Affinage

MICAL1

[F-actin]-monooxygenase MICAL1 · UniProt Q8TDZ2

Length
1067 aa
Mass
117.9 kDa
Annotated
2026-06-10
100 papers in source corpus 30 papers cited in narrative 30 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MICAL1 is a multidomain FAD-dependent flavoprotein monooxygenase that couples redox chemistry to actin cytoskeleton remodeling, serving as the effector that links semaphorin-plexin signaling to F-actin reorganization in vivo (PMID:20148037, PMID:16275925). Its N-terminal flavoenzyme domain is structurally related to p-hydroxybenzoate hydroxylase and uses NADPH and molecular oxygen to drive catalysis, with a flavin ring that switches between positions coupled to opening of a substrate channel (PMID:16275925, PMID:16275926). The enzyme directly binds and disassembles individual and bundled F-actin by stereospecifically oxidizing actin methionine residues Met44 and Met47; this post-translational oxidation reorients the Met44 side chain and induces a new intermolecular contact that destabilizes the filament, simultaneously severing it and blocking reassembly (PMID:22116028, PMID:29259197). Oxidation is reversed by the methionine sulfoxide reductase SelR/MsrB, which restores normal polymerization and establishes a reversible redox switch on actin (PMID:24212093). MICAL1-mediated oxidation also primes filaments for accelerated cofilin binding and severing — overriding the protection normally conferred by tropomyosin and fascin bundling — so that cofilin synergizes with MICAL1 to dramatically amplify disassembly (PMID:27454820, PMID:33393173, PMID:37725655). MICAL1 catalytic activity is held in an autoinhibited state by an intramolecular interaction between the N-terminal catalytic domain and the C-terminal coiled-coil region, resolved by cryo-EM, and is relieved by upstream regulators including GTP-bound Rab8, PAK1-mediated phosphorylation, and CRMP/Plexin association downstream of semaphorin signaling (PMID:18305261, PMID:30242933, PMID:39532862, PMID:36198272). Its substrate range extends beyond actin: MICAL1 oxidizes Met308 of CaMKII to reduce calmodulin binding and kinase activity, and oxidizes Cys322 of Tau to alter cytoskeletal interactions and aggregation (PMID:32749237, PMID:35379354). Through these activities MICAL1 controls axon guidance and growth-cone IgCAM trafficking, dendrite pruning, cytokinesis-related membrane events, HIV-1 budding, shear-dependent platelet adhesion, and cardiac CaMKII homeostasis (PMID:25007825, PMID:32749237, PMID:39556735, PMID:40783397, PMID:19881505). Gain-of-function MICAL1 mutations that elevate its oxidoreductase activity cause autosomal dominant lateral temporal epilepsy (PMID:29394500).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2002 Medium

    Established the first physical partners of MICAL1, placing it at cytoskeletal adaptor junctions before its enzymatic role was known.

    Evidence Far Western screening, co-IP, and immunofluorescence in cells identifying CasL SH3 and vimentin interactions

    PMID:11827972

    Open questions at the time
    • No enzymatic function assigned at this stage
    • Functional consequence of vimentin/CasL binding unresolved
  2. 2003 Medium

    Linked MICAL1 to Rab GTPase signaling by showing nucleotide-dependent binding to active Rab1, implicating it in vesicle-related processes.

    Evidence Yeast two-hybrid, GST pulldown, and cell fractionation with domain mapping

    PMID:12788069

    Open questions at the time
    • No catalytic consequence of Rab1 binding tested
    • Cytosolic localization not connected to a pathway
  3. 2005 High

    Defined MICAL1 as a FAD monooxygenase with a PHBH-like fold and a conformational flavin switch, and showed it produces H2O2 from NADPH/O2, framing the enzymatic basis of its cytoskeletal effects.

    Evidence 1.45 Å X-ray crystallography of the mouse flavodomain plus enzyme kinetics measuring H2O2 production

    PMID:16275925 PMID:16275926

    Open questions at the time
    • Physiological protein substrate not yet identified
    • Whether H2O2 or direct oxidation drives actin disassembly unresolved
  4. 2008 Medium

    Resolved how MICAL is switched on, showing C-terminal autoinhibition relieved by CRMP and Plexin binding downstream of semaphorin signaling.

    Evidence Co-IP, domain mapping, and activity assays with truncation mutants in cells

    PMID:18305261

    Open questions at the time
    • Structural basis of autoinhibition not defined
    • Single lab
  5. 2009 Medium

    Placed Mical in a transcriptional pathway for developmental remodeling by identifying Sox14 as a direct upstream activator driving dendrite pruning.

    Evidence Drosophila genetic epistasis, rescue, and ChIP of Sox14 at the mical promoter

    PMID:19881505

    Open questions at the time
    • Vertebrate transcriptional regulation not addressed
    • Downstream actin events inferred from genetics
  6. 2011 High

    Identified the core catalytic mechanism — direct oxidation of actin Met44 that simultaneously severs and depolymerizes filaments — defining MICAL as an actin-modifying enzyme.

    Evidence In vitro biochemistry with purified protein, mutagenesis, and mass spectrometry

    PMID:22116028

    Open questions at the time
    • Reversibility of the modification not yet shown
    • Additional oxidized residues not yet mapped
  7. 2011 Medium

    Expanded MICAL1's reach beyond the cytoskeleton by showing it competes with MST1 for NDR kinase binding to suppress proapoptotic signaling.

    Evidence Proteomic screen, co-IP, kinase assays, and knockdown/overexpression apoptosis readouts

    PMID:21730291

    Open questions at the time
    • Redox activity not required for the scaffold function
    • Single lab
  8. 2013 High

    Established MICAL-driven actin oxidation as a reversible redox switch by identifying SelR/MsrB as the stereospecific reductase opposing MICAL in vivo.

    Evidence Drosophila genetic epistasis and in vitro stereospecific reduction of Mical-oxidized actin

    PMID:24212093

    Open questions at the time
    • Regulation of the MICAL/SelR balance in vivo not detailed
  9. 2014 High

    Connected MICAL1 redox actin control to growth-cone biology, showing it governs IgCAM vesicle targeting and lamina-specific axon targeting in mouse.

    Evidence MICAL1 knockout mouse, surface biotinylation, and live imaging

    PMID:25007825

    Open questions at the time
    • Direct vesicle-actin coupling mechanism not fully resolved
  10. 2016 High

    Demonstrated cofilin synergy with MICAL oxidation and refined the residues to Met44/Met47, explaining how oxidation potentiates accelerated disassembly.

    Evidence In vitro disassembly assays, TIRF microscopy, and Drosophila genetics; plus kinetic dissection of domain autoinhibition and the H2O2-versus-direct-oxidation question

    PMID:26845023 PMID:27454820

    Open questions at the time
    • Relative contributions of direct oxidation versus H2O2 still debated between studies
    • Mechanism of cofilin enhancement structurally undefined at the time
  11. 2017 High

    Provided near-atomic structural mechanism for how oxidation destabilizes filaments via Met44 reorientation and a new M47-O-T351 contact enabling ultrafast disassembly.

    Evidence 3.9 Å cryo-EM, single-filament TIRF, and mutagenesis

    PMID:29259197

    Open questions at the time
    • Structure of the full autoinhibited enzyme not yet solved
  12. 2018 Medium

    Showed how upstream signals activate MICAL1, with GTP-Rab8 stabilizing the active conformation and relieving C-terminal autoinhibition.

    Evidence Enzyme kinetics and SAXS modeling of the 1:1 MICAL1-Rab8 complex; epilepsy mutations shown to be enzymatic gain-of-function

    PMID:29394500 PMID:30242933

    Open questions at the time
    • SAXS provides low-resolution architecture only
    • Mechanism connecting elevated activity to seizures untested in neurons
  13. 2020 High

    Established a non-actin substrate, showing MICAL1 oxidizes CaMKII Met308 to limit kinase activity and protect against cardiac arrhythmia.

    Evidence MICAL1 knockout mouse, CaMKII biochemistry, mutagenesis, Drosophila and iPSC-cardiomyocyte models

    PMID:32749237

    Open questions at the time
    • Spatial regulation of MICAL1-CaMKII oxidation in cardiomyocytes not mapped
  14. 2021 High

    Mechanistically explained how oxidation overrides filament protection, allowing even phosphomimetic cofilin to sever and stripping tropomyosin protection.

    Evidence Single-filament TIRF assays with purified proteins; plus identification of Myo15 as a spatial positioner of Mical activity

    PMID:33393173 PMID:33980493

    Open questions at the time
    • In vivo significance of tropomyosin override not directly tested
    • Myo15-Mical coupling shown in Drosophila only
  15. 2022 Medium

    Identified PAK1 phosphorylation as an extracellular-signal-driven activation input and added Tau Cys322 as another oxidation substrate relevant to tauopathy.

    Evidence Co-IP, phosphoproteomics, kinase and disassembly assays; Drosophila tauopathy genetics with MS of cysteine oxidation

    PMID:35379354 PMID:36198272

    Open questions at the time
    • PAK1 phospho-sites not structurally placed in the autoinhibition model
    • Human relevance of Tau oxidation beyond colocalization unestablished
  16. 2023 High

    Defined the interplay between bundling and oxidative disassembly, showing fascin dampens while cofilin amplifies MICAL action, and characterized a distinct ASAP1-SH3/MICAL1-PRM binding mode.

    Evidence In vitro bundling/disassembly assays and Drosophila genetics; crystal structure and ITC of the ASAP1-SH3/MICAL1-PRM complex

    PMID:36674928 PMID:37725655

    Open questions at the time
    • Functional consequence of ASAP1 binding to MICAL1 in cells not defined
  17. 2024 High

    Solved the human autoinhibited enzyme structure, defining the N-terminal catalytic / C-terminal coiled-coil intramolecular lock and the tripartite CH-L2α1-LIM assembly required for activation.

    Evidence 3.1 Å cryo-EM with biochemical binding assays, mutagenesis, and cell-based assays; plus role in HIV-1 budding via cortical actin depolymerization

    PMID:39532862 PMID:39556735

    Open questions at the time
    • How each upstream regulator engages the activation assembly not fully mapped
    • Rab35 recruitment mechanism at budding sites incompletely defined
  18. 2025 Medium

    Extended MICAL1 function to mechanotransduction in platelets, showing shear-activated F-actin disassembly enables GPIb-IX-V translocation to lipid rafts and stable VWF adhesion.

    Evidence MICAL1 knockout mice, microfluidics shear assays, superresolution imaging, lipid raft fractionation, and in vivo thrombosis

    PMID:40783397

    Open questions at the time
    • Molecular sensor coupling shear to MICAL1 activation unidentified
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple activation inputs (Rab8, Rab35, PAK1, CRMP/Plexin, NEDD9, PlexinA1) are integrated to spatially and temporally tune MICAL1 oxidative activity, and how substrate selection between actin, CaMKII, and Tau is governed, remain unresolved.
  • No unified model of competitive/cooperative activation
  • Substrate-selectivity determinants unknown
  • Several Rac1/ROS regulatory links rest on single co-IP studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016491 oxidoreductase activity 7 GO:0008092 cytoskeletal protein binding 4 GO:0140096 catalytic activity, acting on a protein 4 GO:0098772 molecular function regulator activity 1
Localization
GO:0005856 cytoskeleton 3 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-109582 Hemostasis 1
Partners
ASAP1CASLCRMPNDR1PAK1PLXNA1RAB1RAB8

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2011 Mical directly oxidizes the methionine 44 (Met44) residue within the D-loop of actin filament subunits, simultaneously severing filaments and decreasing polymerization. This post-translational oxidation is the biochemical mechanism underlying Mical-mediated actin filament disassembly. In vitro biochemical assays with purified Mical protein and actin; site-directed mutagenesis; mass spectrometry identification of Met44 oxidation Science High 22116028
2010 Mical directly binds F-actin and disassembles both individual and bundled actin filaments using its redox enzymatic activity. Mical is both necessary and sufficient for semaphorin-plexin-mediated F-actin reorganization in vivo, linking plexin receptors to actin dynamics. Purified protein binding and disassembly assays in vitro; genetic loss-of-function and gain-of-function in Drosophila; pharmacological inhibition of redox activity Nature High 20148037
2013 The methionine sulfoxide reductase SelR (MsrB) specifically reduces Mical-oxidized actin (Met44-R-sulfoxide) back to methionine, restoring normal actin polymerization properties, establishing a reversible redox actin regulatory system. SelR opposes Mical activity and semaphorin-plexin repulsion in vivo. Genetic epistasis in Drosophila; in vitro enzymatic reduction assays with purified SelR and Mical-oxidized actin; stereospecificity analysis Nature Cell Biology High 24212093
2005 The N-terminal region of MICAL-1 is a FAD-containing flavoprotein monooxygenase domain structurally similar to p-hydroxybenzoate hydroxylase (PHBH). The flavin ring can switch between two discrete positions coupled to opening of a channel to the active site, suggesting a protein substrate. Crystal structure resolved at 1.45 Å. X-ray crystallography at 1.45 Å resolution of mouse MICAL-1 residues 1–489 Proceedings of the National Academy of Sciences of the United States of America High 16275925
2005 The N-terminal flavoenzyme domain of MICAL performs an NADPH-dependent reaction reducing molecular oxygen to H2O2 (Km,NADPH = 222 μM; kcat = 77 sec−1). H2O2 production was proposed as a signaling molecule in axon guidance. Biochemical enzyme kinetics assay with purified MICAL flavodomain; measurement of H2O2 production Proceedings of the National Academy of Sciences of the United States of America High 16275926
2008 MICAL enzymatic activity is autoinhibited by its C-terminal domain. CRMP (collapsin response mediator protein) and Plexin physically associate with non-enzymatic and enzymatic domains of MICAL respectively, and together release MICAL enzymatic autoinhibition. Semaphorin signaling promotes the CRMP–MICAL physical association. Co-immunoprecipitation; domain mapping; enzyme activity assays with truncation and domain mutants; cell-based assays The Journal of Neuroscience Medium 18305261
2011 MICAL-1 interacts with the hydrophobic motif of NDR1/2 kinases and negatively regulates MST-NDR kinase signaling by competing with MST1 for NDR binding, thereby inhibiting NDR-dependent proapoptotic signaling. Overexpression of MICAL-1 reduces NDR activation; knockdown augments it. Proteomics/mass spectrometry screen; co-immunoprecipitation; kinase activity assays; siRNA knockdown and overexpression with apoptosis readout Molecular and Cellular Biology Medium 21730291
2012 Human MICAL1 is autoinhibited by its C-terminal coiled-coil region. All three human MICALs (MICAL1, MICAL2, MICAL3) regulate actin stress fibers in non-neural cells and require ROS generation for their actin-regulatory function. siRNA knockdown; overexpression of truncation mutants; fluorescence microscopy of actin structures; ROS measurement Journal of Cell Science Medium 22331357
2016 Mical-mediated oxidation of actin (Met44/Met47) improves cofilin binding to filaments, and the combined effect dramatically accelerates F-actin disassembly compared to either alone. This synergism is necessary and sufficient for F-actin disassembly in vivo and magnifies effects on axon guidance and semaphorin-plexin repulsion. In vitro actin disassembly assays with purified Mical and cofilin; TIRF microscopy; Drosophila genetic assays Nature Cell Biology High 27454820
2017 Mical stereospecifically oxidizes actin M44 and M47 residues. CryoEM reconstruction at 3.9 Å reveals oxidation reorients the M44 side chain and induces a new intermolecular interaction M47-O-T351 that promotes Mox-actin instability. Mox-actin can undergo extremely fast disassembly (84 subunits/s) and allows cofilin-mediated severing even in the presence of inorganic phosphate. Near-atomic resolution cryo-EM; single filament TIRF microscopy; site-directed mutagenesis Nature Communications High 29259197
2021 MICAL1-induced oxidation of actin filaments suppresses their protection from cofilin by: increasing cofilin binding and severing rates by several orders of magnitude; allowing non-activated phosphomimetic S3D-cofilin to bind and sever oxidized filaments; and causing tropomyosin Tpm1.8 to lose its ability to protect filaments from cofilin severing. Single filament experiments in vitro; fluorescence microscopy; TIRF assays with purified proteins EMBO Reports High 33393173
2002 MICAL1 was identified as a novel protein interacting with the CasL SH3 domain via its PPKPP proline-rich sequence. MICAL1 also associates with vimentin intermediate filaments through its C-terminal region, and colocalizes with vimentin and CasL at the perinuclear area. Far Western screening; co-immunoprecipitation; immunofluorescence colocalization The Journal of Biological Chemistry Medium 11827972
2003 MICAL-1 (isoforms 1a and 1b) specifically interacts with active GTP-bound Rab1 in a nucleotide-dependent manner, with the interaction domain mapped to the C-terminus of MICAL-1, which also mediates binding to vimentin. MICAL-1 displays predominantly cytosolic localization by cell fractionation. Yeast two-hybrid; GST pulldown; cell fractionation; domain mapping Biochemical and Biophysical Research Communications Medium 12788069
2014 Vertebrate MICAL-1 regulates the targeting of secretory vesicles containing IgCAM cell adhesion molecules to the neuronal growth cone membrane through its ability to control the actin cytoskeleton via redox chemistry, thereby maintaining appropriate IgCAM cell surface levels. This is required for lamina-specific mossy fibre axon targeting in the mouse hippocampus in vivo. MICAL-1 knockout mouse; live imaging; cell surface biotinylation assays; immunofluorescence Nature Communications High 25007825
2016 Human MICAL1 catalytic properties are regulated by its CH, LIM, and C-terminal domains. The C-terminal domain causes ~10-fold decrease in kcat, establishing an inactive/active conformational equilibrium (autoinhibition). F-actin lowers Km,NADPH and increases kcat for all MICAL forms, and actin depolymerization may be mediated by H2O2 produced by the NADPH oxidase reaction rather than direct actin methionine hydroxylation. Enzyme kinetics with purified full-length and truncated MICAL1 forms; NADPH oxidase assays; F-actin depolymerization assays Archives of Biochemistry and Biophysics Medium 26845023
2018 Rab8 in its active GTP-bound state binds MICAL1 and stabilizes its active conformation, causing a specific ~4-fold increase in kcat of the NADPH oxidase reaction. SAXS measurements support a 1:1 complex between full-length MICAL1 and Rab8 with Kd ~8 μM. Free full-length MICAL1 adopts an autoinhibited conformation in which the C-terminal region interferes with catalytic conformational changes. Enzyme kinetics; small-angle X-ray scattering (SAXS); SAXS-based structural modeling Protein Science Medium 30242933
2024 Cryo-EM structure of human MICAL1 at 3.1 Å resolution reveals that autoinhibition is mediated by an intramolecular interaction between the N-terminal catalytic domain and C-terminal coiled-coil domain, blocking F-actin interaction. Allosteric changes in the coiled-coil domain and binding of the tripartite CH-L2α1-LIM assembly to the coiled-coil domain are required for MICAL1 activation. Cryo-EM structure determination; biochemical binding assays; functional cell-based assays; mutagenesis Nature Communications High 39532862
2020 MICAL1 oxidizes Met308, a conserved residue in the calmodulin-binding domain of CaMKII, reducing CaM binding and CaMKII activity. Loss of MICAL1 in mice causes cardiac arrhythmias and premature death due to CaMKII hyperactivation, establishing CaMKII as a non-actin substrate of MICAL1. MICAL1 knockout mouse model; biochemical assays for CaMKII activity and CaM binding; site-specific mutagenesis; Drosophila genetic model; human iPSC-derived cardiomyocytes The Journal of Clinical Investigation High 32749237
2022 PAK1 (a CDC42 GTPase effector) associates with MICAL1 via its N-terminal catalytic monooxygenase and calponin homology domains, and phosphorylates MICAL1 on two serine residues, leading to accelerated F-actin disassembly. Extracellular ligand stimulation leads to PAK-dependent MICAL1 phosphorylation, linking external signals to MICAL1 activation. Co-immunoprecipitation; mass spectrometry phosphoproteomics; in vitro kinase assays; F-actin disassembly assays Cell Reports Medium 36198272
2021 The unconventional myosin Myo15 physically interacts with Mical and uses its motor and MyTH4-FERM domains to broaden Mical's distribution, thereby spatiotemporally positioning and expanding Mical-mediated F-actin disassembly and cellular remodeling in response to Semaphorin/Plexin signals. Protein-protein interaction assays; Drosophila genetic epistasis; imaging of cellular remodeling Science Advances Medium 33980493
2018 Two MICAL-1 mutations causing autosomal dominant lateral temporal epilepsy (p.Gly150Ser in the monooxygenase domain and p.Ala1065fs frameshift in the C-terminal domain) both significantly increased MICAL-1 oxidoreductase activity and induced cell contraction in COS7 cells, demonstrating gain-of-function effects on MICAL-1 enzymatic activity leading to dysregulation of F-actin dynamics. Cell-based oxidoreductase activity assays; cell contraction assay in COS7 cells; whole exome sequencing Annals of Neurology Medium 29394500
2022 Mical oxidizes Tau at Cys322 via its monooxygenase domain, altering Tau interactions with microtubules and the actin cytoskeleton, and greatly affecting Tau aggregation propensity and Tau-associated toxicity in a Drosophila Tauopathy model. MICAL1 co-localizes with Tau in Pick bodies in human Tauopathy samples. Drosophila genetic interaction studies; Mical inhibitor treatment; monooxygenase domain-specific mutation; Tau cysteine mutant transgenes; mass spectrometry quantification of cysteine oxidation Acta Neuropathologica Communications Medium 35379354
2024 MICAL1 locally depolymerizes cortical actin at HIV-1 budding sites to promote viral budding and release. MICAL1 directly disassembles branched actin networks. The Rab35 activator of MICAL1 is also recruited at budding sites and functions in the same pathway. MICAL1 depletion prevents timely ESCRT scission machinery recruitment. Superresolution microscopy; MICAL1 siRNA depletion; F-actin disassembly assays; in vitro branched-actin network assays; ESCRT recruitment imaging Proceedings of the National Academy of Sciences of the United States of America Medium 39556735
2025 MICAL1 is a shear-activated regulator that promotes local F-actin disassembly around the GPIb-IX-V complex in platelets, enabling its translocation to lipid rafts and reinforcing VWF binding under high-shear conditions. MICAL1-deficient platelets display impaired VWF-GPIbα adhesion, increased deformability under shear, and defective thrombus formation in vivo. MICAL1-knockout mice; microfluidics shear assay; TIRF/superresolution microscopy; lipid raft fractionation; in vivo thrombosis model Nature Communications Medium 40783397
2023 F-actin bundled with fascin is extensively disassembled by Mical; moreover, Mical-oxidized actin is poorly bundled by fascin, amplifying disassembly. Cofilin synergizes with Mical to dramatically amplify disassembly of bundled F-actin beyond the sum of their individual effects. Fascin bundling dampens Mical's disassembly activity, establishing a balance between crosslinking and oxidative disassembly. Biochemical actin bundling/disassembly assays with purified proteins; structural imaging; Drosophila genetic epistasis assays; high-resolution cellular imaging Proceedings of the National Academy of Sciences of the United States of America High 37725655
2023 The SH3 domain of ASAP1 binds to the proline-rich motif (PRM) of MICAL1 with sub-μM affinity. Crystal structure of the ASAP1-SH3/MICAL1-PRM complex reveals a unique binding mode where two negatively charged patches in the SH3 pocket recognize an 'xPx+Px+' sequence in MICAL1-PRM, differing from typical SH3/PRM interactions. Crystal structure determination; isothermal titration calorimetry (ITC); mutagenesis International Journal of Molecular Sciences Medium 36674928
2028 MICAL1 co-immunoprecipitates with RAB35, and activated RAB35 (GTP-bound) increases MICAL1 interaction. Silencing of RAB35 reduced ROS generation and Akt phosphorylation downstream of MICAL1 in breast cancer cells. Co-immunoprecipitation; Rac1 pulldown assay; ROS measurement; siRNA knockdown BMC Cancer Low 27430308
2019 NEDD9 interacts with MICAL1 under hypoxic conditions, and NEDD9 stabilizes MICAL1 protein. Silencing NEDD9 reduced MICAL1 stability. MICAL1 overexpression selectively increased GTP-Rac1 (but not Cdc42 or RhoA), implicating MICAL1 in Rac1-dependent migration. Co-immunoprecipitation; siRNA knockdown; Rac1/Cdc42/RhoA pulldown activity assay Frontiers in Pharmacology Low 31019460
2024 PlexinA1 forms a complex with MICAL1 and promotes Rac1 activation and ROS production, which in turn prevents MICAL1 ubiquitin/proteasome-mediated degradation and stabilizes MICAL1 protein. Co-immunoprecipitation; immunofluorescence; siRNA-mediated knockdown; Rac1 pulldown assay; ROS measurement; ubiquitination assay Biochimica et Biophysica Acta. Molecular Basis of Disease Low 38508474
2009 Sox14 transcription factor directly regulates expression of mical in Drosophila, establishing a genetic pathway where Sox14 → Mical governs dendrite severing during pruning. Overexpression of Mical significantly rescues pruning defects in sox14 mutants. Genetic epistasis; loss-of-function and gain-of-function in Drosophila; chromatin immunoprecipitation (Sox14 binding to mical promoter) Nature Neuroscience Medium 19881505

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.) 255 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 151 19864458
2014 Redox modification of nuclear actin by MICAL-2 regulates SRF signaling. Cell 140 24440334
2013 SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics. Nature cell biology 124 24212093
2002 MICAL, a novel CasL interacting molecule, associates with vimentin. The Journal of biological chemistry 120 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 102 18094055
2013 MICAL-family proteins: Complex regulators of the actin cytoskeleton. Antioxidants & redox signaling 96 23834433
2016 F-actin dismantling through a redox-driven synergy between Mical and cofilin. Nature cell biology 91 27454820
2011 MICAL-L1 is a tubular endosomal membrane hub that connects Rab35 and Arf6 with Rab8a. Traffic (Copenhagen, Denmark) 91 21951725
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
2013 Cooperation of MICAL-L1, syndapin2, and phosphatidic acid in tubular recycling endosome biogenesis. Molecular biology of the cell 89 23596323
2012 Differential regulation of actin microfilaments by human MICAL proteins. Journal of cell science 85 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 67 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
2011 MICAL-1 is a negative regulator of MST-NDR kinase signaling and apoptosis. Molecular and cellular biology 53 21730291
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
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 37 25364729
2021 A junctional PACSIN2/EHD4/MICAL-L1 complex coordinates VE-cadherin trafficking for endothelial migration and angiogenesis. Nature communications 34 33972531
2019 MICAL-L2 potentiates Cdc42-dependent EGFR stability and promotes gastric cancer cell migration. Journal of cellular and molecular medicine 33 31034158
2020 GRAF2, WDR44, and MICAL1 mediate Rab8/10/11-dependent export of E-cadherin, MMP14, and CFTR ΔF508. The Journal of cell biology 32 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
2023 MICAL-mediated oxidation of actin and its effects on cytoskeletal and cellular dynamics. Frontiers in cell and developmental biology 28 36875759
2011 MICAL-like1 mediates epidermal growth factor receptor endocytosis. Molecular biology of the cell 28 21795389
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
2012 Trafficking cascades mediated by Rab35 and its membrane hub effector, MICAL-L1. Communicative & integrative biology 18 23060965
2014 Regulation of Src trafficking and activation by the endocytic regulatory proteins MICAL-L1 and EHD1. Journal of cell science 17 24481818
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
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 13 37725655
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
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
2020 Signal-regulated oxidation of proteins via MICAL. Biochemical Society transactions 10 32219383
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
2016 A simple and efficient method for generating high-quality recombinant Mical enzyme for in vitro assays. Protein expression and purification 9 27223600
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 8 39556735
2008 Identification and characterization of JRAB/MICAL-L2, a junctional Rab13-binding protein. Methods in enzymology 8 18413246
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 7 38508474
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
2016 MICAL-like Regulates Fasciclin II Membrane Cycling and Synaptic Development. Molecules and cells 7 27770767
2007 Investigation of the four cooperative unfolding units existing in the MICAL-1 CH domain. Biophysical chemistry 7 17662518
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 Endosomal actin branching, fission, and receptor recycling require FCHSD2 recruitment by MICAL-L1. Molecular biology of the cell 4 39382837
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
2025 CIN85 and CD2AP Are Novel Constituents of Dynamic Tubular Recycling Endosomes That Regulate Recycling Upon Recruitment by MICAL-L1. Traffic (Copenhagen, Denmark) 3 40740057
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 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
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 Endosomal actin branching, fission and receptor recycling require FCHSD2 recruitment by MICAL-L1. bioRxiv : the preprint server for biology 0 38979241
2024 Mical1 deletion in tyrosinase expressing cells affects mouse running gaits. Genes, brain, and behavior 0 39344934

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