 is an NADPH-dependent flavoprotein monooxygenase that serves as a central actin-disassembly enzyme, linking upstream signaling cues to rapid cytoskeletal remodeling across diverse cellular contexts including axon guidance, cytokinesis, platelet mechanotransduction, and viral budding. Its N-terminal FAD-containing catalytic domain stereospecifically oxidizes Met44 and Met47 in the D-loop of F-actin, destabilizing intersubunit contacts and synergizing with cofilin to drive catastrophic filament disassembly — a modification reversed by SelR/MsrB methionine sulfoxide reductases (PMID:22116028, PMID:27454820, PMID:24212093). MICAL1 is maintained in an autoinhibited state by intramolecular interaction between its C-terminal coiled-coil domain and catalytic domain, and is activated by GTP-bound Rab GTPases (Rab8, Rab35), PAK1-mediated phosphorylation downstream of CDC42, and semaphorin–plexin–CRMP signaling (PMID:39532862, PMID:30242933, PMID:36198272, PMID:18305261). Beyond actin, MICAL1 oxidizes CaMKII Met308 to restrain kinase activity and protect against cardiac arrhythmias, modulates Tau via Cys322 oxidation, and suppresses MST–NDR proapoptotic signaling; gain-of-function variants cause autosomal dominant lateral temporal lobe epilepsy (ADLTE) (PMID:32749237, PMID:35379354, PMID:21730291, PMID:29394500).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 Medium

    The initial molecular identity of MICAL1 was established as a cytoplasmic protein associating with CasL and vimentin intermediate filaments, providing the first interaction partners but leaving enzymatic function unknown.

    Evidence Far Western screening and co-immunoprecipitation with domain mapping in human cells

    PMID:11827972

    Open questions at the time
    • No enzymatic activity characterized
    • Functional consequence of CasL/vimentin interactions not defined
    • Single-lab study without independent replication
  2. 2005 High

    Structural and enzymatic characterization revealed that MICAL1's N-terminal domain is an FAD-containing monooxygenase resembling p-hydroxybenzoate hydroxylase that consumes NADPH and generates H₂O₂, establishing it as a redox enzyme but leaving its physiological substrate unidentified.

    Evidence Two independent crystal structures (1.45 Å and 2.0 Å) plus in vitro NADPH oxidase kinetics

    PMID:16275925 PMID:16275926

    Open questions at the time
    • Physiological protein substrate not identified
    • Relationship to cytoskeletal function not established
  3. 2008 High

    Discovery that MICAL is autoinhibited by its C-terminal domain and that semaphorin–plexin–CRMP signaling relieves this autoinhibition established how upstream guidance cues activate the enzyme, though the structural basis remained unclear.

    Evidence Co-immunoprecipitation of CRMP and Plexin with MICAL domains, enzyme activity assays with truncations

    PMID:18305261

    Open questions at the time
    • No structural model of full-length autoinhibited state
    • Mechanism of autoinhibition release not resolved at atomic level
  4. 2010 High

    The breakthrough demonstration that MICAL directly binds and disassembles F-actin using its redox activity — and is necessary and sufficient for semaphorin-plexin cytoskeletal remodeling in vivo — identified actin as the physiological substrate.

    Evidence Purified-protein F-actin disassembly assay plus Drosophila genetic loss/gain-of-function

    PMID:20148037

    Open questions at the time
    • Specific chemical modification on actin not yet identified
    • Mechanism of filament destabilization unknown
  5. 2011 High

    Identification of Met44 in actin's D-loop as the stereospecifically oxidized residue defined MICAL as a post-translational modifier of actin that simultaneously severs filaments and inhibits repolymerization, while a parallel study revealed MICAL1 suppresses NDR kinase–MST proapoptotic signaling through a distinct scaffolding interaction.

    Evidence In vitro biochemistry with site-specific modification analysis (actin); MS-based proteomics and co-IP with kinase assays (NDR)

    PMID:21730291 PMID:22116028

    Open questions at the time
    • Role of Met47 oxidation not characterized
    • Structural basis of filament instability upon oxidation unknown
    • Whether NDR regulation depends on redox activity unclear
  6. 2013 High

    Discovery that SelR/MsrB specifically reduces Mical-oxidized actin Met44-R-sulfoxide back to methionine established that MICAL-mediated actin modification is a reversible regulatory switch, not irreversible damage.

    Evidence Drosophila genetic screen, in vitro enzymatic reconstitution with purified SelR and Mical-oxidized actin

    PMID:24212093

    Open questions at the time
    • Spatiotemporal regulation of SelR-MICAL balance in cells not characterized
    • Whether additional reductases contribute is unknown
  7. 2016 High

    Demonstration that MICAL-oxidized actin synergizes with cofilin — by increasing cofilin binding and overriding tropomyosin protection — revealed how two independent disassembly pathways converge for rapid F-actin destruction in vivo; kinetic characterization quantified the ~10-fold autoinhibition by the C-terminal domain.

    Evidence In vitro TIRF single-filament assays, Drosophila genetics, steady-state enzyme kinetics with truncation constructs

    PMID:26845023 PMID:27454820

    Open questions at the time
    • Structural mechanism of cofilin recognition of oxidized actin not resolved
    • Regulation of MICAL1 versus MICAL2 activity in non-neuronal cells poorly defined
  8. 2017 High

    Cryo-EM of Mical-oxidized actin filaments revealed how Met44 reorientation and a new Met47-O–Thr351 intermolecular bond destabilize intersubunit contacts, causing nucleotide-state-dependent catastrophic disassembly at ~84 subunits/s.

    Evidence 3.9 Å cryo-EM of oxidized F-actin, single-filament TIRF, site-directed mutagenesis

    PMID:29259197

    Open questions at the time
    • No structure of MICAL bound to F-actin
    • Whether oxidation affects actin-binding protein interactions beyond cofilin and fascin not fully explored
  9. 2018 High

    Rab8-GTP was shown to bind and allosterically activate MICAL1 (4-fold kcat increase), defining a Rab-based activation mechanism; separately, ADLTE-associated MICAL1 variants were found to be gain-of-function, linking hyperactive actin oxidation to human epilepsy.

    Evidence Enzyme kinetics and SAXS for Rab8 activation; cell-based oxidoreductase and morphology assays for ADLTE variants

    PMID:29394500 PMID:30242933

    Open questions at the time
    • How Rab8 binding relieves autoinhibition structurally was not resolved
    • ADLTE mechanism in neurons not demonstrated in vivo
    • ADLTE finding from a single family study with limited mechanistic depth
  10. 2020 High

    MICAL1 was established as a CaMKII regulator: stereospecific oxidation of CaMKII Met308 restrains kinase activity, and MICAL1 knockout mice develop lethal cardiac arrhythmias from CaMKII hyperactivation, demonstrating a non-actin substrate with major physiological consequences.

    Evidence Mouse knockout, in vitro biochemistry, human iPSC-derived cardiomyocytes, Drosophila genetics

    PMID:32749237

    Open questions at the time
    • Whether additional MICAL1 substrates beyond actin and CaMKII exist is unknown
    • Tissue-specific regulation of MICAL1 toward actin versus CaMKII not defined
  11. 2022 High

    PAK1 phosphorylation of MICAL1 on N-terminal serine residues (downstream of CDC42) was identified as an activation mechanism that accelerates F-actin disassembly, adding a kinase-dependent input alongside Rab-GTPase activation; separately, Mical was shown to oxidize Tau Cys322 to modulate tauopathy.

    Evidence Co-IP, MS phosphosite mapping, F-actin assays for PAK1; Drosophila genetics and MS for Tau oxidation

    PMID:35379354 PMID:36198272

    Open questions at the time
    • Whether PAK1 and Rab activation are synergistic or independent is unknown
    • Tau oxidation only shown in Drosophila model, human relevance unclear
  12. 2024 High

    Full-length cryo-EM structure at 3.1 Å finally resolved the autoinhibition mechanism: the C-terminal coiled-coil directly contacts the catalytic domain to block F-actin access, with CH-L2α1-LIM domains stabilizing this conformation; in parallel, MICAL1 was shown to disassemble branched actin at HIV-1 budding sites in a Rab35-dependent pathway enabling ESCRT recruitment.

    Evidence Cryo-EM of full-length human MICAL1 with biochemical validation; superresolution microscopy, siRNA/KO, in vitro branched-actin disassembly

    PMID:39532862 PMID:39556735

    Open questions at the time
    • No structure of activated MICAL1 bound to F-actin or Rab
    • How MICAL1 is spatially targeted to HIV budding sites beyond Rab35 is unclear
  13. 2025 High

    MICAL1 was identified as a shear-activated actin regulator in platelets that promotes GPIb-IX-V translocation to lipid rafts for VWF binding, establishing a role in hemostasis and thrombus formation.

    Evidence MICAL1 knockout mice, live-cell imaging under shear, lipid raft fractionation, in vivo thrombus assay

    PMID:40783397

    Open questions at the time
    • Mechanism of shear-dependent MICAL1 activation is unknown
    • Whether MICAL1 oxidizes platelet-specific substrates beyond actin is untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of MICAL1's interaction with F-actin in the activated state, how multiple activation inputs (Rab GTPases, PAK1 phosphorylation, plexin/CRMP) are integrated, the full scope of MICAL1's substrate repertoire beyond actin and CaMKII, and the pathogenic mechanism of MICAL1 gain-of-function in ADLTE at the neural circuit level.
  • No structure of MICAL1-F-actin complex
  • Integration of multiple activation pathways not studied
  • Complete substrate repertoire undefined
  • ADLTE circuit-level mechanism unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 6 GO:0008092 cytoskeletal protein binding 4 GO:0140096 catalytic activity, acting on a protein 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2 R-HSA-5357801 Programmed Cell Death 2 R-HSA-109582 Hemostasis 1
Partners
ASAP1CFL1CRMP1NDR1PAK1PLXNA1RAB35RAB8A

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Crystal structure of the FAD-containing monooxygenase (MO) domain of mouse MICAL-1 (residues 1-489) at 1.45 Å resolution reveals topology closely resembling NADPH-dependent flavoenzyme p-hydroxybenzoate hydroxylase (PHBH); the flavin ring switches between two discrete positions coupled with opening of a channel to the active site, suggestive of a protein substrate. X-ray crystallography (1.45 Å), NADPH reaction comparison Proceedings of the National Academy of Sciences of the United States of America High 16275925
2005 The N-terminal FAD-containing domain of MICAL is a flavoenzyme that in the presence of NADPH reduces molecular oxygen to H2O2 (Km,NADPH = 222 μM; kcat = 77 s−1), suggesting H2O2 as a signaling molecule in axon guidance. Biochemical in vitro enzyme assay, X-ray crystallography (2.0 Å) Proceedings of the National Academy of Sciences of the United States of America High 16275926
2010 MICAL directly binds F-actin and disassembles both individual and bundled actin filaments using its redox (monooxygenase) activity; MICAL is necessary and sufficient for semaphorin-plexin-mediated F-actin reorganization in vivo. Purified protein in vitro F-actin disassembly assay, genetic loss-of-function and gain-of-function in Drosophila, NADPH-dependent redox activity requirement Nature High 20148037
2011 Mical directly and stereospecifically oxidizes methionine 44 (Met44) in the D-loop of actin, simultaneously severing filaments and decreasing polymerization; actin is a specific substrate of the Mical monooxygenase. In vitro biochemical assay with purified Mical and actin, site-specific modification analysis, polymerization assays Science High 22116028
2013 SelR (MsrB methionine sulfoxide reductase) specifically reduces Mical-oxidized actin (actin Met-44-R-sulfoxide) back to methionine, restoring normal polymerization properties and reversing Mical-mediated F-actin disassembly and Semaphorin-Plexin repulsion in vivo. Genetic screen (Drosophila), in vitro enzyme assay with purified SelR and Mical-oxidized actin, polymerization assays Nature cell biology High 24212093
2008 MICAL enzymatic activity is autoinhibited by its own C-terminal domain; CRMP and Plexin associate with non-enzymatic and enzymatic domains of MICAL respectively, and together release this autoinhibition; Semaphorin signaling promotes the CRMP-MICAL physical association. Co-immunoprecipitation, domain-deletion biochemical assays, enzyme activity measurements The Journal of neuroscience High 18305261
2016 Mical-mediated oxidation of actin Met44 (and Met47) improves cofilin binding to filaments; combined Mical oxidation and cofilin dramatically accelerates F-actin disassembly (synergism) compared to either effector alone, and this synergism is necessary and sufficient for F-actin disassembly in vivo. In vitro F-actin disassembly assays with purified proteins, TIRF microscopy, genetic experiments in Drosophila Nature cell biology High 27454820
2017 Mical oxidizes actin's M44 and M47 residues; cryo-EM (3.9 Å) reveals that oxidation reorients M44 side chain and induces a new M47-O-T351 intermolecular interaction promoting Mox-actin instability; Mox-actin undergoes catastrophically fast disassembly (84 subunits/s) that is nucleotide-state dependent; Mical oxidation allows cofilin severing even in presence of inorganic phosphate. Near-atomic cryo-EM (3.9 Å), single-filament TIRF microscopy, site-directed mutagenesis Nature communications High 29259197
2020 MICAL1 oxidizes Met308 in the calmodulin-binding domain of CaMKII stereospecifically; oxidized or mutant M308V CaMKII shows decreased CaM binding and CaMKII activity; absence of MICAL1 in mice causes cardiac arrhythmias and premature death due to CaMKII hyperactivation; MSRB reverses this oxidation. Mouse knockout, in vitro biochemical assays, cell-based functional assays, human iPSC-derived cardiomyocytes, Drosophila genetics The Journal of clinical investigation High 32749237
2021 MICAL1-mediated oxidation of actin filaments suppresses their protection from cofilin severing: oxidation increases cofilin binding and severing rates by orders of magnitude, allows phosphomimetic S3D-cofilin (normally inactive) to sever oxidized filaments, and abolishes tropomyosin Tpm1.8 protection of filaments. Single-filament in vitro assays with purified proteins, fluorescence microscopy EMBO reports High 33393173
2024 Cryo-EM structure of full-length human MICAL1 at 3.1 Å shows autoinhibition is mediated by intramolecular interaction between N-terminal catalytic domain and C-terminal coiled-coil domain that blocks F-actin interaction; allosteric changes in the coiled-coil and binding of CH-L2α1-LIM domains to the coiled-coil are required for activation/autoinhibition. Cryo-EM (3.1 Å nominal resolution), biochemical and functional validation Nature communications High 39532862
2018 Active GTP-bound Rab8 binds full-length MICAL1 (apparent Kd ~8 μM, 1:1 complex) and stabilizes its active conformation, causing a specific 4-fold increase in kcat of the NADPH oxidase reaction; the region preceding the C-terminal Rab-binding domain masks one Rab-binding site in the autoinhibited state. Enzyme kinetics, small-angle X-ray scattering (SAXS), binding assays Protein science High 30242933
2011 MICAL-1 interacts with the hydrophobic motif of NDR1/2 kinases; overexpression or knockdown of MICAL-1 reduces or augments NDR kinase activation respectively; MICAL-1 competes with MST1 for NDR binding and thereby antagonizes MST1-induced NDR kinase activation and NDR-dependent proapoptotic signaling. Proteomics/mass spectrometry, co-immunoprecipitation, kinase activity assays, siRNA knockdown, overexpression Molecular and cellular biology High 21730291
2002 MICAL (human MICAL1) associates with CasL through its PPKPP proline-rich sequence and with vimentin intermediate filaments through its C-terminal region; MICAL colocalizes with vimentin intermediate filaments as a cytoplasmic protein. Far Western screening, co-immunoprecipitation, domain-deletion mapping, immunostaining The Journal of biological chemistry Medium 11827972
2003 MICAL-1 isoforms interact with Rab1 GTPase in a nucleotide-dependent manner (active GTP-bound form); the Rab1-interacting domain maps to the C-terminus of MICAL-1, which also mediates vimentin binding; MICAL-1 is predominantly cytosolic. Yeast two-hybrid, GST pulldown, cell fractionation Biochemical and biophysical research communications Medium 12788069
2009 Mical (Drosophila ortholog) mediates dendrite severing during pruning downstream of Sox14 transcription factor; Sox14 directly regulates mical expression, and overexpression of Mical significantly rescues pruning defects in sox14 mutants, establishing a Sox14-Mical pathway for dendrite severing. Drosophila genetics (mutant analysis, epistasis, rescue experiments) Nature neuroscience High 19881505
2014 Vertebrate MICAL-1 regulates targeting of secretory vesicles containing IgCAM cell adhesion molecules to the neuronal growth cone membrane via its ability to control the actin cytoskeleton using redox chemistry, thereby maintaining appropriate IgCAM cell surface levels essential for mossy fibre axon lamina-specific targeting in vivo. Mouse in vivo loss-of-function, live cell imaging, biochemical fractionation Nature communications High 25007825
2016 MICAL1 is autoinhibited by its C-terminal coiled-coil region in non-neural cells; MICAL2 is constitutively active; both MICAL1 and MICAL2 regulate actin stress fibers through ROS generation. Overexpression and knockdown of truncation mutants in HeLa cells, actin staining, ROS measurement Journal of cell science Medium 22331357
2016 MICAL1 NADPH oxidase and F-actin depolymerizing activity is regulated by C-terminal, LIM, and CH domains: the C-terminus causes ~10-fold decrease of kcat (autoinhibition) and ~10-fold increase in Km for actin; F-actin lowers Km,NADPH and increases kcat for all MICAL forms. In vitro biochemical characterization of truncated/full-length MICAL1 forms, kinetic measurements Archives of biochemistry and biophysics High 26845023
2022 The CDC42 GTPase effector PAK1 physically associates with and phosphorylates MICAL1 on two serine residues at the N-terminal catalytic monooxygenase and calponin homology domains, leading to accelerated F-actin disassembly; extracellular ligand stimulation leads to PAK-dependent MICAL1 phosphorylation. Co-immunoprecipitation, mass spectrometry, phosphorylation assays, F-actin disassembly assays, domain-mapping Cell reports High 36198272
2021 Myosin 15 (Myo15) physically and functionally interacts with the Mical F-actin disassembly enzyme using its motor and MyTH4-FERM cargo-transporting functions to broaden Mical's distribution, thereby spatiotemporally propagating and directionally orienting Mical-mediated F-actin disassembly in response to Semaphorin/Plexin signals. Co-immunoprecipitation, genetic epistasis in Drosophila, high-resolution cellular imaging Science advances Medium 33980493
2023 Mical disassembles fascin-bundled F-actin; Mical-oxidized actin is poorly bundled by fascin (amplifying disassembly); cofilin synergizes with Mical to dramatically amplify disassembly of bundled F-actin beyond additive effects; Mical counteracts crosslinking/bundled F-actin in vivo to control cellular extension and Semaphorin/Plexin repulsion. In vitro biochemical assays with purified proteins, cryo-EM structural analysis, genetic experiments in Drosophila, high-resolution imaging Proceedings of the National Academy of Sciences of the United States of America High 37725655
2024 MICAL1 locally depolymerizes branched actin at HIV-1 budding sites; MICAL1 directly disassembles branched-actin networks; MICAL1 controls timely recruitment of ESCRT machinery during viral budding; Rab35 (MICAL1 activator) is recruited at budding sites and functions in the same pathway as MICAL1 for viral release. Superresolution microscopy, MICAL1 depletion (siRNA/KO), in vitro branched-actin disassembly assay, genetic epistasis with Arp2/3 inhibition Proceedings of the National Academy of Sciences of the United States of America High 39556735
2025 MICAL1 is shear-activated in platelets and promotes local F-actin disassembly around the GPIb-IX-V complex, enabling its translocation to lipid rafts and reinforcing VWF binding; MICAL1-deficient platelets display impaired adhesion and defective thrombus formation in vivo. Mouse MICAL1 KO, live-cell imaging under shear, lipid raft fractionation, in vivo thrombus formation assay Nature communications High 40783397
2018 ADLTE-causing MICAL-1 variants (p.Gly150Ser in the MO domain; p.Ala1065fs frameshift in C-terminal domain) significantly increase MICAL-1 oxidoreductase activity and induce cell contraction in COS7 cells, indicating gain-of-function dysregulation of actin dynamics as the disease mechanism. Cell-based oxidoreductase activity assay, cell morphology assay (COS7), genetic variant analysis Annals of neurology Medium 29394500
2022 Mical modulates Tau toxicity via oxidation of Tau cysteine residue Cys322 (not methionine); Mical-mediated cysteine oxidation of Tau alters its interactions with microtubules and actin cytoskeleton and affects Tau aggregation propensity in Drosophila Tauopathy model. Drosophila genetic interactions, Mical inhibitor, monooxygenase domain mutation, Tau cysteine mutant transgenes, mass spectrometry quantification of cysteine oxidation Acta neuropathologica communications Medium 35379354
2023 The SH3 domain of ASAP1 binds the proline-rich motif (PRM) of MICAL1 with sub-μM affinity through a unique interaction in which two negatively charged patches in ASAP1-SH3 recognize the 'xPx+Px+' sequence in MICAL1-PRM; crystal structure of the ASAP1-SH3/MICAL1-PRM complex was determined. Crystal structure determination, binding affinity measurements (ITC/SPR), mutational biochemistry International journal of molecular sciences Medium 36674928
2020 MICAL1 and WDR44 are direct GRAF2-binding partners; MICAL1 links GRAF1b/2 to Rab8a/b and Rab10; dominant negative mutants of MICAL1 interfere with Rab8/10/11-dependent export of E-cadherin, MMP14, and CFTR ΔF508 to the plasma membrane. Co-immunoprecipitation, colocalization, dominant-negative overexpression, cargo trafficking assays The Journal of cell biology Medium 32344433
2007 Drosophila MICAL is required in muscles for higher-order arrangement of myofilaments; in mical mutants, actin and myosin filaments are disorganized and accumulate beneath the plasma membrane instead of being integrated into regular sarcomeric patterns, causing synaptic growth defects. Drosophila loss-of-function genetics, RNAi transgene, immunohistochemistry, electron microscopy Mechanisms of development Medium 17350233
2015 MICAL1 depletion in BRAF-mutant melanoma cells restores MST-1-dependent NDR phosphorylation and promotes rapid NDR-dependent apoptosis, confirming MICAL1 as a negative regulator of apoptosis in this context. siRNA knockdown, Western blot (NDR phosphorylation), apoptosis assays Oncotarget Medium 25576923
2016 MICAL1 controls breast cancer cell invasion by generating ROS that activates PI3K/Akt signaling; activated RAB35 binds to MICAL1, and RAB35 silencing represses ROS generation, Akt phosphorylation, and cell invasion in response to EGF. Co-immunoprecipitation, RAB35 pulldown activity assay, ROS measurement, Akt phosphorylation analysis, matrigel invasion assay BMC cancer Medium 27430308

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Direct redox regulation of F-actin assembly and disassembly by Mical. Science (New York, N.Y.) 253 22116028
2010 Mical links semaphorins to F-actin disassembly. Nature 212 20148037
2009 MICAL-L1 links EHD1 to tubular recycling endosomes and regulates receptor recycling. Molecular biology of the cell 149 19864458
2014 Redox modification of nuclear actin by MICAL-2 regulates SRF signaling. Cell 139 24440334
2013 SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics. Nature cell biology 123 24212093
2002 MICAL, a novel CasL interacting molecule, associates with vimentin. The Journal of biological chemistry 119 11827972
2009 A genetic pathway composed of Sox14 and Mical governs severing of dendrites during pruning. Nature neuroscience 107 19881505
2007 The interaction of JRAB/MICAL-L2 with Rab8 and Rab13 coordinates the assembly of tight junctions and adherens junctions. Molecular biology of the cell 101 18094055
2013 MICAL-family proteins: Complex regulators of the actin cytoskeleton. Antioxidants & redox signaling 94 23834433
2016 F-actin dismantling through a redox-driven synergy between Mical and cofilin. Nature cell biology 91 27454820
2008 Release of MICAL autoinhibition by semaphorin-plexin signaling promotes interaction with collapsin response mediator protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 90 18305261
2011 MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a. Traffic (Copenhagen, Denmark) 89 21951725
2013 Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis. Molecular biology of the cell 85 23596323
2012 Differential regulation of actin microfilaments by human MICAL proteins. Journal of cell science 84 22331357
2006 JRAB/MICAL-L2 is a junctional Rab13-binding protein mediating the endocytic recycling of occludin. Molecular biology of the cell 84 16525024
2017 Catastrophic disassembly of actin filaments via Mical-mediated oxidation. Nature communications 79 29259197
2011 Extracellular inhibitors, repellents, and semaphorin/plexin/MICAL-mediated actin filament disassembly. Cytoskeleton (Hoboken, N.J.) 74 21800438
2014 Rab35 promotes the recruitment of Rab8, Rab13 and Rab36 to recycling endosomes through MICAL-L1 during neurite outgrowth. Biology open 71 25086062
2005 High-resolution structure of the catalytic region of MICAL (molecule interacting with CasL), a multidomain flavoenzyme-signaling molecule. Proceedings of the National Academy of Sciences of the United States of America 71 16275925
2017 Emerging roles of MICAL family proteins - from actin oxidation to membrane trafficking during cytokinesis. Journal of cell science 69 28373242
2009 Rab13 regulates neurite outgrowth in PC12 cells through its effector protein, JRAB/MICAL-L2. Molecular and cellular biology 68 20008558
2005 Structure and activity of the axon guidance protein MICAL. Proceedings of the National Academy of Sciences of the United States of America 68 16275926
2018 MICAL1 facilitates breast cancer cell proliferation via ROS-sensitive ERK/cyclin D pathway. Journal of cellular and molecular medicine 66 29524295
2005 MICAL flavoprotein monooxygenases: expression during neural development and following spinal cord injuries in the rat. Molecular and cellular neurosciences 65 16230022
2007 Drosophila MICAL regulates myofilament organization and synaptic structure. Mechanisms of development 58 17350233
2005 The MICAL proteins and rab1: a possible link to the cytoskeleton? Biochemical and biophysical research communications 58 15694364
2015 Sema6A and Mical1 control cell growth and survival of BRAFV600E human melanoma cells. Oncotarget 57 25576923
2016 MICAL1 controls cell invasive phenotype via regulating oxidative stress in breast cancer cells. BMC cancer 55 27430308
2014 The intracellular redox protein MICAL-1 regulates the development of hippocampal mossy fibre connections. Nature communications 54 25007825
2003 MICAL-1 isoforms, novel rab1 interacting proteins. Biochemical and biophysical research communications 54 12788069
2015 A complex of Rab13 with MICAL-L2 and α-actinin-4 is essential for insulin-dependent GLUT4 exocytosis. Molecular biology of the cell 52 26538022
2011 MICAL-1 is a negative regulator of MST-NDR kinase signaling and apoptosis. Molecular and cellular biology 52 21730291
2008 Involvement of actinin-4 in the recruitment of JRAB/MICAL-L2 to cell-cell junctions and the formation of functional tight junctions. Molecular and cellular biology 48 18332111
2015 Silencing of MICAL-L2 suppresses malignancy of ovarian cancer by inducing mesenchymal-epithelial transition. Cancer letters 42 25864591
2014 GRAF1 forms a complex with MICAL-L1 and EHD1 to cooperate in tubular recycling endosome vesiculation. Frontiers in cell and developmental biology 36 25364729
2019 MICAL-L2 potentiates Cdc42-dependent EGFR stability and promotes gastric cancer cell migration. Journal of cellular and molecular medicine 33 31034158
2021 A junctional PACSIN2/EHD4/MICAL-L1 complex coordinates VE-cadherin trafficking for endothelial migration and angiogenesis. Nature communications 31 33972531
2020 GRAF2, WDR44, and MICAL1 mediate Rab8/10/11-dependent export of E-cadherin, MMP14, and CFTR ΔF508. The Journal of cell biology 31 32344433
2007 Involvement of Rab13 and JRAB/MICAL-L2 in epithelial cell scattering. Oncogene 31 17891173
2018 Mutations in MICAL-1cause autosomal-dominant lateral temporal epilepsy. Annals of neurology 30 29394500
2013 MICAL, the flavoenzyme participating in cytoskeleton dynamics. International journal of molecular sciences 30 23535333
2016 Properties and catalytic activities of MICAL1, the flavoenzyme involved in cytoskeleton dynamics, and modulation by its CH, LIM and C-terminal domains. Archives of biochemistry and biophysics 29 26845023
2011 MICAL-like1 mediates epidermal growth factor receptor endocytosis. Molecular biology of the cell 28 21795389
2023 MICAL-mediated oxidation of actin and its effects on cytoskeletal and cellular dynamics. Frontiers in cell and developmental biology 27 36875759
2020 MICAL1 constrains cardiac stress responses and protects against disease by oxidizing CaMKII. The Journal of clinical investigation 26 32749237
2021 Actin filament oxidation by MICAL1 suppresses protections from cofilin-induced disassembly. EMBO reports 25 33393173
2011 Kinetic and spectroscopic characterization of the putative monooxygenase domain of human MICAL-1. Archives of biochemistry and biophysics 25 21864500
2019 MICAL-L1 coordinates ciliogenesis by recruiting EHD1 to the primary cilium. Journal of cell science 24 31615969
2010 Important relationships between Rab and MICAL proteins in endocytic trafficking. World journal of biological chemistry 24 21537482
2013 Actin stimulates reduction of the MICAL-2 monooxygenase domain. Biochemistry 23 23927065
2010 MICAL-L1: An unusual Rab effector that links EHD1 to tubular recycling endosomes. Communicative & integrative biology 23 20585517
2007 MICAL flavoprotein monooxygenases: structure, function and role in semaphorin signaling. Advances in experimental medicine and biology 23 17607945
2019 NEDD9 Facilitates Hypoxia-Induced Gastric Cancer Cell Migration via MICAL1 Related Rac1 Activation. Frontiers in pharmacology 22 31019460
2014 Novel functions for the endocytic regulatory proteins MICAL-L1 and EHD1 in mitosis. Traffic (Copenhagen, Denmark) 22 25287187
2021 Propagation of F-actin disassembly via Myosin15-Mical interactions. Science advances 21 33980493
2021 MICAL1 regulates actin cytoskeleton organization, directional cell migration and the growth of human breast cancer cells as orthotopic xenograft tumours. Cancer letters 19 34314753
2016 Conformational plasticity of JRAB/MICAL-L2 provides "law and order" in collective cell migration. Molecular biology of the cell 18 27582384
2014 Regulation of Src trafficking and activation by the endocytic regulatory proteins MICAL-L1 and EHD1. Journal of cell science 17 24481818
2012 Trafficking cascades mediated by Rab35 and its membrane hub effector, MICAL-L1. Communicative & integrative biology 17 23060965
2022 MICAL1 facilitates pancreatic cancer proliferation, migration, and invasion by activating WNT/β-catenin pathway. Journal of translational medicine 16 36371204
2011 Expression pattern of Mical-1 in the temporal neocortex of patients with intractable temporal epilepsy and pilocarpine-induced rat model. Synapse (New York, N.Y.) 16 21638339
2017 MICAL redox enzymes and actin remodeling: New links to classical tumorigenic and cancer pathways. Molecular & cellular oncology 15 29404387
2022 Mical modulates Tau toxicity via cysteine oxidation in vivo. Acta neuropathologica communications 14 35379354
2022 MICAL1 activation by PAK1 mediates actin filament disassembly. Cell reports 14 36198272
2010 Identification and expression analysis of mical family genes in zebrafish. Journal of genetics and genomics = Yi chuan xue bao 14 21035094
2021 MICAL1 inhibits colorectal cancer cell migration and proliferation by regulating the EGR1/β-catenin signaling pathway. Biochemical pharmacology 13 34902339
2019 Actin Cytoskeletal Reorganization Function of JRAB/MICAL-L2 Is Fine-tuned by Intramolecular Interaction between First LIM Zinc Finger and C-terminal Coiled-coil Domains. Scientific reports 13 31488862
2023 Disassembly of bundled F-actin and cellular remodeling via an interplay of Mical, cofilin, and F-actin crosslinkers. Proceedings of the National Academy of Sciences of the United States of America 12 37725655
2021 MICAL-L2 Is Essential for c-Myc Deubiquitination and Stability in Non-small Cell Lung Cancer Cells. Frontiers in cell and developmental biology 11 33520979
2018 Human MICAL1: Activation by the small GTPase Rab8 and small-angle X-ray scattering studies on the oligomerization state of MICAL1 and its complex with Rab8. Protein science : a publication of the Protein Society 11 30242933
2014 MICAL-L1-related and unrelated mechanisms underlying elongated tubular endosomal network (ETEN) in human dendritic cells. Communicative & integrative biology 10 26478765
2022 MICAL1 Monooxygenase in Autosomal Dominant Lateral Temporal Epilepsy: Role in Cytoskeletal Regulation and Relation to Cancer. Genes 9 35627100
2021 MICAL1 (molecule interacting with CasL 1) protects oligodendrocyte cells from oxidative injury through regulating apoptosis, autophagy in spinal cord injury. Neuroscience letters 9 33647394
2020 Signal-regulated oxidation of proteins via MICAL. Biochemical Society transactions 9 32219383
2016 A simple and efficient method for generating high-quality recombinant Mical enzyme for in vitro assays. Protein expression and purification 9 27223600
2008 Identification and characterization of JRAB/MICAL-L2, a junctional Rab13-binding protein. Methods in enzymology 8 18413246
2024 HIV-1 budding requires cortical actin disassembly by the oxidoreductase MICAL1. Proceedings of the National Academy of Sciences of the United States of America 7 39556735
2023 Crystal Structure of the SH3 Domain of ASAP1 in Complex with the Proline Rich Motif (PRM) of MICAL1 Reveals a Unique SH3/PRM Interaction Mode. International journal of molecular sciences 7 36674928
2007 Investigation of the four cooperative unfolding units existing in the MICAL-1 CH domain. Biophysical chemistry 7 17662518
2024 PlexinA1 promotes gastric cancer migration through preventing MICAL1 protein ubiquitin/proteasome-mediated degradation in a Rac1-dependent manner. Biochimica et biophysica acta. Molecular basis of disease 6 38508474
2016 MICAL-like Regulates Fasciclin II Membrane Cycling and Synaptic Development. Molecules and cells 6 27770767
2010 Neuronal guidance: a redox signal involving Mical. Current biology : CB 6 21749956
2024 MICAL-L2, as an estrogen-responsive gene, is involved in ER-positive breast cancer cell progression and tamoxifen sensitivity via the AKT/mTOR pathway. Biochemical pharmacology 5 38729448
2018 Dancing Styles of Collective Cell Migration: Image-Based Computational Analysis of JRAB/MICAL-L2. Frontiers in cell and developmental biology 5 29468157
2024 Structural basis of MICAL autoinhibition. Nature communications 4 39532862
2021 MICAL-L1 is required for cargo protein delivery to the cell surface. Biology open 4 34100897
2018 Common effects of attractive and repulsive signaling: Further analysis of Mical-mediated F-actin disassembly and regulation by Abl. Communicative & integrative biology 4 29497471
2017 Podocyte Shape Regulation by Semaphorin 3A and MICAL-1. Methods in molecular biology (Clifton, N.J.) 4 27787866
2024 A de novo pathogenic variant in MICAL-1 causes epilepsy with auditory features. Epilepsia open 3 38654463
2021 Enhanced Production of the Mical Redox Domain for Enzymology and F-actin Disassembly Assays. International journal of molecular sciences 3 33671465
2014 MICAL-like1 in endosomal signaling. Methods in enzymology 3 24377937
2024 Elucidating the role of MICAL1 in pan-cancer using integrated bioinformatics and experimental approaches. Cell adhesion & migration 2 38555517
2024 Endosomal actin branching, fission, and receptor recycling require FCHSD2 recruitment by MICAL-L1. Molecular biology of the cell 2 39382837
2024 High MICAL-L2 promotes cancer progression and drug resistance in renal clear cell carcinoma cells through stabilization of ACTN4 following vimentin expression. Biochimica et biophysica acta. Molecular basis of disease 2 39689763
2025 MICAL1 Mediates TGF-β1-Induced Epithelial-to-Mesenchymal Transition and Metastasis of Hepatocellular Carcinoma by Activating Smad2/3. Cell biochemistry and biophysics 1 39954154
2025 CIN85 and CD2AP Are Novel Constituents of Dynamic Tubular Recycling Endosomes That Regulate Recycling Upon Recruitment by MICAL-L1. Traffic (Copenhagen, Denmark) 1 40740057
2023 Actin Isoform Composition and Binding Factors Fine-Tune Regulatory Impact of Mical Enzymes. International journal of molecular sciences 1 38068973
2025 F-actin disassembly by the oxidoreductase MICAL1 promotes mechano-dependent VWF-GPIbα interaction in platelets. Nature communications 0 40783397
2024 A novel splicing variant in MICAL-1 gene is associated with epilepsy. European journal of medical genetics 0 38705457
2024 Endosomal actin branching, fission and receptor recycling require FCHSD2 recruitment by MICAL-L1. bioRxiv : the preprint server for biology 0 38979241