MICAL1: A Multidomain Flavoprotein Monooxygenase Regulating Actin Dynamics and Cell Signaling
Comprehensive genomic, functional, and clinical overview of MICAL1 (Molecule Interacting with CasL 1)
Gene Information Card
| Symbol | MICAL1 |
|---|---|
| Full Name | Molecule Interacting with CasL 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q21 |
| NCBI Gene ID | 64780 ncbi.nlm.nih.gov/gene/64780 |
| Ensembl ID | ENSG00000111816 |
| UniProt ID | Q8TDZ2 |
| OMIM ID | 607129 |
| HGNC ID | 24686 |
| Aliases | MICAL, MICAL-1, FLJ11933, MICAL1 variant 1 |
Description
MICAL1 encodes a multidomain flavoprotein monooxygenase that catalyzes the stereospecific oxidation of actin methionine residues, leading to actin filament disassembly. It contains a flavin adenine dinucleotide (FAD)-binding monooxygenase domain, a calponin homology (CH) domain, a LIM domain, and a C-terminal coiled-coil region. MICAL1 integrates redox signaling with cytoskeletal remodeling and is implicated in cell migration, axon guidance, and cancer progression.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | MICAL1 overexpression promotes actin disassembly, enhancing cell migration and invasion; altered expression linked to poor prognosis. | COSMIC; PMID: 25944712; PMID: 29353810 |
| Neurodevelopmental disorders | MICAL1 mutations affect axon guidance and neuronal connectivity via dysregulated actin dynamics. | ClinVar; PMID: 25446529 |
| Intellectual disability | Homozygous loss-of-function variants in MICAL1 associated with intellectual disability and developmental delay. | ClinVar; PMID: 25446529 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 9.7 | Low |
| Testis | 15.2 | Medium |
| Spleen | 4.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.2 | High expression |
| HeLa | 11.8 | Moderate expression |
| A549 | 9.5 | Low expression |
| SH-SY5Y | 16.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2152C>T (p.Arg718Trp) | Missense | <0.01% | Loss of monooxygenase activity; associated with intellectual disability |
| c.287G>A (p.Arg96His) | Missense | <0.01% | Reduced actin binding; reported in ClinVar |
| c.1234_1236del (p.Lys412del) | In-frame deletion | <0.01% | Altered protein stability; COSMIC |
Mutation functional classification
Loss of Function (LOF)
Homozygous missense variants (e.g., p.Arg718Trp) impair FAD binding and monooxygenase activity, leading to defective actin regulation and neurodevelopmental phenotypes.
Gain of Function (GOF)
Overexpression of wild-type MICAL1 in cancers leads to increased actin disassembly and enhanced cell motility, but no activating mutations have been confirmed.
Dominant Negative (DN)
Not reported for MICAL1.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Actin cytoskeleton regulation (Reactome: R-HSA-5663222)
• Semaphorin signaling (Reactome: R-HSA-373755)
• MICAL-mediated actin disassembly (Reactome: R-HSA-5663213)
Protein Summary
MICAL1 is a 1067-amino acid flavoprotein monooxygenase that uses FAD and NADPH to specifically oxidize Met44 and Met47 in actin, causing filament severing and disassembly. The N-terminal CH domain binds F-actin, while the LIM and coiled-coil domains mediate protein-protein interactions. MICAL1 activity is regulated by redox state and is essential for dynamic actin remodeling during cell migration, vesicle trafficking, and neuronal growth cone guidance. Dysregulation of MICAL1 contributes to cancer metastasis and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| MICAL1 Knockout HEK293 Cell Line | EDJ-KQ11972 | Human | 64780 | Details Get a Quote |
| MICAL1 Knockout A-549 Cell Line | EDJ-KQ40532 | Human | 64780 | Details Get a Quote |
| MICAL1 Knockout HCT 116 Cell Line | EDJ-KQ40533 | Human | 64780 | Details Get a Quote |
| MICAL1 Knockout HeLa Cell Line | EDJ-KQ40534 | Human | 64780 | Details Get a Quote |
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